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Katsuhiko Shimizu,1 Masao Nakata,1 Shinsuke Saisho,1 Masayuki Inubushi,2 Norihito Okumura,3 Tomohiro Murakawa,4 Motohiro Yamashita,5 Hiroshige Nakamura,6 Yoshifumi Sano,7 Kazuhiko Kataoka,8 Shinichi Toyooka9 1Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Japan; 2Division of Nuclear Medicine, Department of Radiology, Kawasaki Medical School, Kurashiki, Japan; 3Department of Thoracic Surgery, Kurashiki Central Hospital, Kurashiki, Japan; 4Department of Thoracic Surgery, Kansai Medical University, Osaka, Japan; 5Department of Thoracic Surgery, Shikoku Cancer Center, Matsuyama, Japan; 6Division of General Thoracic Surgery, Tottori University Hospital, Yonago, Japan; 7Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Toon, Japan; 8Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan; 9Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, JapanCorrespondence: Katsuhiko Shimizu, Department of General Thoracic Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan, Tel +81-86-462-1124, Fax +81-86-464-1124, Email kshimizu@med.kawasaki-m.ac.jpBackground: Induction therapy followed by surgery is recommended as an alternative treatment strategy for locally advanced non-small cell lung cancer (NSCLC). Patients who achieve pathologic response after induction therapy have better outcomes than non-responders; therefore, therapeutic response must be evaluated. Recently, new approaches for monitoring therapeutic responses, which are based on 18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET), have been developed. In this study, we evaluated the predictive value of Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), which uses standardized uptake values corrected for lean body mass (SUL) and total lesion glycolysis (TLG).Methods: A total of 130 patients in the Setouchi Lung Cancer Group who underwent FDG-PET imaging before and after induction therapy prior to a planned surgical resection for NSCLC between 2007 and 2016 were studied retrospectively. The pathologic responses of the primary lung tumors and metastatic lymph nodes were compared with their responses based on evaluation using PERCIST.Results: Postoperative pathologic studies revealed pathologic complete response (pCR) in 42 (32.3%) patients. PERCIST was significantly correlated with pathologic response (p < 0.001). The sensitivity, specificity, and accuracy of PERCIST for predicting pCR were 16.7% (7/42), 88.6% (78/88), and 65.4% (85/130), respectively. Patients with pCR had significantly higher reduction rates in SULpeak for both primary lung tumors and metastatic lymph nodes and TLG for primary tumors than non-responders. In a multivariate Cox regression analysis, tumor site in upper lobes, reduction rate of TLG in primary tumor, and pathologic N0 were independent predictors of favorable recurrence-free survival (RFS).Conclusion: Our study suggested that PERCIST, especially the rate of TLG reduction rate, are useful to predict the pathological response and prognosis after induction therapy. Although improvement is necessary, PERCIST can be a promising method of the post-induction status in lung cancer. Further research is needed to confirm our findings.Keywords: non-small cell lung cancer, FDG PET, PERCIST, SUL, TLG

Purpose: The purpose of this study was to evaluate altered pulmonary function retrospectively after RFA. Methods: This retrospective study comprised 41 ablation sessions for 39 patients (22 men and 17 women; mean age, 64.8 years). Vital capacity (VC) and forced expiratory volume in 1 s (FEV(1)) at 1 and 3 months after RFA were compared with the baseline (i.e., values before RFA). To evaluate the factors that influenced impaired pulmonary function, univariate analysis was performed by using multiple variables. If two or more variables were indicated as statistically significant by univariate analysis, these variables were subjected to multivariate analysis to identify independent factors. Results: The mean VC and FEV(1) before RFA and 1 and 3 months after RFA were 3.04 and 2.24 l, 2.79 and 2.11 l, and 2.85 and 2.13 l, respectively. The values at 1 and 3 months were significantly lower than the baseline. Severe pleuritis after RFA was identified as the independent factor influencing impaired VC at 1 month (P = 0.003). For impaired FEV(1) at 1 month, only severe pleuritis (P = 0.01) was statistically significant by univariate analysis. At 3 months, severe pleuritis (VC, P = 0.019; FEV(1), P = 0.003) and an ablated parenchymal volume ≥20 cm(3) (VC, P = 0.047; FEV(1), P = 0.038) were independent factors for impaired VC and FEV(1). Conclusions: Pulmonary function decreased after RFA. RFA-induced severe pleuritis and ablation of a large volume of marginal parenchyma were associated with impaired pulmonary function. [ABSTRACT FROM AUTHOR]

Study design:A pilot cross-sectional study of patients with acute cervical spinal cord injury (SCI).Objectives:The precise evaluation of the severity of SCI is important for developing novel therapies. Although several biomarkers in cerebrospinal fluid have been tested, few analyses of blood samples have been reported. A novel biomarker for axonal injury, phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H), has been reported to be elevated in blood from rodent SCI model. The aim of this study is to investigate whether pNF-H values in blood can serve as a biomarker to evaluate the severity of patients with SCI.Setting:Tokyo Metropolitan Bokutoh Hospital and National Rehabilitation Center, Japan.Methods:This study enrolled 14 patients with acute cervical SCI. Sequential plasma samples were obtained from 6 h to 21 days after injury. Patients were classified according to American Spinal Injury Association impairment scale (AIS) at the end of the follow-up (average, 229.1 days). Plasma pNF-H values were compared between different AIS grades.Results:In patients with complete SCI, pNF-H became detectable at 12 h after injury and remained elevated at 21 days after injury. There was a statistically significant difference between AIS A (complete paralysis) patients and AIS C (incomplete paralysis) patients.Conclusions:Plasma pNF-H was elevated in accordance with the severity of SCI and reflected a greater magnitude of axonal damage. Therefore, pNF-H is a potential biomarker to independently distinguish AIS A patients (complete SCI) from AIS C-E patients (incomplete SCI). However, further studies are required to evaluate its utility in predicting prognosis of patients in the incomplete category. [ABSTRACT FROM AUTHOR]

Background: Although conventional CT scan-guided needle biopsy is an established diagnostic method for pulmonary lesions, few large studies have been conducted on the diagnostic outcomes of CT fluoroscopy-guided lung biopsy. We have conducted a retrospective analysis to evaluate the diagnostic outcomes of 1,000 CT fluoroscopy-guided lung biopsies performed with 20-gauge coaxial cutting needles.Methods: We determined the diagnostic yield of CT fluoroscopy-guided lung biopsies performed with 20-gauge coaxial cutting needles for 1,000 lesions in 901 patients. Independent risk factors for diagnostic failure (ie, nondiagnostic, false-positive, and false-negative results) were determined with multivariate logistic regression analysis.Results: The biopsy results were nondiagnostic in 0.6% of the lesions (6 of 1,000 lesions). The sensitivity and specificity for the diagnosis of malignancy was 94.2% (741 of 787 lesions) and 99.1% (211 of 213 lesions), respectively; diagnostic accuracy was 95.2% (952 of 1,000 lesions). For lesions measuring or= 3.1 cm (OR, 4.32; p = 0.007).Conclusions: CT fluoroscopy-guided lung biopsy performed with 20-gauge coaxial cutting needles resulted in a high diagnostic yield, even in the case of small lesions. Factors such as the acquisition of two or fewer specimens, lesions in the lower lobe, malignant lesions, and lesions measuring or= 3.1 cm significantly increased the rate of diagnostic failure. [ABSTRACT FROM AUTHOR]

The human DOC-2/DAB2 interactive protein (hDAB2IP) gene is a novel member of the Ras GTPase-activating family and has been demonstrated to be a tumour-suppressor gene inactivated by methylation in several cancers. In this study, we analysed the methylation and expression status of hDAB2IP in gastrointestinal tumours. The promoter region of hDAB2IP was divided into two regions (m2a and m2b) based on our previous report, and the methylation status was determined by bisulphite DNA sequencing in gastric cancer cell lines. The gene expression was semiquantified by real-time RT-PCR, and the results indicated that the m2b promoter region might be an authentic methylation-mediated key regulator of the gene expression. Based on the sequence data, we developed a methylation-specific PCR (MSP) for the m2a and m2b regions and applied it to the samples. Methylation-specific PCR revealed aberrant methylation in the m2a region in eight of 12 gastric cancer cell lines (67%), 16 of 35 gastric cancer tissues (46%) and 29 of 60 colorectal cancer tissues (48%), and in the m2b region in eight of 12 cell lines (67%), 15 of 35 gastric cancer tissues (43%) and 28 of 60 colorectal cancer tissues (47%). On the other hand, seven (12%) and 11 (19%) of 59 gastrointestinal nonmalignant mucosal specimens showed methylation in the m2a and m2b regions, respectively, suggesting that hDAB2IP methylation might play a causative role in carcinogenesis. The 5-aza-2'-deoxycytidine treatment restored the gene expression in the m2b-methylated cell lines, confirming that the methylation caused gene downregulation. We also examined the relationship between hDAB2IP methylation and the clinicopathological features in patients with primary tumours, and determined that methylation in the m2b region was associated with location of the tumour in the stomach. In summary, our results demonstrated that hDAB2IP methylation is frequently present in gastrointestinal tumours and that the resulting gene silencing plays an important role in gastrointestinal carcinogenesis.British Journal of Cancer (2005) 92, 1117-1125. doi:10.1038/sj.bjc.6602458 www.bjcancer.com Published online 15 March 2005 [ABSTRACT FROM AUTHOR]

The present study examined the relationship between methylation of five genes (p16(INK4a), RASSF1A, APC, RARbeta and CDH13) and patient survival in 351 cases of surgically resected lung cancers. While there was no relationship between the other genes and survival, p16(INK4a) methylation was significantly related to unfavourable prognosis in lung adenocarcinomas. [ABSTRACT FROM AUTHOR]