Numerous molecular target drugs have been introduced for the treatment of advanced malignancies. In the treatment of lung cancer, epidermoid growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) demonstrate striking antitumor activity in selected EGFR mutation positive patients. Patient selection by biomarker is extremely important to obtain successful results. The anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab, shows a markedly increased response rate, progression free survival of advanced non-squamous cell lung cancer when combined with cytotoxic drugs. The classification of lung cancer is rapidly changing based on the advances in molecular biology. Here, the recent development of new molecular target drugs against lung cancer is thoroughly reviewed in addition to EGFR-TKIs and bevacizumab with special emphasis on the clinical application.

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Objective To clarify the efficacy and safety of therapeutic endoscopic retrograde cholangiopancreatography for the elderly with choledocholithiasis compared with younger patients.
Methods Consecutive therapeutic ERCPs performed between 2005 and 2007 at our institution for 118 patients aged 80 years or older (group A) and 205 patients younger than 80 years old (group B) were retrospectively reviewed. Successful cannulation rate, complete stone clearance rate, complications and prognosis were compared between the two groups.
Results Successful cannulation was achieved in 99.2% in group A versus 99.5% in group B. The complete stone clearance rate was significantly lower in group A than in group B (92.4% versus 99.0%, p<0.01). Plastic stent placement was performed for patients with incomplete duct clearance. There was no significant difference in the early complication rate between group A (5.5%) and group B (6.6%). Procedure-related mortality did not occur. Cholangitis-free survival was similar between the two groups. The short-term prognosis was comparable between those with complete duct clearance and those with biliary stent placement.
Conclusion With a duct clearance rate of more than 90% and plastic stent placement for patients with poor general condition, therapeutic ERCP for choledocholithiasis in patients 80 years of age or older is comparable in safety and effectiveness to that in younger patients.

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Background The elevated D-dimer value is one of the clues used to diagnose acute aortic dissection (AAD), but the rapid D-dimer assay is not used at all emergency hospitals. The fibrinogen/fibrin degradation products (FDP) value is also an indicator of enhanced fibrinolysis and may therefore be a useful marker in patients with AAD. In addition, the association between FDP values and partial thrombosis of the false lumen is not elucidated.
Patients The present study enrolled 50 patients (66.5±11.2 years of age; median, 66.5 years of age, male subjects comprised 60.0% of the series) with AAD who were admitted to the hospital between July 2005 and December 2007 and 57 patients with acute myocardial infarction (AMI; 70.8±10.4 years of age; median, 71.0 years of age, male subjects comprised 71.9% of the current series) served as a control group.
Results The FDP values (μg/mL) in patients with AAD were significantly higher than those of AMI patients (40.2±78.6; median, 14.7 vs. 5.2±9.8; median, 1.7, p<0.001). A receiver operating characteristic curves analysis showed that an elevated FDP level (2.05 μg/mL) was predictive of a diagnosis of AAD with a sensitivity and specificity of 98% and 54%, respectively. The FDP levels of patients (n=14) who had partial thrombosis of the false lumen were significantly higher than in discharged patients without a surgical repair (n=21) who had a patent or complete thrombosis of the false lumen (35.8±43.2; median, 18.8 vs. 14.0±21.3; median, 5.5, p=0.01).
Conclusion The measurement of FDP may therefore be useful for the initial assessment of patients with suspected AAD and in the prediction of thrombotic status of the false lumen.

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Background The progression rate of pneumoconiosis in retired coal miners over ten years has not been studied in Japan.
Methods A retrospective longitudinal study was undertaken using chest X-rays of 1091 pneumoconiosis subjects in Hokkaido, Japan between 1985 and 2005.
Results The final numbers of subjects were 207 (19% of the entry) after 1 decade and 85 (8%) after 2 decades. Sixty-two percent of 207 subjects after 1 decade and 29% of 85 showed progression in 2 decades. Thirty-one percent of ILO category 1 and 55% of category 2 subjects showed progression to complicated pneumoconiosis after 1 decade, and 6% (4 of 64) of category 1 and 6% (5 of 77) of category 2 subjects progressed to complicated pneumoconiosis during 2 decades.
Conclusion The progression of pneumoconiosis was observed after the cessation of dust exposure, especially during the first 10 years.

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Background Empyema due to Candida species is a rare entity, and the significance of isolation of Candida species from the pleural effusion is not fully understood.
Objective To elucidate the clinical features of Candida empyema.
Methods We retrospectively reviewed the cases of 128 patients with culture-positive empyema.
Results These 128 patients included 7 whose cause of empyema was esophago- or gastropleural fistula. Empyema was due to Candida species in 5 of the 7 patients. Primary diseases of these 5 patients were spontaneous esophageal rupture in 3 patients, esophageal rupture due to lung cancer invasion in 1 patient, and gastric ulcer perforation in 1 patient. None of these 5 patients had esophageal candidiasis. Among the 121 other patients with empyema not due to esophago- or gastropleural fistula, no patient had empyema due to Candida.
Conclusion We believe that the empyema in these 5 patients was caused by normal commensal Candida species entering the pleural cavity when the fistula between the gastrointestinal tract and pleural cavity was formed. Isolation of Candida species can be an important clue for suspecting gastrointestinal tract perforation as a cause of empyema.

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Objective In the present study we aim to describe the clinical features and related complications of severe measles requiring hospitalization in Japan in 2007 and 2008.
Methods We extracted the records of patients diagnosed with measles between July and December in 2007 and 2008 from the Diagnosis Procedure Combination (DPC) inpatient database and the verified age distribution of patients with measles requiring hospitalization and the rate of measles-related complications. We also examined the rate of measles patients who were pregnant or had malignancies.
Results We identified 1,037 inpatients in 377 hospitals; 879 in 2007 and 158 in 2008. Overall, 554 (53.4%) were male. Patient age distribution showed two peaks; ≤4 years (21%) and 15-29 years (45%). Ninety (8.7%) patients had pneumonia, 22 (2.1%) had encephalitis, 7 (0.7%) had intestinal complications, 7 (0.7%) had conjunctivitis, 6 (0.6%) had meningitis, and 4 (0.4%) had otitis media. Patients aged ≤14 years were significantly more likely to have pneumonia (16.4%; p<0.001). The rate of encephalitis was relatively low in patients aged ≤14 years (0.9%) compared with those aged 15-29 years (3.0%) and those aged ≥30 years (2.0%); the difference was not statistically significant (p=0.141). Of 31 pregnant women, 10 had spontaneous abortion or stillbirth. Twenty-eight patients had malignancies.
Conclusion The present study adds important information to our knowledge of the clinical features of severe measles. Follow-up monitoring of the trends of this distressing disease using the DPC database will be essential.

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The therapeutic options available for central nervous system (CNS) infections due to resistant Gram-positive cocci remain limited. We report an unusual case of community-acquired methicillin-resistant Staphylococcus aureus meningitis complicated by cerebral infarction in the middle cerebral artery territory in a previously healthy young male. After an initial vancomycin-based regimen, treatment was completed with a seven-week course of linezolid and levofloxacin. The potential role of such a combination and, particularly, linezolid as a first-line therapy in serious CNS infections is also discussed.

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A 67-year-old man suffered an acute anteroseptal myocardial infarction complicated by multiple episodes of ventricular fibrillation, which were not systematically defibrillated by maximum, internal 35-J shocks delivered by an implanted cardioverter defibrillator (ICD). He had suffered from acute inferior myocardial infarction 6 years earlier, complicated with sustained polymorphic ventricular tachycardia (VT). Due to inducibility of sustained VT on an electrophysiologic study, an ICD was implanted. Defibrillation testing performed after healing of anteroseptal infarction was successful with a 10-J safety margin, suggesting that acute myocardial ischemia transiently elevated the internal defibrillation threshold.

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A 75-year-old man was admitted to our hospital in January 2010 for evaluation of syncope and abnormal ECG. ECG showed type 1 ST elevation in lead V₁ and he was diagnosed as Brugada syndrome. During cardiac catheterization, baseline coronary angiography was normal, but intracoronary ergonovine maleate induced spasms of the right and left coronary arteries concomitant with chest pain and ST elevation on ECG. J waves were accentuated or newly developed. Soon after an intracoronary injection of nitroglycerin, chest pain was relieved and ischemia-induced J wave disappeared and the ST segment returned to the same morphology as baseline. Extrastimuli induced ventricular fibrillation. He received an implantable cardioverter-defibrillator. He was also treated with Ca antagonist and isosorbide dinitrate and has had an uneventful course for 5 months.

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Localization of insulinomas by preoperative imaging is critical for successful surgical resection. However, the visualization and localization of small insulinomas by recent imaging modalities still remains a challenge. Here, we report a 77-year-old woman with a small insulinoma successfully localized by performing arterial stimulation and venous sampling (ASVS), and subsequent super-selective CTA (SSCTA). It was not visualized by routine non-invasive imaging tests such as digital subtraction angiography (DSA). The small size (1.0 cm) of the surgically removed tumor supports the usefulness of SSCTA for localizing very small insulinomas.

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We report a case of type 1 diabetes onset and recurrence of Graves' disease during pegylated interferon (PEG-IFN)-alpha plus ribavirin treatment for chronic hepatitis C. The patient was a 55-year-old woman diagnosed with chronic hepatitis at age 46 years. She was treated for Graves' disease at 50 years of age. Because Graves' disease remitted, PEG-IFN-alpha plus ribavirin treatment was started for chronic hepatitis C. She was examined because of complaints of general fatigue, weight loss, and palpitations after 24 weeks of the treatment. She was diagnosed with a recurrence of Graves' disease, and methimazole treatment was started. However, she complained of malaise, thirst, polyuria, and loss of body weight. Her fasting blood glucose level was 292 mg/dL and HbA1c was 9.3%. Serum anti-GAD (glutamic acid decarboxylase) antibodies were 2.2 U/mL. She was diagnosed with type 1 diabetes with ketosis, and insulin treatment was started. Serum anti-GAD antibodies gradually increased to 15.1 U/mL. Graves' disease and type 1 diabetes are often complicated, and the coincidental occurrence of these 2 diseases is known as autoimmune polyglandular syndrome type III. However, only a few cases have shown that these diseases occur after IFN treatment.

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Here we report the case of a 50-year-old woman presenting with weight gain, whole-body edema, and massive ascites. Blood examination revealed primary hypothyroidism with TSH-blocking antibody, and the echocardiogram showed diffuse hypokinesis of the left ventricle with pericardial effusion. Although she received thyroid hormone replacement therapy immediately, her ascites increased and she developed type II respiratory failure requiring transient noninvasive positive pressure ventilation (NIPPV). She recovered following the temporary drainage of the ascites, administration of diuretics, and continuous thyroid hormone replacement. The amount of ascites decreased during therapy, along with an increase in thyroid hormone levels. Finally, the ascites disappeared completely, followed by the normalization of the cardiac wall motion. Herein we report this rare case in detail, and also discuss the mechanism by which primary hypothyroidism induced such severe conditions in our patient.

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In July 2009, a 69-year-old man was admitted to our hospital because an abnormal chest shadow had been noted on medical examination. Chest radiography and computed tomography showed mediastinal and bilateral hilar lymphadenopathy. Bronchoalveolar lavage fluid (BALF) from the right B⁵ revealed an increased CD4/CD8 ratio. Histological examination of the biopsy specimens obtained from the tumor in the left upper bronchus revealed small cell lung cancer, whereas examination of the specimens obtained from the left B³ revealed noncaseating epithelioid cell granulomas containing giant cells, confirming the diagnosis of sarcoidosis. The patient underwent chemotherapy with carboplatin and etoposide without any steroids. After 4 courses of chemotherapy, bronchoscopic examination revealed that the tumor had shrunk, and the BALF CD4/CD8 ratio had decreased; further, no histological evidence of sarcoidosis was seen in specimens obtained from the left B³. Concomitant small cell lung cancer and sarcoidosis is rare. Interestingly, cancer chemotherapy might improve pulmonary sarcoidosis.

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A 21-year-old man had sudden-onset right hemiplegia and aphasia with respiratory infection. A chest X-ray disclosed consolidation in both lungs and magnetic resonance imaging showed an embolism in the left middle cerebral artery. A pelvic computed tomography scan revealed deep venous thrombus in both femoral veins. Patent foramen ovale was detected by transesophageal echocardiogram. Antibodies to M. pneumoniae were highly elevated, and hypercoagulability was subsequently detected. This case suggests that the possible pathogenic mechanism for M. pneumoniae infection-related stroke might be paradoxical brain embolism with deep venous thrombus as a consequence of the hypercoagulability related to this infection.

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A 59-year-old man with a history of prostate hyperplasia was admitted to our hospital for further examination of a lung mass and renal dysfunction. Lung biopsy specimens revealed that inflammatory cells had infiltrated into the blood vessel walls. We initially suspected lymphomatoid granulomatosis, but Epstein Barr virus-encoded small RNA was negative. However, 50% of the infiltrating plasma cells were positive for IgG4. Furthermore, the kidneys and prostate contained abundant IgG4-positive plasma cells. He was diagnosed with IgG4-related sclerosing disease even though serum IgG4 levels were not elevated (45.7 mg/dL). Prednisolone reduced the lung masses and ameliorated renal function, but the serum IgG4 level increased (377 mg/dL). Seronegative IgG4-related sclerosing disease should be considered when patients present with such symptoms and treatment responses, and the secretion of IgG4 might be blocked by its active synthesis.

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We report a 29-year-old woman with a 2.5 year history of mixed connective tissue disease (MCTD) who developed idiopathic portal hypertension (IPH) and thrombocytopenia as a result of hypersplenism. She had recurrent esophagogastric variceal rupture. Hematological examination also revealed low levels of protein C activity. The liver biopsy specimen showed non-specific mild inflammation and no thrombi. However, portal vein thrombosis developed after splenectomy. This was a rare case of severe complications of IPH accompanying MCTD and protein C deficiency.

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We had encountered a 74-year-old woman on hemodialysis therapy suffering from liver abscess of Actinomyces israelii. Percutaneous drainage of the abscess before starting antimicrobial therapy followed by correct microbiological identification and susceptibility test led us to determine long treatment with ampicillin and to a successful outcome. Periodontitis was thought to be a possible entry of actinomyces. Hepatic actinomycosis should be recognized as one of the important infectious diseases among patients of end-stage renal disease.

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