Jeroen L.A. van Vugt

Systematic Review and Meta‐Analysis of the Impact of Computed Tomography–Assessed Skeletal Muscle Mass on Outcome in Patients Awaiting or Undergoing Liver Transplantation

Liver transplant outcome has improved considerably as a direct result of optimized surgical and anesthesiological techniques and organ allocation programs. Because there remains a shortage of human organs, strict selection of transplant candidates remains of paramount importance. Recently, computed tomography (CT)‐assessed low skeletal muscle mass (i.e. sarcopenia) was identified as a novel prognostic parameter to predict outcome in liver transplant candidates. A systematic review and meta‐analysis on the impact of CT‐assessed skeletal muscle mass on outcome in liver transplant candidates were performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis guidelines. Nineteen studies, including 3803 patients in partly overlapping cohorts, fulfilled the inclusion criteria. The prevalence of sarcopenia ranged from 22.2% to 70%. An independent association between low muscle mass and posttransplantation and waiting list mortality was described in 4 of the 6 and 6 of the 11 studies, respectively. The pooled hazard ratios of sarcopenia were 1.84 (95% confidence interval 1.11–3.05, p = 0.02) and 1.72 (95% confidence interval 0.99–3.00, p = 0.05) for posttransplantation and waiting list mortality, respectively, independent of Model for End‐stage Liver Disease score. Less‐consistent evidence suggested a higher complication rate, particularly infections, in sarcopenic patients. In conclusion, sarcopenia is an independent predictor for outcome in liver transplantation patients and could be used for risk assessment.

Sarcopenia is highly prevalent in patients undergoing surgery for gastric cancer but not associated with worse outcomes

Aim of this study was to assess the prevalence of sarcopenia and body composition (i.e., subcutaneous and visceral fat) in gastric cancer surgical patients and its association with adverse postoperative outcome.

A comparative study of software programmes for cross-sectional skeletal muscle and adipose tissue measurements on abdominal computed tomography scans of rectal cancer patients

The association between body composition (e.g. sarcopenia or visceral obesity) and treatment outcomes, such as survival, using single‐slice computed tomography (CT)‐based measurements has recently been studied in various patient groups. These studies have been conducted with different software programmes, each with their specific characteristics, of which the inter‐observer, intra‐observer, and inter‐software correlation are unknown. Therefore, a comparative study was performed.

A model including sarcopenia surpasses the MELD score in predicting waiting list mortality in cirrhotic liver transplant candidates: A competing risk analysis in a national cohort

BACKGROUND & AIMS Frail patients with low model for end-stage liver disease (MELD) scores may be under-prioritised. Low skeletal muscle mass, namely sarcopenia, has been identified as a risk factor for waiting list mortality. A recent study proposed incorporating sarcopenia in the MELD score (MELD-Sarcopenia score). We aimed to investigate the association between sarcopenia and waiting list mortality, and to validate the MELD-Sarcopenia score (i.e. MELD + 10.35 * Sarcopenia). METHODS We identified consecutive patients with cirrhosis listed for liver transplantation in the Eurotransplant registry between 2007-2014 and measured skeletal muscle mass on computed tomography. A competing risk analysis was used to compare survival of patients with and without sarcopenia, and concordance (c) indices were calculated to assess performance of the MELD and MELD-Sarcopenia score. We created a nomogram of the best predictive model. RESULTS We included 585 patients with a median MELD score of 14 (interquartile range 9-19), of which 254 (43.4%) were identified as having sarcopenia. Median waiting list survival was shorter in patients with sarcopenia than those without (p <0.001). This effect was even more pronounced in patients with MELD ≤15. The discriminative performance of the MELD-Sarcopenia score (c-index 0.820) for three-month mortality was lower than MELD score alone (c-index 0.839). Apart from sarcopenia and MELD score, other predictive variables were occurrence of hepatic encephalopathy before listing and recipient age. A model including all these variables yielded a c-index of 0.851. CONCLUSIONS Sarcopenia was associated with waiting list mortality in liver transplant candidates with cirrhosis, particularly in patients with lower MELD scores. The MELD-Sarcopenia score was successfully validated in this cohort. However, incorporating sarcopenia in the MELD score had limited added value in predicting waiting list mortality. LAY SUMMARY In this study among patients with liver cirrhosis listed for liver transplantation, low skeletal muscle mass was associated with mortality on the waiting list, particularly in patients who were listed with low priority based on a low MELD score. However, adding these measurements to the currently used system for donor and organ allocation showed no added value.

The new Body Mass Index as a predictor of postoperative complications in elective colorectal cancer surgery

BACKGROUND & AIMS A new Body Mass Index (BMI) formula has been developed for a better approximation of under and overweight. The aim of this study was to investigate the predictive value of this newly proposed BMI formula for postoperative complications in elective colorectal cancer surgery compared with the conventional BMI formula. METHODS A digital database of patients undergoing elective colorectal cancer surgery was prospectively maintained in three centers and retrospectively analyzed. Data consisted of patient characteristics, surgical procedure, length of hospital stay (LOS), postoperative complications, mortality, reoperation and readmission. The BMI was calculated using both the conventional and new BMI formula. Patients were divided into four groups (BMI <20, 20-25, 25-30, ≥30 kg/m(2)). RESULTS A total of 1614 patients were included. There was no significant difference in mean BMI between males and females using the conventional BMI formula (26.0 versus 26.2, p = 0.347), whereas a trend was observed using the new BMI formula (26.3 versus 25.6, p = 0.071). The proportion of overweight (BMI ≥25) male patients was significantly higher compared with the proportion of overweight female patients using the conventional formula (58.9% versus 51.0%, p = 0.021), whereas a non-significant difference was observed using the new formula (51.7% versus 53.4%, p = 0.515). Neither the conventional nor the new BMI were associated with postoperative complications and LOS. Higher age, higher ASA classification, male gender, and conventional surgery were independent predictors of the occurrence of postoperative complications. A longer LOS was also independently predicted by higher age, higher ASA classification and conventional surgery. CONCLUSIONS This study showed no superiority of the new BMI formula in predicting postoperative complications after colorectal cancer surgery. Confirmation of the results in a larger cohort is desirable.

Performance of prognostic scores and staging systems in predicting long-term survival outcomes after surgery for intrahepatic cholangiocarcinoma

We sought to validate the commonly used prognostic models and staging systems for intrahepatic cholangiocarcinoma (ICC) in a large multi‐center patient cohort.

Validation of the Mayo Clinic Staging System in Determining Prognoses of Patients With Perihilar Cholangiocarcinoma

BACKGROUND & AIMS: Most systems for staging perihilar cholangiocarcinoma (PHC) have been developed for the minority of patients with resectable disease. The recently developed Mayo Clinic system for staging PHC requires only clinical and radiologic variables, but has not yet been validated. We performed a retrospective study to validate the Mayo Clinic staging system. METHODS: We identified consecutive patients with suspected PHC who were evaluated and treated at 2 tertiary centers in The Netherlands, from January 2002 through December 2014. Baseline characteristics (performance status, carbohydrate antigen 19‐9 level) used in the staging system were collected from medical records and imaging parameters (tumor size, suspected vascular involvement, and metastatic disease) were reassessed by 2 experienced abdominal radiologists. Overall survival was analyzed using the Kaplan–Meier method and comparison of staging groups was performed using the log‐rank test and Cox proportional hazard regression analysis. Discriminative performance was quantified by the concordance index and compared with the radiologic TNM staging of the American Joint Committee on Cancer (7th ed). RESULTS: PHCs from 600 patients were staged according to the Mayo Clinic model (23 stage I, 80 stage II, 357 stage III, and 140 stage IV). The median overall survival time was 11.6 months. The median overall survival times for patients with stages I, II, III, and IV were 33.2 months, 19.7 months, 12.1 months, and 6.0 months, respectively; with hazard ratios of 1.0 (reference), 2.02 (95% confidence interval [CI], 1.14–3.58), 2.71 (95% CI, 1.59–4.64), and 4.00 (95% CI, 2.30–6.95), respectively (P < .001). The concordance index score was 0.59 for the entire cohort (95% CI, 0.56–0.61). The Mayo Clinic model performed slightly better than the radiologic American Joint Committee on Cancer TNM system. CONCLUSIONS: In a retrospective study of 600 patients with PHC, we validated the Mayo Clinic system for staging PHC. This 4‐tier staging system may aid clinicians in making treatment decisions, such as referral for surgery, and predicting survival times.

Anatomical Resections Improve Disease-Free Survival in Patients With KRAS-mutated Colorectal Liver Metastases

Objective: To investigate the potential clinical advantage of anatomical resection versus nonanatomical resection for colorectal liver metastases, according to KRAS mutational status. Background: KRAS-mutated colorectal liver metastases (CRLM) are known to be more aggressive than KRAS wild-type tumors. Although nonanatomical liver resections have been demonstrated as a viable approach for CRLM patients with similar oncologic outcomes to anatomical resections, this may not be the case for the subset of KRAS-mutated CRLM. Methods: 389 patients who underwent hepatic resection of CRLM with known KRAS mutational status were identified. Survival estimates were calculated using the Kaplan-Meier method, and multivariable analysis was conducted using the Cox proportional hazards regression model. Results: In this study, 165 patients (42.4%) underwent nonanatomical resections and 140 (36.0%) presented with KRAS-mutated CRLM. Median disease-free survival (DFS) in the entire cohort was 21.3 months, whereas 1-, 3-, and 5-year DFS was 67.3%, 34.9%, and 31.5% respectively. Although there was no difference in DFS between anatomical and nonanatomical resections in patients with KRAS wild-type tumors (P = 0.142), a significant difference in favor of anatomical resection was observed in patients with a KRAS mutation (10.5 vs. 33.8 months; P < 0.001). Five-year DFS was only 14.4% in the nonanatomically resected group, versus 46.4% in the anatomically resected group. This observation persisted in multivariable analysis (hazard ratio: 0.45; 95% confidence interval: 0.27–0.74; P = 0.002), when corrected for number of tumors, bilobar disease, and intraoperative ablations. Conclusions: Nonanatomical tissue-sparing hepatectomies are associated with worse DFS in patients with KRAS-mutated tumors. Because of the aggressive nature of KRAS-mutated CRLM, more extensive anatomical hepatectomies may be warranted.

The impact of sarcopenia on survival and complications in surgical oncology: A review of the current literature: Comment on Joglekar et al

Dear Editor, We read with great interest the paper by Joglekar and colleagues that systematically reviewed the current literature regarding the impact of sarcopenia on survival and complications in patients undergoing cancer surgery [1]. To date, sarcopenia is a burning topic of clinical relevance, since preoperative body composition deviation has been identified as a strong prognostic marker in surgical oncological populations. In the last 5 years, many studies have investigated the effect of sarcopenia on outcomes in surgical oncology. As readers may go astray as a result of the plethora of publications on this topic, a systematic review enables a clear overview of all available evidence. Therefore, we congratulate the authors with their initiative. However, we would like to address some issues regarding the methodology of their study. First of all, the definition of the investigated patient population (i.e., “surgical oncology”) remains ambiguous for the uncommitted reader. On the one hand, studies describing the impact of sarcopenia in patients undergoing bladder cancer resection and lymph node resection for melanoma were included [1], whereas studies in patients undergoing surgery for endometrial [2] or penile [3] cancer were not. Besides the fact that only one database (PubMed) has been searched, the strings for the systematic search consisted of a limited number of search terms. For example, only sarcopenia was used, instead of the combination with terms like body composition, myopenia, or skeletal muscle wasting, -depletion, -atrophy, or -loss [4]. Consequently, this has led to the exclusion of multiple relevant studies that have reported the impact of sarcopenia in patients undergoing cancer surgery and were published (on-line) before the last search date (May 4th 2015). For instance, two studies among patients with perihilar cholangiocarcinoma [5,6], one with pancreatic cancer patients [7], one with colorectal cancer patients [8], and one with primary liver tumor patients [9] undergoing resection, which are populations known for their high postoperative morbidity and mortality rates and poor prognosis, were missed. Moreover, a study that has frequently been cited in the studies that were included in the review—and thus should have been identified by crossreferencing as described in themethods section—was not included [10]. Notably, the results of two studies that described an association between skeletal muscle mass and impaired postoperative outcome after colorectal cancer surgery that were referred to in the introduction of the article [11,12], have not been included. Finally, a study among patients undergoing resection for colorectal liver metastases is briefly mentioned in the text, but not depicted in table II [13]. These concerns would probably have been prevented if the authors would have complied with the PRISMA guidelines for systematic reviews and its corresponding flow-chart, depicting study selection [14]. Since all included studies have an observational, retrospective design, no causative relationship between sarcopenia and outcome measures has been established. Therefore, findings should be placed in perspective and confirmed in prospective studies. Furthermore, the majority of studies measured skeletal muscle mass using abdominal computed tomography (CT) scans. As explained by the authors, a great diversity in methods to measure or define sarcopenia (i.e., different cutoff values used, various muscles measured) was observed in these studies. These measures and definitions may not be applicable to all populations. We feel that it is important to emphasize that one should strive for a uniform definition of CT-assessed sarcopenia with outcomerelated cut-off values adjusted for age, gender, ethnicity, and tumor type to improve future comparability of studies.

Low skeletal muscle mass is associated with increased hospital costs in patients with cirrhosis listed for liver transplantation–a retrospective study

Low skeletal muscle mass (sarcopenia) is associated with increased morbidity and mortality in liver transplant candidates. We investigated the association between sarcopenia and hospital costs in patients listed for liver transplantation. Consecutive patients with cirrhosis listed for liver transplantation between 2007 and 2014 in a Eurotransplant centre were identified. The skeletal muscle index (SMI, cm2/m2) was measured on CT performed within 90 days from waiting list placement. The lowest sex‐spe cific quartile represented patients with sarcopenia. In total, 224 patients were included. Median time on the waiting list was 170 (IQR 47–306) days, and median MELD score was 16 (IQR 11–20). The median total hospital costs in patients with sarcopenia were €11 294 (IQR 3570–46 469) compared with €6878 (IQR 1305–20 683) in patients without sarcopenia (P = 0.008). In multivariable regression analysis, an incremental increase in SMI was significantly associated with a decrease in total costs (€455 per incremental SMI, 95% CI 11–900, P = 0.045), independent of the total time on the waiting list. In conclusion, sarcopenia is independently associated with increased health‐related costs for patients on the waiting list for liver transplantation. Optimizing skeletal muscle mass may therefore lead to a decrease in hospital expenditure, in addition to greater health benefit for the transplant candidate.