Activities of daily living (ADL) of single elderly individuals using social assistive programs in a rural community.

Objectives　The proportion of elderly individuals living alone is increasing in Japan. Matsumoto city office provides social assistive programs such as home help, lunch delivery, life advice, and safety check telephone calls. The purpose of this study was to compare the level of ADL between the elderly using social assistive programs (the use group) and those who did not (the non-use group).Methods　We conducted a cross-sectional study at Shiga district of Matsumoto city in September 2014. A total of 128 elderly individuals participated in this study. Health volunteers asked these subjects to complete a questionnaire without assistance. Measurement items included lifestyle variables and social support networks. With respect to the frequency of use, we used questions that inquired about the use of the social assistive program. We included a set of instruments commonly used in the health assessment of elderly populations: functional capacity (Instrumental ADL, Intellectual Activity, Social Role), social support, nutrition (Mini Nutrition Assessment [MNA]) and depressive symptoms (Geriatric Depression Scale [GDS]).Results　The use group consisted of 24 elderly individuals participating in the social support program. The non-use group consisted of 89 elderly individuals living alone without programs. The mean age of those who completed the survey was 83.9±4.2 years for the use group and 82.3±4.3 years for the non-use group. Comparisons between the two groups did not show significant difference in terms of their intellectual activity, social role, emotional social support, and MNA or GDS scores. The use group was more likely to use the public transfer service and receive instrumental social support from children and relatives.Conclusions　By means of utilizing the public transfer service, and receiving family support, the elderly living alone who used social assistive programs could live independently. These findings suggest a need for improvement in the public transfer service and social network.

Availability, usage, and factors affecting usage of electrophysical agents by physical therapists: a regional cross-sectional survey.

[Purpose] The aim of this study was to investigate the availability, usage, and factors affecting usage of electrophysical agents by physical therapists in Nagano Prefecture, Japan. [Subjects and Methods] Questionnaires were sent to all 1,571 physical therapists working in 245 institutions within Nagano Prefecture. A total of 1,110 questionnaires were returned, out of which 1,099 (70%) questionnaires containing valid responses were analyzed. Frequencies and percentages were calculated for 22 modalities with regards to availability, usage, rate of usage, and confidence level in usage. Factors affecting usage and the relationship between rate of usage and confidence level (Spearman's rho) were also determined. [Results] The top three responses for the various outcome measures were as follows: (1) hot packs (88%), low frequency stimulators (76%), and ultrasound (68%) for availability; (2) hot packs (72%), ultrasound (61%), and cold packs (59%) for usage; (3) hot packs (75%), cold spray (49%), and ultrasound (44%) for confidence in usage; and (4) equipment availability (80%), past experience (79%), and research evidence (78%) for factors affecting usage. There was a significant positive relationship between confidence and usage for all modalities, except for ultraviolet radiation, iontophoresis, and magnetic field. [Conclusion] Usage was strongly correlated with confidence, with the top three used modalities also being the ones with the highest confidence in usage.

[A case of squamous cell carcinoma of the nipple skin successfully treated with S-1 alone].

Squamous cell carcinoma of the breast is uncommon, but that of the nipple skin is rarer. The effect of chemotherapy in these cases is yet to reach consensus. We report a rare case in which primary squamous cell carcinoma of the nipple skin was successfully treated with S-1 alone. A 64-year-old woman was admitted to our hospital because of a granulomatous tumor mass over the right nipple, which she was aware of for 10 years; the tumor showed a rapid increase in growth before admission. The tumor was approximately 4 cm at the first visit, and was diagnosed as squamous cell carcinoma by incisional biopsy. We administered preoperative systemic chemotherapy owing to the presence of metastasis in an axillary lymph node. After 2 courses of chemotherapy with oralS -1 at 100mg/day for 28 days followed by a 14-day resting period, the primary tumor and metastatic lymph node showed a remarkable reduction in size. The patient subsequently underwent a radical operation and is currently healthy without any recurrence.

Tropomyosin-related Kinase B Is Potentially a Biomarker of Prognosis and Therapeutic Target for Malignant Thymic Epithelial Tumors.

BACKGROUND/AIM: Thymic epithelial tumors (TETs) mainly consist of thymoma and thymic carcinoma. Complete surgical resection is vital for the successful management of these TETs, and adjuvant therapy such as systematic chemotherapy and/or radiotherapy plays important roles in the management of recurrent or metastasized disease. However, there is still a lack of a standard treatment after the failure of these adjuvant therapies. There is thus a need to develop molecular targeted therapies for advanced malignant TETs. In the present study, we evaluated the biological significance of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling for TETs. MATERIALS AND METHODS: The expression of TrkB in 48 formalin-fixed, paraffin-embedded TET specimens (43 thymoma and 5 thymic carcinoma) collected by surgical resection was evaluated immunohistochemically. A thymic carcinoma cell line was evaluated for the role of BDNF/TrkB signaling pathway in an in vitro assay. RESULTS: High TrkB expression was related to significantly poor prognosis in patients with TETs. In vitro experiments showed that BDNF/TrkB signaling was involved in the proliferation of Ty-82 cells, but not their invasion and migration. CONCLUSION: TrkB expression is a biomarker of the prognosis for TETs and the BDNF/TrkB signaling pathway is potentially a new therapeutic target for mTETs.

PTPN3 is a potential target for a new cancer immunotherapy that has a dual effect of T cell activation and direct cancer inhibition in lung neuroendocrine tumor.

In our previous study, we found that inhibition of protein tyrosine phosphatase non-receptor type 3 (PTPN3), which is expressed in lymphocytes, enhances lymphocyte activation, suggesting PTPN3 may act as an immune checkpoint molecule. However, PTPN3 is also expressed in various cancers, and the biological significance of PTPN3 in cancer cells is still not well understood, especially for lung neuroendocrine tumor (NET).Therefore, we analyzed the biological significance of PTPN3 in small cell lung cancer and examined the potential for PTPN3 inhibitory treatment as a cancer treatment approach in lung NET including small cell lung cancer (SCLC) and large cell neuroendocrine cancer (LCNEC). Experiments in a mouse xenograft model using allo lymphocytes showed that PTPN3 inhibition in SCLC cells enhanced the anti-tumor effect of PTPN3-suppressed activated lymphocytes. In addition, PTPN3 was associated with increased vascularization, decreased CD8/FOXP3 ratio and cellular immunosuppression in SCLC clinical specimens. Experiments in a mouse xenograft model using autocrine lymphocytes also showed that PTPN3 inhibition in LCNEC cells augmented the anti-tumor effect of PTPN3-suppressed activated lymphocytes. In vitro experiments showed that PTPN3 is involved in the induction of malignant traits such as proliferation, invasion and migration. Signaling from PTPN3 is mediated by MAPK and PI3K signals via tyrosine kinase phosphorylation through CACNA1G calcium channel. Our results show that PTPN3 suppression is associated with lymphocyte activation and cancer suppression in lung NET. These results suggest that PTPN3 suppression could be a new method of cancer treatment and a major step in the development of new cancer immunotherapies.

High efficacy of disopyramide in the management of ventricular fibrillation storms in a patient with Brugada syndrome.

The patient was a 57-year-old man with Brugada syndrome, who had been implanted with a implantable cardioverter defibrillator (ICD). The frequency of ventricular fibrillation (VF) started to increase about 4 years after ICD implantation, occurring, at worst, six times in one night. Immediately after starting oral administration of disopyramide, VF stopped occurring. He then discontinued taking disopyramide, but immediately after the discontinuation VF started occurring again, so he restarted taking disopyramide. Thereafter, VF completely stopped occurring. Findings observed in our case suggest that disopyramide could be added in our arsenal of medications for treating arrhythmic storms in patient with Brugada syndrome.

Beneficial effect of combination therapy comprising angiotensin II receptor blocker plus calcium channel blocker on plasma adiponectin levels.

The study aim was to examine the effect of combination therapy comprising angiotensin receptor blocker plus calcium antagonist on post-treatment plasma adiponectin levels compared to pretreatment levels. There was a significant gender difference in the relationship between preadiponectin level and age. In the search for contributing factors for treatment-based changes in adiponectin levels, these effects of gender and age were considered in statistical analysis. The adiponectin level in the combination therapy group was further increased compared to that in each of the monotherapy groups, despite there being no significant difference in antihypertensive effect, indicating that the combined medication provided an effect beyond that of lowering blood pressure.

Surgical treatment of clinical N1 non-small cell lung cancer: ongoing controversy over diagnosis and prognosis.

PURPOSE: The preoperative assessment of nodal status in lung cancer is complicated and problematic for physicians and surgeons. Although many patients with clinical N1 (cN1) non-small cell lung cancer (NSCLC) are candidates for surgical treatment, these patients represent a heterogeneous subgroup with unpredictable survival. We conducted this study to evaluate the surgical results of cN1 disease and to attempt to clarify the delicate issues surrounding its diagnosis and prognosis. METHODS: The subjects of this study were 187 consecutive patients with cN1 adenocarcinoma or squamous cell carcinoma of the lung, who underwent complete resection without induction therapy. RESULTS: Only 25% of the adenocarcinomas and 54% of the squamous cell carcinomas were correctly diagnosed as N1 disease preoperatively. Multiple logistic regression analyses revealed that adenocarcinoma (P = 0.0141) was a significant predictor of pN2. Multivariate analyses revealed that nodal metastasis (P < 0.0001), large tumor size (P = 0.0079), and high serum carcinoembryonic antigen value (P = 0.0096) were significantly poor prognostic factors in cN1 patients. CONCLUSIONS: It is difficult to diagnose nodal status in patients with cN1 disease, which requires various surgical procedures, including plasty, possibly with adjuvant therapy in a defined high-risk subgroup.

Chemotherapeutic agents potentiate adenoviral gene therapy for pancreatic cancer.

Adenovirus-mediated gene therapy combined with chemotherapeutic agents is expected to represent a new approach for treating pancreatic cancer. However, there have been no reports of definitive effects of chemotherapeutic agents on adenovirus-mediated gene therapies. In the present study, we investigated the effects of chemotherapeutic agents on the transduction efficiency of an adenovirus-based gene therapy. Adenovirus (Ad-NK4) expressing NK4, which acts as a hepatocyte growth factor antagonist, was used as a representative gene therapy. Pancreatic cancer cells infected with Ad-NK4 were treated with chemotherapeutic agents (5-fluorouracil [5FU], cisplatin or etoposide), and the NK4 levels in their culture media were measured. To examine the effects of chemotherapeutic agents in vivo, Ad-NK4 was administered to subcutaneous tumors in mice after treatment with the agents, and the tumor NK4 levels were measured. The NK4 levels in culture media from cells treated with 5FU, cisplatin and etoposide were 5.2-fold (P = 0.026), 6-fold (P < 0.001) and 4.3-fold (P < 0.001) higher than those of untreated cells, respectively. The chemotherapeutic agents also increased Ad-NK4 uptake. The NK4 levels in tumors treated with 5FU, cisplatin and etoposide were 5.4-fold (P = 0.006), 11.8-fold (P < 0.001) and 4.9-fold (P = 0.017) higher than those in untreated tumors, respectively. The present findings suggest that chemotherapeutic agents significantly improve the efficiency of adenovirus-mediated gene transfer in pancreatic cancer. Furthermore, they will contribute to decreases in the adenovirus doses required for gene transfer, thereby controlling the side-effects of adenovirus infection in normal tissues.

Tumor-stromal interactions with direct cell contacts enhance proliferation of human pancreatic carcinoma cells.

Pancreatic ductal adenocarcinoma is often characterized by an abundant desmoplastic stroma that is partially induced by activated pancreatic stellate cells (PSCs). Indirect co-culture has often been used to investigate the effects of cancer-stromal interactions on the proliferation of cancer cells, but the effects of cell-cell adhesion and juxtacrine signaling between cancer and stromal cells cannot be evaluated using this method. This study aimed to establish a simplified direct co-culture system that could be used to quantify populations of cancer cells in co-culture with PSCs, and to evaluate the effects of direct cell contact on the proliferation of cancer cells. We established three green fluorescent protein (GFP)-expressing pancreatic cancer cell lines and were able to quantify them with high reliability and reproducibility, even when co-cultured directly with PSCs, using a color plate reader. We assessed the differential effects of direct and indirect co-culture with PSCs on the proliferation of cancer cells, and found that the proliferation of GFP-expressing pancreatic cancer cell lines was dramatically enhanced by direct co-culture with PSCs, compared with the indirect co-culture system. We also found that direct co-culture of cancer cells and PSCs activated the Notch signaling pathway in both cell types. Direct cell contact between cancer cells and PSCs plays an important role in the control of cancer cell proliferation, and is essential to the understanding of tumor-stromal interactions.

Takotsubo cardiomyopathy complicated by high-grade atrioventricular block: A report of two cases.

The present report describes two female patients aged 39 and 57 years who experienced loss of consciousness and chest pain due to high-grade atrioventricular block. Both patients demonstrated noncontraction centred on the cardiac apex and excessive contraction at the cardiac base on cardiac ultrasonography and left ventriculography, but neither of them demonstrated any significant stenotic lesions on coronary angiography. Furthermore, neither patient showed elevated serum biomarkers of cardiac injury or serum viral antibodies. In a repeat left ventriculogram two weeks later, the left ventricular wall motion disorder had improved in both patients. Based on these findings, the patients were diagnosed with takotsubo cardiomyopathy. Because the high-grade atrioventricular conduction disorder did not improve in spite of the improvement of left ventricular wall motion disorder, permanent pacemaker implantation was performed. It is extremely rare for takotsubo cardiomyopathy to be complicated by high-grade atrioventricular block. In the present study, both patients had takotsubo cardiomyopathy complicated by high-grade atrioventricular block and eventually underwent permanent pacemaker implantation.

Ventricular pacing thresholds following high-energy implantable cardioverter defibrillator shocks in integrated bipolar defibrillation systems.

BACKGROUND: Increased ventricular pacing thresholds have been observed following monophasic implantable cardioverter defibrillator (ICD) shocks. AIM: To examine changes following high-energy biphasic shocks delivered by integrated bipolar ICD systems. METHOD: Ten episodes of ventricular fibrillation (VF) were induced at 10 min intervals in nine pigs with integrated ICD systems. After 10 s of each episode of VF, a 40 J biphasic shock was delivered, which successfully terminated VF (a total of 10 shocks). The bipolar pacing threshold at the right ventricular apex was measured before each shock and at 1 min intervals after each shock. RESULTS: The mean pacing threshold was 0.029+/-0.059 muJ before the first shock and gradually increased to 0.14+/-0.10 muJ after the 10th shock. CONCLUSION: It may be necessary to pace at a high-voltage output following biphasic shocks delivered by integrated bipolar ICD systems.

S100P regulates the collective invasion of pancreatic cancer cells into the lymphatic endothelial monolayer.

Lymph node metastasis is an independent prognostic factor in pancreatic cancer. However, the mechanisms of lymph node colonization are unknown. As a mechanism of lymphatic metastasis, it has been reported for other types of cancer that spheroids from tumor cells cause circular chemorepellent­induced defects (CCIDs) in lymphatic endothelial monolayers. In pancreatic cancer, such mechanisms of metastasis have not been elucidated. The present study evaluated the involvement of this new mechanism of metastasis in pancreatic cancer and investigated the associated factors. In human pancreatic cancer tissue, it was observed that clusters of cancer cells penetrated the wall of lymphatic ducts around the primary tumor. An in vitro co­culture system was then used to analyze the mechanisms of tumor cell­mediated disruption of lymphatic vessels. Time­lapse microscopic imaging revealed that spheroids from pancreatic cancer cells caused circular defects in lymphatic endothelial monolayers. CCID formation ability differed depending on the cell line. Neither aggregation of spheroids nor adhesion to lymphatic endothelial cells (LECs) exhibited a significant correlation with this phenomenon. The addition of supernatant from cultured cancer cells enhanced CCID formation. Microarray analysis revealed that the expression of S100 calcium binding protein P (S100P) was significantly increased when LECs were treated with supernatant from cultured cancer cells. Addition of a S100P antagonist significantly suppressed the migration of LECs and CCID formation. The present findings demonstrated that spheroids from pancreatic cancer cells caused circular defects in lymphatic endothelial monolayers. These CCIDs in pancreatic cancer were partly regulated by S100P, suggesting that S100P may be a promising target to inhibit lymph node metastasis.

Mercury-free preparation and selective reactions of propargyl (and propargylic) Grignard reagents.

ZnBr2 was found to catalyze formation of propargyl and propargylic Grignard reagents, and thus put an end to the standard method using a mercury catalyst. The Grignard reagents were submitted to addition reaction with carbonyl compounds and allylation with the cyclic monoacetate to afford the propargyl-type products selectively. Furthermore, the product from the monoacetate was transformed to an acetylene analogue of 2-(5,6-epoxyisoprostane A2)phosphorylcholines.

Orally administered levofloxacin as prophylaxis against pacemaker infection.

OBJECTIVES: Despite paying careful attention to surgical details and sterile procedures, infection often occurs after pacemaker implantation. The prophylactic use of intravenously or orally administered antibiotics should therefore be considered. The present study aimed to evaluate the efficacy of orally administered levofloxacin (LVFX) as prophylaxis against pacemaker infection. METHODS: Thirty-nine patients who underwent permanent pacemaker implantation or pacemaker generator replacement due to battery depletion were included in the present study. Patients were divided into two groups (groups 1 and 2) and administered different antibiotics accordingly. Group 1 included 19 patients (75.7+/-9.3 years of age; 10 men and nine women) who were intravenously administered 2 g of cefazolin daily for five days postoperatively. Group 2 included 20 patients (73.7+/-14.4 years of age; 10 men and 10 women) who were orally administered 200 mg of LVFX 2 h before surgery and then 400 mg daily for five days thereafter. RESULTS: In group 1, the mean white blood cell concentrations before, and one, four and seven days after surgery were 4979+/-1330/mm(3), 6453+/-1200/mm(3), 5463+/-1303/mm(3) and 5632+/-1154/mm(3), respectively, and in group 2, they were 5931+/-1316/mm(3), 7062+/-1774/mm(3), 5708+/-1402/mm(3) and 5345+/-1506/mm(3), respectively. In group 1, the mean blood C-reactive protein concentrations before, and one, four and seven days after surgery were 0.27+/-0.34 mg/dL, 0.48+/-0.48 mg/dL, 1.04+/-0.99 mg/dL and 0.52+/-0.48 mg/dL, respectively, and in group 2, they were 0.43+/-0.54 mg/dL, 0.52+/-0.27 mg/dL, 0.61+/-0.42 mg/dL and 0.56+/-0.63 mg/dL, respectively. The inflammatory parameters showed similar responses in both groups. CONCLUSIONS: Orally administered LVFX following permanent pacemaker implantation can prevent pacemaker infection as successfully as intravenously administered cefazolin.

Hybrid surgical approach of video-assisted minithoracotomy for lung cancer: significance of direct visualization on quality of surgery.

STUDY OBJECTIVES: Controversy regarding the most suitable surgical approach for treating malignancies of the lung is a matter of continuous discussions. "Complete" video-assisted thoracic surgery (VATS) that is performed using only the vision of a monitor is generally limited to lung resections of minimal difficulty. With the great interest in minimally invasive techniques for treating various pathologies, we have widely applied an integrated surgical approach that combines muscle-sparing minithoracotomy (incision, 4 to 10 cm) and video assistance using mainly direct visualization of the lung resection, which we have called hybrid VATS. The aim of this study is to evaluate the usefulness of hybrid VATS. DESIGN: Retrospective single-center study. INTERVENTIONS: From January 1998 to October 2004, 405 of 678 lobectomies (60%) and 165 of 226 segmentectomies (73%) were performed for primary lung cancer using hybrid VATS. RESULTS: Bronchoplasty was performed in 93 of the 678 patients (14%) who underwent lobectomy and in 11 of the 226 patients (5%) who underwent segmentectomy. Hybrid VATS was utilized in 33% of sleeve lobectomy procedures and in 27% of sleeve segmentectomy procedures. The mean (+/- SD) surgical time using hybrid VATS was 164 +/- 48 min for lobectomy and 158 +/- 35 min for segmentectomy, and the mean blood loss was 166 +/- 120 and 109 +/- 80 mL, respectively. There was one operative mortality (0.2%) secondary to cardiogenic shock. Postoperative complications developed in 11% of patients with p-stage IA disease after undergoing hybrid VATS, in contrast to 19% of patients after undergoing open thoracotomy. The prognosis of patients treated by hybrid VATS was equivalent to that obtained with open thoracotomy. CONCLUSIONS: Minithoracotomy combined with video support that is performed predominantly via direct visualization is a secure, integrated, minimally invasive approach to performing major resection for lung cancer, including atypical procedures such as bronchoplasty. This hybrid VATS can be an acceptable and satisfactory option whenever the performance of complete VATS is considered to be challenging.

Border between N1 and N2 stations in lung carcinoma: lessons from lymph node metastatic patterns of lower lobe tumors.

OBJECTIVE: Distinction of lymph node stations is one of the most crucial topics still not entirely resolved by many lung cancer surgeons. The nodes around the junction of the hilum and mediastinum are key points at issue. We examined the spread pattern of lymph node metastases, investigated the prognosis according to the level of the involved nodes, and conclusively analyzed the border between N1 and N2 stations. METHODS: We reviewed the records of 604 consecutive patients who underwent complete resection for non-small cell lung carcinoma of the lower lobe. RESULTS: There were 390 patients (64.6%) with N0 disease, 127 (21.0%) with N1, and 87 (14.4%) with N2. Whereas 11.3% of patients with right N2 disease had skip metastases limited to the subcarinal nodes, 32.6% of patients with left N2 disease had skip metastases, of which 64.2% had involvement of N2 station nodes, except the subcarinal ones. The overall 5-year survivals of patients with N0, N1, and N2 disease were 71.0%, 50.8%, and 16.7%, respectively (N0 vs N1 P = .0001, N1 vs N2, P < .0001). Although there were no significant differences in survival according to the side of the tumor among patients with N0 or N1 disease, patients with a left N2 tumor had a worse prognosis than those with a right N2 tumor (P = .0387). The overall 5-year survivals of patients with N0, intralobar N1, hilar N1, lower mediastinal N2, and upper mediastinal N2 disease were 71.0%, 60.1%, 38.8%, 24.8%, and 0%, respectively. Significant differences were observed between intralobar N1 and hilar N1 disease ( P = .0489), hilar N1 and lower mediastinal N2 disease (P = .0158), and lower and upper mediastinal N2 disease (P = .0446). Also, the 5-year survivals of patients with involvement up to station 11, up to station 10, and up to station 7 were 41.4%, 37.9% and 37.7%, respectively (difference not significant). CONCLUSIONS: N1 and N2 diseases appeared as a combination of subgroups: intralobar N1 disease, hilar N1 disease, lower mediastinal N2 disease, and upper mediastinal N2 disease. Interestingly, the survivals of patients with involvement up to interlobar nodes (station 11), main bronchus nodes (station 10), and subcarinal nodes (station 7) were identical. These data constitute the basis for a larger investigation to develop a lymph node map in lung cancer.

Successful catheter ablation of ventricular tachycardia originating from the idiopathic saccular apical left ventricular aneurysm.

Left ventricular (LV) aneurysm has been recognized to frequently become a substrate of ventricular tachyarrhythmias. We report a case of a 66-year-old woman with symptomatic sustained monomorphic ventricular tachycardia (SMVT) originating from saccular apical LV aneurysm without definite underlying diseases. We performed catheter ablation using electroanatomical and conventional bipolar potential mapping. During SMVT, we found an area of fragmented potential -40 ms preceding the earliest wide QRS complex in the area of the apical LV aneurysm. Radiofrequency applications were delivered to this area. Since then, SMVT was no longer inducible by programmed electrical stimulation. The patient has remained free of VT recurrences during a subsequent 12-month follow-up period.

Atrial septal defect in apical hypertrophic cardiomyopathy associated with coronary spasm.

Apical hypertrophic cardiomyopathy (HCM) is a well-known myocardial disease, but the additional coexistence of an atrial septal defect (ASD) and coronary spasm is quite rare. We report here on a 62-year-old man suffering from congestive heart failure due to apical HCM complicated by coronary spasm and secundum-type ASD. The transthoracic, transesophageal echocardiography and cardiac catheterization were useful for diagnosing and evaluating of the patient's status. A calcium channel blocker was given to prevent coronary spasm, and a surgical patch closure operation was successfully performed. Afterwards, his symptoms were alleviated.