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.

CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection.

Host defense against viruses probably depends on targeted death of infected host cells and then clearance of cellular corpses by macrophages. For this process to be effective, the macrophage must presumably avoid its own virus-induced death. Here we identify one such mechanism. We show that mice lacking the chemokine Ccl5 are immune compromised to the point of delayed viral clearance, excessive airway inflammation and respiratory death after mouse parainfluenza or human influenza virus infection. Virus-inducible levels of Ccl5 are required to prevent apoptosis of virus-infected mouse macrophages in vivo and mouse and human macrophages ex vivo. The protective effect of Ccl5 requires activation of the Ccr5 chemokine receptor and consequent bilateral activation of G(alphai)-PI3K-AKT and G(alphai)-MEK-ERK signaling pathways. The antiapoptotic action of chemokine signaling may therefore allow scavengers to finally stop the host cell-to-cell infectious process.

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.

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.

Clinical response of large cell neuroendocrine carcinoma of the lung to perioperative adjuvant chemotherapy.

Patients with large cell neuroendocrine carcinoma (LCNEC) of the lung are considered to have poor prognosis. However, the benefit of adjuvant chemotherapy for these patients has not been established. In this study, we retrospectively evaluated the efficacy of perioperative chemotherapy for patients with completely resected LCNEC in a single-center setting. From 1999 through 2007, 45 patients with surgically resected LCNEC or mixed LCNEC containing at least one portion of the neuroendocrine differentiation or morphology in non-small cell lung carcinoma were enrolled as participants of this study. Survival rates were calculated by the Kaplan-Meier method. Differences between survival curves were computed with the log-rank test. For multivariate analysis, the Cox's proportional hazards regression model was used to evaluate variables that were significant predictors of survival. Of 1397 patients undergoing surgical resection for primary lung cancer from 1999 to 2007, 45 (3.2%) were classified as LCNEC. Thirty-six (80%) patients were men, and nine (20%) were women. Twenty-four (92%) of 26 patients were present or past smokers. Twenty-three (41%) of 45 patients received perioperative chemotherapy, including seven induction chemotherapies and 16 adjuvant chemotherapies. Survival of patients who underwent perioperative adjuvant chemotherapy was significantly higher than that of those who received surgery alone (P = 0.04). The 5-year survival rate of patients who underwent perioperative adjuvant chemotherapy was 87.5%, whereas that of patients who underwent surgery alone was 58.5%. Even in stage I cases, perioperative adjuvant chemotherapy still favors survival compared with surgery alone. In the Cox proportional hazard multivariate analysis, surgery with or without chemotherapy showed an independent prognostic influence on overall survival (P = 0.0457). Patients who received surgery alone were 9.5 times more likely to die than patients who underwent surgery plus chemotherapy. In conclusion, perioperative chemotherapy will be needed to improve survival in patients with LCNEC. As the population of LCNEC is small, it has been difficult to conduct randomized controlled trials to show the survival benefit of adjuvant chemotherapy. This should be, therefore, evaluated further in prospective multi-institutional phase II trials.

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.

Jugular bulb desaturation during off-pump coronary artery bypass surgery.

PURPOSE: Off-pump coronary artery bypass grafting surgery (OPCAB) frequently results in significant jugular bulb desaturation. Although jugular bulb desaturation during OPCAB may be associated with postoperative cerebral injury, routine jugular bulb oximetry appears to be invasive and expensive. We hypothesized that intraoperative hemodynamic compromise during OPCAB due to cardiac displacement is associated with jugular bulb desaturation which correlates with specific hemodynamic and physiological changes. METHODS: Hemodynamic and physiological data were measured at the following points: (1) before anastomosis of the coronary artery (baseline); (2) during anastomosis of the left anterior descending artery; (3) during anastomosis of the circumflex branch or posterior descending artery; and (4) after chest closure. Arterial, mixed venous, and jugular venous bulb blood gas analyses were performed serially. RESULTS: Jugular bulb desaturation (or= 8 mmHg were likely predictors of the occurrence of jugular bulb desaturation. CONCLUSION: Changes in S(VO2) and Pa(CO2) were associated with jugular bulb oxygen saturation, and S(VO2) or= 8 mmHg had a significant odds ratio for jugular bulb desaturation. We suggest that achieving normal values of S(VO2), Pa(CO2) and CVP may be important to prevent cerebral desaturation during OPCAB.

[Comparative study of anesthesia with remifentanil VS fentanyl in terms of postoperative pain and shivering].

BACKGROUND: Remifentanil is reported to be cleared rapidly more than other any opioids. It is considered that this characteristic may lead to an increase in postoperative pain and shivering after general anesthesia with remifentanil. This study was aimed to examine the influence of remifentanil to these adverse symptoms in comparison with fentanyl. METHODS: The subjects consisted of 41 female patients having undergone a total intravenous anesthesia with remifentanil or/and fentanyl for gynecological laparoscopic surgery. RESULTS: There was no significant difference in the occurrence of postoperative pain. Shivering occurred significantly more frequently in patients who had received remifentanil anesthesia, associated with a significant lower body temperature after general anesthesia. CONCLUSIONS: Careful management of intraoperative body temperature is important to prevent the occurrence of shivering after total intravenous general anesthesia with remifentanil.

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.

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.

Quantitative p16 and ESR1 methylation in the peripheral blood of patients with non-small cell lung cancer.

Inactivation of the p16 and ESR1 tumor suppressor genes by promoter lesion methylation has been reported in many tumor types, including lung cancer. We examined the blood of 95 non-small cell lung cancer patients (66 cases of adenocarcinoma, 23 of squamous cell carcinoma and 6 of large cell carcinoma) and 30 controls consisting of normal subjects and benign disease patients to determine the methylation ratios of p16 and ESR1 using real-time PCR. For both genes, there was a statistically significant difference in the methylation ratio between non-small cell lung cancer patients and controls (p16; p<0.01, ESR1; p<0.001). In addition, there was a strong correlation between the methylation ratio of each gene and old age (p16; p<0.01, ESR1; p<0.001 and p16 or ESR1; p<0.001), and between p16 or ESR1 methylation rate and smoking history (p<0.01). Moreover in Stage I cases, the methylation positive rate of each gene (p16, ESR1 and p16 or ESR1) was higher than the CEA positive rate (p<0.05, p<0.001, p<0.001). Evaluation of p16 and ESR1 promoter methylation in blood using real-time PCR appears to be very useful for lung cancer diagnosis and there is some possibility that these methylated genes might come to represent useful biomarkers for the early detection of lung cancer. Our study results also suggested that comparative evaluation of the methylation ratio before and after surgery might be a powerful tool to predict the prognosis of lung cancer patients.

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.

The present status of postoperative adjuvant chemotherapy for completely resected non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancers, with patients having a poor prognosis. Approximately one third of NSCLC patients present with early-stage disease in which potentially curative resection and multi-modality therapy. Although adjuvant chemotherapy is the standard practice for patients with stages I-III breast and colorectal cancer, the therapeutic efficacy of adjuvant chemotherapy, following complete surgical resection of early stage NSCLC, has not been fully established. Several prospective randomized trials for patients with early stage NSCLC (stages I-IIIA) have confirmed a survival benefit with cisplatin-based adjuvant chemotherapy, as demonstrated in the 1995 meta-analysis performed by the NSCLC Collaborative Group. Studies from Japan have reported that adjuvant therapy with uracil-tegaful (UFT) afforded an improvement of 4% in the 5-year survival rate and a relative risk reduction of 26% in mortality at 5 years among patients with T1-2N0 (stage I) disease. In particular, the Japan Lung Cancer Research Group has demonstrated an improvement in the 5-year survival rate of 11%, favoring chemotherapy with UFT in the subset of patients with T2N0 (stage IB) disease. Two published meta-analyses based on abstracts have estimated a relative risk reduction in mortality of 11-13% at 5 years. The Lung Adjuvant Cisplatin Evaluation (LACE), which was based on a pooled analysis of five randomized trials, has demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with completely resected NSCLC. This benefit depended on stage, being greatest in patients with stage II or IIIA disease. This analysis has suggested that platinum-based adjuvant chemotherapy may have no benefit for patients with stage IA and only a marginal benefit for patients with stage IB. Thus, the information available at the current time supports the administration of adjuvant chemotherapy for patients who have undergone complete resection of stages IB-IIIA NSCLC. Further research is needed to define the role of adjuvant platinum-based chemotherapy and its use, in conjunction with chest radiotherapy as the treatment for patients with resected stages IB and IIIA NSCLC.

Met-RANTES ameliorates fibrous airway obliteration and decreases ERK expression in a murine model of bronchiolitis obliterans.

OBJECTIVES: Bronchiolitis obliterans (BO) is the main cause of late mortality among long-term survivors of lung transplantation. Chemokine-chemokine receptor (CCR) interaction and subsequent recruitment of infiltrating cells to the graft are early events in the development of chronic rejection of transplanted lungs. The present study investigated whether blockade of chemokine receptors CCR1 and CCR5 with Met-regulated-on-activation, normal T cells expressed and secreted (RANTES), an amino-terminal modified derivative of RANTES/CCL5, affects the development of BO in murine model and we sought to determine the expression of RANTES/CCL5 and their relationship with extracellular signal-regulated kinase (ERK). MATERIALS AND METHODS: BALB/c mouse tracheas were heterotopically transplanted into C57Black6 recipients and treated for 21 days with either Met-RANTES at 20 microg/day or vehicle. Animals were killed at 21 days after transplantation for histologic examination of ERK expression. RESULTS: RANTES/CCL5 was highly expressed in allografts compare to isografts. Met-RANTES treatment ameliorated fibrous airway obliteration in a mouse model of BO and decreased ERK expression. CONCLUSION: Blockade of chemokine receptors by Met-RANTES ameliorated airway obliteration and decreased ERK expression. These findings suggest that chemokine receptors CCR1 and CCR5 play significant roles in the development of chronic rejection and ERK may be a new molecular target for chronic rejection.

Cytokine responsiveness in cultured human small airway epithelial cells in relation to lung transplantation.

BACKGROUND: We report a new method for collecting and establishing small airway epithelial cells (SAEC). This method enables the evaluation of the cytokine responsiveness of SAEC, which is still unknown. In this study we evaluated intercellular adhesion molecule-1 (ICAM-1) expression on SAEC stimulated with several inflammatory cytokines and compared it with that on large airway epithelial cells (LAEC). MATERIALS AND METHODS: LAEC and SAEC were treated with IFN-gamma, TNF-alpha, IL-1beta, or their combination. ICAM-1 expression under various conditions was quantified by flow cytometry. Furthermore, immunocytochemical staining was performed to determine intranuclear displacement of signal transducer and activator transcription 1 (Stat1) during ICAM-1 expression by various cytokine stimulations. RESULTS: 1) ICAM-1 expression on both LAEC and SAEC was significantly increased by IFN-gamma stimulation alone and synergistically enhanced by IFN-gamma plus TNF-alpha or IL-1beta stimulation, 2) intranuclear displacement of Stat1 in SAEC by the stimulation with IFN-gamma plus TNF-alpha or IL-1beta was recognized earlier in comparison with that by IFN-gamma stimulation alone. CONCLUSION: The previously unknown peripheral cytokine responsiveness and its mechanisms of SAEC were revealed by this study, which contributes to the understanding of chronic lung allograft rejection recognized around small airways.

[Successful management after cardiopulmonary bypass without administration of protamine in a patient with severe food allergy--beneficial result with the use of heparin-coated bypass circuit].

We experienced the anesthetic management for cardiac surgery without the administration of protamine in a patient with severe food allergy. The patient, a 15-year-old boy, who had been avoiding many kinds of food including fish due to severe food allergy, received a correction of ventricular septal defect under cardiopulmonary bypass (CPB). To detect intraoperative drugs, including protamine, which might induce allergic reaction, we performed intradermal tests and prick tests. We used heparin-coated bypass circuit to minimize the amount of heparin necessary for anticoagulation during CPB. After CPB, hemostasis was achieved without the administration of protamine, and the patient received neither transfusion nor blood product throughout the perioperative period. Avoidance of protamine is advisable if the patient is allergic to food especially fish. The use of heparin-coated bypass circuit should be considered to establish hemostasis without protamine after CPB and to reduce blood products.

[Anesthetic experience of endoscopic umbilical cord ligation in a case of twin pregnancy with acardia].

We had an opportunity to engage in anesthetic management for umbilical cord ligation under endoscopy in a case of twin pregnancy with acardia. The patient was a 24-year-old woman. At the time of surgery, she was at 18 weeks and 2 days of pregnancy. Anesthesia was induced with diazepam 10 mg, fentanyl 150 micrograms, and vecuronium 8 mg, and it was maintained with oxygen (1 l.min-1), air (3 l.min-1) and isoflurane 0.8 to 1.2%. To prevent uterine contraction, ritodrine administration was started before surgery and continued throughout the anesthesia. Throughout the surgery, the fetuses remained immobile, with no sign of uterine contractions. However, an arterial blood sample obtained after anesthetic induction showed mild lactic acidosis, suggesting its relation to ritodrine administration. Anesthetic management for fetal surgery is unique in that it is a non-obstetrical surgical procedure performed on a pregnant patient. Particular attention must be directed to specific aspects, such as the anesthetic effect on the fetus, uterine relaxation during peri-operative period, and prevention of spontaneous abortion or premature labor after surgery. The use of tocolytic agents and fetal monitoring remain for further investigation.