The prognostic value of a geriatric risk score for older patients undergoing emergency surgery of colorectal cancer: A retrospective cohort study.

INTRODUCTION: Emergency surgery of colorectal cancer is associated with high mortality rates in older patients. We investigated whether information on four geriatric domains has prognostic value for 30-day mortality and postoperative morbidity including severe complications. MATERIALS AND METHODS: All consecutive patients aged 70 years or older who underwent emergency colorectal cancer surgery in six Dutch hospitals (2014-2017) were studied. Presence of geriatric risk factors was scored prior to surgery as either 0 (risk absent) or 1 (risk present) in each of four geriatric domains and summed up to calculate a sumscore with a value between 0 and 4. In addition, we separately investigated the use of a mobility aid. Primary outcome was 30-day mortality. Secondary outcomes were any postoperative complications and severe complications. Multivariable logistic regression model was used to evaluate the sumscore and outcomes. RESULTS: Two hundred seven patients were included. Median age was 79.4 years. One hundred seventy-five patients (76%) presented with obstruction, 22 (11%) with a perforation, and 17 (8%) with severe anemia. Mortality rates were 2.9%, 13.6%, and 29.6% for patients with a sumscore of 0, 1-2, and 3-4 respectively, with odds ratio (OR) 4.8 [95% confidence interval (CI) 1.03-22.95] and OR 10.6 [95% CI 1.99-56.34] for a sumscore of 1-2 and 3-4 respectively. Use of a mobility aid was associated with increased mortality OR 8.0 [95% CI 2.74-23.43] and severe complications OR 2.31 [95% CI 1.17-4.55]. DISCUSSION: This geriatric sumscore and the use of a mobility aid have strong association with 30-day mortality after emergency surgery of colorectal cancer. This could provide better insight into surgical risk and help select high-risk patients for alternative strategies.

Validation of the ACS NSQIP surgical risk calculator in older patients with colorectal cancer undergoing elective surgery.

BACKGROUND: For clinical decision making it is important to identify patients at risk for adverse outcomes after colorectal cancer (CRC) surgery, especially in the older population. Because the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator is potentially useful in clinical practice, we performed an external validation in a Dutch multicenter cohort of patients ≥70 years undergoing elective non-metastatic CRC surgery. METHODS: We compared the ACS NSQIP calculator mean predicted risk to the overall observed rate of anastomotic leakage, return to operation room, pneumonia, discharge not to home, and readmission in our cohort using a one-sample Z-test. Calibration plots and receiver operating characteristic (ROC) curves were used to determine the calculator's performance. RESULTS: Six hundred eighty-two patients were included. Median age was 76.2 years. The ACS NSQIP calculator accurately predicted the overall readmission rate (predicted: 8.6% vs. observed: 7.8%, p = 0.456), overestimated the rate of discharge not to home (predicted:11.2% vs. observed: 7.0% p = 0.005) and underestimated the observed rate of all other outcomes. The calibration plots showed poor calibration for all outcomes. The ROC-curve showed an area under the curve (AUC) of 0.75 (95% confidence interval [CI] 0.67-0.83) for pneumonia and 0.70 (0.62-0.78) for discharge not to home. The AUC for all other outcomes was poor. CONCLUSIONS: The ACS NSQIP surgical risk calculator had a poor individual risk prediction (calibration) for all outcomes and only a fair discriminative ability (discrimination) to predict pneumonia and discharge not to home. The calculator might be considered to identify patients at high risk of pneumonia and discharge not to home to initiate additional preoperative interventions.

Loss of skeletal muscle density during neoadjuvant chemotherapy in older women with advanced stage ovarian cancer is associated with postoperative complications.

OBJECTIVE: To assess the association between loss of lumbar skeletal muscle mass and density during neoadjuvant chemotherapy (NACT) and postoperative complications after interval cytoreductive surgery (CRS) in older patients with ovarian cancer. MATERIALS AND METHODS: This multicenter, retrospective cohort study included patients aged 70 years and older with primary advanced stage ovarian cancer (International Federation of Gynecology and Obstetrics stage III-IV), treated with NACT and interval CRS. Skeletal muscle mass and density were retrospectively assessed using Skeletal Muscle Index (SMI) and Muscle Attenuation (MA) on routinely made Computed Tomography scans before and after NACT. Loss of skeletal muscle mass or density was defined as >2% decrease per 100 days in SMI or MA during NACT. RESULTS: In total, 111 patients were included. Loss of skeletal muscle density during NACT was associated with developing any postoperative complication ≤30 days after interval CRS both in univariable (Odds Ratio (OR) 3.69; 95% Confidence Interval (CI) 1.57-8.68) and in multivariable analysis adjusted for functional impairment and WHO performance status (OR 3.62; 95%CI 1.27-10.25). Loss of skeletal muscle density was also associated with infectious complications (OR 3.67; 95%CI 1.42-9.52) and unintended discontinuation of adjuvant chemotherapy (OR 5.07; 95%CI 1.41-18.19). Unlike loss of skeletal muscle density, loss of skeletal muscle mass showed no association with postoperative outcomes. CONCLUSION: In older patients with ovarian cancer, loss of skeletal muscle density during NACT is associated with worse postoperative outcomes. These results could add to perioperative risk assessment, guiding the decision to undergo surgery or the need for perioperative interventions.

A Prediction Model for Severe Complications after Elective Colorectal Cancer Surgery in Patients of 70 Years and Older.

Introduction Older patients have an increased risk of morbidity and mortality after colorectal cancer (CRC) surgery. Existing CRC surgical prediction models have not incorporated geriatric predictors, limiting applicability for preoperative decision-making. The objective was to develop and internally validate a predictive model based on preoperative predictors, including geriatric characteristics, for severe postoperative complications after elective surgery for stage I-III CRC in patients ≥70 years. PATIENTS AND METHODS: A prospectively collected database contained 1088 consecutive patients from five Dutch hospitals (2014-2017) with 171 severe complications (16%). The least absolute shrinkage and selection operator (LASSO) method was used for predictor selection and prediction model building. Internal validation was done using bootstrapping. RESULTS: A geriatric model that included gender, previous DVT or pulmonary embolism, COPD/asthma/emphysema, rectal cancer, the use of a mobility aid, ADL assistance, previous delirium and polypharmacy showed satisfactory discrimination with an AUC of 0.69 (95% CI 0.73-0.64); the AUC for the optimism corrected model was 0.65. Based on these predictors, the eight-item colorectal geriatric model (GerCRC) was developed. CONCLUSION: The GerCRC is the first prediction model specifically developed for older patients expected to undergo CRC surgery. Combining tumour- and patient-specific predictors, including geriatric predictors, improves outcome prediction in the heterogeneous older population.

Low preoperative skeletal muscle density is predictive for negative postoperative outcomes in older women with ovarian cancer.

OBJECTIVE: To determine the predictive value of lumbar skeletal muscle mass and density for postoperative outcomes in older women with advanced stage ovarian cancer. METHODS: A multicenter, retrospective cohort study was performed in women ≥ 70 years old receiving surgery for primary, advanced stage ovarian cancer. Skeletal muscle mass and density were assessed in axial CT slices on level L3. Low skeletal muscle mass was defined as skeletal muscle index < 38.50 cm2/m2. Low skeletal muscle density was defined as one standard deviation below the mean (muscle attenuation < 22.55 Hounsfield Units). The primary outcome was any postoperative complication ≤ 30 days after surgery. Secondary outcomes included severe complications, infections, delirium, prolonged hospital stay, discharge destination, discontinuation of adjuvant chemotherapy and mortality. RESULTS: In analysis of 213 patients, preoperative low skeletal muscle density was associated with postoperative complications ≤ 30 days after surgery (Odds Ratio (OR) 2.83; 95% Confidence Interval (CI) 1.41-5.67), severe complications (OR 3.01; 95%CI 1.09-8.33), infectious complications (OR 2.79; 95%CI 1.30-5.99) and discharge to a care facility (OR 3.04; 95%CI 1.16-7.93). Preoperative low skeletal muscle mass was only associated with infectious complications (OR 2.32; 95%CI 1.09-4.92). In a multivariable model, low skeletal muscle density was of added predictive value for postoperative complications (OR 2.57; 95%CI 1.21-5.45) to the strongest existing predictor functional impairment (KATZ-ADL ≥ 2). CONCLUSION: Low skeletal muscle density, as a proxy of muscle quality, is associated with poor postoperative outcomes in older patients with advanced stage ovarian cancer. These findings can contribute to postoperative risk assessment and clinical decision making.

Risk prediction models for postoperative outcomes of colorectal cancer surgery in the older population - a systematic review.

BACKGROUND: An increasing number of patients with Colorectal Cancer (CRC) is 65 years or older. We aimed to systematically review existing clinical prediction models for postoperative outcomes of CRC surgery, study their performance in older patients and assess their potential for preoperative decision making. METHODS: A systematic search in Pubmed and Embase for original studies of clinical prediction models for outcomes of CRC surgery. Bias and relevance for preoperative decision making with older patients were assessed using the CHARMS guidelines. RESULTS: 26 prediction models from 25 publications were included. The average age of included patients ranged from 61 to 76. Two models were exclusively developed for 65 and older. Common outcomes were mortality (n = 10), anastomotic leakage (n = 7) and surgical site infections (n = 3). No prediction models for quality of life or physical functioning were identified. Age, gender and ASA score were common predictors; 12 studies included intraoperative predictors. For the majority of the models, bias for model development and performance was considered moderate to high. CONCLUSIONS: Prediction models are available that address mortality and surgical complications after CRC surgery. Most models suffer from methodological limitations, and their performance for older patients is uncertain. Models that contain intraoperative predictors are of limited use for preoperative decision making. Future research should address the predictive value of geriatric characteristics to improve the performance of prediction models for older patients.

The impact of colorectal surgery on health-related quality of life in older functionally dependent patients with cancer - A longitudinal follow-up study.

BACKGROUND: Older patients who are functionally compromised or frail may be at risk for loss of quality of life (QoL) after colorectal cancer (CRC) surgery. We prospectively studied health-related QoL (HRQoL) and its association with functional dependency on multiple time points before and after CRC surgery. METHODS: Included were patients aged 70 years and older who underwent elective CRC surgery between 2014 and 2015 in combination with an oncogeriatric care path. HRQoL (EORTC QLQ-C30 and CR38) and activities of daily living (ADL, Barthel Index) were measured at four time-points; prior to (T0) and at 3 (T3), 6 (T6), and 12 (T12) months after surgery. Functional dependency was defined as a Barthel Index <19. Using mixed-model regression analysis associations between dependency, time and HRQoL outcomes were tested and corrected for confounders. RESULTS: Response rate was 67% (n = 106) to two or more questionnaires; 26 (25%) patients were functionally dependent. Overall, functionally independent patients experienced a higher HRQoL than dependent patients. Compared to T0, significant and clinically relevant improvements in HRQoL after surgery were observed in functionally dependent patients: better role functioning, a higher global health, a higher summary score, less fatigue and less gastrointestinal problems (p < .05). In functional independent patients, we observed no clinically relevant change in HRQoL. CONCLUSION: Colorectal surgery embedded in geriatric-oncological care has a positive impact on HRQoL in older functionally dependent patients with cancer. Moderate functional dependency should not be considered a generic reason for withholding surgical treatment. Information derived from this study could be used in shared decision making.

Risk stratification for surgical outcomes in older colorectal cancer patients using ISAR-HP and G8 screening tools.

BACKGROUND: Older patients are at risk for adverse outcomes after surgical treatment of cancer. Identifying patients at risk could affect treatment decisions and prevent functional decline. Screening tools are available to select patients for Geriatric Assessment. Until now their predictive value for adverse outcomes in older colorectal cancer patients has not been investigated. OBJECTIVE: To study the predictive value of the Geriatric 8 (G8) and Identification of Seniors at Risk for Hospitalized Patients (ISAR-HP) screening tools for adverse outcomes after elective colorectal surgery in patients older than 70years. Primary outcomes were 30-day complication rates, secondary outcomes were the length of hospital stay and six-month mortality. STUDY DESIGN AND METHODS: Multicentre cohort study from two hospitals in the Netherlands. Frail was defined as a G8 ≤14 and/or ISAR-HP ≥2. Odds ratio (OR) is given with 95% CI. RESULTS: Overall, 139 patients (52%) out of 268 patients were included; 32 patients (23%) were ISAR-HP-frail, 68 (50%) were G8-frail, 20 were frail on both screening tools. Median age was 77.7years. ISAR-HP frail patients were at risk for 30-day complications OR 2.4 (CI 1.1-5.4, p=0.03), readmission OR 3.4 (1.1-11.0), cardiopulmonary complications OR 5.9 (1.6-22.6), longer hospital stay (10.3 versus 8.9day) and six-months mortality OR 4.9 (1.1-23.4). When ISAR-HP and G8 were combined OR increased for readmission, 30-day and six-months mortality. G8 alone had no predictive value. CONCLUSIONS: ISAR-HP-frail patients are at risk for adverse outcomes after colorectal surgery. ISAR-HP combined with G8 has the strongest predictive value for complications and mortality. KEY POINTS: Patients screening frail on ISAR-HP are at increased risk for morbidity and mortality. Screening results of G8 alone was not predictive for postoperative outcomes. Predictive value increased when G8 and ISAR-HP were combined.

Prognostic Value of Geriatric 8 and Identification of Seniors at Risk for Hospitalized Patients Screening Tools for Patients With Lung Cancer.

BACKGROUND: Because of the time-consuming aspect of geriatric assessments, cancer specialists are seeking shorter screening tools to distinguish fit and frail patients. We analyzed the predictive value of the Geriatric 8 (G8) and Identification of Seniors at Risk for Hospitalized Patients (ISAR-HP) in elderly patients with lung cancer. PATIENTS AND METHODS: From January 2014 to April 2016, the data from patients with lung cancer aged > 70 years at 2 teaching hospitals in the Netherlands were included in a database. The patients were classified as potentially frail if they had a G8 of ≤ 14 or ISAR-HP of ≥ 2. RESULTS: Of the 142 included patients (median age, 77 years; interquartile range, 73-82 years), 108 (76%) were potentially frail. After correction for possible confounders, the potentially frail patients had a significantly greater risk of 1-year mortality (hazard ratio [HR], 4.08; 95% confidence interval [CI] 1.67-9.99; P = .02). Higher disease stage (HR, 1.72; 95% CI, 1.40-2.12; P < .001) was also a significant predictor of mortality; however, initial treatment (standard or otherwise) and age were not. When using both screening instruments separately, an impaired score on the G8 and higher disease stage were the variables remaining in the regression analyses (HR for impaired G8, 3.01; 95% CI, 1.35-6.72; P < .001). Patients with impaired scores on the ISAR-HP and G8 had more geriatric impairments than did patients with only an impaired G8 score. CONCLUSION: G8 screening is useful for the prognostication of elderly patients with lung cancer and could be used in combination with ISAR-HP to increase specificity at the cost of sensitivity. Using the ISAR-HP as the only screening tool would be insufficient.

The Effect of A Geriatric Assessment on Treatment Decisions for Patients with Lung Cancer.

BACKGROUND: Decision-making for older patients with lung cancer can be complex and challenging. A geriatric assessment (GA) may be helpful and is increasingly being used since 2005 when SIOG advised to incorporate this in standard work-up for the elderly with cancer. Our aim was to evaluate the value of a geriatric assessment in decision-making for patients with lung cancer. METHODS: Between January 2014 and April 2016, data on patients with lung cancer from two teaching hospitals in the Netherlands were entered in a prospective database. Outcome of geriatric assessment, non-oncologic interventions, and suggested adaptations of oncologic treatment proposals were evaluated. RESULTS: 83 patients (median age 79 years) were analyzed with a geriatric assessment, of which 59% were treated with a curative intent. Half of the patients were classified as ECOG PS 0 or 1. The majority of the patients (78%) suffered from geriatric impairments and 43% (n = 35) of the patients suffered from three or more geriatric impairments (out of eight analyzed domains). Nutritional status was most frequently impaired (52%). Previously undiagnosed impairments were identified in 58% of the patients, and non-oncologic interventions were advised for 43%. For 33% of patients, adaptations of the oncologic treatment were proposed. Patients with higher number of geriatric impairments more often were advised a reduced or less intensive treatment (p < 0.001). CONCLUSION: A geriatric assessment uncovers previously unknown health impairments and provides important guidance for tailored treatment decisions in patients with lung cancer. More research on GA-stratified treatment decisions is needed.

Follow up of intima-media thickness after severe early-onset preeclampsia.

OBJECTIVE: Early-onset preeclampsia is associated with premature cardiovascular disease. We previously demonstrated that femoral intima-media thickness (IMT) and markers of cardiovascular disease were increased in women 1 year after early-onset preeclampsia. The current study measured (progression of) IMT, cardiovascular disease risk factors and markers of endothelial cell dysfunction 4-5 years postpartum in the same women. STUDY DESIGN: Case-control study. POPULATION: Formerly preeclamptic women. METHODS: IMT of carotid and femoral arteries was measured by ultrasound, as a marker of subclinical atherosclerosis. Various conventional cardiovascular risk factors were determined, as well as serum markers of endothelial cell activation and inflammation. Values were compared with those 1 year after the first (preeclamptic) pregnancy. MAIN OUTCOME MEASURES IMT RESULTS: We included 17 formerly preeclamptic women (cases) and 16 controls. Mean interval between index delivery and day of investigation was 4.7 years for the cases and 4.3 years for the controls. Neither differences nor progression of IMT was observed between the cases and the controls. Increased blood pressure, body mass index, serum triglycerides and inflammatory markers were found in the cases compared with the controls. CONCLUSION: IMT was not increased in women with an almost 5-year history of severe preeclampsia as an indicator of increased cardiovascular risk. This study suggests a transient adaptive response of the arteries in formerly preeclamptic women. The persistence of cardiovascular risk factors in this group emphasizes the need for long-term follow-up.

Decreased arterial elasticity in formerly early-onset preeclamptic women.

OBJECTIVE: Preeclampsia is associated with cardiovascular atherosclerotic events later in life. Impaired arterial elasticity is considered to be a marker of vascular (endothelial) dysfunction and to be involved in the atherosclerotic process. We investigated whether previously preeclamptic women have lower arterial elasticity indices in comparison with controls. DESIGN: Case-control study. SETTING: University Medical Center Groningen, the Netherlands. SAMPLE: 14 non-pregnant women with a history of early-onset preeclampsia (cases) and 16 non-pregnant women (controls) with an uncomplicated pregnancy in 2003-2004. METHODS: Measurement of radial artery elasticity indices combined with the brachial blood pressure using pulse wave contour analysis. The assessment of traditional risk factors for cardiovascular diseases (CVD) including body mass index, serum high-sensitivity C-reactive protein (hsCRP), serum insulin and plasma homocysteine. MEAN OUTCOME MEASURES: Arterial elasticity indices and traditional risk factors for CVD in cases and controls. RESULTS: Arterial elasticity was impaired in cases as compared with controls. Body mass index, blood pressure, pulse pressure, hsCRP and triglycerides were significantly higher in cases. CONCLUSION: Arterial elasticity indices are reduced in formerly preeclamptic women, indicating vascular dysfunction. This and the more established risk factors for CVD are likely to contribute to a higher risk of CVD in women with a history of early-onset preeclampsia.

Skin autofluorescence as marker of tissue advanced glycation end-products accumulation in formerly preeclamptic women.

CONDENSATION: In women with a history of preeclampsia skin autofluorescence as marker of tissue AGEs accumulation is increased, supporting a common causal metabolic or vascular link between preeclampsia and cardiovascular diseases. OBJECTIVE: To investigate whether skin autofluorescence (AF), as marker of tissue accumulation of advanced glycation end-products (AGEs), is elevated in women with a 4-year history of severe preeclampsia. METHODS: About 17 formerly preeclamptic women and 16 controls were included. Skin AF and several traditional cardiovascular risk factors were recorded. RESULTS: In comparison to controls, formerly preeclamptic women had higher skin AF of the legs, body mass index (BMI), blood pressure, and high-sensitivity C-reactive protein (hsCRP), HbA1C, and triglycerides in serum. CONCLUSION: Skin AF as well as cardiovascular risk factors is elevated in formerly preeclamptic women. These results suggest a common causal vascular link between preeclampsia and cardiovascular diseases.