Background
Sarcopenia might function as an indicator for frailty, and as such as a risk factor for the development of postoperative complications. The aim of this study was to meta‐analyse the ...relation between preoperative sarcopenia and the development of severe postoperative complications in patients undergoing oncological surgery.
Methods
PubMed and Embase databases were systematically searched from inception until May 2018. Included were studies reporting on the incidence of severe postoperative complications and radiologically determined preoperative sarcopenia. Studies reporting the skeletal muscle as a continuous variable only were excluded. Data were extracted independently by two reviewers. Random effect meta‐analyses were applied to estimate the pooled odds ratio (OR) with 95% confidence intervals (95% CI) for severe postoperative complications, defined as Clavien‐Dindo grade ≥3, including 30‐day mortality. Heterogeneity was evaluated with I2 testing. Analyses were performed overall and stratified by measurement method, tumour location and publication date.
Results
A total of 1924 citations were identified, and 53 studies (14 295 patients) were included in the meta‐analysis. When measuring the total skeletal muscle area, 43% of the patients were sarcopenic, versus 33% when measuring the psoas area. Severe postoperative complications were present in 20%, and 30‐day mortality was 3%. Preoperative sarcopenia was associated with an increased risk of severe postoperative complications (ORpooled: 1.44, 95% CI: 1.24–16.8, P<0.001, I2=55%) and 30‐day mortality (ORpooled: 2.15, 95% CI: 1.46–3.17, P<0.001, I2=14%). A low psoas mass was a stronger predictor for severe postoperative complications compared with a low total skeletal muscle mass (ORpooled: 2.06, 95% CI: 1.37–3.09, ORpooled: 1.32, 95% CI: 1.14–1.53, respectively) and 30‐day mortality ORpooled: 6.17 (95% CI: 2.71–14.08, ORpooled: 1.80 (95% CI: 1.24–2.62), respectively. The effect was independent of tumour location and publication date.
Conclusions
The presence of low psoas mass prior to surgery, as an indicator for sarcopenia, is a common phenomenon and is a strong predictor for the development of postoperative complications. The presence of low total skeletal muscle mass, which is even more frequent, is a less informative predictor for postoperative complications and 30‐day mortality. The low heterogeneity indicates that the finding is consistent over studies. Nevertheless, the value of sarcopenia relative to other assessments such as frailty screening is not clear. Research is needed in order to determine the place of sarcopenia in future preoperative risk stratification.
To determine the predictive value of the "Timed Up & Go" (TUG), a validated assessment tool, on a prospective cohort study and to compare these findings to the ASA classification, an instrument ...commonly used for quantifying patients' physical status and anesthetic risk.
In the onco-geriatric surgical population it is important to identify patients at increased risk of adverse post-operative outcome to minimize the risk of over- and under-treatment and improve outcome in this population.
280 patients ≥70 years undergoing elective surgery for solid tumors were prospectively recruited. Primary endpoint was 30-day morbidity. Pre-operatively TUG was administered and ASA-classification was registered. Data were analyzed using multivariable logistic regression analyses to estimate odds ratios (OR) and 95% confidence intervals (95%-CI). Absolute risks and area under the receiver operating characteristic curves (AUC's) were calculated.
180 (64.3%) patients (median age: 76) underwent major surgery. 55 (20.1%) patients experienced major complications. 50.0% of patients with high TUG and 25.6% of patients with ASA≥3 experienced major complications (absolute risks). TUG and ASA were independent predictors of the occurrence of major complications (TUG:OR 3.43; 95%-CI = 1.14-10.35. ASA1 vs. 2:OR 5.91; 95%-CI = 0.93-37.77. ASA1 vs. 3&4:OR 12.77; 95%-CI = 1.84-88.74). AUCTUG was 0.64 (95%-CI = 0.55-0.73, p = 0.001) and AUCASA was 0.59 (95%-CI = 0.51-0.67, p = 0.04).
Twice as many onco-geriatric patients at risk of post-operative complications, who might benefit from pre-operative interventions, are identified using TUG than when using ASA.
Background
Skeletal muscle depletion or sarcopenia is related to multiple adverse clinical outcome. However, frailty questionnaires are currently applied in the daily practice to identify patients ...who are potentially (un)suitable for treatment but are time consuming and straining for patients and the clinician. Screening for sarcopenia in patients with head and neck cancer (HNC) could be a promising fast biomarker for frailty. Our objective was to quantify sarcopenia with pre‐treatment low skeletal muscle mass from routinely obtained neck computed tomography scans at level of third cervical vertebra in patients diagnosed with HNC and evaluate its association with frailty.
Methods
A total of 112 HNC patients with Stages III and IV disease were included from a prospective databiobank. The amount of skeletal muscle mass was retrospectively defined using the skeletal muscle index (SMI). Correlation analysis between SMI and continuous frailty data and the observer agreement were analysed with Pearson's r correlation coefficients. Sarcopenia was present when SMI felt below previously published non‐gender specific thresholds (<43.2 cm2/m2). Frailty was evaluated by Geriatrics 8 (G8), Groningen Frailty Indicator, Timed Up and Go test, and Malnutrition Universal Screening Tool. A univariate and multivariate logistic regression analysis was performed for all patients and men separately to obtain odds ratios (ORs) and 95% confidence intervals (95% CIs).
Results
The cohort included 82 men (73%) and 30 women (27%), with a total mean age of 63 (±9) years. The observer agreement for cross‐sectional measurements was excellent for both intra‐observer variability (r = 0.99, P < 0.001) and inter‐observer variability (r = 0.98, P < 0.001). SMI correlated best with G8 frailty score (r = 0.38, P < 0.001) and did not differ per gender. Sarcopenia was present in 54 (48%) patients, whereof 25 (46%) men and 29 (54%) women. Prevalence of frailty was between 5% and 54% depending on the used screening tool. The multivariate regression analysis for all patients and men separately isolated the G8 questionnaire as the only independent variable associated with sarcopenia (OR 0.76, 95% CI 0.66–0.89, P < 0.001 and OR 0.76, 95% CI 0.66–0.88, P < 0.001, respectively).
Conclusions
This is the first study that demonstrates that sarcopenia is independently associated with frailty based on the G8 questionnaire in HNC patients. These results suggest that in the future, screening for sarcopenia on routinely obtained neck computed tomography scans may replace time consuming frailty questionnaires and help to select the (un)suitable patients for therapy, which is highly clinically relevant.
Summary Background Investigators of registry-based studies report improved survival for breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer. As these studies ...did not present long-term overall and breast cancer-specific survival, the effect of breast-conserving surgery plus radiotherapy might be overestimated. In this study, we aimed to evaluate 10 year overall and breast cancer-specific survival after breast-conserving surgery plus radiotherapy compared with mastectomy in Dutch women with early breast cancer. Methods In this population-based study, we selected all women from the Netherlands Cancer Registry diagnosed with primary, invasive, stage T1–2, N0–1, M0 breast cancer between Jan 1, 2000, and Dec 31, 2004, given either breast-conserving surgery plus radiotherapy or mastectomy, irrespective of axillary staging or dissection or use of adjuvant systemic therapy. Primary outcomes were 10 year overall survival in the entire cohort and breast cancer-specific survival in a representative subcohort of patients diagnosed in 2003 with characteristics similar to the entire cohort. We estimated breast cancer-specific survival by calculating distant metastasis-free and relative survival for every tumour and nodal category. We did multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs) for overall and distant metastasis-free survival. We estimated relative survival by calculating excess mortality ratios using life tables of the general population. We did multiple imputation to account for missing data. Findings Of the 37 207 patients included in this study, 21 734 (58%) received breast-conserving surgery plus radiotherapy and 15 473 (42%) received mastectomy. The 2003 representative subcohort consisted of 7552 (20%) patients, of whom 4647 (62%) received breast-conserving surgery plus radiotherapy and 2905 (38%) received mastectomy. For both unadjusted and adjusted analysis accounting for various confounding factors, breast-conserving surgery plus radiotherapy was significantly associated with improved 10 year overall survival in the whole cohort overall compared with mastectomy (HR 0·51 95% CI 0·49–0·53; p<0·0001; adjusted HR 0·81 0·78–0·85; p<0·0001), and this improvement remained significant for all subgroups of different T and N stages of breast cancer. After adjustment for confounding variables, breast-conserving surgery plus radiotherapy did not significantly improve 10 year distant metastasis-free survival in the 2003 cohort overall compared with mastectomy (adjusted HR 0·88 0·77–1·01; p=0·07), but did in the T1N0 subgroup (adjusted 0·74 0·58–0·94; p=0·014). Breast-conserving surgery plus radiotherapy did significantly improve 10 year relative survival in the 2003 cohort overall (adjusted 0·76 0·64–0·91; p=0·003) and in the T1N0 subgroup (adjusted 0·60 0·42–0·85; p=0·004) compared with mastectomy. Interpretation Adjusting for confounding variables, breast-conserving surgery plus radiotherapy showed improved 10 year overall and relative survival compared with mastectomy in early breast cancer, but 10 year distant metastasis-free survival was improved with breast-conserving surgery plus radiotherapy compared with mastectomy in the T1N0 subgroup only, indicating a possible role of confounding by severity. These results suggest that breast-conserving surgery plus radiotherapy is at least equivalent to mastectomy with respect to overall survival and may influence treatment decision making for patients with early breast cancer. Funding None.
Summary Background The main challenge in CT screening for lung cancer is the high prevalence of pulmonary nodules and the relatively low incidence of lung cancer. Management protocols use thresholds ...for nodule size and growth rate to determine which nodules require additional diagnostic procedures, but these should be based on individuals' probabilities of developing lung cancer. In this prespecified analysis, using data from the NELSON CT screening trial, we aimed to quantify how nodule diameter, volume, and volume doubling time affect the probability of developing lung cancer within 2 years of a CT scan, and to propose and evaluate thresholds for management protocols. Methods Eligible participants in the NELSON trial were those aged 50–75 years, who have smoked 15 cigarettes or more per day for more than 25 years, or ten cigarettes or more for more than 30 years and were still smoking, or had stopped smoking less than 10 years ago. Participants were randomly assigned to low-dose CT screening at increasing intervals, or no screening. We included all participants assigned to the screening group who had attended at least one round of screening, and whose results were available from the national cancer registry database. We calculated lung cancer probabilities, stratified by nodule diameter, volume, and volume doubling time and did logistic regression analysis using diameter, volume, volume doubling time, and multinodularity as potential predictor variables. We assessed management strategies based on nodule threshold characteristics for specificity and sensitivity, and compared them to the American College of Chest Physicians (ACCP) guidelines. The NELSON trial is registered at www.trialregister.nl , number ISRCTN63545820. Findings Volume, volume doubling time, and volumetry-based diameter of 9681 non-calcified nodules detected by CT screening in 7155 participants in the screening group of NELSON were used to quantify lung cancer probability. Lung cancer probability was low in participants with a nodule volume of 100 mm3 or smaller (0·6% 95% CI 0·4–0·8) or maximum transverse diameter smaller than 5 mm (0·4% 0·2–0·7), and not significantly different from participants without nodules (0·4% 0·3–0·6, p=0·17 and p=1·00, respectively). Lung cancer probability was intermediate (requiring follow-up CT) if nodules had a volume of 100–300 mm3 (2·4% 95% CI 1·7–3·5) or a diameter 5–10 mm (1·3% 1·0–1·8). Volume doubling time further stratified the probabilities: 0·8% (95% CI 0·4–1·7) for volume doubling times 600 days or more, 4·0% (1·8–8·3) for volume doubling times 400–600 days, and 9·9% (6·9–14·1) for volume doubling times of 400 days or fewer. Lung cancer probability was high for participants with nodule volumes 300 mm3 or bigger (16·9% 95% CI 14·1–20·0) or diameters 10 mm or bigger (15·2% 12·7–18·1). The simulated ACCP management protocol yielded a sensitivity and specificity of 90·9% (95% CI 81·2–96·1), and 87·2% (86·4–87·9), respectively. A diameter-based protocol with volumetry-based nodule diameter yielded a higher sensitivity (92·4% 95% CI 83·1–97·1), and a higher specificity (90·0% 89·3–90·7). A volume-based protocol (with thresholds based on lung cancer probability) yielded the same sensitivity as the ACCP protocol (90·9% 95% CI 81·2–96·1), and a higher specificity (94·9% 94·4–95·4). Interpretation Small nodules (those with a volume <100 mm3 or diameter <5 mm) are not predictive for lung cancer. Immediate diagnostic evaluation is necessary for large nodules (≥300 mm3 or ≥10 mm). Volume doubling time assessment is advocated only for intermediate-sized nodules (with a volume ranging between 100–300 mm3 or diameter of 5–10 mm). Nodule management protocols based on these thresholds performed better than the simulated ACCP nodule protocol. Funding Zorgonderzoek Nederland Medische Wetenschappen and Koningin Wilhelmina Fonds.
Delirium is a serious and common postoperative complication, especially in frail elderly patients. The aim of this study was to evaluate the effect of a geriatric liaison intervention in comparison ...with standard care on the incidence of postoperative delirium in frail elderly cancer patients treated with an elective surgical procedure for a solid tumour.
Patients over 65 years of age who were undergoing elective surgery for a solid tumour were recruited to a multicentre, prospective, randomized, controlled trial. The patients were randomized to standard treatment versus a geriatric liaison intervention. The intervention consisted of a preoperative geriatric consultation, an individual treatment plan targeted at risk factors for delirium, daily visits by a geriatric nurse during the hospital stay and advice on managing any problems encountered. The primary outcome was the incidence of postoperative delirium. The secondary outcome measures were the severity of delirium, length of hospital stay, complications, mortality, care dependency, quality of life, return to an independent preoperative living situation and additional care at home.
In total, the data of 260 patients were analysed. Delirium occurred in 31 patients (11.9%), and there was no significant difference between the incidence of delirium in the intervention group and the usual-care group (9.4% vs. 14.3%, OR: 0.63, 95% CI: 0.29-1.35).
Within this study, a geriatric liaison intervention based on frailty for the prevention of postoperative delirium in frail elderly cancer patients undergoing elective surgery for a solid tumour has not proven to be effective.
Nederlands Trial Register Trial ID NTR 823.
Summary Background US guidelines now recommend lung cancer screening with low-dose CT for high-risk individuals. Reports of new nodules after baseline screening have been scarce and are inconsistent ...because of differences in definitions used. We aimed to identify the occurrence of new solid nodules and their probability of being lung cancer at incidence screening rounds in the Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON). Methods In the ongoing, multicentre, randomised controlled NELSON trial, between Dec 23, 2003, and July 6, 2006, 15 822 participants who had smoked at least 15 cigarettes a day for more than 25 years or ten cigarettes a day for more than 30 years and were current smokers, or had quit smoking less than 10 years ago, were enrolled and randomly assigned to receive either screening with low-dose CT (n=7915) or no screening (n=7907). From Jan 28, 2004, to Dec 18, 2006, 7557 individuals underwent baseline screening with low-dose CT; 7295 participants underwent second and third screening rounds. We included all participants with solid non-calcified nodules, registered by the NELSON radiologists as new or smaller than 15 mm3 (study detection limit) at previous screens. Nodule volume was generated semiautomatically by software. We calculated the maximum volume doubling time for nodules with an estimated percentage volume change of 25% or more, representing the minimum growth rate for the time since the previous scan. Lung cancer diagnosis was based on histology, and benignity was based on histology or stable size for at least 2 years. The NELSON trial is registered at trialregister.nl, number ISRCTN63545820. Findings We analysed data for participants with at least one solid non-calcified nodule at the second or third screening round. In the two incidence screening rounds, the NELSON radiologists registered 1222 new solid nodules in 787 (11%) participants. A new solid nodule was lung cancer in 49 (6%) participants with new solid nodules and, in total, 50 lung cancers were found, representing 4% of all new solid nodules. 34 (68%) lung cancers were diagnosed at stage I. Nodule volume had a high discriminatory power (area under the receiver operating curve 0·795 95% CI 0·728–0·862; p<0·0001). Nodules smaller than 27 mm3 had a low probability of lung cancer (two 0·5% of 417 nodules; lung cancer probability 0·5% 95% CI 0·0–1·9), nodules with a volume of 27 mm3 up to 206 mm3 had an intermediate probability (17 3·1% of 542 nodules; lung cancer probability 3·1% 1·9–5·0), and nodules of 206 mm3 or greater had a high probability (29 16·9% of 172 nodules; lung cancer probability 16·9% 12·0–23·2). A volume cutoff value of 27 mm3 or greater had more than 95% sensitivity for lung cancer. Interpretation Our study shows that new solid nodules are detected at each screening round in 5–7% of individuals who undergo screening for lung cancer with low-dose CT. These new nodules have a high probability of malignancy even at a small size. These findings should be considered in future screening guidelines, and new solid nodules should be followed up more aggressively than nodules detected at baseline screening. Funding Zorgonderzoek Nederland Medische Wetenschappen and Koningin Wilhelmina Fonds Kankerbestrijding.
Aim: Coronary artery disease (CAD) and cognitive impairment are common in the elderly, with evidence for shared risk factors and pathophysiological processes. The coronary artery calcium (CAC) score ...is a marker of subclinical CAD, which may allow early detection of individuals prone to cognitive decline. Prior studies on associations of CAC and clinical CAD with cognitive impairment had discrepant results. This systematic review aims to evaluate the association of (sub)clinical CAD with cognitive function, cognitive decline, and diagnosis of mild cognitive impairment (MCI) or dementia. Methods: A systematic search was conducted in MEDLINE, Embase, and Web of Science until February 2019, supplemented with citations tracking. Two reviewers independently screened studies and extracted information including odds ratios (ORs) and hazard ratios (HRs). Results: Forty-six studies, 10 on CAC and 36 on clinical CAD, comprising 1,248,908 participants were included in the systematic review. Studies about associations of (sub)clinical CAD with cognitive function and cognitive decline had heterogeneous methodology and inconsistent findings. Two population-based studies investigated the association between CAC and risk of dementia over 6–12.2 years using different CAC scoring methods. Both found a tendency toward higher risk of dementia as CAC severity increased. Meta-analysis in 15 studies (663,250 individuals) showed an association between CAD and MCI/dementia (pooled OR 1.32, 95%CI 1.17–1.48) with substantial heterogeneity (I2=87.0%, p＜0.001). Pooled HR of CAD for incident MCI/dementia over 3.2–25.5 years in six longitudinal studies (70,060 individuals) was 1.51 (95%CI 1.24–1.85), with low heterogeneity (I2=14.1%, p=0.32). Sensitivity analysis did not detect any study that was of particular influence on the pooled OR or HR. Conclusions: Limited evidence suggests the CAC score is associated with risk of dementia. In clinical CAD, risk of MCI and dementia is increased by 50%, as supported by stronger evidence.
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