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Purpose: Resilience engineering is the ability of a system to adjust its own functions and maintain the required behavior in the face of changes and disturbances, and resilience potential is a necessary requirement. We aimed to clarify the relationship between resilience potential and error prevention cases., Method: Based on the error cases reported in our department, we aggregated the relationship with resilience potential for each radiation treatment process., Result: As a result of tabulating the relationship, we were able to recognize and prevent errors by taking preventive measures from past cases. On the other hand, in cases that slipped through the check mechanism, errors were discovered because of a sense of discomfort in unusual situations, and some error cases could be prevented by increasing the resilience potential., Conclusion: This study found that preparation, observation, coping, and utilization of past experiences are related to resilience potential in preventive cases.

Aim: When elderly people return to their daily lives after inpatient treatment, they may be offered a chance to change the residence to which they are accustomed. The present study clarified the changes in the residence of elderly patients through an Integrated Community Care Ward (ICCW)., Subjects and Methods: Patients were admitted to and discharged from the ICCW (53 beds) of Hospital A, located in a city with a population of 30,000 and an aging rate of 37%, for 2 years from April 1, 2018, to March 31, 2020. Patients ≥65 years old were included in the study. We conducted a retrospective survey of information recorded in the electronic medical record system and collected information on activities of daily living, medical procedures at the time of discharge, residence before and after hospitalization, and intentions regarding discharge destination within seven days of hospitalization., Results: Of the 735 patients ≥65 years old who were admitted to the ICCW, 608 were included, excluding 127 patients admitted for scheduled surgeries. The average age was 82.9 years old, with 52% being over 85 years and 26% being over 90 years old. Of the 465 people hospitalized from home, 64% were discharged, 23% changed to a facility or hospital, and the remaining 13% died. More than 80% of the 143 discharged from facilities or hospitals returned to facilities, but 36 (25%) were discharged to a different facility from before admission. Of the 404 patients who were admitted from home and discharged alive, independence in eating, independence in movement, and having family members living with them were independently related factors for achieving discharge home. Regarding the intended discharge destination within 7 days after hospitalization, of the 246 hospitalized patients who wished to be discharged home, 56 said they wanted to be discharged to a facility or hospital, showing a discrepancy of 23%., Conclusions: Many elderly people changed their residences after admission to the ICCW. While coordinating disagreements within families as well as navigating medical and nursing care constraints, dialogue across multiple professions should be continued to help elderly patients live their own lives.

A closed system drug transfer device (CSTD) helps to minimize unnecessary exposure of healthcare workers such as pharmacists to hazardous drugs. One of the concerns in using CSTDs to prepare anticancer drugs is their influence on preparation time. Therefore, we compared the time needed to prepare anticancer drugs with the CSTDs NEOSHIELD ® and BD PhaSeal ® system and with an injection needle. In the comparison of NEOSHIELD ® and an injection needle, the preparation time of the liquid formulations of the cytotoxic drugs irinotecan, eribulin, cisplatin, docetaxel, and paclitaxel was significantly shorter with the injection needle and that of gemcitabine was significantly shorter with NEOSHIELD ® , but that of oxaliplatin, carboplatin, and doxorubicin was not significantly different between the two methods; the preparation time of the liquid formulations of the molecular-targeted drugs atezolizumab, obinutuzumab, cetuximab, daratumumab and vorhyaluronidase alfa, nivolumab, ramucirumab, and rituximab was significantly shorter with NEOSHIELD ® and that of bevacizumab and pembrolizumab was significantly shorter with the injection needle; and the preparation time of the lyophilized formulation of cytotoxic and molecular-targeted drugs was not significantly different between the two methods. In the comparison of NEOSHIELD ® and BD PhaSeal ® system, the preparation time of cyclophosphamide and ifosfamide was significantly shorter with NEOSHIELD ® , but that of bendamustine was not significantly different between the two CSTDs. In conclusion, these results suggest that the preparation time with CSTDs may be similar to or shorter than that with an injection needle, depending on the type of CSTD and the drug formulation and type.

The standard treatment of locally advanced rectal cancer is preoperative chemoradiotherapy(CRT)in Europe and the United States, while that is surgical excision and lateral pelvic lymph node dissection followed by adjuvant chemotherapy in Japan. Recently, total neoadjuvant therapy(TNT), which combines neoadjuvant chemotherapy and preoperative CRT, have been popular. We performed curative excision for initially locally advanced rectal cancer with liver metastasis after TNT. A 61- year-old woman was diagnosed as having rectal cancer with liver metastasis and invasion of the uterus, vagina, bladder, and left ureter. The patient underwent 8 courses of FOLFOX plus bevacizumab, followed by radiotherapy, and totally pelvic excision for the primary tumor. Because of liver metastasis progression, hepatectomy was performed after 6 courses of FOLFIRI plus panitumumab. The patient has been cancer free for 20 months to date. TNT is considered to be an effective strategy for the treatment of large locally advanced rectal cancer.

A 72-year-old woman was admitted to the gastroenterology division of our hospital due to abdominal pain and vomiting. Dynamic contrast-enhanced CT showed a tumor at the body of the pancreas and main pancreatic duct dilation. She was diagnosed with carcinoma of the body of the pancreas via EUS-FNA. There was no vascular invasion or distant metastasis on preoperative imaging. She was introduced to the Gastrointestinal Surgery division where a mesenteric nodule was found at the time of the surgery. Intraoperative frozen section confirmed the diagnosis of occult peritoneal metastases. After consulting with her family, we completed the pancreatosplenectomy. On histopathological examination, this case was TS2, tub2, pT3, mpd0, S1, RP1, PV0, A0, PL0, OO0, N0, M1(PER), CY1, PCM0, DPM0, R1, stage Ⅳ. After the operation, we treated the patient with gemcitabine(GEM)plus nab-paclitaxel for 3 months(4 courses). She then developed side effects such as anorexia and tiredness. After discussing with the patient, chemotherapy was discontinued. The patient remains alive without recurrence 19 months after the operation. Patients with metastatic pancreatic adenocarcinoma have poor prognoses because they are no longer candidates for surgical therapy. We encountered a case of pancreatic body cancer with peritoneal dissemination, followed up for 15 months without recurrence.

An 82-year-old man visited our department with a chief complaint of penile pain and swelling. He was receiving maintenance dialysis for chronic renal failure and was catheterized because of urinary retention associated with prostatic hypertrophy. The penis was reddened with swelling extending to the root and marked tenderness. Blood tests indicated inflammation and imaging revealed an abscess with emphysematous changes in the cavernous region of the penis. The diagnosis was purulent penile cavernitis. His symptoms improved after decompression with incision and drainage. There has been no recurrence of the abscess in the 4 months since treatment.

The patient, a man in his 80s, presented with diarrhea following one year of treatment for non-small cell lung cancer with Nivolumab. CT results showed discontinuous wall thickening of the large bowel and cholangitis. Blood and stool culture tests ruled out immune-related adverse events and identified Edwardsiella tarda;bacterial colitis was diagnosed in the patient. This case confirmed that basic examination should not be neglected, and culture tests should be performed.

The Wnt signaling pathway is known to play an important role in various biological processes including embryonic development and tissues homeostasis. Following the identification of the mutations in LRP5 , encoding for the Wnt co-receptor low density lipoprotein receptor-related protein 5, associated with bone disorders in human, numerous studies have demonstrated the importance of Wnt signaling in bone cells. The Wnt signaling pathway is one of the key regulators of bone metabolism, hence the treatment using a monoclonal antibody against sclerostin, a bone-specific endogenous Wnt inhibitor, could improve bone mass and decrease fracture risk.

Objective: The aim of this study is to investigate the outcomes of induction chemoradiotherapy (ICRT) followed by surgery in patients with non-small cell lung cancer( NSCLC)., Methods: We retrospectively analyzed consecutive patients with NSCLC who underwent ICRT followed by surgery at our hospital between January 2006 and December 2015., Results: A total of 102 patients were eligible for evaluation (cStage/I B/II A/II B/III A/III B, 1/8/14/75/4). The median age was 66 years. Forty-one patients had adenocarcinoma, 42 patients had squamous cell carcinoma, and 19 patients had others. The regimen consisted of carboplatin and paclitaxel in 94 patients, and the others in 8 patients plus concurrent radiation at a dose of 28 Gy in 1 patient, 30 Gy in 28 patients, 40 Gy in 42 patients, 45 Gy in 3 patients, and 50 Gy in 28 patients. Major response was obtained in 84 patients. Grade 3/4 toxicity of ICRT reported in 57 patients. The 5-year relapse-free and overall survival rate was 51.4% and 62.7%, respectively., Conclusion: ICRT (carboplatin and paclitaxel plus concurrent standard radiation) followed by surgery in NSCLC can be safely performed and may contribute to satisfactory outcomes in locally advanced NSCLC. It is likely that 28~50 Gy radiation dose contributes to satisfactory outcomes in ICRT.

Recent studies of mouse genetics and human gene mutations has greatly contributed to clarifying the molecular mechanism of bone metabolism. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication among bone component cells such as osteoclasts, osteoblasts, osteocytes and endothelial cells. An imbalance of this process is often linked to various bone diseases. Thus, the elucidation of the molecular mechanisms involved in bone remodeling is critical for a deeper understanding of the maintenance of healthy skeleton and bone disease.

Cognitive dysfunction is a public health issue, which is one of the main contributing factors for need-of-care, afflicting patients and their caretakers. It is well accepted that physical activity is in close relationship with brain function. Accumulating data has indicated that exercise training can improve brain functions both directly and indirectly via the alleviation of the diseases underlying, including hypertension and diabetes. Recently, mechanisms bridging brain functions and physical exercises have begun to be clarified. Further studies are required for the understanding of the whole picture of neuropsychiatric diseases and for the development of effective exercise therapy for these diseases.

A 40-year-old female presented with a skin rash, hepatosplenomegaly, hypothyroidism, IgG-λ monoclonal gammopathy, slightly elevated serum VEGF levels, and >1-year history of weakness in the posterior cervical muscles. Based on these symptoms and her clinical course, she was suspected of having POEMS syndrome. However, because there was no sign of peripheral neuropathy (PN), the criteria for the diagnosis of POEMS syndrome were not met. Consequently, she continued follow-up and was under close observation as an outpatient. She complained of slowly progressive dyspnea that was identified as type 2 respiratory failure requiring non-invasive positive pressure ventilation. She received systemic chemotherapy, including thalidomide and dexamethasone, as the respiratory failure was predominantly a result of POEMS-associated PN. Although the skin eruptions improved upon treatment, respiratory failure gradually worsened, and she required mechanical ventilation. The patient was suspected of having sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance (SLONM-MGUS), because of resistant to chemotherapy and second opinion suggestion. A thigh muscle biopsy revealed the presence of nemaline rods and led to the definitive diagnosis of SLONM-MGUS. Unfortunately, she was unable to receive autologous stem cell transplantation, and finally died because of progressive respiratory failure. SLONM-MGUS is an extremely rare disease but should be considered as a critical, monoclonal-protein related condition.

Background: Pituitary metastasis of lung cancer is rare; however, it often causes diabetes insipidus. Although the majority of such patients are treated with radiation therapy, it remains unclear whether diabetes insipidus can be controlled by radiation therapy., Case: A 72-year-old man was admitted to our hospital for hemosputum, headache, and polyuria. A chest CT scan showed a 3.0 cm mass in the left upper lobe of his lung. Bronchofiberscopy results confirmed the pathological diagnosis of lung adenocarcinoma. Based on the findings from PET-CT, head MRI, and endocrine tests, the diagnosis of lung adenocarcinoma( cT1bN0M1b, stage IV)accompanied with central diabetes insipidus caused by pituitary metastasis was made. Oral administration of desmopressin reduced urine volumes; however, chemotherapy for achieving stable disease in the primary tumor was ineffective in controlling the symptoms of diabetes insipidus. Chemotherapy was discontinued after 4 months because of severe hematological toxicity. During 2 months after the cessation of chemotherapy, polyuria worsened and, therefore, radiation therapy for pituitary metastasis was started. Following the radiation therapy, an apparent reduction in urine volume was observed., Conclusion: Our experience of this case suggests that radiation therapy for pituitary metastasis should be considered at the time when diabetes insipidus becomes clinically overt.

Receptor activator of nuclear factor-κB ligand(RANKL),a transmembrane protein of the tumor necrosis factor(TNF) superfamily cytokine, currently provides a paradigm that enables the molecular understanding of the linkage among bone metabolism, organization of lymphoid tissues, establishment of the thymic microenviroment, thermoregulation, metabolic regulation, mammary gland development and tumorigenesis. Here we summarize the recent progress in the understanding of RANKL biology by focusing on the investigation of RANKL expressing cells/organs, signaling and related diseases in the context of the newly established interdisciplinary field of osteonetwork. The elucidation of both physiological and pathological RANKL function will provide a scientific basis for future therapeutic approaches to several RANKL-related diseases.

Reports of drug-induced interstitial pneumonia caused by Cetuximab have been increasing. Pneumocystis pneumonia is important as a differential diagnosis of drug-induced interstitial pneumonia. We report herein on a 64-year-old man with pneumocystis pneumonia after cetuximab-based bioradiotherapy for laryngeal cancer. After radiotherapy, the patient developed multi-drug resistant pneumonia. Chest CT imaging revealed diffuse ground-glass opacities in the lung field. He was diagnosed as having pneumocystis pneumonia based on the bronchoalveolar lavage (BAL) findings, and then his symptoms improved after treatment with Trimethoprim/Sulfamethoxazole. It is important to assess the risk factor for pneumocystis pneumonia for early its detection and treatment.

When the medical fee system was revised in 2012, the category of perioperative oral management was newly organized. However, the calculation of additional fees for such management required referral from medical to dental departments. In addition, requests for such management were limited, possibly owing to an increased burden on doctors engaged in outpatient services. This study examined the usefulness of an approach to promote patients' use of dental services by increasing their awareness of the importance of oral management. In this approach, pharmacists explained doctors' instructions to patients at a chemotherapy center within the study facility. Explanations were provided to 114 patients, 75 (65.8%) of whom subsequently used dental services in the facility. For patients using dental services, oral care was performed most frequently (40; 53.3%), followed by invasive procedures (23; 30.7%). Furthermore, the facility's ethics committee approved a survey to measure the satisfaction of patients undergoing chemotherapy at the center. Of the 110 patients invited to participate in the survey, 77(70.0%) did not respond. Researchers concluded the low response rate was associated with patients' belief that dental services were intended primarily for treating oral cavities and their lack of awareness of the importance of preventive dental care. However, in 2014, the number of calculations of additional fees for perioperative oral management markedly increased each month after the above-mentioned approach, from 62 (January) to 162 (December). Both the hospital-to family and family-to-hospital dentist referral rates significantly increased, from 11.2% and 10.7%, respectively (June 2013), to 21.0% and 41.9%, respectively(June 2014). Future evaluations of the outcomes of perioperative oral management and promoting cooperation between medical and dental communities may be necessary.

Although Semaphorins were originally identified as neuronal axon guidance molecules, recent research has revealed the functions of Semaphorins in many organs, tissues and cells. Among Semaphorin family members, Semaphorin 3A(Sema3A)and Sema4D are highly expressed in bone cells and play critical roles in the regulation of bone homeostasis. Other semaphorins and their receptors are also shown to be involved in bone metabolism. In contrast, the function of Semaphorins expressed in lung is not well understood althogh many of Semaphorins are highly expressed in lung among various tissues examined. As growing evidence reveals that the link between chronic obstructive pulmonary disease(COPD)and osteoporosis, the crosstalk between bone and lung through Semaphorin signaling should be investigated.

The weight-bearing exercises help to build bones and to maintain them strength. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication between bone component cells such as osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often linked to various bone diseases. During bone remodeling, resorption by osteoclasts precedes bone formation by osteoblasts. Based on the osteocyte location within the bone matrix and the cellular morphology, it is proposed that osteocytes potentially contribute to the regulation of bone remodeling in response to mechanical and endocrine stimuli.

A 48-year-old woman with a history of autoimmune hemolytic anemia and taking long-term corticosteroid therapy presented with a 3-month history of general fatigue, abdominal distension, and pigmentation. A computed tomography scan of the abdomen showed a tumor in the sigmoid colon and multiple metastatic nodules in the liver. A colonoscopy revealed an obstructing mass with the presence of an irregular ulcer in the sigmoid colon. Following biopsy and histopathological analysis, the patient was diagnosed with neuroendocrine carcinoma (NEC) of the colon. She received her first cycle of chemotherapy, with carboplatin and etoposide. During hospitalization, her pigmentation and hypertension worsened and hypokalemia was observed, all of which suggsted Cushing's syndrome. Her plasma adrenocorticotropic hormone (ACTH) and cortisol levels were high, and an ectopic ACTH-producing tumor was suspected. After a second chemotherapy cycle, she developed neutropenic fever and subsequently died. At autopsy, two histological types were found in the tumor: small cell carcinoma and large cell NEC. Immunohistochemical analysis revealed ACTH in the large cell NEC. This is the first reported case of an ectopic ACTH syndrome caused by NEC of the colon.

Bone, which support motile organ and periodontal tissue, is renewing throughout our life. This restructuring process is called "bone remodeling" , and osteoclasts and osteoblasts play a crucial role in this process. Bone remodeling is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication between bone component cells such as osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often linked to various bone diseases. Alveolar bone remodeling is directly influenced by occlusal force from the teeth. Thus, the elucidation of the regulatory mechanisms involved in alveolar bone remodeling is critical for a deeper understanding of the maintenance of healthy tooth and dental disease.

Osteocytes, the most numerous and least well studied bone cells, are stellate-shaped cells enclosed within the bone lacuno-canalicular network of bone. Based on the osteocyte location within the bone matrix and the cellular morphology, it is proposed that osteocytes potentially contribute to the regulation of bone remodeling in response to mechanical and endocrine stimuli. Although the potential importance of osteocytes has been recognized, there has been limited evidence for functional roles of osteocytes in bone remodeling. However, studies of mice gene targeting and human gene mutations have contributed to recent progress of osteocyte biology. Furthermore, bone has been traditionally regarded as a part of the skeletal and locomotor system, but recent studies suggest that osteocytes regulate systemic biological functions based on the inseparable link between bone and other systems.

Laryngeal papillomatosis is the most common benign neoplasm of the larynx. Juvenile onset laryngeal papillomatosis tends to recur. In patients with adult onset laryngeal papillomatosis, laryngeal cancer rarely develops. This paper reports a clinical analysis of 60 patients with laryngeal papillomatosis who were treated at our clinic between January 1971 and September 2009. We analyzed the sex ratio, age at the onset of papilloma, type of developing papilloma (single or multiple type), site of developing papilloma, recurrence rate, and therapeutic modalities. Furthermore, the clinical characteristics of the patients with malignant transformation were examined. The patients were classified according to their age at the onset of the papilloma and the type of developing papilloma. The patients were grouped into a juvenile-onset group and an adult-onset group according to their age at the onset of the papilloma. They were also classified into single-type or multiple-type according to whether the initial papilloma appeared singly or multiply. The male to female sex ratios were 1.2 in the juvenile-onset group and 5.1 in the adult-onset group. Among the patients who developed papilloma at an age of under 10 years old, most of the juvenile cases had experienced onset by 4 years of age. Furthermore, the frequency of multiple-type papilloma was significantly higher in the juvenile-onset group, compared with the adult-onset group. The vocal fold was the most frequent site of the papilloma. The recurrence rate in the juvenile-onset group was significantly higher than that of the adult-onset group. A stratified analysis according to the type of papilloma occurrence, however, showed no significant difference in recurrences between the juvenile-onset and adult-onset groups. A stratified analysis according to the age at the onset of papilloma showed that the recurrence rate of multiple-type papilloma was significantly higher than that of single-type papilloma in the adult-onset group. Among multiple therapeutic modalities, vaporization by carbon dioxide laser was the most frequently used. Adjuvant therapy was performed in 6 cases who suffered from multiple relapses. The injection of interferon was performed in 5 cases, and the local injection of cidofovir was performed in 1 case. Malignant transformation of the papilloma was confirmed in 3 cases. The periods between the onset of papilloma and the malignant transformation were 40 years, 14 years, and 3 years. The present study indicates that patients with laryngeal papilloma developing at multiple sites have a significantly higher rate of relapse, even in the adult-onset group. There was no tendency in the period observed between the onset of papilloma and malignant transformation. From the standpoint of recurrence and malignant transformation, patients with papillomatosis should be carefully followed up for a long period of time.

In January 2009, a 62-year-old man presented with diarrhea, leg edema, and thrombopenia and was admitted to our hospital. The past medical history revealed Sjögren's syndrome and autoimmune hepatitis for which he had been administered prednisolone. On admission, a laboratory examination revealed massive hypoalbuminemia and high levels of C-reactive protein and platelet-associated IgG. Anti-double stranded DNA and anti-Sm antibodies were negative. Analysis of the bone marrow aspirate and Tc-99m albumin scintigraphy findings suggested autoimmune thrombocytopenic purpura (AITP) and protein-losing enteropathy (PLE), respectively. We diagnosed him as SLE, because past immunoserological testing had showed positivity for anti-double stranded DNA antibody and LE cells. Methylprednisolone pulse therapy and intravenous immunoglobulin therapy were ineffective. Rituximab was ineffective against PLE but was effective against AITP. Cyclosporine and Cyclophosphamide were ineffective against PLE. Subcutaneous injection of 200-μg octreotide daily and a medium chain triglyceride (MCT) diet was effective against PLE, and the patient's condition dramatically improved. The effectiveness of octreotide treatment and an MCT diet in the treatment of PLE with SLE is discussed.

Bone is constantly renewed by the balanced action of bone formation and bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. An imbalance of bone remodeling is often linked to various bone diseases. During bone remodeling, resorption by osteoclasts precedes bone formation by osteoblasts. Based on the osteocyte location within the bone matrix and the cellular morphology, it is proposed that osteocytes potentially contribute to the controls of bone remodeling by sensing mechanical stress and hormones. Furthermore, bone has been traditionally regarded as a part of the skeletal and locomotor system, but recent studies suggest that osteocytes regulate systemic biological functions based on the inseparable link between bone and other systems.

We examined the efficacy of recombinant thrombomodulin (rTM) for treatment of patients with disseminated intravascular coagulation (DIC) caused by urinary tract infections. Thirteen DIC patients treated with rTM (rTM group) and 11 not receiving rTM (non-rTM group) were enrolled in this study. Blood data including coagulation markers collected before and after the treatment,a hospitalized term,and period of antibiotic treatment were compared. There were no significant differences in baseline characteristics between the two groups. Both groups showed significant improvement in all parameters such as blood biochemical data,coagulation markers,and DIC score 5-7 days after treatment. However, changes in platelet and DIC score from baseline to early phase (day 1-3) were significantly greater in the rTM group than in the non-rTM group (p＜0.05). In addition,changes in FDP value showed slight but not significant improvement in rTM group compared to the non-rTM group in the early treatment phase (p＝ 0.084). The period of antibiotic usage was significantly shorter in the rTM group,whereas the hospitalized term showed no significant difference between the groups. Definite adverse effects were not present in the rTM group. In conclusion,administration of rTM may have a beneficial effect in patients with DIC induced by urinary tract infections,compared with conventional treatment.

The bony skeleton enables the locomotive activity, the storage of calcium, and the harboring of the hematopoietic stem cells from which blood and immune cells are derived. The immune and skeletal systems share various molecules including cytokines, signaling molecules, transcription factors and membrane receptors. Investigation into rheumatoid arthritis (RA) as well as cloning of RANKL and various bone phenotypes found in immune-compromised gene deficient mice has highlighted the importance of the dynamic interplay between the both systems. These findings have recently led to both the emergence and subsequent rapid evolution of the field of osteoimmunology. The scope of osteoimmunology has been extended to encompass a wide range of molecular and cellular interactions, the elucidation of which will provide a scientific basis for future therapeutic approaches to diseases related to the immune and skeletal systems.

The aim of this study was to investigate distinctive change in the hearing impaired elderly listeners, especially about speech recognition. Subjects were 525 patients (235 males, 290 females), from 60 to 98 years of age who had visited the Hearing Aid Clinic of Otorhinolaryngology, National Center for Geriatrics and Gerontology Hospital, between June 2001 and December 2012. Pure-tone air conduction threshold determination was administered to each subject. The speech audiometry materials used to define speech discrimination ability were Japanese monosyllabic word lists, 67S word lists. Sex- and age-specific trends in maximum discrimination score (MDS) and rollover index (RI) were shown in this study. RI was computed by the formula (PBmax-PBmin)/PBmax. PBmax has almost the same meaning as MDS in Japan. PBmin represented the lowest PB score above the test intensity level of PBmax. Mean MDSs were 80.8% in their sixties, 75.3% in their seventies, 60.7% in their eighties, and 45.5% in their nineties. The rate of decrease in mean MDS per decade accelerated in the older generation. Mean RIs were 0.18 in patients in their sixties, 0.24 in their seventies, 0.30 in their eighties, and 0.30 in their nineties. It increased until the age of eighties. In the model 1, multiple logistic analyses were performed to examine the effect of age (in 10-year increments), sex and mean hearing levels in pure tone average of values at 500, 1000, 2000, 4000 Hz (in 10 dB increments) on the MDS < 60%. Significant associations were observed between MDS < 60% and age (odds ratio, 3.03; 95% confidence interval, 2.38 to 3.85), and mean hearing levels in pure tone average of values at 500, 1000, 2000, 4000 Hz (2.33; 2.03 to 2.68). Sex was not associated with MDS < 60%. In the model 2, multiple logistic analyses adjusted for age and sex were performed to examine the effect of hearing level at test frequencies of 125, 250, 500, 1000, 2000, 4000, and 8000 Hz (in 10 dB increments)on the MDS < 60%. Significant associations were observed between MDS < 60% and hearing level at 250 Hz (2.04; 1.44 to 2.89), and 2000 Hz (1.46; 1.16 to 1.83), and 4000 Hz(1.24; 1.02 to 1.50). These outcomes suggest that the important point in qualifying the fitting of hearing aid is to present the list words at an adequate sound pressure level for evaluation of speech understanding especially in the hearing impaired elderly listeners.

The mice with a disruption of Rank or Rankl exhibit normal mammary development during puberty, but their mammary epithelium fails to proliferate and form lobuloalveolar structures during pregnancy, resulting in the death of newborns. Hormone replacement therapy is associated with an increased risk of breast cancer. Importantly, specific deletion of RANK in mammary epithelium cells prevents both the onset and progression of medroxyprogesterone acetate (MPA) -driven mammary cancer and impairs self-renewal of breast cancer stem cells. Furthermore, RANK is highly expressed in several cancer cells. Functionally, it has been shown that RANKL can stimulate the directed migration of mammary epithelial cells as well as prostate cancer and melanoma cells toward a source of RANKL. In an in vivo metastasis model, OPG reduced the tumor burden in bones and ameliorated clinical paralysis, but did not affect the frequency of the spread of metastases into other tissues. These findings show that the RANK/RANKL system is crucial for mammary development, breast tumorigenesis and bone metastasis.

We herein present a review of the surgical approach of lateral temporal bone resection (LTBR) in the treatment of 5 cases of head and neck cancers invading the jugular foramen between 2008 to 2013. The patients comprised 3 males and 2 females with ages ranging from 25 to 76 and observation times were between 13 and 22 months. In this study we reviewed the method of operation and treatment. Four patients are alive, but one patient died from the primary disease. Complications occurred including postoperative facial nerve palsy and hearing loss. Although the LTBR with jugular foramen approach can cause postoperative facial nerve palsy and hearing loss, this method would be recommended as a safe surgical procedure for its wide surgical field. We therefore propose that this LTBR technique is useful for patients with head and neck cancer extending to the jugular foramen.

Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Coupling has been understood as a balanced induction of osteoblastic bone formation in response to osteoclastic bone resorption. An imbalance of this coupling is often linked to various bone diseases. TGF-β and IGF released from bone matrix during osteoclastic bone resorption are the favored candidates as classical coupling factor. Recently, several reports suggest that osteoclast-derived molecules/cytokines (clastokine) mediate directional signaling between osteoblasts and osteoclasts into the bone microenvironment. Thus, the elucidation of the regulatory mechanisms involved in bone cell communication and coupling is critical for a deeper understanding of the skeletal system in health and disease.

Gefitinib anderlotinib, which are epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs), have been usedfor the treatment of inoperable andrecurrent non-small cell lung cancer(NSCLC)patients. These drugs are known to cause a skin rash, one of the major side effects, at a high frequency. Biotin is a water-soluble vitamin, andit belongs to the vitamin B family. It is well known that biotin deficiency increases the risk of skin dermatitis. We administered biotin to four patients with skin rash, all of whom were treatedwith either gefitinib or erlotinib andwere unable to be treatedby a steroid ointment alone. In all patients, administration of biotin reduced the skin rash. Surprisingly, in 2 patients in whom EGFR-TKI therapy was discontinued because of the skin rash, the administration of biotin allowed for long-term gefitinib or erlotinib treatment. Biotin may be considereduseful for the treatment of skin rash causedby EGFR-TKIs. Further trials may be needed to confirm the value of biotin in this setting.

Mononuclear myeloid lineage cells, which are attracted to bone surfaces by chemokines and other factors, differentiate into multinucleated bone resorbing osteoclasts by cell fusion. Receptor activator of nuclear factor-κB ligand (RANKL) , which is expressed in mesenchymal cells, including osteocytes and hypertrophic chondrocytes, is essential for osteoclast differentiation and function. Osteoclasts have the capacity to resorb bone and impaired osteoclast differentiation and/or function leads to osteopetrosis, a rare disease in which mineralized bone cannot be removed. In contrast, excessive osteoclastogenesis causes diseases such as osteoporosis. Recent findings suggest that osteoclasts can also function as positive and negative regulators of osteoblastic bone formation. Thus, understanding of the molecular mechanisms that regulate osteoclastogenesis is important to develop therapeutic approaches to prevent bone diseases. This paper reviews recent findings of the molecular mechanisms regulating osteoclast differentiation and function.

Purpose: Liver image guided radiation therapy (IGRT) based on bone matching risks generating serious target positioning errors for reasons of lack of reproducibility of expiration breath hold. We therefore investigated the feasibility of 3D image matching between planning CT images and pretreatment cone-beam computed tomography (CBCT) images based on diaphragm surface matching., Method: 27 liver stereotactic body radiotherapy (SBRT) cases in whom trancecatheter arterial chemoembolization (TACE) had been performed in advance of radiotherapy were manually image-matched based on contrast, Lipiodol used in the TACE as the marker of the tumor, and the relative coordinates of the isocenter obtained by contrast matching, defined as the reference coordinate. The target positioning difference between diaphragm matching and bone matching were evaluated by using relative coordinates of the isocenter from the reference obtained for each matching technique., Results: The target positioning error using diaphragm matching and bone matching was 1.31±0.83 and 3.10±2.80 mm in the cranial-caudal (C-C) direction, 1.04±0.95 and 1.62±1.02 mm in the anterior-posterior (A-P) direction, and 0.93±1.19 and 1.12±0.94 mm in the left-right (L-R) direction, respectively. The positioning error due to diaphragm matching was significantly smaller than for bone matching in the C-C direction (p<0.05)., Conclusion: IGRT based on diaphragm matching has potential as an alternative image matching technique for the positioning of liver patients.

Patients with MPO-ANCA related angitis sometimes experience the onset of sonsorineural hearing loss and facial palsy. The main aim of this study was to investigate the relationship between the inflammation in the inner ear and sensorineural hearing loss, or between the inflammation of the facial nerve and facial nerve palsy in patients with MPO-ANCA related angitis. From 2007 to 2011, the inner ear was evaluated in 16 ears from 8 patients with MPO-ANCA related angitis with 3D-FLAIR MRI. In 12 ears of the 16 ears the onset of sensorineural hearing loss was noted, and the signal intensity ratio (SIR) in the cochlea was 0.62 +/- 0.15 on pre-enhancement 3D-FLAIR MRI, and 0.97 +/- 0.5 on post-enhancement. These SIR values were significantly higher than the SIR of non-sensorineural hearing loss patients. The onset of facial palsy was noted in 9 of 16 sides and the facial nerve SIR was 0.83 +/- 0.23 on post-contrast 3D-FLAIR MRI. The SIR in the facial nerve of facial nerve palsy patients was higher than non-facial palsy patients. The conclusion is that sensorineural hearing loss and facial palsy in patients with MPO-ANCA related angitis occurred due to strong inflammation in the cochlea or facial nerve. 3D-FLAIR MRI made this pathology clear.

Bone is constantly renewed by the balanced action of bone formation and bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication between bone component cells such as osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often linked to various bone diseases. During bone remodeling, resorption by osteoclasts precedes bone formation by osteoblasts. Based on the osteocyte location within the bone matrix and the cellular morphology, it is proposed that osteocytes potentially contribute to the controls of bone remodeling as well as sensing mechanical stress.

A 66-year-old man visited our hospital with a chief complaint of a sore throat. On examination, the pharyngeal and laryngeal mucosa was reddish and localized mucosal erosion was present on the left side. Based on an initial diagnosis of acute pharyngitis caused by bacteriological infection or mycotic infection, treatment with antibacterial and antimycotic agents was initiated. However, the patient's sore throat gradually worsened and he developed intractable hiccups. Intravenous steroids were given for the treatment of the severe sore throat, and this symptom was gradually alleviated. However, the intractable hiccups persisted. In addition, the patient began to have convulsive syncope episodes and was subsequently admitted to our hospital. Further examination revealed that the syncope episodes were linked to the hiccups. To treat the hiccups, baclofen and Chinese medicine were prescribed, and the convulsive syncope episodes disappeared immediately. The patient's hiccups also improved and disappeared six days thereafter. Based on this clinical evidence, we concluded that the hiccups were caused by pharyngitis, resulting in the stimulation of the glossopharyngeal nerve, while the convulsive syncope episodes were a type of situational syncope related to hiccups.

Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication between bone component cells such as osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often linked to various bone diseases. During bone remodeling, resorption by osteoclasts precedes bone formation by osteoblasts. Based on the osteocyte location within the bone matrix and the cellular morphology, it is proposed that osteocytes potentially contribute to the controls of bone remodeling. Thus, the elucidation of the regulatory mechanisms involved in bone remodeling is critical for a deeper understanding of the skeletal system in health and disease.

Objective: The diagnosis of cervical tuberculous lymphadenitis has been performed by histological examination using excisional biopsy specimens. However a non-invasive diagnostic procedure alternative to invasive excisional biopsy has been required and fine needle aspiration cytology as well the polymerase chain reaction (PCR) technique have become useful modalities. The aim of this study was to clarify the effectiveness of needle aspiration as a less invasive and more rapid diagnostic procedure than excisional biopsy., Material and Methods: Twenty-one excisinal biopsy specimens and 20 needle aspiration specimens were collected from 29 patients who were diagnosed as having cervical tuberculous lymphadenitis. The detection of mycobacterium tuberculosis with a smear microscopy was performed in 20 specimens, with the culture method in 20 and with the PCR test in 14 specimens. The histopathological positive rates, the detection ratio of mycobacterium, the rupture rate of the local skin lesion and the period necessary for diagnosis were compared between the two percutaneous approaches., Results: The diagnosis of tuberculous lymphadenitis was successful in all cases either by cytological examination in 8 of 21 (40%) or with the histological approach in the other 21 cases. The detection ratios of smear, culture and PCR were 20%, 40% and 64%, respectively. The rupture rate of the local skin after the excisional biopsy was higher than that of the needle aspiration procedure (p = 0.05). The period for diagnosis was significantly longer than that of the needle aspiration procedure (p < 0.001)., Conclusion: As a less invasive method of diagnosis of cervical tuberculous lymphadenitis, cytology as well as the detection of mycobacterium using an aspiration procedure is highly recommended.

Bone is continuously remodeled by osteoclastic bone resorption and osteoblastic bone formation to maintain the structural integrity and mineral homeostasis. This process is called "bone remodeling" . These bone cells are regulated by mechanical stimulation and systemic (hormonal) factors in addition to autocrine, paracrine factors and cell-cell interactions. Recently, we reported that two semaphorin molecules Sema4D and Sema3A have a crucial role in the regulation of bone remodeling. Sema4D derived from osteoclasts inhibits osteoblast differentiation not to hamper osteoclastic bone resorption. Sema3A derived from osteoblast lineage cells inhibits osteoclast differentiation and promotes osteoblast differentiation synchronously to increase bone mass. These studies provide a scientific basis for future therapeutic approaches to bone diseases.

Were port a 51-year-old male left renal pelvic cancer patient with paclitaxel (PTX)-induced peripheral neuropathy, which was successfully treated with pregabalin. From June 2010, a gemcitabine/PTX (GP) regimen was used as third-line treatment. In order to relieve the PTX-induced peripheral neuropathy, pregabalin (75mg/day, at night) was administered from day 6 of the 16th course. Moreover, pregabalin was increased to 150mg/day from day 12 of the course. Sensory neurotoxicity after the administration of pregabalin was decreased from CTCAE (version 4. 0) grade 3 to 1 at day 19 of the course. Therefore, there is a possibility that the PTX -induced peripheral neuropathy may be improved by pregabalin administration. Further trials may be needed to confirm the value of pregabalin.

Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Using a newly established method for the isolation of high purity osteocytes from bone matrix, we showed that osteocytes express a much higher amount of RANKL and have a much greater capacity to support osteoclastogenesis than osteoblasts and bone marrow stromal cells. The crucial role of RANKL expressed by osteocytes was validated by the severe osteopetrotic phenotype observed in mice lacking RANKL specifically in osteocytes. Thus, osteocytes are the commander cell at the initiation of the bone remodeling through regulation of osteoclastogenesis.

When performing R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)for diffuse large B-cell lymphoma(DLBCL), neurotoxicity of vincristine(VCR)is the serious dose-limiting factor.Pregabalin is one of the first-line treatments for painful diabetic peripheral neuropathy in many countries, and we have administered it to relieve the neurotoxicity associated with adverse effects of VCR in a DLBCL patient treated with the R-CHOP regimen.A 49-year-old man with kidney DLBCL had surgery performed.Afterward, the R-CHOP regimen was introduced.In order to relieve the neurotoxicity of VCR, pregabalin was used from day 8 in the second course.The severity of sensory neurotoxicity after the administration of pregabalin was improved from CTCAE(v4.0)grade 3 to grade 1.Therefore, there is a possibility that VCR-induced neurotoxicity is relieved by pregabalin.Further trials are needed to confirm the value of pregabalin.

The objective of this study was to analyze the outcome of hypopharyngeal cancer patients who underwent triple combination treatment with S-1, vitamin A and radiation(TAR therapy), and to analyze the role of TAR therapy for treating locally advanced hypopharyngeal cancer patients. 146 patients(stage I: 10 cases, stage II : 22 cases, stage III : 23 cases, stage IV: 91 cases)with hypopharyngeal squamous cell carcinoma were treated with TAR therapy(S-1; orally, 65mg/m²day, twice a day; vitamin A(retinol palmitate): 50, 000 I U/day, intra-musculary on each day of radiation; radiation: 1. 5-2 Gy/day, 5 days/week). Histologic complete responders at 30-40 Gy continued TAR therapy up to 60-70 Gy. Nonresponders at 30-40 Gy underwent surgery. The overall 5-year survival and disease-specific 5-year survival rates were 50. 5%and 59%respectively. The cumulative 3-year laryngeal preservation rate for stage I was 100%, 82. 5% for stage II, 66. 6% for stage III, and 35%for stage IV. Laryngeal preservation was fair in T1/T2 patients(81%), but not satisfactory in T3/T4 patients(21. 4%). S- 1 is administered orally, and TAR therapy can be conducted in the clinic with low toxicity. However, protocols with high intensity may be necessary to improve laryngeal preservation for locally advanced(T4)hypopharyngeal cancer.

Aim: In this study we aimed to evaluate the frequency of cerumen impaction in Japanese elderly and clarify the associations between cerumen, cognitive function, and hearing impairment., Methods: The subjects enrolleded in this study were participants in the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA). The data of 792 community-dwelling participants aged 60 to 88 years old were collected. All had taken the Mini-Mental State Examination (MMSE) and had undergone pure tone audiometry (PTA) assessment and video recording of an otoscopic examination. We then analyzed associations between the incidence of the cerumen impaction of better-hearing ear, hearing level and MMSE scores using a general linear model., Results: Cerumen impaction of the better-hearing ear was observed in 10.7% of all participants. In participants with an MMSE score of less than 24, the frequency of cerumen impaction was 23.3%. Cerumen was significant associated with poorer hearing after adjustment for sex and age (p=0.0001). Cerumen impaction also showed a significant association with a low MMSE score after adjustment for sex, age, hearing level and education (p=0.02)., Conclusions: The frequency of cerumen impaction in Japanese elderly was estimated to be approximately 10%. The existence of cerumen impaction was associated with poorer hearing level and lower MMSE score.