Follistatin-like 1 is a myokine regulating lipid mobilization during endurance exercise and recovery.

OBJECTIVE: The aim of this study was to investigate the role of the follistatin-like 1 (Fstl1) and disco-interacting protein 2 homolog A (DIP2a) axis in relation to lipid metabolism during and after endurance exercise and to elucidate the mechanisms underlying the metabolic effects of Fstl1 on adipocytes, considering its regulation by exercise and muscle mass and its link to obesity. METHODS: Twenty-nine sedentary males participated in endurance exercise, and blood samples were collected during and after the exercise. Body composition, Fstl1, glycerol, epinephrine, growth hormone, and atrial natriuretic peptide were measured. 3T3-L1 adipocytes, with or without DIP2a knockdown, were treated with Fstl1 to assess glycerol release, cyclic AMP/cyclic GMP production, and hormone sensitive lipase phosphorylation. The association between DIP2a gene expression levels in human adipose tissues and exercise-induced lipolysis was examined. RESULTS: Fstl1 levels significantly increased during endurance exercise and following recovery, correlating with lean body mass and lipolysis. In 3T3-L1 adipocytes, Fstl1 increased glycerol release, cyclic GMP production, and hormone sensitive lipase activation, but these effects were attenuated by DIP2a knockdown. DIP2a gene expression in human adipose tissues correlated with serum glycerol concentrations during endurance exercise. CONCLUSIONS: Fstl1 is a myokine facilitating lipid mobilization during and after endurance exercise through DIP2a-mediated lipolytic effects in adipocytes.

Clinical Significance of Combining Preoperative and Postoperative Albumin-Bilirubin Score in Colorectal Cancer.

PURPOSE: Albumin-bilirubin (ALBI) score is a well-known prognostic factor for various diseases, including colorectal cancer (CRC). However, little is known about the significance of postoperative ALBI score changes in patients with CRC. MATERIALS AND METHODS: A total of 723 patients who underwent surgery were enrolled. Preoperative ALBI (ALBI-pre) and postoperative ALBI (ALBI-post) scores were divided into low and high score groups. ALBI-trend was defined as a combination of four groups comprising the low and high ALBI-pre and ALBI-post score groups. Kaplan-Meier survival curves were used to compare the overall survival (OS) between the different ALBI groups. The Cox proportional hazards model was used to examine the independent relevant factors of OS. Stratification performance was compared between the different ALBI groupings using Harrell's concordance index (C-index). RESULTS: ALBI-pre, ALBI-post, and ALBI-trend score groups were significant prognostic factors of OS in the univariable analysis. However, multivariable analysis showed that ALBI-trend was an independent prognostic factor while ALBI-pre and ALBI-post were not. The C-index of ALBI-trend (0.622; 95% confidence interval [CI], 0.587 to 0.655) was higher than that of ALBI-pre (0.589; 95% CI, 0.557 to 0.621; bootstrap mean difference, 0.033; 95% CI, 0.013 to 0.057) and ALBI-post (0.575; 95% CI, 0.545 to 0.605; bootstrap mean difference, 0.047; 95% CI, 0.024 to 0.074). CONCLUSION: Combining ALBI-pre and ALBI-post scores is an independent prognostic factor of OS and shows superior predictive power compared to ALBI-pre or ALBI-post alone in patients with CRC.

Combining prognostic nutritional index (PNI) and controlling nutritional status (CONUT) score as a valuable prognostic factor for overall survival in patients with stage I-III colorectal cancer.

Background and aims: This study compared the prognostic significance of various nutritional and inflammatory indicators such as neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio, prognostic nutritional index, and controlling nutritional status score. In addition, we aimed to establish a more accurate prognostic indicator. Methods: We retrospectively evaluated 1112 patients with stage I-III colorectal cancer between January 2004 and April 2014. The controlling nutritional status scores were classified as low (0-1), intermediate (2-4), and high (5-12) scores. The cut-off values for prognostic nutritional index and inflammatory markers were calculated using the X-tile program. P-CONUT, a combination of prognostic nutritional index and the controlling nutritional status score, was suggested. The integrated areas under the curve were then compared. Results: The multivariable analysis showed that prognostic nutritional index was an independent prognostic factor for overall survival, whereas the controlling nutritional status score, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio were not. The patients were divided into three P-CONUT groups as follows: G1, controlling nutritional status (0-4) and high prognostic nutritional index; G2, controlling nutritional status (0-4) and low prognostic nutritional index; and G3, controlling nutritional status (5-12) and low prognostic nutritional index. There were significant survival differences between the P-CONUT groups (5-year overall survival of G1, G2, and G3 were 91.7%, 81.2%, and 64.1%, respectively; p < 0.0001). The integrated areas under the curve of P-CONUT (0.610, CI: 0.578-0.642) was superior to those of the controlling nutritional status score alone (bootstrap integrated areas under the curve mean difference=0.050; 95% CI=0.022-0.079) and prognostic nutritional index alone (bootstrap integrated areas under the curve mean difference=0.012; 95% CI=0.001-0.025). Conclusion: Prognostic effect of P-CONUT may be better than inflammatory markers such as neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio. Thus, it could be used as a reliable nutritional risk stratification tool in patients with colorectal cancer.

A preoperative scoring system to predict lymph node metastasis in intrahepatic cholangiocarcinoma.

BACKGROUND: The abnormality of imaging finding of lymph node (LN) has demonstrated unsatisfactory diagnostic accuracy for pathologic lymph node metastasis (LNM). We aimed to develop and validate a simple scoring system predicting LNM in patients with intrahepatic cholangiocarcinoma (iCCA) prior to surgery based on MRI and clinical findings. METHODS: We retrospectively enrolled consecutive patients who underwent surgical resection for treatment-naïve iCCA from six institutions between January 2009 and December 2015. Patients who underwent lymph node dissection (LND) were randomly assigned to the training and validation cohorts at a 2:1 ratio, an¹ìd pathologic LN status was evaluated. Patients who did not undergo LND were assigned to the test cohort, and clinical LN status was evaluated. Using MRI and clinical findings, a preoperative LNM score was developed in the training cohort and validated in the validation and test cohorts. RESULTS: The training, validation, and test cohorts included 102, 53, and 118 patients, respectively. The preoperative LNM score consisted of serum carcinoembryonic antigen and two MRI findings (suspicious LN and bile duct invasion). The preoperative LNM score was associated with pathologic LNM in training (p < 0.001) and validation (p = 0.010) cohorts and clinical LNM in test cohort (p < 0.001). The preoperative LNM score outperformed MRI-suspicious LN alone in predicting pathologic LNM (area under the curve, 0.703 vs. 0.604, p = 0.004). The preoperative LNM score was also associated with overall survival in all cohorts (p < 0.001). CONCLUSIONS: Our preoperative LNM score was significantly associated with pathologic or clinical LNM and outperformed MRI-suspicious LN alone.

Albumin-myosteatosis gauge as a novel prognostic risk factor in patients with non-metastatic colorectal cancer.

BACKGROUND: Myosteatosis and systemic inflammation are well-known prognostic factors in patients with colorectal cancer (CRC). The serum albumin level is a reflection of malnutrition and systemic inflammation, which in turn plays a key role in the development of myosteatosis. However, few studies have been conducted on these synergistic effects. This study aimed to examine the individual and synergistic effects of different prognostic markers related to skeletal muscle quality and serum albumin levels in patients with CRC. METHODS: This study enrolled patients with stage I-III CRC who underwent surgical resection between July 2006 and February 2014. Skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) were calculated using computed tomography at the L3 level obtained within 2 months prior to surgery. The albumin-myosteatosis gauge (AMG) was defined as SMD × albumin. Patients were divided into sex-specific quartiles (G1 to G4) according to the AMG, and analysis of variance for continuous variables and chi-square test for categorical variables were used to compare variables among quartiles. Cox proportional hazard models were constructed and integrated receiver operating characteristic curve (iAUC) analysis was used to compare the prognostic performance of SMD, albumin and AMG. RESULTS: Among the 906 participants, the median (interquartile) age was 64 (55-72) years, and 365 (40.3%) were female. AMG was significantly correlated with the occurrence of complications, albumin level, SMI and SMD (all P < 0.001). Overall survival (OS) differed significantly according to the AMG group, with 5-year OS for G1-G4 being 73.4%, 86.2%, 91.1% and 95.5%, respectively (P < 0.0001). Although SMI, SMD, albumin and AMG were all significant individual prognostic markers of OS in the univariable analysis, AMG remained the only independent prognostic factor in the multivariable analysis (G1 vs. G2, P = 0.045, G1 vs. G3, P = 0.005, G1 vs. G4, P < 0.001, respectively). The iAUC value of AMG [0.681, 95% confidence interval (CI) = 0.638-0.723] was superior to that of SMD (0.610, 95% CI = 0.566-0.654) (bootstrap iAUC mean difference = 0.071, 95% CI = 0.034-0.106), SMI (0.551, 95% CI = 0.511-0.594) (bootstrap iAUC mean difference = 0.129, 95% CI = 0.076-0.181) and albumin (0.627, 95% CI = 0.585-0.668) (bootstrap iAUC mean difference = 0.053, 95% CI = 0.010-0.098). CONCLUSIONS: In patients with stage I-III CRC, AMG is a meaningful predictor of survival, with superior prognostic value compared to SMI, SMD or albumin alone. Further studies are needed to determine their significance in different ethnic groups.

Clinical Significance of Early Carcinoembryonic Antigen Change in Patients With Nonmetastatic Colorectal Cancer.

Background: This study aimed to evaluate the prognostic significance of preoperative, postoperative, and trajectory changes in carcinoembryonic antigen (CEA) levels in patients with colorectal cancer (CRC). Methods: This retrospective study included patients who underwent surgical resection for nonmetastatic CRC. The optimal cutoff values of preoperative CEA (CEA-pre), early postoperative CEA (CEA-post), and CEA level change (CEA-delta) were determined to maximize the differences in overall survival (OS) among groups. The patients were divided into three groups according to CEA-trend: normal, low CEA-pre; normalized, high CEA-pre/low CEA-post; elevated, high CEA-pre/high CEA-post. The integrated area under the curve (iAUC) was used to compare the discriminatory power of all variables. Results: A total of 1019 patients diagnosed with stage I-III CRC were enrolled. The optimal cutoff values of CEA level were determined as 2.3 ng/mL for CEA-pre, 2.3 ng/mL for CEA-post, and -0.93 ng/mL for CEA-delta. Although subgroup dichotomization showed that CEA-pre, CEA-post, CEA-delta, and CEA-trend were all associated with OS in univariate analysis, CEA-trend was the only independent prognostic factor in multivariate analysis. The iAUC of CEA-trend was superior to that of CEA-pre, CEA-post, and CEA-delta. Compared with the normal group, the normalized group showed worse OS (p=.0007) in stage II patients but similar OS (p=.067) in stage III patients. Conclusion: The optimal cutoff value of CEA level in the preoperative and postoperative periods was determined to be 2.3 ng/mL, and the combination of CEA-pre and CEA-post showed better prognostic stratification. However, its prognostic significance may differ depending on the CRC stage.

Association of Albumin-Bilirubin Grade and Myosteatosis with its Prognostic Significance for Patients with Colorectal Cancer.

BACKGROUND: The albumin-bilirubin (ALBI) grade is a useful prognostic and predictive marker for patients with liver disease. Its clinical significance has been limited to patients with colorectal cancer (CRC). Furthermore, the association between the ALBI grade and skeletal muscle-related indices is unclear. METHODS: This study enrolled 1015 patients who underwent computed tomography (CT) scans within 31 days before surgery. The prognostic value of the ALBI grade in predicting overall survival (OS) was assessed using the Cox proportional hazards model. The correlation between the ALBI grade and the skeletal muscle index or radiodensity (myosteatosis) was evaluated. The predictive accuracy of ALBI alone and in combination with myosteatosis was compared using Harrell's concordance index (C-index). RESULTS: The significant prognostic factors for OS identified in the multivariable analysis were the ALBI group (low vs high: hazard ratio [HR], 1.566; 95 % confidence interval [CI], 1.174-2.089; p = 0.002) and myosteatosis (low vs. high: HR, 0.648; 95 % CI, 0.486-0.865; p = 0.003). The rate of low-grade myosteatosis increased as the ALBI grade increased. The C-index of combined ALBI and myosteatosis (0.650; 95 % CI, 0.618-0.683) was superior to that of ALBI alone (0.603; 95 % CI, 0.575-0.631; bootstrap incremental area under the curve [iAUC] mean difference, 0.047; 95 % CI, 0.012-0.070) and myosteatosis alone (0.608; 95 % CI, 0.577-0.640; bootstrap iAUC mean difference, 0.042; 95 % CI, 0.023-0.064). CONCLUSION: The ALBI grade is significantly associated with myosteatosis. The ALBI grade is a significant prognostic factor, and the combination of ALBI and myosteatosis show an additive value in discriminating survival of patients with CRC.

Preoperative magnetic resonance imaging-based prognostic model for mass-forming intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: As most staging systems for intrahepatic cholangiocarcinoma (iCCA) are based on pathological results, preoperative prognostic prediction is limited. This study aimed to develop and validate a prognostic model for the overall survival of patients with mass-forming iCCA (MF-iCCA) using preoperative magnetic resonance imaging (MRI) and clinical findings. METHODS: We enrolled a total of 316 patients who underwent preoperative MRI and surgical resection for treatment-naive MF-iCCA from six institutions, between January 2009 and December 2015. The subjects were randomly assigned to a training set (n = 208) or validation set (n = 108). The MRIs were independently reviewed by three abdominal radiologists. Using MRI and clinical findings, an MRI prognostic score was established. We compared the discrimination performance of MRI prognostic scores with those of conventional pathological staging systems. RESULTS: We developed an MRI prognostic score consisting of serum CA19-9 and three MRI findings (tumour multiplicity, lymph node metastasis and bile duct invasion). The MRI prognostic score demonstrated good discrimination performance in both the training set (C-index, 0.738; 95% confidence interval [CI], 0.698-0.780) and validation set (C-index, 0.605; 95% CI, 0.526-0.680). In the validation set, MRI prognostic score showed no significant difference with AJCC 8th TNM stage, MEGNA score and Nathan's stage. CONCLUSIONS: Our MRI prognostic score for overall survival of MF-iCCA showed comparable discriminatory performance with pathological staging systems and might be used to determine an optimal treatment strategy.

The Clinical Impact of Combining Neutrophil-to-Lymphocyte Ratio with Sarcopenia for Improved Discrimination of Progression-Free Survival in Patients with Colorectal Cancer.

This study aimed to evaluate the clinical impact of combined sarcopenia and inflammation classification (CSIC) in patients with colorectal cancer (CRC). The skeletal muscle index (SMI) and neutrophil-to-lymphocyte ratio (NLR) were measured in 1270 patients who underwent surgery between January 2005 and April 2014. A Cox proportional hazards model was used to evaluate the correlation of sarcopenia, NLR, and CSIC, with progression-free survival (PFS). The integrated area under the curve (iAUC) was used to compare the discriminatory performance of each model. Using the cut-off values for SMI suggested by Martin et al. and for an NLR of 2.26, the CSIC was defined as follows: nonsarcopenia with low NLR (group 1), nonsarcopenia with high NLR (group 2), sarcopenia with low NLR (group 3), and sarcopenia with high NLR (group 4). Sarcopenia alone was not statistically significant. Multivariate analysis identified that CSIC (group 4 vs. group 1; hazard ratio (HR), 1.726; 95% CI, 1.130-2.634; p = 0.011) and NLR (HR, 1.600; 95% CI, 1.203-2.128; p = 0.001) were independently associated with PFS. The CSIC improved the prediction accuracy of PFS compared with NLR (iAUC mean difference = 0.011; 95% CI, 0.0018-0.028). In conclusion, the combination of sarcopenia and NLR could improve prognostic accuracy, and thus compensate for the limitation of sarcopenia.

Impact of subcutaneous and visceral fat adiposity in patients with colorectal cancer.

BACKGROUND: Although different body composition including fat adiposity has known to be associated with survival in patients with colorectal cancer (CRC), the clinical significance was inconsistent. We investigated prognostic impact of visceral and subcutaneous fat adiposity in patients with CRC after surgical resection. MATERIAL AND METHODS: This retrospective single center study included 987 stage I-III CRC patients (583 males, and 404 females) who underwent surgical resection between March 2005 and April 2014. Preoperative diagnostic computed tomography images were used to quantify visceral fat area (VFA) and subcutaneous fat area (SFA). The sex-specific optimal cut-off value for body fat composition was defined using the X-tile program. The Cox proportional hazards model was used to determine the correlation fat composition and disease-free survival (DFS). Harrell's concordance index (C-index) and integrated area under curve (iAUC) were used to evaluate the predictive ability of cut-derived stratification. RESULTS: In univariate analysis, high SFA (≥141.73 cm2 in males and ≥168.71 cm2 in females) and high VFA (≥174.38 cm2 in male and ≥83.65 cm2 in female) were identified as significant prognostic factors for better DFS (p = .001 and p = .003 respectively). However, multivariate analysis revealed that high SFA independently predicted longer DFS (HR 0.505; 95% CI 0.266-0.957; p = .036) whereas, high VFA did not (HR 0.656; 95% CI 0.402-1.071; p = .092). Combining stage and SFA-cutoff showed better discriminatory performance than the model using stage solitary with respect to C-index (0.667; 95% CI 0.623-6.711; p = .0098) and iAUC (0.601; 95% CI 0.556-0.620). CONCLUSION: High SFA was correlated with better DFS in patients with CRC. Subcutaneous fat can have additive predictive capability when incorporated into clinical decision-making.

Skeletal muscle gauge as a prognostic factor in patients with colorectal cancer.

BACKGROUND: Although skeletal muscle index (SMI) and radiodensity (SMD) are well-known prognostic factors, the clinical impact of the integrated measure, known as skeletal muscle gauge (SMG), has been limited in patients with colorectal cancer (CRC). PATIENTS AND METHODS: A total of 727 and 268 patients with CRC at two tertiary centers were included and allocated into the training and test sets, respectively. Preoperative slice computed tomography images of the third lumbar area were evaluated for SMI and SMD. SMG was calculated as SMI × SMD and expressed as an arbitrary unit (AU). The optimal cutoff SMG value was determined to maximize the overall survival (OS) difference between the groups with respect to sex in the training set. The multivariate Cox proportional hazard model evaluated the association of its clinical significance. RESULTS: With regard to SMG, 1640 and 1523 AU were identified as cutoff values for males and females, respectively. The patients with low SMG values showed significantly worse 5-year OS than those with high SMG values in the two datasets (both p < 0.001). In the multivariate analysis, low SMG was identified as an independent poor prognostic factor of OS in the training set (hazard ratio 2.18, 95% confidence interval 1.43-3.32, p < 0.001) and test set (hazard ratio 1.79, 95% confidence interval 1.07-3.00, p = 0.025), whereas SMI and SMD were not. CONCLUSION: SMG acts synergistically to improve its prognostic predictive accuracy as compared with SMI or SMD alone in patients with CRC. Additional research is warranted to define its significance in different ethnic groups.

Elevated Neutrophil-to-Lymphocyte Ratio in Perioperative Periods is Suggestive of Poor Prognosis in Patients with Colorectal Cancer.

BACKGROUND: Recent data suggest that alterations in the neutrophil-to-lymphocyte ratio (NLR) in the perioperative periods can serve as prognostic factors. However, research on the clinical impact has been limited and even discordant in patients with colorectal cancer (CRC). PATIENTS AND METHODS: The optimal cut-off value of preoperative NLR (NLR-pre), postoperative NLR (NLR-post), and its change (NLR-delta) were determined to maximize differences in overall survival (OS) between groups. Patients were categorized into four groups (NLR-trend) as follows: G1, low NLR-pre and NLR-post; G2, low NLR-pre and high NLR-post; G3, high NLR-pre and low NLR-post; and G4, high NLR-pre and NLR-post. Discriminatory performance was compared using integrated AUC (iAUC) between all indicators. RESULTS: A total of 576 patients diagnosed with stage I-IV CRC were included. The cut-off points were determined as 2.33 for NLR-pre, 2.06 for NLR-post, and -1.08 for NLR-delta. Subgroup dichotomization using NLR-pre, NLR-post, NLR-delta and NLR-trend were all identified as significant prognostic factors by univariate analysis. However, NLR-trend was only remained as an independent prognostic factor in the multivariate analysis. The iAUC of the NLR-trend was superior to that of NLR-pre (bootstrap iAUC mean difference=0.036; 95% CI 0.013-0.073), NLR-post (bootstrap iAUC mean difference=0.045; 95% CI 0.019-0.081) and NLR-delta (bootstrap iAUC mean difference=0.061; 95% CI 0.025-0.104). CONCLUSION: Risk stratification and combining of preoperative and postoperative NLR (NLR-trend) can improve prognostic discrimination compared with single measurements or simple changes in NLR in patients with CRC.

Clinical Staging of Mass-Forming Intrahepatic Cholangiocarcinoma: Computed Tomography Versus Magnetic Resonance Imaging.

We compared the performance of computed tomography (CT) and magnetic resonance imaging (MRI) for preoperative clinical staging of mass-forming intrahepatic cholangiocarcinoma (iCCA), using the eighth American Joint Committee on Cancer (AJCC) system. This retrospective, multicenter, cohort study consecutively identified patients who underwent partial hepatectomy for mass-forming iCCA and had preoperative CT and MRI performed from January 2009 to December 2015. CT and MRI characteristics were used to determine clinical stage based on the eighth AJCC system. Performances of CT and MRI for clinical T and N staging were compared using generalized estimating equations. In 334 patients (median age, 63 years; 221 men), MRI sensitivities were significantly higher than CT sensitivities for detecting T1b or higher stages (91.0% vs. 80.5%, respectively, P < 0.001), T2 or higher stages (89.1% vs. 73.8%, respectively, P < 0.001), and T3 or T4 stage (77.8% vs. 58.0%, respectively, P < 0.001). MRI was also more sensitive at identifying multiple tumors than CT (66.7% vs. 50.0%, respectively, P = 0.026), without a significant difference in specificity (78.1% vs. 80.1%, respectively, P = 0.342). Sensitivities were comparable between CT and MRI for determination of size >5 cm (i.e., T1b for single tumor) and extrahepatic organ invasion (i.e., T4). Sensitivities of CT and MRI were not different for N stage (65.0% vs. 64.0%, respectively, P = 0.808), but the specificity of CT was significantly higher than that of MRI (80.7% vs. 72.9%, respectively, P = 0.001) when using a composite reference standard. Conclusion: MRI showed superior sensitivity to CT for diagnosing T2 and T3 stages, particularly multiple tumors. CT and MRI had comparable sensitivity for N staging, but CT provided higher specificity than MRI.

Effects of cooling systems on physiological responses and intestinal microflora in early gestating sows exposed to high-temperature stress.

This study was conducted to investigate the effect of cooling systems on reproductive performance, body temperature, blood metabolites, and the intestinal microbiome in early gestating sows exposed to high ambient temperature. In total, 39 pregnant sows (Landrace × Yorkshire; 2 parities) were randomly assigned to and maintained in the following three treatment groups (13 sows per group) over days 0 to 35 of pregnancy: (i) air cooling (AC; 26.87 ± 1.23°C), (ii) water-drip cooling (WC; 28.81 ± 0.91°C), and (iii) a lack of cooling with heat stress (HS; 30.72 ± 0.70°C). Backfat thickness was measured before and after HS. Feces were collected on day 0 and 35 d of the trial for microbiome analysis, whereas blood was taken at day 35 of pregnancy and analyzed. Reproductive performance and physiological responses were identified at day 35. Respiration rate along with rectal and skin temperatures were lower (p < 0.05) in the AC group than in the HS and WC groups. Serum blood urea nitrogen values were increased (p < 0.05) in the WC group compared with those measured in the AC and HS groups. Triiodothyronine was found at greater levels (p < 0.05) in the AC than in the HS group. Reproductive performance was not affected by the cooling systems. At the phylum level, fecal pathogenic Spirochaete and Euryarchaeota were found in higher numbers (p < 0.05) in all groups after HS. Similarly, at the genus level, the amount of Treponema was greater (p < 0.05) in all groups after HS. In conclusion, our results suggest that AC or WC can ameliorate or mitigate the adverse effects of HS on the physiological parameters of pregnant sows reared under high temperatures.

Intralymphatic immunotherapy with tyrosine-adsorbed allergens: a double-blind, placebo-controlled trial.

BACKGROUND: Most previous studies used aluminum hydroxide-absorbed allergen extracts in evaluating the potential therapeutic roles of intralymphatic allergen-specific immunotherapy (ILAIT). In this study, we evaluated the therapeutic efficacy and safety of ILAIT with L-tyrosine-adsorbed allergen extracts of Dermatophagoides farinae, D. pteronyssinus, cat, dog, or mixtures thereof, in patients with allergic rhinitis induced by these allergens. METHODS: In this randomized, double-blind, placebo-controlled trial, study subjects received three intralymphatic injections of L-tyrosine-adsorbed allergen extracts (active group) or saline (placebo group) at 4-week intervals. RESULTS: Although ILAIT reduced daily medication use and skin reactivity to HDM and cat allergens at 4 months after treatment, overall symptom score on a visual analog scale (VAS), sinonasal outcome test-20 (SNOT-20), rhinoconjunctivitis quality of life questionnaire (RQLQ), daily symptom score (dSS), daily medication score (dMS), daily symptom medication score (dSMS), nasal reactivity to HDM allergen, and basophil activity to HDM, cat, and dog allergens at 4 months and 1 year after treatment were similar between the treatment and control groups. Intralymphatic injection was more painful than a venous puncture, and pain at the injection site was the most frequent local adverse event (12.8%); dyspnea and wheezing were the most common systemic adverse events (5.3%). CONCLUSIONS: ILAIT with L-tyrosine-adsorbed allergen extracts does not exhibit profound therapeutic efficacy in allergic rhinitis and can provoke moderate-to-severe systemic reactions and cause pain at the injection site. TRIAL REGISTRATION: clinicaltrials.gov: NCT02665754; date of registration: 28 January 2016.

Preoperative prediction of postsurgical outcomes in mass-forming intrahepatic cholangiocarcinoma based on clinical, radiologic, and radiomics features.

OBJECTIVES: Current prognostic systems for intrahepatic cholangiocarcinoma (IHCC) rely on surgical pathology data and are not applicable to a preoperative setting. We aimed to develop and validate preoperative models to predict postsurgical outcomes in mass-forming IHCC patients based on clinical, radiologic, and radiomics features. METHODS: This multicenter retrospective cohort study included patients who underwent curative-intent resection for mass-forming IHCC. In the development cohort (single institution data), three preoperative multivariable Cox models for predicting recurrence-free survival (RFS) were constructed, including the clinical-radiologic, radiomics, and clinical-radiologic-radiomics (CRR) models based on clinical and CT findings, CT-radiomics features, and a combination of both, respectively. Model performance was evaluated in the test cohort (data from five institutions) using Harrell's C-index and compared with postoperative prognostic systems. RESULTS: A total of 345 patients (233, development cohort; 112, test cohort) were evaluated. The clinical-radiologic model included five independent CT predictors (infiltrative contour, multiplicity, periductal infiltration, extrahepatic organ invasion, and suspicious metastatic lymph node) and showed similar performance in predicting RFS to the radiomics model (C-index, 0.65 vs. 0.68; p = 0.43 in the test cohort). The CRR model showed significantly improved performance (C-index, 0.71; p = 0.01) than the clinical-radiologic model and demonstrated similar performance to the postoperative prognostic systems in predicting RFS (C-index, 0.71-0.73 vs. 0.70-0.73; p ≥ 0.40) and overall survival (C-index, 0.68-0.71 vs. 0.64-0.74; p ≥ 0.27) in the test cohort. CONCLUSIONS: A model integrating clinical, CT, and radiomics information may be useful for the preoperative assessment of postsurgical outcomes in patients with mass-forming IHCC. KEY POINTS: • The radiomics analysis had incremental value in predicting recurrence-free survival of patients with intrahepatic mass-forming cholangiocarcinoma. • The clinical-radiologic-radiomics model demonstrated similar performance to the postoperatively available prognostic systems (including 8th AJCC system) in predicting recurrence-free survival and overall survival. • The clinical-radiologic-radiomics model may be useful for the preoperative assessment of postsurgical outcomes in patients with mass-forming intrahepatic cholangiocarcinoma.

Corona enhancement can substitute enhancing capsule in the imaging diagnosis of small (≤ 3 cm) HCCs on gadoxetic acid-enhanced MRI.

OBJECTIVES: This study aimed to elucidate the relationship between gadoxetic acid-enhanced magnetic resonance imaging (MRI) features-enhancing capsule, corona enhancement or hypointense rim-observed in hepatocellular carcinomas (HCCs). METHODS: Of the HCCs surgically confirmed during a 5-year period (2013-2017), ≤ 3-cm lesions (n = 83) in 78 patients were evaluated. Presence of corona enhancement and enhancing capsule on multiphasic dynamic imaging and presence of hypointense rim on hepatobiliary phase imaging were determined retrospectively by two independent observers. The relationship among the three imaging features was statistically analysed and correlated with the presence of histologic fibrous capsules, tumour differentiation and gross morphologic type. RESULTS: There was substantial overall interobserver agreement in determining the presence of the three imaging features. Sixty (72.3%) lesions had histologic fibrous capsule positively correlated with all three imaging features (p < 0.05). Corona enhancement was the most common (66.3%) feature followed by enhancing capsule (61.4%) and hypointense rim (33.7%), and the correspondence rate of enhancing capsule to corona enhancement was 68.6% (p = 0.004). Corona enhancement was more frequently observed in moderately differentiated HCCs than other lesions (p = 0.012) and not dependent (p = 0.465) on the tumour size, while enhancing capsule was significantly dependent on tumour size, as indicated by univariate (p < 0.001) and multivariate analyses (odds ratio, 4.241; p = 0.002). CONCLUSIONS: Among the capsular features, corona enhancement might closely relate to enhancing capsule in HCCs. Corona enhancement was not dependent on tumour size and had the highest incidence of appearance on gadoxetic acid-enhanced multiphasic dynamic MRI. KEY POINTS: • Enhancing capsule has a limited role in the LI-RADS categorisation during gadoxetic acid-enhanced MRI. • Appearance of corona enhancement is closely related to enhancing capsule and is not dependent on size of HCCs. • Corona enhancement can substitute enhancing capsule in the diagnosis of HCCs during multiple arterial and portal venous phase gadoxetic acid-enhanced MRI.

Radiomics Features of 18F-Fluorodeoxyglucose Positron-Emission Tomography as a Novel Prognostic Signature in Colorectal Cancer.

The aim of this study was to investigate the prognostic value of radiomics signatures derived from 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) in patients with colorectal cancer (CRC). From April 2008 to Jan 2014, we identified CRC patients who underwent 18F-FDG-PET before starting any neoadjuvant treatments and surgery. Radiomics features were extracted from the primary lesions identified on 18F-FDG-PET. Patients were divided into a training and validation set by random sampling. A least absolute shrinkage and selection operator Cox regression model was applied for prognostic signature building with progression-free survival (PFS) using the training set. Using the calculated radiomics score, a nomogram was developed, and its clinical utility was assessed in the validation set. A total of 381 patients with surgically resected CRC patients (training set: 228 vs. validation set: 153) were included. In the training set, a radiomics signature labeled as a rad_score was generated using two PET-derived features, such as gray-level run length matrix long-run emphasis (GLRLM_LRE) and gray-level zone length matrix short-zone low-gray-level emphasis (GLZLM_SZLGE). Patients with a high rad_score in the training and validation set had a shorter PFS. Multivariable analysis revealed that the rad_score was an independent prognostic factor in both training and validation sets. A radiomics nomogram, developed using rad_score, nodal stage, and lymphovascular invasion, showed good performance in the calibration curve and comparable predictive power with the staging system in the validation set. Textural features derived from 18F-FDG-PET images may enable detailed stratification of prognosis in patients with CRC.

Gadoxetic acid-enhanced MRI of macrotrabecular-massive hepatocellular carcinoma and its prognostic implications.

BACKGROUND & AIMS: Despite the clinical and genetic significance of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC), its characteristics on imaging have not been described. This study aimed to characterise MTM-HCC on gadoxetic acid-enhanced MRI and to evaluate the diagnostic accuracy and prognostic value of these imaging characteristics. METHODS: We enrolled 3 independent cohorts from 2 tertiary care centres. The 3 cohorts consisted of a total of 476 patients who underwent gadoxetic acid-enhanced MRI and surgical resection for treatment-naïve single HCCs. Independent review of histopathology and MRI by 2 reviewers was performed for each cohort, and inter-reader agreement was evaluated. Based on the result of MRI review in the training cohort (cohort 1), we developed 2 diagnostic criteria for MTM-HCC and evaluated their prognostic significance. The diagnostic performance and prognostic significance were validated in 2 validation cohorts (cohorts 2 and 3). RESULTS: We developed 2 diagnostic MRI criteria (MRIC) for MTM-HCC: MRIC-1, ≥20% arterial phase hypovascular component; MRIC-2, ≥50% hypovascular component and 2 or more ancillary findings (intratumoural artery, arterial phase peritumoural enhancement, and non-smooth tumour margin). MRIC-1 showed high sensitivity and negative predictive value (88% and 95% in the training cohort, and 88% and 97% in the pooled validation cohorts, respectively), whereas MRIC-2 demonstrated moderate sensitivity and high specificity (47% and 94% in the training cohort, and 46% and 96% in the pooled validation cohorts, respectively). MRIC-2 was an independent poor prognostic factor for overall survival in both training and pooled validation cohorts. CONCLUSIONS: Using gadoxetic acid-enhanced MRI findings, including an arterial phase hypovascular component, we could stratify the probability of MTM-HCC and non-invasively obtain prognostic information. LAY SUMMARY: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a histopathologic subtype of HCC characterised by aggressive biological behaviour and poor prognosis. We developed imaging criteria based on liver MRI that could be used for the non-invasive diagnosis of MTM-HCC. HCCs showing imaging findings of MTM-HCC were associated with poor outcomes after hepatic resection.

Retrospective Comparison of Renal Ultrasonographic and Clinical Findings in Patients with Rhabdomyolysis.

BACKGROUND: This study evaluated the ultrasonographic and clinical findings of two groups with rhabdomyolysis, who showed abnormal or normal ultrasonographic findings of kidneys. METHODS: Two groups (n = 78) of abnormal (A) and normal (B) renal ultrasonographic findings were included. Multiple laboratory findings were assessed within 2 days before or after ultrasonography. Student's t-test or Mann-Whitney U-test was used for statistical analysis. RESULTS: The variable causes of rhabdomyolysis were intense exercise, burn, operation, shivering, and drug intoxication, etc. Group A (n = 26; M:F = 19:7) showed enlarged both kidneys, increased parenchymal thickness, and increased (n = 23, 88.5%) or decreased (n = 3, 11.5%) cortical echogenicity. Group A also showed elevated blood urea nitrogen (BUN), creatinine, potassium, and prolonged activated partial thromboplastin time (aPTT), compared with those in Group B (n = 52; M:F = 36:16), and these results were statistically significant (P < 0.01). The myoglobin in serum and urine, creatine kinase, prothrombin time, dark urine, and microscopic hematuria were not statistically different between the two groups. CONCLUSION: Patients with elevated BUN, creatinine, potassium, and prolonged aPTT showed the ultrasonographic findings of acute kidney injury, but other parameters were not statistically different between the two groups.