Development of beryllium-based neutron target system with three-layer structure for accelerator-based neutron source for boron neutron capture therapy.

The iBNCT project team with University of Tsukuba is developing an accelerator-based neutron source. Regarding neutron target material, our project has applied beryllium. To deal with large heat load and blistering of the target system, we developed a three-layer structure for the target system that includes a blistering mitigation material between the beryllium used as the neutron generator and the copper heat sink. The three materials were bonded through diffusion bonding using a hot isostatic pressing method. Based on several verifications, our project chose palladium as the intermediate layer. A prototype of the neutron target system was produced. We will verify that sufficient neutrons for BNCT treatment are generated by the device in the near future.

A case of orbital metastasis as disease progression of anaplastic lymphoma kinase-positive lung cancer treated with crizotinib.

Orbital metastasis of lung cancer is rare. It often causes visual disorder. To date, there are only a few case reports. Crizotinib is an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor that leads to responses in most patients with ALK-positive non-small-cell lung cancer. Visual disorder is one of the popular adverse events of crizotinib, but the symptom almost decreases over time. We report a case of orbital metastasis as the disease progression of ALK-positive lung cancer treated with crizotinib. It should be kept in mind that orbital metastasis can be the disease progression of lung adenocarcinoma with ALK translocation treated with crizotinib. When physicians encounter a patient receiving crizotinib with visual disorder, we must distinguish between adverse events and orbital metastasis.

Efficacy of azithromycin for treatment of acute exacerbation of chronic fibrosing interstitial pneumonia: a prospective, open-label study with historical controls.

BACKGROUND: Acute exacerbation of chronic fibrosing interstitial pneumonia (AE-CFIP) is an often fatal condition with no established treatment. Recently, macrolides were found to be beneficial in cases of acute lung injury. OBJECTIVES: To examine the clinical effectiveness and safety of intravenous azithromycin in patients hospitalized for AE-CFIP. METHODS: A prospective, open-label study with historical controls was conducted. Twenty consecutive patients with AE-CFIP received azithromycin. They were compared with a historical cohort treated with fluoroquinolone (n = 56). All patients received high-dose steroid pulse therapy. The primary end point was mortality at 60 days. The secondary end point was safety of intravenous azithromycin in patients with AE-CFIP. Inverse probability of treatment weighting (IPTW) using the propensity score was performed to investigate the relationship between azithromycin use and survival time. RESULTS: Mortality was significantly lower in the patients treated with azithromycin than in those treated with fluoroquinolone (mortality rate at 60 days: 20 vs. 69.6%, p < 0.001; median survival time: not reached vs. 29.5 days, p < 0.001). The IPTW adjusted hazard of mortality at 60 days in patients receiving azithromycin was 0.17 (95% CI 0.05-0.61). No serious adverse events were observed. CONCLUSIONS: Azithromycin was associated with improved outcomes in patients with AE-CFIP. Further studies are needed to verify this finding (Clinical trial JMA-IIA00095).

Alkaline phosphatase flare phenomenon following epidermal growth factor receptor-tyrosine kinase inhibitor treatment of non-small cell lung cancer: Report of a case and case review.

Alkaline phosphatase (ALP) flare phenomenon documented as scintigraphic flare phenomenon due to elevated serum ALP levels produced by osteoblasts reflects an osteoblastic reaction in response to the effective therapy of non-small cell lung cancer (NSCLC). Here, we report a case of ALP flare following gefitinib treatment for NSCLC. We also retrospectively analyzed the prevalence of ALP flare in lung cancer patients treated via epidermal growth factor receptor-tyrosine kinase inhibitor in our hospital. Recognition of this phenomenon is important for physicians treating NSCLC patients to avoid discontinuation of a potentially beneficial treatment because of misdiagnosis for refractory multiple bone metastasis or adverse effect.

Successful polymyxin B hemoperfusion treatment associated with serial reduction of serum anti-CADM-140/MDA5 antibody levels in rapidly progressive interstitial lung disease with amyopathic dermatomyositis.

Clinically amyopathic dermatomyositis (CADM), a subtype of dermatomyositis with subtle or no muscle involvement, is occasionally accompanied by fatal, rapidly progressive interstitial lung disease (RP-ILD) that is resistant to aggressive immunosuppressive therapy. The presence of anti-CADM-140/MDA5 antibodies is diagnostic for patients with dermatomyositis (particularly CADM) and is known to be strongly associated with the pathogenesis, disease activity, and mortality of RP-ILD. Polymyxin-B direct hemoperfusion (PMX-DHP), originally developed for the removal of endotoxin, has been demonstrated to be effective for treating various types of acute respiratory failure. We describe a patient with amyopathic dermatomyositis who developed RP-ILD characterized by elevated anti-CADM-140/MDA5 autoantibodies, was resistant to combined steroid and immunosuppressant therapy, and was treated successfully with PMX-DHP. To our knowledge, this is the first case to indicate a serial reduction of anti-CADM-140/MDA5 autoantibodies, associated with clinical improvement, following PMX-DHP. Early intervention using PMX-DHP may improve the prognosis of RP-ILD accompanied by CADM.

Hermansky-Pudlak syndrome type 4 with interstitial pneumonia.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, bleeding tendency, and lysosomal accumulation of ceroid-like material, with occasional development of interstitial pneumonia (IP). Nine genetically distinct subtypes of HPS are known in humans; IP develops primarily in types 1 and 4. Most reported cases of HPS with IP are type 1, and there are no published reports of type 4 in Japanese individuals. A 58-year-old man with congenital oculocutaneous albinism and progressive dyspnea for 1 month was admitted to our hospital. We administered high-dose corticosteroids on the basis of a diagnosis of acute exacerbation of interstitial pneumonia. Respiratory symptoms and the findings of high-resolution computed tomography (CT) showed improvement. He was diagnosed with HPS type 4 with interstitial pneumonia on the basis of gene analysis. He has been receiving pirfenidone for 1 year and his condition is stable. This is the first report on the use of pirfenidone for HPS with IP caused by a novel mutation in the HPS4 gene. We conclude that HPS should be suspected in patients with albinism and interstitial pneumonia. High-dose corticosteroid treatment may be useful in cases of acute exacerbation of interstitial pneumonia due to HPS-4, and pirfenidone may be useful and well tolerated in patients with HPS-4.

Fibroproliferative changes on high-resolution CT in the acute respiratory distress syndrome predict mortality and ventilator dependency: a prospective observational cohort study.

OBJECTIVES: To examine whether the extent of fibroproliferative changes on high-resolution CT (HRCT) scan influences prognosis, ventilator dependency and the associated outcomes in patients with early acute respiratory distress syndrome (ARDS). DESIGN: A prospective observational cohort study. SETTING: Intensive care unit in a teaching hospital. PARTICIPANTS: 85 patients with ARDS who met American-European Consensus Conference Criteria and eligible criteria. INTERVENTIONS: HRCT scans were performed and prospectively evaluated by two independent observers on the day of diagnosis and graded into six findings according to the extent of fibroproliferation. An overall HRCT score was obtained by previously published method. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was 60-day mortality. Secondary outcomes included the number of ventilator-free days, organ failure-free days, the incidence of barotraumas and the occurrence of ventilator-associated pneumonia. RESULTS: Higher HRCT scores were associated with statistically significant decreases in organ failure-free days as well as ventilator-free days. Multivariate Cox proportional hazards model showed that the HRCT score remained an independent risk factor for mortality (HR 1.20; 95% CI 1.06 to 1.36; p=0.005). Multivariate analysis also revealed that the CT score had predictive value for ventilator weaning within 28 days (OR 0.63; 95% CI 0.48 to 0.82; p=0.0006) as well as for an incidence of barotraumas (OR 1.61; 95% CI 1.08 to 2.38; p=0.018) and for an occurrence of ventilator-associated pneumonia (OR 1.46; 95% CI 1.13 to 1.89; p=0.004). A HRCT score <210 enabled prediction of 60-day survival with 71% sensitivity and 72% specificity and of ventilator-weaning within 28 days with 75% sensitivity and 76% specificity. CONCLUSIONS: Pulmonary fibroproliferation assessed by HRCT in patients with early ARDS predicts increased mortality with an increased susceptibility to multiple organ failure, including ventilator dependency and its associated outcomes.

A case of primary mediastinal ependymoma.

A 50-year-old female complained of back pain. Computed tomography showed a well-defined spindle-shaped mass 3.4 x 1.0 cm in size in the left paravertebral posterior mediastinum at the Th 3-4 level. The tumor was completely resected via thoracoscopic surgery, which showed no invasion into the surrounding tissue. It consisted of a cyst with a tiny mural solid element. By means of histological and immunohistochemical examinations, we diagnosed the tumor as ependymoma, and the patient remains alive 59 months after resection. As far as we know, 8 reported cases with primary mediastinal ependymoma have been reported. They had the following specific characteristics: (1) All patients were adult females; (2) The tumors were usually located at the paravertebral upper mediastinum; (3) Most of the tumors consisted of cystic and solid elements; (4) The tumors usually made no invasion into the surrounding tissues, though 2 cases had lymph-node metastases.

Selection of sublobar resection for c-stage IA non-small cell lung cancer based on a combination of structural imaging by CT and functional imaging by FDG PET.

PURPOSE: The purpose of this study was to establish criteria for the indication of sublobar resection or lobectomy in cT1N0M0 non-small cell lung cancer (NSCLC), based on information from both computed tomography (CT) and fluorodeoxyglucose positron emission tomography (FDG PET). MATERIALS AND METHODS: A total of 248 cT1N0M0 NSCLC tumors treated surgically were subjected to high-resolution or thin-slice CT (HR/TSCT) study, and 99 of these tumors were also subjected to FDG PET study. Four types of data were collected: (1) tumor size based on HR/TSCT (0-10 mm, 11-20 mm or 21-30 mm); (2) percentage of ground-glass opacity (GGO) region (GGO type or solid type); (3) pathological type (invasive cancer [INVC] or non-INVC [NINVC]); (4) FDG uptake in the tumor (grades 0, 1, and 2). RESULTS: One of 42 tumors (2.4%) less than 1 cm in size, 29 of 132 tumors (22.0%) 1-2 cm in size, and 25 of 74 tumors (33.8%) 2-3 cm in size were judged to be INVC (p = 0.0002). GGO type tumors (2.3%) were less likely to be INVC than solid type tumors (32.9%) (p <0.0001). None of the 28 GGO tumors less than 1 cm in size was INVC; however, the possibility of INVC remained in solid type tumors less than 1 cm in size. In tumors whose diameter was more than 1 cm, INVC was possible regardless of their size or character (GGO or solid). One of 23 (4.3%), 4 of 33 (12.1%) and 14 of 43 tumors (32.6%) whose FDG uptake showed grades 0, 1, and 2, respectively, microscopically revealed INVC (p = 0.0028). All tumors whose FDG uptake was grade 0 and whose size was less than 1 cm were NINVC. On the other hand, tumors whose FDG uptake was grade 1 or 2 or whose size was more than 1 cm retained the possibility of INVC. All 5 tumors (5.0%) which were found to have lymph node metastasis showed grade 2 FDG uptake. CONCLUSION: The criteria for operation for cT1N0M0 NSCLC based on HR/TSCT and FDG PET findings are the following: (1) a tumor less than 1 cm in size and either a GGO type or whose PET grade is 0 (wedge resection); (2) a tumor greater than 1 cm in size and whose PET grade is 0 or 1 (segmentectomy with lymph node dissection); or (3) a tumor whose PET grade is 2 (lobectomy with systemic lymph node dissection).

Radical excision of thymic adenocarcinoma with selective cerebral perfusion.

Most cases of thymic carcinoma have some invasion to neighboring organs when diagnosed, and it is generally difficult to completely remove. We adopted selective cerebral perfusion as a cerebral protection and successfully performed resection of a thymic adenocarcinoma that involved the superior vena cava, left brachiocephalic vein, right brachiocephalic artery and vein, and left common carotid artery in a 47-year-old woman. Even if multiple great vessels were involved by mediastinal malignant tumor, complete resection with selective cerebral perfusion could be safely performed.

Treatment of a fractured ultraflex stent causing tracheal stenosis.

We report on a case of a fractured Ultraflex stent after placement for malignant tracheal stenosis. The patient was a 49-year-old female with adenoid cystic carcinoma of the trachea causing airway stenosis. She was treated by non-covered Ultraflex stent followed by chemoradiotherapy. Twenty months after stent placement, more than half of the distal end of the stent was fractured and caused airway stenosis, while there was no tumor regrowth. After dilation by balloon and bougienage using an endotracheal tube, an additional non-covered Ultraflex stent was placed within the first one, resulting in successful dilation. The patient is now well without any problem with the stent, 12 months after the second stent placement.

Three cases of multiple thymoma with a review of the literature.

Three cases of patients with synchronous multiple thymoma are reported. Two patients had two thymomas each and the remaining patient had three. The thymomas in each patient all displayed similar histological findings, of which the WHO histological classification were type B2, A and B1, respectively. With a modified Masaoka staging system, the thymomas were determined to be stages II-1 and I in patient 1, one of stage III and two of stage I in patient 2, and two of stage II-1 in patient 3. We reviewed nine reported cases of multiple thymoma in which histological findings were provided and discuss whether they developed from multi-centric origin or from intra-thymic metastasis.

Microscopic-sized "microthymoma" in patients with myasthenia gravis.

BACKGROUND: In 2005, Cheuk et al reported two patients with microscopic-sized thymomas and proposed the term microthymoma to distinguish it from the nodular hyperplasia of thymic epithelium, so-called microscopic thymoma. Here, we present microthymomas that were found in 196 patients with myasthenia gravis (MG) who had undergone thymectomy. MATERIALS AND METHODS: Thymic tissues in 196 patients with MG who underwent thymectomy or thymothymomectomy were examined. Of these patients, 73 patients had thymoma indicated by CT before surgery, and the other 123 patients had no mediastinal tumors. From the resected thymic tissues, an average of 14 hematoxylin-eosin-stained sections (range, 4 to 55 sections) were prepared for microscopic examination. The histologic type of the thymoma was classified according to the World Health Organization (WHO) classification. RESULTS: From the 196 patients, we found three microthymomas in 3 patients (1.5%). While these three tumors could not be seen grossly in pathology section, they were found microscopically (range, 2 to 4 mm). The histologic subtype according to the WHO classification system was B1 in one patient and B2 in two patients. CONCLUSION: Microthymoma was found in 3 of 196 patients (1.5%) with MG. Microthymoma might exist in thymus of patients with MG, even in patients who have no thymoma indicated by CT.

Successful steroid treatment for fibrosing mediastinitis and sclerosing cervicitis.

The use of steroids to successfully treat a 75-year-old woman with fibrosing mediastinitis and sclerosing cervicitis causing a stricture of the left common carotid artery is reported. Biopsy specimens showed collagenous fibers and fibroblasts with moderate infiltration of lymphocytes. The mediastinal and neck lesions were significantly reduced, with almost complete resolution of arterial stricture, 3 months after initiating administration of prednisolone at 20 mg/d.

The efficacy of epidural analgesia after video-assisted thoracoscopic surgery: a randomized control study.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) is known to reduce the severity of pain after surgery. However, it has not yet been established whether epidural anesthesia/analgesia (EA) is necessary after VATS. We therefore conducted a randomized control study to examine whether or not EA is necessary for pain control after VATS. PATIENTS AND METHODS: Forty-six patients undergoing VATS were randomly allocated to one of 2 groups: 24 who were given EA after the procedure (EA group) and 22 who were not (NEA group). Patients in the EA group received a continuous infusion of fentanyl and bupivacaine via an epidural catheter for 2 days after VATS. The degree of postoperative pain was assessed on the total dose of additional analgesics administered, a visual analog scale (VAS), a verbal pain score at rest (VPS-R) and on movement (VPS-M), from the day of surgery to the 2nd postoperative day (2 POD). RESULTS: Additional use of rectal diclofenac sodium and intramuscular pentazocine was more frequent in the NEA group than in the EA group (p<0.05). The VAS, VPS-R, and VPS-M scores were significantly lower in the EA group than in the NEA group at 0 POD, from 0 to 1 POD, and from 0 to 2 POD, respectively (p<0.0001-0.05). Stepwise regression analysis revealed that EA was a significant independent variable of VPS-R and VPS-M from 0 to 1 POD (p<0.05). However, the incidence of nausea/vomiting in the EA group was 29%, which was more frequent than in the NEA group (5%) (p<0.05). CONCLUSION: While EA causes nausea/vomiting in some patients, it is effective for pain control until 1 POD after VATS, especially for pain on movements.

Extrapleural pneumonectomy via a lower door open thoracotomy with reconstruction of the diaphragm and pericardium using autologous materials for mesothelioma.

We performed extrapleural pneumonectomy (EPP) with combined resection of the diaphragm and pericardium via a lower door open (LDO) thoracotomy to treat right malignant pleural mesothelioma (MPM) in a 57-year-old man. Specifically, we extended the standard posterolateral thoracotomy skin incision along the anterior costal arch, and performed the thoracotomy by cutting into the 6th to 9th costal cartilage. The resulting defect of the diaphragm and pericardium were reconstructed with a reversed latissimus dorsi (LD) muscle flap and a fascia lata graft, respectively. The patient had an uneventful postoperative course without dyspnea or dysfunction of the extremities. The LDO thoracotomy provided a good operative field, especially for the costo- and cardiophrenic angles, allowing a complete resection of the diaphragm to be performed easily. Furthermore, the reversed LD muscle flap and fascia lata graft proved to be ideal autologous materials for reconstruction of both the diaphragm and the pericardium.

Sparganum mansoni parasitic infection in the lung showing a nodule.

Reported herein is a 57-year-old man infected by Sparganum mansoni, a kind of tapeworm, showing a solitary nodule of the middle lobe of the right lung. Because a transbronchial biopsy could not diagnose the nodule, a right middle lobectomy was performed on suspicion of malignant tumor. The lesion was diagnosed as sparganosis by histological and immuno-serological examinations. Histological examination revealed granulomatous inflammation with neutrophil and eosinophil infiltration around the worm and interstitial pneumonia surrounding the nodule. Moreover, vasculitis with foreign body giant cell was seen around the lesion. To the authors' knowledge this is the second case of sparganosis limited in the lung, and the current report presents the first detailed histological description of a pulmonary sparganosis case.

Kissing pleural metastases from metastatic osteosarcoma of the lung.

Two patients with osteosarcoma lung metastases of which migrated to the parietal pleura due to contact are reported. The first patient was a 16-year-old male who had a pleural metastasis in the diaphragm within an area in contact with a single lung metastasis. Both of the tumors were resected, followed by systemic chemotherapy. Nine months after the resection of the first metastases, two other lung metastases were found which were resected after chemotherapy. The patient is alive without recurrence 84 months after the first resection of the metastases. The second patient was an 11-year-old female with a pleural metastasis of osteosarcoma which was within an area in contact with a single lung metastasis, which had been resected 4 months before. We concluded (1) that a lung metastasis of osteosarcoma occasionally metastasizes to the pleura due to contact; and (2) that because this kissing metastases of osteosarcoma could be cured by a complete resection, the intrathoracic cavity should be thoroughly observed.

Absence of gallium uptake in unicentric and multicentric Castleman's disease.

Castleman's disease is a rare and poorly understood condition involving lymph nodes at various sites, predominantly in the mediastinum. Individuals with this disease often present with lymphadenopathy and general symptoms suggestive of lymphomatous disease, and they are at risk of developing malignant lymphoma. It is thus important to distinguish Castleman's disease from other lymphoproliferative disorders. 67Ga scintigraphy is a non-invasive and practical diagnostic tool for the investigation of patients with lymphoproliferative disorders. However, the value of this technique for the diagnosis of Castleman's disease is not clear. Here, we describe five consecutive patients with various types of Castleman's disease and show that none of these individuals exhibited 67Ga uptake. Our results suggest the potential value of 67Ga scintigraphy in both the diagnosis and management of Castleman's disease.

Changes in respiratory condition after thymectomy for patients with myasthenia gravis.

BACKGROUND: Anesthesia without muscle relaxants has been reported to be effective for early extubation after thymectomy, but postoperative respiratory status of the patients has not been studied intensively. METHODS: Fifty-two consecutive patients undergoing thymectomies for myasthenia gravis (MG) were evaluated. RESULTS: Forty-two (81%) of the 52 patients were extubated in the operating room, and 49 (94%) patients were extubated within 24 hours. However, 6 (12%) patients required subsequent reintubation for respiratory support. There was a sudden increase in the respiratory rate (RR) and PaCO(2). The mean value of the increase in PaCO(2) at the time of reintubation was 23 mmHg (12-58 mmHg). The mean value of the increase in RR above the preoperative level at the time of reintubation was 16/min (7-30/min). In univariate analysis, vital capacity (VC), %VC, the preoperative pyridostigmine dose and the duration of surgery correlated with reintubation, but with multivariate analyses, the pyridostigmine dose was the only significant factor related to reintubation. CONCLUSION: The patients who received at least or more than 240 mg of pyridostigmine should be monitored carefully after tracheal extubation.