The link between the early surgery-induced inflammatory response and postoperative cognitive dysfunction in older patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication in older patients with cancer and is associated with decreased quality of life and increased disability and mortality rates. Systemic inflammation resulting in neuroinflammation is considered important in the pathogenesis of POCD. The aim of this study was to explore the association between the early surgery-induced inflammatory response and POCD within 3 months after surgery in older cancer patients. METHODS: Patients ≥65 years in need of surgery for a solid tumor were included in a prospective cohort study. Plasma levels of C-reactive protein (CRP), interleukin-1 beta (IL-1ß), IL-6, IL-10, and Neutrophil gelatinase-associated lipocalin (NGAL) were measured perioperatively. Cognitive performance was assessed preoperatively and 3 months after surgery. POCD was defined as a decline in cognitive test scores of ≥25% on ≥2 of five tests within the different cognitive domains of memory, executive functioning, and information processing speed. Logistic regression analysis was performed. RESULTS: POCD was observed in 44 (17.7%) of 248 included patients. Age >75, preoperative Mini-Mental State Examination (MMSE) score ≤26 and major surgery were independent significant predictors for POCD. In multivariate logistic regression analysis, no significant associations were shown between the early surgery-induced inflammatory response and either POCD or decline within the different cognitive domains. CONCLUSIONS: This study shows that one out of six older patients with cancer developed POCD within 3 months after surgery. The early surgery-induced inflammatory response was neither associated with POCD, nor with decline in the separate cognitive domains. Further research is necessary for better understanding of the complex etiology of POCD.

The Association Between Intraoperative Compromised Intestinal Integrity and Postoperative Complications in Cancer Patients.

BACKGROUND: Because of perioperative splanchnic hypoperfusion, the gut wall becomes more permeable for intraluminal microbes to enter the splanchnic circulation, possibly contributing to development of complications. Hypoperfusion-related injured enterocytes release intestinal fatty acid binding protein (I-FABP) into plasma, which is used as proxy of intestinal integrity. This study investigates the occurrence of intestinal integrity loss during oncologic surgery, measured by I-FABP change. Secondary the relationship between compromised intestinal integrity, and related variables and complications were studied. METHODS: Patients undergoing oncologic surgery from prospective cohort studies were included. Urine I-FABP samples were collected preoperatively (T0) and at wound closure (T1), and in a subgroup on Day 1 (D1) and Day 2 (D2) postoperatively. I-FABP dynamics were investigated and logistic regression analyses were performed to study the association between I-FABP levels and patient-related, surgical variables and complications. RESULTS: A total of 297 patients were included with median age of 70 years. Median I-FABP value increased from 80.0 pg/mL at T0 (interquartile range [IQR] 38.0-142.0) to 115 pg/mL at T1 (IQR 48.0-198.0) (p < 0.05). Age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02-1.08) and anesthesia time (OR 1.13, 95% CI 1.02-1.25) were related to stronger I-FABP increase. When comparing I-FABP change in patients experiencing any complications versus no complications, relative I-FABP change at T1 was 145% of T0 (IQR 86-260) versus 113% (IQR 44-184) respectively (p < 0.05). CONCLUSIONS: A significant change in I-FABP levels was seen perioperatively indicating compromised intestinal integrity. Age and anesthesia time were related to higher I-FABP increase. In patients experiencing postoperative complications, a higher I-FABP increase was found.

Association between anaesthesia-related factors and postoperative neurocognitive disorder: a post-hoc analysis.

BACKGROUND: Postoperative neurocognitive disorder (pNCD) is common after surgery. Exposure to anaesthetic drugs has been implicated as a potential cause of pNCD. Although several studies have investigated risk factors for the development of cognitive impairment in the early postoperative phase, risk factors for pNCD at 3 months have been less well studied. The aim of this study was to identify potential anaesthesia-related risk factors for pNCD at 3 months after surgery. METHODS: We analysed data obtained for a prospective observational study in patients aged ≥ 65 years who underwent surgery for excision of a solid tumour. Cognitive function was assessed preoperatively and at 3 months postoperatively using 5 neuropsychological tests. Postoperative NCD was defined as a postoperative decline of ≥ 25% relative to baseline in ≥ 2 tests. The association between anaesthesia-related factors (type of anaesthesia, duration of anaesthesia, agents used for induction and maintenance of anaesthesia and analgesia, the use of additional vasoactive medication, depth of anaesthesia [bispectral index] and mean arterial pressure) and pNCD was analysed using logistic regression analyses. Furthermore, the relation between anaesthesia-related factors and change in cognitive test scores expressed as a continuous variable was analysed using a z-score. RESULTS: Of the 196 included patients, 23 (12%) fulfilled the criteria for pNCD at 3 months postoperatively. A low preoperative score on Mini-Mental State Examination (OR, 8.9 [95% CI, (2.8-27.9)], p < 0.001) and a longer duration of anaesthesia (OR, 1.003 [95% CI, (1.001-1.005)], p = 0.013) were identified as risk factors for pNCD. On average, patients scored higher on postoperative tests (mean z-score 2.35[± 3.13]). CONCLUSION: In this cohort, duration of anaesthesia, which is probably an expression of the complexity of the surgery, was the only anaesthesia-related predictor of pNCD. On average, patients' scores on cognitive tests improved postoperatively.

The association between the inflammatory response following surgery and post-operative delirium in older oncological patients: a prospective cohort study.

INTRODUCTION: Post-operative delirium (POD) is associated with increased morbidity and mortality rates in older patients. Neuroinflammation, the activation of the intrinsic immune system of the brain, seems to be one of the mechanisms behind the development of POD. The aim of this study was to explore the association between the perioperative inflammatory response and the development of POD in a cohort of older oncological patients in need for surgery. METHODS: In this prospective cohort study, patients 65 years and older in need for oncologic surgery were included. Inflammatory markers C-reactive protein (CRP), interleukin-1 beta (IL-1ß), IL-6, IL10 and Neutrophil gelatinase-associated lipocalin (NGAL) were measured in plasma samples pre- and post-operatively. Delirium Observation Screening Scale (DOS) was used as screening instrument for POD in the first week after surgery. In case of positive screening, diagnosis of POD was assessed by a clinician. RESULTS: Between 2010 and 2016, plasma samples of 311 patients with median age of 72 years (range 65-89) were collected. A total of 38 (12%) patients developed POD in the first week after surgery. The perioperative increase in plasma levels of IL-10 and NGAL were associated with POD in multivariate logistic regression analysis (OR 1.33 [1.09-1.63] P = 0.005 and OR 1.30 [1.03-1.64], P = 0.026, respectively). The biomarkers CRP, IL-1ß and IL-6 were not significantly associated with POD. CONCLUSIONS: Increased surgery-evoked inflammatory responses of IL-10 and NGAL are associated with the development of POD in older oncological patients. The outcomes of this study contribute to understanding the aetiology of neuroinflammation and the development of POD.

Compromised intestinal integrity in older adults during daily activities: a pilot study.

BACKGROUND: Malnutrition is a common and significant problem in older adults. Insight into factors underlying malnutrition is needed to develop strategies that can improve the nutritional status. Compromised intestinal integrity caused by gut wall hypoperfusion due to atherosclerosis of the mesenteric arteries in the aging gastrointestinal tract may adversely affect nutrient uptake. The presence of compromised intestinal integrity in older adults is not known. The aim of this study is to provide a proof-of-concept that intestinal integrity is compromised in older adults during daily activities. METHODS: Adults aged ≥75 years living independently without previous gastrointestinal disease or abdominal surgery were asked to complete a standardized walking test and to consume a standardized meal directly afterwards to challenge the mesenteric blood flow. Intestinal fatty acid-binding protein (I-FABP) was measured as a plasma marker of intestinal integrity, in blood samples collected before (baseline) and after the walking test, directly after the meal, and every 15 min thereafter to 75 min postprandially. RESULTS: Thirty-four participants (median age 81 years; 56% female) were included. Of the participants, 18% were malnourished (PG-SGA score ≥ 4), and 32% were at risk of malnutrition (PG-SGA score, 2 or 3). An I-FABP increase of ≥50% from baseline was considered a meaningful loss of intestinal integrity and was observed in 12 participants (35%; 8 females; median age 80 years). No significant differences were observed in either baseline characteristics, walking test scores, or calorie/macronutrient intake between the groups with and without a ≥ 50% I-FABP peak. CONCLUSION: This study is first to indicate that intestinal integrity is compromised during daily activities in a considerable part of older adults living independently.

Remote Home Monitoring of Older Surgical Cancer Patients: Perspective on Study Implementation and Feasibility.

BACKGROUND: Remote home monitoring might fill the perceived surveillance gap after hospital discharge. However, it is unclear whether older oncologic patients will be able to use the required new digital technologies. The study aimed to assess the feasibility of postoperative remote home monitoring for this population. METHODS: This observational cohort study recruited patients aged 65 years or older scheduled for oncologic surgery. The study patients used a mobile application and activity tracker preoperatively until 3 months postoperatively. A subset of the patients used additional devices (thermometer, blood pressure monitor, weight scale) and completed electronic health questionnaires 2 weeks after hospital discharge. Feasibility was assessed by the study completion rate, compliance in using components of the information technology system, acceptability [Net Promotor Score (NPS)] and usability [System Usability Scale (SUS)]. The NPS score varied from - 100 to + 100. An SUS higher than 68 was considered above average. RESULTS: Of 47 participants (mean age, 72 years; range, 65-85 years), 37 completed a follow-up assessment, yielding a completion rate of 79%. Compliance in using the activity tracker (n = 41) occurred a median of 81 days [interquartile range (IQR), 70-90 days] out of 90 post-discharge days. Compliance in measuring vital signs and completing health questionnaires varied from a median of 10.5 days (IQR, 4.5-14.0 days) to 12 days (IQR, 5-14 days) out of 14 days. The NPS was + 29.7%, and the mean SUS was 74.4 ± 19.3. CONCLUSION: Older oncologic patients in the study considered postoperative home monitoring acceptable and usable. Once they consented to participate, the patients were compliant, and the completion rate was high.

The association between the inflammatory response to surgery and postoperative complications in older patients with cancer; a prospective prognostic factor study.

BACKGROUND: Accurate prognostic biomarkers would substantially improve surgical planning and decisions making yet no studies have been reported exploring the inflammatory response in surgically treated older patients with cancer. The aim of this study was to explore inflammatory biomarkers as potential prognostic factors for postoperative complications within 30 days in older patients with cancer. METHOD: Patients 65 years and older undergoing surgery for removal of a solid malignant tumour were included in an observational cohort study. All complications occurring up to 30 days postoperatively were documented prospectively. Inflammatory markers were measured in plasma samples pre- and postoperatively: C-reactive protein (CRP), Interleukin-1 beta (IL-1ß), IL-6, IL-10, IL-12, and Tumour necrosis factor-alpha (TNF-α). Associations between inflammatory markers and postoperative complications were explored using logistic regression analysis. RESULTS: Between July 2010 and April 2014, plasma samples of 224 patients were collected. Median age was 72 (65-89) years and 116 (51.8%) patients were female. Approximately half of the patients developed postoperative complications (49.6%) of whom 62 patients (55.9%) developed >1 complication. An independent prognostic effect was observed for the inflammatory biomarkers IL-6 and IL-10 for the occurrence of postoperative complications. CONCLUSION: The perioperative inflammatory response is associated with complications, independently from patient and surgical factors which are also associated with outcome. Research is warranted towards further exploration of the perioperative inflammatory response with the aim to improve perioperative care and outcome, and might help to improve surgical planning and decision making for older patients with cancer.

The association of preoperative anxiety and depression with neurocognitive disorder following oncological surgery.

BACKGROUND: The proposed underlying mechanisms of anxiety and depression, and of postoperative neurocognitive disorder (NCD), each include immune system involvement. Therefore, the aims of this study were to investigate the incidence of postoperative NCD 3 months after surgery among oncological patients undergoing surgery and to evaluate the role of preoperative anxiety and depression. METHOD: A consecutive series of patients (age ≥ 18 years) undergoing surgery for the removal of solid tumors were included (n = 218). Cognitive performance was assessed preoperatively and at 3 months postoperatively. Preoperative anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale. RESULTS: NCD affected 12.3% of elderly patients (age ≥ 70 years, n = 57) at 3 months after surgery, with executive function mostly affected. By contrast, 8.4% of younger patients (age < 70 years, n = 107) were affected, with information processing speed mostly affected. Low educational attainment was a risk factor (OR, 6.0; 95% CI, 1.9-19.0) of overall NCD, whereas preoperative anxiety was associated with decline in the domain of executive function. CONCLUSION: Postoperative NCD is a complication of oncological surgery for all adults instead of the elderly only. Preoperative anxiety was associated with an increased risk of executive function decline, and low educational attainment was a key factor for overall NCD.

The systemic impact of a surgical procedure in older oncological patients.

BACKGROUND: An excessive inflammatory response accounts partially for the increased morbidity and mortality seen in elderly surgical patients. The aim of this study was to investigate the association between a range of pre- and peroperative factors and the extent of the inflammatory response, and to identify patients at risk of a greater inflammatory response following surgery. METHODS: Patients 65 years and older undergoing a surgical procedure for a solid malignant tumour were prospectively included in an observational cohort study. Inflammatory markers were measured in plasma samples pre- and postoperatively: C-reactive protein (CRP), Interleukin-1 beta (IL-1ß), IL-6, IL-10, IL-12, and Tumour necrosis factor alpha (TNF-α). Preoperative and postoperative inflammatory factor assay results were compared, and associations between inflammatory markers and pre- and peroperative factors were explored using multivariate linear regression analysis. RESULTS: Between July 2010 and April 2014, plasma samples of 224 patients were obtained. Median age was 72 (65-89) years and 108 (48.2%) patients were male. The predominant diagnosis was carcinoma, 156 (69.6%). Anaesthesia duration was associated with increase in CRP, IL-1ß and IL-6; intracavitary surgery with increase in IL-6; blood loss with decrease in CRP and IL-1ß; total fluid volume administered with a decrease in IL-1ß and disease stage was associated with increase in IL-6. CONCLUSIONS: The perioperative inflammatory response is related more to surgical characteristics rather than to preoperative factors (with the exception of disease stage). Elderly oncological patients undergoing longer lasting, intracavitary surgical procedures for more advanced disease stages develop the most intense inflammatory response.

Incidence and predictors of postoperative delirium after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Incidence of, and baseline characteristics associated with delirium in patients after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), were subject of investigation. METHODS: The study was conducted among a consecutive series of prospectively included patients who underwent CRS-HIPEC at the University Medical Center Groningen, Groningen, the Netherlands, between February 2006 and January 2015. A chart-based instrument for delirium during hospitalization was used to identify patients with symptoms of delirium who were not diagnosed by a psychiatrist during admission. Uni- and multivariate logistic regression analyses were performed. RESULTS: Data of 136 patients were included in the analysis. Median age was 60 years (range: 18-76) and 50 (37%) patients were male. During hospitalization, 38 (28%) patients were diagnosed with delirium. Factors that differed significantly between the patients with and without delirium by univariate analysis were included in multivariate analysis. Multivariate analysis showed that after adjustment for age and complications other than delirium, having three or more organs resected and the CRP serum levels were independent predictors for delirium (OR: 3.97; 95% 1.24-12.76; OR: 1.01; 95% 1-1.01, respectively). CONCLUSIONS: This report shows an incidence of 28% of delirium, occurring after CRS-HIPEC and suggests a role for systemic inflammation in the development of postoperative delirium.