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Background: A six-minute walk test (6MWT) is a reproducible, easily performed test, and is widely used to determine functional exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). However, there is currently a paucity of data on the clinical significance of baseline and serial 6-minute walk tests in patients with IPF, especially in Asian patients. Objectives: We aimed to investigate the clinical significance of serial 6MWT in patients with IPF, especially in Asian patients. Design: This is a single-center retrospective cohort study. Methods: Clinical data of patients diagnosed with IPF at a tertiary center in Korea were retrospectively analyzed. IPF diagnosis was defined according to the clinical guidelines of the American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society/Latin American Thoracic Association. Results: There were 216 patients diagnosed with IPF from December 2012 to January 2022, of whom 198 had a baseline of 6MWT data. The mean age of the cohort was 66.9 ± 8.6, and 89% were male. The non-survivors showed significantly lower six-minute walk distance (6MWD), minimum saturation of peripheral oxygen (SpO2) during 6MWT, forced vital capacity, and diffusing capacity of the lung for carbon monoxide than survivors at baseline. A multivariate Cox analysis demonstrated that lower minimum SpO2 was independently associated with increased mortality rates (Hazard ratio (HR): 1.081, 95% confidence interval (CI): 1.024–1.142, p = 0.005). Higher mortality rates were also associated with echocardiographic-determined pulmonary hypertension (HR: 2.466, 95% CI: 1.149–5.296, p = 0.021) at diagnosis. Among 144 patients with 6MWT results at 12 months, patients with a decline of 50 m or more in the 6MWD showed poorer overall survival than others (median survival: 45.0 months vs 58.0 months, p < 0.001). Conclusions: Baseline lower minimum SpO2 during 6MWT was an independent prognostic factor in patients with IPF, and a decline in 6MWD in serial follow-up was also associated with a poorer prognosis. These findings suggest that both baseline 6MWT and follow-up data are important in the prognostication of patients with IPF. [ABSTRACT FROM AUTHOR]

Background/Purpose: Extranodal extension (ENE) is an established prognostic factor in various malignancies, affecting survival in pancreatic head cancer (PHC). However, its significance in pancreatic body/tail cancer (PBTC) remains unclear. Therefore, we aimed to investigate the impact of ENE on PTBC prognosis. Methods: We analyzed data collected from electronic medical records of patients with PBTC who underwent distal pancreatectomy at a single center between January 2011 and December 2015. The patients were categorized based on ENE presence and prognostic implications were evaluated using Kaplan–Meier survival curves and Cox proportional hazards model. Results: PBTC cases involving lymph node (LN) metastasis and ENE exhibited significantly lower disease‐free (DFS) and overall survival (OS) rates compared to cases without LN metastasis or ENE (median DFS; N0, 23 months; LN+/ENE−, 10 months; LN+/ENE+, 5 months; p <.001). No statistically significant difference was observed in DFS and OS rates between patients with N1/N2 in the group without ENE and those with ENE+. Multivariate analysis confirmed ENE as a significant adverse prognostic factor. Conclusions: ENE significantly predicts poor prognosis in PBTC, particularly in cases with nodal metastasis. The current cancer staging system for PBTC should incorporate ENE status. Moreover, different staging systems should be considered for PHC and PBTC. [ABSTRACT FROM AUTHOR]

Background: This study aimed to analyze the correlation between the cycle threshold (Ct) values of severe fever with thrombocytopenia syndrome (SFTS) virus small (S) and middle (M) segments and the SFTS viral load, aiming to estimate the initial viral load and predict prognosis in the early clinical course. Method: A retrospective study was conducted with confirmed SFTS patients at Jeju National University Hospital (2016–2022). Patients were categorized into non-fatal and fatal groups. Results: This study included 49 patients with confirmed SFTS (non-fatal group, n = 42; fatal group, n = 7). A significant negative correlation (−0.783) was observed between the log SFTS viral load and Ct values (p < 0.001). This negative correlation was notably stronger in the fatal group (correlation coefficient −0.940) than in the non-fatal group (correlation coefficient −0.345). Conclusion: In this study, we established a correlation between SFTS viral load and Ct values for estimating the initial viral load and early predicting prognosis. These results are expected to offer valuable insights for SFTS patient treatment and prognosis prediction. [ABSTRACT FROM AUTHOR]

Background: Extranodal extension (ENE) is an established prognostic factor in several gastrointestinal cancers. However, the prognostic impact remains unclear. Here, we investigated the prognostic implications of ENE in patients with surgically resected pancreatic cancer. Methods: We retrospectively reviewed 476 surgically resected pancreatic head cancer patients who consecutively underwent upfront pancreaticoduodenectomy for pathologically confirmed pancreatic ductal adenocarcinoma between January 2009 and December 2013. We compared the disease‐free survival (DFS) rates of the patients according to ENE status. Results: Among the 476 patients, patients with ENE had lower DFS rates than those without ENE (N0, 13 months; LN+/ENE−, 7 months; LN+/ENE+, 6 months; P <.001). In addition, even in the same N stage, patients with ENE had lower DFS rates than those without ENE (N0, 13 months; N1/ENE− 8 months; N1/ENE+, 7 months; N2/ENE−, 7 months; N2/ENE+, 4 months, P <.001). However, there was no significant difference in survival rates between patients in the N1/ENE+ group and those in the N2/ENE− group. Additionally, ENE was an independent prognostic factor for pancreatic cancer. Conclusions: Extranodal extension significantly predicted a poor prognosis among patients with pancreatic head cancer, especially those with nodal metastasis. Therefore, ENE should be considered a prognostic factor in future editions of the staging system. [ABSTRACT FROM AUTHOR]

Determination of vessel resection in patients with pancreatectomy after neo-adjuvant chemotherapy remains controversial. The recently introduced computed tomography-based vascular burden index presents a potential solution to this challenge. This study aimed to evaluate the model performance for the prediction of vascular resection and pathological invasion. Patients who underwent surgery after neo-adjuvant chemotherapy were included. Two independent reviewers measured the vascular tumour burden index around the adjacent artery (AVBI), and vein (VVBI). The area under the curve was compared to assess the predictive capacity of vascular burden index values and their changes for vascular resection and pathological vascular invasion. Among 252 patients, 179 and 73 had borderline resectable and locally advanced pancreatic cancer, respectively. Concurrent vessel resection and pathological vascular invasion were observed in 121 (48.0 %) and 42 (16.6 %) patients, respectively. In all patients, the VVBI (area under the curve: 0.872) and AVBI (0.911) after neo-adjuvant therapy significantly predicted vessel resection. In patients with vascular resection, the VVBI after neo-adjuvant chemotherapy (0.752) and delta value of the AVBI (0.706) demonstrated better performance for predicting pathological invasion of the resected vein. The regression of the AVBI and VVBI was an independent prognostic factor for survival (hazard ratio: 0.54, 95 % confidence interval: 0.34–0.85; P = 0.009) Regressed VVBI on serial computed tomography scans is useful for predicting vein resection and pathological venous invasion before surgery. The delta value of the AVBI may therefore be helpful for predicting pathological arterial invasion after neo-adjuvant chemotherapy. • Adjacent vessels were resected in 50 % of patients after neo-adjuvant chemotherapy, and pathological invasion of resected vessels occurred in approximately 30 % of cases. • A regressed VVBI or VVBI score <6 was associated with a reduced likelihood of venous invasion based on pathological reports. • Patients with regressed AVBI and VVBI could achieve longer survival. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a clinical syndrome caused by various etiologies that results in systolic and diastolic cardiac dysfunction with congestion. While evaluating HF and planning for treatment, physicians utilize various laboratory tests, including electrocardiography, diverse imaging tests, exercise testing, invasive hemodynamic evaluation, or endomyocardial biopsy. Among these, cardiac imaging modalities and biomarkers are the mainstays during HF diagnosis and treatment. Recent developments in non-invasive imaging modalities, such as echocardiography, computed tomography, magnetic resonance imaging, and nuclear imaging, have helped us understand the etiology, pathophysiology, and hemodynamics of HF, and determine treatment options and predict the outcomes. Due to the convenience of their use and potential impact on HF management, biomarkers are increasingly adopted in our clinical practice as well as research purpose. Natriuretic peptide is the most widely used biomarker for the diagnosis of HF, evaluation of treatment response, and prediction of future outcomes. Other cardiac biomarkers to evaluate the pathophysiological mechanisms of HF include myocardial injury, oxidative stress, inflammation, fibrosis, hypertrophy, and neurohormonal activation. Because HF results from complex cardiac disorders, it is essential to assess the disease status multidimensionally. The proper utilization of multimodality imaging and cardiac biomarkers can improve the quality of patient management and predict clinical outcomes in HF in the era of personalized medicine. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the characteristics and clinical outcomes of patients with nonsmoking small cell lung cancer (SCLC) using a nationwide registry in Korea.Methods: The Korean Association for Lung Cancer developed a registry in cooperation with the Korean Central Cancer Registry (KCCR) and surveyed approximately 10% of recorded lung cancer cases.Results: From 2014 to 2016, the KCCR registered 1,043 patients newly diagnosed with SCLC among a total of 8,110 lung cancer patients. In subgroup analysis, Kaplan meier survival analysis showed that the overall survival (OS) was significantly shorter in the nonsmoking subgroup than the ever-smoking subgroup of SCLC patients with extensive disease (6.99 vs. 9.68 months; P = 0.016). Among SCLC patients with limited disease, OS was also shorter in the nonsmoking subgroup, without statistical significance (19.4 vs. 23.5 months; P = 0.247). In a multivariate analysis using a Cox regression model, never smoking was not associated with shorter OS, but older age, extensive stage, poor performance status (Eastern Cooperative Oncology Group grade ≥ 2), male sex, no prophylactic cranial irradiation, and no active treatment (chemotherapy and/or radiotherapy) were associated with poor prognosis.Conclusion: This evaluation of an unbiased nationwide survey dataset revealed that a significant proportion of Korean SCLC patients were never-smokers. No history of smoking appeared to be a significant prognostic factor according to the univariate analysis but was confirmed to be statistically insignificant through a multivariate analysis of the total population. Reasons for a poor prognosis may include the possibility that a high rate of the elderly population is composed of nonsmokers who did not receive active treatment. [ABSTRACT FROM AUTHOR]

This study estimated the outcome of delayed intravitreal anti-vascular endothelial growth factor (VEGF) therapy due to the coronavirus (COVID-19) disease pandemic on the prognosis of patients with neovascular age-related macular degeneration (nAMD). This study retrospectively enrolled 57 nAMD patients whose intravitreal anti-VEGF injections were delayed for >2 weeks between February and June 2020. Best-corrected visual acuity (BCVA), central subfield thickness (CST), and anatomical characteristics were evaluated before (baseline), on the day, and at 2, 4, and 6 months after the delayed injection, and risk factors were identified. The average injection interval before and after treatment delay was 3.05 ± 1.45 and 2.41 ± 1.46 months, respectively (p = 0.002). The CST at baseline and on the day of delayed injection was 227.82 ± 62.46 and 267.26 ± 77.74 µm, respectively (p < 0.001). The average BCVA decreased from 0.29 ± 0.29 logMAR (baseline) to 0.38 ± 0.31 logMAR (6 months) (p = 0.001). The maximum subretinal fluid (SRF) height increased from 84.32 ± 89.33 µm (baseline) to 121.38 ± 103.36 µm (6 months) (p = 0.027). A higher baseline maximum SRF height was associated with less SRF height deterioration 6 months later (p < 0.001). Delayed intravitreal anti-VEGF therapy caused by the COVID-19 pandemic has worsened BCVA and residual SRF in nAMD patients after a temporary recovery. The baseline SRF reduce the degree of SRF height deterioration. [ABSTRACT FROM AUTHOR]

Background: Although a minimally invasive extended cholecystectomy (MIEC) for T2 gallbladder cancer (T2 GBC) has been performed in many experienced centers, no oncologic comparison with open extended cholecystectomy (OEC) has yet been reported. Methods: T2 GBC patients who underwent MIEC (n = 60) or OEC (n = 135) were enrolled. We used propensity score matching (PSM) using pre- and intraoperative variables. Short- and long-term outcomes were then compared before and after PSM. Results: Before PSM, OEC patients more frequently showed completion of surgery after a simple cholecystectomy (standardized mean difference [SMD] = -0.551), and lymph node enlargement on preoperative computed tomography (SMD = -0.471). PSM was used to select 56 patients from each of the 2 patient groups. MIEC patients showed comparable complication rate (7.1% versus 12.5%, P = .365) and shorter hospital stay (5.7 days versus 9.8 days, P < .001). The median follow-up period was 26.2 months, and 5-year overall survival (OS) rate (96.8% versus 91.1%, P = .464) and 5-year recurrence free survival (RFS) (54.7% versus 44.4%, P = .580) outcomes were still comparable between MIEC and OEC groups. Conclusion: MIEC have advantages such as early recovery and comparable short-term outcomes compared with OEC. MIEC showed comparable OS and RFS outcomes compared with OEC. MIEC is a safe option without oncological compromise for T2 GBC. [ABSTRACT FROM AUTHOR]

Locally advanced rectal cancer patients often display favorable responses and favorable oncologic outcomes. Due to the low recurrence rate, there is scarcity of studies investigating the prognostic factors influencing their survival. Therefore, our study sought to assess the prognostic factors associated with survival in rectal cancer patients who achieved either a pathologic complete response or a pathologic stage I after neoadjuvant chemoradiotherapy combined with radical resection. In this retrospective study, we analyzed data from cohort of 1394 patients diagnosed with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy combined with total mesorectal excision from January 2008 to April 2017. Finally, we selected 474 (34.2 %) who exhibited either a pathologic complete response or attained pathologic stage I following the treatment. Subsequently, we analyzed the prognostic factors influencing disease-free and overall survival. A total of 161 (34 %) achieved a pathologic complete response. Our analysis revealed that circumferential resection margin and the administration of adjuvant chemotherapy were prognostic factors for disease-free survival (p = 0.011, p = 0.022). Furthermore, factors influencing overall survival included the clinical N stage and administration of adjuvant chemotherapy (p = 0.035, p = 0.015). In conclusion, the circumferential resection margin, clinical N stage, and administration of adjuvant chemotherapy were prognostic factors for survival in patients showing good response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. For patients with a positive circumferential resection margin and clinical N (+) stage, intensive follow-up might be needed to achieve favorable oncologic outcomes. Also, we recommend considering adjuvant chemotherapy as a beneficial treatment approach for these patients. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objective: The aim of the study was to perform mRNA-miRNA regulatory network analyses to identify a miRNA panel for molecular subtype identification and stratification of high-risk patients with pancreatic ductal adenocarcinoma (PDAC). Background: Recent transcriptional profiling effort in PDAC has led to the identification of molecular subtypes that associate with poor survival; however, their clinical significance for risk stratification in patients with PDAC has been challenging. Methods: By performing a systematic analysis in The Cancer Genome Atlas and International Cancer Genome Consortium cohorts, we discovered a panel of miRNAs that associated with squamous and other poor molecular subtypes in PDAC. Subsequently, we used logistic regression analysis to develop models for risk stratification and Cox proportional hazard analysis to determine survival prediction probability of this signature in multiple cohorts of 433 patients with PDAC, including a tissue cohort (n = 199) and a preoperative serum cohort (n = 51). Results: We identified a panel of 9 miRNAs that were significantly upregulated (miR-205-5p and -934) or downregulated (miR-192-5p, 194-5p, 194-3p, 215-5p, 375-3p, 552-3p, and 1251-5p) in PDAC molecular subtypes with poor survival [squamous, area under the receiver operating characteristic curve (AUC) = 0.90; basal, AUC = 0.89; and quasimesenchymal, AUC = 0.83]. The validation of this miRNA panel in a tissue clinical cohort was a significant predictor of overall survival (hazard ratio = 2.48, P < 0.0001), and this predictive accuracy improved further in a risk nomogram which included key clinicopathological factors. Finally, we were able to successfully translate this miRNA predictive signature into a liquid biopsy–based assay in preoperative serum specimens from PDAC patients (hazard ratio: 2.85, P = 0.02). Conclusion: We report a novel miRNA risk-stratification signature that can be used as a noninvasive assay for the identification of high-risk patients and potential disease monitoring in patients with PDAC. [ABSTRACT FROM AUTHOR]

Acral lentiginous melanoma (ALM) is the most common subtype of cutaneous melanoma among Asians; punch biopsy is widely performed for its diagnosis. However, the pathologic parameters evaluated via punch biopsy may not be sufficient for predicting disease prognosis compared to the parameters evaluated via excisional biopsy. We investigated whether changes in Breslow thickness (BT) between initial punch biopsy results and final pathology reports can affect the prognosis of ALM. Pathologic parameters were recorded from specimens acquired through the initial punch biopsy and wide excision. Patients were classified into two groups based on a change in Breslow depth: the BT increased or decreased on comparing the samples from the initial punch biopsy and final wide excision. We compared clinical characteristics, and a Cox regression model was used to identify independent prognostic factors influencing melanoma-specific death (MSD). Changes in BT did not affect MSD (hazard ratio [HR]: 0.55, P = 0.447). In multivariate analysis, a higher BT (> 2 mm) (HR: 9.93, P = 0.046) and nodal metastasis (HR: 5.66, P = 0.041) were significantly associated with an increased MSD risk. The use of punch biopsy did not affect MSD despite the inaccuracy of BT measurement as long as ALM was accurately diagnosed. [ABSTRACT FROM AUTHOR]

Background: Preserved ratio impaired spirometry (PRISm) is a common spirometric pattern that is associated with respiratory symptoms and higher mortality rates. However, the relationship between lung cancer and PRISm remains unclear. This study investigated the clinical characteristics of lung cancer patients with PRISm and the potential role of PRISm as a prognostic factor. Methods: We retrospectively reviewed data collected from 2014 to 2015 in the Korean Association for Lung Cancer Registry. We classified all patients into three subgroups according to lung function as follows: normal lung function; PRISm (forced expiratory volume in 1 s [FEV1] < 80% predicted and FEV1/forced vital capacity [FVC] ≥ 0.7); and chronic obstructive pulmonary disease (COPD; FEV1/FVC < 0.7). In non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the overall survival period was compared among the three subgroups. The prognostic factors were investigated using Cox regression analysis. Results: Of the 3763 patients, 38.6%, 40.1%, and 21.3% had normal lung function, COPD, and PRISm, respectively. Patients with PRISm had poorer overall survival than those with COPD or normal lung function in NSCLC and SCLC (Mantel–Cox log‐rank test, p < 0.05). In the risk‐adjusted analysis, overall survival was independently associated with COPD (hazard ratio [HR] 1.209, p = 0.027) and PRISm (HR 1.628, p < 0.001) in NSCLC, but was only associated with PRISm (HR 1.629, p = 0.004) in SCLC. Conclusions: PRISm is a significant pattern of lung function in patients with lung cancer. At the time of lung cancer diagnosis, pre‐existing PRISm should be considered a predictive factor of poor prognosis. [ABSTRACT FROM AUTHOR]

Introduction: The prognostic factors of pancreatic neuroendocrine tumor (PNET) are unclear, and the treatment guidelines are insufficient. This study aimed to suggest a treatment algorithm for PNET based on risk factors for recurrence in a large cohort. Methods: Data of 918 patients who underwent curative intent surgery for PNET were collected from 14 tertiary centers. Risk factors for recurrence and survival analyses were performed. Results: The 5-year disease-free survival (DFS) rate was 86.5%. Risk factors for recurrence included margin status (R1, hazard ratio [HR] 2.438; R2, HR 3.721), 2010 WHO grade (G2, HR 3.864; G3, HR 7.352), and N category (N1, HR 2.273). A size of 2 cm was significant in the univariate analysis (HR 8.511) but not in the multivariate analysis (p = 0.407). Tumor size was not a risk factor for recurrence, but strongly reflected 2010 WHO grade and lymph node (LN) status. Tumors ≤2 cm had lower 2010 WHO grade, less LN metastasis (p < 0.001), and significantly longer 5-year DFS (77.9 vs. 98.2%, p < 0.001) than tumors >2 cm. The clinicopathologic features of tumors <1 and 1-2 cm were similar. However, the LN metastasis rate was 10.3% in 1-2-cm sized tumors and recurrence occurred in 3.0%. Tumors <1 cm in size did not have any LN metastasis or recurrence. Discussion/Conclusion: Radical surgery is needed in suspected LN metastasis or G3 PNET or tumors >2 cm. Surveillance for <1-cm PNETs should be sufficient. Tumors sized 1-2 cm require limited surgery with LN resection, but should be converted to radical surgery in cases of doubtful margins or LN metastasis. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the outcomes of large angiomyolipoma (AML) treatment by selective arterial embolization (SAE) versus nephron-sparing surgery (NSS) using a robotic surgical system. Materials and Methods: Between January 2011 and June 2018, we retrospectively reviewed 25 patients who underwent robot-assisted partial nephrectomy (RAPN) or SAE for large AMLs. Ten patients underwent RAPN, and 15 underwent SAE. Patient demographics, AML characteristics, and operative and postoperative clinical outcomes were recorded and analyzed. Outcomes were compared between patients who underwent RAPN and patients who underwent SAE. Specifically, changes in renal function and size were evaluated after the treatment. Results: The mean age of the patients was 52.9 years, and 22 of 25 patients were female. The mean maximum AML diameter on computed tomography was 8.9 cm, and 8 patients had multiple masses. Twenty-two of 25 patients had moderate to high RENAL complexity. Patients who underwent SAE had more symptoms (p = 0.018) and higher RENAL complexity scores (p = 0.013) on average. On average, tumor size decreased by 99% among RAPN patients and by 58% among SAE patients (p = 0.001). Although the mean pretreatment estimated glomerular filtration rate (eGFR) was higher among RAPN patients (99.8 vs. 80.0 mL/min/1.73 m2, p = 0.043), there were no significant changes in eGFR in either group after the treatment. One patient in the RAPN group experienced complications, but the postoperative ileus resolved without intervention. Conclusions: Both RAPN and SAE were effective and feasible treatment options for large AMLs. The AML characteristics and the condition of the patient might be important in determining the appropriate treatment method. [ABSTRACT FROM AUTHOR]

Background and objective: RA‐ILD has a variable clinical course, and its prognosis is difficult to predict. Moreover, risk prediction models for prognosis remain undefined. Methods: The prediction model was developed using retrospective data from 153 patients with RA‐ILD and validated in an independent RA‐ILD cohort (n = 149). Candidate variables for the prediction models were screened using a multivariate Cox proportional hazard model. C‐statistics were calculated to assess and compare the predictive ability of each model. Results: In the derivation cohort, the median follow‐up period was 54 months, and 38.6% of the subjects exhibited a UIP pattern on HRCT imaging. In multivariate Cox analysis, old age (≥60 years, HR: 2.063), high fibrosis score (≥20% of the total lung extent, HR: 4.585), a UIP pattern (HR: 1.899) and emphysema (HR: 2.596) on HRCT were significantly poor prognostic factors and included in the final model. The prediction model demonstrated good performance in the prediction of 5‐year mortality (C‐index: 0.780, P < 0.001); furthermore, patients at risk were divided into three groups with 1‐year mortality rates of 0%, 5.1% and 24.1%, respectively. Predicted and observed mortalities at 1, 2 and 3 years were similar in the derivation cohort, and the prediction model was also effective in predicting prognosis of the validation cohort (C‐index: 0.638, P < 0.001). Conclusion: Our results suggest that a risk prediction model based on HRCT variables could be useful for patients with RA‐ILD. [ABSTRACT FROM AUTHOR]

During left ventricular opacification (LVO), myocardial contrast uptake (MCU) is frequently observed, but its clinical implication is uncertain. We aimed to investigate the diagnostic performance of MCU and its prognostic value in known or suspected coronary artery disease (CAD). Contrast echocardiography was retrospectively analyzed in 457 patients who had previous coronary angiography <12 mo before LVO. MCU was classified into replacement or interstitial patterns. Subendocardial patterns were further inspected. Events were defined as a primary composite of the occurrence of acute coronary syndrome, heart failure hospitalization, sustained ventricular tachycardia and all-cause mortality. MCU had an 87.6% sensitivity, 75.5% specificity, 73.0% positive predictive value and 87.7% negative predictive value in detecting CAD. After a median follow-up of 17.3 mo, 52 events occurred. Replacement, interstitial and subendocardial MCU patterns were associated with events. In conclusion, the presence of MCU was useful in identifying CAD and provided incremental prognostic value for clinical outcomes. [ABSTRACT FROM AUTHOR]

Background and objective: Idiopathic interstitial pneumonia (IIP) with autoimmune features that does not fulfil connective tissue disease (CTD) criteria has been recently defined as interstitial pneumonia with autoimmune features (IPAF). However, its long‐term clinical course and outcome are poorly understood. Methods: We included consecutive patients diagnosed with IIP (n = 586) or CTD‐related interstitial lung disease (CTD‐ILD, n = 149). Some patients with IIP were reclassified as IPAF based on recent guidelines. Results: The median follow‐up period was 45 months. Among the IIP patients, 109 (18.6%) were reclassified as IPAF. Compared to the non‐IPAF‐IIP group, the IPAF group had slower diffusing capacity of the lung for carbon monoxide (DLCO) and total lung capacity declines, and more frequent CTD development during follow‐up periods. The prognosis of the IPAF was better than that of the non‐IPAF‐IIP and similar to that of the CTD‐ILD. IPAF was associated with better prognosis in the IIP cohort on univariate but not on multivariate analysis. Usual interstitial pneumonia (UIP) pattern, old age and low DLCO independently predicted mortality in the IPAF group. Conclusion: Compared to the non‐IPAF‐IIP group, the IPAF group had slower lung function declines and more frequent CTD development during follow‐up. Although the prognosis of IPAF group was better than that of non‐IPAF‐IIP group and similar to that of CTD‐ILD group, it showed poor prognosis in patients with old age, UIP pattern, and low DLCO. The interstitial pneumonia with autoimmune feature (IPAF) group showed better survival than the non‐IPAF‐idiopathic interstitial pneumonia (IIP) group but similar survival to the connective tissue disease (CTD)‐related interstitial lung disease (ILD) group and its prognosis is largely influenced by the presence of the usual interstitial pneumonia (UIP) pattern. The IPAF group had slower lung function declines and more frequent CTD development than the non‐IPAF‐IIP group. [ABSTRACT FROM AUTHOR]

Background: The diagnostic impact of lymphovascular invasion (LVI), perineural invasion (PNI), and tumor budding in stage I colon cancer is currently unknown. This study was conducted to evaluate the prognostic impact of LVI, PNI, and tumor budding in stage I colon cancer. Methods: From January 2008 to December 2013, 720 patients who underwent curative surgery and were diagnosed with stage I colon cancer were reviewed retrospectively. These patients were categorized into two groups based on LVI, PNI, and tumor budding: the no risk group (n = 566) and risk group (n = 154). Results: Median follow-up period was 103.5 months, and the 5-year disease-free survival rate of the risk group was significantly lower than that of the no risk group (p = 0.025). In multivariate analysis, only the risk group had prognostic factors for 5-year disease-free survival (p = 0.036). In addition, only differentiation was an independent predictor in the risk group (p = 0.009). Conclusion: LVI, PNI, and tumor budding are strong prognostic factors for stage I colon cancer. Therefore, patients with positive LVI, PNI, or tumor budding should receive close follow-up and potentially be considered for chemotherapy. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are key effectors in cancer immunosurveillance and can be used as a prognostic biomarker in diverse cancers. Nonetheless, the role of NK cells in pancreatic cancer (PC) remains elusive, given conflicting data on their association with disease prognosis. In this study, using conventional K562 target cells and complementary engineered target cells providing defined and synergistic stimulation for NK cell activation, a correlation between impaired NK cell cytotoxic degranulation and PC progression was determined. Peripheral blood mononuclear cells (PBMCs) from 31 patients with newly diagnosed PC, 24 patients with non-malignant tumors, and 37 healthy controls were analyzed by flow cytometry. The frequency, phenotype, and effector functions of the NK cells were evaluated, and correlations between NK cell functions and disease stage and prognosis were analyzed. The results demonstrated that effector functions, but not frequency, of NK cells was progressively decreased on a per-cell basis during PC progression. Impaired cytotoxic degranulation, but not IFN-γ production, was associated with clinical features indicating disease progression, such as high serum CA19-9 and high-grade tumors. Significantly, this impairment correlated with cancer recurrence and mortality in a prospective analysis. Furthermore, the impaired cytotoxic degranulation was unrelated to NKG2D downregulation but was associated with increased circulating and tumor-associated TGF-β1 expression. Thus, NK cell cytotoxic activity was associated with PC progression and may be a favorable biomarker with predictive and prognostic value in PC. [ABSTRACT FROM AUTHOR]

Background: While there is growing interest in the correlation between chronic obstructive pulmonary disease (COPD) and non‐small cell lung cancer, very few studies have examined the interaction between COPD and small cell lung cancer (SCLC). Therefore, the aim of this study was to examine the impact of COPD on the survival of patients with SCLC. Methods: The medical records of 110 patients with SCLC who received chemotherapy from July 2006 until April 2014 were retrospectively examined. The overall survival (OS) and progression‐free survival (PFS) rates of spirometry‐diagnosed COPD and non‐COPD groups were compared. Predictors for poorer survival were analyzed using Cox proportional hazards regression. Results: Of the 110 SCLC patients, 57 (51.8%) had coexistent COPD. The median OS for the COPD group was 11.6 months and for the non‐COPD group was 11.2 months (log‐rank test, P = 0.581), whereas the median PFS rates were 6.65 and 6.57 months, respectively (log‐rank test, P = 0.559). Multivariate analysis identified Eastern Cooperative Oncology Group performance status ≥ 2 and extensive‐stage SCLC as independent risk factors for shorter OS; however, coexisting COPD was not a predictor of survival. Conclusions: Although over half of the SCLC patients receiving chemotherapy had COPD, coexisting COPD had no impact on the survival of patients with SCLC. [ABSTRACT FROM AUTHOR]

Purpose nab-paclitaxel plus gemcitabine (AG) and FOLFIRINOX have been established as standard first-line treatment in metastatic pancreatic cancer (mPC). We performed retrospective analysis comparing the efficacies of AG and FOLFIRINOX in daily practice setting. Materials and Methods We analyzed 308 patients who presented initially as mPC and received AG (n = 149) or FOLFIRINOX (n = 159) as first-line treatment between 2013 and 2016. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Result There were no significant differences between the two groups in terms of baseline characteristics, except older age and higher Charlson Comorbidity Index (CCI) score in AG group. The response rates (34% vs 34%) and median PFS (6.8 vs 5.1 months) were comparable between two groups (p = 0.88 and p = 0.19, respectively), while median OS was significantly better with AG than FOLFIRINOX (11.4 vs 9.6 months; p = 0.002). Elevated baseline CA19-9 level and liver metastasis were independent adverse prognostic factors for PFS and OS. In subgroup analyses, PFS with AG was better in patients with age ≥ 65 years, peritoneal metastasis, and higher CCI than that with FOLFIRINOX. Conclusion Both AG and FOLFIRINOX showed comparable efficacy outcomes in daily practice setting. AG might be preferentially considered in patients with peritoneal metastasis, comorbid medical conditions or old age. [ABSTRACT FROM AUTHOR]

OBJECTIVE Given the rarity of the disease, the post-resection clinical course of localized pancreatic acinar cell carcinoma (ACC) is largely unknown. Therefore, we aimed to analyze the outcomes of patients with localized pancreatic ACC who underwent curative surgical resection. METHODS We retrospectively analyzed the outcomes of 20 patients with resectable pancreatic ACC who underwent surgery. RESULTS Altogether 20 patients were included in the study, with a median age of 57 years and a male predominance. There were eight pure ACC, 10 mixed acinar-neuroendocrine carcinomas and two mixed acinar-ductal adenocarcinomas. Among the 15 patients who were staged histologically, 3, 8 and 4 were at stages IB, IIA and IIB, respectively. Eleven patients received adjuvant chemotherapy (5-fluorouracil-based [ n = 9]; gemcitabine [ n = 1]; etoposide plus cisplatin [ n = 1]). In a median follow-up period of 27.1 months, disease recurred in 10 patients, most commonly in the liver (90%). Median recurrence-free survival and overall survival were 16.9 months and 75.0 months, respectively. Elevation of cancer antigen 19-9 (CA19-9), lymph node metastasis and neural invasion were significantly associated with poor overall survival ( P = 0.007, P = 0.027 and P = 0.016, respectively). CONCLUSIONS Compared with ductal adenocarcinoma, resectable pancreatic ACC has a favorable prognosis after surgery. Considering that distant metastasis is the most common pattern of recurrence, further studies are necessary to define the role of adjuvant chemotherapy for improving survival outcomes. [ABSTRACT FROM AUTHOR]

Background Hemoconcentration (HC) is associated with reduced mortality, whereas hyponatremia (HN) has been associated with an increased risk of adverse outcomes in patients with acute decompensated heart failure (ADHF). We sought to determine if the presence of HN influences the beneficial prognostic value of HC in ADHF patients. Methods We analyzed 2046 ADHF patients from the Korean Heart Failure Registry. We defined HC as an increased hemoglobin level from admission to discharge, and HN as sodium <135 mmol/L at admission. Our primary composite endpoint was all-cause mortality and/or HF re-hospitalization. Results Overall, HC occurred in 889 (43.5%) patients and HN was observed in 418 patients (20.4%). HC offered higher 2-year event-free survival in patients without HN (73.2% vs. 63.1% for no-HC, log-rank p < 0.001), but not in patients with HN (54.2% vs. 58.7% for no-HC, log-rank p = 0.879, p for interaction = 0.003). In a multiple Cox proportional hazard analysis, HC without HN conferred a significant event-free survival benefit (hazard ratio: 0.703, 95% confidence interval 0.542–0.912, p = 0.008) over no-HC with HN. Conclusions Only HC occurring in ADHF without HN was associated with improved clinical outcomes. These results provide further support for the importance of HN as a challenging therapeutic target in ADHF patients. [ABSTRACT FROM AUTHOR]

Background Perineural invasion ( PNI) may influence the prognosis of colon cancer, but little is known about its predictive value. The aim of this study was to reveal the role of PNI in predicting prognosis after curative resection of colon cancer, especially T3N0. Methods Two hundred and fifty-five patients who underwent curative resection for colon cancer at Samsung Medical Center and were later diagnosed with stage T3N0 by a pathological report between November 2004 and December 2007 were retrospectively recruited into the study. Results Among the 255 patients, 156 were male and 99 were female. The mean age was 61 years (range, 25 to 88 years). The most common tumour location was the sigmoid colon (93 patients, 36.5%). The median follow-up period was 61 months (range, 1 to 98 months). PNI was detected in 18 patients (7.1%). Adjuvant chemotherapy was performed in 205 patients (80.4%). The 5-year disease-free survival rate was greater for patients with PNI negative tumours compared with those with PNI positive tumours (92.0% versus 76.0%, P = 0.025). Adjuvant chemotherapy was not associated with significant differences in survival rate (94.8% versus 96.9%, P = 0.625). On multivariate analysis, PNI was an independent prognostic factor for disease-free and overall survival ( P = 0.046, hazard ratio (HR) = 3.113, 95% confidence interval ( CI) = 1.020-9.505 and P = 0.019, HR = 9.395, 95% CI = 1.453-60.755 respectively). Conclusions PNI is the only significant prognostic factor affecting disease-free and overall survival in patients with T3N0 colon cancer. [ABSTRACT FROM AUTHOR]

Background: The role of laparoscopic resection in patients with clinically suspicious T4 colorectal cancer remains controversial. The aim of this study was to compare the long-term and oncologic outcomes of laparoscopic resection and the open approach in clinical T4 colorectal cancer.Methods: Two hundred ninety-three consecutive patients undergoing curative surgery for colorectal cancer suspected to be T4 by computed tomography and/or magnetic resonance imaging were reviewed.Results: Despite clinical suspicion of T4 disease in all cases, concordance with pathologic determination of T4 was only 37.9 %. Of the 71 patients in the laparoscopic group, four (5.6 %) were converted to the open technique. Patients in the laparoscopic group had significantly lower estimated blood loss (p < 0.001), fewer days to first flatus (p = 0.001), shorter length of hospital stay (p < 0.001), and fewer adverse events (14.1 % versus 31.5 %, p = 0.004). After a median follow-up of 36 months, 5-year disease-free survival was not significantly different between the two groups (81.8 % in laparoscopic versus 73.9 % in open surgery, p = 0.433). The clinical factors that predicted T4 staging on pathologic examination were found to be male sex (p = 0.038), preoperative carcinoembryonic antigen status (p = 0.021), clinical N status (p = 0.046), and clinical cancer perforation (p = 0.004).Conclusions: Laparoscopic colorectal resection for T4 colorectal cancer has perioperative and long-term oncologic outcomes similar to those of the open approach when performed by an experienced surgeon. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic performance of rectal MRI in predicting candidates for local excision (LE; ypT0-1N0) after neoadjuvant chemoradiation therapy (CRT) in patients with rectal cancer.Materials and Methods: The institutional review board approved our retrospective study and waived informed consent. Inclusion criteria were as follows: patients with pathologically confirmed mid to lower rectal cancer (cT3NxM0 before neoadjuvant CRT) who underwent neoadjuvant CRT and had MRI performed at 3T before and after neoadjuvant CRT. A total of 168 patients met the study criteria between 2011 and 2012. Two observers independently assessed tumor and nodal stages on MR images obtained after neoadjuvant CRT. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for identifying a candidate for LE (ypT0-1N0) were calculated. Interobserver agreement was assessed with kappa value. Predictive factors for ypT0-1N0 were evaluated by logistic regression models.Results: MRI had relatively high accuracy, specificity, and NPV (85.9%, 93.8%, and 88.9% for observer 1 and 85.3%, 96.1%, and 86.6% for observer 2), moderate PPV (71.4% and 76.2%), and relatively low sensitivity (57.1% and 45.7%) for predicting ypT0-1N0. The interobserver agreement was fair (kappa value = 0.593). Carcinoembryonic antigen levels after neoadjuvant CRT and the maximal extramural depth of tumor spread were significant predictors of ypT0-1N0 (P = 0.037 and 0.017, respectively).Conclusion: MRI after neoadjuvant CRT can predict a candidate for LE (ypT0-1N0) after neoadjuvant CRT with moderate PPV and relatively high NPV. J. Magn. Reson. Imaging 2016;44:471-477. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare oncologic outcomes and perioperative variables following conventional laparoscopic surgery (LAP) versus hand-assisted laparoscopic surgery (HALS) for rectal cancer.Methods: Between January 2008 and December 2012, 2680 consecutive patients who underwent curative resection for rectal cancer were analyzed. We used 1:1 propensity score matching to adjust for potential baseline confounders between groups including age, sex, body mass index, American Society of Anesthesiologists score, tumor distance from the anal verge, clinical T and N categories, pathologic T and N categories, preoperative carcinoembryonic antigen level, and the status of preoperative concurrent chemoradiotherapy. After matching, we analyzed 278 patients in each group (n = 556).Results: The median follow-up period was 36.2 and 37.4 months in the HALS group and the conventional LAP group, respectively. Postoperative complications were not significantly different between the two groups (P = 0.531). The 5-year overall survival rate was 88.8 % in the HALS group and 91.2 % in the conventional LAP group (P = 0.329). The 5-year disease-free survival rate was 77.0 % in the HALS group and 79.7 % in the conventional LAP group (P = 0.591).Conclusions: HALS is considered a safe and feasible approach for rectal cancer treatment that enables the preservation of the advantages of conventional laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Background/Aims: Limited treatment options are available for patients with hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). Transarterial radioembolization using Yttrium-90 microspheres is a new treatment modality for HCC with PVT. For this analysis, we compared responses to treatment with radioembolization and with sorafenib. Methods: We evaluated 32 patients who were part of a multicenter retrospective cohort. All patients had PVT without extrahepatic metastasis and were treated with radioembolization in one of six tertiary referral hospitals in Korea. We retrospectively enrolled another 31 consecutive PVT patients without extrahepatic metastasis from a single center who received sorafenib treatment to serve as the control group. We used inverse probability weighting (IPW) using propensity scores to adjust for the between-group differences in baseline characteristics. Results: At 3 months, the response rate and disease control rate were 32.1% (9/32) and 57.1% (16/32), respectively, in the radioembolization group and 3.2% (1/31) and 41.9% (13/31) in the sorafenib group. Median overall survival (OS) and time to progression (TTP) were not significantly different between the radioembolization group and the sorafenib group (13.8 months and 10.0 months, P = 0.22; and 6.0 months and 6.0 months, P = 0.08; respectively). No differences in OS (P = 0.97) or TTP (P = 0.34) were observed after IPW was applied to balance the population characteristics. The sorafenib group showed significantly more grade 3/4 adverse effects than the radioembolization group (P < 0.01). Conclusion: HCC patients with PVT who underwent radioembolization achieved comparable survival to patients who received sorafenib, even after application of IPW. The radioembolization group also experienced fewer severe adverse effects. Radioembolization can be considered a new treatment option for patients with HCC with PVT. [ABSTRACT FROM AUTHOR]

Background: To elucidate the association between growth plate injury size and the beginning of physeal growth disturbance by MRI. Methods: Thirty-two 5-week-old male Japanese white rabbits were used. Injuries were made to the right tibial proximal growth plate central region with a 3.0-mm and a 1.2-mm drill. The left tibia was used as a control. MRI (7.04 Tesla [T], gradient echo: repetition time [TR], 71.68 ms; echo time [TE], 3.60 ms; proton-density weighted imaging: TR, 2000 ms; TE, 12 ms) of the growth plates was performed at 1, 4, 8, 10, and 12 weeks postinjury. Tibia length, histology, radiography, and microcomputed tomography (µCT) were studied. Results: MRI showed that at 10 and 12 weeks postinjury in the 3.0-mm group, the medial and lateral growth plates in the noninjured regions were significantly reduced compared with the controls (P < 0.05). At 12 weeks postinjury in the 1.2-mm group, medial and lateral growth plates in the noninjured regions were significantly reduced (P < 0.05). Tibia length and histological growth plate height of injured side in both groups were significantly shorter than controls at 12 weeks postinjury (P < 0.05). Comparison with the controls showed no significant difference at any of the time periods in either the 3.0- or 1.2-mm group according to the radiographic studies (P > 0.05). Bony bridges developed in all the subjects of the 3.0-mm group and in five of eight subjects of the 1.2-mm group, as shown by µCT images. Conclusion: This study suggested that growth plate injury size was associated with the timing of the beginning of physeal growth disturbance. [ABSTRACT FROM AUTHOR]

Background: The prognosis of acute heart failure (HF) can be determined by cardio-renal function which is assessed by cystatin-C (Cys-C). We evaluated whether Cys-C could be a more useful prognostic indicator in acute HF, compared with uric acid (UA) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Methods: Two hundred thirty-two HF patients in the emergency room were studied using measurements of Cys-C, UA, and NT-proBNP. During the follow-up, cardiac events, defined as the composites of recurrent HF or cardiac death, were determined. Results: Seventy-seven cardiac events (28 cardiac deaths, 49 recurrent HFs) occurred over two years. The events group revealed higher levels of Cys-C, UA, and NT-proBNP. They showed increased blood urea nitrogen and creatinine, reduced septal tissue Doppler velocity (TVI-Sm), and low frequencies of beta-blockers (BB), diuretics and angiotensin-converting enzyme inhibitors/-receptor blockers. Cys-C (the best cutoff: 1.7 mg/l) had a steady, persistent hazard ratio (HR) over two years. On multivariate analysis, Cys-C, TVI-Sm, and BB were significant predictors for adverse events. Cys-C provided an incremental value for prognosis more than NT-proBNP and UA did over the follow-up period. Conclusions: Compared with UA and NT-proBNP, Cys-C could be better prognostic biomarker for cardiac events two years after acute HF. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to investigate the expression of Hsp90β and GRP94, and elucidate the clinical significance of their expression, in patients with resectable non-small-cell lung cancer ( NSCLC). Methods and results Surgical tissue specimens were obtained from 208 patients with NSCLC who underwent surgical resection. The expression levels of Hsp90β and GRP94 were assessed with tissue microarrays and immunohistochemistry. No correlations were observed between Hsp90β or GRP94 expression and several clinicopathological factors. The high-Hsp90β group [median overall survival ( OS) 20.4 months; 95% confidence interval ( CI) 0.000-40.864] showed a significant decrease in OS as compared with the low-Hsp90β group (median OS not reached; P = 0.003). In contrast to the Hsp90β analysis, the GRP94 analysis did not show a difference in OS. Moreover, in subgroup analyses of patients with squamous cell carcinoma histology, OS ( P = 0.012) and relapse-free survival ( P = 0.044) were significantly worse in the high-Hsp90β group than in the low-Hsp90β group. Multivariate analysis suggested that old age [hazard ratio ( HR) 1.568; 95% CI 1.019-2.412; P = 0.041], advanced disease ( HR 2.066; 95% CI 1.218-3.502; P = 0.007) and high Hsp90β expression ( HR 1.802; 95% CI 1.061-3.060; P = 0.029) were independent poor prognostic factors for OS. Conclusions Hsp90β expression might be a useful marker of poor OS, although further large prospective studies are warranted to validate our findings. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis even after curative resection. A deep learning-based stratification of postoperative survival in the preoperative setting may aid the treatment decisions for improving prognosis. This study was aimed to develop a deep learning model based on preoperative data for predicting postoperative survival.Methods: The patients who underwent surgery for PDAC between January 2014 and May 2015. Clinical data-based machine learning models and computed tomography (CT) data-based deep learning models were developed separately, and ensemble learning was utilized to combine two models. The primary outcomes were the prediction of 2-year overall survival (OS) and 1-year recurrence-free survival (RFS). The model's performance was measured by area under the receiver operating curve (AUC) and was compared with that of American Joint Committee on Cancer (AJCC) 8th stage.Results: The median OS and RFS were 23 and 10 months in training dataset (n = 229), and 22 and 11 months in test dataset (n = 53), respectively. The AUC of the ensemble model for predicting 2-year OS and 1-year RFS in the test dataset was 0.76 and 0.74, respectively. The performance of the ensemble model was comparable to that of the AJCC in predicting 2-year OS (AUC, 0.67; P = 0.35) and superior to the AJCC in predicting 1-year RFS (AUC, 0.54; P = 0.049).Conclusion: Our ensemble model based on routine preoperative variables showed good performance for predicting prognosis for PDAC patients after surgery. [ABSTRACT FROM AUTHOR]

Background Because of the rarity of duodenal adenocarcinoma, little is known regarding its natural history or prognostic factors for survival. We therefore evaluated surgical treatment, and prognostic factors for survival in patients with duodenal adenocarcinoma. Methods We retrospectively reviewed the medical records of patients who were diagnosed with duodenal adenocarcinoma at Asan Medical Center between December 1999 and December 2009. Results Of the 76 patients, 47 (61%) underwent surgery with curative intent and 29 (39%) underwent palliative operation. Of the former, 25 underwent pancreaticoduodenectomy ( PD), 19 underwent pylorus-preserving PD, 2 underwent segmental duodenectomy and 1 underwent transduodenal excision. The median survival of the 41 patients who achieved R0 resection was 25.1 months (range 4-134 months), with overall 1-, 3- and 5-year survival rates of 80.4%, 63.4% and 60.9%, respectively. Median survival was significantly longer in patients who underwent curative resection than in those who underwent palliative surgery (28.2 versus 6.6 months, P < 0.001). Univariate analysis showed that transfusion and lymph node metastasis were related to survival, and multivariate analysis revealed that lymph node metastasis was independently associated with survival ( P = 0.036). Survival differences were observed between stages of the seventh edition of the American Joint Committee on Cancer staging system. Conclusion In the absence of distant metastasis, curative resection enhances the long-term survival of patients with duodenal adenocarcinoma. Lymph node metastasis is prognostic factor of overall survival. [ABSTRACT FROM AUTHOR]

Purpose: The epithelial-mesenchymal transition (EMT) is known to be associated with tumor progression, invasion and metastasis in colorectal cancer (CRC). Materials and Methods: Tissue samples obtained from 409 patients with stage III CRC treated from 2006 to 2007 were examined by immunohistochemistry to reveal the expression levels of E-cadherin, fibronectin, vimentin and α-smooth muscle actin (SMA). Results: Among the 409 patients, 402 cases (98.3%) showed positive E-cadherin expression. Positive E-cadherin expression was associated with well or moderately differentiated cell types and a stable microsatellite status. In multivariate analysis, a preoperative carcinoembryonic antigen level >5 ng/ml (p = 0.021), advanced N stage (p = 0.017), positive vascular invasion (p = 0.048), positive perineural invasion (p = 0.002) and negative E-cadherin expression (p = 0.002, relative risk = 5.098, 95% CI = 1.801-14.430) were poor prognostic factors affecting disease-free survival. The declining E-cadherin expression was associated with a poor outcome in terms of overall survival in univariate (p = 0.016) but not in multivariate analyses (p = 0.303, relative risk = 1.984, 95% CI = 0.539-7.296). Fibronectin, vimentin and α-SMA were of no prognostic value in this study. Conclusion: The expression pattern of EMT markers in stage III CRC suggests that declining E-cadherin expression is a possible immunohistochemical predictor of patient prognosis. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Transforming growth factor beta (TGF-β) plays an important role in tumorigenesis and metastasis. It works as a tumor suppressor in the normal colon, but acts as a cancer promoter during the late stages of colorectal carcinogenesis. High expression of TGF-β is known to be associated with advanced stages, tumor recurrence and decreased survival of patients. We investigated the expression of TGF-β and its signaling axis molecules and evaluated their prognostic significance in patients with stage III rectal cancers. Methods: Tissues from 201 cases of stage III rectal cancer were subjected to immunohistochemistry for TGF-β1, type II TGF-β receptor, Smad3, Smad4 and Smad7 proteins. The immunoactivities of these molecules were evaluated and the results were compared with clinicopathological variables including patient survival. Results: Low expression of TGF-β1 protein was correlated with a decreased disease-free survival in univariate Kaplan-Meier (p = 0.003) and multivariate Cox regression (HR 9.188 and 95% CI 1.256-67.198, p = 0.029) analyses. The loss of Smad4 protein expression was associated with a reduction in disease-free survival in the univariate analysis, but this finding was not significant after the multivariate analysis. Conclusion: Low expression of TGF-β1 protein is associated with a poor prognosis for patients with stage III rectal cancers. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Fascin is an actin-binding protein that provides mechanical support and cell motility, and involves cancer cell metastasis. We investigated fascin protein expression in gastric cancer and assessed their relationship with clinicopathologic parameters and survival rates. In addition, we researched galectin-3 protein expression to study fascin action mechanisms. We performed immunohistochemisty with fascin and galectin-3 antibodies in 471 gastric carcinomas, using tissue microarrays. Fascin was positive in 14.9% (70/471) of the samples, and fascin expression was related to worse survival rates ( P < 0.001), high clinical stage ( P < 0.001), high T stage ( P < 0.001), nodal metastasis ( P < 0.001), lymphovascular invasion ( P= 0.001) and the intestinal type of Lauren classification ( P= 0.015). Galectin-3 protein expression was positive in 83.9% (395/471) of the samples and was reversely correlated with fascin protein expression ( P= 0.020). Galectin-3 expression was related to low clinical stage ( P < 0.001), but not to survival rates in multivariate analysis. In multivariate analysis, fascin expression was related to worse survival rates (HR = 1.56, P= 0.036), and can be an independent poor prognostic factor in gastric cancer. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated prognostic factors affecting relapse-free survival (RFS) and overall survival (OS), and investigated the role of adjuvant chemotherapy in patients with small bowel adenocarcinoma (SBA). Methods: Data from 52 patients with SBA who underwent curative surgery at the Asan Medical Center between January 1989 and December 2009 were retrospectively analyzed. Patients were divided into two groups: those who did (n = 23) and did not (n = 29) receive adjuvant chemotherapy. Results: At a median follow-up of 32.2 months (range, 5.5-212.2 months), relapses had occurred in 17 patients (32.7%), with a 5-year RFS rate of 52.9% (95% CI, 39.3-66.5%), and 19 patients (36.5%) had died, with a 5-year OS rate of 59.0% (95% CI, 45.6-72.4%). The most frequent sites of relapse were the peritoneum and liver. Multivariate analysis showed that lymph node involvement was the only factor independently associated with poor RFS and OS. After inverse probability of treatment weighting adjustment, adjuvant chemotherapy did not enhance RFS [hazard ratio (HR), 1.399; 95% CI, 0.498-3.933] or OS (HR 0.797; 95% CI, 0.307-2.068). Conclusions: Lymph node involvement is a predictor of poor prognosis in patients with SBA who undergo curative surgery. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In this study, we evaluated the prognostic value of inflammation-based prognostic scores in patients undergoing curative surgery for pancreatic ductal adenocarcinoma (PDAC). A retrospective analysis was conducted for 914 patients undergoing curative surgical resection for PDAC between January 2011 and April 2016. Inflammation-based scores of modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio, and platelet-lymphocyte ratio were assessed. mGPS was classified as high (1 or 2) or low (0). Median age was 63 (range, 33–88) years; 538 patients (58.9%) were male. A high mGPS was independently associated with poor overall survival (OS) and disease-free survival (DFS) (median OS: 25.4 months vs. 20.4 months, p = 0.001; median DFS: 11.6 months vs. 9.3 months, p = 0.002), poor OS in patients with TNM stage I PDAC (44 months vs. 24.8 months, p = 0.001), and poor OS and DFS in patients with tumors located at the pancreatic head or uncinate process (OS: 25.4 months vs. 20.4 months; p = 0.007, DFS: 11.4 months vs. 8.87 months; p = 0.005). Preoperative mGPS was a significant prognostic factor for PDAC after curative resection; thus, mGPS can be a useful prognostic predictive factor in patients with TNM stage I PDAC, especially for tumors located at the head and uncinate. [ABSTRACT FROM AUTHOR]

Aim: To assess the incidence and clinicopathological significance of microsatellite instability (MSI) and the protein expression of hMLH1 and hMSH2 in sporadic endometrioid endometrial adenocarcinoma (SEEA). Methods: A total of 50 patients with pure endometrioid sporadic endometrial adenocarcinoma were enrolled in the study. MSI analysis was done using five polymorphic markers (BAT26, D5S346, BAT25, D17S250, D2S123) and the protein expression of the hMLH1 and hMSH2 genes was determined by immunohistochemical staining. MSI was detected in 24% (12/50) of SEEA cases. Results: There was a significant correlation between MSI status and loss of hMLH1, hMSH2 expression, respectively. No significant association was found between MSI status and clinicopathological parameters, including age, grade, stage, depth of myometrial invasion, lymph-vascular space invasion (LVI), lymph node involvement or peritoneal cytology. However, significant correlations were found between loss of hMLH1 and a lower histological grade and the absence of LVI in patients with SEEA. Conclusions: According to these results, MSI and a loss of protein expression of hMLH1 and hMSH2 may be associated with the pathogenesis of SEEA. In addition, hMLH1 immunostaining might have a role as a prognostic parameter. Further research using a large number of cases is needed to confirm our observations. [ABSTRACT FROM AUTHOR]

We aimed to examine the predictive value of changes in perioperative carbohydrate antigen (CA) 19-9 levels for patients operated for perihilar cholangiocarcinoma (pCCA). A total of 322 patients who underwent curative resection for pCCA were divided into three groups: normal preoperative CA19-9 (CA19-9 ≤ 37 U/mL), normalization (preoperative CA19-9 > 37 U/mL, postoperative CA19-9 ≤ 37 U/mL), and non-normalization (pre- and postoperative CA19-9 > 37 U/mL) groups. The association of clinicopathological factors with overall survival (OS) was investigated. The non-normalization group (n = 82) demonstrated significantly worse OS than the normal CA19-9 (n = 114) and normalization (n = 126) groups (5-year OS, 16.9%, 29.4%, and 34.4%, respectively; both p ≤ 0.001). The cutoff points of 300 U/mL for preoperative (p = 0.001) and 37 U/mL for postoperative (p < 0.001) CA19-9 levels showed the strongest prognostic values. In the non-normalization group, patients who underwent R1 resection displayed significantly worse OS than those who underwent R0 resection (median OS, 10.2 vs. 15.7 months; p = 0.016). Multivariate analysis revealed that lymph node metastasis (hazard ratio (HR), 2.07; p < 0.001), postoperative CA19-9 > 37 U/mL (HR, 1.94; p < 0.001), transfusion (HR, 1.74; p = 0.002), and T stage (T3,4) (HR, 1.67; p = 0.006) were related to worse OS. Persistent high CA19-9 level after resection of pCCA and R1 resection, especially in the non-normalization group, was associated with poor OS. A high postoperative CA19-9 level was an independent prognostic factor in resected pCCA. [ABSTRACT FROM AUTHOR]

The prognostic value of copeptin in subarachnoid hemorrhage (SAH) has been reported, but the prognosis was largely affected by the initial clinical severity. Thus, the previous studies are not very useful in predicting delayed cerebral ischemia (DCI) in poor-grade SAH patients. Here, we first investigated the feasibility of predicting DCI in poor-grade SAH based on consecutive measurements of plasma copeptin. We measured copeptin levels of 86 patients on days 1, 3, 5, 7, 9, 11, and 13 using ELISA. The primary outcome was the association between consecutive copeptin levels and DCI development. The secondary outcomes were comparison of copeptin with C-reactive protein (CRP) in predicting DCI. Additionally, we compared the prognostic value of transcranial Doppler ultrasonography (TCD) with copeptin using TCD alone to predict DCI. Increased copeptin (OR = 1.022, 95% CI: 1.008–1.037) and modified Fisher scale IV (OR = 2.841; 95% CI: 0.998–8.084) were closely related to DCI. Consecutive plasma copeptin measurements showed significant differences between DCI and non-DCI groups (p < 0.001). Higher CRP and DCI appeared to show a correlation, but it was not statistically significant. Analysis of copeptin changes with TCD appeared to predict DCI better than TCD alone with AUCROC differences of 0.072. Consecutive measurements of plasma copeptin levels facilitate the screening of DCI in poor-grade SAH patients. [ABSTRACT FROM AUTHOR]