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Cancer sarcopenia is highly prevalent in patients with advanced cancer, which is closely related to the disease prognosis. Overcoming cancer sarcopenia is important for cancer treatment. Cystine and theanine (CT), antioxidant amino acids, have been applied to the nutritional intervention of various diseases but their effects remain unclear on cancer sarcopenia. We attempt to examine the effect of CT on cancer sarcopenia. Both mouse and in vitro cachexia models showed that CT reduced oxidative stress, inhibited autophagy and apoptosis, improved oxidative phosphorylation and the suppression of high mobility group box-1 production, and improved sarcopenia and muscle maturity. When treated with 5-fluorouracil in a mouse cachexia model, tumor weight decreased but oxidative stress increased and muscle weight and muscle maturity were suppressed regardless of diet. However, in the CT group, oxidative stress was reduced and the exacerbation of sarcopenia by 5-fluorouracil was suppressed. Thus, in cancer cachexia, oxidative stress plays a major role in skeletal muscle damage, and CT, which has an anti-oxidative stress effect, has a strong protective effect on skeletal muscle. In the future, it will be important to conduct clinical studies on nutritional intervention for cancer sarcopenia using CT.

Skeletal muscle aging and sarcopenia result in similar changes in the levels of aging markers. However, few studies have examined cancer sarcopenia from the perspective of aging. Therefore, this study investigated aging in cancer sarcopenia and explored its causes in vitro and in vivo. In mouse aging, in vitro cachexia, and mouse cachexia models, skeletal muscles showed similar changes in aging markers including oxidative stress, fibrosis, reduced muscle differentiation potential, and telomere shortening. Furthermore, examination of mitochondrial DNA from skeletal muscle revealed a 5 kb deletion in the major arc; truncation of complexes I, IV, and V in the electron transport chain; and reduced oxidative phosphorylation (OXPHOS). The mouse cachexia model demonstrated high levels of high-mobility group box-1 (HMGB1) and tumor necrosis factor-α (TNFα) in cancer ascites. Continuous administration of neutralizing antibodies against HMGB1 and TNFα in this model reduced oxidative stress and abrogated mitochondrial DNA deletion. These results suggest that in cancer sarcopenia, mitochondrial oxidative stress caused by inflammatory cytokines leads to mitochondrial DNA damage, which in turn leads to decreased OXPHOS and the promotion of aging.

Background A common method for diagnosing sarcopenia involves estimating the muscle mass by computed tomography (CT) via measurements of the cross‐sectional muscle area (CSMA) of all muscles at the third lumbar vertebra (L3) level. Recently, single‐muscle measurements of the psoas major muscle at L3 have emerged as a surrogate for sarcopenia detection, but its reliability and accuracy remain to be demonstrated. Methods This prospective cross‐sectional study involved 29 healthcare establishments and recruited patients with metastatic cancers. The correlation between skeletal muscle index (SMI = CSMA of all muscles at L3/height2, cm2/m2) and psoas muscle index (PMI = CSMA of psoas at L3/height2, cm2/m2) was determined (Pearson's r). ROC curves were prepared based on SMI data from a development population (n = 488) to estimate suitable PMI thresholds. International low SMI cut‐offs according to gender were studied for males (<55cm2/m2) and for females (<39 cm2/m2). Youden's index (J) and Cohen's kappa (κ) were calculated to estimate the test's accuracy and reliability. PMI cut‐offs were validated in a validation population (n = 243) by estimating the percentage concordance of sarcopenia diagnoses with the SMI thresholds. Results Seven hundred and sixty‐six patients were analysed (mean age 65.0 ± 11.8 years, 50.1% female). Low SMI prevalence was 69.1%. Correlation between the SMI and PMI for the entire population was 0.69 (n = 731, P < 0.01). PMI cut‐offs for sarcopenia were estimated in the development population at <6.6cm2/m2 in males and at <4.8 cm2/m2 for females. The J and κ coefficients for PMI diagnostic tests were weak. The PMI cut‐offs were tested in the validation population where 33.3% of the PMI measurements were dichotomously discordant. Conclusions A diagnostic test employing single‐muscle measurements of the psoas major muscle as a surrogate for sarcopenia detection was evaluated but found to be unreliable. The CSMA of all muscles must be considered for evaluating cancer sarcopenia at L3.

Background Body water measured by bioelectrical impedance analysis (BIA) predicts the outcomes of many diseases. This study aimed to evaluate the relationship between body water and the prognosis of cancer patients with sarcopenia. Methods This study employed 287 cancer patients with sarcopenia underwent BIA from a prospective multicenter study of patients with cancer in China from 2013 to 2020. The primary outcome of interest was all-cause mortality presented as the longest time to follow-up available. Eight indicators of body water [total body water, extracellular water, intracellular water, free fat mass, active cell mass, extracellular water/intracellular water, extracellular water/total body water (ECW/TBW), and intracellular water/total body water] were included in the research. Neutrophil–lymphocyte ratio (NLR) = neutrophil (× 10 9 )/lymphocyte (× 10 9 ). The discriminatory ability and prediction accuracy of each factor were assessed using the C-index. The hazard ratios (HR) and 95% confidence intervals (CI) were calculated using the Cox proportional hazard model. Results The median age was 65 years old, and 138 (48%) patients were men. During a mean follow-up of 46 months, 140 deaths were recorded, resulting in a rate of 204.6 events per 1000 patient-years. ECW/TBW showed the best predictive accuracy (C-index = 0.619) compared to the other indicators [ p  = 0.004, adjusted HR (95% CI) 1.70 (1.18,2.44)]. In the middle tertile (0.385–0.405), ECW/TBW had a strong independent negative association with patient survival [adjusted HR (95% CI) 2.88 (1.39–5.97), p  = 0.004]. Patients who had a high ECW/TBW (ECW/TBW ≥ 0.395) combined with a high NLR had 3.84-fold risk of mortality ( p  < 0.001, 95% CI 1.99,7.38). Conclusions ECW/TBW was better than other indicators in predicting survival of cancer patients with sarcopenia. High ECW/TBW combined with high NLR would further increase the risk of mortality. Trial registration : The Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) (Chinese Clinical Trial Registry: ChiCTR1800020329, URL of registration: http://www.chictr.org.cn/showprojen.aspx?proj=31813 ).

Although the prognostic value of sarcopenic factors, such as loss of muscle mass and quality, have been widely reported in patients with cancer during the last decade, the value in those with ovarian cancer remains unclear. Therefore, this study evaluated the prognostic impact of sarcopenic factors in patients with ovarian cancer. We retrospectively evaluated the data of 94 ovarian cancer patients who underwent surgery and chemotherapy at the Shimane University Hospital between March 2006 and 2013. Preoperative computed tomography scan at the level of the third lumbar vertebra was used to evaluate skeletal muscle volume and quality based on the skeletal muscle index (SMI) and intramuscular adipose tissue content (IMAC), respectively. The impact of preoperative SMI and IMAC on outcomes was subsequently investigated. Low SMI and high IMAC were not significantly associated with disease-free survival (p = 0.329 and p = 0.3370, respectively) or poor overall survival (p = 0.921 and p = 0.988, respectively). Neither preoperative low muscle volume nor low muscle quality was a poor prognostic factor in ovarian cancer.

Literature concerning nutritional interventions in elderly patients with gastrointestinal cancer, with special reference to randomized clinical trials, has been critically reviewed. This segment of oncologic population was found to be penalized by a high prevalence of malnutrition and sarcopenia which translated in an increased rate of toxicity from chemotherapy, poor compliance with oncologic treatments, and, finally, with a poor prognosis. Attempts to reverse this condition included a potentiation of nutrients intake which should sequentially proceed through the use of dietary counseling and administration of standard or ω-3 fatty acid–enriched oral supplements to finally come to enteral or parenteral nutrition. Randomized clinical trials investigating the effects of simple dietary advice and use of standard oral supplements were disappointing as regards long-term compliance and results. Nutritional and clinical benefits were reported with the use of ω-3 fatty acid–enriched oral supplements and especially with long-term supplemental parenteral nutrition. Despite the general recommendation of the scientific community that emphasizes the use of the enteral route, whenever possible, for delivering the nutritional support, it appears from the literature that more consistent benefits can be achieved, especially in the long-term nutritional support, when an insufficient oral nutrition is partnered with intravenous nutrition.

Metabolic syndrome is a long-term complication of systemic chemotherapy for testicular germ cell tumor (TGCT). It is believed to be caused by secondary hypogonadism or toxic medicines because of orchidectomy followed by systemic chemotherapy. In this study, changes in the body composition of patients over time were quantitatively analyzed up to 24 months after chemotherapy. This study retrospectively analyzed 44 patients with TGCT who underwent chemotherapy at our institution from January 2008 to December 2016. Subcutaneous and visceral fat areas and psoas and skeletal muscle areas were measured by computed tomography before and immediately after chemotherapy as well as 3 months, 6 months, 12 months, and 24 months after chemotherapy. The subcutaneous and visceral fat indices and psoas and skeletal muscle indices were calculated as each area divided by body height squared. The total fat area had already significantly increased 3 months after the initiation of chemotherapy (P = 0.004). However, it did not return to prechemotherapeutic levels even at 24 months after chemotherapy. The skeletal muscle area was significantly decreased at the end of chemotherapy (P < 0.001); however, the value returned to baseline within 12 months. In multivariable analysis, the prechemotherapeutic skeletal muscle index and number of chemotherapy cycles were independently associated with the reduction of skeletal muscle at the end of chemotherapy (P = 0.001 and P = 0.027, respectively). In patients with TGCT, skeletal muscle mass decreased during chemotherapy and recovered within 12 months, whereas fat mass progressively increased from the initiation of chemotherapy until 24 months after chemotherapy.

Sarcopenia is associated with reduced survival and increased toxicity in malignant diseases. The prevalence of sarcopenia increases with age and is an important cause of functional decline. We analyzed sarcopenia and sarcopenia dynamics in elderly head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiation. Skeletal muscle mass of 280 elderly HNSCC-patients (>65 yrs) receiving curative (chemo)radiation was manually outlined and quantified on CT scans at the level of the C3 (C3MA). Cross-sectional muscle area at L3 (L3MA) was calculated and normalized to height (L3MI). Frequency distributions of clinical parameters as well as overall survival (OS), progression-free survival (PFS) and locoregional control (LRC) were calculated regarding sarcopenia. Calculated L3MA correlated with pretherapeutic hemoglobin-levels (ρ = 0.280) bodyweight (ρ = 0.702) and inversely with patient-age (ρ = −0.290). Sarcopenic patients featured larger tumors (T3/4 69.0% vs. 52.8%, p < 0.001), a higher burden of comorbidity (age-adjusted Charlson Comorbidity Index 4.8 vs. 4.2, p = 0.015) and more severe chronic toxicities (CTCAE grade 3/4 24.0% vs. 11.8%, p = 0.022). OS was significantly deteriorated in sarcopenic patients with a median of 23 vs. 91 months (logrank p = 0.002) (HR 1.79, CI 1.22–2.60, p = 0.003) and sarcopenia remained an independent prognostic factor for reduced OS in the multivariate analysis (HR 1.64, CI 1.07–2.52, p = 0.023). After therapy, 33% of previously non-sarcopenic patients developed sarcopenia, while 97% of pre-treatment sarcopenic remained sarcopenic. Median bodyweight decreased by 6.8%, whereas median calculated L3MA decreased by 2.4%. In contrast to pretherapeutic, post-therapeutic sarcopenia is no prognosticator for reduced OS. Pretherapeutic sarcopenia is a significant prognostic factor in elderly HNSCC patients undergoing (chemo-)radiation and should be considered in pretherapeutic decision-making. Its role as a predictive marker for tailored supportive interventions merits further prospective evaluation.

We sought to elucidate the prognostic impact of the SARC-F score among patients with gastrointestinal advanced malignancies (n = 421). A SARC-F score ≥ 4 was judged to have a strong suspicion for sarcopenia. In patients with ECOG-PS 4 (n = 43), 3 (n = 61), and 0–2 (n = 317), 42 (97.7%), 53 (86.9%) and 8 (2.5%) had the SARC-F score ≥ 4. During the follow-up period, 145 patients (34.4%) died. All deaths were cancer-related. The 1-year cumulative overall survival (OS) rate in patients with SARC-F ≥ 4 (n = 103) and SARC-F < 4 (n = 318) was 33.9% and 61.6% (p < 0.0001). In the multivariate analysis for the OS, total lymphocyte count ≥ 1081/μL (p = 0.0014), the SARC-F score ≥ 4 (p = 0.0096), Glasgow prognostic score (GPS) 1 (p = 0.0147, GPS 0 as a standard), GPS 2 (p < 0.0001, GPS 0 as a standard), ECOG-PS 2 (p < 0.0001, ECOG-PS 0 as a standard), ECOG-PS 3 (p < 0.0001, ECOG-PS 0 as a standard), and ECOG-PS 4 (p < 0.0001, ECOG-PS 0 as a standard) were independent predictors. In the receiver operating characteristic curve analysis on the prognostic value of the SARC-F score, the sensitivity/specificity was 0.59/0.70, and best cutoff point of the SARC-F score was two. In conclusion, the SARC-F score is useful in patients with gastrointestinal advanced malignancies.

The Interuniversity Institute of Myology (IIM) has been formally approved in late autumn 2003 by the University of Chieti Board of the first Director, Giorgio Fanò. Many Italian Myologists, coming from Italian Universities such as Università degli Studi di Chieti, Università degli Studi di Brescia, Università degli Studi di Firenze, Università degli Studi di Messi, Università degli Studi di Milano, Università degli Studi di Padova, Università degli Studi di Pavia, Università degli Studi di Perugia, Università degli Studi di Roma 'La Sapienza', Università degli Studi di Sie, who excel in Myology Research, recognized IIM and its potentiality for intertiol joined collaboration.