[Paraneoplastic Anti-N-methyl-D-aspartate Receptor Encephalitis Associated with Anterior Mediastinal Mature Teratoma].

We report a 27 years-old previously healthy male admitted to a psychiatric hospital because of abnormal behavior. He was suspected meningoencephalitis with fever, abnormal sweating, muscle tone, confusion, and introduced to the neurology department of our hospital. After admission, increasing convulsions and apnea attack required mechanical ventilation therapy. Anti-N-methyl-D-aspartate( NMDA) - receptor encephalitis was diagnosed based on positive (20-fold) anti-NMDA antibody in cerebrospinal fluid examination. An enhanced chest computed tomography (CT) showed a 43 mm cystic mass with calcification of the anterior mediastinum. He underwent the tumor resection under median sternotomy on the 18th hospital day. The plasmapheresis and steroid therapies were treated after the operation. The consciousness level gradually improved, the patient was withdrawn from the respirator on the post operative day( POD) 35, and transferred to a rehabilitation hospital on POD 60. The pathological result was mature teratoma. However, no specific findings such as inflammatory cell infiltration into nerve components were observed. Anti-NMDA receptor encephalitis was established by Dalmau in 2007 as encephalitis associated with ovarian teratoma. It presents mainly in young adult women with psychiatric symptoms, and requires mechanical ventilation management due to disturbance of consciousness, convulsions, and central hypoventilation in a short period of time. It presents severe symptoms in the acute phase and shows a unique clinical finding with a good prognosis even though it shows a protracted course. Treatment requires prompt tumor detection and early resection, as well as methylprednisolone (mPSL) pulse, plasmapheresis, and high-dose gamma globulin therapy. It is a neurological disease that requires emergency response, and the understanding and prompt response of related departments is important.

[Accuracy of VSRAD Analysis Using Scout Images: Comparison with Conventional 3D-T1WI].

The voxel-based specific regional analysis system for Alzheimer's disease (VSRAD), which targets volume loss in medial temporal lobe, was developed as a sensitive diagnostic tool to detect early stages of Alzheimer's disease. However, conventional three-dimensional T1 -weighted image (3D-T1WI) for VSRAD analysis acquires relatively long acquisition time. Recently, it became possible to acquire Scout images (Scout) for positioning as a 3D image in a short time. The aim of this study was to determine whether Scout was reliable in VSRAD. We measured voxel-based analysis of gray matter volume using VBM and Z-score of medial temporal lobe atrophy using VSRAD advance 2 from conventional 3D-T1WI and Scout. It showed significantly different gray mass between conventional 3D-T1WI and Scout. However, there was no significant difference in Z-score (p=0.41). The Z-scores measured from Scout and conventional 3D-T1WI were significantly correlated (r=0.96, p<0.05). There is a possibility that Scout can be used to detect brain morphometry abnormalities instead of conventional 3D-T1WI in the VSRAD analysis.

Sternal Metastasis of Brain Meningioma - A Case Report.

BACKGROUND: Metastases of meningiomas are infrequent and the site of extracranial metastasis such as the bone is extremely rare. CASE REPORT: A 75-year-old male had a history of five sessions of surgery and gamma-knife treatment for brain meningioma over a period of 29 years. He visited our hospital because he noticed a swelling in his anterior chest 2 years and 6 months after the final treatment. After an open biopsy, histopathological analysis revealed the mass to be a metastatic grade II meningioma. We resected the tumor along with the sternum, ribs, pleura, and pericardium. The patient had recurrences in the thoracic cavity and pericardium postoperatively and received radiation therapy. He also had metastasis in the abdominal cavity, which spread rapidly. CONCLUSION: We report on a rare instance of metastasis to the sternum in a case of atypical meningioma, showing rapid growth and invasion after long-term treatment.

[Lung Metastasis from High-grade Uterine Endometrial Stromal Sarcoma;Report of a Case].

We report a rare case of surgical treatment for lung metastasis from high-grade uterine endometrial stromal sarcoma( ESS) with deep vein thrombosis( DVT) and pulmonary embolism(PE) in a 66-yearold woman. Chest computed tomography (CT) revealed 3 nodules of 3.9 cm, 3.3 cm, 1.2 cm in diameter in the left S6, S8, S9 of the lung. About 1 month after the hysterectomy following anticoagulant treatment with unfractionated heparin/warfarin, the patient underwent left lower lobectomy of the lung and lymph node dissection by video-assisted thoracoscopic surgery( VATS). Microscopic and immunohistochemical examination showed that those tumors were metastases of high-grade ESS. The postoperative course was uneventful and adjuvant chemotherapy by ifosfamide, adriamycin, cisplatin was performed.

[Idiopathic Diffuse Pulmonary Ossification Diagnosed by Lung Biopsy].

A case of a 64-year-old woman who had undergone resection of a femoral giant cell tumor in another hospital 35 years before was referred to our hospital for diabetes education. Chest radiography and computed tomography (CT) revealed diffuse densely calcified nodular lesions that appear to be in both lung fields. Since pulmonary metastases of the giant cell tumor of the bone was suspected, she underwent a lung biopsy, which showed diffuse pulmonary ossification (DPO) of the dendriform type. It is extremely rare that idiopathic DPO is diagnosed by lung biopsy.

[Pigmented Paraganglioma in the Anterior Mediastinum].

Pigmented paraganglioma of the anterior mediastinum is extremely rare. We report a 72-year-old female patient who was pointed out an anterior mediastinum tumor showed by chest computed tomography(CT) scan during a medical check up. The tumor was 50×35 mm showing gradual enlargement and was slightly homogenously contrasted by CT scan and magnetic resonance imaging(MRI). During the resection of the tumor, sudden elevations of both blood pressure up to 205 mmHg and tachycardia up to 131 beat per minate(bpm)was noted on tumor manipulation. Pathologically, the tumor was diagnosed as pigmented paraganglioma with adjacent lymph node metastasis and microscopic extracapsular invasion. The patient is well 5 years post-surgery without recurrence.

[Two Cases of Invasive Thymoma with Taste Disorder].

Two 50s female patients with the taste disorder of sweet taste loss and stage IV a type B2 invasive thymoma underwent surgery at our hospital. One patient with myasthenia gravis (MG) developed postoperative myasthenic crisis and recovered by the treatment with plasma apheresis and steroid pulse therapy. Her taste disorder fully recovered together with her MG symptom. The taste disorder of the other patient without MG had persisted for 3 years after the surgery. The taste disorder of sweet taste loss was reported as one of non-motor symptoms caused by MG-related autoimmune mechanisms associated with thymoma, improving with the therapy for MG. Anti-Kv 1.4 antibody was reported to be positive in nearly half patients with the taste disorder and MG and is speculated to affect selectively the sweet taste receptor.

Paravertebral block via the surgical field versus epidural block for patients undergoing thoracotomy: a randomized clinical trial.

PURPOSE: A paravertebral block (PVB) given via the surgical field can be safer and technically simpler than an epidural block (EP) for postoperative pain control. We conducted this clinical trial to confirm the effectiveness of PVB after thoracotomy. METHODS: In this non-inferiority trial, patients were randomly assigned to receive PVB (n = 35) or EP (n = 35). The primary endpoint was the pain assessed using the visual analog scale (VAS) at rest, 2, 24, and 48 h after thoracotomy, with the non-inferiority margin set at 15 mm. The secondary end points were the pain assessed using the VAS on exercising and on coughing, 2, 24, and 48 h after surgery, respectively, and the complications and need for additional analgesic agents. RESULTS: This trial revealed that PVB was not inferior to EP with respect to the primary end point: The mean VAS scores at rest, 2, 24, and 48 h after thoracotomy were 26.3, 10.8, and 8.3 mm in the PVB group and 23.6, 12.4, and 12.6 mm in the EP group, respectively (P < 0.01 for non-inferiority at all points). There were no significant differences between the groups in the incidence of complications or the need for additional analgesic agents. CONCLUSION: PVB may replace EP for postoperative pain control because of its technical simplicity and safety.

Safety of the paravertebral block in patients ineligible for epidural block undergoing pulmonary resection.

OBJECTIVE: We previously reported the noninferiority of paravertebral block (PVB) to epidural block. In this study, we assessed whether PVB via an intrathoracic approach was also safe for the patients ineligible for epidural block because of, for example, anticoagulation or antiplatelet therapy. METHODS: Patients admitted to our hospital for pulmonary resection between April 2010 and March 2012, and who were ineligible for epidural block for various reasons, were enrolled in this study. A catheter for PVB was inserted in the operative field by the surgeons just before closing the chest. Ropivacaine of 0.2 % was injected at 4 ml/h using an infuser pump for 5 days. Concurrent use of intravenous patient controlled analgesia (IVPCA) for 2 days with PVB was permitted as a post-operative analgesic at the discretion of anesthesiologists. We estimated the post-operative complications in these patients. RESULTS: A total of 35 (15.8 %) consecutive patients were enrolled in this study and successfully completed the study protocol. Thirty-two patients received concurrent IVPCA treatment. Post-operative complications due to PVB were not observed, but other complications included 1 incidence of atrial fibrillation, 1 hypertension, 1 pleural fluid accumulation, 1 respiratory failure requiring mechanical ventilation, and 1 of late chest pain requiring intercostal nerve block. CONCLUSION: This study suggests that PVB is safe in patients ineligible for epidural block and can contribute to their pain relief following pulmonary resection procedure including video-assisted thoracic surgery.

[Effect of the continuous epidural saline infusion for patients with postdural puncture headache after pulmonary resection].

The dual puncture is one of the diseaseful complications at the induction of the epidural anesthesia, which causes severe symptoms of intracranial hypotension such as headache and nausea. The clinical courses of 3 patients with the dual puncture symptoms after pulmonary resections were retrospectively reviewed, and the effect of the continuous epidural saline infusion treatment (CESI) for the dual puncture was evaluated. Pneumococcal empyema developed in 1 patient who had been treated with conservative management. In contrast, the symptoms of the others who were treated with the CESI were quickly recovered or were effectively prevented. This report strongly suggested that the CESI was convenient and effective treatment for dual punctune symptoms by suppressing the cerebrospinal fluid leakage by elevation of the fluid pressure in the extradural space.

Inflammatory pseudotumor suspected of lung cancer treated by thoracoscopic resection.

We report a relatively rare surgical treatment for two cases of inflammatory pseudotumors of the lung. In case 1, a 52-year-old male with a history of left chest pain was admitted to our hospital for an abnormal nodule with an irregular margin that was detected in the left upper lung field. The nodule, measuring 15 mm in diameter, was larger than the one observed six months earlier, which had been removed by a thoracoscopic resection. In case 2, a 64-year-old female with a history of chronic cough and hemoptysis was admitted to our hospital, and an abnormal nodule with pleural indentation was detected in the lower left lung field. The nodule, measuring 8 mm in diameter, was also removed by a thoracoscopic resection. In both cases, the histologic examination enabled us to diagnose the lesion as an inflammatory pseudotumor. In general, it is very difficult to differentiate inflammatory pseudotumors from malignant tumors of the lung. The best treatment for inflammatory pseudotumors is usually early and complete surgical resection, since it can lead to improved survival. Therefore, we consider thoracoscopy-aided surgery to be less invasive and more useful than other surgical methods in the diagnosis and treatment of inflammatory pseudotumor of the lung.

Reciprocal and complementary role of MET amplification and EGFR T790M mutation in acquired resistance to kinase inhibitors in lung cancer.

PURPOSE: In epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy for lung cancer patients, acquired resistance develops almost inevitably and this limits the improvement in patient outcomes. EGFR T790M mutation and MET amplification are the two main mechanisms underlying this resistance, but the relationship between these two mechanisms is unclear. In this study, we explored their relationship using in vitro models and autopsy specimens. EXPERIMENTAL DESIGN: Erlotinib-resistant HCC827 (HCC827ER) cells were developed by chronic exposure to erlotinib at increasing concentrations. HCC827EPR cells were also developed by chronic exposure to erlotinib in the presence of PHA-665,752 (a MET TKI). The erlotinib-resistant mechanisms of these cells were analyzed. In addition, 33 autopsy tumor samples from 6 lung adenocarcinoma patients harboring multiple gefitinib-refractory tumors were analyzed. RESULTS: HCC827ER developed MET amplification, and clinically relevant resistance occurred at ≥4-fold MET gene copy number gain (CNG). By contrast, HCC827EPR developed T790M without MET CNG. Of six patients harboring gefitinib-refractory tumors, three exhibited T790M only, one exhibited MET amplification only, and the other two exhibited T790M and/or MET amplification depending on the lesion sites. In these gefitinib-refractory tumors, T790M developed in 93% (14 of 15) of tumors without MET gene CNGs, in 80% (4 of 5) of tumors with moderate MET gene CNGs (<4-fold), and in only 8% (1 of 13) of tumors with MET amplification (≥4-fold). CONCLUSIONS: These results indicate a reciprocal and complementary relationship between T790M and MET amplification and the necessity of concurrent inhibition of both for further improving patient outcomes.

Serum carcinoembryonic antigen level as a surrogate marker for the evaluation of tumor response to chemotherapy in nonsmall cell lung cancer.

PURPOSE: Carcinoembryonic antigen (CEA) is a tumor marker widely used for nonsmall cell lung cancer (NSCLC). The aim of this study was to evaluate changes in serum CEA levels as a surrogate marker for tumor response to chemotherapy in NSCLC. METHODS: From 1995 through 2005, we retrospectively analyzed 24 NSCLC patients who had high serum CEA levels (>5 ng/ml) and who received chemotherapy followed by surgery. We compared serum CEA levels with tumor response, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) or World Health Organization (WHO) criteria, as well as with histological response. RESULTS: Serum CEA levels after chemotherapy significantly decreased in patients who achieved partial response, defined by RECIST or WHO criteria (p = 0.004 and p = 0.008, respectively), when compared with the CEA levels before chemotherapy. In contrast, there was no significant difference in CEA levels in patients with either stable disease or no response to chemotherapy. They decreased significantly, however, in patients in whom less than one-third of tumor cells was viable by pathological examination, but not in patients in whom more than a third was viable (p = 0.008). Using the receiver-operating characteristic (ROC) curve analysis, we found that a 60% reduction of CEA levels was an appropriate cutoff value in predicting a good response to chemotherapy. When the value was set at that level, the sensitivity of CEA for RECIST was 82%, and the specificity was 69%. CONCLUSION: Serum CEA concentration was a useful surrogate marker for the evaluation of tumor response to chemotherapy and seemed to be comparable with RECIST in NSCLC patients who had elevated CEA levels prior to treatment.

Effect of gefitinib on the survival of patients with recurrence of lung adenocarcinoma after surgery: a retrospective case-matching cohort study.

BACKGROUND: Patients with lung adenocarcinoma who carry epidermal growth factor receptor (EGFR) gene mutations respond remarkably well to EGFR tyrosine kinase inhibitor (EGFR-TKI), gefitinib, or erlotinib. However, the effect of EGFR-TKI treatment on the prolongation of overall survival (OS) of these patients remains uncertain, although several recent studies have shown prolongation of progression free survival compared with cytotoxic chemotherapy. METHODS: A total of 304 patients with lung adenocarcinoma who had postoperative recurrent disease were studied. To eliminate potential biases as possible, the matching of four potential predictive factors of responsiveness to EGFR-TKI led to the identification of 81 pairs of patients (those who were treated with gefitinib and those who were not). A deletion mutation in exon 19 and a point mutation (L858R) in exon 21 of the EGFR gene were also analyzed. We compared the OS between the two groups. RESULTS: OS in the gefitinib group was significantly longer than in the control group (median, 63 vs. 41 months; p = 0.015). EGFR mutations were detected in 65 out of 129 patients (50%) in the whole sample. EGFR mutational status was not an independent prognostic factor of gefitinib benefit; rather, it was a predictive factor. CONCLUSIONS: This study strongly suggested that gefitinib treatment improved OS of lung adenocarcinoma patients who had postoperative recurrence, especially those carrying EGFR mutations.

Efficacy of erlotinib for brain and leptomeningeal metastases in patients with lung adenocarcinoma who showed initial good response to gefitinib.

INTRODUCTION: The efficacy of high-dose (1250 mg/d) gefitinib for the treatment of leptomeningeal metastasis in a patient with lung cancer harboring a mutation in the epidermal growth factor receptor (EGFR) gene was previously reported. We speculate that erlotinib, instead of high dose of gefitinib, may be also effective for the treatment of central nervous system (CNS) lesions, as trough serum concentration of erlotinib is nine times higher than that of gefitinib. PATIENTS AND METHODS: Patients with lung cancer in whom CNS lesions developed after an initial good response to gefitinib for extra CNS lesions were enrolled in the study. Tumor response, performance status, neurologic symptoms, and survival were retrospectively evaluated. RESULTS: All seven patients had EGFR mutations in their primary tumors except one patient. The median interval between gefitinib withdrawal and erlotinib administration was 5 days. Three patients showed partial response, three had stable disease, and one had progressive disease. Performance status and symptoms improved in five patients. The overall survival from the initiation of erlotinib treatment ranged from 15 to 530 days (median, 88 days). CONCLUSIONS: Erlotinib was a reasonable option for the treatment of CNS diseases that appeared after a good initial response of extra CNS disease to gefitinib.

Comparison of methods for placing and managing a silastic drain after pulmonary resection.

We have been using a silastic drain [Blake drain (BD)] after pulmonary resection by different placement methods and reviewed the daily amount of drainage in each patient. A 19-Fr BD was placed for each of 110 patients. First, a drain was inserted from the anterior chest wall and the tip reached the dorsal part of the diaphragm [anterior-to-posterior (AP)]. For the others [posterior-to-anterior (PA); n=37], we inserted a drain from the lower intercostal space, turned it around the apex and placed its tip in the lower front. Patients in the AP group included those placed under a water seal (AP-WS; n=43) or suction (AP-SC; n=30). The reference group consisted of 68 patients with a 32-Fr plastic drain during the same period [conventional drains (CD)]. The amount of drainage on the day of surgery in the PA group was significantly higher than that in the AP-WS group (P<0.0001) and similar to that in the CD group (P=0.54). The mean amount of drainage on postoperative day 1 and total amounts accumulating during drain placement showed no significant differences between the four groups. A BD placed using a PA approach with suction might be efficient for drainage.

Clinicopathological features of small-sized non-small cell lung cancer with mediastinal lymph node metastasis.

INTRODUCTION: In clinical practice, peripheral small-sized lung cancers with positive mediastinal lymph nodes are sometimes detected. To understand the characteristics of these aggressive tumors, we reviewed the clinicopathological features of small-sized non-small cell lung cancer patients with mediastinal lymph node metastasis resected in our institution. METHODS: We studied 360 patients with small-sized lung lesions with a maximum diameter of 2 cm or less. The clinicopathological characteristics of each patient were reviewed and compared among the subgroups, which were stratified according to pathological nodal status. RESULTS: 21 patients (5.8%) had a positive mediastinal lymph node. Among them, 17 patients had lung lesions larger than 1.5 cm. No mediastinal nodal involvement was found in patients with squamous cell carcinomas. In contrast, mediastinal nodal involvement was significantly common in patients with poorly differentiated carcinoma (P=0.004) and high serum carcinoembryonic antigen levels detected during preoperative evaluation (P=0.006). None of the 14 patients with upper lobe tumor had a positive subcarinal lymph node. Lower lobe tumors frequently developed extensive multiple-level involvement, which included the upper mediastinum. Radiographic evaluation of pN2 patients using computed tomography revealed a total absence of ground-glass opacity, or the presence of a small area of ground-glass opacity. CONCLUSIONS: Most small-sized non-small cell lung cancer cases with mediastinal lymph node metastasis were invasive adenocarcinoma with poor differentiation, which usually showed a solid shadow without ground-glass opacity on computed tomography.

Regulation of the human PDZK1 expression by peroxisome proliferator-activated receptor alpha.

Although PDZK1 is a well-known adaptor protein, the mechanisms for its role in transcriptional regulation are largely unknown. The peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-activated transcription factor that plays an important role in the regulation of lipid homeostasis. Previously, we established a tetracycline-regulated human cell line that can be induced to express PPARalpha and identified candidate target genes, one of which was PDZK1. In this study, we cloned and characterized the promoter region of the human pdzk1 gene and determined the PPAR response element. Finally, we demonstrate that endogenous PPARalpha regulates PDZK1 expression.

Antisense activity of 2',4'-BNA targeted to PPAR gamma in THP-1 and HCT116 cells.

2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) is a nucleic acid analogue that has high affinity binding to its complementary RNA. Peroxisome proliferator-activated receptor (PPAR) y belongs to the nuclear hormone receptor superfamily and is a drug target in the treatment of type 2 diabetes. Here, we show the antisense effects of 2',4'-BNA oligonucleotides against PPARy in the human monocytic leukaemia cell line THP-1 and the human colorectal tumor cell line HCT116.