Cardiopulmonary exercise testing, computed tomography-derived body composition, systemic inflammation and survival after elective abdominal aortic aneurysm repair: A retrospective cohort study.

BACKGROUND: Cardio-pulmonary exercise testing (CPEX) is selectively used before intervention for abdominal aortic aneurysm (AAA). Sarcopenia, a chronic condition defined by reduced skeletal muscle function and volume, can be assessed radiologically by computed tomography (CT)-derived body composition analysis (CT-BC), and is associated with systemic inflammation. OBJECTIVE: The aim was to describe the association between CT-BC, CPEX, inflammation and survival in patients undergoing elective intervention for AAA. SETTING: Patients were recruited retrospectively from a single, secondary-care centre-operative database. Cases undergoing elective endovascular aneurysm repair (EVAR) and open surgical repair (OSR) between 31 March 2015 and 25 June 2020 were included. PATIENTS: There were 176 patients (130 EVAR, 46 OSR) available for analysis in the final study; median (interquartile range [IQR]) follow-up was 60.5 [27] months, and all completed a minimum of 2 years follow-up. MAIN OUTCOME MEASURES: Preoperative CPEX tests were recorded. CT sarcopenia score [CT-SS, range 0 to 2, calculated based on normal/low SMI (0/1) and normal/low SMD (0/1)] assessed radiological sarcopenia. Preoperative modified Glasgow Prognostic score (mGPS) was used to assess systemic inflammation. RESULTS: Mean [95% confidence interval (CI) survival in the CT-SS 0 vs. CT-SS 1 vs. CT-SS 2 subgroups was 80.1 (73.6 to 86.6) months vs. 70.3 (63.5 to 77.1) months vs. 63.8 (53.4 to 74.2) months] (P = 0.01). CT-SS was not associated with CPEX results (P > 0.05). Elevated CT-SS [hazard ratio (HR) 1.83, 95% CI, 1.16 to 2.89, P < 0.01] was independently associated with increased hazard of long-term mortality; however, CPEX results were not (P > 0.05). CONCLUSION: CPEX test results were not consistently associated with body composition and did not have significant prognostic value in patients undergoing elective treatment for AAA.

A systematic review of the neutrophil to lymphocyte and platelet to lymphocyte ratios in patients with lower extremity arterial disease.

Lower extremity arterial disease (LEAD) is caused by atherosclerotic plaque in the arterial supply to the lower limbs. The neutrophil to lymphocyte and platelet to lymphocyte ratios (NLR, PLR) are established markers of systemic inflammation which are related to inferior outcomes in multiple clinical conditions, though remain poorly described in patients with LEAD. This review was carried out in accordance with PRISMA guidelines. The MEDLINE database was interrogated for relevant studies. Primary outcome was the prognostic effect of NLR and PLR on clinical outcomes following treatment, and secondary outcomes were the prognostic effect of NLR and PLR on disease severity and technical success following revascularisation. There were 34 studies included in the final review reporting outcomes on a total of 19870 patients. NLR was investigated in 21 studies, PLR was investigated in two studies, and both NLR & PLR were investigated in 11 studies. Relating to increased levels of systemic inflammation, 20 studies (100%) reported inferior clinical outcomes, 13 (92.9%) studies reported increased disease severity, and seven (87.5%) studies reported inferior technical results from revascularisation. The studies included in this review support the role of elevated NLR and PLR as key components influencing the clinical outcomes, severity, and success of treatment in patients with LEAD. The use of these easily accessible, cost effective and routinely available markers is supported by the present review.

CT-derived body composition: Differential association with disease, age and inflammation in a retrospective cohort study.

BACKGROUND: Low skeletal muscle mass and density, as assessed by CT-body composition (CT-BC), are recognised to have prognostic value in non-cancer and cancer patients. The aim of the present study was to compare CT-BC parameters between non-cancer (abdominal aortic aneurysm, AAA) and cancer (colorectal cancer, CRC) patients. METHODS: Two retrospective multicentre cohorts were compared. Thresholds of visceral fat area (VFA, Doyle), skeletal fat index (SFI, Ebadi), skeletal muscle index (SMI, Martin), and skeletal muscle density (SMD, Martin) were applied to these cohorts and compared. The systemic inflammatory response (SIR) was measured by the systemic inflammatory grade (SIG). RESULTS: 1695 patients were included; 759 patients with AAA and 936 patients with CRC. Low SMD (33% vs. 66%, p <0.001) was more prevalent in the CRC cohort. Low SMI prevalence was similar in both cohorts (51% vs. 51%, p = 0.80). Compared with the AAA cohort, the CRC cohort had a higher prevalence of raised SIG (p <0.001). Increasing age (OR 1.54, 95% CI 1.38-1.72, p < 0.001) and elevated SIG (OR 1.23, 95% CI 1.09-1.40, p = 0.001) were independently associated with increased odds of low SMI. Increasing age (OR 1.90, 95% CI 1.66-2.17, p < 0.001) CRC diagnosis (OR 5.89, 95% CI 4.55-7.62, p < 0.001), ASA > 2 (OR 1.37, 95% CI 1.08-1.73, p = 0.01), and elevated SIG (OR 1.19, 95% CI 1.03-1.37, p = 0.02) were independently associated with increased odds of low SMD. CONCLUSIONS: Increasing age and systemic inflammation appear to be important determinants of loss of skeletal muscle mass and quality irrespective of disease.

The prognostic value of clinical frailty and American Society of Anesthesiology score in patients with chronic limb threatening ischaemia.

Background: Frailty is a complex multisystem syndrome associated with increased comorbidity and decreased physiological reserve. There are associations between frailty and adverse outcome in surgical patients. Chronic limb threatening ischemia (CLTI) is increasingly prevalent, with a typically frail patient population. Existing frailty scoring systems focus on functional measures and do not reliably assess comorbidities. The present study aims to describe the prognostic value of multimodal frailty assessment in patients with CLTI. Patients and methods: Patients >50 years old admitted as an emergency with CLTI between May 2020 to June 2021 were included. Frailty was measured using Clinical Frailty Score (CFS), and comorbidities with American Society of Anesthiologists score (ASA). A composite score combining CFS and ASA was derived and the prognostic value compared with each component score. The primary outcome was overall survival. Results: There were 249 eligible patients, 53.4% (n=133) had CFS>4. The mean (95% CI) overall survival for the CFS>4 cohort was 15.9 (13.6-18.3) months vs. 28.5 (26.1-30.9) months for CFS≤4 cohort (p<0.001). Increasing CFS-ASA score was associated with inferior survival on univariate (HR=2.84, 95% CI [1.96-4.11], p<0.001) and multivariate (HR=1.78, 95% CI [1.20-2.64], p<0.01) analyses. ROC-analysis showed comparable prognostic value of CFS and CFS-ASA to predict one-year survival. Conclusions: Frailty is highly prevalent and a poor prognostic indicator in patients with CLTI admitted as an emergency. Our results suggest that incorporating assessment of comorbidities into frailty assessment may offer prognostic value, but comparable to existing clinical frailty assessment. Further work to identify patients with inferior prognosis is required.

The relationship between computed tomography-derived body composition, systemic inflammation, and survival in patients with abdominal aortic aneurysm.

OBJECTIVE: Patient selection and risk stratification for elective repair of abdominal aortic aneurysm (AAA), either by open surgical repair or by endovascular aneurysm repair, remain challenging. Computed tomography (CT)-derived body composition analysis (CT-BC) and systemic inflammation-based scoring systems such as the systemic inflammatory grade (SIG) appear to offer prognostic value in patients with AAA undergoing endovascular aneurysm repair. The relationship between CT-BC, systemic inflammation, and prognosis has been explored in patients with cancer, but data in noncancer populations are lacking. The present study aimed to examine the relationship between CT-BC, SIG, and survival in patients undergoing elective intervention for AAA. METHODS: A total of 611 consecutive patients who underwent elective intervention for AAA at three large tertiary referral centers were retrospectively recruited for inclusion into the study. CT-BC was performed and analyzed using the CT-derived sarcopenia score (CT-SS). Subcutaneous and visceral fat indices were also recorded. SIG was calculated from preoperative blood tests. The outcomes of interest were overall and 5-year mortality. RESULTS: Median (interquartile range) follow-up was 67.0 (32) months, and there were 194 (32%) deaths during the follow-up period. There were 122 (20%) open surgical repair cases, 558 (91%) patients were male, and the median (interquartile range) age was 73.0 (11.0) years. Age (hazard ratio [HR]: 1.66, 95% confidence interval [CI]: 1.28-2.14, P < .001), elevated CT-SS (HR: 1.58, 95% CI: 1.28-1.94, P < .001), and elevated SIG (HR: 1.29, 95% CI: 1.07-1.55, P < .01) were independently associated with increased hazard of mortality. Mean (95% CI) survival in the CT-SS 0 and SIG 0 subgroup was 92.6 (84.8-100.4) months compared with 44.9 (30.6-59.2) months in the CT-SS 2 and SIG ≥2 subgroup (P < .001). Patients with CT-SS 0 and SIG 0 had 90% (standard error: 4%) 5-year survival compared with 34% (standard error: 9%) in patients with CT-SS 2 and SIG ≥2 (P < .001). CONCLUSIONS: Combining measures of radiological sarcopenia and the systemic inflammatory response offers prognostic value in patients undergoing elective intervention for AAA and may contribute to future clinical risk predication strategies.

The Relationship between Clinical Frailty Score, CT-Derived Body Composition, Systemic Inflammation, and Survival in Patients with Chronic Limb-Threatening Ischemia.

BACKGROUND: Frailty is a chronic condition with complex etiology and impaired functional performance that has been associated with altered body composition and chronic inflammation. Chronic limb-threatening ischemia (CLTI) carries significant morbidity and mortality and is associated with poor quality of life. The present study aims to examine these relationships and their prognostic value in patients with CLTI. METHODS: Consecutive patients presenting as unscheduled admissions to a single tertiary center with CLTI were included over a 12-month period. Frailty was diagnosed using the Clinical Frailty Scale (CFS). Body composition was assessed using computerised tomography (CT) at the L3 vertebral level (CT-BC) to generate visceral and subcutaneous fat indices, skeletal muscle index, and skeletal muscle density. Skeletal muscle index and skeletal muscle density were combined to form the CT-sarcopenia score (CT-SS). Systemic inflammation was assessed by the modified Glasgow prognostic score (mGPS). The primary outcome was overall mortality. RESULTS: There were 190 patients included with a median (interquartile range) follow-up of 22 (6) months (range 15-32 months) and 79 deaths during the follow-up period. One hundred patients (53%) had a CFS >4. CFS >4 (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.25-3.66, P < 0.01), CT-SS (HR 1.47, 95% CI 1.03-2.09, P < 0.05), and mGPS (HR 1.54, 95% CI 1.11-2.13, P < 0.01) were independently associated with increased mortality. CT-SS (odds ratio 1.88, 95% CI 1.09-3.24, P < 0.01) was independently associated with CFS >4. Patients with CT-SS 0 and CFS ≤4 had 90% (standard error [SE] 5%) 1-year survival, compared with 35% (SE 9%) in patients with CT-SS 2 and CFS >4 (P < 0.001). Patients with mGPS 0 and CFS ≤4 had 94% (SE 4%) 1-year survival compared with 44% (SE 6%) in the mGPS 2 and CFS >4 subgroup (P < 0.001). CONCLUSIONS: Frailty assessed by CFS was associated with CT-BC. CFS, CT-SS, and mGPS were associated with poorer survival in patients presenting as unscheduled admissions with CLTI. CT-SS and mGPS may contribute to part of frailty and prognostic assessment in this patient cohort.

Evaluation of the prognostic value of computed tomography-derived body composition in patients undergoing endovascular aneurysm repair.

BACKGROUND: Endovascular aneurysm repair (EVAR) is the most common mode of repair of abdominal aortic aneurysms (AAA) in the UK. EVAR ranges from standard infrarenal repair to complex fenestrated and branched EVAR (F/B-EVAR). Sarcopenia is defined by lower muscle mass and function, which is associated with inferior perioperative outcomes. Computed tomography-derived body composition analysis offers prognostic value in patients with cancer. Several authors have evaluated the role of body composition analysis in predicting outcomes in patients undergoing EVAR; however, the evidence base is limited by heterogeneous methodology. METHODS: Six hundred seventy-four consecutive patients (58 (8.6%) female, mean (SD) age 74.4 (6.8) years) undergoing EVAR and F/B-EVAR at three large tertiary centres were retrospectively recruited. Subcutaneous and visceral fat indices (SFI and VFI), psoas and skeletal muscle indices, and skeletal muscle density were measured at the L3 vertebral level from pre-operative computed tomographies. The maximally selected rank statistic technique was used to define optimal thresholds to predict mortality. RESULTS: There were 191 deaths during the median follow-up period of 60.0 months. Mean (95% CI) survival in the low SMI versus high SMI subgroups was 62.6 (58.5-66.7) versus 82.0 (78.7-85.3) months (P < 0.001). Mean (95% CI) survival in the low SFI versus high SFI subgroups was 56.4 (48.2-64.7) versus 77.1 (74.2-80.1) months (P < 0.001). One-year mortality in the low SMI versus high SMI subgroups was 10% versus 3% (P < 0.001). Low SMI was associated with increased odds of one-year mortality (OR 3.19, 95% CI 1.60-6.34, P < 0.001). Five-year mortality in the low SMI versus high SMI subgroups was 55% versus 28% (P < 0.001). Low SMI was associated with increased odds of five-year mortality (OR 1.54, 95% CI 1.11-2.14, P < 0.01). On multivariate analysis of all patients, low SFI (HR 1.90, 95% CI 1.30-2.76, P < 0.001) and low SMI (HR 1.88, 95% CI 1.34-2.63, P < 0.001) were associated with poorer survival. On multivariate analysis of asymptomatic AAA patients, low SFI (HR 1.54, 95% CI 1.01-2.35, P < 0.05) and low SMI (HR 1.71, 95% CI 1.20-2.42, P < 0.01) were associated with poorer survival. CONCLUSIONS: Low SMI and SFI are associated with poorer long-term survival following EVAR and F/B-EVAR. The relationship between body composition and prognosis requires further evaluation, and external validation of the thresholds proposed in patients with AAA is required.

The prognostic value of preoperative systemic inflammation-based scoring in patients undergoing endovascular repair of abdominal aortic aneurysm.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a common condition that is predominantly managed in the United Kingdom by endovascular aneurysm repair (EVAR). Activation of the systemic inflammatory response (SIR) appears to offer prognostic value in patients with vascular disease. The present study examines the relationship between the SIR and survival in patients undergoing standard and complex endovascular aneurysm repair (EVAR and fenestrated/branched [F/B]-EVAR). METHODS: Consecutive patients undergoing elective EVAR and F/B-EVAR were retrospectively identified from three tertiary vascular centers over a 5-year period. Neutrophil:lymphocyte ratio and modified Glasgow Prognostic Score were calculated from preoperative blood results and combined into the systemic inflammatory grade (SIG). The primary outcome was all-cause mortality during the follow-up period, which was compared between subgroups of SIGs. RESULTS: There were 506 patients included in the final study, with a median follow-up of 68.0 months (interquartile range, 27.3 months), and there were 163 deaths during the follow-up period. Mean survival in the SIG 0 vs SIG 1 vs SIG 2 vs SIG 3 vs SIG 4 subgroups was 80.7 months (95% confidence interval [CI], 76.5-85.0 months) vs 78.7 months (95% CI, 72.7-84.7 months) vs 61.0 months (95% CI, 51.1-70.8 months) vs 65.1 months (95% CI, 45.0-85.2 months) vs 54.9 months (95% CI, 34.4-75.3 months) (P < .05). In the entire cohort, age (P < .001), body mass index (P < .05), high creatinine (P < .05), and SIG (P < .05) were associated with survival on univariate analysis, with retained independent association for age (hazard ratio, 1.72; 95% CI, 1.29-2.31; P < .001) and SIG (hazard ratio, 1.20; 95% CI, 1.02-1.40; P < .05) on multivariate analysis. Increasing SIG (area under the curve, 0.68; 95% CI, 0.58-0.78; P < .01) predicted 1-year mortality. CONCLUSIONS: Markers of the SIR such the SIG may be used to identify patients at higher risk of adverse outcome in patients undergoing EVAR and F/B-EVAR for abdominal aortic aneurysms. These findings warrant further investigation in large prospective cohort studies.

Predicting necrotising soft tissue infections in people who inject drugs: poor performance of the Laboratory Risk Indicator for Necrotising Fasciitis score and development of a novel clinical predictive nomogram in a retrospective cohort with internal validation.

INTRODUCTION: Necrotising soft tissue infections (NSTI) can threaten life and limb. Early identification and urgent surgical debridement are key for improved outcomes. NSTI can be insidious. Scoring systems, like the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC), exist to aid diagnosis. People who inject drugs (PWID) are high risk for NSTI. This study aimed to assess the utility of the LRINEC in PWID with lower limb infections and develop a predictive nomogram. METHODS: A retrospective database of all hospital admissions due to limb-related complications secondary to injecting drug use between December 2011 and December 2020 was compiled through discharge codes and a prospectively maintained Vascular Surgery database. All lower limb infections were extracted from this database, dichotomised by NSTI and non-NSTI with the LRINEC applied. Specialty management times were evaluated. Statistical analyses involved: chi-square; Analysis of "variance"; Kaplan-Meier, and receiver operating characteristic curves. Nomograms were developed to facilitate diagnosis and predict survival. RESULTS: There were 557 admissions for 378 patients, with 124 (22.3%; 111 patients) NSTI. Time from admission to: theatre and computed tomography imaging respectively varied significantly between specialties ( P =0.001). Surgical specialties were faster than medical ( P =0.001). Vascular surgery received the most admissions and had the quickest time to theatre. During follow-up there were 79 (20.9%) deaths: 27 (24.3%) NSTI and 52 (19.5%) non-NSTI. LRINEC ≥6 had a positive predictive value of 33.3% and sensitivity of 74% for NSTI. LRINEC <6 had a negative predictive value of 90.7% and specificity of 63.2% for non-NSTI. Area under the curve was 0.697 (95% CI: 0.615-0.778). Nomogram models found age, C-reactive protein, and non-linear albumin to be significant predictors of NSTI, with age, white cell count, sodium, creatinine, C-reactive protein, and albumin being significant in predicting survival on discharge. CONCLUSION: There was reduced performance of the LRINEC in this PWID cohort. Diagnosis may be enhanced through use of this predictive nomogram.

The Needle and the Damage Done: A Retrospective Review of the Health Impact of Recreational Intravenous Drug Use and the Collateral Consequences for Vascular Surgery.

BACKGROUND: The UK has one of the highest rates of recreational drug use and consequent deaths in Europe. Scotland is the "Drug deaths capital of Europe." Intravenous drug use can result in limb- and life-threatening pathology. This study aimed to characterise limb-related admissions associated with intravenous drug use, outcomes and healthcare expenditure. METHODS: Retrospective data collection between December 2011 and August 2018. Patients were identified through discharge codes. Admission details were extracted from electronic records and a database compiled. Statistical analyses were performed using Statistical Package for the Social Science, P < 0.05 denoted significance. RESULTS: There were 558 admissions for 330 patients (1-9 admissions/patient), mean age 37 years (+/-7.6 SD) and 196 (59.2%; 319 admissions, 57.2%) were male. Three hundred forty-eight (62.4%) admissions were to surgical specialties, predominantly Vascular Surgery (247). Including onward referrals, Vascular ultimately managed 54.8% of admissions. Patients presented with multiple pathologies: 249 groin abscesses; 38 other abscesses; 74 pseudoaneurysms; 102 necrotising soft tissue infections (NSTI); 85 cellulitis; 138 deep venous thrombosis (DVTs); 28 infected DVTs and 70 other diagnoses. Two hundred and seventy-seven admissions (220 patients) required operations, with 361 procedures performed (1-7 operations/admission). There were 24 major limb amputations and 74 arterial ligations. Eleven amputations were due to NSTI and 13 followed ligation (17.6% of ligations). During follow-up 50 (15.2%) patients died, of which 6 (12%) had amputations (OR 3.2, 95% CI 1.04-9.61, P = 0.043). Cumulative cost of acute care was £4,783,241. CONCLUSIONS: Limb-related sequalae of intravenous drug use represents a substantial surgical workload, especially for Vascular. These are complex, high-risk patients with poor outcomes and high healthcare costs.

Giant Carotid Artery Aneurysm.

Carotid artery aneurysms account for 4% of peripheral aneurysms and may present as a neck mass, with hemispheric ischaemic symptoms, or with symptoms secondary to local compression. This case explores the presentation, investigations and management of a presumed mycotic common carotid artery aneurysm in a 77-year-old male, which was repaired using end-to-end interposition vein graft using long saphenous vein. This report discusses the aetiology, presentation and surgical management for carotid artery aneurysms, as well as focusing on that of the rare mycotic carotid artery aneurysm.

Postimplantation syndrome in endovascular aortic aneurysm repair - a systematic review.

Postimplantation syndrome (PIS) following endovascular aortic aneurysm repair (EVAR) is a poorly understood phenomenon occurring in the early post-operative course. The underlying aetiology, risk factors, clinical sequalae, and treatment options, are largely unknown. The lack of any standardised diagnostic criteria limits current research in this field. The MEDLINE database was interrogated using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) search strategy. Five search terms were used; "postimplantation syndrome" AND "aneurysm", AND "infection", AND "complications", AND "biomarkers", AND "outcomes". 19 studies were included in the review process, reporting a 17.4%-39.0% incidence of PIS. IL-6 was the most commonly elevated biomarker in PIS vs. non-PIS patients. There was a higher incidence of PIS in patients who received polyester rather than expanded-polytetrafluoroethylene (ePTFE) grafts. There was a lower rate of type 2 endoleaks observed in patients who developed PIS. Early major adverse cardiovascular events (MACE) were higher in PIS patients, however there were no studies reporting long-term MACE. Length of stay was higher in PIS patients. Current data support the role of IL-6 as being key to the development of PIS following EVAR. Further work describing the effect that PIS has on long-term clinical outcomes is needed. Lack of standardised diagnostic criteria limit the reporting of PIS between centres, the criteria proposed by this review may resolve this.

A prospective observational study of the utility of early diagnostic laparoscopy for right lower abdominal pain: a safe and effective diagnostic and therapeutic tool.

BACKGROUND AND AIMS: Diagnostic laparoscopy is commonly performed for diagnosis of right lower abdominal pain and its use is increasing in the emergency setting. Some studies have reported that diagnostic laparoscopy and laparoscopic appendicectomy have advantages over conventional surgery. Many emergency surgeons now perform diagnostic laparoscopy for both clinically diagnosed appendicitis and when the diagnosis is in doubt. The aim of the present study was to assess whether the use of diagnostic laparoscopy is justified and safe for those admitted with right lower abdominal pain. METHODS AND RESULTS: Data were collected prospectively on consecutive patients attending the acute surgical receiving unit with right iliac fossa pain or a suspected diagnosis of acute appendicitis. A total of 284 patients underwent diagnostic laparoscopy. Of them 233 (82%) had a positive finding at laparoscopy, 207 (88%) underwent appendicectomy, the majority of which were carried out laparoscopically. Surgical trainees performed the majority of operations and this did not have a negative impact on operative findings (p 0.856), operation performed (0.642), or operative duration (0.831). No intra-operative complications were sustained. Ultrasound examination was carried out in 49 patients, while CT was carried out in 24. CONCLUSION: The results of the present study highlight the utility of early diagnostic laparoscopy as both a diagnostic and therapeutic tool in the acute setting.

Improved arterial exposure and ergonomics with use of elasticated retractors in vascular surgery.

Traditional self-retaining retraction devices do not always provide adequate exposure and, on occasion, hamper economy of movement during vascular surgical procedures. We report the novel use of elasticated retractors to improve surgical exposure for vascular access procedures that may be transferable to other vascular surgical procedures.

The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer.

There is increasing and consistent evidence that cancer-associated inflammation is a key determinant of outcome in patients with cancer. Various markers of inflammation have been examined over the past decade in an attempt to refine stratification of patients to treatment and predict survival. One routinely available marker of the systemic inflammatory response is the neutrophil-lymphocyte ratio (NLR), which is derived from the absolute neutrophil and absolute lymphocyte counts of a full blood count. To date, over 60 studies (>37,000 patients) have examined the clinical utility of the NLR to predict patient outcomes in a variety of cancers. The present systematic review examines and comments on the clinical utility of the NLR. The NLR had independent prognostic value in (a) unselected cohorts (1 study of >12,000 patients), (b) operable disease (20 studies, >4000 patients), (c) patients receiving neoadjuvant treatment and resection (5 studies, >1000 patients), (d) patients receiving chemo/radiotherapy (12 studies, >2000 patients) and (e) patients with inoperable disease (6 studies, >1200 patients). These studies originated from ten different countries, in particular UK, Japan, and China. Further, correlative studies (15 studies, >8500 patients) have shown that NLR is elevated in patients with more advanced or aggressive disease evidenced by increased tumour stage, nodal stage, number of metastatic lesions and as such these patients may represent a particularly high-risk patient population. Further studies investigating the tumour and host-derived factors regulating the systemic inflammatory response, in particular the NLR, may identify novel treatment strategies for patients with cancer.

Is perioperative systemic inflammation the result of insufficient cortisol production in patients with colorectal cancer?

BACKGROUND: Patients with colorectal cancer who have a raised systemic inflammatory response before surgery have been shown to have poorer long-term and short-term outcomes. The presence of an ongoing systemic inflammatory response in these patients may be due to impaired cortisol production. The aim of the present study was to examine the relationship between the perioperative systemic inflammatory response and endogenous cortisol production. METHODS: A prospective study was performed to incorporate the assessment of adrenocortical function using synthetic adrenocorticotrophic hormone, a short Synacthen test, as part of the preoperative assessment of patients undergoing resection for colorectal cancer. RESULTS: A total of 80 patients underwent short Synacthen testing. There were no significant associations between the baseline, 30 min, or change (both relative and absolute) in cortisol and age (all p > 0.10), sex (all p > 0.10), site (all p > 0.10), TNM stage (all p > 0.10), modified Glasgow prognostic score (all p > 0.10), NLR (all p > 0.10), white cell count (all p > 0.10) or postoperative C-reactive protein concentrations (all p > 0.10). CONCLUSIONS: Impaired cortisol production was uncommon in patients with potentially curable colorectal cancer. The presence of a perioperative systemic inflammatory response was not significantly associated with impaired cortisol production.

Does interleukin-6 link explain the link between tumour necrosis, local and systemic inflammatory responses and outcome in patients with colorectal cancer?

Cancer-associated inflammation has been identified as a key determinant of disease progression and survival in colorectal cancer. In particular, it has been consistently reported that both the local and systemic inflammatory responses play an important role in determining outcome in colorectal cancer. Given the importance of cancer-associated inflammation, up-regulation or attenuation of these respective inflammatory responses may be important for progression and survival in colorectal cancer. Recent work has focused on the inter-relationships between the tumour and these key inflammatory processes. In particular, tumour necrosis has been reported to be associated with decreased local inflammatory infiltrate and with elevated markers of systemic inflammation in colorectal cancer and has been proposed as a potential link between the systemic and local inflammatory responses. Thus there is increasing interest in the potential biochemical mediators of this link. In this review we examine the evidence for IL-6 in the natural history of colorectal cancer and its relationship with tumour necrosis and the local and systemic inflammatory responses. There is now good evidence that tumour concentrations of IL-6 have been directly associated with increased necrosis, proliferation, differentiation and vascular invasion, while circulating concentrations of IL-6 are directly associated with T-stage, CRP concentrations and poorer survival. Also, interleukin-6 and down-stream pathways, such as the JAK/STAT pathway, have emerged as important factors in the modulation of cancer-associated inflammation. Therefore, IL-6 has emerged as a key mediator of the relationship between tumour necrosis, local and systemic inflammatory responses and outcome in patients with colorectal cancer.

The relationships between body composition and the systemic inflammatory response in patients with primary operable colorectal cancer.

BACKGROUND: Weight loss is recognised as a marker of poor prognosis in patients with cancer but the aetiology of cancer cachexia remains unclear. The aim of the present study was to examine the relationships between CT measured parameters of body composition and the systemic inflammatory response in patients with primary operable colorectal cancer. PATIENT AND METHODS: 174 patients with primary operable colorectal cancer who underwent resection with curative intent (2003-2010). Image analysis of CT scans was used to measure total fat index (cm(2)/m(2)), subcutaneous fat index (cm(2)/m(2)), visceral fat index (cm(2)/m(2)) and skeletal muscle index (cm(2)/m(2)). Systemic inflammatory response was measured by serum white cell count (WCC), neutrophil:lymphocyte ratio (NLR) and the Glasgow Prognostic Score (mGPS). RESULTS: There were no relationships between any parameter of body composition and serum WCC or NLR. There was a significant relationship between low skeletal muscle index and an elevated systemic inflammatory response, as measured by the mGPS (p = 0.001). This was confirmed by linear relationships between skeletal muscle index and both C-reactive protein (r = -0.21, p = 0.005) and albumin (r = 0.31, p<0.001). There was no association between skeletal muscle index and tumour stage. CONCLUSIONS: The present study highlights a direct relationship between low levels of skeletal muscle and the presence of a systemic inflammatory response in patients with primary operable colorectal cancer.