Cachexia Versus Sarcopenia in Clinical Characteristics and Prognostic Value After Radical Gastrectomy for Gastric Cancer: A Large-Scale Prospective Study.

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.

Precision functional sphincter-preserving surgery (PPS) for ultralow rectal cancer: a natural orifice specimen extraction (NOSE) surgery technique.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Laparoscopic versus open resection for elderly patients with gastric cancer: a double-center study with propensity score matching method.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Laparoscopic colorectal cancer surgery reduces the adverse impacts of sarcopenia on postoperative outcomes: a propensity score-matched analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Laparoscopic surgery for colorectal cancer is a safe and feasible option with better short-term outcomes in patients with sarcopenia.

Impact of Visceral Obesity and Sarcopenia on Short-Term Outcomes After Colorectal Cancer Surgery.

BACKGROUND: With the increased prevalence of obesity and sarcopenia, those patients with both visceral obesity and sarcopenia were at higher risk of adverse outcomes. AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Effect of surgery-induced acute muscle wasting on postoperative outcomes and quality of life.

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.

Sarcopenia: a new predictor of postoperative complications for elderly gastric cancer patients who underwent radical gastrectomy.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Sarcopenia, presented as a new geriatric assessment factor, was a strong and independent risk factor for postoperative complications of elderly patients with gastric cancer.

A novel scoring system associating with preoperative platelet/lymphocyte and clinicopathologic features to predict lymph node metastasis in early gastric cancer.

BACKGROUND: Precise determination of the lymph node status is critical for determining appropriate treatment for early gastric cancer (EGC). This study attempted to establish a simple, effective risk scoring system to predict lymph node metastasis (LNM) in EGC by investigating the relationship between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and EGC LNM. MATERIALS AND METHODS: We retrospectively reviewed 312 operable patients with EGC. The clinical utility of PLR and NLR was tested by receiver operating characteristic curves. The scoring system was developed using independent risk factors. Finally, 89 EGC patients were collected from prospective database to validate the scoring system's accuracy. RESULTS: The optimal PLR and NLR cut-off values were 106 and 2.97, respectively. High NLR (P = 0.009) and PLR (P = 0.007) values were associated with LNM of EGC in univariate analyses, although only high PLR (P = 0.025) was an independent risk factor in multivariate analyses, together with age (P = 0.009), differentiation (P = 0.017), invasive depth (P < 0.001), and tumor size (P = 0.003). The scoring system's accuracy for retrospective and prospective data was 0.781 (95% confidence interval: 0.721-0.841) and 0.817 (95% confidence interval 0.714-0.920), respectively. CONCLUSIONS: Preoperative PLR and NLR correlate with EGC LNM. Our scoring system is reliable, accurate, and effective in predicting LNM in EGC patients.

Sarcopenia Adversely Impacts Postoperative Clinical Outcomes Following Gastrectomy in Patients with Gastric Cancer: A Prospective Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.001), nutritional risk (NRS 2002 score ≥3; p = 0.003), advanced age (≥75 years; p = 0.014), anemia (p = 0.012), hypoalbuminemia (p = 0.029), and diabetes (p = 0.014) were associated with postoperative complications. Multivariable analysis revealed that sarcopenia (p < 0.001) and diabetes (p = 0.006) were independent predictors of postoperative complications. CONCLUSIONS: Sarcopenia is an independent predictor of postoperative complications in patients with gastric cancer after gastrectomy.

Role of frailty and nutritional status in predicting complications following total gastrectomy with D2 lymphadenectomy in patients with gastric cancer: a prospective study.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Synthetic miRNA sponges driven by mutant hTERT promoter selectively inhibit the progression of bladder cancer.

The mutant promoter of human telomerase reverse transcriptase (hTERT) shows high transcriptional activity in bladder cancer cells. Some up-regulated microRNAs (miRNAs) are reported as oncogenic factors in bladder cancer. Previous studies report that miRNAs can be inhibited by base-pairing interactions. The purpose of this study is to construct a synthetic device driven by mutant hTERT promoter to suppress four up-regulated miRNAs and to verify its effects on phenotypes of bladder cancer cells and human normal cells. Tandem bulged miRNA binding sites targeting oncogenic miRNAs were inserted into the 3' untranslated region (3' UTR) of mutant hTERT promoter-driven Renilla luciferase gene to construct a synthetic tumor-specific device, miRNA sponges. A negative control was generated by using tandem repeated sequences without targeting any known miRNA. Bladder cancer cells (T24, 5637, UM-UC-3) and human fiber cells (HFC) were transfected with devices. Various functional assays were used to detect the effects of this device. The activity of the mutant hTERT promoter detected by luciferase assay was about three times as large as the wild-type hTERT promoter in bladder cancer cells, while it could not be measured in HFC. Other assays indicated that the synthetic device can significantly inhibit cell growth, decrease motility, and induce apoptosis in bladder cancer cells but not in HFC. A synthetic biology platform is employed to construct tumor-specific miRNA sponges that can be used to target oncogenic miRNAs to inhibit the progression of bladder cancer cells without affecting normal cells.

Risk factors for postoperative fatigue after gastrointestinal surgery.

BACKGROUND: Postoperative fatigue (POF) is an important complication that is commonly observed postoperatively and is also one of the most serious obstacles to postoperative convalescence. However, the risk factors for POF have not been fully addressed, and there is no effective method to predict POF. The aim of the present study was to investigate the risk factors for POF and to explore prediction of the degree of POF. METHODS: A prospective observational study was conducted of patients undergoing elective gastrointestinal surgery. Fatigue score, grip strength, length of postoperative hospital stay (LOS), as well as preoperative and intraoperative factors were collected. χ(2) was used to compare categorical variables, and multivariate logistic regression analysis was used to further analyze correlation between POF and preoperative and intraoperative factors. RESULTS: A total of 155 patients were included in our analysis without loss in follow-up. Multivariate logistic regression analysis after adjustment for factors with severe POF in univariate analysis including preoperative fatigue, plasma albumin and hemoglobin level, and cardiopulmonary function demonstrated that old age, gastrectomy, and a nutritional risk screening 2002 score ≥ 3 were associated with a higher relative risk of severe POF. Moreover, laparoscopic-assisted surgery was associated with lower relative risk of severe POF. CONCLUSIONS: Old age, nutritional risk screening 2002 score ≥ 3 and gastrectomy were risk factors for POF in patients undergoing elective gastrointestinal surgery. POF was reduced in laparoscopic-assisted surgery. Consideration of these factors could be important for the prevention and treatment of POF.

Laparoscopic versus open colorectal surgery within enhanced recovery after surgery programs: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Laparoscopic surgery and enhanced recovery after surgery (ERAS) programs were two major improvements for the management of colorectal diseases. The purpose of this systemic review was to examine whether laparoscopic colorectal surgery still improved short-term postoperative outcomes in comparison with open surgery when both groups of patients received ERAS programs. METHODS: 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 laparoscopic with open surgery in patients undergoing colorectal resection in the context of ERAS programs. The outcome measures were analyzed, and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Five randomized clinical trials encompassing 598 patients were included in the final analysis. Two of them were multicenter trials. The ERAS programs implemented in the five included trials cannot be classified as optimal ERAS programs, but suboptimal ERAS programs. Laparoscopic colorectal surgery significantly reduced total hospital stay (weighted mean difference (WMD) -1.92 days; 95 % confidence interval (CI) -2.61--1.23 days; P < 0.00001) and number of complications (relative risk (RR) 0.78; 95 % CI 0.66-0.94; P = 0.007) compared with open surgery in the setting of ERAS programs. No significant differences were found between groups for primary hospital stay, number of patients with complications, readmission rates, and mortality. The quality of evidence for all outcomes was low-to-moderate on the GRADE scale, and none had high quality. CONCLUSIONS: Laparoscopic colorectal resection significantly reduced total hospital stay and number of complications when compared with open surgery in the setting of suboptimal ERAS programs, but the benefits of laparoscopic colorectal resection remain to be proved within optimal ERAS programs.

Prevention of postoperative fatigue syndrome in rat model by ginsenoside Rb1 via down-regulation of inflammation along the NMDA receptor pathway in the hippocampus.

Postoperative fatigue syndrome (POFS) is a common complication which decelerates recovery after surgery. The present study investigated the anti-fatigue effect of ginsenoside Rb1 (GRb1) through the inflammatory cytokine-mediated N-methyl-D-aspartate (NMDA) receptor pathway. A POFS rat model was created by major small intestinal resection and assessed with an open field test. Real-time quantitative polymerase chain reaction, western blot analysis, high performance liquid chromatography and a transmission electron microscopic analysis were used to determine typical biochemical parameters in the hippocampus. Our results showed that POFS rats exhibited fatigue associated with an increased expression of inflammatory cytokines and NMDA receptor 1, higher (kynurenine)/(tryptophan) and (kynurenine)/(kynurenic acid) on postoperative days 1 and 3, and an increased expression of indoleamine 2,3-dioxygenase (IDO) on postoperative day 1. Degenerated neurons were found in the hippocampus of POFS rats. The NMDA receptor antagonist MK801 had a significant effect on central fatigue on postoperative day 1. GRb1 had no effect on IDO or tryptophan metabolism, but exhibited a significant effect on POFS by inhibiting the expression of inflammatory cytokines and NMDA receptor 1. These data suggested that inflammatory cytokines could activate tryptophan metabolism to cause POFS through the NMDA receptor pathway. GRb1 had an anti-fatigue effect on POFS by reducing inflammatory cytokines and NMDA receptors.

Fast-track surgery in gastrectomy for gastric cancer: a systematic review and meta-analysis.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Fast-track surgery is safe and effective in gastrectomy for gastric cancer. Further randomized trials are needed to strengthen the conclusions.

Characteristics and prognostic impact of cancer cachexia defined by the Asian Working Group for Cachexia consensus in patients with curable gastric cancer.

BACKGROUND: Cachexia is prevalent in cancer patients. The conventional diagnostic criteria for cachexia are often based on Western evidence, lacking consensus for Asian populations. This study aims to compare Asian Working Group for Cachexia (AWGC) criteria with Fearon's criteria, assessing their differences in population characteristics and prognostic impact. METHODS: The clinical data of patients who underwent radical gastrectomy between 2013 and 2019 were prospectively collected. Cachexia diagnosis involves the utilization of either AWGC criteria and the previous international consensus proposed by Fearon et al. A scoring model is established based on the optional criteria according to the AWGC criteria. Univariate and multivariate logistic and Cox regression analysis were conducted to determine the independent effect factors for postoperative complications and overall survival. RESULTS: In a total of 1330 patients, 461 met AWGC cachexia criteria and 311 met Fearon's criteria. Excluding 262 overlapping cases, those diagnosed solely with AWGC-cachexia had higher age and lower BMI, albumin, hemoglobin, and handgrip strength compared to those by Fearon's criteria alone. AWGC-cachexia independently increased the risk of postoperative complications, whereas Fearon's criteria did not. Patients with AWGC-cachexia also exhibited shorter overall survival than Fearon's criteria. The AWGC-based cachexia grading system effectively stratifies the risks of postoperative complications and mortality. CONCLUSIONS: The AWGC criteria is more effective in diagnosing cancer cachexia in the Asian population and provide better prognostic indicators.

Muscle attenuation, not skeletal muscle index, is an independent prognostic factor for survival in gastric cancer patients with overweight and obesity.

OBJECTIVES: Skeletal muscle index (SMI) is insufficient for evaluating muscle in obesity, and muscle attenuation (MA) may be a preferred indicator. This study aimed to investigate whether MA has greater prognostic value than SMI in gastric cancer patients with overweight and obesity. METHODS: Clinical parameters of 1312 patients with gastric cancer who underwent radical gastrectomy were prospectively collected between 2013 and 2019. MA and SMI were analyzed by computed tomography scan. Overweight/obesity was defined as body mass index (BMI) ≥24 kg/m2. The hazard ratio (HR) for death was calculated using Cox regression analysis. RESULTS: Among all patients, 405 were identified as overweight and obese, and 907 were identified as normal and underweight. MA was inversely associated with BMI and visceral fat area. Among the 405 patients with overweight and obesity, 212 patients (52%) were diagnosed with low MA. In the overweight/obese group, MA was an independent predictor for overall survival (HR, 1.610; P = 0.021) in multivariate Cox regression analyses, whereas SMI did not remain in the model. In the normal/underweight group, both low MA (HR, 1.283; P = 0.039) and low SMI (HR, 1.369; P = 0.008) were independent factors of overall survival. Additionally, 318 patients were identified as having visceral obesity in the overweight/obese group, and low MA was also an independent prognostic factor for survival in these patients (HR, 1.765; P = 0.013). CONCLUSION: MA had a higher prognostic value than SMI in overweight and obese patients with gastric cancer after radical gastrectomy.

Transcriptome profiling of fast/glycolytic and slow/oxidative muscle fibers in aging and obesity.

Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.

Discovery of distinct cancer cachexia phenotypes using an unsupervised machine-learning algorithm.

OBJECTIVES: Cancer cachexia is a debilitating condition with widespread negative effects. The heterogeneity of clinical features within patients with cancer cachexia is unclear. The identification and prognostic analysis of diverse phenotypes of cancer cachexia may help develop individualized interventions to improve outcomes for vulnerable populations. The aim of this study was to show that the machine learning-based cancer cachexia classification model generalized well on the external validation cohort. METHODS: This was a nationwide multicenter observational study conducted from October 2012 to April 2021 in China. Unsupervised consensus clustering analysis was applied based on demographic, anthropometric, nutritional, oncological, and quality-of-life data. Key characteristics of each cluster were identified using the standardized mean difference. We used logistic and Cox regression analysis to evaluate 1-, 3-, 5-y, and overall mortality. RESULTS: A consensus clustering algorithm was performed for 4329 patients with cancer cachexia in the discovery cohort, and four clusters with distinct phenotypes were uncovered. From clusters 1 to 4, the clinical characteristics of patients showed a transition from almost unimpaired to mildly, moderately, and severely impaired. Consistently, an increase in mortality from clusters 1 to 4 was observed. The overall mortality rate was 32%, 40%, 54%, and 68%, and the median overall survival time was 21.9, 18, 16.7, and 13.6 mo for patients in clusters 1 to 4, respectively. Our machine learning-based model performed better in predicting mortality than the traditional model. External validation confirmed the above results. CONCLUSIONS: Machine learning is valuable for phenotype classifications of patients with cancer cachexia. Detection of clinically distinct clusters among cachexic patients assists in scheduling personalized treatment strategies and in patient selection for clinical trials.