Serum Cytokines Correlate with Pretreatment Body Mass Index-adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery.

Serum Cytokines Correlate with Pretreatment Body Mass Index-Adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery. Circulating cytokines have been linked to the development of esophageal squamous cell carcinoma (ESCC) and its associated malnutrition process. Nonetheless, given the varied disease stages and treatment modalities in previous studies, the clinical relevance of their findings is limited. We retrospectively studied 52 patients with stage III ESCC who underwent neoadjuvant chemoradiotherapy and curative-intent surgery. We investigated the association of clinicopathological features, pretreatment laboratory data, and pretreatment inflammatory status, as indicated by the levels of albumin, C-reactive protein, and 10 circulating cytokines, namely tumor necrosis factor-alpha (TNF-α), interferon-gamma, interleukin-1-beta (IL-1ß), IL-4, IL-6, IL-8, IL-12, IL-13, IL-17A, and IL-23, with malnutrition, as shown by body mass index-adjusted body weight loss (BMI-BWL) grading, cancer progression. Half the patients showed severe malnutrition and high BMI-BWL grades (3 and 4). Multivariate analysis revealed an independent association between the levels of three cytokines (TNF-α, ≤ 5.8 pg/ml; IL-1ß, > 0.4 pg/ml; IL-6, ≤ 12.4 pg/ml) and high BMI-BWL grades and between IL-4 levels > 22.5 pg/ml and cancer progression. All 10 cytokines were closely correlated with each other. In conclusion, TNF-α, IL-1ß, and IL-6 were independent markers of malnutrition status and IL-4 was a prognostic factor for cancer progression in this patient population.

Frailty is an independent factor for health-related quality of life in patients with head and neck cancer receiving definitive concurrent chemoradiotherapy.

PURPOSE: Health-related quality of life (HRQoL) is associated with treatment-related complications and poor survival in patients with head and neck cancer (HNC). We investigated the effects of frailty on HRQoL in patients with HNC receiving definitive concurrent chemoradiotherapy (CCRT). METHODS: A total of 461 consecutive patients with locally advanced HNC who received CCRT between 2017 and 2018 at three medical centers in Taiwan were included. Frailty and HRQoL were assessed using the Comprehensive Geriatric Assessment and QLQ-H&N35 before CCRT. The sum score was calculated based on the first 30 questions of QLQ-H&N35. Multivariate analysis was performed to evaluate the impact of frailty on HRQoL. RESULTS: The overall sum score was 39 (34-49). The sum scores of patients with impairments in 0, 1, 2, 3, and ≥ 4 frailty domains were 34 (32-38), 40 (34-47), 46 (36-55), 48 (41-64), and 56 (50-60), respectively. Patients with impairments in more frailty domains had a higher symptom burden (p for trend < 0.001). Frail patients tended to experience symptoms across all QLQ-H&N35 subscales. Sex, body mass index, tumor type, tumor stage, Eastern Cooperative Oncology Group performance status, and frailty were determinants of HRQoL in the univariate analysis. Frailty was an independent determinant of HRQoL in the multivariate analysis. CONCLUSION: Routine frailty assessment may serve as a surrogate for the selection of patients with HNC with poor HRQoL before CCRT. Further studies are needed to determine whether appropriate interventions in frail patients would improve their HRQoL during CCRT.

Impact of pretreatment quality of life on tolerance and survival outcome in head and neck cancer patients undergoing definitive CCRT.

BACKGROUND: Health-related quality of life (HRQoL) is a predictor of treatment outcomes in cancer patients. This study aimed to evaluate the effect of pretreatment HRQoL on treatment tolerance and survival outcomes in patients with HNC planned for concurrent chemoradiotherapy (CCRT) in Taiwan. METHODS: This study included 461 patients with HNC planned for definitive CCRT at three medical centers in Taiwan between August 2017 and December 2018. HRQoL was assessed using the QLQ-HN35 one week before the initiation of CCRT. Patients were grouped based on the sum scores of QLQ-HN35 (

Effect of prophylactic tube feeding in head and neck cancer patients with high Mallampati score undergoing definitive concurrent chemoradiotherapy.

PURPOSE: There is no consensus on the selection of appropriate prophylactic tube feeding in patients with head and neck squamous cell carcinoma (HNSCC) undergoing concurrent chemoradiotherapy (CCRT). This study aimed to evaluate the effect of prophylactic tube feeding in patients with HNSCC who presented with a high Mallampati score and underwent CCRT. METHODS: We prospectively enrolled 185 consecutive patients with stage II to IVa HNSCC and a pre-treatment Mallampati score of 3 or 4 who received CCRT between August 2017 and December 2018 with follow-up data collected retrospectively. Patients were divided to either with or without prophylactic tube feeding group for comparison of treatment tolerance, toxicities, and quality of life(QOL). Propensity score matching (PSM) was used to achieve balanced covariates across the two groups. RESULTS: Of the cohort, 52 (28.1%) and 133 (71.9%) patients were allocated to the prophylactic and non-prophylactic tube feeding groups, respectively. Before and after PSM, patients in the tube feeding group had a significantly lower incidence of incomplete radiotherapy, incompletion of chemotherapy, emergency room visits, and grade 3 or higher infection, and improved symptoms of quality of life after CCRT than those in the non-tube feeding group. CONCLUSION: Prophylactic tube feeding was associated with better treatment tolerance, safety profiles, and quality of life in patients with HNSCC and high Mallampati scores who underwent CCRT. Therefore, Mallampati score might serve as a clinical tool for proactive selection of patients receiving prophylactic tube feeding in HNSCC patients upon receiving CCRT.

Pretreatment Nutrition-Inflammation Biomarkers Correlated with Differential Cytokine Profiles in Taiwanese Patients with Colorectal Cancer.

Systemic inflammation plays a pivotal role in colorectal cancer (CRC) development. Two hallmarks reflect the severity of inflammation-circulating cytokines and nutrition-inflammation biomarkers (NIBs); however, their interplay has not been fully investigated. In total, 128 CRC patients were included. Ten circulating cytokines (TNF-α, TGF-ß, IFN-γ, IL-1ß, IL-4, IL-6, IL-10, IL-12, IL-13, and IL-23) and NIBs were analyzed. The relationship between cytokines, NIBs, clinicopathological variables, and overall survival (OS) was assessed using univariate and multivariate analyses. Three NIBs (CRP-to-albumin ratio [CAR]), neutrophil-to-lymphocyte ratio [NLR]), and prognostic nutritional index [PNI]) were associated with OS in univariate analysis; however, CAR was better for OS prediction in multivariate analysis (P = 0.015). None of the serum cytokines analyzed showed a significant association with OS. High CAR (≥0.25) and high IL-10 (≥76.6 pg/mL), high NLR (≥8.2) and high IL-23 (≥51.2 pg/mL), and high PNI (≥42.4) and high IL-1ß (≥14.3 pg/mL) values were correlated. CAR, NLR, and PNI were not correlated with each other, whereas circulating cytokines were closely interrelated. High CAR was an independent predictor of poor OS in patients with CRC. Different NIBs have unique cytokine profiles, but show no correlation with each other. There is a close association among the circulating cytokines.

Clinical Significance of Frailty on Treatment Outcome in Nongeriatric Patients With Head and Neck Cancer and Esophageal Cancer Undergoing Curative-Intent Concurrent Chemoradiotherapy.

BACKGROUND: Whether the prevalence of frailty and its clinical significance are relevant to treatment outcomes in younger (aged < 65 years) cancer patients remains uncertain. This study aimed to evaluate the impact of frailty on treatment outcomes in younger cancer patients with head and neck and esophageal malignancy. MATERIAL AND METHODS: This multicenter prospective study recruited 502 patients with locally advanced head and neck and esophageal cancer during 2016-2017 in Taiwan, aged 20-64 years who received curative-intent concurrent chemoradiotherapy (CCRT) as first-line antitumor treatment. Baseline frailty assessment using geriatric assessment (GA) was performed for each patient within 7 days before CCRT initiation. RESULTS: Frailty was observed in 169 (33.7%) of 502 middle-aged patients. Frail patients had significantly higher incidences of chemotherapy incompletion (16.6% versus 3.3%, P < .001) and radiotherapy incompletion (16.6% versus 3.6%, P < .001) than fit patients. During CCRT, frail patients had a significantly higher percentage of hospitalizations (42.0% versus 24.6%, P < .001) and a trend toward a higher percentage of emergency room visits (37.9% versus 30.0%, P = .08) than fit patients. Frail patients more likely had a significantly higher incidence of grade ≥ 3 adverse events than fit patients during CCRT. The 1-year survival rate was 68.7% and 85.2% (hazard ratio 2.56, 95% confidence interval 1.80-3.63, P < .001) for frail and fit patients, respectively. CONCLUSIONS: This study demonstrated the significance of pretreatment frailty on treatment tolerance, treatment-related toxicity, and survival outcome in younger patients with head and neck and esophageal cancer undergoing CCRT. While GA is commonly targeted toward the older population, frailty assessment by GA may also be utilized in younger patients for decision-making guidance and prognosis prediction.

Deficiency of Adipose Triglyceride Lipase Induces Metabolic Syndrome and Cardiomyopathy in Zebrafish.

Lipid metabolism dysfunction is related to clinical disorders including obesity, cancer, liver steatosis, and cardiomyopathy. Impaired lipolytic enzymes result in altered release of free fatty acids. The dramatic change in dyslipidemia is important in lipotoxic cardiomyopathy. Adipose triglyceride lipase (ATGL) catalyzes the lipolysis of triacylglycerol to reduce intramyocardial triglyceride levels in the heart and improve myocardial function. We examined the role of ATGL in metabolic cardiomyopathy by developing an Atgl knockout (ALKO) zebrafish model of metabolic cardiomyopathy disease by continuously expressing CRISPR/Cas9 protein and atgl gene guide RNAs (gRNAs). The expressed Cas9 protein bound to four gRNAs targeting the atgl gene locus, facilitating systemic gene KO. Ablation of Atgl interfered with lipid metabolism, which induced hyperlipidemia and hyperglycemia. ALKO adults and embryos displayed hypertrophic hearts. ALKO presented a typical dilated cardiomyopathy profile with a remarkable reduction in four sarcomere genes (myosin heavy chain 7-like, actin alpha cardiac muscle 1b, myosin binding protein C3, and troponin T type 2a) and two Ca2+ handling regulator genes (tropomyosin 4b and ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2b). Immune cell infiltration in cardiac tissue of ALKO provided direct evidence of advanced metabolic cardiomyopathy. The presently described model could become a powerful tool to clarify the underlying mechanism between metabolic disorders and cardiomyopathies.

Body Mass Index-Adjusted Body Weight Loss Grading Predicts Overall Survival in Esophageal Squamous Cell Carcinoma Patients.

PURPOSE: Various malnutrition and inflammation criteria were associated with prognosis of esophageal squamous cell carcinoma (ESCC) patients. Nonetheless, the interplay of clinicopathological features, malnutrition, and inflammation criteria with overall survival in ESCC patients remains unclear. METHODS: We retrospectively reviewed medical records of 205 patients diagnosed with ESCC between 2007 and 2012, and evaluated the status of participant malnutrition and inflammation, including body mass index < 18.5 kg/m2, body weight loss > 5.0%, serum albumin level < 3.5 g/dl, neutrophil-to-lymphocyte ratio > 3.5, platelet-to-lymphocyte ratio > 20, prognostic nutrition index < 40, blood total lymphocyte count < 1600 cells/mm3, and grades of body mass index-adjusted body weight loss (combined BMI-BWL). We assessed the association of clinicopathological features, nutritional status, and inflammation condition with overall survival using univariate and multivariate Cox regression analyses. RESULTS: The mean overall survival of ESCC patients was 28.8 mo,. The multivariate logistic regression model after adjustment for clinicopathological variables, malnutrition status, inflammation condition, and co-morbid status found that tumor stage and grades of combined BMI-BML served as equally important prognostic factors for overall survival. CONCLUSIONS: Advanced tumor stage and high grades of combined BMI-BWL were independent prognostic factors for overall survival in ESCC patients.

A comparison of the MNA-SF, MUST, and NRS-2002 nutritional tools in predicting treatment incompletion of concurrent chemoradiotherapy in patients with head and neck cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) treatment incompletion is a known negative prognosticator for patients with head and neck cancer (HNC). Malnutrition is a common phenomenon which leads to treatment interruption in patients with HNC. We aimed to compare the performance of three nutritional tools in predicting treatment incompletion in patients with HNC undergoing definitive CCRT. MATERIAL AND METHODS: Three nutritional assessment tools, Mini Nutritional Assessment-Short Form (MNA-SF), Malnutritional Universal Screening Tool (MUST), and Nutritional Risk Screening 2002 (NRS-2002), were prospectively assessed prior to CCRT for HNC patients. Patients were stratified into either normal nutrition or malnourished groups using different nutrition tools. Treatment incompletion and treatment-related toxicities associated with CCRT were recorded. RESULTS: A total of 461 patients were included in the study; malnourished rates ranged from 31.0 to 51.0%. The CCRT incompletion rates were 4.9-6.3% and 14.5-18.2% for normal nutrition patients and malnourished patients, respectively. The tools had significant correlations with each other (Pearson correlation 0.801-0.837, p<0.001 for all) and accurately predicted the incompletion of CCRT. MNA-SF had the highest performance in predicting treatment-related toxicity, including emergency room visits, need for hospitalization, any grade III or higher hematological adverse events, and critical body weight loss, compared to the other tools. CONCLUSIONS: MNA-SF, MUST, and NRS2002 were all shown to be competent tools for prediction of treatment incompletion and treatment-related toxicity in HNC patients undergoing CCRT. We suggest implementing nutritional assessment prior to treatment to improve the rate of treatment completion and to reduce treatment-related toxicity in HNC patients.

Impact of early nutrition counseling in head and neck cancer patients with normal nutritional status.

BACKGROUND: Nutritional counseling is frequently overlooked in cancer patients with normal nutritional status. This study aimed to evaluate the impact of nutritional counseling in head and neck cancer (HNC) patients with normal nutritional status prior to concurrent chemoradiotherapy (CCRT). METHODS: A total of 243 patients with pretreatment normal nutritional status and locally advanced HNC receiving concurrent chemoradiotherapy (CCRT) at three medical centers were enrolled. All patients were retrospectively allocated into the early (≤ 2 weeks, n = 105, 43.2%), late (> 2 weeks, n = 102, 42.0%), and no nutritional counseling groups (n = 36, 14.8%) according to the time interval between the date of CCRT initiation and the first date of nutritional counseling for comparison. RESULTS: The 1-year overall survival rates were 95.0%, 87.5%, and 81.3% in the early, late, and no nutritional counseling groups (p = 0.035), respectively. The median body weight changes at end of CCRT were - 4.8% (range, - 13.3 to 8.7%), - 5.6% (range, - 21.9 to 5.6%), and - 8.6% (range, - 20.3 to 2.4%) in patients in the early, late, and no nutritional counseling groups, respectively. The early termination of chemotherapy rates and the incompletion rates of planned radiotherapy were 1.9% and 1.9%, 2.9%, and 2.0%, 13.9%, and 19.4% in patients in the early, late, and no nutritional counseling groups, respectively. CONCLUSIONS: Our findings strongly suggest that while some HNC patients may have pretreatment normal nutritional status, early nutritional counseling is nevertheless essential for the improvement of treatment tolerance and survival outcome.

A prospective nutritional assessment using Mini Nutritional Assessment-short form among patients with head and neck cancer receiving concurrent chemoradiotherapy.

BACKGROUND: No gold standard of nutritional assessment is established among patients with head and neck cancer (HNC) receiving concurrent chemoradiotherapy (CCRT). This study aimed to evaluate the clinical significance of pre-treatment nutritional status using the Mini Nutritional Assessment-short form (MNA-SF) among HNC patients receiving CCRT. METHODS: A total of 461 consecutive patients with newly diagnosed HNC treated with definitive CCRT at three medical institutes were prospectively enrolled. Nutritional status was assessed using MNA-SF within 7 days before CCRT initiation. Patients were classified as having normal nutrition, at risk of malnutrition, and malnourished groups according to MNA-SF for comparison. RESULTS: The 1-year overall survival rates were 89.8%, 76.8%, and 67.7% in the normal nutrition, at risk of malnutrition, and malnourished groups, respectively. Patients with normal nutrition had significantly lower rates of uncompleted radiotherapy and chemotherapy (4.5% and 4.1%, respectively) compared with patients at risk for malnutrition (14.1% and 11.5%, respectively) and those malnourished (11.1% and 11.1%, respectively). Patients with normal nutrition had significantly lower treatment-related complication rates regarding emergency room visits, hospital admission, and need for tubal feeding than those with at risk of malnutrition and malnourished. Patients with normal nutrition had significantly fewer severe hematologic toxicities (p = 0.044) and severe non-hematologic toxicities (p = 0.012) of CCRT than those malnourished. CONCLUSION: Pre-CCRT nutritional status identifies HNC patients vulnerable to treatment interruption and treatment complications. We suggest that nutritional assessment with MNA-SF should be incorporated in pre-CCRT evaluation for all HNC patients.

The objective structured clinical examination as an assessment strategy for clinical competence in novice nursing practitioners in Taiwan.

BACKGROUND: The conventional written tests and professional assessment have limitation in fair judgement of clinical competence. Because the examiners may not have total objectivity and may lack standardization throughout the assessment process. We sought to design a valid method of competence assessment in medical and nursing specialties. This work was aimed to develop an Objective Structured Clinical Exam (OSCE) to evaluate novice nursing practitioners' clinical competency, work stress, professional confidence, and career satisfaction. METHODS: A Quasi-experimental study (pre-post). Fifty-five novice nursing practitioners received the OSCE three-months following their graduation, which consisted of four stations: history taking, physical examination, problem-directed management, interpersonal communication, and the required techniques of related procedures. The examiners had to complete an assessment checklist, and the participants had to complete a pre-post questionnaire (modified from a Nursing Competency Questionnaire, a Stress scale, and Satisfaction with Learning scale). RESULTS: Among the novice nursing practitioners, 41 of them (74.5 %) passed the exam with a mean score of 61.38 ± 8.34. There was a significantly higher passing rate among nurses who were working in medical-surgical wards (85.7 %) and the intensive care unit-emergency department (77.8 %) compared to novice nursing practitioners working in other units. All the novice nursing practitioners at Station A had poor performance in assessing patients with a fever. OSCE performance was more associated with educational attainment and work unit, rather than the gender. Finally, the participants showed statistically significant increases in their clinical competency, confidence in their professional competence, satisfaction with the clinical practice, and decreased work stress after the OSCE. CONCLUSIONS: We found that the OSCE process had a positive educational effect, in providing a meaningful and accurate assessment of the competence of novice nursing practitioners. An appropriate OSCE program is vital for novice nursing practitioners, educators, and administrators. The effective application of OSCEs can help novice nursing practitioners gain confidence in their clinical skills.

The association between immune-related adverse events and survival outcomes in Asian patients with advanced melanoma receiving anti-PD-1 antibodies.

BACKGROUND: The association between immune-related adverse events (irAEs) and survival outcomes in patients with advanced melanoma receiving therapy with immune checkpoint inhibitors (ICIs) has not been well established, particularly in Asian melanoma. METHODS: We retrospectively reviewed 49 melanoma patients undergoing therapy with ICIs (anti-PD-1 monotherapy), and analyzed the correlation between irAEs and clinical outcomes including progression-free survival (PFS) and overall survival (OS). RESULTS: Overall, the patients who experienced grade 1-2 irAEs had longer PFS (median PFS, 4.6 vs. 2.5 months; HR, 0.52; 95% CI: 0.27-0.98; p = 0.042) and OS (median OS, 15.2 vs. 5.7 months; HR, 0.50; 95% CI: 0.24-1.02; p = 0.058) than the patients who did not experience irAEs. Regarding the type of irAE, the patients with either skin/vitiligo or endocrine irAEs showed better PFS (median PFS, 6.1 vs. 2.7 months; HR, 0.40, 95% CI: 0.21-0.74; p = 0.003) and OS (median OS, 18.7 vs. 4.5 months; HR, 0.34, 95% CI: 0.17-0.69, p = 0.003) than patients without any of these irAEs. CONCLUSIONS: Melanoma patients undergoing anti-PD-1 monotherapy and experiencing mild-to-moderate irAEs (grade 1-2), particularly skin (vitiligo)/endocrine irAEs had favorable survival outcomes. Therefore, the association between irAEs and the clinical outcomes in melanoma patients undergoing anti-PD-1 ICIs may be severity and type dependent.

External validation of the Besançon nomogram in Asian patients with advanced pancreatic cancer receiving second-line chemotherapy: A multi-institute experience in Taiwan.

BACKGROUND: Determining survival outcome in advanced pancreatic ductal adenocarcinoma (aPDAC) patients receiving second-line (L2) chemotherapy is important for clinical decision-making. The Besançon group from France recently proposed a prognostic nomogram to predict overall survival (OS) for aPDAC patients receiving L2 chemotherapy. The present study aimed to externally validate the performance of the Besançon nomogram in predicting OS in an Asian cohort. METHODS: We retrospectively enrolled 349 patients who received L2 chemotherapy for aPDAC between 2010 and 2016 at four institutes in Taiwan. The performance of the Besançon model in this cohort was evaluated with C-index and calibration plots. RESULTS: The median OS time in our patient cohort was 4.5 months (95% confidence interval [CI], 3.0-5.0). Using the Besançon nomogram-predicted risk groups, the median OS times in the low, intermediate, and high-risk groups were 6.7 (95% CI, 5.3-8.2), 3.2 (95% CI, 2.4-3.9), and 1.7 months (95% CI, 0.6-2.7), respectively. The C-index of the predicted six- and 12-month survival probabilities for the Besançon nomogram were 0.766 (95% CI, 0.715-0.816) and 0.698 (95% CI, 0.641-0.754), respectively. The calibration plot showed that the observed six-month survival probability was close to the diagonal line, while that for 12-month survival deviated below the diagonal line compared to the survival probability predicted by the Besançon nomogram. CONCLUSIONS: Although the Besançon nomogram tended to over-estimate the 12-month survival probability, our study demonstrated that the nomogram is a reliable and readily applicable model to estimate survival outcomes of aPDAC patients receiving L2 chemotherapy.

Development and validation of a prognostic nomogram to predict survival in patients with advanced pancreatic cancer receiving second-line palliative chemotherapy.

BACKGROUND AND AIM: Given that a wide variation in tumor response rates and survival times suggests heterogeneity among the patients with advanced pancreatic cancer (APC) who underwent second-line (L2) chemotherapy, it is a challenge in clinical practice to identify patients who will receive the most benefit from L2 treatment. METHODS: We selected 183 APC patients who received L2 palliative chemotherapy between 2010 and 2016 from a medical center as the development cohort. A Cox proportional hazard model was used to identify the prognostic factors and construct the nomogram. An independent cohort of 166 patients from three other hospitals was selected for external validation. RESULTS: The nomogram was based on eight independent prognostic factors from the multivariate Cox model: sex, Eastern Cooperative Oncology Group performance status, reason for first-line treatment discontinuation, duration of first-line treatment, neutrophil-to-lymphocyte ratio, tumor stage, body mass index, and serum carbohydrate antigen 19-9 levels at the beginning of L2 treatment. The model exhibited good discrimination ability, with a C-index of 0.733 (95% confidence interval, 0.681-0.785) and 0.724 (95% confidence interval, 0.661-0.787) in the development and validation cohorts, respectively. The calibration plots of the development and validation cohorts showed optimal agreement between model prediction and actual observation in predicting survival probability at 6 months, 1 year, and 2 years. CONCLUSIONS: This study developed and externally validated a prognostic model that accurately predicts the survival outcome of APC patients before L2 palliative chemotherapy, which could assist in clinical decision-making, counseling for treatment, and most importantly, prognostic stratification of patients.

Effect of Chemotherapy on Dual-Energy X-ray Absorptiometry (DXA) Body Composition Precision Error in Head and Neck Cancer Patients.

BACKGROUND: Precision error in dual-energy X-ray absorptiometry (DXA) is defined as difference in results due to instrumental and technical factors given no biologic change. The aim of this study is to compare precision error in DXA body composition scans in head and neck cancer patients before and 2 months after chemotherapy. METHODOLOGY: A total of 34 male head and neck cancer patients with normal body mass index (BMI) were prospectively enrolled and all patients received 2 consecutive DXA scans both before and after 2 months of chemotherapy for a total of 4 scans. The precision error of 3 DXA body composition values (lean mass, fat mass, and bone mineral content) was calculated for total body and 5 body regions (arms, legs, trunk, android, and gynoid). Precision errors before and after treatment were compared using generalized estimating equation model. RESULTS: There was no significant change in precision error for the DXA total body composition values following chemotherapy; lean mass (0.33%-0.40%, p = 0.179), total fat mass (1.39%-1.70%, p = 0.259) and total bone mineral content (0.42%-0.56%, p = 0.243). However, there were significant changes in regional precision error; trunk lean mass (1.19%-1.77%, p = 0.014) and android fat mass (2.17%-3.72%, p = 0.046). CONCLUSIONS: For head and neck cancer patients, precision error of DXA total body composition values did not change significantly following chemotherapy; however, there were significant changes in fat mass in the android and lean mass in the trunk. Caution should be exercised when interpreting longitudinal DXA body composition data in those body parts.

Liver-directed microRNA-7a depletion induces nonalcoholic fatty liver disease by stabilizing YY1-mediated lipogenic pathways in zebrafish.

Nonalcoholic fatty liver disease (NAFLD) has been associated with the function and changes in expression levels of microRNAs (miRs). MiR-7 has been proven to play an important role in many cellular processes; however, its functions in the context of liver lipogenesis remain unknown. We applied the microRNA-sponge (miR-SP) technology and generated transgenic miR-7a-SP models (hC7aSP and bC7aSP), which disrupted the activities of hepatic miR-7a and induced the early onset of NAFLD and nonalcoholic steatohepatitis (NASH) in zebrafish. We identified a novel miR-7a target, YY1, and demonstrated novel miR-7a functions to regulate zebrafish hepatic lipid metabolism by controlling YY1 stabilization through the regulation of the expression of lipogenic signaling pathways. Correspondingly, liver specific miR-7a depletion functionally promoted lipid accumulation in hC7ASP livers. NASH hC7aSP increased the expression of inflammatory genes (il-1b, il-6, tnf-α, ifn-γ, nfkb2, and NF-kB) and endoplasmic reticulum stress markers (atf6, ern2, ire1, perk, hspa5 and ddit3). Molecular analysis revealed that miR-7a-SP can stabilize YY1 expression and contribute to the accumulation of hepatic triglycerides by reducing the CHOP-10 expression in the hC7aSP and then inducing the transactivation of C/EBP-α and PPAR-γ expression. PPAR-γ antagonists and miR-7a mimic treatment ameliorate hC7aSP NASH phenotypes. CONCLUSION: Our results suggest that miR-7a-SP acts as a lipid enhancer by directly increasing YY1 stability to disrupt CHOP-10-dependent suppression of lipogenic pathways, resulting in increased lipid accumulation. MiR-7a expression improves liver steatosis and steatohepatitis in hC7aSPs, which suggests a novel strategy for the prevention and early treatment of NASH in humans.

Prognostic Significance of Low Body Mass Index and Betel-Quid Use in the 5-Year Survival Rates of Esophageal Squamous Cell Carcinoma Patients.

AIM: This study aimed to examine the relationship between clinicopathological features, varied malnutrition criteria, and survival in esophageal squamous cell carcinoma (ESCC) patients. METHODS: Six malnutrition criteria (body mass index (BMI) < 18.5 kg/m2, serum albumin level < 3.5 g/dL, neutrophil-to-lymphocyte ratio (NLR) > 3.5, platelet-to-lymphocyte ratio (PLR) > 17, prognostic nutrition index (PNI) < 40, and blood total lymphocyte count (TLC) < 1,600 cells/mm3) were measured in 205 ESCC patients at the time of diagnosis. Malnutrition status and clinicopathological features were tested for prognostic effects on the 5-year survival rate. RESULTS: Malnutrition rates vary according to nutrition assessment tools, ranging from 21.5% based on BMI < 18.5 kg/m2 to 67.8% based on PNI < 40. These rates are associated with increased inflammation, but they showed no difference among various tumor stages. After adjustment of demographic variables and comorbid status, advanced tumor stage, low BMI at diagnosis, and betel quid use showed prognostic significance in the 5-year survival rate based on a multivariate logistic regression analysis. CONCLUSIONS: Different nutrition assessment criteria produced different malnutrition rates. Advanced tumor stage, low BMI at diagnosis, and betel quid use were independent prognostic factors for worse survival of ESCC patients.

Progressive Sarcopenia in Patients With Colorectal Cancer Predicts Survival.

OBJECTIVE: The purpose of this study was to evaluate the relationship between sarcopenia and overall and progression-free survival in patients with colorectal cancer. MATERIALS AND METHODS: This study was retrospective and complied with HIPAA. Patients with colorectal cancer who underwent CT at the time of and 6-18 months after diagnosis were included. Patients were followed for at least 5 years after diagnosis. Skeletal muscle index (SMI) and mean muscle attenuation of the psoas and paraspinal muscles at the L4 level determined the degree of sarcopenia. Composite measurements combining psoas and paraspinal muscles (total muscle) were also obtained. Univariate and multivariate Cox proportional hazard analysis was performed to evaluate the association between survival and changes in SMI and changes in attenuation. Kaplan-Meier analysis was also performed. RESULTS: A total of 101 patients were included (mean age ± SD, 63.7 ± 13.7 years; 68 men, 33 women). The hazard ratios for overall survival were 2.27, 1.68, and 1.54 for changes in SMI of the psoas muscle, paraspinal muscle, and total muscle (all p < 0.05). The hazard ratios for overall survival were 1.14, 1.18, and 1.24 for changes in attenuation of the psoas muscle, paraspinal muscle, and total muscle, respectively (all p < 0.05). The hazard ratios for progression-free survival were 1.33, 1.41, and 1.23 for changes in SMI of the psoas muscle, paraspinal muscle, and total muscle (not statistically significant). The hazard ratios for progression-free survival were 1.10, 1.21, and 1.23 for changes in attenuation of the psoas muscle, paraspinal muscle, and total muscle, respectively (p < 0.05). Kaplan-Meier analysis showed significant differences in overall and progression-free survival based on sex-specific quartiles of muscle quantity and quality. CONCLUSION: Progressive sarcopenia after diagnosis of colorectal cancer has a significant negative prognostic association with overall and progression-free survival.

MicroRNA-27b Depletion Enhances Endotrophic and Intravascular Lipid Accumulation and Induces Adipocyte Hyperplasia in Zebrafish.

miR-27b has emerged as a regulatory hub in cholesterol and lipid metabolism, and as a potential therapeutic target for treating atherosclerosis and obesity. However, the impact of miR-27b on lipid levels in vivo remains to be determined. Zebrafish lipids are normally stored as triacylglycerols (TGs) and their main storage sites are visceral, intramuscular, and subcutaneous lipid depots, and not blood vessels and liver. In this study, we applied microRNA-sponge (miR-SP) technology and generated zebrafish expressing transgenic miR-27b-SP (C27bSPs), which disrupted endogenous miR-27b activity and induced intravascular lipid accumulation (hyperlipidemia) and the early onset of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Oil Red O staining predominantly increased in the blood vessels and livers of larvae and juvenile C27bSPs, indicating that miR-27b depletion functionally promoted lipid accumulation. C27bSPs also showed an increased weight gain with larger fat pads, resulting from adipocyte hyperplasia. Molecular analysis revealed that miR-27b depletion increased the expression of genes that are associated with lipogenesis and the endoplasmic reticulum (ER). Moreover, miR-27b-SP increased peroxisome proliferator-activated receptor γ (PPAR-γ), CCAAT enhancer binding protein-α (C/EBP-α, and sterol regulatory element binding transcription factor 1c (SREBP-1c) expression and contributed to lipogenesis and adipogenesis. CONCLUSION: Our results suggest that miR-27b-SP acts as a lipid enhancer by directly increasing the expression of several lipogenic/adipogenic transcriptional factors, resulting in increased lipogenesis and adipogenesis. In this study, miR-27b expression improved lipid metabolism in C27bSPs, which suggests that miR-27b is an important lipogenic factor in regulating early onset of hyperlipidemia and adipogenesis in zebrafish.