Tumor Spread Through Air Spaces Identifies a Distinct Subgroup With Poor Prognosis in Surgically Resected Lung Pleomorphic Carcinoma
|
|
- Darrell Atkins
- 5 years ago
- Views:
Transcription
1 Q15 Q1 Q6 Q2 [ Original Research ] Tumor Spread Through Air Spaces Identifies a Distinct Subgroup With Poor Prognosis in Surgically Resected Lung Pleomorphic Carcinoma Shintaro Yokoyama, MD, PhD; Tomoyuki Murakami, MD, PhD; Hiroyuki Tao, MD, PhD; Hideko Onoda, MD, PhD; Akio Hara, MD, PhD; Ryohei Miyazaki, MD, PhD; Masashi Furukawa, MD, PhD; Masataro Hayashi, MD, PhD; Hidetoshi Inokawa, MD, PhD; Kazunori Okabe, MD, PhD; and Yoshito Akagi, MD, PhD BACKGROUND: Tumor spread through air spaces (STAS) has recently been reported as a novel form of lung adenocarcinoma invasion that can negatively affect survival; however, its role in pleomorphic carcinoma remains unclear. The goal of this study was to characterize tumor STAS in pleomorphic carcinoma, including its association with clinicopathologic features and prognosis. METHODS: Tumor specimens obtained from 35 consecutive patients with pleomorphic carcinoma who underwent surgical resection between 9 and 15 were reviewed. Tumor STAS was defined as tumor cells spreading within the air spaces in the surrounding lung parenchyma beyond the edge of the primary tumor. RESULTS: Fourteen patients (%) had evidence of STAS-positive pleomorphic carcinomas. Three types of morphologic findings were observed: single cells, small tumor cell clusters, and tumor nests. Tumor necrosis tended to be more prevalent in STAS-positive tumors than in STAS-negative tumors (P ¼.94). Patients with STAS experienced significantly worse recurrence-free survival (P ¼.5) and overall survival (P ¼.2) rates than those without STAS. Moreover, multivariate analysis revealed that tumor STAS was an independent risk factor for both recurrence (P ¼.14) and poor overall survival (P ¼.42). CONCLUSIONS: In this first study of its kind, tumor STAS in patients with pleomorphic carcinoma was shown to be associated with high recurrence rates and poor survival after surgical resection. Hence, tumor STAS can serve as a predictor of postoperative survival; this information will enable better risk stratification and more effective clinical management of patients with this rare type of tumor. CHEST 18; -(-):--- KEY WORDS: lung cancer; pathology lung cancer; surgery oncology ABBREVIATIONS: HR = hazard ratio; NSCLC = non-small cell lung cancer; OS = overall survival; RFS = recurrence-free survival; STAKS = spread through a knife surface; STAS = spread through air spaces AFFILIATIONS: From the Division of Thoracic Surgery (Drs Yokoyama, Tao, Hara, Miyazaki, Furukawa, Hayashi, Inokawa, and Okabe), Department of Surgery, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Japan; Department of Clinical Research (Drs Yokoyama and Murakami), National Hospital Organization Yamaguchi- Ube Medical Center, Ube, Japan; Department of Surgery (Drs Yokoyama and Akagi), Kurume University School of Medicine, Kurume, Japan; Department of Pathology (Dr Murakami), National Hospital Organization Kanmon Medical Center, Shimonoseki, Japan; and the Department of Radiology (Dr Onoda), National Hospital Organization Yamaguchi- Ube Medical Center, Ube, Japan. FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study. Q3 Q4 CORRESPONDENCE TO: Shintaro Yokoyama, MD, PhD, Division of Thoracic Surgery, Department of Surgery, National Hospital Organization Yamaguchi-Ube Medical Center, 685 Higashi-kiwa, Ube, , Japan; yokoyama_shintarou@med.kurume-u.ac.jp Q5 Copyright Ó 18 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: chestjournal.org 1 FLA 5.5. DTD Š CHEST1778_proof Š 1 July 18 Š 2:7 am Š EO: CHEST
2 Q7 Lung pleomorphic carcinoma, categorized as a subset of sarcomatoid carcinoma according to the latest World Health Organization classification, 1 is rare: it accounts for approximately.4% of all non-small cell lung cancers (NSCLCs). 2,3 It is widely recognized as a high-grade malignancy with a reported 5-year overall survival (OS) of only % to 48%, even after surgical resection. 4-7 Patients with unresectable pleomorphic carcinoma that responds poorly to conventional chemotherapy have been reported; their median OS was only 5 to 8 months. 8-1 Thus far, these tumors have not been sufficiently characterized, largely owing to their rarity. However, selecting appropriate treatment strategies requires understanding the underlying clinicopathologic features and prognostic factors associated with this malignancy. Tumor spread through air spaces (STAS) has recently been described as an important route of tumor Patients and Methods Patient Cohort Our institutional review board approved this retrospective study (approval identification number YUMC 29-12), and written informed consent for using materials and clinical information was obtained from each patient. Thirty-seven consecutive patients with lung pleomorphic carcinoma underwent surgical resection at National Hospital Organization Yamaguchi-Ube Medical Center between 9 and 15. Following a detailed review of the medical records, two patients were excluded from the cohort; one had committed suicide 2 months following surgery, and the other had undergone tumor wedge resection for pathologic diagnosis. Therefore, 35 patients were included in the analysis. Pathologic stage was assigned according to the TNM Classification of Malignant Tumors (8th edition). 16 None of the patients received preoperative chemotherapy and/or radiotherapy, and each received a clinical follow-up examination at least every 6 months following surgery that included CT assessment. Histopathologic Evaluation Hematoxylin and eosin-stained slides of resected tumor specimens acquired from formalin-fixed paraffin-embedded tissues were microscopically reviewed and evaluated by two pathologists (S. Y. and T. M.) who were blinded to the patients clinical features and survival outcomes; any disagreements were resolved by consensus. Pathologic diagnoses were made according to the 15 World Health Organization classification 1 and confirmed with immunohistochemistry when necessary. Given that pleomorphic carcinoma as defined is a poorly differentiated NSCLC comprising at least 1% spindle and/or giant cells, 1 pure spindle cell carcinomas or giant cell carcinomas were excluded. Comprehensive histologic subtyping was performed in each case, including the evaluation of spindle or giant cell components as well as epithelial elements. Because tumor necrosis is reportedly a significant prognostic factor, 6 the presence of necrosis was also recorded. STAS was defined as tumor cells within air spaces in the surrounding lung parenchyma beyond the edge (ie, the smooth surface clearly identified in a low-power field) of the primary tumor. 12,13,15 STAS invasion. It also carries prognostic implications in patients with lung adenocarcinoma given that significantly higher recurrence rates, as well as poorer OS, have consistently been reported in patients with lung adenocarcinoma with STAS following surgical resection Moreover, a recent study revealed that STAS was prognostic in patients with squamous cell carcinoma of the lung who underwent surgical resection. 15 However, the prevalence of STAS in pleomorphic carcinoma and its association with patients clinicopathologic characteristics and prognoses have yet to be characterized. We therefore retrospectively investigated the clinicopathologic findings of patients with resected lung pleomorphic carcinoma and sought to characterize the significance and prognostic implications of STAS. was classified into three groups based on morphologic findings: (1) single cells, defined as the presence of only one floating tumor cell in the alveolar space; (2) small tumor cell clusters, defined as a few tumor cells floating in the same; and (3) tumor nests, which are clearly identifiable within a low-magnification field (Fig 1). The edges of tumors containing an invasive mucinous adenocarcinoma component were defined as the alveolar spaces lacking tumor mucin, because tumor clusters are often observed in alveolar spaces that are filled with mucin products. In addition, previously described discriminative methods were used to distinguish STAS from artificially detached tumor cells arising from tumor dissection, namely spread through a knife surface (STAKS). 12,15,17,18 STAS was identified by the presence of tumor cells within air spaces; these were mostly contiguous but were sometimes randomly scattered across the lung tissue. Tissue fragmentations both with and without jagged edges were carefully identified and deemed to be STAKS. STAS was also distinguished from alveolar macrophages according to morphologic features; the former were characterized by a high nuclear-to-cytoplasmic ratio and nuclear atypia, whereas the latter exhibited small nuclei and foamy cytoplasm that sometimes contained faint pigments. The distance between the edge of the tumor and the farthest STAS was measured by using an ocular WHN1X-H micrometer (Olympus Optical Co. Ltd.). The number of alveolar spaces was also counted to rule out the influence of inconsistent inflation of the lung specimens during processing. The farthest distance between the edge of the tumor and that of the circumferential lung tissue section was also measured with a ruler to determine the size of the area surrounding the pathologically examined tumor. Statistical Analysis The associations between STAS and clinicopathologic features were evaluated by using Fisher exact test for categorical variables and Student t test for numerical variables. Recurrence-free survival (RFS) was defined as the interval between the date of surgical resection and that of detection of recurrence; OS was defined as the interval between the date of surgical resection and that of death or the last follow-up visit. Survival curves to estimate RFS and OS were generated by using Original Research [ - # - CHEST ] FLA 5.5. DTD Š CHEST1778_proof Š 1 July 18 Š 2:7 am Š EO: CHEST
3 print & web 4C=FPO Figure 1 A-D, Representative histopathologic images of tumor spread through air spaces (STAS) in pleomorphic carcinoma. A, Low-power image of a tumor section (magnification, ), comprising spindle cell carcinoma, giant cell carcinoma, and adenocarcinoma components. B, High-power view of the boxed region in (A), showing single-cell STAS (arrowheads) and small tumor cell cluster STAS (arrows) around the tumor (magnification, ). C, Low-power image of tumor section (magnification, ), comprising spindle cell carcinoma and adenocarcinoma components. D, High-power view of the boxed region in (C), showing STAS of tumor nests (arrows) near the tumor (magnification, ). the Kaplan-Meier method and compared by using the log-rank test. Cox proportional hazards regression models were used to assess the prognostic value of each factor found to be significant on univariate analysis, as well as to adjust for potential confounders when Results The baseline clinicopathologic characteristics of the study patients are summarized in Table 1. A total of 27 male (77%) and eight female (23%) patients with a median age of 62 years (range: years) were investigated. The median follow-up period in patients without recurrence was 36 months; the overall 5-year survival rate was 65.5%. Thirty-three patients (94%) underwent pulmonary lobectomy, and two (6%) underwent bilobectomy; all patients underwent routine systematic dissection of the hilar and mediastinal lymph nodes, and were confirmed to have achieved R resection using microscopy. Ten patients (29%) had pathologic stage III disease. Of all patients, 12 (34%) experienced recurrence during the follow-up period; 11 (31%) experienced distant recurrence outside of the ipsilateral hemithorax; and one (3%) experienced regional recurrence of the tumor as an intrapulmonary identifying independent risk factors using multivariate analysis. All P values were based on two-sided tests; P values <.5 were considered statistically significant. JMP software version 13 (SAS Institute, Inc.) was used to perform all statistical analyses. metastasis in a second ipsilateral lobe. With respect to prognosis, eight patients (23%) died following surgery: seven patients (%) died due to recurrence and progression of pleomorphic carcinoma; and one patient (3%) died of acute exacerbation of underlying interstitial pneumoniae 28 months following surgery. STAS was observed in 14 patients (%); representative microphotographs of STAS in pleomorphic carcinoma are shown in Figure 1. In terms of predominant morphologic patterns, there were two patients (14%) with single-cell STAS, 1 (71%) with small tumor cell cluster STAS, and two (14%) with tumor nest STAS. The median distance between the edge of the tumor and the farthest STAS was 1,75 mm (range: 45-5, mm). Moreover, the median number of alveolar spaces between the tumor edge and farthest STAS was seven (range: 1-36). Q chestjournal.org 3 FLA 5.5. DTD Š CHEST1778_proof Š 1 July 18 Š 2:7 am Š EO: CHEST
4 Q12 TABLE 1 ] Patient Characteristics (N ¼ 35) Characteristic Values Clinical factors Sex Male 27 (77.1%) Female 8 (22.9%) Age, y Median [range] 62. [35-91] Smoking Current 19 (54.3%) Ex-smoker 9 (25.7%) Never 7 (.%) Surgical procedure Lobectomy 33 (94.3%) Bilobectomy 2 (5.7%) Pathologic factors Tumor size (mm) Median [range] 38 [11 85] T classification T1 T1b 2 (5.7%) T1c 6 (17.1%) T2 T2a 17 (48.6%) T2b 3 (8.6%) T3 4 (11.4%) T4 3 (8.6%) N classification N 24 (68.6%) N1 4 (11.4%) N2 7 (.%) Stage I IA2 2 (5.7%) IA3 5 (14.3%) IB 13 (37.1%) II IIA 1 (2.9%) IIB 4 (11.4%) III IIIA 7 (.%) IIIB 3 (8.6%) Pleural invasion 19 (54.3%) 1 8 (22.9%) 2 3 (8.6%) 3 5 (14.3%) (Continued) TABLE 1 ] (Continued) Characteristic Values Lymphatic invasion Absent 24 (68.6%) Present 11 (31.4%) Vascular invasion Absent 13 (37.1%) Present 22 (62.9%) Observed distance from tumor edge, mm Median [range] 14 [6 24] Necrosis Absent 19 (54.3%) Present 16 (45.7%) Spindle cell carcinoma component Absent 3 (8.6%) Present 32 (91.4%) Giant cell carcinoma component Absent 1 (28.6%) Present 25 (71.4%) Adenocarcinoma component Absent 7 (.%) Present 28 (.%) Lepidic pattern Absent 8 (22.9%) Present (57.1%) Acinar pattern Absent 6 (17.1%) Present 22 (62.9%) Papillary pattern Absent 16 (45.7%) Present 12 (34.3%) Micropapillary pattern Absent 27 (77.1%) Present 1 (2.9%) Solid pattern Absent 16 (45.7%) Present 12 (34.3%) Mucinous adenocarcinoma Absent 26 (74.3%) Present 2 (5.7%) Squamous cell carcinoma component (Continued) Original Research [ - # - CHEST ] FLA 5.5. DTD Š CHEST1778_proof Š 1 July 18 Š 2:7 am Š EO: CHEST
5 Q8 TABLE 1 ] (Continued) Characteristic Values Absent 26 (74.3%) Present 9 (25.7%) STAS Absent 21 (.%) Present 14 (.%) STAS ¼ spread through air spaces. Table 2 shows the distribution of clinicopathologic characteristics according to the presence of STAS. There were no significant correlations between STAS and most clinicopathologic features, including pathologic findings of spindle cell carcinoma (P ¼ 1.), giant cell carcinoma (P ¼.151), adenocarcinoma (P ¼.676), and squamous cell carcinoma (P ¼ 1.). Furthermore, no significant associations between STAS and histological adenocarcinoma subtypes were found. The most common STAS pattern among our patients was small tumor cell clusters, whereas a micropapillary component was observed in one patient only (Fig 1). Notably, STAS tended to be more prevalent in tumors exhibiting necrosis (P ¼.94). Kaplan-Meier analysis was conducted to compare survival rates according to the presence of STAS (Fig 2). STAS-positive patients had significantly worse RFS and OS than STAS-negative patients (P ¼.5 and P ¼.2, respectively). Stratified analyses based on pathologic stage were performed to further assess the prognostic relevance of STAS (Fig 3). STAS-positive stage I/II patients experienced reduced RFS and OS rates compared with their STAS-negative counterparts, although the differences were not significant (P ¼.13 and P ¼.319). Conversely, patients with stage III disease who also exhibited STAS experienced significantly poorer RFS and OS (P ¼.23 and P ¼.2). Using Cox proportional hazards regression models, tumor stage, presence of necrosis, and presence of STAS were identified as significant predictors of both RFS (P ¼.31, P ¼.1, and P ¼.6, respectively) and OS (P ¼.19, P ¼.6, and P ¼.2) (Table 3). Additional multivariate models were applied to identify independent prognostic factors, although they may have been of limited value owing to the small number of included patients (Table 4). On multivariate analysis, presence of necrosis (P ¼.29) and STAS (P ¼.14) remained significant predictors of recurrence, whereas tumor stage did not (P ¼.96). However, tumor stage (P ¼.8) and presence of STAS (P ¼.42) were found to be independent risk factors for poorer OS. Discussion Tumor STAS was observed in % of patients with pleomorphic carcinoma in the present study. Its presence was significantly associated with poor RFS and OS following surgical resection. To the best of our knowledge, the present study is the first to clearly show that the presence of STAS in patients with pleomorphic carcinoma is a reliable prognostic indicator. Following extensive debate, tumor STAS was recently designated as a novel invasive pattern in lung adenocarcinoma. Initial studies of STAS were limited to tumor nests or islands; patients with these morphologic findings were found to have distinct pathologic features and poorer prognoses than those without. 11,19 Subsequently, some investigators broadened their definition of STAS to include cell clusters or even single cells; they found that these features were also closely associated with high recurrence rates and poor survival following surgery in patients with small-sized lung adenocarcinomas Recently, Lu et al 15 found that every STAS associated with squamous cell carcinomas formed tumor nests and predicted poor postoperative RFS and OS. Our study, which used a broadened definition of STAS, found that the presence of STAS had a negative prognostic impact in patients with pleomorphic carcinoma, which was consistent with findings in patients with other NSCLCs. Prognostic determinants in patients with pleomorphic carcinoma have yet to be clearly defined. Previous investigators proposed that a higher pathologic stage, nodal involvement, pleural invasion, massive necrosis, and unresectability were predictors of poor OS in patients with pleomorphic carcinoma. 4-6,-23 Our results are generally consistent with their findings; however, it is notable that the negative impact of STAS on both RFS and OS was particularly prominent. Moreover, all the study patients underwent curativeintent lobectomy or bilobectomy followed by systematic lymph nodes dissection; this homogeneity increased the reliability of our results. Given the prognostic relevance of STAS, its associated biologic mechanisms that facilitate tumor invasion ought to be clarified. Studies have shown that lung adenocarcinomas with STAS are more likely to exhibit higher nuclear grade, solid or micropapillary growth patterns, and KRAS or BRAF mutations, whereas those without STAS exhibited lepidic growth patterns and chestjournal.org 5 FLA 5.5. DTD Š CHEST1778_proof Š 1 July 18 Š 2:7 am Š EO: CHEST
6 TABLE 2 ] Clinicopathologic Characteristics of the Study Cohort According to the Presence of STAS Characteristic All Patients (N ¼ 35) STAS Negative (n ¼ 21 [.%]) STAS Positive (n ¼ 14 [.%]) P Value Clinical factors Sex Male 27 (77) 15 (71) 12 (86).431 Female 8 (23) 6 (29) 2 (14) Age, y Median [range] 62. [35 91] 62. [35 86] 63.5 [44 91].32 Smoking Current/ex-smoker 28 () 15 (71) 13 (93).3 Nonsmoker 7 () 6 (29) 1 (7) Pathologic factors Tumor size, mm Median [range] 38. [11 85] 33. [15 85]. [11 ].873 T classification T1/T2 28 () 17 (81) 11 (79) 1. Q13 T3/T4 7 () 4 (19) 3 (21) N classification N 24 (69) 15 (71) 9 (64).566 N1 4 (11) 3 (14) 1 (7) N2 7 () 3 (14) 4 (29) Stage I/II 25 (71) 16 (76) 9 (64).474 III 1 (29) 5 (24) 5 (36) Pleural invasion Absent 19 (54) 1 (48) 9 (64).491 Present 16 (46) 11 (52) 5 (36) Lymphatic invasion Absent 24 (69) 14 (67) 1 (71) 1. Present 11 (31) 7 (33) 4 (29) Vascular invasion Absent 13 (37) 7 (33) 6 (43).724 Present 22 (63) 14 (67) 8 (57) Observed distance from tumor edge, mm Median [range] 14. [6 24] 14. [6 24] 13.5 [1 24].493 Spindle cell carcinoma component Absent 3 (9) 2 (1) 1 (7) 1. Present 32 (91) 19 (91) 13 (93) Giant cell carcinoma component Absent 1 (29) 4 (19) 6 (43).151 Present 25 (71) 17 (81) 8 (57) Adenocarcinoma component Absent 7 () 5 (24) 2 (14).676 Present 28 () 16 (76) 12 (86) Lepidic pattern Absent 8 (23) 6 (38) 2 (17).1 (Continued) Original Research [ - # - CHEST ] FLA 5.5. DTD Š CHEST1778_proof Š 1 July 18 Š 2:7 am Š EO: CHEST
7 print & web 4C=FPO TABLE 2 ] (Continued) Characteristic All Patients (N ¼ 35) STAS Negative (n ¼ 21 [.%]) STAS Positive (n ¼ 14 [.%]) P Value Present (57) 1 (63) 1 (83) Acinar pattern Absent 6 (17) 2 (13) 4 (33).354 Present 22 (63) 14 (88) 8 (67) Papillary pattern Absent 16 (46) 9 (56) 7 (58) 1. Present 12 (34) 7 (44) 5 (42) Micropapillary pattern Absent 27 (77) 16 () 11 (92).429 Present 1 (3) 1 (8) Solid pattern Absent 16 (46) 1 (63) 6 (5).72 Present 12 (34) 6 (38) 6 (5) Mucinous adenocarcinoma Absent 26 (74) 15 (94) 11 (92) 1. Present 2 (6) 1 (6) 1 (8) Squamous cell carcinoma component Absent 26 (74) 16 (76) 1 (71) 1. Present 9 (26) 5 (24) 4 (29) Necrosis Absent 19 (54) 14 (67) 5 (36).94 Present 16 (46) 7 (33) 9 (64) Data are presented as No. (%) or as median [range]. See Table 1 legend for expansion of abbreviation. EGFR mutations. 11,12,14,19 Similarly, squamous cell carcinomas with STAS were significantly more associated with lymphatic and vascular invasion as well as tumor necrosis. 15 Moreover, squamous cell A Recurrence-free survival rate (%) STAS (+) (n = 14) STAS ( ) (n = 21) carcinomas with STAS had higher Ki-67 indices than those without. Notably, we found that STAS-positive tumors occurred concomitantly with tumors exhibiting necrosis more frequently than STAS-negative tumors. B Overall survival rate (%) STAS (+) (n = 14) STAS ( ) (n = 21) Figure 2 A, B, Kaplan-Meier curves estimating recurrence-free survival (RFS) and overall survival (OS) according to the presence of tumor spread through air spaces (STAS) in pleomorphic carcinoma. A, RFS in patients with STAS vs without STAS (P ¼.5). B, OS in patients with STAS vs without STAS (P ¼.2) chestjournal.org 7 FLA 5.5. DTD Š CHEST1778_proof Š 1 July 18 Š 2:7 am Š EO: CHEST
8 Q16 Mochizuki et al 6 showed that tumor necrosis is an independent negative predictor of RFS and OS in patients with pleomorphic carcinoma, possibly because the rapid proliferation of malignant cells results in an undersupply of blood flows. Hence, it is possible that the poor prognoses of patients with pleomorphic carcinoma with STAS stems from this association with tumor necrosis, implying that common molecular pathways may be involved in eliciting both features; this hypothesis warrants further investigation. print & web 4C=FPO To properly assess the prognostic impact of STAS in a clinical setting, some investigators classified STAS into extensive vs limited categories. Warth et al 11 concluded A Recurrence-free survival rate (%) C Overall survival rate (%) STAS (+) (n = 9) STAS (+) (n = 9) STAS ( ) (n = 16) STAS ( ) (n = 16) that extensive STAS (ie, that which is > 3 alveolar spaces away from the edge of the tumor) accounted for approximately 29% of adenocarcinomas and was prevalent in tumors with micropapillary components. However, survival rates in such cases were virtually similar to those with limited STAS. Applying the same definition to squamous cell carcinomas revealed that extensive STAS accounted for 23% of cases; moreover, their study also found that RFS and cancer-specific survival did not differ based on the extent of STAS. 15 When 14 patients with STAS in the present study were similarly subcategorized into extensive vs limited STAS, 13 (93%) were classified as having extensive STAS, which in turn was significantly correlated with tumor B Recurrence-free survival rate (%) D Overall survival rate (%) STAS ( ) (n = 5) STAS (+) (n = 5) STAS (+) (n = 5) STAS ( ) (n = 5) Figure 3 A-D, Kaplan-Meier survival curves based on the presence of tumor spread through air spaces (STAS) stratified according to pathologic stage. A, Recurrence-free survival (RFS) in stage I/II patients with STAS vs without STAS (P ¼.13). B, RFS in stage III patients with STAS vs without STAS (P ¼.23). C, Overall survival (OS) in stage I/II patients with STAS vs without STAS (P ¼.319). D, OS in stage III patients with STAS vs without STAS (P ¼.2) Original Research [ - # - CHEST ] FLA 5.5. DTD Š CHEST1778_proof Š 1 July 18 Š 2:7 am Š EO: CHEST
9 TABLE 3 ] Univariate Analysis of Risk Factors Associated With Recurrence-free and Overall Survival Characteristic, Risk Factor HR 95% CI P Value HR 95% CI P Value Clinical factors Sex, male Age, older (per year) Smoking, current/ex-smoker Pathologic factors Tumor size, larger (per mm) Stage III (vs I/II) Pleural invasion, present Lymphatic invasion, present Vascular invasion, present Spindle cell carcinoma component, absent Giant cell carcinoma component, present Adenocarcinoma component, present Squamous cell carcinoma component, present Necrosis, present STAS, present HR ¼ hazard ratio. See Table 1 legend for expansion of other abbreviation. necrosis (P ¼.43). Furthermore, the statistical differences in RFS and OS curves between patients with extensive STAS and those with other subcategories significantly increased (P ¼.2 and.1, respectively) compared with patients in which STAS was merely classified as positive or negative. Although our cohort s small size precludes deriving definitive conclusions, these results indicate that the presence of extensive STAS in pleomorphic carcinoma reinforces the increased risk of poor survival in clinical settings. The present study had certain limitations. First, the statistical power may have been insufficient owing to the small number of patients; hence, additional larger series are required to confirm our findings. Second, it may sometimes be challenging to accurately distinguish STAS Recurrence-free Survival from the STAKS that results from specimen processing. However, there were no disagreements among the observers regarding the identification and assessment of STAS in our study, which attested to our results reproducibility. Third, the retrospective nature of our study created the possibility of selection bias; therefore, future prospective studies are required to validate these findings. Conclusions Overall Survival This study showed for the first time that STAS is somewhat common in patients with lung pleomorphic carcinoma, which was up to % in our study. We also found that STAS occurred concomitantly with tumor necrosis in these patients. Furthermore, we found that the presence of STAS was associated with poor RFS following TABLE 4 ] Multivariate Analysis of Risk Factors Affecting Recurrence-free and Overall Survival Recurrence-free Survival Overall Survival Characteristic, Risk Factor HR 95% CI P Value HR 95% CI P Value Stage III (vs I/II) Vascular invasion, present. a. a. a Necrosis, present STAS, present See Table 1 and 3 legends for expansion of abbreviations. a A characteristic with a P value >.1 on the univariate analysis that was therefore not analyzed in the multivariate model chestjournal.org 9 FLA 5.5. DTD Š CHEST1778_proof Š 1 July 18 Š 2:7 am Š EO: CHEST
10 surgical resection and, more importantly, with worse OS. These data indicate that STAS can be used as an additional marker to identify patients with pleomorphic Acknowledgments 998 Author contributions: S. Y. had full access to 999 all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, including 1 and especially any adverse effects. S. Y., T. 2 M., H. T., H. O., A. H., R. M., M. F., M. H., H. I., and K. O. contributed to the conception 3 and design of the study; S. Y., T. M., H. T., 4 and H. O. contributed to the analysis and 5 interpretation of the data; S. Y. and H. T. drafted the submitted article; and K. O. and 6 Y. A. contributed to the critical revision of 7 the manuscript for important intellectual 8 property. 9 Financial/nonfinancial disclosures: None Q9 11 declared. 111 Other contributions: The authors are profoundly grateful to Masami Murakami, 112 Mai Nitta, and Hinata Fukusako for assisting 113 Q1 with the preparation of the lung specimens Q11 References 1. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG, eds. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed. Lyon, France: IARC; Chang YL, Lee YC, Shih JY, Wu CT. Pulmonary pleomorphic (spindle) cell carcinoma: peculiar clinicopathologic manifestations different from ordinary non-small cell carcinoma. Lung Cancer. 1;34(1): Yendamuri S, Caty L, Pine M, et al. Outcomes of sarcomatoid carcinoma of the lung: a Surveillance, Epidemiology, and End Results Database analysis. Surgery. 12;152: Fishback NF, Travis WD, Moran CA, Guinee DG Jr, McCarthy WF, Koss MN. Pleomorphic (spindle/giant cell) carcinoma of the lung. A clinicopathologic correlation of 78 cases. Cancer. 1994;73(12): Yuki T, Sakuma T, Ohbayashi C, et al. Pleomorphic carcinoma of the lung: a surgical outcome. J Thorac Cardiovasc Surg. 7;134: Mochizuki T, Ishii G, Nagai K, et al. Pleomorphic carcinoma of the lung: clinicopathologic characteristics of 7 cases. Am J Surg Pathol. 8;32(11): Chen F, Sonobe M, Sato T, et al. Clinicopathological characteristics of surgically resected pulmonary pleomorphic carcinoma. Eur J Cardiothorac Surg. 12;41(5): Bae HM, Min HS, Lee SH, et al. Palliative chemotherapy for pulmonary pleomorphic carcinoma. Lung Cancer. 7;58: Vieira T, Girard N, Ung M, et al. Efficacy of first-line chemotherapy in patients with advanced lung sarcomatoid carcinoma. J Thorac Oncol. 13;8: Hong JY, Choi MK, Uhm JE, et al. The role of palliative chemotherapy for advanced pulmonary pleomorphic carcinoma. Med Oncol. 9;26: Warth A, Muley T, Kossakowski CA, et al. Prognostic impact of intra-alveolar tumor spread in pulmonary adenocarcinoma. Am J Surg Pathol. 15;39: Kadota K, Nitadori J, Sima CS, et al. Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences after limited resection for small stage I lung adenocarcinomas. J Thorac Oncol. 15;1: Dai C, Xie H, Su H, et al. Tumor spread through air spaces affects the recurrence and overall survival in patients with lung adenocarcinoma >2 to 3 cm. J Thorac Oncol. 17;12: Shiono S, Yanagawa N. Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage I lung carcinoma who are at risk of poor outcomes, consistent with what has been reported in patients with adenocarcinoma and squamous cell carcinoma. adenocarcinoma. Interact Cardiovasc Thorac Surg. 16;23: Lu S, Tan KS, Kadota K, et al. Spread through air spaces (STAS) is an independent predictor of recurrence and lung cancer-specific death in squamous cell carcinoma. J Thorac Oncol. 17;12: Brierley JD, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours. 8th ed. Hoboken, NJ: Wiley-Blackwell; Thunnissen E, Blaauwgeers HJ, de Cuba EM, Yick CY, Flieder DB. Ex vivo artifacts and histopathologic pitfalls in the lung. Arch Pathol Lab Med. 16;1: Blaauwgeers H, Flieder D, Warth A, et al. A prospective study of loose tissue fragments in non-small cell lung cancer resection specimens: an alternative view to spread through air spaces. Am J Surg Pathol. 17;41: Onozato ML, Kovach AE, Yeap BY, et al. Tumor islands in resected early-stage lung adenocarcinomas are associated with unique clinicopathologic and molecular characteristics and worse prognosis. Am J Surg Pathol. 13;37: Ito K, Oizumi S, Fukumoto S, et al. Clinical characteristics of pleomorphic carcinoma of the lung. Lung Cancer. 1;68: Kaira K, Endo M, Abe M, et al. Biologic correlates of 18F-FDG uptake on PET in pulmonary pleomorphic carcinoma. Lung Cancer. 11;71: Yamamoto S, Hamatake D, Ueno T, et al. Clinicopathological investigation of pulmonary pleomorphic carcinoma. Eur J Cardiothorac Surg. 7;32: Miyahara S, Hamasaki M, Hamatake D, et al. Clinicopathological analysis of pleomorphic carcinoma of the lung: diffuse ZEB1 expression predicts poor survival. Lung Cancer. 15;87: Original Research [ - # - CHEST ] FLA 5.5. DTD Š CHEST1778_proof Š 1 July 18 Š 2:7 am Š EO: CHEST
11 本文献由 学霸图书馆 - 文献云下载 收集自网络, 仅供学习交流使用 学霸图书馆 ( 是一个 整合众多图书馆数据库资源, 提供一站式文献检索和下载服务 的 24 小时在线不限 IP 图书馆 图书馆致力于便利 促进学习与科研, 提供最强文献下载服务 图书馆导航 : 图书馆首页文献云下载图书馆入口外文数据库大全疑难文献辅助工具
Supporting Information. Electrochemiluminescence for Electric-Driven Antibacterial. Therapeutics
Supporting Information Electrochemiluminescence for Electric-Driven Antibacterial Therapeutics Shanshan Liu, a,b Huanxiang Yuan, a Haotian Bai, a Pengbo Zhang, a Fengting Lv, a Libing Liu, a Zhihui Dai,
More informationRacial disparities in the management of acne: evidence from the National Ambulatory Medical Care Survey,
Journal of Dermatological Treatment ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: http://www.tandfonline.com/loi/ijdt20 Racial disparities in the management of acne: evidence from the National
More informationPrognostic Impact of Margin Distance and Tumor Spread Through Air Spaces in Limited Resection for Primary Lung Cancer
Accepted Manuscript Prognostic Impact of Margin Distance and Tumor Spread Through Air Spaces in Limited Resection for Primary Lung Cancer Kyohei Masai, Hiroyuki Sakurai, Aoi Sukeda, Shigeki Suzuki, Keisuke
More informationOptimization of Processing Parameters of Stabilizers After Enzymes Hydrolysis for Cloudy Ginkgo Juice
Optimization of Processing Parameters of Stabilizers After Enzymes Hydrolysis for Cloudy Ginkgo Juice Haifeng Yu, Junyan Liu and Jingxi Yang 1 Introduction Ginkgo biloba, dating back 300 million years,
More informationAccepted Manuscript. Hemorrhagic cystitis associated with gefitinib treatment: a case report. Peng Zhang, Jinjing Tu, Tieding Chen, Rubing Li
Accepted Manuscript Hemorrhagic cystitis associated with gefitinib treatment: a case report Peng Zhang, Jinjing Tu, Tieding Chen, Rubing Li PII: S0090-4295(18)30555-7 DOI: 10.1016/j.urology.2018.05.035
More informationOriginal Articles. Current Evidence Does Not Warrant Frozen Section Evaluation for the Presence of Tumor Spread Through Alveolar Spaces
Original Articles Current Evidence Does Not Warrant Frozen Section Evaluation for the Presence of Tumor Spread Through Alveolar Spaces Ann E. Walts, MD; Alberto M. Marchevsky, MD Context. Tumor spread
More informationChapter 5 Trimalleolar Ankle Fracture: Posterior Plate for Posterior Malleolus Fractures
Chapter 5 Trimalleolar Ankle Fracture: Posterior Plate for Posterior Malleolus Fractures Roy I. Davidovitch and Alexander M. Crespo Introduction Trimalleolar ankle fractures with a posterior malleolus
More informationPleomorphic carcinoma of the lung: which CT findings predict poor prognosis?
Pleomorphic carcinoma of the lung: which CT findings predict poor prognosis? Poster No.: C-1887 Congress: ECR 2015 Type: Scientific Exhibit Authors: A. Fujisaki, T. Aoki, S. Kinoshita, Y. Hayashida, Y.
More informationThe conundrum of hodgkin lymphoma nodes: To be or not to be included in the involved node radiation fields. The EORTC-GELA lymphoma group guidelines
Radiotherapy and Oncology 88 (2008) 202 210 www.thegreenjournal.com Hodgkin guidelines The conundrum of hodgkin lymphoma nodes: To be or not to be included in the involved node radiation fields. The EORTC-GELA
More informationThinking & Reasoning Publication details, including instructions for authors and subscription information:
This article was downloaded by: [Umeå University Library] On: 07 October 2013, At: 11:46 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer
More informationFetal Response to Intramuscular Epinephrine for Anaphylaxis during Maternal Penicillin Desensitization for Secondary Syphilis
The Journal of Maternal-Fetal & Neonatal Medicine ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20 Fetal Response to Intramuscular Epinephrine for Anaphylaxis
More informationAccepted Manuscript. Robotics in Orthopedics: A Brave New World. Brian S. Parsley, MD, Associate Professor
Accepted Manuscript Robotics in Orthopedics: A Brave New World Brian S. Parsley, MD, Associate Professor PII: S0883-5403(18)30163-3 DOI: 10.1016/j.arth.2018.02.032 Reference: YARTH 56428 To appear in:
More informationACCEPTED ARTICLE PREVIEW. Accepted manuscript
First in Class Angiotensin Receptor Neprilysin Inhibitor in Heart Failure Orly Vardeny, PharmD, MS, Travis Tacheny, Scott D. Solomon, MD Cite this article as: Orly Vardeny, PharmD, MS, Travis Tacheny,
More informationIndacaterol, a once-daily beta 2 -agonist, versus twice-daily beta-agonists or placebo for chronic obstructive pulmonary disease (Protocol)
Indacaterol, a once-daily beta 2 -agonist, versus twice-daily beta-agonists or placebo for chronic obstructive pulmonary disease (Protocol) Geake JB, Dabscheck EJ, Wood-Baker R This is a reprint of a Cochrane
More informationAccepted Manuscript. Red yeast rice preparations: are they suitable substitutions for statins?
Accepted Manuscript Red yeast rice preparations: are they suitable substitutions for statins? Carlos A. Dujovne, MD, Fellow NLA, Certified Clinical Lipidologist PII: S0002-9343(17)30591-0 DOI: 10.1016/j.amjmed.2017.05.013
More informationSynthetic Tannins Structure by MALDI-TOF Mass Spectroscopy
Synthetic Tannins Structure by MALDI-TOF Mass Spectroscopy S. Giovando, 1 A. Pizzi, 2 H. Pasch, 3,4 K. Rode 4 1 Centro Ricerche per la Chimica Fine Srl, S.Michele Mondovi, Italy 2 ENSTIB-LERMAB, Nancy
More informationEffects of idebenone on electroencephalograms of patients with cerebrovascular disorders
Arch. Gerontol. Geriatr., 8 (1989) 355-366 355 Elsevier AGG 00266 Effects of idebenone on electroencephalograms of patients with cerebrovascular disorders Takashi Nakano a Matu6 Miyasaka a, Katsumi Mori
More informationuncorrected proof version
Galley Proof 8/02/2017; 9:17 File: jcm 1-jcm708.tex; BOKCTP/ljl p. 1 Journal of Computational Methods in Sciences and Engineering -1 (2017) 1 10 1 DOI 10.3233/JCM-170708 IOS Press 1 2 3 Comparison of sliding
More informationYang S-S, Gao Y, Wang D-Y, Xia B-R, Liu Y-D, Qin Y, Ning X-M, Li G-Y, Hao L-X, Xiao M & Zhang Y-Y (2016) Histopathology. DOI: /his.
Histopathology 2016 DOI: 10.1111/his.12933 Overexpression of eukaryotic initiation factor 5A2 (EIF5A2) is associated with cancer progression and poor prognosis in patients with early-stage cervical cancer
More informationHow might treatment of ALK-positive non-small cell lung cancer change in the near future?
Expert Review of Anticancer Therapy ISSN: 1473-7140 (Print) 1744-8328 (Online) Journal homepage: http://www.tandfonline.com/loi/iery20 How might treatment of ALK-positive non-small cell lung cancer change
More informationSOME PRACTICAL IMPROVEMENTS IN THE CONTINUAL REASSESSMENT METHOD FOR PHASE I STUDIES
STATISTICS IN MEDICINE, VOL. 14, 1149-1161 (1995) SOME PRACTICAL IMPROVEMENTS IN THE CONTINUAL REASSESSMENT METHOD FOR PHASE I STUDIES STEVEN N. GOODMAN, MARIANNA L. ZAHURAK AND STEVEN PIANTADOSI Johns
More informationJournal of Chromatography A 819 (1998)
Journal of Chromatography A 89 (998) 33 42 Investigation of potential degradation products of a newly synthesised b-lactam antibiotic by multi-stage liquid chromatography electrospray mass spectrometry
More informationSmall pulmonary nodules in baseline and incidence screening rounds of low-dose CT lung cancer screening
Review Article Small pulmonary nodules in baseline and incidence screening rounds of low-dose CT lung cancer screening Joan E. Walter, Marjolein A. Heuvelmans, Matthijs Oudkerk University Medical Center
More informationPharmacokinetics of a Novel Orodispersible Tablet of Sildenafil in Healthy Subjects
Clinical Therapeutics/Volume 36, Number 2, 2014 Pharmacokinetics of a Novel Orodispersible Tablet of Sildenafil in Healthy Subjects Bharat Damle, PhD 1 ; Gregory Duczynski, MS 2 ; Barrett W. Jeffers, PhD
More informationDifferent estrogen receptor β expression in distinct histologic subtypes of lung adenocarcinoma B
Human Pathology (2008) 39, 1465 1473 www.elsevier.com/locate/humpath Original contribution Different estrogen receptor β expression in distinct histologic subtypes of lung adenocarcinoma B Greta Alì MD
More informationCost-Effectiveness of Adding Rh-Endostatin to First-Line Chemotherapy in Patients With Advanced Non-Small-Cell Lung Cancer in China
Clinical Therapeutics/Volume 33, Number 10, 2011 Cost-Effectiveness of Adding Rh-Endostatin to First-Line Chemotherapy in Patients With Advanced Non-Small-Cell Lung Cancer in China Bin Wu, PhD 1, Huafeng
More informationEffects of regular exercise on asthma control in young adults
Journal of Asthma ISSN: 0277-0903 (Print) 1532-4303 (Online) Journal homepage: http://www.tandfonline.com/loi/ijas20 Effects of regular exercise on asthma control in young adults Dr Sirpa A.M. Heikkinen,
More informationIncidence and predictors of synchronous liver metastases in patients with gastrointestinal stromal tumors (GISTs)
Accepted Manuscript Incidence and predictors of synchronous liver metastases in patients with gastrointestinal stromal tumors (GISTs) Apostolos Gaitanidis, Michail Alevizakos, Alexandra Tsaroucha, Constantinos
More informationCharacterization of a prototype MR-compatible Delta4 QA-system in a 1.5 tesla MR-linac
Physics in Medicine and Biology ACCEPTED MANUSCRIPT Characterization of a prototype MR-compatible Delta QA-system in a. tesla MR-linac To cite this article before publication: J H Wilfred de Vries et al
More informationComparison of Carotid Artery Stenting and Carotid Endarterectomy in Patients with Symptomatic Carotid Artery Stenosis: A Single Center Study
Adv Ther (2013) 30:845 853 DOI 10.1007/s25-013-0058-8 ORIGINAL RESEARCH Comparison of Carotid Artery Stenting and Carotid Endarterectomy in Patients with Symptomatic Carotid Artery Stenosis: A Single Center
More informationORIGINAL ARTICLE ABSTRACT SUMMARY AT A GLANCE INTRODUCTION
bs_bs_banner ORIGINAL ARTICLE Budesonide/formoterol maintenance and reliever therapy via Turbuhaler versus fixed-dose budesonide/formoterol plus terbutaline in patients with asthma: Phase III study results
More informationAccepted Manuscript. Dural arteriovenous fistula between the inferolateral trunk and cavernous sinus draining to the ophthalmic vein: a case report
Accepted Manuscript Dural arteriovenous fistula between the inferolateral trunk and cavernous sinus draining to the ophthalmic vein: a case report Kan Xu, Kun Hou, Baofeng Xu, Yunbao Guo, Jinlu Yu PII:
More informationTHE RATIONALITY/EMOTIONAL DEFENSIVENESS SCALE- I. INTERNAL STRUCTURE AND STABILITY
Joouml of Psychosomaric Research, Vol. 35. No. 4/S, pp. 545-554, 1991. 0534-3999191 $3.00+.00 Printed in Great Britain 0 1991 Pergamon Press plc THE RATIONALITY/EMOTIONAL DEFENSIVENESS SCALE- I. INTERNAL
More informationEffects of Angle of Approach on Cursor Movement with a Mouse: Consideration of Fitts' Law
Pergamon Computers in Human Behavior, Vol. 12, No. 3, pp. 481-495, 1996 Copyright 1996 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0747-5632/96 $15.00 + 0.00 S0747-5632(96) 00020-9
More informationOvarian cancer is the most lethal gynecologic malignancy
Original Research Laparoscopy Compared With Laparotomy for Debulking Ovarian Cancer After Neoadjuvant Chemotherapy Alexander Melamed, MD, MPH, Roni Nitecki, MD, David M. Boruta II, MD, Marcela G. del Carmen,
More informationHow Advertising Slogans
How Advertising Slogans Can Prime Evaluations of Brand Extensions David M. Boush University of Oregon ABSTRACT Different versions of a brand slogan were presented to each of three treatment groups before
More informationDivergent Thinking and Evaluation Skills: Do They Always Go Together?
Journal of Creative Behavior MAGDALENA GROHMAN ZOFIA WODNIECKA MARCIN KLUSAK Divergent Thinking and Evaluation Skills: Do They Always Go Together? ABSTRACT INTRODUCTION The aim of the present study was
More informationMastering the Initial Dissection and Cannulation: Making Ablation Easy and Safe
Chapter 5 Mastering the Initial Dissection and Cannulation: Making Ablation Easy and Safe 1 INTRODUCTION A good initial dissection with wide mobilization of the left atrium (LA) by dividing its attachments
More informationNON-NARCOTIC ORALLY EFFECTIVE, CENTRALLY ACTING ANALGESIC FROM AN AYURVEDIC DRUG
Journal of Ethnopharmocology, ll(l984) 309-317 Elsevier Scientific Publishers Ireland Ltd. 309 NON-NARCOTIC ORALLY EFFECTIVE, CENTRALLY ACTING ANALGESIC FROM AN AYURVEDIC DRUG CX ATAL, M.A. SIDDIQUI, USHA
More informationLung cancer is now a major cause of death in developed
Original Article New IASLC/ATS/ERS Classification and Invasive Tumor Size are Predictive of Disease Recurrence in Stage I Lung Adenocarcinoma Naoki Yanagawa, MD, PhD,* Satoshi Shiono, MD, PhD, Masami Abiko,
More informationThe role of air plethysmography in the diagnosis of chronic venous insufficiency
The role of air plethysmography in the diagnosis of chronic venous insufficiency Enrique Criado, MD, Mark A. Farber, MD, William A. Marston, MD, Patty F. Daniel, RN, RVT, Cynthia B. Burnham, RN, RVT, and
More informationSerum mir-182 and mir-331-3p as diagnostic and prognostic markers in patients with hepatocellular carcinoma
Tumor Biol. (2015) 36:7439 7447 DOI 10.1007/s13277-015-3430-2 RESEARCH ARTICLE Serum mir-182 and mir-331-3p as diagnostic and prognostic markers in patients with hepatocellular carcinoma Lin Chen 1 & Feihu
More informationTitle: Clinical and histopathological features of immunoglobulin G4-associated autoimmune hepatitis in children
Title: Clinical and histopathological features of immunoglobulin G4-associated autoimmune hepatitis in children Short title: Immunoglobulin G4-associated autoimmune hepatitis in children Yusuf Aydemir¹,
More informationLONG-TERM RESULTS OF A PHASE III TRIAL COMPARING ONCE-DAILY RADIOTHERAPY WITH TWICE-DAILY RADIOTHERAPY IN LIMITED- STAGE SMALL-CELL LUNG CANCER
doi:10.1016/j.ijrobp.2004.01.055 Int. J. Radiation Oncology Biol. Phys., Vol. 59, No. 4, pp. 943 951, 2004 Copyright 2004 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/04/$ see front
More informationRAVEN'S COLORED PROGRESSIVE MATRICES AND INTELLECTUAL IMPAIRMENT IN PATIENTS WITH FOCAL BRAIN DAMAGE
RAVEN'S COLORED PROGRESSIVE MATRICES AND INTELLECTUAL IMPAIRMENT IN PATIENTS WITH FOCAL BRAIN DAMAGE Claudio Villardita (Neuropsychology Unit, Department of Neurology, University of Catania) INTRODUCTION
More informationPulmonary Vein Stenosis After Catheter Ablation of Atrial Fibrillation
Pulmonary Vein Stenosis After Catheter Ablation of Atrial Fibrillation E.B. SAAD Introduction Catheter ablation around the pulmonary veins (PVs) has become the treatment of choice for symptomatic patients
More informationPrevalence of different HIV-1 subtypes in sexual transmission in China: a systematic review and meta-analysis
Epidemiol. Infect. (2016), 144, 2144 2153. Cambridge University Press 2016 doi:10.1017/s0950268816000212 Prevalence of different HIV-1 subtypes in sexual transmission in China: a systematic review and
More informationParallel Stent Graft Techniques to Facilitate Endovascular Repair in the Aortic Arch
Parallel Stent Graft Techniques to Facilitate Endovascular Repair in the Aortic Arch 35 Frank J. Criado Introduction Whether using a traditional open-chest approach or endovascular techniques, the arch
More informationavailable at journal homepage:
Lung Cancer (2006) 54, 217 225 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/lungcan Eg5 expression is closely correlated with the response of advanced non-small cell lung
More informationValidation of ATS clinical practice guideline cut-points for FeNO in asthma
Accepted Manuscript Validation of ATS clinical practice guideline cut-points for FeNO in asthma Maria Jeppegaard, Sandra Veidal, Asger Sverrild, Vibeke Backer, Celeste Porsbjerg PII: S0954-6111(18)30296-8
More informationAuthor s Accepted Manuscript
Author s Accepted Manuscript Rheumatologic symptoms in oncologic patients on PD-1 inhibitors Wilson F. Kuswanto, Lindsey A. MacFarlane, Lydia Gedmintas, Alexandra Mulloy, Toni K. Choueiri, Bonnie Bermas
More informationContrasting timing of virological relapse after discontinuation of. tenofovir or entecavir in hepatitis B e antigen-negative patients.
Contrasting timing of virological relapse after discontinuation of tenofovir or entecavir in hepatitis B e antigen-negative patients. Running title: Difference after stopping TDF or ETV Christoph Höner
More informationLow- vs. high-pressure suction drainage after total knee arthroplasty: a double-blind randomized controlled trial
JAN JOURNAL OF ADVANCED NURSING ORIGINAL RESEARCH Low- vs. high-pressure suction drainage after total knee arthroplasty: a double-blind randomized controlled trial Rafael Calvo, M a José Martínez-Zapata,
More informationEnergy Metabolism in Oreochromis niloticus
Aquuculture, 79 (1989) 283-291 Eisevier Science Pubhshers B.V., Amsterdam - Printed in The Netherlands 283 Energy Metabolism in Oreochromis niloticus K.-H. MEYER-BURGDORFF, M.F. OSMAN and K.D. GUNTHER
More informationLung cancer is one of the major tumors that causes human
ORIGINAL RESEARCH Analysis of Contrast-Enhanced Ultrasound Perfusion Patterns and Time-Intensity Curves for Metastatic Lymph Nodes From Lung Cancer Preliminary Results Shanshan Yin, MD, Qiuli Cui, MSc,
More informationHard-tissue alterations following immediate implant placement in extraction sites
J Clin Periodontol 2004; 31: 820 828 doi: 10.1111/j.1600-051X.2004.00565.x Copyright r Blackwell Munksgaard 2004 Printed in Denmark. All rights reserved Hard-tissue alterations following immediate implant
More informationORIGINAL PAPER. Marginal pulmonary function is associated with poor short- and long-term outcomes in lung cancer surgery
Nagoya J. Med. Sci. 79. 37 ~ 42, 2017 doi:10.18999/nagjms.79.1.37 ORIGINAL PAPER Marginal pulmonary function is associated with poor short- and long-term outcomes in lung cancer surgery Naoki Ozeki, Koji
More informationThe Use of Transdermal Buprenorphine to Relieve Radiotherapy-Related Pain in Head and Neck Cancer Patients
Cancer Investigation, 31:412 420, 2013 ISSN: 0735-7907 print / 1532-4192 online Copyright C 2013 Informa Healthcare USA, Inc. DOI: 10.3109/07357907.2013.800094 IMAGING, DIAGNOSIS, PROGNOSIS The Use of
More informationThe clinical significance of mesenchyme forkhead 1 (FoxC2) in gastric carcinoma
Histopathology 2013, 62, 1038 1048. DOI: 10.1111/his.12132 The clinical significance of mesenchyme forkhead 1 (FoxC2) in gastric carcinoma Jin-Liang Zhu,* Yong-Xi Song,* Zhen-Ning Wang, Peng Gao, Mei-Xian
More informationA. Alonso-Burgos a, *, E. García-Tutor b, G. Bastarrika a, D. Cano a, A. Martínez-Cuesta a, L.J. Pina a
Journal of Plastic, Reconstructive & Aesthetic Surgery (2006) 59, 585 593 Preoperative planning of deep inferior epigastric artery perforator flap reconstruction with multislice-ct angiography: imaging
More information164 J.A.H. an Laarho en et al. / International Journal of Pharmaceutics 232 (2002) An example of a sustained release system is a contraceptive
International Journal of Pharmaceutics 232 (2002) 163 173 www.elsevier.com/locate/ijpharm In vitro release properties of etonogestrel and ethinyl estradiol from a contraceptive vaginal ring J.A.H. van
More informationHYDRONEPHROSIS DUE TO THE INFERIOR POLAR ARTERY :
HYDRONEPHROSIS DUE TO THE INFERIOR POLAR ARTERY : LATE RESULTS AFTER NEPHROPLICATION. Appendix of Recent Cases By A. WILFRID ADAMS, F.R.C.S. Bristol Royal Infirmary FOR hydronephrosis due to an aberrant,
More informationSYSTEMATIC REVIEW PROTOCOL
Effectiveness of Silexan oral lavender essential oil compared to inhaled lavender essential oil aromatherapy on sleep in adults: a systematic review protocol Martha J. Greenberg 1,2 Jason T. Slyer 1,2
More informationNebulized Magnesium for Moderate and Severe Pediatric Asthma: A Randomized Trial
50:1191 1199 (2015) Nebulized Magnesium for Moderate and Severe Pediatric Asthma: A Randomized Trial Khalid Alansari, MD, FRCPC, FAAP(PEM), 1,2,3 * Wessam Ahmed, 2 Bruce L. Davidson, MD, MPH, 4 Mohamed
More informationSplenomegaly and Hemolytic Anemia Induced in Rats by Methylcellulose - An electron microscopic study '
Splenomegaly and Hemolytic Anemia Induced in Rats by Methylcellulose - An electron microscopic study ' EMMA WENNBERG AND LEON WEISS Department of Anatomy, The johns Hopkins University School of Medicine,
More informationABSTRACT. questions in the version of NorAQ administered to men (m-noraq) against the interview model.
GENDER MEDICINE/VOL. 8,NO. 2, 2011 NorVold Abuse Questionnaire for Men (m-noraq): Validation of New Measures of Emotional, Physical, and Sexual Abuse and Abuse in Health Care in Male Patients Katarina
More informationComputerized Quantitative Coronary Angiography Applied to Percutaneous Transluminal Coronary Angioplasty: Advantages and Limitations
Computerized Quantitative Coronary Angiography Applied to Percutaneous Transluminal Coronary Angioplasty: Advantages and Limitations P.W. Serruys, F. Booman, G.J. Troost, J.H.C. Reiber, J.J. Gerbrands*,
More informationClinical investigation of chronic subdural hematoma with impending brain herniation on arrival
DOI 10.1007/s10143-017-0861-9 ORIGINAL ARTICLE Clinical investigation of chronic subdural hematoma with impending brain herniation on arrival Hiroaki Matsumoto 1 & Hiroaki Hanayama 1 & Takashi Okada 1
More informationMarlowe Crowne Social Desirability Scale and Short Form C: Forensic Norms
Marlowe Crowne Social Desirability Scale and Short Form C: Forensic Norms Paul Andrews Private Practice, Tyler, Texas Robert G. Meyer University of Louisville Marlowe Crowne Social Desirability Scale (MC)
More informationIntroduction. urinary erythropoietin, and the two are indistinguishable
BIOPHARMACEUTICS & DRUG DISPOSITION Biopharm. Drug Dispos. 21: 211 219 (2000) DOI: 10.1002/bdd.231 Comparative Pharmacokinetics, Safety, and Tolerability After Subcutaneous Administration of Recombinant
More informationHepatitis B virus (HBV) infection is a global health
GASTROENTEROLOGY 2012;142:1140 1149 High Levels of Hepatitis B Surface Antigen Increase Risk of Hepatocellular Carcinoma in Patients With Low HBV Load TAI CHUNG TSENG,*,, ** CHUN JEN LIU,, HUNG CHIH YANG,,#
More informationJournal of Chromatography B, 857 (2007)
Journal of Chromatography B, 857 (2007) 287 295 Determination of serum uric acid using high-performance liquid chromatography (HPLC)/isotope dilution mass spectrometry (ID-MS) as a candidate reference
More informationA Motivational Intervention to Reduce Cigarette
A Motivational Intervention to Reduce Cigarette Smoking Among College Students: Overview and Exploratory Investigation Keith C. Herman and Beth Fahnlander College counselors can play an important role
More informationAbsolute monocyte count predicts overall survival in mantle cell lymphomas: correlation with tumourassociated
Hematological Oncology Hematol Oncol 2014; 32: 178 186 Published online 29 October 2013 in Wiley Online Library (wileyonlinelibrary.com).2106 Original Research Article Absolute monocyte count predicts
More informationEfficacy, safety and impact on β
J Endocrinol Invest (2016) 39:1061 1074 DOI 10.1007/s40618-016-0465-1 ORIGINAL ARTICLE Efficacy, safety and impact on β cell function of dipeptidyl peptidase 4 inhibitors plus metformin combination therapy
More informationGlucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes*
ORIGINAL ARTICLE doi: 10.1111/j.1463-1326.2008.00876.x Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes* J. Rosenstock, 1 S. Sankoh
More informationPrognostic factors in curatively resected pathological stage I lung adenocarcinoma
Original Article Prognostic factors in curatively resected pathological stage I lung adenocarcinoma Yikun Yang 1, Yousheng Mao 1, Lin Yang 2, Jie He 1, Shugeng Gao 1, Juwei Mu 1, Qi Xue 1, Dali Wang 1,
More informationEndoscopic resection therapies for rectal neuroendocrine tumors: A systematic review and meta-analysis
bs_bs_banner doi:.1111/jgh.12395 META-ANALYSIS AND SYSTEMATIC REVIEW for rectal neuroendocrine tumors: A systematic review and meta-analysis Xin Zhou,* Haiting Xie,* Lingduo Xie,* Jing Li, Weihua Cao and
More informationColchicine for prevention and treatment of cardiac diseases: A meta-analysis
DOI: 10.1111/1755-5922.12226 ORIGINAL RESEARCH ARTICLE Colchicine for prevention and treatment of cardiac diseases: A meta-analysis Nikolaos Papageorgiou 1,2, Alexandros Briasoulis 3, George Lazaros 2
More informationLung cancer pleural invasion was recognized as a poor prognostic
Visceral pleural invasion classification in non small cell lung cancer: A proposal on the basis of outcome assessment Kimihiro Shimizu, MD a Junji Yoshida, MD a Kanji Nagai, MD a Mitsuyo Nishimura, MD
More informationNatural Course of Peripartum Cardiomyopathy
Natural Course of Peripartum Cardiomyopathy By JOHN G. DEMAKIS, M.D., SHAHBUDIN H. RAHIMTOOLA, M.B., M.R.C.P.E., GEORGE C. SUTrON, M.D., W. ROBERT MEADOWS, M.D., PAUL B. SZANTO, M.D., JoHN R. TOBIN, M.D.,
More informationA Diabetes Mobile App With In-App Coaching From a Certified Diabetes Educator Reduces A1C for Individuals With Type 2 Diabetes
765650TDEXXX10.1177/0145721718765650Impact of a Diabetes App and Coaching Program on A1CKumar et al research-article2018 Impact of a Diabetes App and Coaching Program on A1C 1 A Diabetes Mobile App With
More informationPulley lesions in rotator cuff tears: prevalence, etiology, and concomitant pathologies
Arch Orthop Trauma Surg (2017) 137:1097 1105 DOI 10.1007/s00402-017-2721-z ARTHROSCOPY AND SPORTS MEDICINE Pulley lesions in rotator cuff tears: prevalence, etiology, and concomitant pathologies Nael Hawi
More informationEffect of health Baduanjin Qigong for mild to moderate Parkinson s disease
bs_bs_banner Geriatr Gerontol Int 2016; 16: 911 919 ORIGINAL ARTICLE: EPIDEMIOLOGY, CLINICAL PRACTICE AND HEALTH Effect of health Baduanjin Qigong for mild to moderate Parkinson s disease Chun-Mei Xiao
More informationLisfranc Arthrodesis for Chronic Pain: A Cannulated Screw Technique
Lisfranc Arthrodesis for Chronic Pain: A Cannulated Screw Technique Nine patients with injury to the tarsometatarsal joint underwent fusion with cannulated screw fixation after conservative treatment had
More informationCongenital absence of teeth is a common dental
CASE REPORT Management of congenitally missing second premolars with orthodontics and single-tooth implants Roy Sabri, DDS, MS Beirut, Lebanon This article describes the treatment of an adolescent girl
More informationFunctional Outcome of Unstable Distal Radius Fractures: ORIF With a Volar Fixed-Angle Tine Plate Versus External Fixation
Functional Outcome of Unstable Distal Radius Fractures: ORIF With a Volar Fixed-Angle Tine Plate Versus External Fixation Thomas W. Wright, MD, MaryBeth Horodyski, EdD, Gainesville, FL, Dean W. Smith,
More informationA LABORATORY TASK FOR INDUCTION OF MOOD STATES*
khav. Res. & Therapy. 1968. Vol. 6. pp. 473 to 462. Pergamon Press. Printed in Englmd A LABORATORY TASK FOR INDUCTION OF MOOD STATES* EMMETT VELTEN, JR.? University of Southern California (Received 15
More informationResearch Article Prognostic Implication of Predominant Histologic Subtypes of Lymph Node Metastases in Surgically Resected Lung Adenocarcinoma
BioMed Research International, Article ID 64568, 6 pages http://dx.doi.org/.55/24/64568 Research Article Prognostic Implication of Predominant Histologic Subtypes of Lymph Node Metastases in Surgically
More informationAddress: Department of General Surgery, Royal Bolton Hospital, Bolton, UK. ; tel:
Article type : Systematic Review Accepted Article 875-2017.R1 Systematic Review Effect of mesalazine on recurrence of diverticulitis in patients with symptomatic uncomplicated diverticular disease: a meta-analysis
More informationProtective effect of HTK solution on postoperative pulmonary function in infants with CHD and PAH
Bioscience Reports: this is an Accepted Manuscript, not the final Version of Record. You are encouraged to use the Version of Record that, when published, will replace this version. The most up-to-date
More informationTraining for Lung Ultrasound Score Measurement in Critically Ill Patients
Page 1 of 1 Training for Lung Ultrasound Score Measurement in Critically Ill Patients Jean-Jacques Rouby, M.D., Ph.D. Charlotte Arbelot, M.D., Multidisciplinary Intensive Care Unit, Department of Anesthesiology
More informationEGC Diagnosis of Paroxysmal Supraventricular Tachycardias in Patients without Preexcitation
REVIEW ARTICLE EGC Diagnosis of Paroxysmal Supraventricular Tachycardias in Patients without Preexcitation Esteban González-Torrecilla, M.D., Ph.D., Angel Arenal, M.D., Felipe Atienza, M.D., Ph.D., Tomás
More informationIn vivo diagnosis of early-stage gastric cancer found after. Helicobacter pylori eradication using probe-based confocal laser endomicroscopy
DR. NAOKI OHMIYA (Orcid ID : 0000-0002-7651-402X) Accepted Article Article type : Original article In vivo diagnosis of early-stage gastric cancer found after Helicobacter pylori eradication using probe-based
More informationDevelopment and psychometric evaluation of the Thirst Distress Scale for patients with heart failure
728624CNU0010.1177/1474515117728624European Journal of Cardiovascular Nursing 0(0)Waldréus et al. research-article2017 Original Article Development and psychometric evaluation of the Thirst Distress Scale
More informationBJR UNCORRECTED PROOFS
Title Page 2017 The Authors. Published by the British Institute of Radiology Title: Radio-Pathological Correlation of Organising Pneumonia: A Pictorial Review Authors: 1- Mohammad Zare Mehrjardi, M.D.
More informationEffects of Mattress Material on Body Pressure Profiles in Different Sleeping Postures
Effects of Mattress Material on Body Pressure Profiles in Different Sleeping Postures Fan-Zhe Low, BEng, Matthew Chin-Heng Chua, PhD, Pan-Yin Lim, BEng, and Chen-Hua Yeow, PhD ABSTRACT Objectives: This
More informationExtent of visceral pleural invasion and the prognosis of surgically resected node-negative non-small cell lung cancer
Thoracic Cancer ISSN 1759-7706 ORIGINAL ARTICLE Extent of visceral pleural invasion and the prognosis of surgically resected node-negative non-small cell lung cancer Yangki Seok 1, Ji Yun Jeong 2 & Eungbae
More informationAntiproliferative, antimigratory, and anticlonogenic effects of Hedyotis diffusa, Panax ginseng, and their combination on colorectal cancer cell lines
Journal of Herbs, Spices & Medicinal Plants ISSN: 1049-6475 (Print) 1540-3580 (Online) Journal homepage: http://www.tandfonline.com/loi/whsm20 Antiproliferative, antimigratory, and anticlonogenic effects
More informationCombining ECMO with IABP for the Treatment of Critically Ill Adult Heart Failure Patients
Heart, Lung and Circulation (2014) 23, 363 368 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2013.10.081 ORIGINAL ARTICLE Combining ECMO with IABP for the Treatment of Critically Ill Adult Heart
More information