Zhang QH, Ma JD, Lu YM, Zhang RN, Zhao ZH, Li YT, Chen QP. Sarcopenia adversely impacts clinical outcomes in patients undergoing pancreaticoduodenectomy: A systematic review and meta-analysis. World J Gastrointest Surg 2024; 16(6): 1857-1870 [PMID: 38983342 DOI: 10.4240/wjgs.v16.i6.1857]
Corresponding Author of This Article
Qiang-Pu Chen, MM, Chief Doctor, Professor, Surgeon, Department of Hepatobiliary Surgery, Binzhou Medical University Hospital, 2nd Huanghe Road, Binzhou 256603, Shandong Province, China. drcqp@263.net
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Meta-Analysis
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Qi-Hui Zhang, Jin-Dong Ma, Yan-Min Lu, Run-Nan Zhang, Qiang-Pu Chen, Department of Clinical Nutrition, Binzhou Medical University Hospital, Binzhou 256603, Shandong Province, China
Zhong-Hua Zhao, Ya-Tong Li, Qiang-Pu Chen, Department of Hepatobiliary Surgery, Binzhou Medical University Hospital, Binzhou 256603, Shandong Province, China
Author contributions: Zhang QH and Ma JD contributed equally to this work and are co-first authors. Zhang QH, Ma JD, Lu YM, Zhang RN, and Zhao ZH participated in the data curation; Zhang QH, Ma JD, Lu YM, Zhang RN, Zhao ZH, Li YT, and Chen QP were involved in the writing - review and editing; Zhang QH and Ma JD contributed to the software, validation, and writing - original draft of this manuscript; Lu YM and Chen QP took part in conceptualization and supervision; Zhang QH was involved in the methodology of this study.
Supported bythe Shandong Province Biliary Pancreatic Cancer Clinical Quality Specialty Construction Fund, No. SLCZDZK-2401; and Provincial Key Clinical Discipline Construction Fund of Shandong Province, No. SLCZDZK-0701.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qiang-Pu Chen, MM, Chief Doctor, Professor, Surgeon, Department of Hepatobiliary Surgery, Binzhou Medical University Hospital, 2nd Huanghe Road, Binzhou 256603, Shandong Province, China. drcqp@263.net
Received: January 22, 2024 Revised: April 14, 2024 Accepted: April 28, 2024 Published online: June 27, 2024 Processing time: 159 Days and 17.3 Hours
Abstract
BACKGROUND
Sarcopenia is a syndrome marked by a gradual and widespread reduction in skeletal muscle mass and strength, as well as a decline in functional ability, which is associated with malnutrition, hormonal changes, chronic inflammation, disturbance of intestinal flora, and exercise quality. Pancreatoduodenectomy is a commonly employed clinical intervention for conditions such as pancreatic head cancer, ampulla of Vater cancer, and cholangiocarcinoma, among others, with a notably high rate of postoperative complications. Sarcopenia is frequent in patients undergoing pancreatoduodenectomy. However, data regarding the effects of sarcopenia in patients undergoing pancreaticoduodenectomy (PD) are both limited and inconsistent.
AIM
To assess the influence of sarcopenia on outcomes in patients undergoing PD.
METHODS
The PubMed, Cochrane Library, Web of Science, and Embase databases were screened for studies published from the time of database inception to June 2023 that described the effects of sarcopenia on the outcomes and complications of PD. Two researchers independently assessed the quality of the data extracted from the studies that met the inclusion criteria. Meta-analysis using RevMan 5.3.5 and Stata 14.0 software was conducted. Forest and funnel plots were used, respectively, to demonstrate the outcomes of the sarcopenia group vs the non-sarcopenia group after PD and to evaluate potential publication bias.
RESULTS
Sixteen studies encompassing 2381 patients were included in the meta-analysis. The patients in the sarcopenia group (n = 833) had higher overall postoperative complication rates [odds ratio (OR) = 3.42, 95% confidence interval (CI): 1.95-5.99, P < 0.0001], higher Clavien-Dindo class ≥ III major complication rates (OR = 1.41, 95%CI: 1.04-1.90, P = 0.03), higher bacteremia rates (OR = 4.46, 95%CI: 1.42-13.98, P = 0.01), higher pneumonia rates (OR = 2.10, 95%CI: 1.34-3.27, P = 0.001), higher pancreatic fistula rates (OR = 1.42, 95%CI: 1.12-1.79, P = 0.003), longer hospital stays (OR = 2.86, 95%CI: 0.44-5.28, P = 0.02), higher mortality rates (OR = 3.17, 95%CI: 1.55-6.50, P = 0.002), and worse overall survival (hazard ratio = 2.81, 95%CI: 1.45-5.45, P = 0.002) than those in the non-sarcopenia group (n = 1548). However, no significant inter-group differences were observed regarding wound infections, urinary tract infections, biliary fistulas, or postoperative digestive bleeding.
CONCLUSION
Sarcopenia is a common comorbidity in patients undergoing PD. Patients with preoperative sarcopenia have increased rates of complications and mortality, in addition to a poorer overall survival rate and longer hospital stays after PD.
Core Tip: Muscle wasting has a significant impact on the clinical outcomes and prognosis of patients undergoing major surgery, but there is limited research on the impact of muscle wasting on patients undergoing pancreaticoduodenectomy (PD), and the conclusions are inconsistent. This article aims to evaluate the impact of sarcopenia on the clinical outcomes of PD patients through meta-analysis, in order to provide evidence-based management for PD patients during the perioperative period. Strictly screen articles based on pre-set inclusion and exclusion criteria.
Citation: Zhang QH, Ma JD, Lu YM, Zhang RN, Zhao ZH, Li YT, Chen QP. Sarcopenia adversely impacts clinical outcomes in patients undergoing pancreaticoduodenectomy: A systematic review and meta-analysis. World J Gastrointest Surg 2024; 16(6): 1857-1870
Sarcopenia is a syndrome characterized by a gradual, widespread reduction in mass within the skeletal musculature, together with decreased muscle strength or impaired capacity to engage in routine daily activities. Afflicted individuals often experience compromised mobility, reduced quality of life, and heightened susceptibility to undesirable outcomes including falls and mortality[1]. The development of sarcopenia is associated with e.g., malnutrition, hormonal changes, chronic inflammation, disturbance of intestinal flora, and exercise quality, as well as genetic and psychosocial factors[2]. Sarcopenia is a risk factor for poor prognosis in patients with pancreatic cancer, gastric cancer, lung cancer, and other surgical procedures[3]. Pancreatoduodenectomy is clinically used to treat pancreatic head cancer, ampulla of Vater cancer, cholangiocarcinoma, and other diseases, and the incidence of postoperative complications is extremely high[4]. In light of this complication risk, the perioperative management of patients is crucial. According to the literature, the prevalence of sarcopenia in patients undergoing pancreatoduodenectomy is high[5-7]. However, the effects of sarcopenia on clinical outcomes and prognosis following pancreaticoduodenectomy (PD) remain unclear. Therefore, the purpose of the present systematic review and meta-analysis was to assess the influence of sarcopenia on postoperative results in patients undergoing PD. Additionally, we aimed to provide an evidence-based foundation for the management of patients in the perioperative period after PD.
MATERIALS AND METHODS
Literature search strategy
Zhang QH and Ma JD conducted a thorough search of credible databases; i.e., PubMed, Cochrane Library, Web of Science, and Embase, to gather relevant literature. The search was conducted from the initiation of the databases until June 2023 and was limited to English-language publications. The search terms used included “sarcopenia”, “frailty”, “muscle weakness”, “muscle atrophy”, “pancreaticoduodenectomy”, “Whipple procedure”, “pancreaticoduodenectomies”, “duodenopancreatectomy”, and “pancreatoduodenectomy”. To refine the results, the search terms were combined utilizing the Boolean operators “AND” and “OR”. Synonyms of all terms were considered during the search.
Inclusion and exclusion criteria
To be considered for inclusion in the meta-analysis, studies needed to meet a series of specific criteria. These included having well-defined standards for assessing sarcopenia and measuring skeletal muscle, focusing on patients who were undergoing PD, and examining the correlation between sarcopenia and clinical outcomes after surgery. It was essential that the original text was accessible and that the study data could be accurately extracted. Furthermore, the studies had to be published in their entirety and fall into the category of cohort studies. Specific exclusion criteria included non-randomized controlled trials including reviews, systematic reviews, case reports, and commentaries, non-clinical trials, and any repeated publications reporting on the same study population. Studies with incomplete data on crucial clinical outcome indicators or significant bias were also excluded.
Data extraction
Data of studies were extracted separately by two authors (Zhang QH and Ma JD). In cases of disagreement, the authors discussed and resolved the issue. If necessary, a third investigator was consulted for judgment. The following main parameters were considered: Basic information (i.e., first author, country, publication date, study duration, type of literature, number of cases, sex ratio, mean age, type of disease, body mass index, diagnostic criteria and prevalence of sarcopenia), clinical outcome parameters [i.e., overall complications, complications classified as Clavien-Dindo (C-D) class ≥ III, wound infection, bacteremia, urinary tract infection, pneumonia, pancreatic fistula, biliary fistula, and death], and length of stay. Means and standard deviations were utilized to describe continuous outcome variables in the context of meta-analysis. When the initial data were presented as medians or ranges, the averages and standard deviations were approximated using the approach outlined by Hozo et al[8].
Quality assessment
The quality of each study was evaluated separately by two authors. In cases where the evaluations differed, a third investigator was consulted to decide whether the literature should be included or not. The Newcastle-Ottawa Scale was applied to evaluate the methodological rigor of the literature, taking into account three factors: Selection of the study population (4 points), comparability between groups (2 points), and outcome parameters (3 points). A maximum of nine points could be obtained, with studies having a score of six or more deemed as being of high quality[9].
Statistical analysis
To conduct the meta-analysis, we utilized RevMan 5.3.5 and Stata 14.0 software (Cochrane Collaboration, Oxford, United Kingdom). For continuous variables, we calculated the weighted mean differences along with their corresponding 95% confidence intervals (CIs). Similarly, for categorical variables, we computed odds ratios (ORs) with their respective 95%CIs. To assess heterogeneity, we performed a chi-square test, considering P > 0.05 as non-significant. Statistical heterogeneity was assessed using I2 values, with a threshold of 50% or higher indicating the presence of heterogeneity. When the studies exhibited homogeneity (I2 < 50%), we adopted the fixed-effects model. Conversely, if studies presented heterogeneity (I2 ≥ 50%), we utilized the random-effects model.
Risk of bias
We employed funnel plots to assess potential publication bias based on major complication rates (C-D ≥ III).
RESULTS
Eligible studies
Initially, 398 relevant publications were retrieved. After layer-by-layer screening, 16 studies with a total of 2381 patients were finally included (n = 833 and n = 1548 in the sarcopenia and non-sarcopenia groups, respectively). All studies were cohort studies. The screening process is shown in Figure 1. The basic information and results of the literature quality evaluation are shown in Tables 1-3.
Overall rates of postoperative and major complications (C-D ≥ III)
Four studies reported the overall rate of postoperative complications, which was statistically significant after combining the effects across studies (OR = 3.42, 95%CI: 1.95-5.99, P < 0.0001)[7,14,18,21] (Figure 3A). Nine studies reported major postoperative complications (C-D ≥ III), yielding statistically significant combined effects (OR = 1.41, 95%CI: 1.04-1.90, P = 0.03)[5-7,12,15,16,19,20,22] (Figure 3B).
Figure 3 Comparison of the overall rate of postoperative complications, major complications (Clavien-Dindo ≥ III), the occurrence of bacteremia, the occurrence of pneumonia, wound infection rates, urinary tract infection rates, the incidence of pancreatic fistula, biliary fistula rates, the occurrence of postoperative bleeding, length of stay, postoperative mortality rates, and overall survival between the sarcopenia and non-sarcopenia groups.
A: Comparison of the overall rate of postoperative complications between the sarcopenia and non-sarcopenia groups; B: Comparison of major complications (Clavien-Dindo ≥ III) between the sarcopenia and non-sarcopenia groups; C: Comparison of the occurrence of bacteremia between the sarcopenia and non-sarcopenia groups; D: Comparison of the occurrence of pneumonia between the sarcopenia and non-sarcopenia groups; E: Comparison of wound infection rates between the sarcopenia and non-sarcopenia groups; F: Comparison of urinary tract infection rates between the sarcopenia and non-sarcopenia groups; G: Comparison of the incidence of pancreatic fistula between the sarcopenia and non-sarcopenia groups; H: Comparison of biliary fistula rates between the sarcopenia and non-sarcopenia groups; I: Comparison of the occurrence of postoperative bleeding between the sarcopenia and non-sarcopenia groups; J: Comparison of length of stay between the sarcopenia and non-sarcopenia groups; K: Comparison of postoperative mortality rates between the sarcopenia and non-sarcopenia groups; L: Comparison of overall survival between the sarcopenia and non-sarcopenia groups. (multivariate analysis). CI: Confidence interval.
Infectious complications
Three studies reported the occurrence rate of bacteremia, which was statistically significant after combining effects (OR = 4.46, 95%CI: 1.42-13.98, P = 0.01)[5,14,17] (Figure 3C). Six studies reported that of pneumonia, yielding statistically significant combined effects (OR = 2.10, 95%CI: 1.34-3.27, P = 0.001)[5,7,13,14,21,23] (Figure 3D). No inter-group statistical difference was noted regarding wound (OR = 1.39, 95%CI: 0.89-2.19, P = 0.15) (Figure 3E) or urinary tract (OR = 1.25, 95%CI: 0.56-2.80, P = 0.59) infections (Figure 3F).
Non-infectious complications
Eleven studies presented statistically significant combined effects for the occurrence of pancreatic fistula (OR = 1.42, 95%CI: 1.12-1.79, P = 0.003)[5,7,12-17,21,23,24] (Figure 3G). There was no significant difference of the occurrence rate of biliary fistula between the two groups (OR = 1.22, 95%CI: 0.75-1.99, P = 0.43) (Figure 3H) or postoperative bleeding (OR = 1.44, 95%CI: 0.90-2.29, P = 0.13) (Figure 3I).
Hospital length of stay
The length of hospitalization was recorded in six studies[6,14,15,18,19,21]. The duration of stay was significantly longer for the sarcopenia group than that of the non-sarcopenia group (OR = 2.86, 95%CI: 0.44-5.28, P = 0.02) (Figure 3J).
Mortality
Postoperative mortality was described in six studies[7,12,14,16,18,21]. The sarcopenia group had a higher rate of postoperative mortality than that of the non-sarcopenia group (OR = 3.17, 95%CI: 1.55-6.50, P = 0.002) (Figure 3K).
Overall survival
Overall survival was reported in two studies included in the literature. The sarcopenic group had a worse overall survival (multivariate analysis: Hazard ratio = 2.81, 95%CI: 1.45-5.45, P = 0.002) compared with the non-sarcopenic group as shown in (Figure 3L).
Publication bias
Major complications (C-D ≥ III), a main parameter of clinical outcome, were well represented and included in a large number of studies. Evaluation for publication bias revealed a roughly symmetrical distribution within the inverted funnel plot, suggesting a low risk of publication bias (Figure 4).
Figure 4 Funnel plot of the observed complications (Clavien-Dindo ≥ III).
OR: Odds ratio.
DISCUSSION
Sarcopenia, first described by Rosenberg in 1989, is mainly observed in the elderly population and in patients with chronic diseases[23,24]. Following an investigation of 58 studies encompassing different regions within China, Chen et al[25] revealed that the occurrence rates of sarcopenia were 12.9% and 11.2% for elderly men and women within the community, respectively. Moreover, recent research has indicated a greater occurrence among individuals requiring surgical intervention, particularly in those diagnosed with malignant tumors; for example, the frequency of sarcopenia in patients diagnosed with liver cancer is estimated to range from 11% to 45%[26]. Similarly, patients diagnosed with cholangiocarcinoma and gallbladder cancer exhibited a sarcopenia rate of 33%[27], whereas those undergoing pancreatic surgery exhibited a range of 17% to 62%[28]. Pancreaticobiliary tumors in particular, which are accompanied by obstructive jaundice, malnutrition, impairment of the intestinal mucosal barrier function, and dysbiosis of the intestinal flora, result in the occurrence of preoperative sarcopenia[29]. In line with these findings, the results of the current meta-analysis showed that the occurrence rate of sarcopenia in individuals who undergo PD was 37% (0.29, 0.45). Therefore, preoperative screening and evaluation of sarcopenia in patients undergoing pancreatoduodenectomy is essential, and sarcopenia may adversely affect the clinical outcome of patients undergoing pancreatoduodenectomy.
Only a few comprehensive research studies have examined the effects of sarcopenia on the clinical outcomes of patients who undergo PD. To address this gap, we conducted a meta-analysis incorporating 16 studies, comprising a total of 2381 participants, of whom 833 were diagnosed with sarcopenia. We evaluated 14 factors, including the duration of the operation, rates of overall and major (C-D ≥ III) complications[30], wound infection, bacteremia, urinary tract infection, pneumonia, pancreatic fistula, biliary fistula, and postoperative digestive hemorrhage, together with length of hospital stay and overall survival. Our results indicate a notable correlation between sarcopenia and different negative consequences in comparison to that in patients without sarcopenia. Specifically, patients within the sarcopenia group exhibited an increase in postoperative complications (both overall and major), occurrences of bacteremia, pneumonia, and pancreatic fistula, in addition to a poorer overall survival rate and prolonged hospital length of stay. However, no significant differences were noted between the two cohorts regarding postoperative digestive hemorrhage, wound infection, biliary fistula, and urinary tract infection.
Sarcopenia has a significant effect on patients during their perioperative phase. Decreased muscle function may render patients undergoing major abdominal surgery less active, whereas respiratory muscle weakness predisposes them to hypoxia and respiratory function impairment[31]. Furthermore, the metabolic processes involving proteins and carbohydrates heavily rely on skeletal muscle tissue; accordingly, the depletion of muscle mass disrupts metabolism, resulting in functional disruption. In addition, recent research indicates that individuals with sarcopenia experience immune abnormalities, persistent elevation of inflammatory biomarkers including tumor necrosis factor-α, interleukin-6, and dysbiosis of the gut microbiota. Notably, these biomarkers have the potential to increase the perioperative hazards associated with PD[29,31-34].
The results of the present meta-analysis revealed that preexisting sarcopenia has a significant impact on the negative clinical outcomes observed in patients following PD. Previous research indicates that muscle loss also has a detrimental impact on the long-term survival of patients undergoing major surgical interventions for gastric cancer or hepatocellular carcinoma[35,36]. The occurrence of complications reduces the immune function of patients, and also delays adjuvant therapy (such as chemotherapy, radiotherapy, etc.), thereby shortening the survival of patients.
The SARC-F questionnaire[37] can be used for preoperative screening to identify the population at risk. Subsequently, an evaluation and diagnosis of sarcopenia can be performed by assessing muscle strength, muscle mass, and physical fitness. Methods for assessing skeletal muscle mass comprise computed tomography or magnetic resonance scans at the L3 level, bioelectrical impedance techniques, and dual-energy X-ray absorptiometry scans. Grip strength can be utilized to measure muscle strength. Assessment of physical functional status can be achieved by measuring gait speed and five sit-to-stand times, among other methods. In the studies analyzed in the present meta-analysis, sarcopenia was mainly diagnosed by measuring muscle mass via imaging. However, less attention was paid to muscle strength and physical functional status taking into account the concept of prehabilitation, a combination of nutrition and exercise could potentially be employed to maintain muscle mass, improve muscle strength and functional status, and enhance patient safety during surgical procedures, ultimately enhancing positive surgical outcomes and overall quality of life[38]. This study has some limitations. Validation of the cohort studies included in the meta-analysis is required through randomized controlled trials. The limited number of studies may have resulted in an incomplete inclusion.
CONCLUSION
The high occurrence of preoperative sarcopenia in patients who undergo PD significantly adversely affects postoperative clinical outcomes, such as an elevated likelihood of postoperative complications and a longer duration of hospitalization. To enhance the clinical outcome and prognosis of patients after PD, it is imperative to conduct preoperative screening for sarcopenia and implement suitable interventions.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade B
Novelty: Grade B
Creativity or Innovation: Grade A
Scientific Significance: Grade B
P-Reviewer: Zhao Y, China S-Editor: Wang JJ L-Editor: A P-Editor: Zhang YL
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