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Sarcopenia and sarcopenic obesity in patients with complex abdominal wall hernias
The American Journal of Surgery (2016) -, -–-
Sarcopenia and sarcopenic obesity in patients with complex abdominal wall hernias John M. Rinaldi, B.S.a, Abby K. Geletzke, M.D.a, Brett E. Phillips, Ph.D.a, Jamie Miller, R.N., C.R.N.P.a, Thomas M. Dykes, M.D.b, David I. Soybel, M.D.a,c,* a
Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA; Department of Radiology, The Pennsylvania State University, College of Medicine, Hershey, PA, USA; c Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, PA, USA b
KEYWORDS: Sarcopenia; Sarcopenic obesity; Ventral hernia repair; Micronutrient imbalance; Outcomes; Obesity
Abstract BACKGROUND: Chronic muscle wasting, or sarcopenia, has been associated with poor-health outcomes after major surgical procedures. Here, we explore the utility of CT-generated determinations of sarcopenia as markers of risk in patients undergoing evaluation for complex ventral hernia repair. METHODS: In 148 successive patients being evaluated for complex ventral hernia repair, CT scans were analyzed retrospectively for attributes of the hernia and indices of core-muscle mass, correlating them with preoperative clinical/laboratory profiles and outcomes in 82 patients who had undergone surgery. RESULTS: Prevalence of sarcopenia, and sarcopenia corrected for obesity, was 26% and 20% respectively. Sarcopenia was associated with age, some laboratory indicators, and increased hospital length of stay but not with a higher likelihood of surgical site occurrence. CONCLUSIONS: Obesity may obscure the value of sarcopenia as a marker of metabolic disturbance and postoperative outcome. Image-based measurements of core-muscle mass should be used with caution as predictors of risk in similar surgical populations. Ó 2016 Elsevier Inc. All rights reserved.
Originally described as a consequence of aging, sarcopenia has been defined as a loss of muscle mass associated with impairment of muscle functionality including alterations in strength, balance, exercise capacity, and efficiency
There were no relevant financial relationships or any sources of support in the form of grants, equipment, or drugs. The authors declare no conflicts of interest. * Corresponding author. Tel.: 11-717-531-5272; fax: 11-717-5310884. E-mail address: [email protected] Manuscript received January 26, 2016; revised manuscript March 16, 2016 0002-9610/$ - see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjsurg.2016.03.003
of glucose metabolism.1–3 The loss of muscle mass and its impact has been observed in catabolic states induced by cirrhosis, immunosuppressive agents, and advanced malignancies.4–9 Moreover, it has been suggested that imaging modalities such as computerized tomography (CT) scanning may provide objective and independent measures of volume and density of core musculature.10 In patients with specific malignancies or those undergoing major surgical procedures such as liver transplantation, open aneurysm repair, or major visceral resections, image-based measures of reduced muscle mass has been associated with increased morbidity, longer hospital stays, higher infection rates, and higher mortality.4–9 Similarly, the metabolic burdens of
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general laparotomy and complex abdominal wall hernia repair may be substantial, suggesting that sarcopenia could potentially serve as a predictor of poor recovery and adverse outcomes in a population of patients undergoing complex abdominal hernia repair.11–13 Attention has recently been focused on sarcopenia associated with obesity, an association that is now referred to as an independent entity, ‘‘sarcopenic obesity.’’ This condition, attributed to the infiltration of muscle with fat and associated with inflammatory states such as metabolic syndrome, has been linked with poor long-term health outcomes including poor survival after resection of cancer and mortality in cardiovascular disease.14–17 Obesity itself is a well recognized but not entirely consistent risk factor for adverse outcomes after major abdominal operations.18,19 A singular challenge of the patient group with large and recurrent ventral hernias is the overwhelming prevalence of obesity, a likely driver of many other operative comorbidities. Efforts to identify factors that disturb metabolism or influence surgical outcomes in patients with complex ventral hernias should not underplay the role of obesity. To our knowledge, the prevalence and implications of sarcopenia in the formation and repair of abdominal wall hernias has not been reported. Given the substantial anabolic requirements for recovery after major abdominal operations, we initiated this study to evaluate the hypothesis that sarcopenia would be associated with adverse outcomes and delays in recovery within this medically complex patient group.11,12 The main objective of this study was to use CT-based measurements to determine the prevalence of sarcopenia and sarcopenic obesity in this patient population. An additional objective was to determine whether these measurements would be associated with preoperative clinical and laboratory profiles or postoperative recovery and complications.
elsewhere.20 These laboratory measures included white blood cell count, hemoglobin, mean corpuscular volume, red blood cell distribution width, blood urea nitrogen, creatinine, random glucose, C-reactive protein, albumin, total protein, calcium, zinc, alkaline phosphatase, alanine aminotransferase (ALT), and aspartate ALT. Eight common comorbidities were tracked, including: diabetes, obstructive sleep apnea or lung disease, chronic renal insufficiency, hepatitis or liver disease, hypertension, hyperlipidemia or statin use, gastroesophageal reflux disease, and anxiety or depression. CT image analysis was carried out with Aquarius iNtuition software (version 4.4.7, TeraRecon, Inc., San Mateo, CA).
Methods Patient cohort Data were collated from a prospectively maintained database of 159 consecutive patients referred for evaluation of primary or recurrent complex ventral hernias by a single general surgeon from July 2011 to March 2013 at the Penn State Milton S. Hershey Medical Center. Routine patient assessment included detailed history and physical, and when indicated, an abdominal CT. Inclusion criteria included all the patients 18 years or more of age with a CT scan encompassing all abdominal wall defects and a body habitus that was adequately visualized within the confines of the scanning field. Patients were excluded from the study if clinical documentation was incomplete. Standardized laboratory evaluations including markers for stress, anemia, micronutrient imbalance, and organ functionality were performed in most patients, as described
Dimensions of the hernia defect and hernia contents Attributes of the hernia provide perspective on comparability of patient cohorts and strategies of repair.21–24 CT images were used to quantify the maximum dimensions of the hernia defect (transverse, longitudinal) and hernia sac (transverse, longitudinal, anterioposterior).25 The hernia defect area was calculated using the formula for the area of an ellipsis (A): A5ðpÞðaÞðbÞ
where a and b are the largest transverse and longitudinal measurements divided by 2, respectively. Because different attributes of the hernia defect are potentially relevant to methods of repair and the biological stress placed on the patient, we analyzed images for (a) the area of the single largest defect if multiple defects were present, and reported as the largest defect area (cm2); (b) the sum of the areas of all observable defects on CT, and reported as the summed defect area (cm2); and (c) the total area of the abdominal wall containing all defects, reported as the abdominal defect area (cm2), calculated as the product of the distance between the most lateral margins (maximum transverse) and the most superior aspect of the cranial to most inferior aspect of the caudal (maximum longitudinal) defects. Thus, the abdominal defect area represents the total area of potential weakness in the abdominal wall. Hernia volume was estimated using the formula of an ellipsoid (V): V5ð4=3ÞðpÞðr1Þðr2Þðr3Þ
with r1, r2, and r3 as the largest transverse, longitudinal, and anteroposterior distances divided by 2, respectively.25 The established parameters to describe the hernia volume include both the largest hernia volume (cm3) and the summed hernia volume (cm3), with the latter used as a surrogate for the loss of domain (volume of tissue extending beyond the confines of the peritoneum).
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Dimensions of core-muscle and indices of sarcopenia
recorded and defined to include seroma, surgical site infection, and nonhealing or breakdown of the incision site.
Abdominal cross-sectional images were used to estimate core skeletal muscle, based on prior reports.10,26 As seen in Fig. 1, skeletal muscle area (SMA, cm2) was determined by first identifying the mid-vertebral body of the third lumbar vertebra. The Hounsfield Unit density threshold was set to a range of 229 to 1150 to encompass the skeletal musculature.10 The images were assessed for SMA with the muscle bodies of the psoas, erector spinae, quadratus lumborum, transversus abdominus, rectus abdominus, and internal and external obliques. The average skeletal muscle density (H.U.) was also recorded. Similar to body mass index (BMI), the SMA was normalized for patient height squared and reported as the skeletal muscle index (SMI, cm2/m2). Based on previously established thresholds in obese patients, sarcopenia was defined as the presence of an SMI of 52.4 cm2/m2 or less in men and 38.5 cm2/m2 or less in women.26
Results
Outcomes and analysis Patient demographics were summarized with descriptive statistics. Assuming a non-Gaussian distribution, Spearman correlations were used for continuous data variables. Student t tests were used for group comparison. Chi-square analysis was used for contingency tables. Statistical significance was defined as a P value of less than .05. Surgical outcomes were assessed for length of stay (LOS), duration of ileus, postoperative complications, and recurrence. Also, 90-day postoperative SSOs (surgical site occurrences) were
Clinical and laboratory-based attributes of the patient cohort Among 159 consecutive patients referred for the evaluation of hernia repair, CT scans were available for 152 (95.6%). Full clinical documentation was available for 148 patients. The mean age was 56.8 years, with a female predominance of approximately 3:2. On average, men had lower BMIs (35.0 vs 39.9, P 5 .0009) and fewer comorbid conditions (2.2 vs 3.1, P 5 .009). The range for BMI in the cohort was 20.4 to 72 kg/m2, with only 2 (1%) patients classified as having a normal BMI (%24.9 kg/m2). Nineteen (13%) were classified as overweight (%29.9 kg/m2) and 127 (86%) were classified as obese (R30 kg/m2). The average number of prior hernia repairs was 1.5 per patient with a range of 0 to 9. Details of the biochemical profiles of this patient cohort have been documented in prior reports, with evidence of low-grade systemic inflammation in more than 40% and micronutrient imbalances seen in approximately 30% to 40%.20
Imaging-based attributes of abdominal wall hernias and core-muscle mass Anatomic attributes of the ventral hernias and indices of core-muscle mass are presented in Table 1. For the entire cohort, the average abdominal defect area was 170.9 cm2 and the mean of the summed hernia volumes were more than 1200 cm3, attesting to the reconstructive complexity of this patient population. The dimensions of hernia defects and volume measurements of the hernias tended to be larger in men than in women, and the difference was significant with respect to the average abdominal defect area (P , .05). In addition, SMA and SMI were significantly higher in men (P , .0001).
Prevalence of sarcopenia and correlations to clinical characteristics
Figure 1 SMA (cm2) was collected at the mid-vertebral body of the third lumbar vertebrae (red), with density windows of 229.0 to 150.0 H U. For this 72-year-old woman with a BMI of 42.5 kg/m2, the average skeletal muscle density was 24.7 H U., SMA was 127.0 cm2, and the SMI was 60.4 cm2/m2. SMA, skeletal muscle area; BMI 5 body mass index; SMI 5 skeletal muscle index. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
Sarcopenia was found in 38 (26%) of the 148 patients. As reported previously,26 sarcopenia was more common among men than among women, with 22 (37%) of the 60 men and 16 (18%) of the 88 women meeting predetermined criteria for sarcopenia. Sarcopenic obesity was found to affect 29 (20%) of the 148 patients, seen in 16 (27%) men and 13 (15%) women. Exclusively looking at the 127 obese patients in the cohort, 29 (23%) were identified as having sarcopenia, including 16 (33%) of the 49 obese men and 13 (17%) of the 78 obese women. Previously established correlations between age and sarcopenia were confirmed in this patient cohort.2,27
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4 Table 1
Dimensions of computed hernia defects, loss of domain, and indices of core-muscle mass All n 5 147 Mean 6 SD 2
Largest defect area (cm ) Summed defect area (cm2) Abdominal defect area (cm2) Largest hernia volume (cm3) Summed hernia volume (cm3) Skeletal muscle area (cm2) Skeletal muscle index (cm2/m2) Skeletal muscle density (H.U.)
87.4 95.9 172 1,156 1,210 143.5 50.5 23.9
6 6 6 6 6 6 6 6
123.5 124.7 172.5 2,326 2,358 38 10.5 7.9
Men n 5 58 Mean 6 SD 112.1 120.5 208.6 1,111 1,166 1,73.7 55.25 24.91
6 6 6 6 6 6 6 6
147.5 148.2 197.9 1,735 1,823 33.6 10.2 7.987
Women n 5 89 Mean 6 SD 71.27 79.86 148.2 1,184 1,239 123.8 47.37 23.31
6 6 6 6 6 6 6 6
102.7 104.4 150.2 2,649 2,659 25.84 9.438 7.77
P value .0497* .0532 .0374* .8529 .8560 ,.0001* ,.0001* .2299
SD 5 standard deviation. *Statistical significance.
Fig. 2A illustrates the inverse correlation observed between age and SMI in both men (P 5 .0009, r 5 2.42) and women (P 5 .0006, r 5 2.36). Sarcopenic patients were
also significantly older than nonsarcopenic patients (62.8 vs 54.9 years, respectively, P 5 .0004). In contrast, Fig. 2B demonstrates the direct relationship between BMI and SMI, which positively correlated in men (P 5 .0078, r 5 1.34) and women (P , .0001, r 5 1.52). Overall, sarcopenic patients were significantly less obese than their nonsarcopenic counterparts (BMI 34.0 vs 39.3 kg/m2, P 5 .0012).
Associations of sarcopenia with clinical characteristics, hernia attributes, and laboratory evaluations Summarized in Table 2 are significant relationships between SMI and attributes of age (P , .0001, r 5 2.39) and BMI (P 5 .0007, r 5 1.28). Clear associations with SMI were not observed with the number of comorbid conditions or the number of prior repairs. Furthermore, no relationship was seen between SMI and the presence of any of the comorbidities evaluated in this study, including: diabetes, obstructive sleep apnea or lung disease, chronic renal insufficiency, hepatitis or liver disease, hypertension, hyperlipidemia or statin use, gastroesophageal reflux disease, and anxiety or depression (data not shown). Although there was found to be a significant correlation between SMI and the average abdominal defect area (P 5 .0317, r 5 1.18), other significant associations between SMI and hernia characteristics were lacking. Positive associations were observed for SMI with serum hemoglobin and alanine ALT. No consistent associations emerged between SMI with other biologic markers investigated in this study.
Hernia attributes and core-muscle mass in the operative cohort Figure 2 Scatter-plot of Age and BMI vs SMI. (A) Correlation between age (years) and skeletal muscle index (cm2/m2) in men (P 5 .0029, r5 2.38) and women (P , .0001, r 5 2.43), (B) Correlation between BMI (kg/m2) and skeletal muscle index (cm2/m2) in men (P 5 .0194, r 5 1.31) and women (P , .0001, r 5 1.50).
A total of 82 underwent elective hernia repair with 2-year follow-up. Summarized in Table 3 are the hernia dimensions and metrics of core-muscle mass in patients who underwent surgery compared with those who have yet to undergo elective operative repair. Patients who underwent
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surgery were significantly younger (54.6 vs 60.1 year, P 5 .0035) and had lower BMIs (34.7 vs 42.1 kg/m2, P , .0001). Although the surgical cohort had similar numbers of prior repairs, they had fewer comorbidities (2.5 vs 3.0, P 5 .0395). Moreover, the surgical cohort had significantly higher muscle density (26.5 vs 20.7 H U., P , .0001), larger hernia volumes (568.0 vs 1954.0 cm3, P 5 .0005), and summed hernia volumes (620.8 vs 1924.0 cm3, P 5 .0005). These data reflect a bias toward surgical selection of healthier patients for elective hernia repair. In our practice, elective complex hernia repair is typically avoided in patients with a BMI greater than 40 kg/m2, poorly controlled diabetes, or active tobacco usage. It is our practice to work with patients and their primary care providers to improve diabetic control, activity tolerance, and controlled weight loss before committing to these procedures.
Table 2 Correlations of SMI with clinical, laboratory, and CT-based attributes SMI (cm2/m2) n5
Pearson r
Clinical attributes and hernia characteristics Age (years) 147 2.39 BMI (kg/m2) 147 .28 No. comorbidities/patient 147 2.10 No. prior repairs/patient 147 2.01 Largest defect area (cm2) 147 .13 Summed defect area (cm2) 147 .13 Abdominal defect area (cm2) 147 .18 147 .03 Largest hernia volume (cm3) Summed hernia volume (cm3) 147 .04 Skeletal muscle density (H.U.) 147 .39 Laboratory-based assessments WBC (K/mL) 131 .07 HgB (g/dL) 131 .31 MCV (fL) 131 2.08 RDW (%) 129 .01 BUN (mg/dL) 126 2.17 Cr (mg/dL) 132 2.04 Random glucose (mg/dL) 124 2.05 CRP (mg/dL) 107 .06 Albumin (g/dL) 119 .14 Total protein (g/dL) 105 .07 Calcium (mg/dL) 121 .06 Zinc (mg/dL) 110 .09 Alkaline phosphatase (U/L) 109 2.14 ALT (U/L) 113 .19 AST (U/L) 113 2.01
5
P ,.0001* .0007* .2166 .936 .1082 .1187 .0317* .6991 .6696 ,.0001* .4122 .0003* .3604 .9166 .0600 .6138 .6192 .5574 .1278 .4715 .5283 .3694 .1352 .0486* .8907
Outcomes in patients who underwent abdominal wall reconstruction In 47 (57%) of the 82 patients who underwent complex ventral hernia repair (cVHR), mesh overlay approaches were used, with or without anterior component separation procedures. In the remainder, open underlay or retrorectus approaches were used. In 63 (77%) cases, extensive (R45 minutes) lysis of adhesions were documented. The SSO rate in the operative cohort was similar to those previously described.21,28 As summarized in Table 4, 28 (34%) patients in this comorbid population had an SSO and 17 (21%) patients had a recurrence with an average length of follow-up of 17 6 12.3 months. The average duration of ileus, as defined by the interval from operation to passage of flatus, was 3.5 days. The average LOS was 5.8 days. When adjusted for the Ventral Hernia Working
ALT 5 alanine aminotransferase; AST 5 aspartate aminotransferase; BUN 5 blood urea nitrogen; Cr 5 creatinine; CRP 5 C-reactive protein; HgB 5 hemoglobin; MCV 5 mean corpuscular volume; RDW 5 red blood cell distribution width; SD 5 standard deviation; WBC 5 white blood cell. *Statistical significance.
Table 3 Hernia and core-muscle mass characteristics in patients who underwent ventral hernia repair and patients who have yet to undergo surgery Surgical n 5 82 Mean 6 SD Age (y) BMI (kg/m2) No. comorbidities/patient No. prior repairs/patient Skeletal muscle area (cm2) Skeletal muscle index (cm2/m2) Skeletal muscle density (H.U.) Largest defect area (cm2) Summed defect area (cm2) Abdominal defect area (cm2) Largest hernia volume (cm3) Summed hernia volume (cm3) BMI 5 body mass index; SD 5 standard deviation. *Statistical significance.
54.57 34.66 2.451 1.402 144.9 50.52 26.49 70.34 79.61 155.8 568 620.8
6 6 6 6 6 6 6 6 6 6 6 6
12.1 6.8 1.786 1.699 40.46 10.47 7.273 101.3 104.9 151.7 1,055 1,166
Nonsurgical n 5 65 Mean 6 SD 60.06 42.08 3.046 1.538 141.7 50.42 20.73 108.9 116.4 192.4 1,954 1,924
6 6 6 6 6 6 6 6 6 6 6 6
9.767 9.379 1.643 1.668 34.81 10.5 7.446 144.8 144.1 195 3,151 3,156
P value .0035* ,.0001* .0395* .6277 .6145 .9533 ,.0001* .0600 .0754 .2022 .0005* .0005*
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6 Table 4
Effect of sarcopenia and sarcopenic obesity on outcomes after ventral hernia repair
No. patients with SSO No. patients with recurrence Duration of ileus (d) LOS (d)
No. patients with SSO No. patients with recurrence Duration of ileus (d) LOS (d)
All hernia repairs n 5 82
Nonsarcopenic patients n 561
Sarcopenic patients n 521
P value
28 (34%) 17 (20.7%)
24 (39.0%) 13 (21.3%)
4 (19.0%) 4 (19.0%)
.1137 1.0000
Mean 6 SD
Mean 6 SD
Mean 6 SD
3.549 6 2.056 5.756 6 3.789
3.23 6 1.596 5.197 6 2.695
4.476 6 2.874 7.381 6 5.714
.0156* .0218*
Nonsarcopenic-obese patients n 5 70
Sarcopenic-obese patients n 5 12
P value
25 (35.7%) 14 (20.0%)
3 (25.0%) 3 (25.0%)
.7429 .7061
Mean 6 SD
Mean 6 SD
3.314 6 1.655 5.243 6 2.59
4.917 6 3.397 8.75 6 7.225
.0117* .0025*
LOS 5 length of stay; SD 5 standard deviation; SSO 5 surgical site occurrence. *Statistical significance.
Group grading system, SSOs for grade 1 (n 5 7), grade 2 (n 5 51), and grade 3 (n 5 24) occurred in 1 (14%), 16 (31%), and 11 (46%) patients, respectively.21,22 Of the 82 patients who underwent surgery, 21 (26%) met CT-based criteria for sarcopenia. As shown in Table 4, the rates of SSO and recurrence were not significantly prolonged in sarcopenic patients compared with their nonsarcopenic counterparts; however, LOS (7.4 vs 5.2 days, P 5 .0218) and duration of ileus (4.5 vs 3.2 days, P 5 .0156) were both significantly prolonged in the sarcopenic population. Twelve (15%) patients in the surgical treatment group were found to have sarcopenic obesity, affecting 6 (17%) of the 36 men and 6 (13%) of the 46 women. Those with sarcopenic obesity did not have significantly dissimilar rates of SSO or recurrence, but did, again, have significantly longer LOS (8.8 vs 5.2 days, P 5 .0025) and duration of ileus (4.9 vs 3.3 days, P 5 .0117). A number of attributes of the abdominal wall defects were correlated to duration of ileus and LOS, including the areas of largest measured defect (P 5 .0011 and P 5 .0039, respectively), the sum of defect areas (P 5 .0016 and P 5 .0023, respectively) and the area of abdominal wall involving any of the hernias (P 5 .0038 and P 5 .0048, respectively). The volume of herniated contents, including the largest (P 5 .0092) and summed (P 5 .0113) volumes, were closely correlated to duration of ileus but not clearly to LOS. Skeletal muscle density, but not SMA or SMI, had a significant inverse correlation with LOS (P 5 .0237), but not with the duration of ileus (P 5 .0534). As shown in Fig. 3A, B, both the largest and summed hernia volume were predictive of SSO (P 5 .0043 and P 5 .0046, respectively) and recurrence (P 5 .0073 and P 5 .0072, respectively). In contrast to patients without an SSO, those with this complication had significantly elevated SMI (48.7 vs 54.0 cm2/m2, P 5 .0299) and BMI (33.4 vs 37.1 kg/m2, P 5 .0187), suggesting that an
elevated BMI, and not a reduced SMI, is a stronger driver of SSO.
Comments Sarcopenic obesity has been recognized as a predictor of long-term health and is associated with metabolic syndrome.14,17 Sarcopenia and sarcopenic obesity have been shown as potential markers for adverse outcomes in surgically treated conditions.4–7,9,26 Given the substantial metabolic requirements for recovery after major abdominal operations, we evaluated whether sarcopenia was associated with adverse outcomes and delays in recovery in these patients.11,12 To our knowledge, this is the first report exploring the prevalence and implications of sarcopenia in a complex ventral hernia repair (VHR) patient population. The principal findings of this study were: first, that 26% of the patients who underwent evaluation for complex hernia repair were sarcopenic, and 1 in every 5 patients met the criteria for sarcopenic obesity; second, that lower muscle mass in this population was not clearly associated with serum indices of metabolic disturbance, micronutrient imbalance, or low-grade systemic inflammation; and, third, in-hospital and early follow-up data suggested that the CTbased indices of core musculature were associated with increased LOS, largely due to the duration of ileus but were otherwise unreliable discriminators for adverse postoperative events in our patient population. We also noted that positive outcomes may be associated with higher coremuscle density (H.U.), perhaps reflecting a higher quality tissue containing less fatty infiltrate. It should be noted that our study is not fully powered to identify significant differences in the likelihood of SSO between sarcopenic and nonsarcopenic patients. However, as shown in Table 4,
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Figure 3 Bar graph of hernia volume (cm3) and surgical outcomes. Error bars represent standard deviation. (A) Largest hernia volume in patients with and without SSO (1,022.0 6 1,674.0 vs 332.6 6 327.9 cm3, P 5 .0043) and total hernia volume in patients with and without SSO (1,120.0 6 1,859.0 vs 362.0 6 339.8 cm3, P 5 .0046), (B) Largest hernia volume in patients with and without hernia recurrence (1,171 6 2,043 vs 410.4 6 492.5 cm3, P 5 .0073) and total hernia volume in patients with and without hernia recurrence (1,289 6 2,296 vs 446 6 501.9 cm3, P 5 .0072). SSO 5 surgical site occurrence.
the preliminary analysis indicated that the incidence of SSO among sarcopenic patients was in fact lower than among nonsarcopenic patients. This observation argues against a principal hypothesis of the study, that sarcopenia would be associated with unfavorable outcomes for SSO. An additional implication is that it is unlikely that the trend would be reversed with greater numbers of patients. In contrast to CT-derived measurements of core-muscle characteristics, the CT-based attributes of the hernia, including the size (area) and the loss of domain (volume) were more closely related to postoperative events. Interestingly, increased hernia area seemed to correlate with LOS, whereas increased hernia volume was more predictive of SSO and recurrence. This is congruent with existing literature, as the variables most clearly associated with extended LOS and postoperative adverse occurrence include the overall medical complexity of the patient and the attributes of the hernia itself.21–24,28 Our study provides the additional perspective that the physical attributes of the
defect and the content could be used as additional parameters for risk adjustment and comparability of studies reporting outcomes. In this cohort of referred patients, more than 85% were obese. Our findings support the impression that higher BMI levels are likely to be confounders in the correlation between age and muscle mass.29 In this study, as in others, core-muscle mass generally increases with BMI.30 Our previous work has confirmed that obesity, when defined by a BMI higher than 30, is associated with low-grade disturbances in circulating micronutrients and markers of systemic inflammation.20 Furthermore, it has been suggested that, in groups of surgical patients with advanced malignancy or candidates for organ transplant, systemic inflammation and nutritional imbalances are associated with loss of muscle mass and deconditioning, consequentially leading to antagonized recovery, healing, and complication rates.4–9,16,26,30 Thus, in the obese patient, the increased metabolic requirements for maintaining core-muscle mass
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and functionality could potentially interfere with the acute metabolic requirements of surgical stress, potentially influencing or masking poor outcomes.29,30 Although sarcopenia has been shown to adversely influence outcomes in other surgical populations, the results here suggest that caution should be taken when using analytic morphometrics of muscle mass in the obese and morbidly obese patient. Although a number of studies with patient populations similar to our own have emphasized the contributions of obesity on imbalances of muscle metabolism, these findings are not always consistent.14,15,20 A strong relationship was demonstrated to exist between core musculature and obesity. Patients with lower muscle mass recovered more slowly in the hospital after complex VHR but, in contrast to prior studies of sarcopenia in other surgical patient groups, they were not clearly more susceptible to adverse wound occurrences or systemic complications. Although our study does not provide information to directly address this potential discrepancy, the following observations may be relevant. The first is that the influence of sarcopenia on outcomes after surgery has previously been studied in patient groups with malignancy or severe liver disease.4–6,8,9,31 In such patients, there is a substantial likelihood of poor-protein intake as well as malignancyinduced systemic inflammation and catabolism. The confluence of these conditions leads directly to muscle wasting and deconditioning, even among patients who are also obese. The primary indication for surgery is also a principal driver for sarcopenia. Under these conditions, sarcopenia is a reporter of serious postoperative adverse events because it has the same underlying causes of exacerbated inflammation, catabolism, hypoalbuminemia, and poor-nutrient intake. In this regard, we have reported20 that the complex VHR patients are not generally malnourished or hypoalbuminemic. In this group, however, there is a substantial prevalence of low-grade systemic inflammation (as measured by serum C-reactive protein levels) and mild imbalances in micronutrient metabolism not nearly as severe as those found in patients with advanced malignancy or organ failure and driven not by the presence of the hernia but the presence of comorbid conditions, in particular obesity. Moreover, in experimental studies, we recently demonstrated that mild diet-induced imbalances in micronutrients such as zinc can lead to a self-sustaining state of low-grade systemic inflammation and disturbances in other micronutrients involved in oxidative stress. Also impaired was the resolution of macrophage-driven responses to chemical peritonitis and mechanical irritation of the peritoneum, leading to prolonged ileus.32 Thus, we might speculate that when the primary disease is the principal driver for sarcopenia, catabolic effects and the associated impairments in metabolism of macronutrients and micronutrients are substantial, thereby increasing susceptibility to more severe wound and systemic complications after major abdominal operations. In contrast, when sarcopenia is present but
incidental to the condition requiring surgery, metabolic disturbance is milder and would be reflected in subtle impairments in recovery and convalescence. Further studies, both clinical and experimental, are required to tease out the role of micronutrient imbalance, mild systemic inflammation, and oxidative stress in responses to acute surgical stresses in medically complex patients. In summary, our investigations demonstrated that indices of sarcopenia and core-muscle mass did not reliably reflect underlying biological disturbance or predict adverse outcomes and delays in recovery after complex hernia repair. Weaknesses in this study include a retrospective design, bias in selection of surgical candidates, and the relatively small subgroup of patients with sarcopenic obesity. Recognizing these limitations, our findings provide previously unreported, yet somewhat disappointing, evidence that in a largely obese population, the CT-based attributes of muscle mass fail to serve as reporters of preexisting biological stress or as predictors of outcomes after complex abdominal wall hernia repair. In contrast, the anatomic attributes of complex abdominal wall herniasdthe dimensions of the defect and volume of herniated contentsdcorrelated closely with attributes of core-muscle mass and postoperative outcomes. Here, additional insight may be offered by our findings: obesity, a widely accepted independent risk factor for adverse surgical outcomes, may influence or mask muscle catabolism, mass, and the presence of image-guided surrogate markers of sarcopenia. Thus, the utilization of image-based measurements of coremuscle mass and sarcopenia to gauge negative biologic disturbances and outcomes in a largely obese population undergoing cVHR should be used with caution. Although a globally accepted definition of sarcopenia is yet to emerge, it has been suggested that the diagnosis of sarcopenia can be made more meaningful by including indices of muscle mass and function.3 Future work to examine sarcopenia and sarcopenic obesity in cVHR patients should include concurrent measurements of such indices.
References 1. Rosenberg IH, Roubenoff R. Stalking sarcopenia. Ann Intern Med 1995;123:727–8. 2. Evans WJ. What is sarcopenia? J Gerontol A Biol Sci Med Sci 1995; 50 Spec No:5–8. 3. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing 2010;39:412–23. 4. Peng P, Hyder O, Firoozmand A, et al. Impact of sarcopenia on outcomes following resection of pancreatic adenocarcinoma. J Gastrointest Surg 2012;16:1478–86. 5. Lieffers JR, Bathe OF, Fassbender K, et al. Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery. Br J Cancer 2012;107:931–6. 6. Lee JS, He K, Harbaugh CM, et al. Frailty, core muscle size, and mortality in patients undergoing open abdominal aortic aneurysm repair. J Vasc Surg 2011;53:912–7. 7. Englesbe MJ, Lee JS, He K, et al. Analytic morphomics, core muscle size, and surgical outcomes. Ann Surg 2012;256:255–61.
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8. Montano-Loza AJ, Meza-Junco J, Prado CM, et al. Muscle wasting is associated with mortality in patients with cirrhosis. Clin Gastroenterol Hepatol 2012;10:166–73. 173.e161. 9. Tandon P, Ney M, Irwin I, et al. Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value. Liver Transpl 2012;18:1209–16. 10. Mitsiopoulos N, Baumgartner RN, Heymsfield SB, et al. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol 1998;85:115–22. 11. Moore FD. Bodily changes in surgical convalescence. I. The normal sequence observations and interpretations. Ann Surg 1953;137: 289–315. 12. Lind L. Metabolic gas exchange during different surgical procedures. Anaesthesia 1995;50:304–7. 13. Sadava EE, Krpata DM, Gao Y, et al. Wound healing process and mediators: implications for modulations for hernia repair and mesh integration. J Biomed Mater Res A 2014;102:295–302. 14. Lu CW, Yang KC, Chang HH, et al. Sarcopenic obesity is closely associated with metabolic syndrome. Obes Res Clin Pract 2013;7:e301–7. 15. Park SH, Park JH, Park HY, et al. Additional role of sarcopenia to waist circumference in predicting the odds of metabolic syndrome. Clin Nutr 2014;33:668–72. 16. Tan BH, Birdsell LA, Martin L, et al. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res 2009;15:6973–9. 17. Atkins JL, Whincup PH, Morris RW, et al. Sarcopenic obesity and risk of cardiovascular disease and mortality: a population-based cohort study of older men. J Am Geriatr Soc 2014;62:253–60. 18. Mullen JT, Davenport DL, Hutter MM, et al. Impact of body mass index on perioperative outcomes in patients undergoing major intraabdominal cancer surgery. Ann Surg Oncol 2008;15:2164–72. 19. Mullen JT, Moorman DW, Davenport DL. The obesity paradox: body mass index and outcomes in patients undergoing nonbariatric general surgery. Ann Surg 2009;250:166–72. 20. Geletzke AK, Rinaldi JM, Phillips BE, et al. Prevalence of systemic inflammation and micronutrient imbalance in patients with complex abdominal hernias. J Gastrointest Surg 2014;18:646–55.
9 21. Ventral Hernia Working G, Breuing K, Butler CE, et al. Incisional ventral hernias: review of the literature and recommendations regarding the grading and technique of repair. Surgery 2010;148: 544–58. 22. Kanters AE, Krpata DM, Blatnik JA, et al. Modified hernia grading scale to stratify surgical site occurrence after open ventral hernia repairs. J Am Coll Surg 2012;215:787–93. 23. Krpata DM, Blatnik JA, Novitsky YW, et al. Evaluation of high-risk, comorbid patients undergoing open ventral hernia repair with synthetic mesh. Surgery 2013;153:120–5. 24. Muysoms FE, Miserez M, Berrevoet F, et al. Classification of primary and incisional abdominal wall hernias. Hernia 2009;13:407–14. 25. Tanaka EY, Yoo JH, Rodrigues Jr AJ, et al. A computerized tomography scan method for calculating the hernia sac and abdominal cavity volume in complex large incisional hernia with loss of domain. Hernia 2010;14:63–9. 26. Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 2008;9:629–35. 27. Poehlman ET, Toth MJ, Fishman PS, et al. Sarcopenia in aging humans: the impact of menopause and disease. J Gerontol A Biol Sci Med Sci 1995;50:73–7. 28. Helgstrand F, Rosenberg J, Kehlet H, et al. Nationwide prospective study of outcomes after elective incisional hernia repair. J Am Coll Surg 2013;216:217–28. 29. Gallagher D, Ruts E, Visser M, et al. Weight stability masks sarcopenia in elderly men and women. Am J Physiol Endocrinol Metab 2000; 279:E366–75. 30. Choi KM. Sarcopenia and sarcopenic obesity. Endocrinol Metab 2013; 28:86–9. 31. Levolger S, van Vugt JL, de Bruin RW, et al. Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies. Br J Surg 2015;102:1448–58. 32. Phillips BE, Geletzke AK, Smith PB, et al. Impaired recovery from peritoneal inflammation in a mouse model of mild dietary zinc restriction. Mol Nutr Food Res 2016;60:672–81.
Sarcopenia and sarcopenic obesity in patients with complex abdominal wall hernias John M. Rinaldi, B.S.a, Abby K. Geletzke, M.D.a, Brett E. Phillips, Ph.D.a, Jamie Miller, R.N., C.R.N.P.a, Thomas M. Dykes, M.D.b, David I. Soybel, M.D.a,c,* a
Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA; Department of Radiology, The Pennsylvania State University, College of Medicine, Hershey, PA, USA; c Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, PA, USA b
KEYWORDS: Sarcopenia; Sarcopenic obesity; Ventral hernia repair; Micronutrient imbalance; Outcomes; Obesity
Abstract BACKGROUND: Chronic muscle wasting, or sarcopenia, has been associated with poor-health outcomes after major surgical procedures. Here, we explore the utility of CT-generated determinations of sarcopenia as markers of risk in patients undergoing evaluation for complex ventral hernia repair. METHODS: In 148 successive patients being evaluated for complex ventral hernia repair, CT scans were analyzed retrospectively for attributes of the hernia and indices of core-muscle mass, correlating them with preoperative clinical/laboratory profiles and outcomes in 82 patients who had undergone surgery. RESULTS: Prevalence of sarcopenia, and sarcopenia corrected for obesity, was 26% and 20% respectively. Sarcopenia was associated with age, some laboratory indicators, and increased hospital length of stay but not with a higher likelihood of surgical site occurrence. CONCLUSIONS: Obesity may obscure the value of sarcopenia as a marker of metabolic disturbance and postoperative outcome. Image-based measurements of core-muscle mass should be used with caution as predictors of risk in similar surgical populations. Ó 2016 Elsevier Inc. All rights reserved.
Originally described as a consequence of aging, sarcopenia has been defined as a loss of muscle mass associated with impairment of muscle functionality including alterations in strength, balance, exercise capacity, and efficiency
There were no relevant financial relationships or any sources of support in the form of grants, equipment, or drugs. The authors declare no conflicts of interest. * Corresponding author. Tel.: 11-717-531-5272; fax: 11-717-5310884. E-mail address: [email protected] Manuscript received January 26, 2016; revised manuscript March 16, 2016 0002-9610/$ - see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjsurg.2016.03.003
of glucose metabolism.1–3 The loss of muscle mass and its impact has been observed in catabolic states induced by cirrhosis, immunosuppressive agents, and advanced malignancies.4–9 Moreover, it has been suggested that imaging modalities such as computerized tomography (CT) scanning may provide objective and independent measures of volume and density of core musculature.10 In patients with specific malignancies or those undergoing major surgical procedures such as liver transplantation, open aneurysm repair, or major visceral resections, image-based measures of reduced muscle mass has been associated with increased morbidity, longer hospital stays, higher infection rates, and higher mortality.4–9 Similarly, the metabolic burdens of
2
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general laparotomy and complex abdominal wall hernia repair may be substantial, suggesting that sarcopenia could potentially serve as a predictor of poor recovery and adverse outcomes in a population of patients undergoing complex abdominal hernia repair.11–13 Attention has recently been focused on sarcopenia associated with obesity, an association that is now referred to as an independent entity, ‘‘sarcopenic obesity.’’ This condition, attributed to the infiltration of muscle with fat and associated with inflammatory states such as metabolic syndrome, has been linked with poor long-term health outcomes including poor survival after resection of cancer and mortality in cardiovascular disease.14–17 Obesity itself is a well recognized but not entirely consistent risk factor for adverse outcomes after major abdominal operations.18,19 A singular challenge of the patient group with large and recurrent ventral hernias is the overwhelming prevalence of obesity, a likely driver of many other operative comorbidities. Efforts to identify factors that disturb metabolism or influence surgical outcomes in patients with complex ventral hernias should not underplay the role of obesity. To our knowledge, the prevalence and implications of sarcopenia in the formation and repair of abdominal wall hernias has not been reported. Given the substantial anabolic requirements for recovery after major abdominal operations, we initiated this study to evaluate the hypothesis that sarcopenia would be associated with adverse outcomes and delays in recovery within this medically complex patient group.11,12 The main objective of this study was to use CT-based measurements to determine the prevalence of sarcopenia and sarcopenic obesity in this patient population. An additional objective was to determine whether these measurements would be associated with preoperative clinical and laboratory profiles or postoperative recovery and complications.
elsewhere.20 These laboratory measures included white blood cell count, hemoglobin, mean corpuscular volume, red blood cell distribution width, blood urea nitrogen, creatinine, random glucose, C-reactive protein, albumin, total protein, calcium, zinc, alkaline phosphatase, alanine aminotransferase (ALT), and aspartate ALT. Eight common comorbidities were tracked, including: diabetes, obstructive sleep apnea or lung disease, chronic renal insufficiency, hepatitis or liver disease, hypertension, hyperlipidemia or statin use, gastroesophageal reflux disease, and anxiety or depression. CT image analysis was carried out with Aquarius iNtuition software (version 4.4.7, TeraRecon, Inc., San Mateo, CA).
Methods Patient cohort Data were collated from a prospectively maintained database of 159 consecutive patients referred for evaluation of primary or recurrent complex ventral hernias by a single general surgeon from July 2011 to March 2013 at the Penn State Milton S. Hershey Medical Center. Routine patient assessment included detailed history and physical, and when indicated, an abdominal CT. Inclusion criteria included all the patients 18 years or more of age with a CT scan encompassing all abdominal wall defects and a body habitus that was adequately visualized within the confines of the scanning field. Patients were excluded from the study if clinical documentation was incomplete. Standardized laboratory evaluations including markers for stress, anemia, micronutrient imbalance, and organ functionality were performed in most patients, as described
Dimensions of the hernia defect and hernia contents Attributes of the hernia provide perspective on comparability of patient cohorts and strategies of repair.21–24 CT images were used to quantify the maximum dimensions of the hernia defect (transverse, longitudinal) and hernia sac (transverse, longitudinal, anterioposterior).25 The hernia defect area was calculated using the formula for the area of an ellipsis (A): A5ðpÞðaÞðbÞ
where a and b are the largest transverse and longitudinal measurements divided by 2, respectively. Because different attributes of the hernia defect are potentially relevant to methods of repair and the biological stress placed on the patient, we analyzed images for (a) the area of the single largest defect if multiple defects were present, and reported as the largest defect area (cm2); (b) the sum of the areas of all observable defects on CT, and reported as the summed defect area (cm2); and (c) the total area of the abdominal wall containing all defects, reported as the abdominal defect area (cm2), calculated as the product of the distance between the most lateral margins (maximum transverse) and the most superior aspect of the cranial to most inferior aspect of the caudal (maximum longitudinal) defects. Thus, the abdominal defect area represents the total area of potential weakness in the abdominal wall. Hernia volume was estimated using the formula of an ellipsoid (V): V5ð4=3ÞðpÞðr1Þðr2Þðr3Þ
with r1, r2, and r3 as the largest transverse, longitudinal, and anteroposterior distances divided by 2, respectively.25 The established parameters to describe the hernia volume include both the largest hernia volume (cm3) and the summed hernia volume (cm3), with the latter used as a surrogate for the loss of domain (volume of tissue extending beyond the confines of the peritoneum).
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3
Dimensions of core-muscle and indices of sarcopenia
recorded and defined to include seroma, surgical site infection, and nonhealing or breakdown of the incision site.
Abdominal cross-sectional images were used to estimate core skeletal muscle, based on prior reports.10,26 As seen in Fig. 1, skeletal muscle area (SMA, cm2) was determined by first identifying the mid-vertebral body of the third lumbar vertebra. The Hounsfield Unit density threshold was set to a range of 229 to 1150 to encompass the skeletal musculature.10 The images were assessed for SMA with the muscle bodies of the psoas, erector spinae, quadratus lumborum, transversus abdominus, rectus abdominus, and internal and external obliques. The average skeletal muscle density (H.U.) was also recorded. Similar to body mass index (BMI), the SMA was normalized for patient height squared and reported as the skeletal muscle index (SMI, cm2/m2). Based on previously established thresholds in obese patients, sarcopenia was defined as the presence of an SMI of 52.4 cm2/m2 or less in men and 38.5 cm2/m2 or less in women.26
Results
Outcomes and analysis Patient demographics were summarized with descriptive statistics. Assuming a non-Gaussian distribution, Spearman correlations were used for continuous data variables. Student t tests were used for group comparison. Chi-square analysis was used for contingency tables. Statistical significance was defined as a P value of less than .05. Surgical outcomes were assessed for length of stay (LOS), duration of ileus, postoperative complications, and recurrence. Also, 90-day postoperative SSOs (surgical site occurrences) were
Clinical and laboratory-based attributes of the patient cohort Among 159 consecutive patients referred for the evaluation of hernia repair, CT scans were available for 152 (95.6%). Full clinical documentation was available for 148 patients. The mean age was 56.8 years, with a female predominance of approximately 3:2. On average, men had lower BMIs (35.0 vs 39.9, P 5 .0009) and fewer comorbid conditions (2.2 vs 3.1, P 5 .009). The range for BMI in the cohort was 20.4 to 72 kg/m2, with only 2 (1%) patients classified as having a normal BMI (%24.9 kg/m2). Nineteen (13%) were classified as overweight (%29.9 kg/m2) and 127 (86%) were classified as obese (R30 kg/m2). The average number of prior hernia repairs was 1.5 per patient with a range of 0 to 9. Details of the biochemical profiles of this patient cohort have been documented in prior reports, with evidence of low-grade systemic inflammation in more than 40% and micronutrient imbalances seen in approximately 30% to 40%.20
Imaging-based attributes of abdominal wall hernias and core-muscle mass Anatomic attributes of the ventral hernias and indices of core-muscle mass are presented in Table 1. For the entire cohort, the average abdominal defect area was 170.9 cm2 and the mean of the summed hernia volumes were more than 1200 cm3, attesting to the reconstructive complexity of this patient population. The dimensions of hernia defects and volume measurements of the hernias tended to be larger in men than in women, and the difference was significant with respect to the average abdominal defect area (P , .05). In addition, SMA and SMI were significantly higher in men (P , .0001).
Prevalence of sarcopenia and correlations to clinical characteristics
Figure 1 SMA (cm2) was collected at the mid-vertebral body of the third lumbar vertebrae (red), with density windows of 229.0 to 150.0 H U. For this 72-year-old woman with a BMI of 42.5 kg/m2, the average skeletal muscle density was 24.7 H U., SMA was 127.0 cm2, and the SMI was 60.4 cm2/m2. SMA, skeletal muscle area; BMI 5 body mass index; SMI 5 skeletal muscle index. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
Sarcopenia was found in 38 (26%) of the 148 patients. As reported previously,26 sarcopenia was more common among men than among women, with 22 (37%) of the 60 men and 16 (18%) of the 88 women meeting predetermined criteria for sarcopenia. Sarcopenic obesity was found to affect 29 (20%) of the 148 patients, seen in 16 (27%) men and 13 (15%) women. Exclusively looking at the 127 obese patients in the cohort, 29 (23%) were identified as having sarcopenia, including 16 (33%) of the 49 obese men and 13 (17%) of the 78 obese women. Previously established correlations between age and sarcopenia were confirmed in this patient cohort.2,27
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4 Table 1
Dimensions of computed hernia defects, loss of domain, and indices of core-muscle mass All n 5 147 Mean 6 SD 2
Largest defect area (cm ) Summed defect area (cm2) Abdominal defect area (cm2) Largest hernia volume (cm3) Summed hernia volume (cm3) Skeletal muscle area (cm2) Skeletal muscle index (cm2/m2) Skeletal muscle density (H.U.)
87.4 95.9 172 1,156 1,210 143.5 50.5 23.9
6 6 6 6 6 6 6 6
123.5 124.7 172.5 2,326 2,358 38 10.5 7.9
Men n 5 58 Mean 6 SD 112.1 120.5 208.6 1,111 1,166 1,73.7 55.25 24.91
6 6 6 6 6 6 6 6
147.5 148.2 197.9 1,735 1,823 33.6 10.2 7.987
Women n 5 89 Mean 6 SD 71.27 79.86 148.2 1,184 1,239 123.8 47.37 23.31
6 6 6 6 6 6 6 6
102.7 104.4 150.2 2,649 2,659 25.84 9.438 7.77
P value .0497* .0532 .0374* .8529 .8560 ,.0001* ,.0001* .2299
SD 5 standard deviation. *Statistical significance.
Fig. 2A illustrates the inverse correlation observed between age and SMI in both men (P 5 .0009, r 5 2.42) and women (P 5 .0006, r 5 2.36). Sarcopenic patients were
also significantly older than nonsarcopenic patients (62.8 vs 54.9 years, respectively, P 5 .0004). In contrast, Fig. 2B demonstrates the direct relationship between BMI and SMI, which positively correlated in men (P 5 .0078, r 5 1.34) and women (P , .0001, r 5 1.52). Overall, sarcopenic patients were significantly less obese than their nonsarcopenic counterparts (BMI 34.0 vs 39.3 kg/m2, P 5 .0012).
Associations of sarcopenia with clinical characteristics, hernia attributes, and laboratory evaluations Summarized in Table 2 are significant relationships between SMI and attributes of age (P , .0001, r 5 2.39) and BMI (P 5 .0007, r 5 1.28). Clear associations with SMI were not observed with the number of comorbid conditions or the number of prior repairs. Furthermore, no relationship was seen between SMI and the presence of any of the comorbidities evaluated in this study, including: diabetes, obstructive sleep apnea or lung disease, chronic renal insufficiency, hepatitis or liver disease, hypertension, hyperlipidemia or statin use, gastroesophageal reflux disease, and anxiety or depression (data not shown). Although there was found to be a significant correlation between SMI and the average abdominal defect area (P 5 .0317, r 5 1.18), other significant associations between SMI and hernia characteristics were lacking. Positive associations were observed for SMI with serum hemoglobin and alanine ALT. No consistent associations emerged between SMI with other biologic markers investigated in this study.
Hernia attributes and core-muscle mass in the operative cohort Figure 2 Scatter-plot of Age and BMI vs SMI. (A) Correlation between age (years) and skeletal muscle index (cm2/m2) in men (P 5 .0029, r5 2.38) and women (P , .0001, r 5 2.43), (B) Correlation between BMI (kg/m2) and skeletal muscle index (cm2/m2) in men (P 5 .0194, r 5 1.31) and women (P , .0001, r 5 1.50).
A total of 82 underwent elective hernia repair with 2-year follow-up. Summarized in Table 3 are the hernia dimensions and metrics of core-muscle mass in patients who underwent surgery compared with those who have yet to undergo elective operative repair. Patients who underwent
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surgery were significantly younger (54.6 vs 60.1 year, P 5 .0035) and had lower BMIs (34.7 vs 42.1 kg/m2, P , .0001). Although the surgical cohort had similar numbers of prior repairs, they had fewer comorbidities (2.5 vs 3.0, P 5 .0395). Moreover, the surgical cohort had significantly higher muscle density (26.5 vs 20.7 H U., P , .0001), larger hernia volumes (568.0 vs 1954.0 cm3, P 5 .0005), and summed hernia volumes (620.8 vs 1924.0 cm3, P 5 .0005). These data reflect a bias toward surgical selection of healthier patients for elective hernia repair. In our practice, elective complex hernia repair is typically avoided in patients with a BMI greater than 40 kg/m2, poorly controlled diabetes, or active tobacco usage. It is our practice to work with patients and their primary care providers to improve diabetic control, activity tolerance, and controlled weight loss before committing to these procedures.
Table 2 Correlations of SMI with clinical, laboratory, and CT-based attributes SMI (cm2/m2) n5
Pearson r
Clinical attributes and hernia characteristics Age (years) 147 2.39 BMI (kg/m2) 147 .28 No. comorbidities/patient 147 2.10 No. prior repairs/patient 147 2.01 Largest defect area (cm2) 147 .13 Summed defect area (cm2) 147 .13 Abdominal defect area (cm2) 147 .18 147 .03 Largest hernia volume (cm3) Summed hernia volume (cm3) 147 .04 Skeletal muscle density (H.U.) 147 .39 Laboratory-based assessments WBC (K/mL) 131 .07 HgB (g/dL) 131 .31 MCV (fL) 131 2.08 RDW (%) 129 .01 BUN (mg/dL) 126 2.17 Cr (mg/dL) 132 2.04 Random glucose (mg/dL) 124 2.05 CRP (mg/dL) 107 .06 Albumin (g/dL) 119 .14 Total protein (g/dL) 105 .07 Calcium (mg/dL) 121 .06 Zinc (mg/dL) 110 .09 Alkaline phosphatase (U/L) 109 2.14 ALT (U/L) 113 .19 AST (U/L) 113 2.01
5
P ,.0001* .0007* .2166 .936 .1082 .1187 .0317* .6991 .6696 ,.0001* .4122 .0003* .3604 .9166 .0600 .6138 .6192 .5574 .1278 .4715 .5283 .3694 .1352 .0486* .8907
Outcomes in patients who underwent abdominal wall reconstruction In 47 (57%) of the 82 patients who underwent complex ventral hernia repair (cVHR), mesh overlay approaches were used, with or without anterior component separation procedures. In the remainder, open underlay or retrorectus approaches were used. In 63 (77%) cases, extensive (R45 minutes) lysis of adhesions were documented. The SSO rate in the operative cohort was similar to those previously described.21,28 As summarized in Table 4, 28 (34%) patients in this comorbid population had an SSO and 17 (21%) patients had a recurrence with an average length of follow-up of 17 6 12.3 months. The average duration of ileus, as defined by the interval from operation to passage of flatus, was 3.5 days. The average LOS was 5.8 days. When adjusted for the Ventral Hernia Working
ALT 5 alanine aminotransferase; AST 5 aspartate aminotransferase; BUN 5 blood urea nitrogen; Cr 5 creatinine; CRP 5 C-reactive protein; HgB 5 hemoglobin; MCV 5 mean corpuscular volume; RDW 5 red blood cell distribution width; SD 5 standard deviation; WBC 5 white blood cell. *Statistical significance.
Table 3 Hernia and core-muscle mass characteristics in patients who underwent ventral hernia repair and patients who have yet to undergo surgery Surgical n 5 82 Mean 6 SD Age (y) BMI (kg/m2) No. comorbidities/patient No. prior repairs/patient Skeletal muscle area (cm2) Skeletal muscle index (cm2/m2) Skeletal muscle density (H.U.) Largest defect area (cm2) Summed defect area (cm2) Abdominal defect area (cm2) Largest hernia volume (cm3) Summed hernia volume (cm3) BMI 5 body mass index; SD 5 standard deviation. *Statistical significance.
54.57 34.66 2.451 1.402 144.9 50.52 26.49 70.34 79.61 155.8 568 620.8
6 6 6 6 6 6 6 6 6 6 6 6
12.1 6.8 1.786 1.699 40.46 10.47 7.273 101.3 104.9 151.7 1,055 1,166
Nonsurgical n 5 65 Mean 6 SD 60.06 42.08 3.046 1.538 141.7 50.42 20.73 108.9 116.4 192.4 1,954 1,924
6 6 6 6 6 6 6 6 6 6 6 6
9.767 9.379 1.643 1.668 34.81 10.5 7.446 144.8 144.1 195 3,151 3,156
P value .0035* ,.0001* .0395* .6277 .6145 .9533 ,.0001* .0600 .0754 .2022 .0005* .0005*
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6 Table 4
Effect of sarcopenia and sarcopenic obesity on outcomes after ventral hernia repair
No. patients with SSO No. patients with recurrence Duration of ileus (d) LOS (d)
No. patients with SSO No. patients with recurrence Duration of ileus (d) LOS (d)
All hernia repairs n 5 82
Nonsarcopenic patients n 561
Sarcopenic patients n 521
P value
28 (34%) 17 (20.7%)
24 (39.0%) 13 (21.3%)
4 (19.0%) 4 (19.0%)
.1137 1.0000
Mean 6 SD
Mean 6 SD
Mean 6 SD
3.549 6 2.056 5.756 6 3.789
3.23 6 1.596 5.197 6 2.695
4.476 6 2.874 7.381 6 5.714
.0156* .0218*
Nonsarcopenic-obese patients n 5 70
Sarcopenic-obese patients n 5 12
P value
25 (35.7%) 14 (20.0%)
3 (25.0%) 3 (25.0%)
.7429 .7061
Mean 6 SD
Mean 6 SD
3.314 6 1.655 5.243 6 2.59
4.917 6 3.397 8.75 6 7.225
.0117* .0025*
LOS 5 length of stay; SD 5 standard deviation; SSO 5 surgical site occurrence. *Statistical significance.
Group grading system, SSOs for grade 1 (n 5 7), grade 2 (n 5 51), and grade 3 (n 5 24) occurred in 1 (14%), 16 (31%), and 11 (46%) patients, respectively.21,22 Of the 82 patients who underwent surgery, 21 (26%) met CT-based criteria for sarcopenia. As shown in Table 4, the rates of SSO and recurrence were not significantly prolonged in sarcopenic patients compared with their nonsarcopenic counterparts; however, LOS (7.4 vs 5.2 days, P 5 .0218) and duration of ileus (4.5 vs 3.2 days, P 5 .0156) were both significantly prolonged in the sarcopenic population. Twelve (15%) patients in the surgical treatment group were found to have sarcopenic obesity, affecting 6 (17%) of the 36 men and 6 (13%) of the 46 women. Those with sarcopenic obesity did not have significantly dissimilar rates of SSO or recurrence, but did, again, have significantly longer LOS (8.8 vs 5.2 days, P 5 .0025) and duration of ileus (4.9 vs 3.3 days, P 5 .0117). A number of attributes of the abdominal wall defects were correlated to duration of ileus and LOS, including the areas of largest measured defect (P 5 .0011 and P 5 .0039, respectively), the sum of defect areas (P 5 .0016 and P 5 .0023, respectively) and the area of abdominal wall involving any of the hernias (P 5 .0038 and P 5 .0048, respectively). The volume of herniated contents, including the largest (P 5 .0092) and summed (P 5 .0113) volumes, were closely correlated to duration of ileus but not clearly to LOS. Skeletal muscle density, but not SMA or SMI, had a significant inverse correlation with LOS (P 5 .0237), but not with the duration of ileus (P 5 .0534). As shown in Fig. 3A, B, both the largest and summed hernia volume were predictive of SSO (P 5 .0043 and P 5 .0046, respectively) and recurrence (P 5 .0073 and P 5 .0072, respectively). In contrast to patients without an SSO, those with this complication had significantly elevated SMI (48.7 vs 54.0 cm2/m2, P 5 .0299) and BMI (33.4 vs 37.1 kg/m2, P 5 .0187), suggesting that an
elevated BMI, and not a reduced SMI, is a stronger driver of SSO.
Comments Sarcopenic obesity has been recognized as a predictor of long-term health and is associated with metabolic syndrome.14,17 Sarcopenia and sarcopenic obesity have been shown as potential markers for adverse outcomes in surgically treated conditions.4–7,9,26 Given the substantial metabolic requirements for recovery after major abdominal operations, we evaluated whether sarcopenia was associated with adverse outcomes and delays in recovery in these patients.11,12 To our knowledge, this is the first report exploring the prevalence and implications of sarcopenia in a complex ventral hernia repair (VHR) patient population. The principal findings of this study were: first, that 26% of the patients who underwent evaluation for complex hernia repair were sarcopenic, and 1 in every 5 patients met the criteria for sarcopenic obesity; second, that lower muscle mass in this population was not clearly associated with serum indices of metabolic disturbance, micronutrient imbalance, or low-grade systemic inflammation; and, third, in-hospital and early follow-up data suggested that the CTbased indices of core musculature were associated with increased LOS, largely due to the duration of ileus but were otherwise unreliable discriminators for adverse postoperative events in our patient population. We also noted that positive outcomes may be associated with higher coremuscle density (H.U.), perhaps reflecting a higher quality tissue containing less fatty infiltrate. It should be noted that our study is not fully powered to identify significant differences in the likelihood of SSO between sarcopenic and nonsarcopenic patients. However, as shown in Table 4,
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Sarcopenia and abdominal wall hernias
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Figure 3 Bar graph of hernia volume (cm3) and surgical outcomes. Error bars represent standard deviation. (A) Largest hernia volume in patients with and without SSO (1,022.0 6 1,674.0 vs 332.6 6 327.9 cm3, P 5 .0043) and total hernia volume in patients with and without SSO (1,120.0 6 1,859.0 vs 362.0 6 339.8 cm3, P 5 .0046), (B) Largest hernia volume in patients with and without hernia recurrence (1,171 6 2,043 vs 410.4 6 492.5 cm3, P 5 .0073) and total hernia volume in patients with and without hernia recurrence (1,289 6 2,296 vs 446 6 501.9 cm3, P 5 .0072). SSO 5 surgical site occurrence.
the preliminary analysis indicated that the incidence of SSO among sarcopenic patients was in fact lower than among nonsarcopenic patients. This observation argues against a principal hypothesis of the study, that sarcopenia would be associated with unfavorable outcomes for SSO. An additional implication is that it is unlikely that the trend would be reversed with greater numbers of patients. In contrast to CT-derived measurements of core-muscle characteristics, the CT-based attributes of the hernia, including the size (area) and the loss of domain (volume) were more closely related to postoperative events. Interestingly, increased hernia area seemed to correlate with LOS, whereas increased hernia volume was more predictive of SSO and recurrence. This is congruent with existing literature, as the variables most clearly associated with extended LOS and postoperative adverse occurrence include the overall medical complexity of the patient and the attributes of the hernia itself.21–24,28 Our study provides the additional perspective that the physical attributes of the
defect and the content could be used as additional parameters for risk adjustment and comparability of studies reporting outcomes. In this cohort of referred patients, more than 85% were obese. Our findings support the impression that higher BMI levels are likely to be confounders in the correlation between age and muscle mass.29 In this study, as in others, core-muscle mass generally increases with BMI.30 Our previous work has confirmed that obesity, when defined by a BMI higher than 30, is associated with low-grade disturbances in circulating micronutrients and markers of systemic inflammation.20 Furthermore, it has been suggested that, in groups of surgical patients with advanced malignancy or candidates for organ transplant, systemic inflammation and nutritional imbalances are associated with loss of muscle mass and deconditioning, consequentially leading to antagonized recovery, healing, and complication rates.4–9,16,26,30 Thus, in the obese patient, the increased metabolic requirements for maintaining core-muscle mass
8
The American Journal of Surgery, Vol -, No -, - 2016
and functionality could potentially interfere with the acute metabolic requirements of surgical stress, potentially influencing or masking poor outcomes.29,30 Although sarcopenia has been shown to adversely influence outcomes in other surgical populations, the results here suggest that caution should be taken when using analytic morphometrics of muscle mass in the obese and morbidly obese patient. Although a number of studies with patient populations similar to our own have emphasized the contributions of obesity on imbalances of muscle metabolism, these findings are not always consistent.14,15,20 A strong relationship was demonstrated to exist between core musculature and obesity. Patients with lower muscle mass recovered more slowly in the hospital after complex VHR but, in contrast to prior studies of sarcopenia in other surgical patient groups, they were not clearly more susceptible to adverse wound occurrences or systemic complications. Although our study does not provide information to directly address this potential discrepancy, the following observations may be relevant. The first is that the influence of sarcopenia on outcomes after surgery has previously been studied in patient groups with malignancy or severe liver disease.4–6,8,9,31 In such patients, there is a substantial likelihood of poor-protein intake as well as malignancyinduced systemic inflammation and catabolism. The confluence of these conditions leads directly to muscle wasting and deconditioning, even among patients who are also obese. The primary indication for surgery is also a principal driver for sarcopenia. Under these conditions, sarcopenia is a reporter of serious postoperative adverse events because it has the same underlying causes of exacerbated inflammation, catabolism, hypoalbuminemia, and poor-nutrient intake. In this regard, we have reported20 that the complex VHR patients are not generally malnourished or hypoalbuminemic. In this group, however, there is a substantial prevalence of low-grade systemic inflammation (as measured by serum C-reactive protein levels) and mild imbalances in micronutrient metabolism not nearly as severe as those found in patients with advanced malignancy or organ failure and driven not by the presence of the hernia but the presence of comorbid conditions, in particular obesity. Moreover, in experimental studies, we recently demonstrated that mild diet-induced imbalances in micronutrients such as zinc can lead to a self-sustaining state of low-grade systemic inflammation and disturbances in other micronutrients involved in oxidative stress. Also impaired was the resolution of macrophage-driven responses to chemical peritonitis and mechanical irritation of the peritoneum, leading to prolonged ileus.32 Thus, we might speculate that when the primary disease is the principal driver for sarcopenia, catabolic effects and the associated impairments in metabolism of macronutrients and micronutrients are substantial, thereby increasing susceptibility to more severe wound and systemic complications after major abdominal operations. In contrast, when sarcopenia is present but
incidental to the condition requiring surgery, metabolic disturbance is milder and would be reflected in subtle impairments in recovery and convalescence. Further studies, both clinical and experimental, are required to tease out the role of micronutrient imbalance, mild systemic inflammation, and oxidative stress in responses to acute surgical stresses in medically complex patients. In summary, our investigations demonstrated that indices of sarcopenia and core-muscle mass did not reliably reflect underlying biological disturbance or predict adverse outcomes and delays in recovery after complex hernia repair. Weaknesses in this study include a retrospective design, bias in selection of surgical candidates, and the relatively small subgroup of patients with sarcopenic obesity. Recognizing these limitations, our findings provide previously unreported, yet somewhat disappointing, evidence that in a largely obese population, the CT-based attributes of muscle mass fail to serve as reporters of preexisting biological stress or as predictors of outcomes after complex abdominal wall hernia repair. In contrast, the anatomic attributes of complex abdominal wall herniasdthe dimensions of the defect and volume of herniated contentsdcorrelated closely with attributes of core-muscle mass and postoperative outcomes. Here, additional insight may be offered by our findings: obesity, a widely accepted independent risk factor for adverse surgical outcomes, may influence or mask muscle catabolism, mass, and the presence of image-guided surrogate markers of sarcopenia. Thus, the utilization of image-based measurements of coremuscle mass and sarcopenia to gauge negative biologic disturbances and outcomes in a largely obese population undergoing cVHR should be used with caution. Although a globally accepted definition of sarcopenia is yet to emerge, it has been suggested that the diagnosis of sarcopenia can be made more meaningful by including indices of muscle mass and function.3 Future work to examine sarcopenia and sarcopenic obesity in cVHR patients should include concurrent measurements of such indices.
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