Pain management in community-dwelling older adults with moderate-to-severe dementia.

BACKGROUND: This study explored visiting nurses' knowledge and beliefs regarding pain management in community-dwelling older adults with moderate-to-severe dementia. METHODS: A cross-sectional study design was used to collect data in 2019. A questionnaire was mailed to nursing managers at 1037 home-visiting nursing stations in Japan. FINDINGS: The final analysis included 230 responses. The mean score on the knowledge and belief statements was 14 out of a possible 18, and respondents with more pain management training obtained a higher total score on knowledge than those without such training (p<.001). More than 95% indicated that they needed training on pain management for older adults with dementia. CONCLUSION: Visiting nurses in Japan require training in pain management for older adults with moderate-to-severe dementia. Despite its usefulness, the current pain management training programme should be improved to enable visiting nurses to manage dementia patients' pain more confidently.

Evaluation of oral immunotherapy efficacy and safety by maintenance dose dependency: A multicenter randomized study.

BACKGROUND: Generally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described. METHODS: A multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes. RESULTS: The year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months. CONCLUSIONS: Reduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT. TRIAL REGISTRATION: UMIN000009373, Multicenter Oral Immunotherapy for Hen's Egg, Cow's Milk, and Wheat-Allergic Children at Outpatient Clinic.

A case report of resected ectopic malignant meningioma with lung metastasis.

INTRODUCTION: Meningioma is mostly a benign tumor, but sometimes it is malignant, and there have been reports of distant metastases. PATIENT CONCERNS: The patient, a woman in her 40s, was under follow-up after resection of an ectopic malignant meningioma originating in the left axilla. She was referred to our department because of a nodule shadow in the right lung on chest computed tomography (CT) 3 years and 5 months postoperatively. DIAGNOSIS: Chest CT showed a 1.0 cm nodule shadow in the right S4, which was positive on positron emission tomography-CT; no abnormality was found in any other organ. Therefore, it was considered to be a metastatic lung tumor. INTERVENTIONS: Right middle lobe partial resection was performed using thoracoscopic surgery, and a diagnosis of pulmonary metastasis of ectopic malignant meningioma was made by histopathology and immunohistochemistry. OUTCOMES: In this case, complete resection was possible. CONCLUSION: Meningioma occurs mainly in the cranium, and occurrence in the soft tissue of the extremities is extremely rare. To our knowledge, ours is the first report of a histologically malignant ectopic meningioma with metastasis to the thoracic cavity.

Frequency and significance of epidermal growth factor receptor mutations detected by PCR methods in patients with non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) is the most important driver gene of non-small cell lung cancer (NSCLC) as EGFR mutations determine the efficacy of EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. In the present study, the comprehensive ability of widely used polymerase chain reaction (PCR) methods to detect EGFR mutations was determined. Among the 35 EGFR mutations detected via the direct sequencing of 73 patients with NSCLC, 11 types were identified in exons 18, 19 and 21. Among the 11 mutation types, all exon 18 and 21 mutations were identified by 2 widely used PCR methods, namely, Scorpion-Amplification Refractory Mutation System and cobas v2. However, among the 9 different exon 19 deletions, 3 types were not identified by the 2 methods. In addition, 25 samples with EGFR mutations were analyzed by the 2 methods, including a sample from a patient with an unidentified exon 19 deletion, the T751_I759 deletion and insertion S; this patient had long-term disease control as a result of EGFR-TKI therapy. The 2 methods could not detect this unidentified deletion, whereas sizing capillary electrophoresis for the comprehensive detection of exon 19 deletions detected this deletion. It is generally thought that patients with exon 19 mutations have higher response rates to EGFR-TKI therapy than patients with exon 21 mutations. The present study confirmed the EGFR mutation status by comparing the mutations with the Catalog Of Somatic Mutations In Cancer, which is the world's largest and most comprehensive resource for analyzing the effects of somatic mutations in human cancers. The predicted frequency of EGFR mutations identified by the 2 methods was 85%. The frequency of mutations detectable by the 2 methods was less for exon 19 than exon 21. Therefore, the results of the present study suggest that decreasing false-negative detection of exon 19 deletions is crucial for the clinical testing of EGFR mutations.

Lobectomy for subsegmental lymph node metastasis of unknown origin.

We report a very rare case of resected subsegmental lymph node metastasis of unknown origin. Hilar (N1) lymph node metastasis of unknown origin has previously been reported, but intrapulmonary lymph node metastasis has not been reported to date. At this patient's first visit to our hospital, an abnormal nodule was found on the upper lung lobe on a chest radiograph. After 4 years' follow-up, the nodule vanished, but a tiny nodule had emerged. 2-Fluoro-2-deoxy-D-glucose positron-emission tomography (FDG-PET) computed tomography was performed, and abnormal accumulation was observed only in the newly emerged intrapulmonary nodule. Right upper lobectomy was performed and a metastatic subsegmental lymph node, but no primary lesion, was found. Our observations suggest that evanescence of a suspicious primary lesion indicates the possibility of metastasis. FDG-PET was useful in this case for detecting lymph node metastases and demonstrating that the primary and further metastatic lesions were absent.

Factors Associated with Gastric Black Spot, White Flat Elevated Mucosa, and Cobblestone-Like Mucosa: A Cross-Sectional Study.

BACKGROUND/AIMS: Previous studies have reported a possible relevance between proton pump inhibitor (PPI) use and 3 new gastric mucosal changes: black spots (BSs), white flat elevated mucosa (WFEM), and cobblestone-like mucosa (CLM). The aim of this study was to investigate the association between these mucosal changes and multiple factors including PPI use. METHODS: All subjects who underwent a routine esophagogastroduodenoscopy (EGD) were successively enrolled. Endoscopists carried out the EGD after being blinded about -information on patient PPI usage and determined the presence of these mucosal changes. The ratio of each factor was -compared in cases with and without each gastric finding. RESULTS: Out of 1,214 patients, BSs were recognized in 75 (6.2%) cases, WFEM in 59 (4.9%), and CLM in 41 (3.4%). In logistic regression analysis, PPI use was significantly correlated with all of these findings (BSs: OR 2.94; 95% CI 1.66-5.21), (WFEM: OR 3.58; 95% CI 1.94-6.61), and (CLM: OR 4.57; 95% CI 2.34-9.96), and Helicobacter pylori eradication was related to BSs (OR 3.01; 95% CI 1.73-5.24) and WFEM (OR 2.11; 95% CI 1.08-4.11). Decision-tree analyses showed that H. pylori eradication was associated with all findings. CONCLUSIONS: All of the considered findings were correlated with PPI and H. pylori eradication.

The Antemortem Diagnosis of Primary Malignant Pericardial Mesothelioma: A Multidisciplinary Evaluation.

A 64-year-old woman complaining of progressive dyspnea was admitted with recurrence of massive pericardial effusion. The patient had been diagnosed with radiation pericarditis based on a previous case of pericardiocentesis. To make a diagnosis and improve her symptoms, imaging examinations and pericardial fenestration were performed. Because of difficulty making a diagnosis, after some months, pericardiotomy and incision of the epicardium were performed. The patient was ultimately diagnosed with primary malignant pericardial mesothelioma of the epithelioid type. Primary malignant pericardial mesothelioma is a rare tumor that is difficult to diagnose. An antemortem diagnosis can be made by a multidisciplinary evaluation.

Analytical performance of the cobas EGFR mutation assay for Japanese non-small-cell lung cancer.

INTRODUCTION: Clinical outcomes in non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations have been reported to be correlated with the use of EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Therefore, it is essential to confirm the presence of EGFR mutations using highly sensitive testing methods. In this study, we compared the performance of the cobas(®) EGFR Mutation Test (cobas EGFR assay) and the therascreen(®) EGFR RGQ PCR Kit (therascreen EGFR assay) for use as an in vitro diagnostic (IVD) product. METHODS: We extracted DNA from 150 formalin-fixed, paraffin-embedded tissue samples from 150 patients diagnosed with NSCLC, and performed a comparative study of the cobas EGFR and therascreen EGFR assay methods. All discordant results were re-analyzed by direct sequencing. RESULTS: The concordance rate between the cobas EGFR assay and the therascreen EGFR assay was 98.0% (145/148). EGFR mutations were detected at a frequency of 40.9% (61/149) in NSCLC specimens using the cobas EGFR assay and 40.2% (60/149) using the therascreen EGFR assay. Three discrepant results were found in this study. Two double mutations were detected by the cobas EGFR assay but only one in the therascreen EGFR assay. No invalid results resulted from sample analysis by the cobas EGFR assay. CONCLUSIONS: Our results show a high concordance rate (98.0%) of cobas EGFR assay with an existing IVD product, the therascreen EGFR assay. Since they are IVD diagnostic products, both assays proved to be simple, validated methods in detecting the most common, clinically significant EGFR mutations and proved to be helpful for appropriate treatment guidance for NSCLC patients.

A case of paravertebral mediastinal chordoma without bone destruction.

We report a unique case of mediastinal paravertebral chordoma without bone destruction in a 47-year-old Japanese woman. She was admitted to hospital after a tumor was incidentally detected on a chest radiograph. The tumor was located in the paravertebral region of the mediastinum and did not show any destruction of the thoracic vertebra radiologically. The tumor was clinically diagnosed as a benign neurogenic tumor and the tumor was easily removed surgically. Microscopically, the tumor mainly consisted of tumor cells with extensively vacuolated cytoplasm, arranged in cord- and nest-like fashion against a myxoid matrix background. Immunohistochemically, the tumor cells showed diffuse positivity for pancytokeratin (AE1/AE3) and vimentin. The tumor cell nuclei were positive for brachyury, which is a key transcription factor of notochordal development. These results confirmed the tumor to be an extraosseous chordoma in the paravertebral mediastinal region, which is an extremely rare location for a chordoma.

The influence of initial target effect-site concentrations of propofol on the similarity of effect-sites concentrations at loss and return of consciousness in elderly female patients with the Diprifusor system.

BACKGROUND: Whether effect-site concentrations of propofol (Cep) at loss of consciousness and return of consciousness (LOC and ROC, respectively) in elderly women using Diprifusor are similar is unclear. We investigated whether differences in initial target Cep (Ctarget) alter similarities between Cep values at LOC and ROC. MATERIALS AND METHODS: In this study, female patients (n = 58, age = 72.5 ± 1.1 years) undergoing knee arthroplasty were administered propofol with Diprifusor. Cep at LOC and ROC were estimated for different Ctarget values (3.0-4.5 µg/ml). Pearson's correlation coefficient analysis and simple regression were performed to assess the relationship between Cep at LOC and ROC for each Ctarget. Differences in correlation coefficients of regression lines obtained from each Ctarget group were determined using the t-test. RESULTS: The different Ctarget groups did not show significant differences in total propofol levels and in Cep values at LOC or ROC. However, Cep at ROC was significantly higher than Cep at LOC when Ctarget was 4.0 and 4.5 µg/ml, whereas these Cep values were not significantly different in low Ctarget groups. Strong positive correlations were observed between Cep at LOC and ROC for all Ctarget groups. Regression coefficients for the different Ctarget groups were not significantly different. Compared to low (≤3.5 µg/ml) Ctarget groups, high Ctarget groups showed significantly shorter time until LOC. Induction quality was not significantly different among the groups. CONCLUSIONS: In elderly women, Cep values at LOC are strong predictors of Cep at ROC when Ctarget is 3.0-4.5 µg/ml. High Ctarget groups (≥4.0 µg/ml) exhibited shorter induction times with normal cardiovascular stability.

Early experience using the da Vinci Surgical System for the treatment of mediastinal tumors.

PURPOSE: The da Vinci Surgical System has been used in only a few cases for treating mediastinal tumors in Japan. Recently, we used the da Vinci Surgical System for various types of anterior and middle mediastinal tumors in clinical practice. We report our early experience using the da Vinci Surgical System. METHODS: Seven patients gave written informed consent to undergo robotic surgery for mediastinal tumor dissection using the da Vinci Surgical System. We evaluated the safety and feasibility of this system for the surgical treatment of mediastinal tumors. RESULTS: Two specialists in thoracic surgery who are certified to use the da Vinci S Surgical System and another specialist acted as an assistant performed the tumor dissection. We were able to access difficult-to-reach areas, such as the mediastinum, safely. All the resected tumors were classified as benign tumors histologically. The average da Vinci setting time was 14.0 min, the average working time was 55.7 min, and the average overall operating time was 125.9 min. The learning curve for the da Vinci setup and manipulation time was short. CONCLUSION: Robotic surgery enables mediastinal tumor dissection in certain cases more safely and easily than conventional video-assisted thoracoscopic surgery and less invasively than open thoracotomy.

Training in robotic surgery using the da Vinci® surgical system for left pneumonectomy and lymph node dissection in an animal model.

OBJECTIVES: In Japan, as of March 2010, only 13 hospitals were using the da Vinci® system and only for selected cases. Few clinical robotic lung surgery has been done in Japan, and there are no standardized training programs, although some exist in the U.S. and are under consideration by the Japanese society for thoracic surgery. We have used the da Vinci S® Surgical System for pneumonectomy and lymph node dissection in pigs. We report and review future possibilities and problems of robotic surgery, especially concerning education, training, safety management and ethical considerations for pneumonectomy and lymph node dissection in clinical practice. METHODS: The da Vinci® system consists of a surgeon's console connected to a patient-side cart, a manipulator unit with three instrument arms and a central arm to guide the endoscope. The surgeon, sitting at the console, triggers highly sensitive motion sensors that transmit the surgeon's movements to the instrument arm. RESULTS: We experienced exactly the same sensation as when performing standard open thoracotomy. Visual recognition is 3-D, and the high manipulation potential allows free movement of the various accessory instruments, exceeding the capacity of a surgeon's hands in video-assisted thoracic surgery (VATS) or even standard thoracotomy. CONCLUSIONS: Robotic surgery achieves at least the same level of operation technique for pneumonectomy and lymph node dissection under standard open thoracotomy, and it seemed as safe and easily performed as conventional VATS. The training program using pigs was effective and holds promise as a system to train thoracic surgeons in robotic lung surgery.

Klotho predicts good clinical outcome in patients with limited-disease small cell lung cancer who received surgery.

BACKGROUND: The important role of surgery in early-stage small cell lung cancer (SCLC) has been recognized, and curative surgical resection is recommended. However, the role of adjuvant chemotherapy for stage I SCLC has not yet been evaluated, and novel approaches focusing on the specific genomic characteristics of SCLC may be invaluable for customized therapy. In this study, we focused on the Klotho gene, which is an anti-aging gene known to be a potential tumor suppressor. We investigated whether the expression of Klotho, assessed by immunohistochemistry, can predict survival in patients with resected SCLC. METHODS: The medical records of patients diagnosed as having limited-disease (LD) SCLC and treated by surgical resection (n=30) at Tokyo Medical University Hospital were retrospectively reviewed. The expression status of Klotho, and of the ATP-binding cassette (ABC) transporters MRP1, MDR and breast cancer resistant protein (BCRP), which can cause resistance to anticancer drugs, including irinotecan, was assessed by immunohistochemical analysis in resected surgical specimens of patients with early-stage SCLC. RESULTS: Of the 30 patients, Klotho expression was seen in the specimens from 18 patients (60.0%), but not in those of the remaining 12 patients (40.0%). The immunostaining for Klotho was mostly localized in the cytoplasm. The expression of Klotho was significantly associated with the overall survival (OS) (ratio 0.088; 95% confidence interval 0.019-0.409; P=0.002). The administration of perioperative chemotherapy had no significant effect in improving the survival, as assessed by the Kaplan-Meier method. However, the patients showing Klotho expression in the resected specimens in p-stage I and II, may have benefited from perioperative chemotherapy. A multivariate analysis revealed no significant association between the expression status of MRP1, MDR or BCRP and the OS. CONCLUSION: Expression of Klotho was predictive of a favorable outcome following resection in limited-disease SCLC patients, and the Klotho expression status may serve as a new biomarker for the need of additional therapies to be developed in the future.

Klotho is a novel biomarker for good survival in resected large cell neuroendocrine carcinoma of the lung.

BACKGROUND: In terms of prognosis, large cell neuroendocrine carcinoma (LCNEC) differs distinctively from other non-small cell lung cancers, with the prognosis of LCNEC being poor, even for early-stage disease. Improvements in survival require a biomarker capable of defining a subset of patients destined to do poorly so that these patients can be targeted for additional therapies, including chemotherapy. In this study, we focused on the Klotho gene, which is an anti-aging gene known to be a potential tumor suppressor. We investigated whether the immunohistochemical expression of Klotho can predict survival patients with resected LCNEC. METHODS: The histological characteristics of patients receiving an initial diagnosis of LCNEC (n=30) at Tokyo Medical University Hospital were retrospectively reviewed, and multiple variables including stage, lymphangioinvasion, lymph node status and the expression of Klotho as identified using an immunohistochemical analysis, were assessed. RESULTS: Immunostaining for Klotho was mostly cytoplasmic, and Klotho expression was seen in 10 patients (33.3%) but not in 20 patients (66.7%). The expression of Klotho was significantly associated with a good outcome of resected patients with LCNEC and Klotho(-) was associated with increased LCNEC risk by multivariate analysis (hazard ratio 4.92, 95% confidence interval 1.04-23.24, p=0.044). Neither lymph node status nor lymphangioinvasion were significantly associated with a poor survival. However, among patients without lymph node metastasis or angioinvasion, the survival benefit of Klotho expression in the primary tumor was significantly higher, compared with that of patients without Klotho expression. CONCLUSION: Klotho staining provides a new biomarker for a good outcome in patients with LCNEC, especially among patients without lymph node metastasis or lymphangioinvasion.

Outcome of photodynamic therapy using NPe6 for bronchogenic carcinomas in central airways >1.0 cm in diameter.

PURPOSE: Most centrally located early lung cancers (CLELC) <1.0 cm in diameter do not invade beyond the bronchial cartilage, and photodynamic therapy (PDT) with Photofrin is currently recommended as a treatment option for such lesions. NPe6 is a second-generation photosensitizer, and because it has a longer absorption band (664 nm) than Photofrin (630 nm), we hypothesized that NPe6-PDT would exert a strong antitumor effect against cancer lesions >1.0 cm in diameter, which are assumed to involve extracartilaginous invasion and to be unsuitable for treatment with Photofrin-PDT. EXPERIMENTAL DESIGN: Between June 2004 and December 2008, 75 patients (91 lesions) with CLELC underwent NPe6-PDT after the extent of their tumors had been assessed by fluorescence bronchoscopy for photodynamic diagnosis and tumor depth had been assessed by optical coherence tomography. RESULTS: Seventy cancer lesions < or =1.0 cm in diameter and 21 lesions >1.0 cm in diameter were identified, and the complete response rate was 94.0% (66 of 70) and 90.4% (19 of 21), respectively. After the mass of large tumors and deeply invasive tumors had been reduced by electrocautery, NPe6-PDT was capable of destroying the residual cancer lesions. CONCLUSION: NPe6-PDT has a strong antitumor effect against CLELCs >1.0 cm in diameter that have invaded beyond the bronchial cartilage, thereby enabling the destruction of residual cancer lesions after mass reduction of large nodular- or polypoid-type lung cancers by electrocautery. The PDT guidelines for lung cancers should therefore be revised because use of NPe6-PDT will enable expansion of the clinical indications for PDT.

Management of multiple primary lung cancer in patients with centrally located early cancer lesions.

BACKGROUND: Patients with centrally located early lung cancer (CLELC) are often heavy smokers with a considerably high risk of multiple primary lung cancer (MPLC) lesions; treatment strategies for such patients must preserve the cardiopulmonary function. METHODS: Between July 2004 and July 2008, patients with CLELC underwent photodynamic therapy (PDT) using NPe6, second-generation photosensitizer at Tokyo Medical University Hospital. Among these patients, we retrospectively analyzed MPLC, which was treated by surgery plus PDT or PDT alone and examined the effectiveness of PDT, and we propose a treatment strategy for patients with MPLC. RESULTS: A total of 64 patients with CLECL received NPe6-PDT, and MPLCs were found in 22 patients (34.4%) using sputum cytology and a bronchoscopical examination using autofluorescence bronchoscopy. Among these 22 patients, 10 patients underwent surgery for primary lung cancer and underwent NPe6-PDT for the treatment of secondary primary CLELC, one patient underwent PDT for CLELC as a primary lesion followed by an operation for peripheral-type lung cancer as a secondary primary lesion, and 11 patients underwent PDT alone for MPLC lesions (28 lesions) that were roentgenographically occult lung cancers. Among these 22 patients with MPLC including peripheral-type lung cancers, which were resected by surgery, all 39 CLELC lesions exhibited a complete response after PDT, and all patients were alive. CONCLUSIONS: For patients with lung cancer with a long-term history of smoking, careful follow-up examinations after surgical resection are needed considering the incidence of metachronous primary lung cancers. PDT can play an important role for the treatment strategy for MPLC.

Cine MRI enables better therapeutic planning than CT in cases of possible lung cancer chest wall invasion.

THE OBJECTIVE: To evaluate the hypothesis that lung cancer treatment planning (whether or not to use induction therapy) can be improved if respiratory dynamic cine magnetic resonance imaging (RD MR) is used. METHOD: We studied 100 lung cancer patients, 76 men and 21 women, scheduled for thoracotomies between May 1997 and December 2006 wherein it was unclear preoperatively whether chest wall invasion would be found. We evaluated the accuracy of RD MR as compared with the findings at operation and postoperative pathology. The accuracy of RD MRI for evaluating chest wall invasion was compared with the efficacy of CT and MRI within our own group of patients and with data from the studies of other investigators. RESULTS: Concerning the evaluation of chest wall invasion, conventional computed tomography (CT) had 43.9% specificity, 60.0% sensitivity and 47.1% accuracy, while RD MR had 68.5% specificity, 100.0% sensitivity and 77.0% accuracy. RD MRI was particularly useful in the evaluation of cancers around 5 cm in diameter that were located adjacent to the diaphragm. Postoperative evaluation of superior sulcus tumor cases that had received induction therapy also showed that the RD MR procedure enabled an accurate decision in 87.5% of cases, and there were no false negative cases. CONCLUSIONS: RD MR is more useful than CT or standard MRI for evaluating thoracic wall invasion. This noninvasive method enhances the reliability of deciding whether induction therapy should be employed.