Malnutrition and visceral obesity predicted adverse short-term and long-term outcomes in patients undergoing proctectomy for rectal cancer.

BACKGROUND: To the best of our knowledge, no previous studies have explored the relationship between visceral obesity and malnutrition. Therefore, this study has aimed to investigate the association between them in patients with rectal cancer. METHODS: Patients with rectal cancer who underwent proctectomy were included. Malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM). Visceral obesity was measured using computed tomography (CT). The patients were classified into four groups according to the presence of malnutrition or visceral obesity. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors for postoperative complications. Univariate and multivariate cox regression analyses were performed to evaluate the risk factors for overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier survival curves and log-rank tests were performed for the four groups. RESULTS: This study enrolled 624 patients. 204 (32.7%) patients were included in the well-nourished non-visceral obesity (WN) group, 264 (42.3%) patients were included in the well-nourished visceral obesity (WO) group, 114 (18.3%) patients were included in the malnourished non-visceral obesity (MN) group, and 42 (6.7%) patients were included in the malnourished visceral obesity (MO) group. In the multivariate logistic regression analysis, the Charlson comorbidity index (CCI), MN, and MO were associated with postoperative complications. In the multivariate cox regression analysis, age, American Society of Anesthesiologists (ASA) score, tumor differentiation, tumor node metastasis (TNM), and MO were associated with worsened OS and CSS. CONCLUSIONS: This study demonstrated that the combination of visceral obesity and malnutrition resulted in higher postoperative complication and mortality rates and was a good indicator of poor prognosis in patients with rectal cancer.

The geriatric nutritional risk index is an effective tool to detect GLIM-defined malnutrition in rectal cancer patients.

Background: This study aimed to investigate the value of the Geriatric Nutritional Risk Index (GNRI), prognostic nutritional index (PNI), and advanced lung cancer inflammation index (ALI) scores in detecting malnutrition in patients with rectal cancer; the Global Leadership Initiative on Malnutrition (GLIM) was used as the reference criterion. Materials and methods: This study included patients with rectal cancer who underwent proctectomy. GNRI, PNI, and ALI were calculated to detect the GLIM-defined malnutrition using the Receiver operating characteristic (ROC) curves. Univariate and multivariate logistic regression analyses were used to evaluate the association between the nutritional tools and postoperative complications. Kaplan-Meier survival curves, log-rank tests, and univariate and multivariate Cox regression analyses were used to clarify the relationship between nutritional tools and overall survival (OS). Results: This study enrolled 636 patients with rectal cancer. The GNRI demonstrated the highest sensitivity (77.8%), pretty specificity (69.0%), and the largest AUC (0.734). The GNRI showed good property in predicting major postoperative complications. All three nutritional tools were independent predictors of OS. Conclusion: The GNRI can be used as a promising alternative to the GLIM and is optimal in perioperative management of patients with rectal cancer.

Impact of metabolic syndrome on the short- and long-term outcomes for the elderly patients with gastric cancer after radical gastrectomy.

BACKGROUND: Metabolic syndrome (MetS) and gastric cancer are age-related diseases, and their incidence rates have risen in past decades. However, few studies have examined the relationship between MetS and the prognosis of elderly patients who underwent radical gastrectomy, and the conclusions remain controversial. METHODS: We conducted a prospective study of elderly patients who underwent radical gastrectomy for gastric cancer from August 2014 to February 2018. MetS was defined based on visceral fat area (VFA) instead of BMI or waist circumference. Receiver operating characteristic curve analysis was used to determine the cutoff values for VFA. RESULTS: A total of 585 patients were included in this study. The optimal cutoff values for VFA were 96.1 cm2 for men and 105.2 cm2 for women, and 212 patients were diagnosed with MetS. The patients with MetS suffered significantly more postoperative complications than those without MetS (37.3% versus 21.4%, P < 0.001). The multivariable logistic regression analysis demonstrated that MetS (OR 2.923, P < 0.001), BMI < 18.5 kg/m2 (OR 2.086, P = 0.045), cardiac tumor (OR 1.865, P = 0.013), and Nutritional Risk Screening 2002 scores ≥ 3 (OR 1.654, P = 0.015) were independent risk factors for postoperative complications. During a median follow-up period of 56.4 months, the MetS group and the non-MetS group had comparable overall survival and disease-specific survival. CONCLUSIONS: MetS was an independent risk factor for complications of the elderly patients after radical gastrectomy, but had no influence on long-term survival.

Value of Sarcopenia defined by the new EWGSOP2 consensus for the prediction of Postoperative Complications and Long-term Survival after Radical Gastrectomy for Gastric Cancer: A comparison with four common nutritional screening tools.

Background: Nutritional risk and sarcopenia are both associated with increased postoperative morbidity and mortality following elective surgery. This study aimed to investigate whether sarcopenia has additional predictive value for postoperative complications and long-term survival besides nutritional screening tools. Methods: Clinical data of patients underwent radical gastrectomy for gastric cancer was prospectively collected. Sarcopenia was diagnosed by grip strength plus muscle quanlity/quality based on preoperative abdominal CT scans. Nutritional screening was performed using 4 common nutritional screening tools, including Malnutrition Universal Screening Tool (MUST), Nutritional Risk Screening (NRS)-2002, Malnutrition Screening Tool (MST), and Short Nutritional Assessment Questionnaire (SNAQ). Results: A total of 880 patients were analyzed, in which 167 (18.98%) were diagnosed with sarcopenia. The incidence of nutritional risk identified by the 4 tools were 44.66% (MUST ≥1), 35.23% (NRS-2002 ≥3), 29.89% (MST ≥2), and 20.34% (SNAQ ≥2). Multivariate analyses showed that nutritional risk identified by the 4 nutritional screening tools were not independently associated with postoperative complications, overall survival (OS) or disease-free survival (DFS), except for NRS-2002 ≥3 as an independent risk factor of OS. Sarcopenia was always an independent risk factor for postoperative complications, OS, and DFS after adjusting for nutritional risk and the other covariates in the multivariate analyses. Conclusions: MUST, NRS-2002, MST, and SNAQ had low predictive power for postoperative complications and long-term survival in patients underwent radical gastrectomy for gastric cancer. Sarcopenia had additional predictive value for postoperative complications and long-term survival besides these nutritional screening tools and should be implemented in the preoperative assessments.

Nrf2 deficiency promotes the increasing trend of autophagy during aging in skeletal muscle: a potential mechanism for the development of sarcopenia.

This study aims to explore the impact of nuclear factor erythroid 2-related factor 2 (Nrf2) deficiency on skeletal muscle autophagy and the development of sarcopenia. LC3b, P62, Bnip3, Lamp-1, and AMPK protein levels were measured in muscle from young, middle-aged, old Nrf2-/- (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice. Autophagy flux was measured in young WT, young KO, old WT, old KO mice, using colchicine as autophagy inhibitor. There was a trend of higher accumulation of LC3b-II, P62, Bnip3, Lamp-1 induced by colchicine in old WT mice compared with young WT mice. Colchicine induced a significantly higher accumulation of LC3b-II, P62, Bnip3, Lamp-1 in KO mice compared with WT mice, both in the young and old groups. AMPK and reactive oxygen species (ROS) were unregulated following Nrf2 KO and increasing age, which was consistent with the increasing trend of autophagy flux following Nrf2 KO and increasing age. Nrf2 KO and increasing age caused decreased cross-sectional area of extensor digitorum longus and soleus muscles. We concluded that Nrf2 deficiency and increasing age may activate AMPK and ROS signals to cause excessive autophagy activation in skeletal muscle, which can be a potential mechanism for the development of sarcopenia.

A comparison of four common malnutrition risk screening tools for detecting cachexia in patients with curable gastric cancer.

OBJECTIVE: Although there is international consensus regarding the importance of cachexia, no tools exist, to our knowledge, for cachexia screening among patients with cancer. The aim of this study was to evaluate whether patients with cancer and cachexia could be identified using the four most commonly used nutritional screening tools: the Malnutrition Universal Screening Tool (MUST), the Nutritional Risk Screening (NRS)-2002, the Malnutrition Screening Tool (MST), and the Short Nutritional Assessment Questionnaire (SNAQ). METHODS: Clinical data were prospectively collected for patients who underwent elective radical gastrectomy for gastric cancer in two large centers between August 2014 and February 2018. Patients were also screened using the MUST, NRS-2002, MST, and SNAQ tools. The screening results were subsequently compared with the international consensus diagnostic criteria for cancer cachexia. RESULTS: A total of 1001 patients were evaluated, including 363 patients (36.3%) with cancer cachexia. Among the patients "at nutritional risk" based on each tool, the proportions of cachexia were 87.3% for the MUST tool, 84.3% for the MST tool, 76.6% for the NRS-2002 tool, and 54.3% for the SNAQ tool. The MST tool provided the largest area under the curve for identifying cancer cachexia (0.914; P < 0.001). CONCLUSION: Among the tools examined, the MST had the greatest ability to detect cancer cachexia among patients with gastric cancer.

Laparoscopic-assisted colorectal surgery benefits visceral obesity patients: a propensity-matched analysis.

BACKGROUND: We aimed to determine the safety and effectiveness of laparoscopic-assisted surgery (LAS) in visceral obesity patients with colorectal cancer (CRC). PATIENTS AND METHODS: We retrospectively collected the clinical data of consecutive patients who underwent colorectal surgery for CRC between August 2014 and July 2018. The third lumbar vertebra visceral fat area was measured to diagnose visceral obesity. One-to-one propensity score matching was performed to compare the short-term outcomes between the open surgery (OS) and LAS in visceral obesity patients. Univariate and multivariate analyses were performed to evaluate the risk factors of postoperative complications. RESULTS: A total of 280 visceral obesity patients were included in this study with 140 patients for each group. Compared with the OS group, the LAS group had more lymph nodes harvested, longer surgical duration, and shorter postoperative hospital stay. The overall incidence of complications in OS was significantly higher than LAS (32.1 vs. 20.0%, P=0.021). Multivariate analysis revealed that age of at least 65 years (odds ratio: 1.950, 95% confidence interval: 1.118-3.403; P=0.019) was an independent risk factor for postoperative complications, whereas LAS (odds ratio: 0.523, 95% confidence interval: 0.302-0.908; P=0.021) was a protective factor. CONCLUSION: LAS in visceral obesity patients with CRC was a safer and less invasive alternative than open surgery, with fewer complications within the first 30 days postoperatively.

Myosteatosis predicts prognosis after radical gastrectomy for gastric cancer: A propensity score-matched analysis from a large-scale cohort.

BACKGROUND: Increasing evidence has suggested that sarcopenia is linked with cancer prognosis, but only limited data have focused on the impact of myosteatosis on cancer outcomes. This study evaluates the influence of myosteatosis on postoperative complications and survival in those patients who underwent radical resection of gastric carcinoma. METHODS: Patients who underwent elective radical gastrectomy for gastric cancer and had computed tomographic images available were identified from a prospectively collected database between 2008 and 2013. Myosteatosis was diagnosed by the cutoff values obtained from the method of optimum stratification. To obtain 2 well-balanced cohorts for available variables influencing clinical outcomes, the myosteatosis group was matched 1:1 with nonmyosteatosis group by using a propensity score match. RESULTS: Of 973 patients, 584 were matched for analyses. Compared with the nonmyosteatosis group, the myosteatosis group manifested significantly higher severe postoperative complications rates, shorter overall survival, and disease-free survival. Before matching, multivariate analyses identified that myosteatosis was an independent risk factor for severe postoperative complications, and Cox proportions hazards model showed that myosteatosis was an independent predictor for shorter overall survival and disease-free survival. In addition, subgroup analyses of each muscle phenotype showed that patients with both sarcopenia and myosteatosis had a poorer overall survival and disease-free survival than other patients. CONCLUSION: Myosteatosis in gastric cancer is associated with poor prognosis. Classifying the skeletal muscle into subranges of radio density is a promising strategy to understand the impact of skeletal muscle on unfavorable surgical outcomes in gastric cancer patients.

Sarcopenia is an effective prognostic indicator of postoperative outcomes in laparoscopic-assisted gastrectomy.

BACKGROUND: The association between sarcopenia and postoperative outcomes in patients who undergo laparoscopic-assisted gastrectomy is unclear. We aimed to determine the predictive value of sarcopenia for adverse postoperative outcomes after laparoscopic-assisted gastrectomy for gastric cancer. MATERIALS AND METHODS: We prospectively collected the clinical data of patients who underwent elective radical laparoscopic-assisted gastrectomy for gastric cancer in two large centers from August 2014 to October 2017. The third lumbar vertebra skeletal muscle index, handgrip strength, and 6-m usual gait speed were measured to diagnose sarcopenia. Subsequently, we aimed to identify the risk factors for postoperative complications. RESULTS: The study included 313 patients and 37 (11.8%) patients were classified as sarcopenic. Compared with non-sarcopenic patients, sarcopenic patients were significantly older (P < 0.001), had higher nutritional risk screening 2002 scores (P = 0.013), Charlson comorbidity index (CCI) scores (P = 0.033), and neutrophil to lymphocyte ratio (P = 0.004), and lower body mass index (P < 0.001), preoperative serum albumin (P < 0.001), and hemoglobin (P < 0.001). Sarcopenic patients had higher postoperative complication rate (P = 0.002), longer postoperative hospital stays (P = 0.020) and higher total cost of hospitalization (P = 0.001). Multivariate analysis revealed that CCI score ≥1 (odds ratio [OR]: 2.424, 95% confidence interval [CI]: 1.309-4.487; P = 0.005) and sarcopenia (OR: 2.752, 95% CI: 1.274-5.944; P = 0.010) were independent risk factors for short-term postoperative complications. CONCLUSION: Sarcopenia is an independent clinical predictor of short-term postoperative complications after laparoscopic-assisted gastrectomy.

Impact of sarcopenia on clinical outcomes after radical gastrectomy for patients without nutritional risk.

OBJECTIVE: The aim of this study was to investigate the prevalence of sarcopenia in patients without nutritional risk and the association between sarcopenia and postoperative outcomes after radical gastrectomy in these patients. METHOD: We conducted a study of non-nutritional risk patients with gastric cancer who underwent gastrectomy from August 2014 to December 2017 in two centers. Nutritional Risk Screening 2002 (NRS 2002) was used to evaluate the nutritional risk. Patients who with NRS 2002 score <3 were classified as having no nutritional risk and were included in the study. Demographic and perioperative data were gathered. Sarcopenia was diagnosed based on the European Working Group on Sarcopenia in Older People criteria. Univariate and multivariate analysis were performed to determine the association between preoperative risk factors and postoperative complications. RESULTS: In all, 545 patients were included, in which the prevalence of sarcopenia and postoperative complications was 7.3% and 21.1%, respectively. Sarcopenia was significantly associated with higher age, lower body mass index, lower handgrip strength, lower usual walking speed, longer postoperative hospital length of stay, and higher costs. Multivariate analysis of prognostic factors revealed that sarcopenia was an independent predictor (odds ratio, 2.330; 95% confidence interval, 1.132-4.796; P = 0.022] for postoperative complications. Male sex, diabetes, and preoperative anemia also were risk factors for postoperative complications. CONCLUSION: Sarcopenia was a significant independent risk factor for postoperative complications after gastrectomy in patients without nutritional risk. Preoperative assessment and management of sarcopenia should be helpful for improving clinical outcomes for patients without nutritional risk.

Nrf2 deficiency exacerbates frailty and sarcopenia by impairing skeletal muscle mitochondrial biogenesis and dynamics in an age-dependent manner.

AIM: Mitochondrial dysfunction during aging is a key factor that contributes to sarcopenia. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been increasingly recognized to regulate mitochondrial function. The present study aimed to investigate the role of Nrf2 in the development of frailty and sarcopenia during aging, and to demonstrate whether Nrf2 contributes to the maintenance of muscle mass and function by regulation of mitochondrial biogenesis and dynamics during the aging process. METHODS: Young (5-6 months), middle-aged (11-13 months), old (20-24 months) Nrf2-/- (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice were used in this study. Physical function of the mice in the 6 groups was assessed by grip strength test, four paw inverted hanging test, rotarod analysis, open field analysis, and treadmill endurance test. Muscle mass was measured by cross-sectional area (CSA) of tibialis anterior muscles and gastrocnemius muscle weight. The frailty status of the 25 old WT mice and 23 old KO mice were assessed based on the mouse frailty phenotype assessment. Expression levels of genes involved in mitochondrial biogenesis (nuclear respiratory factor 1 (Nrf1), peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM)) and mitochondrial dynamics (optic atrophy protein 1 (Opa1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and dynamin-related protein 1 (Drp1)) were measured in the skeletal muscle. SDH staining was performed and mitochondrial DNA (mtDNA) copy number was measured. Transmission electron microscopy was used to measure the mitochondria number and morphology. RESULTS: Physical function and muscle mass decreased during aging. The mRNA expression levels of Nrf2 decreased with increasing frailty phenotype scores in the old WT mice. There were minimal differences in the physical function and muscle mass between the WT and KO mice in the young groups, whereas Nrf2 deficiency caused a declined physical function and muscle mass in the middle-aged and old mice, and exacerbated frailty in the old mice. The decreases of the physical function and muscle mass were accompanied by the reduced expression levels of genes involved in mitochondrial biogenesis and dynamics, as well as a reduction of mitochondrial number, mitochondrial content, mtDNA copy number, and an impaired mitochondria morphology in the skeletal muscle. CONCLUSION: Nrf2 deficiency exacerbated frailty and sarcopenia during aging, at least partially by impairing skeletal muscle mitochondrial biogenesis and dynamics in an age-dependent manner.

A Novel Nomogram for Predicting Postsurgical Intra-abdominal Infection in Gastric Cancer Patients: a Prospective Study.

BACKGROUND: This study aimed to determine the relationship between intra-abdominal infection (IAI) and sarcopenia prospectively and to construct a nomogram to identify patients at a high risk of IAI. METHODS: We conducted a prospective study of 682 consecutive patients with gastric cancer who underwent radical gastrectomy. The sarcopenia elements, including lumbar skeletal muscle index, handgrip strength, and gait speed, were measured before surgery. Factors contributing to IAI were determined through univariate and multivariate analysis. A nomogram consisting of the independent risk factors was constructed to quantify the individual risk of IAI. RESULTS: Of the 682 patients enrolled in this study, 132 patients were diagnosed with sarcopenia and 61 were diagnosed with IAI. Logistic analysis revealed that sarcopenia, tumor size, pathological type, and multivisceral resection were independent prognostic factors for IAI. The nomogram model for IAI was able to reliably quantify the risk of IAI with a strong optimism-adjusted discrimination (concordance index, 0.736). CONCLUSIONS: Sarcopenia is an independent predictor of IAI. Our nomogram was a simple and practical instrument to quantify the individual risk of IAI and could be used to identify patients at a high risk.

Effect of nutritional risk on short-term outcomes after laparoscopic-assisted gastrectomy: a prospective study from two centers.

BACKGROUND/AIM: The aim of this prospective double-center study was to explore the effect of nutritional risk on short-term outcomes in the patients who had gastric cancer and underwent a laparoscopic-assisted gastrectomy. PATIENTS AND METHODS: We conducted a study of patients who underwent laparoscopic-assisted gastrectomy in two large centers between June 2014 and April 2017. Patients' demographic and clinical characteristics and postoperative short-term outcomes were prospectively analyzed. Patients were divided into two groups depend on the preoperative presence of nutritional risk. Clinical variables were compared. Univariate analyses and multivariate logistic regression analyses evaluating the risk factors for postoperative complications were performed. RESULTS: A total of 256 patients, comprising 187 males and 69 females, met the inclusion criteria and were included in this study. The mean age was 61.81 years, the average BMI was 22.44 kg/m, and the average preoperative serum albumin was 39.42 g/l. Older age (P=0.001), higher tumor stage (P=0.047), lower BMI (P<0.001), lower preoperative serum albumin (P=0.005), and lower hemoglobin (P=0.013) were more common in the nutritional risk group. There were no significant differences in the short-term postoperative outcomes between nutritional risk and non-nutritional risk groups. Advanced age (P=0.024) and hypoalbuminemia (P=0.004) were independent risk factors for postoperative complications after laparoscopic-assisted gastrectomy. CONCLUSION: Nutritional risk may not be a clinical predictor of short-term outcomes after laparoscopic-assisted gastrectomy. Advanced age and preoperative hypoalbuminemia were independent risk factors for grade II or more postoperative complications.

Impact of visceral fat on surgical complications and long-term survival of patients with gastric cancer after radical gastrectomy.

BACKGROUND/OBJECTIVES: The aim of this study was to examine the impact of visceral fat on surgical complications and long-term survival for patients undergoing radical gastrectomy. SUBJECTS/METHODS: From 2009 to 2013, 859 patients who underwent curative resection for gastric cancer were enrolled from a prospectively maintained database. Visceral fat area (VFA) was assessed by preoperative CT scans. Patients were divided into two groups by VFA. Perioperative variables and postoperative outcomes were compared between the high VFA group and low VFA group. Univariable and multivariable analysis were performed to investigate independent risk factors of postoperative complications and survival. RESULTS: Some 859 patients were included in the study, 308 of whom were classified as high VFA. High VFA was correlated with advance age (P = 0.020), higher albumin levels (P = 0.001), hemoglobin levels (P < 0.05), ASA grade (P = 0.043) and Charlson Comorbidity Index (P = 0.004). Relative to patients with low VFA, those with high VFA had longer surgical durations (P = 0.004), higher rate of postoperative complications (P = 0.004), and longer hospital stays (P = 0.004). High VFA was identified as the only determinant for surgical complications by logistic regression analysis (OR, 2.236, 95% CI, 1.537-3.254; P < 0.001). Cox proportional hazards regression revealed no correlation between VFA and overall survival (OS) or disease-free survival (DFS). CONCLUSIONS: Increased VFA independently predicts surgical complications in patients after gastrectomy. However, VFA is not a prognostic biomarker of OS or DFS in patients with gastric cancer.

Sarcopenia predicts 1-year mortality in elderly patients undergoing curative gastrectomy for gastric cancer: a prospective study.

PURPOSE: One-year mortality is vital for elderly oncologic patients undergoing surgery. Recent studies have demonstrated that sarcopenia can predict outcomes after major abdominal surgeries, but the association of sarcopenia and 1-year mortality has never been investigated in a prospective study. METHODS: We conducted a prospective study of elderly patients (≥65 years) who underwent curative gastrectomy for gastric cancer from July 2014 to July 2015. Sarcopenia was determined by the measurements of muscle mass, handgrip strength, and gait speed. Univariate and multivariate analyses were used to identify the risk factors associated with 1-year mortality. RESULTS: A total of 173 patients were included, in which 52 (30.1 %) patients were identified as having sarcopenia. Twenty-four (13.9 %) patients died within 1 year of surgery. Multivariate analysis showed that sarcopenia was an independent risk factor for 1-year mortality. Area under the receiver operating characteristic curve demonstrated an increased predictive power for 1-year mortality with the inclusion of sarcopenia, from 0.835 to 0.868. Solely low muscle mass was not predictive of 1-year mortality in the multivariate analysis. CONCLUSIONS: Sarcopenia is predictive of 1-year mortality in elderly patients undergoing gastric cancer surgery. The measurement of muscle function is important for sarcopenia as a preoperative assessment tool.