Skeletal Muscle Area Research Articles

Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography.

The association of myosteatosis measured using visual muscular quality map in computed tomography (CT) with nonalcoholic fatty liver disease (NAFLD), its severity, and fibrosis was analyzed in a large population. Subjects (n=13,452) with abdominal CT between 2012 and 2013 were measured total abdominal muscle area (TAMA) at L3 level. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, NAMA/TAMA, and LAMA/BMI. NAFLD and its severity were assessed by ultrasonography, and liver fibrosis was measured by calculating the NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB-4) scores. According to multiple logistic regression analyses, as quartiles of SMA/BMI, NAMA/BMI, and NAMA/TAMA increased, the odds ratios (ORs) for NAFLD decreased in each sex (P for trend <0.001 for all). The ORs of moderate/severe NAFLD were significantly higher in the Q1 group than in the Q4 group for SMA/BMI, NAMA/BMI, and NAMA/TAMA in men. The ORs of intermediate/high liver fibrosis scores assessed by NFS and FIB-4 scores increased linearly with decreasing quartiles for SMA/BMI, NAMA/BMI, and NAMA/TAMA in each sex (P for trend <0.001 for all). Conversely, the risk for NAFLD and fibrosis were positively associated with LAMA/BMI quartiles in each sex (P for trend <0.001 for all). A higher proportion of good quality muscle was associated with lower risks of NAFLD and fibrosis.

P429 Patient skeletal muscle area and postoperative clinical recurrence in Crohn’s disease: a retrospective study

Abstract Background Sarcopenia, a reduction in muscle mass and function, is a poorly recognised phenomenon in Crohn’s disease (CD) despite occurring in 16%-68% of CD patients [1-5]. It has been linked to both an increased need for surgery and increased risk of postoperative complications. However, the role of sarcopenia in CD and its long-term impact on surgical outcomes are unknown. We aimed to assess the link between sarcopenia and postoperative clinical recurrence. Methods Retrospective data was collected between 2015 and 2021 from CD patients who had undergone gastrointestinal surgery and a MR or CT scan within 3 months prior to surgery. Follow up data was retrospectively collected for 6 months. MR and CT scans were used to determine skeletal muscle area (SMA) from the cross-sectional L3 vertebrae, which was used to identify patients as sarcopenic or not. Clinical recurrence was defined as a Harvey-Bradshaw Index of 5 or more. Statistical analysis included demographics and inferential analyses. Missing data was attributed to the absence in clinic notes. Results This single centre study included 64 CD patients [56.3% male, median age of 30.0 (18.0-76.0), 87.7% non-smokers] who had undergone gastrointestinal surgery. Most patients had ileocolonic CD (74.6%, 47/63) and either stricturing (46.9%, 30/64) or penetrating (31.3%, 20/64) disease behaviour, and 23.4% (15/64) had perianal disease. 45.3% (29/64) of patients had had at least one previous surgery. Preoperatively, 20.6% (13/63) of patients were on steroids and 55.6% (35/63) were on combined drug therapy. Patient median SMA was 113.6 (61.8 – 281.7) cm2 with sarcopenia found in 74.1% (43/58) of patients. SMA was lower in females (females: 92.1±19.3 cm2 vs males: 137±39.5 cm2, p&amp;lt;0.001) and patients with a BMI&amp;lt;18.5 kg/m2 (BMI&amp;lt;18.5 kg/m2: 91.8±19.1 cm2 vs BMI≥18.5 kg /m2: 120.3±33.3 cm2, p=0.004) (figure 1). Postoperative clinical recurrence was observed in 17.8% (8/45) of patients at 6 months. Patients with clinical recurrence had a significantly lower SMA (87.4 ± 18.5 cm2) compared to those without clinical recurrence (120.9 ± 39.2 cm2) (p=0.001) (figure 2). Patients with a lower SMA were 1.1 times more likely to have clinical recurrence at 6 months compared to patients with a higher SMA (OR 1.05 (CI 1.01-1.10)(p=0.022)). Conclusion Sarcopenia is highly prevalent in preoperative CD patients. Patients with early clinical recurrence had a significantly lower SMA. SMA may be useful in predicting CD patients at risk of early postoperative clinical recurrence. However, more research is needed to confirm study findings.

P757 Visceral adiposity and not subcutaneous adiposity or body mass index is more strongly associated with relapse in inflammatory bowel disease

Abstract Background The role of body composition in inflammatory bowel disease (IBD) has still not been established due to heterogenous evidence. This study aimed to assess if abdominal body composition parameters were associated with outcomes in inflammatory bowel disease. Methods In this retrospective study abdominal body composition was evaluated using routinely acquired computed tomography (CT) from eligible patients with IBD between January 2014 and September 2021. Cross sectional areas of total fat (TFA), subcutaneous fat (SFA), visceral fat (VFA) and skeletal muscle (SMA) including their indices and ratios were measured at lumbar 3 (L3) vertebrae level using appropriate software. The outcome measure was relapse defined as acute flaring of symptoms and/or worsening biochemical markers, endoscopic recurrence requiring dose intensification of current therapy and surgical resection. Spearman’s correlations between body composition parameters were analysed. Binary logistic regression adjusting for demographics, smoking, disease characteristics (type, duration, location, behaviour) and medications was used to test for the relative significance of SFA, VFA, SMA and body mass index (BMI) on the outcome measures. A forward logarithmic likelihood method was used to test for it. Results Fifty-three IBD patients (58% male; 42% female) with 22 (42%) in relapse were included for abdominal CT analysis. Mean age of patients with relapse was 41.8 ± 16.2 years while those without relapse was 48.4 ± 12.5 years (p = 0.360). Mean BMI of patients with relapse was 25.6 ± 4.4 while those without relapse was 28.1 ± 7.0 (p = 0.457). Mean disease duration of patients with relapse was 15.3 ± 9.2 years while those without relapse was 21.3 ± 10.7 years (p = 0.583) [see Table 1]. Mean VFA was not significantly lower in relapse than remission (mean: 95.3 ± 99.5 cm² vs 119.7 ± 89.6 cm²; logarithmic p = 0.222), whereas mean SFA was significantly higher in relapse than remission (mean: 129.0 ± 64.3 cm² vs 225.3 ± 156.8 cm²; logarithmic p = 0.016) [see Table 2]. VFA and BMI correlated strongly with all other body composition parameters according to Spearman’s model (p &amp;lt; 0.001) [see Table 3]. After performing binary logistic regression and accounting for variables including age, gender, smoking status, type of IBD, disease characteristics (duration, location, behaviour), corticosteroid use, biologic therapy, anti-TNF level, VFA (p = 0.013) was significantly associated with relapse in comparison to SFA (p = 0.063) and BMI (p = 0.563). Conclusion Visceral adiposity and not BMI or subcutaneous adiposity is more strongly associated with relapse in IBD.

P481 Visceral fat to skeletal muscle area ratio predicts for Ustekinumab loss of response.

Abstract Background Loss of response (LOR) to anti-TNFα therapy in inflammatory bowel disease (IBD) is common and biologic therapies such as anti-IL12/23 agents have shown greater durability in efficacy. Anti-TNFα LOR is increased in higher body mass index (BMI) patients however the evidence for the association between body composition or BMI and Ustekinumab’s (Ust) therapeutic response is limited, with the latter not impacting clinical efficacy in the ‘IM-MUNITI’ post-hoc analyses. This study’s primary aim was to evaluate the impact of body composition on time to LOR to Ustekinumab in Crohn’s disease (CD) patients. Methods 99 adult CD patients aged ≥16 yrs. from two tertiary IBD centres were studied retrospectively. Included patients had received Ust ≥12 weeks, abdominal imaging (CT or MRI) within 6 months of Ust induction, and documented follow up until 30th April 2022. A single experienced abdominal radiologist blinded to the clinical information measured the area of visceral fat (VFA), skeletal muscle (SMA), and subcutaneous fat at the mid L3 vertebral level. Each compartment was corrected for height2 to derive visceral fat (VFI), skeletal muscle (SMI) and subcutaneous fat (SFI) indices. VFA:SMA ratio was also calculated. Clinico-demographic details including therapeutic and surgical history were recorded. Kaplan Meir survival analyses, univariate and multivariate cox regression analyses were performed to evaluate factors predictive of Ust LOR. Results 99 patients met the inclusion criteria with mean age (±SE) 46.6yrs (±1.6) and 49 (49.5%) male. 63 (63.6%) patients were bio-experienced. Univariate Cox regression analyses of age, sex, BMI, peak C-reactive protein (CRP) and nadir Albumin level within 3 months of the CT/MRI scan, disease duration, prior biologic failure and concurrent immunomodulator used within 6 months of Ust induction showed that none of these were predictive of Ust LOR (P&amp;gt;0.05). There was a numerical trend for the middle VFI tertile (40.01-79.99cm2/m2) to having a lower risk for LOR compared to the lowest and highest VFI tertile (Fig. 1a), (HR=0.37, 95%CI= 0.13, 1.11, P=0.08), as well as a higher SMI for having a lower risk of LOR (Fig. 1b), (HR= 0.6, 95%CI= 0.24,1.31, P= 0.18), but these were not statistically significant. A higher VFA: SMA ratio however, was a significant predictor of LOR (HR=2.98, 95%CI 1.2,7.3, P= 0.02) (Fig. 1c), which persisted when it was adjusted on multivariate analysis for age, sex, albumin, CRP, BMI, disease duration, prior biologic failure and concurrent immunomodulator use (HR= 10.6, 95%CI 2.8-39.8, P=&amp;lt;0.0001). Conclusion The ratio of VFA:SMA, but not BMI, is a superior predictor of losing response to Ustekinumab.

Emerging trends in the prediction of pathological tumour response in rectal cancer following neoadjuvant therapy.

The treatment landscape of locally advanced rectal cancer (LARC) is moving towards total neoadjuvant therapy and potential organ preservation. Multimodality neoadjuvant therapy (NAT) and surgery remain the standard-of-care for LARC, with consideration for adjuvant chemotherapy. Neoadjuvant chemotherapy alone is another emerging strategy.1 Due to variation in multimodality treatment choice, biomarkers to predict response to NAT could personalize treatment plans for patients.2 Of particular interest are predictors of pathologic complete response (pCR) to guide selection for a watch and wait approach, or identify those who would benefit from surgery due to poor response to NAT or a higher risk of disease relapse. Tumour response to NAT is a complex interplay between variables including tumour biology, patient factors, and the sequencing and timing of the selected NAT approach. Presently available modalities (MRI and endoscopy) can aid assessment but do not predict for tumour response. There are currently no clinically actionable biomarkers to predict NAT response, however several promising contenders are emerging.2 Circulating tumour DNA (ctDNA) has been shown as a risk-stratification tool to guide adjuvant therapy choice in patients following colon cancer resection.3 The presence of ctDNA following long course chemoradiation and surgery is an adverse prognostic factor.4 Evidence for ctDNA in the neoadjuvant setting for LARC is also evolving. As a marker for minimal residual disease, studies have demonstrated that detectable ctDNA predicts for poorer response to NAT and potentially identifies patients that should proceed to surgery rather than a watch and wait strategy.5, 6 Other biochemical markers such as microRNA and tumour-infiltrating lymphocytes are also being evaluated.7, 8 The gut microbiome has a role in the carcinogenesis of colorectal cancer, and potentially predicts response to anticancer therapy through the effect of certain bacteria on pharmacokinetics, pharmacodynamics and immune response.9 However, questions remain regarding the specific microbiome biomarkers that can predict LARC response to NAT and its utility in clinical practice is currently limited.9 Immunogenomics is becoming increasingly relevant to the management of LARC, with immune checkpoint inhibitors exhibiting high response rates in mismatch repair deficient (dMMR) tumours and 100% clinical complete response in dMMR LARC.10 Initiatives such as the Cancer Genome Atlas Program are genomically sequencing colorectal cancers to identify genomic alterations beyond microsatellite instability that may predict responsiveness to immunotherapy and the likelihood of a pCR.11 Radiomics is a process whereby disease features, or ‘radiological biomarkers’ are extracted from standard patient imaging, constructing an algorithm which can then aid in predicting treatment response.12 T2 weighted MRI-based software for LARC successfully predicts pCR and nodal status post-NAT.13 Combined radiomics with both multi-parameter MRI (T1/T2/Contrast enhanced) and functional PET-CT may provide better predictive value for pCR.14 Currently, the widespread adoption of radiomics has been hindered by the technological and cost burden, limited reproducibility of data, and time-intensive manual data extraction.13 Larger prospective trials are required to validate its use in LARC management.13, 15 With the adoption of Artificial Intelligence (AI) and deep learning, data extraction will become increasingly accessible and construct reproducible algorithms,13 making clinical application feasible. Body composition measurement based on standard CT-staging is another ‘radiological biomarker’.16 Body composition is more accurate than body surface area for systemic therapy dosing, and predicting poor tolerance to chemotherapy in colorectal cancer.17 Recent evidence has suggested that skeletal muscle area pre-NAT can predict tumour response and survival outcomes for LARC, presenting a promising area for future studies.16 In summary, multiple promising biomarkers are emerging to identify the optimal individualized treatment paradigm for patients with LARC. It is hoped that further research and increasing validation of new technologies such as AI, will tailor future personalized decision making for patients with LARC. Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians. Matthew Y. Wei: Writing – original draft; writing – review and editing. Yasser Arafat: Validation; writing – review and editing. Margaret Lee: Validation; writing – review and editing. Suzanne Kosmider: Validation; writing – review and editing. Matthew Loft: Validation; writing – review and editing. Ian Faragher: Validation; writing – review and editing. Peter Gibbs: Conceptualization; validation; writing – review and editing. Justin Yeung: Conceptualization; supervision; writing – review and editing.

Skeletal muscle area predicts the outcomes of non-small-cell lung cancer after trimodality therapy.

Sarcopenia correlates with poor prognosis in various malignancies. However, the prognostic significance of sarcopenia remains to be determined in patients with non-small-cell lung cancer who undergo surgery after receiving neoadjuvant chemoradiotherapy (NACRT). We retrospectively reviewed the patients with stage II/III non-small-cell lung cancer who underwent surgery following NACRT. The paravertebral skeletal muscle area (SMA) (cm2) at the 12th thoracic vertebra level was measured. We calculated the SMA index (SMAI) as SMA/squared height (cm2/m2). Patients were divided into low and high SMAI groups, and the association of SMAI with clinicopathological factors and prognosis was assessed. The patients' [men, 86 (81.1%)] median age was 63 (21-76) years. There were 106 patients including 2 (1.9%), 10 (9.4%), 74 (69.8%), 19 (17.9%) and 1 (0.9%) patients with stage IIA, IIB, IIIA, IIIB and IIIC, respectively. Of the patients, 39 (36.8%) and 67 (63.2%) were classified in the low and the high SMAI groups, respectively. Kaplan-Meier analysis showed that the low group had a significantly shorter overall survival and disease-free survival than the high group. Multivariable analysis identified low SMAI as an independent poor prognostic factor for overall survival. Pre-NACRT SMAI correlates with poor prognosis; therefore, assessing sarcopenia based on pre-NACRT SMAI may help determine optimal treatment strategies and suitable nutritional and exercise interventions.

High visceral fat-to-muscle ratio is an independent factor that predicts worse overall survival in patients with primary epithelial ovarian, fallopian tube, and peritoneal cancer

BackgroundThe intra-abdominal cavity, surrounded by adipocytes, is the main metastatic site of epithelial ovarian, fallopian tube, and peritoneal cancer. Epidemiological and molecular studies have demonstrated a link between adipose tissue and ovarian cancer. However, the clinical significance of fatty tissue has not been elucidated. Thus, we investigated the clinical significance of body composition in patients with epithelial ovarian, fallopian tube, and peritoneal cancer.MethodsFat and skeletal muscle areas were measured using software based on pretreatment computed tomography scans at the third lumbar vertebra. Fat-to-muscle ratios were calculated using the total (visceral and subcutaneous) fat area or visceral fat area. High fat-to-muscle ratios were defined by values greater than the mean. Sarcopenia was defined as a skeletal muscle index < 38.7 cm2/m2. The clinicopathological parameters and survival of 153 patients were analyzed.ResultsHigh visceral fat-to-muscle ratios and sarcopenia at the time of diagnosis were observed in 43.8% and 33.3% of the patients, respectively. Multivariate analysis showed that high visceral fat-to-muscle ratio (p = 0.014), advanced Federation of Gynecology and Obstetrics stage (p = 0.008), and chemoresistance (p = 0.027) were independent factors for worse overall survival. Patients with high visceral fat-to-muscle ratios were older, had higher body mass indexes, and were more likely to have diabetes/hypertension, serous cancer subtypes, and implementation of neoadjuvant chemotherapy than those with low visceral fat-to-muscle ratios. The platelet count was significantly higher in the high visceral fat-to-muscle ratio group than in the low visceral fat-to-muscle ratio group (p = 0.011).ConclusionsPretreatment visceral fat area could be an independent predictive factor of overall survival in patients with epithelial ovarian, fallopian tube, and peritoneal cancer and may be significantly associated with thrombocytosis.

Assessment of muscle mass using chest computed tomography-based quantitative and qualitative measurements in patients with systemic sclerosis: A retrospective study with cross-sectional and longitudinal analyses

Background/ purposeSarcopenia has been increasingly studied in systemic sclerosis (SSc), which is one of the most lethal autoimmune diseases, mainly due to lung involvement. Our objective was to study the associations of myopenia and/or myosteatosis with clinical features of SSc and subsequent adverse outcomes. MethodsThis is a retrospective study with cross-sectional and longitudinal analyses, in which patients with SSc were consecutively included in the outpatient clinic of a tertiary university hospital between 2012 and 2021. Clinical and laboratory parameters of patients with SSc were collected from their medical records. Skeletal muscle mass was assessed on chest computed tomography (CT) at the level of the first lumbar vertebra (L1) by skeletal muscle area (SMA), skeletal muscle index ([SMI] SMA/height2), and skeletal muscle radiation attenuation (SMRA). Cut-off values for myopenia in women and men were SMA <70.1 cm² and <110.4 cm², and SMI <25.9 cm²/m² and <34.6 cm²/m², respectively; values for myosteatosis in women and men were SMRA <29.8 HU and <36.3 HU, respectively. In a subgroup of 31 patients followed-up between 2017 and 2019, the diagnostic properties of SMA, SMI, and SMRA by CT were compared with the appendicular skeletal muscle mass index (ASMI) by dual-energy X-ray absorptiometry (DXA). Low muscle quantity was defined according to the European Working Group on Sarcopenia in Older People 2: ASMI <5.5 kg/m2 in women and <7.0 kg/m2 in men. Afterwards, a better tomographic index was used for correlating with clinical and laboratory parameters. ResultsMyopenia and/or myosteatosis were present in 75.7 % of patients with SSc. The prevalence rates according to each index were SMA 25.2%, SMI 12.1%, and SMRA 69.2%. In 73% of the patients with overweight/obesity (body mass index [BMI] ≥25 kg/m²), only SMRA was reduced. Considering ASMI as the gold standard, the sensitivity, specificity, positive and negative predictive values for SMA were 60%, 96.2%, 75% and 92.6%, respectively; for SMI, they were 40%, 96.2%, 66.7%, and 89.3%, respectively; for SMRA, these values were 60%, 34.6%, 15%, and 81.8%. Pearson's correlation coefficients were 0.73, 0.74, and 0.10 for SMA, SMI, and SMRA, respectively, and ASMI significantly agreed with SMA (kappa 0.611, p < 0.001) and SMI (kappa 0.431, p = 0.012). After adjustments in a multivariate model, BMI (p < 0.001) and female sex (p < 0.001) remained significantly associated with myopenia by SMA; BMI (p =0.010) remained significantly associated with low muscle mass by ASMI. ConclusionThe SMA index at L1 level on chest CT was demonstrated to be an accurate measure that is useful for detecting myopenia in patients with SSc. BMI and male sex predicted low SMA and BMI was associated with low ASMI on DXA. Statement of clinical significanceIn recent years, great advances have been made in sarcopenia-related research, resulting in broader knowledge on its definition, causes, diagnosis, and treatment options.Regarding the techniques used for assessing muscle composition, computed tomography (CT) was demonstrated by many studies to be an efficient and easy-to-use method that can be employed by professionals of different specialties, including rheumatologists. This study was able to demonstrate that although the L3 image was not present on CT, the analysis of SMA at the L1 level on chest CT proved to be an accurate and useful measure to detect myopenia in patients with SSc.This study identified some associated factors of myopenia and/or myosteatosis according to each method employed for assessing muscle composition. Reduced BMI and male sex were associated factors of myopenia when using SMA, and reduced BMI was associated with myopenia when employing ASMI by DXA.Finally, we highlight the need not to generalize the term “sarcopenia” in clinical studies assessing imaging parameters of body composition. The use of the terms myopenia and/or myosteatosis would be more adequate, because CT allows the assessment of muscle composition and not strength or physical performance.

Associations of muscle and adipose tissue parameters with long-term outcomes in middle and low rectal cancer: a retrospective cohort study

ObjectiveTo investigate the role of preoperative body composition analysis for muscle and adipose tissue distribution on long-term oncological outcomes in patients with middle and low rectal cancer (RC) who received curative intent surgery.MethodsA total of 155 patients with middle and low rectal cancer who underwent curative intent surgery between January 2014 and December 2016 were included for the final analysis. Skeletal muscle area (SMA), skeletal muscle radiodensity (SMD), visceral fat area (VFA) and mesorectal fat area (MFA) were retrospectively measured using preoperative CT images. To standardize the area according to patient stature, SMA was divided by the square of the height (m2) and the skeletal muscle mass index (SMI, cm2/m2) was obtained. Each median values of the distribution in male and female served as cut-off point for SMI, SMD, VFA, and MFA, respectively. Univariate and multivariate analysis were performed to evaluate the association between body composition and long-term oncological outcomes. Overall survival (OS) measured in months from the day of primary surgery until death for any cause. Disease-free survival (DFS) was defined as the interval between surgery and tumor recurrence. The Kaplan-Meier method with log-rank testing was used to validate prognostic biomarkers. Intraclass correlation coefficient (ICC) was used to evaluate interobserver and intraobserver reproducibility for SMA, SMD, MFA,VFA.ResultsDuring the follow-up period, 42 (27.1%) patients had tumor recurrence; 21 (13.5%) patients died. The sex-specific median value of SMI was 28.6 cm2/m2 for females and 48.2 cm2/m2 for males. The sex-specific median value of SMD was 34.7 HU for females and 37.4 HU for males. The sex-specific median value of VFA was 123.1 cm2 for females and 123.2 cm2 for males. The sex-specific median value of MFA was 13.8 cm2 for females and 16.0 cm2 for males. In the Cox regression multivariate analysis, SMI (P = 0.036), SMD (P = 0.022), and postoperative complications grades (P = 0.042) were significantly different between death group and non-death group; SMD (P = 0.011) and MFA (P = 0.022) were significantly different between recurrence group and non-recurrence group. VFA did not show any significant differences. By the Kaplan-Meier method with log-rank testing, DFS was significantly longer in patients with high-MFA (P = 0.028) and shorter in patients with low-SMD (P = 0.010), OS was significantly shorter in patients with low-SMI (P = 0.034) and low-SMD (P = 0.029).ConclusionsQuantitative evaluation of skeletal muscle mass and adipose tissue distributions at initial diagnosis were important predictors for long-term oncologic outcomes in RC patients. SMD and SMI were independent factors for predicting OS in patients with middle and low rectal cancer who had radical surgery. SMD and MFA were independent factors for predicting DFS in patients with middle and low rectal cancer who had radical surgery.

Association between hypertension and myosteatosis evaluated by abdominal computed tomography.

Few studies have examined the relationship between myosteatosis and hypertension, and no studies have enrolled an Asian population. Existing studies also found discordant results, possibly due to the use of conventional myosteatosis indices that are not sufficiently reliable and representative. Therefore, we investigated the association between myosteatosis and hypertension in Asian individuals using novel, objective computed tomography (CT) markers. The total abdominal muscle area (TAMA) was determined from abdominal CT scans taken at the L3 level. Based on the mean CT attenuation, the TAMA was divided into intramuscular adipose tissue and skeletal muscle area (SMA), which was further segmented into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). Among SMA/body mass index (BMI), NAMA/BMI, LAMA/BMI, and the NAMA/TAMA index, NAMA/BMI was chosen through receiver operating characteristic curves as the best predictive marker for hypertension. The hypertension risk for each quartile of NAMA/BMI was calculated by logistic regression analysis. Among the 19,766 participants, 40.3% of men and 23.8% of women had hypertension. People with hypertension showed unhealthier myosteatosis profiles than normotensive controls. Similarly, a lower NAMA/BMI was significantly associated with a greater hypertension risk. The lowest quartile group of NAMA/BMI exhibited 2.3- and 2.6-fold higher risks of hypertension than the highest quartile in men and women, respectively. In conclusion, advanced myosteatosis assessed by abdominal CT was significantly correlated with a higher risk of hypertension. Improving myosteatosis may be a new approach for preventing cardiovascular diseases, including hypertension. Advanced myosteatosis measured by abdominal CT taken at the L3 level was significantly correlated with a higher risk of hypertension even after adjusting for health behaviors, intake of lipid-lowering drugs, plasma lipid levels, and other ectopic fat distribution.

Prognostic significance of preoperative creatine kinase in resected thymic epithelial tumors.

The preoperative serum creatine kinase (CK) concentration is a prognostic factor for malignant diseases. We investigated the significance of CK in surgically resected thymic epithelial tumors and the relationship between CK and clinicopathological factors. We retrospectively evaluated the relationship between preoperative CK levels and prognosis in 120 patients with thymic epithelial tumors who underwent surgical resection at two centers. The cutoff for CK was determined by the standard value in our institution (<62 IU/L for men and <45 IU/L for women). The paravertebral muscle at the Th12 level was used to assess skeletal muscle area to investigate sarcopenia. Eighteen patients (15.0%) were categorized into the low CK group. The CK level was not associated with age, sex, performance status, myasthenia gravis, and pathological findings. Preoperative serum albumin and total cholesterol concentrations were significantly lower in the low CK group than in the normal CK group (both P<0.001). Moreover, the Th12 muscle index was lower in the low CK group (P=0.03), indicating that low CK was related to sarcopenia. Kaplan-Meier curve analysis illustrated that patients in the low CK group had significantly shorter disease-free survival (DFS) and overall survival (OS) than those in the normal CK group (P=0.03 and P=0.002, respectively). Multivariate analysis identified low CK as an independent prognostic factor for DFS (P=0.03) and OS (P=0.005). Preoperative serum CK might reflect the host nutritional status in patients with resected thymic epithelial tumors; therefore, CK could be a biomarker of postoperative prognosis.

Clinical significance of sarcopenia in patients undergoing treatment for gastric cancer.

The aim of this study was to investigate the impact of sarcopenia on prognosis in patients with gastric cancer in order to explore the relationship between sarcopenia and postoperative complications as well as durations of hospital stay and intensive care unit. A total of 175 patients who visited the oncology clinic between 2017 and 2022 with respect to their radiological images, demographic data, and laboratory parameters were perused. The OsiriX software was used to measure the skeletal muscle area that was divided by the body height in order to obtain the skeletal muscle index. A total of 50.28% of 175 patients (41 females and 134 males, with a mean age of 63.5 years) who met the inclusion criteria in the study were sarcopenic. Significant differences appeared between sarcopenic and non-sarcopenic patients with respect to durations of both hospital stay (p<0.01) and intensive care unit stay (p<0.01) (multivariate analysis). Furthermore, patients with sarcopenia had significantly frequent postoperative complications in comparison with those without sarcopenia. Among the patients with sarcopenia, decreased levels of hemoglobin and albumin as well as lymphocytes were encountered in terms of inflammatory markers; nevertheless, no significant differences were determined among other inflammatory markers. In patients undergoing treatment for gastric cancer, sarcopenia increases postoperative complications and prolongs hospital and intensive care stays during the treatment process.

Significance of Skeletal Muscle Loss in Liver Hypertrophy in Patients Undergoing Portal Vein Embolization Before Major Hepatectomy: Assessment With Body Composition and Nutritional Indicators.

The relationship between body composition including skeletal muscle and liver hypertrophy initiated by portal vein embolization (PVE) for major hepatectomy has not been clarified. This study aimed to investigate the effects of skeletal muscle, body adipose, and nutritional indicators on liver hypertrophy. Fifty-nine patients who underwent PVE scheduled for major right-sided hepatectomy were included. The skeletal muscle area of L3 as skeletal muscle index was calculated. The relationship between skeletal muscle loss and clinical variables was assessed. We also evaluated the relationship between >30% liver growth or >12% liver growth/week after PVE. Skeletal muscle loss was observed in 39 patients (66.1%) and associated with zinc deficiency, visceral adipose index, liver growth rate, and liver growth rate/week. Multivariate analysis indicated that future liver volume and skeletal muscle index were associated with >30% liver growth, and functional future liver volume and skeletal muscle index were associated with >12% liver growth/week. Loss of skeletal muscle, and a small future remnant liver volume, attenuates liver hypertrophy initiated by PVE. Strength building and nutritional supplementation may have positive effects on liver hypertrophy after PVE.

Predictors of Improvement of Sarcopenia after Transjugular Intrahepatic Portosystemic Shunt Creation in Cirrhotic Patients

To investigate the risk factors affecting the improvement of sarcopenia after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients, this study retrospectively analyzed the data of 111 cirrhotic patients with sarcopenia who underwent TIPS creation. Computed tomography–based measurement of skeletal muscle area was used to calculate skeletal muscle index (SMI) in all patients at baseline and 6 months after TIPS creation. Multivariate logistic regression analysis was used to identify independent risk factors, which showed a significant increase in 6-month post-TIPS SMI compared with that at baseline in both men and women (for both, P < .001). Pre-TIPS SMI (odds ratio [OR], 0.93; 95% CI, 0.87–0.99; P = .031) and change in portal pressure gradient (OR, 1.13; 95% CI, 1.03–1.24; P = .009) were found to be independent risk factors for experiencing substantial improvement in post-TIPS SMI.

The G protein-coupled receptor ligand apelin-13 ameliorates skeletal muscle atrophy induced by chronic kidney disease.

Targeting of the apelin-apelin receptor (Apj) system may serve as a useful therapeutic intervention for the management of chronic kidney disease (CKD)-induced skeletal muscle atrophy. We investigated the roles and efficacy of the apelin-Apj system in CKD-induced skeletal muscle atrophy. The 5/6-nephrectomized mice were used as CKD models. AST-120, a charcoal adsorbent of uraemic toxins (8 w/w% in diet), or apelin (1μmol/kg) was administered to CKD mice to investigate the mechanism and therapeutic potential of apelin on CKD-induced skeletal muscle atrophy. The effect of indoxyl sulfate, a uraemic toxin, or apelin on skeletal muscle atrophy was evaluated using mouse myoblast cells (C2C12 cells) in vitro. Skeletal muscle atrophy developed over time following nephrectomy at 12weeks, as confirmed by a significant increase of atrogin-1 and myostatin mRNA expression in the gastrocnemius (GA) muscle and a decrease of lower limb skeletal muscle weight (P<0.05, 0.01 and 0.05, respectively). Apelin expression in GA muscle was significantly decreased (P<0.05) and elabela, another Apj endogenous ligand, tended to show a non-significant decrease at 12weeks after nephrectomy. Administration of AST-120 inhibited the decline of muscle weight and increase of atrogin-1 and myostatin expression. Apelin and elabela expression was slightly improved by AST-120 administration but Apj expression was not, suggesting the involvement of uraemic toxins in endogenous Apj ligand expression. The administration of apelin at 1.0μmol/kg for 4weeks to CKD mice suppressed the increase of atrogin-1 and myostatin, increased apelin and Apj mRNA expression at 30min after apelin administration and significantly ameliorated weight loss and a decrease of the cross-sectional area of hindlimb skeletal muscle. This study demonstrated for the first time the association of the Apj endogenous ligand-uraemic toxin axis with skeletal muscle atrophy in CKD and the utility of therapeutic targeting of the apelin-Apj system.

A Novel Use for Pelvic MRI Scans to Estimate Lean Body Mass and Screen for Sarcopenia in Patients With Rectal Cancer.

Sarcopenia, the combination of low lean body mass and decreased muscle strength, is associated with significant morbidity and mortality among patients with colorectal cancer. Standard methods for assessing lean body mass and muscle strength, such as bioelectric impedance analysis and handgrip dynamometry, are rarely obtained clinically. Per National Cancer Center Network recommendations, pelvic MRI is routinely collected for staging and surveillance among patients with rectal cancer. However, there are no data assessing the relationship of pelvic MRI lean body mass measurements at the fifth lumbar vertebrae with bioelectric impedance analysis, handgrip strength, or abdominal CT in patients with rectal cancer. Therefore, we aimed to assess whether pelvic MRI lean body mass correlates with a standard for lean body mass measurement (bioelectric impedance analysis), muscle function (handgrip strength), and an imaging modality frequently used in the literature to identify sarcopenia (abdominal CT at the third lumbar vertebrae). Lean body mass measurements from routinely collected pelvic MRI at the fifth lumbar vertebrae accurately and reproducibly estimate lean body mass and modestly correlate with handgrip strength. Rectal cancer pelvic MRI may be repurposed for identifying sarcopenia without increasing inconvenience, ionizing radiation exposure, or expenditure to patients with rectal cancer. Patients with locally advanced rectal cancer with pretreatment bioelectric impedance analysis and handgrip strength measurements within 3 months of their staging pelvic MRI were eligible. Axial skeletal muscle areas were segmented using T1-weighted series pelvic MRI at the fifth lumbar vertebrae and abdominal CT at the third lumbar vertebrae using Slice-O-Matic (Tomovision, Montreal, Canada). Lean body mass (kilograms) was derived from skeletal muscle area with standard equations. Handgrip strength (kilograms) was the maximum of 3 dominant hand attempts in the standing anatomical position. The primary outcome was the agreement between lean body mass measured by pelvic MRI (at the fifth lumbar vertebrae) and bioelectric impedance analysis. Secondary outcomes included the concordance of pelvic MRI lean body mass (at the fifth lumbar vertebrae) with abdominal CT (at the third lumbar vertebrae) and handgrip strength. Additionally, the intra- and interobserver validity, internal consistency, and the mean difference (bias) between lean body mass measurements by pelvic MRI and bioelectric impedance analysis were evaluated. Sixteen patients were eligible. The average lean body mass was similar and consistent across 2 observers between bioelectric impedance analysis and pelvic MRI. There was a strong correlation between lean body mass measured on pelvic MRI, bioelectric impedance analysis, and abdominal CT. The reliability of 2 pelvic MRI lean body mass measurements (2 weeks apart by blinded observers) and the correlation of lean body mass between pelvic MRI and bioelectric impedance analysis was strong. Inter- and intraobserver correlation, reliability, and internal consistency were strong for the entire cohort. There was a moderate correlation between pelvic MRI lean body mass and handgrip strength. Lean body mass measured at the fifth lumbar vertebrae on pelvic MRI is reproducible and correlates strongly with measurements from bioelectric impedance analysis (standard) and abdominal CT at the third lumbar vertebrae and modestly with handgrip strength. These data suggest that MRI lean body mass measurements may be a method to screen patients with rectal cancer for sarcopenia. Future studies may evaluate changes in lean body mass on serial pelvic MRI studies among patients with rectal cancer.

HPB P36 The influence of sarcopenia and systemic inflammation on survival in resected pancreatic cancer

Abstract Background Sarcopenia, cachexia and systemic inflammation are early hallmarks of pancreatic cancer (PC) which hamper systemic therapy and accelerate the terminal stages of the disease. The significant impact of sarcopenia on survival in PC has been demonstrated in numerous meta-analyses using standardised thresholds to define body composition measurements. We sought to determine the influence of sarcopenia and systemic inflammation on survival in our cohort of resected PC patients. We also interrogated the impact of the introduction of neoadjuvant therapy (NAT) protocols on survival, body composition and systemic inflammation. Finally we investigated the use of varying thresholds to define sarcopenia and the impact of this on survival. Methods Analysis of a prospectively maintained database of resected patients with PC accrued through the tertiary West of Scotland Pancreatic Unit was undertaken. Patients with cancer types other than pancreatic ductal adenocarcinoma were excluded. Body composition analysis was carried out using cross-sectional measurements of skeletal muscle area, skeletal muscle density and visceral fat area at the L3 level from pre-treatment or pre-operative CT scan using Slice-o-Matic software (Tomovision, Montreal). Disease-specific survival was used with Log-rank test for survival differences. Results 188 patients underwent resection between 2008–2020. 44.1% received NAT and 65.9% were resected up-front. Using Prado / Martin cutoffs of skeletal muscle index (SMI) to define sarcopenia demonstrated no significant survival difference in either cohort. Visceral obesity and myosteatosis (defined by Doyle / Martin) also demonstrated no significant survival difference. Modified thresholds tailored to our cohort were used and a median survival difference of 34.5 vs 23.1 months was identified (p &amp;lt; 0.001). Similarly for modified BMI-specific thresholds a median survival difference of 35.2 vs 22.8 months was identified (p &amp;lt; 0.001). On further analysis of the NAT cohort, 60.2% of patients exhibited gain in SMI with treatment and 39.8% of patients exhibited loss of SMI. There was a tendency towards poorer survival in the latter group however this was not significant. On further stratification of cohorts in to NAT and up-front resection it was revealed that the predictive effect of sarcopenia was entirely the effect of the up-front resected cohort, with little difference in survival between sarcopenic and non-sarcopenic groups in the NAT cohort. Median survival in all patients (NAT and up-front resection combined) increased from 27.4 months to 32.6 months (p = 0.016) with the introduction of NAT protocols in 2013. Conclusions Defining sarcopenia using modified thresholds tailored specifically to our cohort of patients demonstrates the significant impact of sarcopenia on survival in resected PC. The introduction of NAT protocols in 2013 has had a significant impact on survival, an effect which may be due to the selection of smaller tumours for up-front resection. Further work is needed as part of intention-to-treat analysis to identify patients who undergo NAT who do not progress to resection. Analysis of this cohort will validate our findings and shed further light on the impact of neoadjuvant therapy on sarcopenia and body composition. This analysis is ongoing and further novel data will be presented in September should this abstract be accepted.

Utility of Normalized Body Composition Areas, Derived From Outpatient Abdominal CT Using a Fully Automated Deep Learning Method, for Predicting Subsequent Cardiovascular Events.

BACKGROUND. CT-based body composition (BC) measurements have historically been too resource intensive to analyze for widespread use and have lacked robust comparison with traditional weight metrics for predicting cardiovascular risk. OBJECTIVE. The aim of this study was to determine whether BC measurements obtained from routine CT scans by use of a fully automated deep learning algorithm could predict subsequent cardiovascular events independently from weight, BMI, and additional cardiovascular risk factors. METHODS. This retrospective study included 9752 outpatients (5519 women and 4233 men; mean age, 53.2 years; 890 patients self-reported their race as Black and 8862 self-reported their race as White) who underwent routine abdominal CT at a single health system from January 2012 through December 2012 and who were given no major cardiovascular or oncologic diagnosis within 3 months of undergoing CT. Using publicly available code, fully automated deep learning BC analysis was performed at the L3 vertebral body level to determine three BC areas (skeletal muscle area [SMA], visceral fat area [VFA], and subcutaneous fat area [SFA]). Age-, sex-, and race-normalized reference curves were used to generate z scores for the three BC areas. Subsequent myocardial infarction (MI) or stroke was determined from the electronic medical record. Multivariable-adjusted Cox proportional hazards models were used to determine hazard ratios (HRs) for MI or stroke within 5 years after CT for the three BC area z scores, with adjustment for normalized weight, normalized BMI, and additional cardiovascular risk factors (smoking status, diabetes diagnosis, and systolic blood pressure). RESULTS. In multivariable models, age-, race-, and sex-normalized VFA was associated with subsequent MI risk (HR of highest quartile compared with lowest quartile, 1.31 [95% CI, 1.03-1.67], p = .04 for overall effect) and stroke risk (HR of highest compared with lowest quartile, 1.46 [95% CI, 1.07-2.00], p = .04 for overall effect). In multivariable models, normalized SMA, SFA, weight, and BMI were not associated with subsequent MI or stroke risk. CONCLUSION. VFA derived from fully automated and normalized analysis of abdominal CT examinations predicts subsequent MI or stroke in Black and White patients, independent of traditional weight metrics, and should be considered an adjunct to BMI in risk models. CLINICAL IMPACT. Fully automated and normalized BC analysis of abdominal CT has promise to augment traditional cardiovascular risk prediction models.

Comprehensive abdominal composition evaluation of rectal cancer patients with anastomotic leakage compared with body mass index-matched controls.

Anastomotic leakage (AL) is a fatal complication in patients with rectal cancer after undergoing anterior resection. However, the role of abdominal composition in the development of AL has not been studied. To investigate the relationship between abdominal composition and AL in rectal cancer patients after undergoing anterior resection. A retrospective case-matched cohort study was conducted. Complete data for 78 patients with AL were acquired and this cohort was defined as the AL group. The controls were matched for the same sex and body mass index (± 1 kg/m2). Parameters related to abdominal composition including visceral fat area (VFA), subcutaneous fat area (SFA), subcutaneous fat thickness (SFT), skeletal muscle area (SMA), skeletal muscle index (SMI), abdominal circumference (AC), anterior to posterior diameter of abdominal cavity (APD), and transverse diameter of abdominal cavity (TD) were evaluated based on computed tomography (CT) images using the following Hounsfield Unit (HU) thresholds: SFA: -190 to -30, SMA: -29 to 150, and VFA: -150 to -20. The significance of abdominal composition-related parameters was quantified using feature importance analysis; an artificial intelligence method was used to evaluate the contribution of each included variable. Two thousand two hundred and thirty-eight rectal cancer patients who underwent anterior resection from 2010 to 2020 in a large academic hospital were investigated. Finally, 156 cases were enrolled in the study. Patients in the AL group showed longer operative time (225.03 ± 55.29 vs 207.17 ± 40.80, P = 0.023), lower levels of preoperative hemoglobin (123.32 ± 21.17 vs 132.60 ±1 6.31, P = 0.003) and albumin (38.34 ± 4.01 vs 40.52 ± 3.97, P = 0.001), larger tumor size (4.07 ± 1.36 vs 2.76 ± 1.28, P < 0.001), and later cancer stage (P < 0.001) compared to the controls. Patients who developed AL exhibited a larger VFA (125.68 ± 73.59 vs 97.03 ± 57.66, P = 0.008) and a smaller APD (77.30 ± 23.23 vs 92.09 ± 26.40, P < 0.001) and TD (22.90 ± 2.23 vs 24.21 ± 2.90, P = 0.002) compared to their matched controls. Feature importance analysis revealed that TD, APD, and VFA were the three most important abdominal composition-related features. AL patients have a higher visceral fat content and a narrower abdominal structure compared to matched controls.

Visceral Adipose Tissue Assessment Enhances the Prognostic Value of GLIM Criteria in Patients with Gastric Cancer Undergoing Radical Gastrectomy after Neoadjuvant Treatment

The Global Leadership Initiative on Malnutrition (GLIM) criteria has been recently published for diagnosing malnutrition in adults. However, the validity of the GLIM criteria has not been well-established in patients with gastric cancer (GC) treated with neoadjuvant treatment (NT) followed by radical gastrectomy. The present study aimed to explore the prognostic value of GLIM-defined malnutrition before NT and after NT in GC patients and to investigate whether additional visceral adipose tissue (VAT) assessment could improve the predictive power of the GLIM criteria for NT-related adverse events (AEs) and long-term survival. GC patients who underwent radical surgery after NT from June 2016 to June 2020 were enrolled in this study. The cross-sectional areas of total skeletal muscle (TSM) and VAT were measured using computed tomography (CT) before NT and after NT. GLIM-defined malnutrition was diagnosed using the two-step approach, including nutritional risk screening and diagnostic assessment. Low VAT was also added to the diagnosis of malnutrition in this study. The predictive value of these malnutrition diagnoses for NT-related AEs, and long-term survival was evaluated in GC patients. A total of 182 GC patients were included in this study, of which 66 (36.3%) patients before NT and 55 (30.2%) patients after NT were diagnosed with GLIM-defined malnutrition, respectively. In addition to GLIM-defined malnutrition, 54 (29.7%) patients had additional low VAT before NT, and 39 (21.4%) patients had additional low VAT after NT. GLIM-defined malnutrition alone before NT was not associated with NT-related AEs in GC patients. The addition of low VAT to GLIM-defined malnutrition led to a significant predictive value for NT-related AEs. Furthermore, GLIM-defined malnutrition before NT and after NT were both identified as independent risk factors for overall survival (OS) and disease-free survival (DFS). The combination of low VAT and GLIM-defined malnutrition showed a higher hazard ratio for the prediction of OS and DFS both before NT and after NT. The addition of VAT assessment using CT improved the predictive value of GLIM-defined malnutrition for NT-related AEs and long-term survival in GC patients treated with NT followed by radical gastrectomy, which further supports the prognostic importance of assessing adipose tissue simultaneously during the routine nutritional assessment in patients with cancer.