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BACKGROUND Sarcopenia and cachexia are two predictors of adverse clinical outcomes, but they are partly overlapping. We aimed to compare the characteristics and prognostic value of cachexia and sarcopenia in patients after gastrectomy. METHODS From 2014 to 2019, a total of 1215 gastric cancer patients were enrolled. Cachexia and sarcopenia were diagnosed according to the most recent consensus definitions. Baseline characteristics and clinical outcomes were compared between the two groups. Risk factors of survival were evaluated by Cox regression analysis. RESULTS Of all patients, 26.5% were diagnosed with cachexia and 19.8% were diagnosed with sarcopenia. Sarcopenia was more prevalent in elderly patients, while cachexia was prone to occur in patients with TMN stage III. Survival curves showed that sarcopenia had adverse effects in patients with TMN stage I and II-III, while cachexia was only associated with poor survival at stages II-III. For the entire cohort, both cachexia and sarcopenia were adverse factors for prognosis. However, for stage I patients, sarcopenia was an independent predictor for overall survival (OS) (HR = 4.939, P < 0.001) and disease-free survival (DFS) (HR = 4.256, P < 0.001), but not cachexia; for stage II-III patients, cachexia was an independent predictor for OS (HR = 1.538, P < 0.001) and DFS (HR = 1.473, P = 0.001), but not sarcopenia. CONCLUSIONS Sarcopenia and cachexia have different clinical characteristics and prognostic values. For patients with early stage gastric cancer, detection for sarcopenia was more meaningful than cachexia. However, the prognostic significance of cachexia exceeded sarcopenia in advanced cancer.

Background Patients with gastric cancer often suffer from generalized and progressive reduction of skeletal muscle mass and strength, which negatively affects the quality of life (QOL). In this study, we explored the impact of sarcopenia on QOL and overall survival (OS). Methods From December 2015 to June 2017, 135 patients underwent radical gastrectomy at the First Affiliated Hospital of Wenzhou Medical University. Based on the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS), data including handgrip strength, 6-m gait speed and muscle mass were collected and analyzed. EORTC QLQ-C30 and EORTC QLQ-STO22 were used to evaluate the QOL before surgery, 1, 3 and 6 months after surgery. Results A total of 27 out of the 135 patients (20.00%) were diagnosed with sarcopenia. Compared with non-sarcopenia group, patients in sarcopenia group had a higher incidence of postoperative complications (14.80% vs. 40.70%, p = 0.003), and more hospitalization costs (p = 0.029). The scores of eating restriction (p = 0.026), anxiety (p = 0.045) and body image (p = 0.046) were significantly higher in sarcopenia group at postoperative 6 months. Besides, sarcopenia was an independent risk factor for global health status at 6 months after operation (OR: 2.881, 95% CI: 1.110–7.475, p = 0.030) and OS (HR: 3.140, 95% CI: 1.255–7.855, p = 0.014). Other factors, including tumor stage III and the postoperative complications, had negative influences on OS. Conclusion Sarcopenia is a predictive factor of poor QOL and prognosis in patients with gastric cancer.

Background The skeletal muscle mass index (SMI) and skeletal muscle radiodensity (SMD) are important components of sarcopenia and malnutrition. However, their assessment requires additional resources in cancer patients, which is inconvenient for the early detection of sarcopenia and malnutrition. Objectives This study aimed to develop and validate nomograms for the prediction of low muscle mass and muscle radiodensity and to examine the application value of the nomograms in the diagnoses of sarcopenia and malnutrition. Methods A total of 1315 patients diagnosed with gastric cancer between July 2014 and May 2019 were included. Random resampling with an 80/20 split ratio was performed to obtain a training cohort (n = 1056) and a validation cohort (n = 259). Nomograms were separately constructed for low SMI (LSMI) and low SMD (LSMD) in the training cohort based on prospectively collected preoperative data. The performance of the nomograms was assessed using the AUC, calibration curve, and Hosmer-Lemeshow test. The application values of the nomograms in the diagnoses of sarcopenia and malnutrition were also evaluated. Results Age, BMI, hemoglobin concentration, and gait speed were included in the nomogram for LSMI predictions. These variables, in addition to sex, were included in the nomogram for LSMD predictions. The diagnostic nomograms exhibited good discrimination, with AUCs of 0.818 (95% CI, 0.791-0.845) for the LSMI nomogram and 0.788 (95% CI, 0.761-0.815) for the LSMD diagnostic nomogram in the training cohort. Calibration was also excellent. The agreement ratios between the nomograms and actual observations in the total population were 92.3% and 95.6% for sarcopenia and malnutrition, respectively. Prognostic nomograms exhibited similar performance in the validation cohort. Conclusions Diagnostic nomograms consisting of preoperative factors can successfully predict LSMI and LSMD. These models facilitate early identification and timely interventions for at-risk populations.

Background Handgrip strength (HGS) is associated with poor clinical outcomes, including all‐cause, non‐cardiovascular, and cardiovascular mortalities. The published cut‐off points for HGS are mostly based on community populations from Western countries, lacking information on cancer patients from China. The objective of this study was to establish sex‐specific cut‐off points for Chinese cancer patients and investigate the effect of low HGS on cancer mortality. Methods We did a retrospective cohort study of patients who were diagnosed with malignant cancer from June 2012 to December 2018. HGS was measured using a hand dynamometer in 8257 cancer patients. Optimal stratification was used to solve threshold points. The hazard ratio (HR) of all cancer mortality and cancer‐specific mortality was calculated using Cox proportional hazard regression models. Results Among all participants, there were 3902 (47.3%) women and 4355 (52.7%) men. The median age was 58 years old. The cut‐off points of HGS to best classify patients with respect to time to mortality were

The applicability of laparoscopic-assisted radical gastrectomy for elderly patients with gastric cancer is still not well clarified. The aim of this double-center study was to explore the feasibility and effectiveness of laparoscopic-assisted radical gastrectomy on elderly patients with gastric cancer. We prospectively collected data of patients who underwent gastrectomy for cancer in two centers from June 2016 to December 2019. Propensity score matching was performed at a ratio of 1:1 to compare the laparoscopic-assisted radical gastrectomy group and open radical gastrectomy group. Univariate analyses and multivariate logistic regression analyses evaluating the risk factors for total, surgical, and medical complications were performed. A total of 481 patients with gastric cancer met the inclusion criteria and were included in this study. After propensity score analysis, 258 patients were matched each other (laparoscopic-assisted radical gastrectomy (LAG) group, n = 129; open radical gastrectomy (OG) group, n = 129). LAG group had lower rate of surgical complications (P = 0.009), lower rate of severe complications (P = 0.046), shorter postoperative hospital stay (P = 0.001), and lower readmission rate (P = 0.039). Multivariate analyses revealed that anemia, Charlson comorbidity index, and combined resection were independent risk factors in the LAG group, whereas body mass index and American Society of Anesthesiology grade in the OG group. Laparoscopic-assisted radical gastrectomy was relative safe even effective in elderly gastric cancer patients. We should pay attention to the different risk factors when performing different surgical procedures for gastric cancer in elderly patients.

Primary liver cancer is a lethal cancer. The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway has been implicated in the pathogenesis of liver cancer. Gomisin N (GN), a lignan isolated from the dried fruits of Schisandra chinensis (Turca.) Baill., has been reported to reduce viability of, and induce apoptosis in, HepG2 liver cancer cells. In preadipocytes, GN was found to inhibit Akt activity. In the present study, Akt signaling-related anti-liver cancer mechanisms of GN were investigated. We confirmed that GN reduces cell viability of, and triggers apoptosis in, more liver cancer cell lines. Mechanistic studies revealed that GN lowers protein levels of phospho-PI3K (p85 tyrosine (Tyr)458), phospho-Akt (serine (Ser)473), and Akt downstream molecules Mcl-1 in HepG2 and HCCLM3 cells. Meanwhile, GN activates mTOR and inhibits ULK1 (a negative downstream effector of mTOR) activities. Activation of mTOR has been reported to suppress ULK1 activity and repress autophagy. Indeed, we observed that GN inhibits autophagy in liver cancer cells. In summary, we for the first time demonstrated that GN inhibits the PI3K-Akt pathway and regulates the mTOR-ULK1 pathway in liver cancer cells.

Summary Background In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) reached a consensus on sarcopenia (EWGSOP1). In 2018, the EWGSOP met again (EWGSOP2) to update original definition of sarcopenia. This study aimed to investigate the association of sarcopenia and survival and compare the prognostic effects of sarcopenia as defined by EWGSOP1 and EWGSOP2 after gastrectomy. Methods We conducted a prospective study including patients who underwent curative gastrectomy for gastric cancer from August 2014 to February 2018. The sarcopenia elements, including skeletal muscle index, muscle attenuation, handgrip strength, and gait speed were measured before surgery. Patients were followed up after gastrectomy to gain the actual clinical outcomes. Results The prevalence of sarcopenia was 17.0% and 18.9% according to the EWGSOP1 and EWGSOP2 respectively. Sarcopenia was independent risk factor for postoperative complications. Compared with EWGSOP1-sarcopenia, EWGSOP2-sarcopenia and had a higher odds ratio (OR) (2.453 vs. 1.550) in multivariate model. Area under the ROC curve of model including EWGSOP2-sarcopenia was larger than that of the model including EWGSOP1-sarcopenia (AUC 0.653 vs. 0.634, P = 0.021). For both of EWGSOP1 and EWGSOP2, sarcopenia was an independent risk factor for overall survival (OS) and disease-free survival (DFS), but EWGSOP2-sarcopenia seemed to have a higher hazard ratio (OS, 1.667 vs. 1.449; DFS, 1.603 vs. 1.563). In addition, severe sarcopenia, as defined by either EWGSOP2 or EWGSOP1, had a strong predictive power (OR 4.909 vs. 3.827) for postoperative complications. Both versions of severe sarcopenia were significantly predictive of OS and DFS in Cox analysis. Conclusion Sarcopenia at uniform diagnosis standard was an independent risk factor for survival in patients undergoing radical gastrectomy for gastric cancer. Sarcopenia defined by EWGSOP2 criteria better predicts clinical outcomes than that defined by EWGSOP1 criteria in patients with gastric cancer after gastrectomy.

Sarcopenia is a negative predictor for postoperative recovery. This study was performed to evaluate the short-term outcomes of laparoscopic surgery in colorectal cancer patients with sarcopenia. We conducted a study of patients who underwent curative surgeries for colorectal cancer in two centers from July 2014 to July 2018. In order to reduce selection bias, we conducted a propensity score matching analysis. Preoperative characteristics including age, gender, anemia, body mass index, hypoalbuminemia, America society of anesthesiology scores, epidural anesthesia, operative procedure, stoma, tumor location, and combined resection were incorporated in the model, and produced 58 matched pairs. The third lumbar skeletal muscle mass, handgrip strength, and 6 m usual gait speed were measured to define sarcopenia. Short-term outcomes were compared between the two groups. In a total of 1136 patients, 272 had sarcopenia diagnosed, and 227 were further analyzed in this study. Among them, 108 patients underwent laparoscopic colorectal surgery and 119 underwent open colorectal surgery. In the matched cohort, the clinical characteristics of the two groups were well matched. The laparoscopic group had significantly reduced overall complications (15.5% vs. 36.2%, P = 0.016) and shorter postoperative hospital stays (10.5 vs. 14, P = 0.027). Subgroup analysis of postoperative complications showed that the incidence of surgical complications (P = 0.032) was lower in the laparoscopic group. Hospitalization costs (P = 0.071) and 30-day readmissions (P = 0.215) were similar between the two groups. Laparoscopic surgery for colorectal cancer is a safe and feasible option with better short-term outcomes in patients with sarcopenia.

Angiogenesis plays an important role in the growth and metastasis of solid tumors including melanoma. Inhibiting tumor-associated angiogenesis is a tactic in treating melanoma. Dioscin restrains angiogenesis in colon tumor and has anti-melanoma effects in cell and animal models. In a previous study, we found that dioscin inhibits Src/STAT3 signaling in melanoma cells. Activation of the Src/STAT3 pathway has been shown to promote tumor angiogenesis. This study aimed to determine whether dioscin's anti-melanoma effects is related to inhibiting Src/STAT3 signaling-mediated angiogenesis. In a B16F10 allograft mouse model, we found that dioscin inhibited melanoma growth and angiogenesis. To exclude the impact of tumor growth on angiogenesis, a chicken chorioallantoic membrane (CAM) model was used to verify the anti-angiogenic effect of dioscin. Results showed that dioscin suppressed vessel formation in CAM. To determine if tumor secreted pro-angiogenic cytokines are involved in the anti-angiogenic effect of dioscin, conditioned media from dioscin-treated A375 melanoma cells were used to culture human umbilical vein endothelial cells (HUVECs), and tube formation was monitored. It was observed that the tube formation of HUVECs was inhibited. Mechanistic studies revealed that dioscin inhibited the activation of Src and STAT3, and lowered mRNA and protein levels of STAT3 transcriptionally-regulated genes, in B16F10 melanomas. ELISA assays showed that dioscin decreased the secretion of MMP-2, MMP-9 and VEGF from A375 cells. Over-activation of STAT3 lessened the effects of dioscin in decreasing the secretion of pro-angiogenic cytokines from melanoma cells, and in inhibiting tube formation of HUVECs cultured with conditioned media from melanoma cell cultures. In summary, we for the first time demonstrated that inhibiting Src/STAT3 signaling-mediated angiogenesis is involved in the anti-melanoma effects of dioscin. This study provides further pharmacological groundwork for developing dioscin as an anti-melanoma agent.

Background and Aims: Sarcopenia is negatively associated with clinical outcomes. However, the definitions of sarcopenia are inconsistent across international consensuses. Thus, the purpose of this study is to compare the impact of the basic definition components of sarcopenia and their combinations in post-operative complications and overall survival, aiming to find the best sarcopenia definition to stratify the prognosis in an Asian population.Methods: A total of 1,307 patients who underwent curative surgery for gastric cancer from July 2014 to May 2019 were prospectively included. The basic sarcopenia components were measured pre-operatively, including low skeletal muscle mass index (LSMI), low skeletal muscle radiodensity (LSMD), low handgrip strength (LHGS), and low gait speed (LGS). Among them, LSMI and LSMD were measured using a CT post-processing software, LHGS was measured using an electronic hand dynamometer, and LGS was represented by a 6-m walk speed.Results: For the single basic component, the muscle function parameters (LHGS or LGS) but not the muscle composition parameters (LSMI or LSMD) showed associations with post-operative complications and mortality. For the combination of the basic combinations, all statistically significant combinations included at least one muscle function parameter. The combination of muscle composition (LSMI or LSMD) and muscle function (LHGS or LGS) had a significantly higher area under the curve in the prediction of post-operative complications compared with the combinations of two muscle function parameters (LSMI plus LSMD) or two muscle composition parameters (LHGS plus LGS).Conclusions: Compared with muscle composition parameters (LSMI and LSMD), muscle function parameters (LHGS and LGS) are better predictors of post-operative complications and overall survival, which should be considered as the principal determinant in the sarcopenia definition. The definition of sarcopenia consists of muscle function (LHGS or LGS) and muscle composition (LSMI or LSMD) separately, which is better than the combination of the two muscle function parameters (LHGS plus LGS) or two muscle composition parameters (LSMI plus LSMD).

BACKGROUND The relationships between sarcopenia and postoperative outcomes in patients with early-stage gastric cancer who undergo radical gastrectomy is unclear. We aimed to investigate the predictive value of sarcopenia on adverse outcomes for stage I gastric cancer. METHODS The clinical data of patients who underwent radical gastrectomy for stage I gastric cancer between July 2013 and May 2019 were prospectively collected. Basic sarcopenia components were measured preoperatively. Univariate and multivariate analyses were conducted to evaluate the risk factors for short- and long-term outcomes. RESULTS A total of 507 patients with early-stage gastric cancer were included in the study, and 73 (14.4%) patients were diagnosed as sarcopenia. Patients with sarcopenia had significantly higher incidence of postoperative complications (32.9% vs. 17.5%, P = 0.002), longer postoperative hospital stays (13 days vs. 12 days, P

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.

Background Completing Patient‐Generated Subjective Global Assessment (PG‐SGA) questionnaires is time consuming. This study aimed to develop and validate an easy‐to‐use modified PG‐SGA (mPG‐SGA) for cancer patients. Methods Seventy professionals assessed the content validity, comprehensibility, and difficulty of the full PG‐SGA. A survey including the PG‐SGA and other questionnaires was completed by 34 071 adult hospitalized cancer patients with first cancer diagnosis or recurrent disease with any tumour comorbidities from the INSCOC study. Among them, 1558 patients were followed for 5 years after admission. Reliability and rank correlation were estimated to assess the consistency between PG‐SGA items and to select mPG‐SGA items. The external and internal validity, test–retest reliability, and predictive validity were tested for the mPG‐SGA via comparison with both the PG‐SGA and abridged PG‐SGA (abPG‐SGA). Results After deleting items that more than 50% of professionals considered difficult to evaluate (Worksheet 4) and items with an item‐total correlation

Background Multifocal-type autoimmune pancreatitis (AIP), sometimes forming multiple pancreatic masses, is frequently misdiagnosed as pancreatic malignancy in routine clinical practice. It is critical to know the imaging features of multifocal-type AIP to prevent misdiagnosis and unnecessary surgery. To the best of our knowledge, there have been no studies evaluating the value of diffusionweighted imaging (DWI), axial fat-suppressed T1 weighted image (T1WI), and dynamic contrast enhanced-computed tomography (DCE-CT) in detecting the lesions of multifocal-type AIP. Aim To clarify the exact prevalence and radiological findings of multifocal AIP in our cohorts and compare the sensitivity of DWI, axial fat-suppressed T1WI, and DCE-CT for detecting AIP lesions. We also compared radiological features between multifocal AIP and pancreatic ductal adenocarcinoma with several key imaging landmarks. Methods Twenty-six patients with proven multifocal AIP were retrospectively included. Two blinded independent radiologists rated their confidence level in detecting the lesions on a 5-point scale and assessed the diagnostic performance of DWI, axial fat-suppressed T1WI, and DCE-CT. CT and magnetic resonance imaging of multifocal AIP were systematically reviewed for typical imaging findings and compared with the key imaging features of pancreatic ductal adenocarcinoma. Results Among 118 patients with AIP, 26 (22.0%) had multiple lesions (56 lesions). Ulcerative colitis was associated with multifocal AIP in 7.7% (2/26) of patients, and Crohn's disease was present in 15.3% (4/26) of patients. In multifocal AIP, multiple lesions, delayed homogeneous enhancement, multifocal strictures of the main pancreatic duct, capsule-like rim, lower apparent diffusion coefficient values, and elevated serum Ig4 level were observed significantly more frequently than pancreatic ductal adenocarcinoma, whereas the presence of capsule-like rim in multifocal-type AIP was lower in frequency than total AIP. Of these lesions of multifocal AIP, DWI detected 89.3% (50/56) and 82.1% (46/56) by the senior and junior radiologist, respectively. Conclusion Multifocal AIP is not as rare as previously thought and was seen in 22.0% of our patients. The diagnostic performance of DWI for detecting multifocal AIP was best followed by axial fat-suppressed T1WI and DCE-CT.

Background Chronic fatigue syndrome (CFS) is a complex disease with few effective and safe therapies. Young Yum Pill (YYP), a proprietary herbal drug, has been used to relieve CFS-like symptoms. The pharmacological basis of this application of YYP is unknown. Purpose This study aimed to investigate the pharmacological effects and mechanisms of action of YYP in a mouse model of CFS. Study design and methods A food restriction and exhaustive swimming-induced mouse CFS model was used to evaluate the effects of YYP. Lymphocyte proliferation was assessed by MTT assays. T-lymphocyte subsets were analyzed by flow cytometry. Serum biochemical parameters were determined using commercial kits. Protein levels were measured by immunoblotting. Results Intragastric administration of YYP (2.85, 5.70, 11.40 g/kg) daily for 21 consecutive days significantly prolonged swimming time and diminished body weight loss of CFS mice. Mechanistic investigations revealed that YYP increased thymus and spleen indices of CFS mice, enhanced proliferation of lipopolysaccharide- or concanavalin A-stimulated spleen lymphocytes, and increased CD3+CD4+ and CD3+CD8+ T-cells in the spleen. YYP increased glycogen content in gastrocnemius muscle and liver, and lowered levels of triglyceride, lactic acid and urea nitrogen in sera of CFS mice. YYP suppressed the elevation of serum level of malondialdehyde, the increase of activities of lactic dehydrogenase and creatine phosphokinase, and the decrease of activity of the serum antioxidant enzyme superoxide dismutase in CFS mice. Moreover, YYP upregulated protein level of activated AMPK in gastrocnemius muscle and liver of CFS mice. Conclusions YYP ameliorates CFS by reversing metabolic changes, reducing oxidative damage, and improving some immune function parameters in mice. This study provides pharmacological justifications for the use of YYP in treating fatigue, including CFS.

Ethnopharmacological relevance Malignant melanoma is a fatal cancer. Signal transducer and activator of transcription 3 (STAT3) has been proposed as a therapeutic target of melanoma. An herbal formula Huai-Hua-San (HHS) comprising Sophorae Flos (SF) and Gardeniae Fructus (GF) is traditionally used for treating cancers including melanoma, but the pharmacological basis is unknown. Aims of this study This study aimed to investigate the anti-melanoma effects of an ethanolic extract of HHS (HHSE), and explore the involvement of STAT3 signaling in the effects. Materials and methods An UPLC-TOF/MS method was developed to control the quality of HHSE. A B16F10 allograft mouse model and three melanoma cell lines (B16F10, A375 and A2058) were used to determine the anti-melanoma effects of HHSE. Dacarbazine (DTIC) and Stattic were used as positive controls. Cell viability was detected using MTT and crystal violet staining assays. Cell apoptosis was analyzed by flow cytometry after the cells were stained with Annexin-V/PI. Cell invasive ability was examined using the transwell assay. Protein levels were determined by Western blotting. Results The contents of crocin I, crocin II, quercetin and kaempferol in HHSE were 0.59%, 0.98%, 4.66% and 1.15%, respectively. A clinically relevant dose of HHSE (0.1 g/kg/day, i.g. for 15 consecutive days) significantly suppressed B16F10 tumor growth in mice. HHSE dose-dependently reduced cell viability and dampened invasion of, and induced apoptosis in, melanoma cells. Mechanistic studies revealed that HHSE inhibited the phosphorylation/activation of STAT3 in B16F10 allografts and in cultured melanoma cells. In cell models, HHSE also inhibited the phosphorylation of STAT3 upstream kinases, JAK2 (Tyr1007/1008) and Src (Tyr416), lowered STAT3 nuclear levels, and down-regulated the protein levels of STAT3-targeted molecules. Over-activation of STAT3 in A375 cells significantly attenuated the cytotoxic effects of HHSE. Conclusions HHSE exhibits anti-melanoma effects in cell and mouse models. Inhibition of STAT3 signaling contributes to the anti-melanoma mechanisms of HHSE. Our findings lay a groundwork for developing HHSE as a modern agent for melanoma management, and provide pharmacological justifications for the traditional use of HHS in treating melanoma.

BACKGROUND Liver fibrosis, defined as the aberrant accumulation of extracellular matrix (ECM) proteins such as collagen in the liver, is a common feature of chronic liver disease, and often culminates in portal hypertension, liver cirrhosis, and hepatic failure. Though therapeutically manageable, fibrosis is not always successfully treated by conventional antifibrotic agents. While the traditional Chinese medicine (TCM) Alisma Shugan Decoction (ASD) has several health benefits, including anti-inflammation, anti-oxidation, and limitation of cardiovascular and respiratory disorders, it remains unclear if it has any hepato-protective potential. MATERIAL AND METHODS The present study examined the therapeutic effect of ASD in thioacetamide (TAA)-induced liver injury and fibrosis rat models. RESULTS We demonstrated that 50 mg/kg ASD significantly reversed TAA-induced elevation of alanine or aspartate transaminase levels, elicited no dyscrasia, and conferred a 40% (p

The aim of this study was to determine the feasibility of substituting handgrip strength (HGS) for muscle mass as a constituent in the Global Leadership Initiative on Malnutrition (GLIM) to diagnose malnourished patients with gastrointestinal (GI) cancer.The study included 2209 patients diagnosed with GI cancer from two centers. All patients were evaluated for nutritional risk using Nutritional Risk Screening 2002 within 24 h of admission. The GLIM consensus was then used to diagnose malnourished patients. The evaluation of muscle mass as one of the constituents contained in the GLIM consensus was measured by computed tomography presented as skeletal muscle mass index (SMI) and HGS, respectively. Consistency test was carried out to evaluate the diagnostic value of SMI and HGS.There were 1042 (47.2%) cases of gastric cancer and 1167 (52.8%) cases of colorectal cancer. Among these cases were 768 patients (34.8%) at nutritional risk. Furthermore, 603 (27.3%) and 593 patients (26.8%) were diagnosed with malnutrition in the GLIM (SMI) group and the GLIM (HGS) group, respectively, and 544 (24.6%) patients in the two groups overlapped. The consistency test results showed that the κ value in the GLIM (HGS) group compared with the GLIM (SMI) group was 0.881 (P0.001) in patients with gastric cancer and 0.872 (P0.001) in those with colorectal cancer.HGS can be a substitute for muscle mass as a constituent in the diagnostic criteria of GLIM in patients with GI cancer.

In patients with ultralow rectal cancer, surgical resection of the tumor without impairing sphincter function remains a technical challenge. The purpose of this study was to describe a new technique of transanal natural orifice specimen extraction (NOSE) surgery using our independently developed devices, aiming to achieve precise cancer resection and preserve sphincter function in patients with ultralow rectal cancer. Precision functional sphincter-preserving surgery (PPS) was performed on nineteen patients with ultralow rectal cancer between June 2019 and April 2020. With the help of our independently developed devices, surgeons directly and accurately removed the lower edge of the tumor and retained healthy rectal tissue on the nontumorous side. Hand-sewn anastomosis with a mattress suture was used to achieve sturdy anastomosis. Preoperative baseline characteristics, operative details, 90-day postoperative complications, costs, and anal function score at 6 months after surgery were documented. Nineteen ultralow rectal cancer patients with a median distance to the dentate line of 2.0 cm successfully underwent PPS without serious postoperative complications. Six out of nineteen patients (31.6%) received a prophylactic stoma. The average cost was 62164.1 yuan. At 6 months after surgery, the average Wexner anal function score and the average Vaizey score were both 3 points. PPS can be employed to precisely resect rectal tumors and preserve sphincter function in ultralow rectal cancer patients. The use of our devices enhanced surgical efficiency, reduced the need for prophylactic stoma, reduced surgery-related costs, and prevented abdominal surgical incisions.

Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE’s anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.

Malignant melanoma is aggressive and has a high mortality rate. Toll-like receptor 4 (TLR4) has been linked to melanoma growth, angiogenesis and metastasis. However, signal transduction mediated by TLR4 for driving melanoma progression is not fully understood. Signal transducer and activator of transcription 3 (STAT3) has been identified as a major oncogene in melanoma progression. We found: that TLR4 expression positively correlates with activation/phosphorylation of STAT3 in human melanoma samples; that TLR4 ligands activate STAT3 through MYD88 and TRIF in melanoma cells; and that intratumoral activation of TLR4 increases STAT3 activation in the tumor and promotes tumor growth, angiogenesis, epithelial–mesenchymal transition (EMT) and the formation of an immunosuppressive tumor microenvironment in mice. Further, we found that the effects mediated by activating TLR4 are weakened by suppressing STAT3 function with a dominant negative STAT3 variant in melanoma. Collectively, our work identifies STAT3 activation as a key event in TLR4 signaling-mediated melanoma progression, shedding new light on the pathophysiology of melanoma.

Ethnopharmacology relevance Si-Jun-Zi-Tang (SJZT) is a traditional Chinese medicine formula used to treat chronic and debilitating diseases including melanoma. SJZT-based therapies have achieved good clinical outcomes in melanoma management. However, the pharmacological basis of SJZT for its clinical use in melanoma treatment is not fully understood. Aim of the study To investigate the anti-melanoma effects and mechanism of action of an ethanolic extract of SJZT. Materials and methods SJZT was extracted using 50% ethanol. A murine B16 melanoma-bearing mouse model was employed to investigate the anti-melanoma effects of SJZT. microRNA (miRNA) and mRNA levels were examined by RT-qPCR, and protein levels were measured by Western blotting. Results SJZT significantly inhibited B16 tumor growth in mice. Mechanistic investigations revealed that SJZT elevated miR-34b (a tumor suppressing miRNA), and lowered c-Met (a miR-34b target gene) and β-catenin (a downstream molecule of c-Met signaling) expression levels in the B16 tumors. Conclusions In this study we found, for the first time, that SJZT exerts anti-melanoma effects and regulates the miR-34b/c-Met/β-catenin pathway in a melanoma mouse model. Our findings provide pharmacological justifications for the clinical use of SJZT in treating melanoma.

With the increased prevalence of obesity and sarcopenia, those patients with both visceral obesity and sarcopenia were at higher risk of adverse outcomes. The aim of this study was to ascertain the combined impact of visceral obesity and sarcopenia on short-term outcomes in patients undergoing colorectal cancer surgery. We conducted a prospective study from July 2014 to February 2017. Patients’ demographic, clinical characteristics, physical performance, and postoperative short-term outcomes were collected. Patients were classified into four groups according to the presence of sarcopenia or visceral obesity. Clinical variables were compared. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed. A total of 376 patients were included; 50.8 and 24.5% of the patients were identified as having “visceral obesity” and “sarcopenia,” respectively. Patients with sarcopenia and visceral obesity had the highest incidence of total, surgical, and medical complications. Patients with sarcopenia or/and visceral obesity all had longer hospital stays and higher hospitalization costs. Age ≥ 65 years, visceral obesity, and sarcopenia were independent risk factors for total complications. Rectal cancer and visceral obesity were independent risk factors for surgical complications. Age ≥ 65 years and sarcopenia were independent risk factors for medical complications. Laparoscopy-assisted operation was a protective factor for total and medical complications. Patients with both visceral obesity and sarcopenia had a higher complication rate after colorectal cancer surgery. Age ≥ 65 years, visceral obesity, and sarcopenia were independent risk factors for total complications. Laparoscopy-assisted operation was a protective factor.

In this study, we aimed to investigate the anti-melanoma effects and the JAK2/STAT3 pathway-related mechanism of action of atractylenolide I in human melanoma cells. Our results showed that atractylenolide I effectively reduced viability, induced apoptosis and inhibited migration of melanoma cells. Meanwhile, atractylenolide I decreased the protein expression levels of phospho-JAK2 and phospho-STAT3, and in turn downregulated the mRNA levels of STAT3-targeted genes, including Bcl-xL, MMP-2 and MMP-9. Furthermore, the cytotoxic effect of atractylenolide I was attenuated in STAT3-overactivated A375 cells. These findings indicate that inhibition of JAK2/STAT3 signalling contributes to the anti-melanoma effects of atractylenolide I.

Background The association between sarcopenia and postoperative outcomes has been well reported. However, the impact of different sarcopenia stages on postoperative outcomes has never been investigated. Methods We conducted a large, prospective study of patients who underwent radical gastrectomy for gastric cancer from August 2014 to December 2015. Sarcopenia was staged as “presarcopenia,” “sarcopenia,” and “severe sarcopenia” according to the definition of the European Working Group on Sarcopenia in Older People. Univariate and multivariate analyses evaluating the risk factors for total, surgical, and medical complications were performed. Results A total of 470 patients were included, in which 20.6%, 10%, and 6.8% of the patients were identified as having “presarcopenia,” “sarcopenia,” and “severe sarcopenia,” respectively. Postoperative complications, duration of hospital stays, and costs increased with advancing sarcopenia stages. Severe sarcopenia, visceral fat area to total abdominal muscle area ratio, American Society of Anesthesiologists grade III, and tumor located at the cardia were independent risk factors for total complications. Visceral fat area to total abdominal muscle area ratio and tumor located at the cardia were independent risk factors for operative complications. Presarcopenia, sarcopenia, and severe sarcopenia were all identified as independent risk factors for medical complications, as well as age ≥75 years and Charlson Comorbidity Index. Conclusion Patients had worse postoperative outcomes after gastric cancer operation with advancing sarcopenia stages. Severe sarcopenia, but not presarcopenia or sarcopenia, was an independent risk factor for total postoperative complications. The 3 sarcopenia stages independently influence medical but not surgical complications. Recognizing sarcopenia stages is important for preoperative risk stratification.

Background Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. This study aims to explore the prevalence of sarcopenia in overweight and obese gastric cancer (GC) patients and figured out the impacts of sarcopenia on the postoperative complication of overweight and obese GC patients. Methods According to the recommended body-mass index (BMI) for Asian populations by WHO, we conducted a prospective study of overweight and obese gastric cancer patients (BMI ≥ 23 kg/m2) under curative gastrectomy from August 2014 to December 2015. Including lumbar skeletal muscle index, handgrip strength and gait speed as the sarcopenic components were measured before surgery. Patients were followed up after gastrectomy to gain the actual clinical outcomes. Factors contributing to postoperative complications were analyzed by univariate and multivariate analysis. Results Total of 206 overweight or obese patients were enrolled in this study, 14 patients were diagnosed sarcopenia and were demonstrated having significantly association with higher risk of postoperative complications, higher hospital costs, and higher rate of 30-days readmission compared with the non-sarcopenic ones. On the basis of univariate and multivariate analysis, sarcopenia was an independent risk factor for postoperative complication of overweight and obese patients with gastric cancer (P = 0.002). Conclusion Sarcopenia is an independent predictor of postoperative complications in overweight or obese patients with gastric cancer after radical gastrectomy.

A traditional Chinese medicine (TCM) formula (SL) comprising Sophorae Flos and Lonicerae Japonicae Flos was used for treating melanoma in ancient China. We have previously shown that an ethanolic extract of SL (SLE) possesses anti-melanoma effects and suppresses STAT3 signaling in vitro and in vivo. STAT3 has been linked to the development of melanoma immunosuppressive microenvironment. In this work, we investigated whether SLE inhibits melanoma growth by reprogramming the tumor microenvironment in mouse and co-culture cell models. In B16F10 melanoma-bearing mice, we found that intragastric administration of SLE (1.2 g/kg) dramatically inhibited tumor growth. This observation was associated with the downregulation of protein levels of phospho-STAT3 (Tyr 705) and STAT3-regulated immunosuppressive cytokines, and mRNA levels of STAT3-targeted genes involved in tumor growth and immune evasion. We also observed increased Th, Tc and dendritic cells in the melanomas and spleens in SLE-treated mice compared to that in control mice. In a co-culture system composed of B16F10 cells and mouse primary splenic lymphocytes, it was found that SLE not only inhibited STAT3 activation in B16F10 cells, but also downregulated mRNA levels of STAT3-targeted genes in the splenic lymphocytes. In this co-culture setting, SLE decreased the levels of STAT3-regulated immunosuppressive cytokines, increased the percentages of Th, Tc and dendritic cells as well. Furthermore, effects of SLE on STAT3 phosphorylation, cytokine levels and immune cell subtype percentages were significantly weaker in the B16STAT3C cells (stable cells harboring a constitutively active STAT3 variant STAT3C)/splenic lymphocytes co-culture system than in the B16V cells (cells stably transfected with the empty vector)/splenic lymphocytes co-culture system, indicating that STAT3 over-activation diminishes SLE’s effects. In summary, our findings indicate that reprograming the immune microenvironment, partially mediated by inhibiting STAT3 signaling, contributes to the anti-melanoma mechanisms of SLE. This study provides further pharmacological groundwork for developing SLE as a modern agent for melanoma prevention/treatment, and supports the notion that reprograming immunosuppressive microenvironment is a viable anti-melanoma strategy.

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. 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. 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. 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.

This study was performed to determine the association of frailty and nutritional status with postoperative complications after total gastrectomy (TG) with D2 lymphadenectomy in patients with gastric cancer.Patients undergoing TG with D2 lymphadenectomy for gastric cancer between August 2014 and February 2016 were enrolled. Frailty was evaluated by sarcopenia which was diagnosed by a combination of third lumbar vertebra muscle index (L3 MI), handgrip strength, and 6-m usual gait speed. Nutritional status was evaluated by the nutritional risk screening 2002 (NRS 2002) score. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed.A total of 158 patients were analyzed, and 27.2 % developed complications within 30 days of surgery. One patient died within 30 days of the operation. In the univariate analyses, NRS 2002 score ≥3 (OR = 2.468, P = 0.012), sarcopenia (OR = 2.764, P = 0.008), and tumor located at the cardia (OR = 2.072, P = 0.046) were associated with the postoperative complications. Multivariable analysis revealed that sarcopenia (OR = 3.084, P = 0.005) and tumor located at the cardia (OR = 2.347, P = 0.026) were independent predictors of postoperative complications.This study showed a significant relationship between postoperative complications and geriatric frailty using sarcopenia in patients with gastric cancer after TG with D2 lymphadenectomy. Frailty should be integrated into preoperative risk assessment and may have implications in preoperative decisionmaking.

Sarcopenia is characterized by decreased skeletal muscle plus low muscle strength and/or physical performance. This study was performed to determine the association of sarcopenia with short-term postoperative outcomes after gastrectomy for gastric cancer. We conducted a prospective study of 255 consecutive patients with gastric cancer who underwent curative gastrectomy. The sarcopenia elements, including lumbar skeletal muscle index, handgrip strength, and gait speed, were measured before surgery. Patients were followed up after gastrectomy to gain the actual clinical outcomes. Factors contributing to postoperative complications were analyzed by univariate and multivariate analysis. Sarcopenia was present in 32 of 255 patients (12.5 %), and was significantly correlated with advance age, lower body mass index, higher nutritional risk screening (NRS) 2002 score, and lower preoperative serum albumin and hemoglobin. Compared with non-sarcopenic patients, sarcopenic patients had a higher risk of postoperative complications, longer postoperative hospital stay, and more hospital costs. In univariate analysis, sarcopenia (p

Background Receptor activator of NF-κB ligand (RANKL) facilitates differentiation of osteoclast precursors into osteoclasts, resulting in bone erosion in rheumatoid arthritis (RA) patients. Fibroblast-like synoviocytes (FLS) are the main cells for producing RANKL. Signal transducer and activator of transcription 3 (STAT3) signaling is activated in FLS of RA patients (RA-FLS), which has been linked to RANKL production. A two-herb formula (RL) comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos is traditionally used for treating RA in China. We have found that a standardized ethanolic extract of RL (RLE for short) alleviates bone erosion in collagen-induced arthritis (CIA) rats. Purpose This study aimed to determine whether RLE inhibits RANKL production and osteoclastogenesis in cell and rat models, and to explore the involvement of the STAT3 pathway in this inhibition. Study Design and Methods A CIA rat model, interleukin-6/soluble interleukin-6 receptor (IL-6/sIL-6R)-stimulated RA-FLS and a co-culture system (IL-6/sIL-6R-stimulated RA-FLS/peripheral blood mononuclear cells) were used to evaluate the effects of RLE. Micro-computed tomography analysis was used to observe bone erosion in CIA rats. Tartrate-resistant acid phosphatase staining was used to evaluate osteoclastogenesis. Western blotting and ELISA assays were employed to examine protein levels. RT-qPCR was used to detect mRNA levels. STAT3-over-activated RA-FLS were used to investigate the involvement of STAT3 signaling in the anti-osteoclastogenic effects of RLE. Results RLE alleviated bone erosion in joints of CIA rats. In both synovial tissues of CIA rats and IL-6/sIL-6R-stimulated RA-FLS, RLE downregulated the protein level of RANKL. In the co-culture system, RLE significantly and dose-dependently inhibited IL-6/sIL-6R-induced osteoclastogenesis. Mechanistic studies revealed that RLE lowered the protein level of phospho-STAT3 (Tyr705) in synovial tissues of CIA rats. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited the activation/phosphorylation of a STAT3 upstream kinase Janus kinase 2 (Tyr1007/1008) and STAT3 (Tyr705), decreased the nuclear localization of STAT3, lowered mRNA levels of STAT3-transcriptionally regulated genes IL-1β and TNF-α. RLE's inhibitory effects on RANKL production in RA-FLS gradually decreased when IL-6/sIL-6R doses increased. Over-activation of STAT3 diminished the inhibitory effects of RLE on RANKL production in IL-6/sIL-6R-stimulated RA-FLS, and attenuated the anti-osteoclastogenic effects of RLE in the co-culture system. Conclusion We, for the first time, demonstrated that suppressing STAT3 signaling contributes to the inhibition of RANKL production and osteoclastogenesis, and thereby supports the mechanisms responsible for the reduction in bone erosion in RLE-treated CIA rats. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug, and supports the notion that targeting STAT3 signaling is a viable strategy for managing bone erosion.

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 Conclusion Among the tools examined, the MST had the greatest ability to detect cancer cachexia among patients with gastric cancer.

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.

Background Metastasized melanoma is extremely difficult to treat. Activation of C-C chemokine receptor type 7 (CCR7) has been linked to melanoma metastasis. CCR7 can be directly regulated by miR-let-7. We have previously shown that an ethanolic extract of an herbal formula comprising Sophorae Flos and Lonicerae Japonicae Flos (SLE) inhibits melanoma cell migration and invasion. Purpose In this study, we determined whether SLE suppresses melanoma metastasis, and whether regulation of miR-let-7a/f-CCR7 signaling is involved in the effect. Study design and methods Small RNA sequencing was conducted to compare miRNA expression profiles of B16F10 tumors dissected from SLE-treated or untreated mice. Western blot and RT-qPCR analyses were employed to examine protein and miRNA levels, respectively. A B16F10 melanoma lung metastasis mouse model was used to evaluate the effects of SLE on melanoma metastasis. MiR-let-7a/f-knockdown and CCR7-overexpression cell models were used to investigate the involvement of miR-let-7a/f-CCR7 signaling in the anti-metastatic effects of SLE. Results It was found that SLE upregulated levels of miR-let-7a/f in B16F10 melanoma tissues. SLE significantly elevated levels of miR-let-7a/f, lowered the protein level of CCR7, inhibited the phosphorylation of CCR7 downstream molecules p38 and JNK in B16F10 and A375 melanoma cells. SLE inhibited B16F10 melanoma lung metastasis in mice. SLE upregulated levels of miR-let-7a/f, and lowered protein levels of CCR7, MMP-2, MMP-9, phospho-p38 (Thr180/Tyr182) and phospho-JNK (Thr183/Tyr185) in melanoma-invaded lung tissues. Knockdown of miR-let-7a/f diminished the effects of SLE on CCR7 signaling in, and invasion of, melanoma cells. Overexpression of CCR7 lessened the effects of SLE in inhibiting the phosphorylation of p38 and JNK in, and the invasive capability of, melanoma cells. Conclusion We for the first time demonstrated that SLE inhibits melanoma metastasis in mice, and that regulation of the miR-let-7a/f-CCR7 pathway contributes to the anti-metastatic mechanisms of SLE. These findings provide a pharmacological basis for developing SLE as a modern agent for treating metastatic melanoma. Additionally and importantly, this study suggests that regulating the miR-let-7a/f-CCR7 pathway is a novel strategy for controlling melanoma metastasis.

Background Melanoma is a lethal cancer. NF-κB has been validated as a molecular target for melanoma treatment. Current therapies for melanoma have limitations. Novel targeted therapeutics are needed. Arnicolide D (Ar-D), a sesquiterpene lactone isolated from the dried whole plant of Centipeda minima (L.) A. Br. et Aschers., has been reported to inhibit NF-κB activity in colorectal cancer cells. Purpose To investigate the anti-melanoma effects of Ar-D in vitro and in vivo; and to determine whether Ar-D inhibits the NF-κB pathway in melanoma cells. Methods A B16F10 allograft mouse model and two melanoma cell lines (A375 and B16F10) were used to investigate the anti-melanoma effects of Ar-D in vivo and in vitro. Dacarbazine was used as a positive control. Cell viability was assessed by MTT and crystal violet staining assays. Cell cycle arrest and apoptosis were analyzed by flow cytometry. Protein levels were determined by Immunoblotting. Results In vivo assays showed that the average tumor weight in Ar-D-treated group (4 mg/kg, i.p, 15 days) was reduced by 53.7%, when compared with the control group. In vitro studies demonstrated that Ar-D reduced cell viability, induced G2/M cell cycle arrest and apoptosis, elevated levels of cell cycle regulatory proteins p53 and p21, and lowered levels of G2/M checkpoint proteins Cdc2 and Cyclin B1 in melanoma cells. Mechanistically, Ar-D inhibited the activity of IKKα/β, the degradation of IκBα, and the phosphorylation and expression of NF-κB p65 in melanoma cells. Conclusion Ar-D has anti-melanoma effects, and inhibition of the IKK/IκBα/NF-κB p65 pathway is involved in the effects.

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.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.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.Sarcopenia is an independent clinical predictor of short-term postoperative complications after laparoscopic-assisted gastrectomy.

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

Background Gastrectomy results in a significant loss of body composition in the long term, but the acute skeletal muscle wasting after gastrectomy has been rarely investigated. Moreover, the association between postoperative muscle wasting and quality of life (QOL) has never been reported. In the present study, we aimed to investigate the risk factors for acute muscle wasting after gastric cancer surgery and its effect on QOL and short-term postoperative outcomes. Methods We conducted a prospective study of patients who underwent curative gastrectomy for gastric cancer between June 2015 and December 2015. Skeletal muscle mass was measured by computed tomography within 1 month before and 1 week after surgery. QOL was assessed 1, 3, and 6 months postoperatively. Univariate and multivariate analyses were performed to identify the risk factors for clinically relevant muscle wasting (muscle wasting ≥10%). Results A total of 110 patients were included, in which 35 patients had muscle wasting ≥10% within 1 week after surgery. Age ≥65 years and diabetes were independent risk factors for muscle wasting ≥10%. Patients with muscle wasting ≥10% had a poorer QOL in terms of fatigue and physical functioning at 1 and 3 months postoperatively, as well as a higher incidence of postoperative complications, a higher incidence of handgrip strength reduction ≥10%, longer hospital stays, and higher costs. Conclusions Age ≥65 years and diabetes were independently associated with clinically relevant muscle wasting within 1 week after gastric cancer surgery. Clinically relevant muscle wasting was associated with a poorer QOL and short-term outcomes after surgery.

A geriatric assessment is needed to identify high-risk elderly patients with gastric cancer. However, the current geriatric assessment has been considered to be either time-consuming or subjective. The present study aimed to investigate the predictive effect of sarcopenia on the postoperative complications for elderly patients who underwent radical gastrectomy.We conducted a prospective study of patients who underwent radical gastrectomy from August 2014 to December 2015. Computed tomography-assessed lumbar skeletal muscle, handgrip strength, and gait speed were measured to define sarcopenia.Sarcopenia was present in 69 of 240 patients (28.8%) and was associated with lower body mass index, lower serum albumin, lower hemoglobin, and higher nutritional risk screening 2002 scores. Postoperative complications significantly increased in the sarcopenic patients (49.3% versus 24.6%, P 0.001), compared with nonsarcopenic patients. The multivariate analysis demonstrated that sarcopenia (odds ratio: 2.959, 95% CI: 1.629-5.373, P 0.001) and the Charlson comorbidity index ≥2 (odds ratio: 3.357, 95% CI: 1.144-9.848, P = 0.027) were independent risk factors for postoperative complications.Sarcopenia, presented as a new geriatric assessment factor, was a strong and independent risk factor for postoperative complications of elderly patients with gastric cancer.

Objective The aim of this study was to evaluate and compare three common nutritional screening tools with the new European Society for Clinical Nutrition and Metabolism (ESPEN) diagnostic criteria for malnutrition among elderly patients with gastrointestinal cancer. Research methodsandprocedures Nutritional screening tools, including the Nutritional Risk Screening 2002 (NRS 2002), the Malnutrition Universal Screening Tool (MUST) and the Short Form of Mini Nutritional Assessment (MNA-SF), were applied to 255 patients with gastrointestinal cancer. We compared the diagnostic values of these tools for malnutrition, using the new ESPEN diagnostic criteria for malnutrition as the ‘gold standards’. Results According to the new ESPEN diagnostic criteria for malnutrition, 20% of the patients were diagnosed as malnourished. With the use of NRS 2002, 52.2% of the patients were found to be at high risk of malnutrition; with the use of MUST, 37.6% of the patients were found to be at moderate/high risk of malnutrition; and according to MNA-SF, 47.8% of the patients were found to be at nutritional risk. MUST was best correlated with the ESPEN diagnostic criteria (К=0.530, p

The aim of this study was to evaluate the short-term safety and long-term benefits of radical gastrectomy for gastric cancer in elderly patients.A total of 729 patients undergoing gastrectomy for adenocarcinoma between December 2008 and December 2011 were enrolled in this retrospective study. Patients were divided into three groups: young group (65 years), young-old group (65-79 years) and old-old group (≥80 years).Lower albumin levels, higher ASA grades, comorbidities, tumors located in the upper third of the stomach and advanced TNM stages were more common in the young-old and old-old age groups. Overall complications increased significantly with advancing age (15.4%, 24.9%, 48.7%, respectively); respiratory complications largely contributed to the dramatic increase. Severe complications were similar between the young and young-old groups (3.9%, 3.7%), but were significantly increased in the old-old group (12.8%). In multivariate analysis, old-old age, multiple comorbidities and no epidural use were strong predictors for overall complications. Both overall survival and disease-specific survival (DSS) rates declined with advancing age. Multivariate analysis showed that old-old age and TNM stage ≥ II were major independent risk factors for the DSS rate. When adjusted for confounding factors, young-old age was not a risk factor. The median survival time for the old-old patients with stage III tumors was 12.9 months.It is relatively safe and beneficial for young-old patients to undergo radical gastrectomy as the young patients. However, the decision to perform radical gastrectomy for old-old patients with TNM stage III tumors should be made carefully.

Aim Recent studies have shown that sarcopenia is associated with negative postoperative outcomes. However, none of these studies analysed muscle strength or physical performance, which are also important components of sarcopenia. The present study aimed to investigate whether sarcopenia itself, as defined by low muscle mass, strength and physical performance, would predict complications after surgery for colorectal cancer. Method We conducted a prospective study of patients who underwent surgery for colorectal cancer at our department between August 2014 and February 2015. Sarcopenia was diagnosed by a combination of third lumbar vertebra muscle index (L3 MI), handgrip strength and 6-m usual gait speed. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed. Only complications classified as Grade II or above according to the Clavien–Dindo classification were analysed in this study. Results A total of 142 patients were included in the study, and 17 patients were diagnosed as having sarcopenia. Postoperative complications of Grade II or above occurred in 40 patients, including 10 with sarcopenia and 30 without sarcopenia. Multivariate analysis showed that sarcopenia and previous abdominal surgery were independent risk factors for postoperative complications. Patients with sarcopenia also had an obvious tendency to a higher incidence of infectious complications. By comparing two logistic regression models, sarcopenia showed a better predictive power for postoperative complications than did low muscle mass. Conclusion Sarcopenia and previous abdominal surgery are independent risk factors for complications after surgery for colorectal cancer. Including a functional aspect to the definition of sarcopenia may result in a better prediction of postoperative complications.

Background Hospital readmission is gathering increasing attention as a measure of health care quality and a potential cost-saving target. The purpose of this prospective study was to determine risk factors for readmission within 30 days of discharge after gastrectomy for patients with gastric cancer. Methods We conducted a prospective study of patients undergoing radical gastrectomy for gastric cancer from October 2013 to November 2014 in our institution. The incidence, cause and risk factors for 30-day readmission were determined. Results A total of 376 patients were included in our analysis without loss in follow-up. The 30-day readmission rate after radical gastrectomy for gastric cancer was 7.2% (27of 376). The most common cause for readmission included gastrointestinal complications and postoperative infections. On the basis of multivariate logistic regression analysis, preoperative nutritional risk screening 2002 score ≥ 3 was an independent risk factor for 30-day readmission. Factors not associated with a higher readmission rate included a history of a major postoperative complication during the index hospitalization, prolonged primary length of hospital stay after surgery, a history of previous abdominal surgery, advanced age, body mass index, pre-existing cardiopulmonary comorbidities, American Society of Anesthesiology grade, type of resection, extent of node dissection and discharge disposition. Conclusions Readmission within 30 days of discharge after radical gastrectomy for gastric cancer is common. Patients with nutritional risk preoperatively are at high risk for 30-day readmission. Preoperative optimization of nutritional status of patients at nutritional risk may effectively decrease readmission rates.

TO THE EDITOR: Kennedy et al recently published an article examining the postoperative outcomes of laparoscopic surgery versus open resection of colorectal cancer within an enhanced recovery program (ERP). The main finding of their trial, called EnROL (Enhanced Recovery Open Versus Laparoscopic), was that laparoscopic surgery reduced the total postoperative hospital stay by 2 days. We congratulate the authors for their efforts because we know the difficulties of conducting such a trial. However, we think that some limitations of the study should be addressed. First, we noticed that compliance with the ERP components was low, especially with respect to early oral feeding, early mobilization, and optimized analgesia. Early oral feeding has been proven to reduce the length of hospital stay and the total postoperative complications. Failure to mobilize has been associated with prolonged length of hospital stay. In addition, Vlug et al found that hospital stay was reduced by 28% when early oral feeding and early mobilization were achieved. Optimized pain relief, allowing early mobilization and early return of gut function, is a prerequisite for enhanced recovery. Strict adherence to the ERP was associated with reduced length of hospital stay and improved outcome in colonic surgery for malignancy. Thus, the low compliance with the ERP components may have introduced a high risk of bias to the EnROL trial. Second, it was reported that the greater the number of evidencebased components included in the ERP, the better the outcome. However, some key ERP items were not included in the EnROL trial, such as prevention of postoperative nausea and vomiting. Postoperative nausea and vomiting lead to intolerance to oral feeding and is a leading cause of patient dissatisfaction and delayed hospital discharge. The absence of this ERP item probably explains the low compliance with early oral feeding. Above all, the low compliance and the absence of some key ERP components might make the EnROL trial underpowered, despite the substantial work of the authors. Therefore, the question regarding the benefits of laparoscopy within an ERP was not adequately answered by the EnROL trial. Additional large-scale randomized clinical trials are needed to examine the benefits of laparoscopic colorectal resection in the context of an even more optimized ERP than that applied in the EnROL trial.

Fast-track surgery aims to attenuate the surgical stress response, reduce complications, and shorten hospital stay. The goal of the present meta-analysis is to assess the safety and effectiveness of fast-track surgery in patients undergoing gastrectomy for gastric cancer compared with conventional perioperative care.PubMed, Embase, the Cochrane Central Register of Controlled Trials, and reference lists of the identified studies were searched to identify randomized clinical trials that compared fast-track surgery with conventional perioperative care in patients undergoing gastrectomy for gastric cancer.Five studies with a total of 400 patients were included in the meta-analysis. Meta-analysis shows that postoperative hospital stay (weighted mean difference (WMD) -1.87 days, 95 % confidence interval (CI), -2.46 to -1.28 days, P 0.00001), time to first passage of flatus (WMD -0.71 days, 95 % CI, -1.03 to -0.39 days, P 0.0001), and hospital costs (WMD -505.87 dollars, 95 % CI, -649.91 to -361.84 dollars, P 0.00001) were significantly reduced for fast-track surgery. No significant differences were found for readmission rates (relative risk (RR), 1.97 95 % CI, 0.37 to 10.64, P = 0.43) and total postoperative complications (RR, 0.99 95 % CI, 0.56 to 1.76, P = 0.97).Fast-track surgery is safe and effective in gastrectomy for gastric cancer. Further randomized trials are needed to strengthen the conclusions.

Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer. From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed. A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm2/m2 for women and 40.8 cm2/m2 for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P

Currently, there is a paucity of study investigating postoperative ileus in gastric cancer surgery. This prospective study aims to identify the risk factors for prolonged postoperative ileus (PPOI) and to use these risk factors to generate a risk stratification scoring system for the occurrence of PPOI. Patients who underwent radical gastrectomy for gastric cancer were included in this study. A multivariate logistic analysis was applied to identify independent risk factors for PPOI and to generate the scoring system. A receiver operating characteristic curve was generated and the area under the curve was calculated to demonstrate the predictive power of the scoring system. Finally, 296 patients were included and analyzed, of whom 96 (32.4%) developed PPOI. The multivariate analysis showed that age ≥65 years, operative duration ≥4 hours, tumor–node–metastasis (TNM) stage = III, open/converted operative technique, and total postoperative opiates dose (TOD) ≥0.3 mg/kg were independent risk factors for PPOI. Based on these factors, a risk stratification scoring system was generated, classified by low-risk (score 0–2), moderate-risk (score 3–4), and high-risk (score 5–6) groups. The incidence of PPOI increased by 7.5-fold from low-risk to high-risk group. The area under the curve of the scoring system was 0.841 (95% CI, 0.793–0.890), indicating a good predictive capability for the occurrence of PPOI. We have identified independent risk factors for the occurrence of PPOI and used these factors to construct a risk stratification scoring system.