Comparison of the prognostic value of inflammation based pathological and biochemical criteria in patients undergoing potentially curative resection for colorectal cancer

<b>Objective</b>: To examine interrelationships between the local inflammatory response (Klintrup and Jass scores) and the systemic inflammatory response (Glasgow prognostic score [GPS]), and compare their prognostic value in patients undergoing curative resection for colorectal cancer. <b>Background</b>: Both localized peritumoral inflammatory cell infiltrate and the host systemic inflammatory response are known to have prognostic value in colorectal cancer. However, the interrelationships of biochemical and cellular components of the systemic inflammatory response and the local inflammatory response are poorly understood. <b>Methods</b>: Retrospective study of 287 patients who underwent surgery between 1997 and 2004. Data were collected from routine preoperative blood tests. Routine pathology specimens were scored according to Jass and Klintrup criteria for peritumoral infiltrate. <b>Results</b>: Increased Dukes stage was associated with less peritumoral infiltrate (Jass criteria: P < 0.001, Klintrup criteria: P < 0.01). Increased modified GPS (mGPS) was associated with increased circulating white cell (P < 0.01) and neutrophil (P < 0.01) counts and low lymphocyte counts (P < 0.01). Increased circulating white cell count was associated with increased neutrophil count (P < 0.001) and low-grade peritumoral infiltrate (P < 0.05, Klintrup criteria). Jass and Klintrup criteria for peritumoral infiltrate were directly associated (P < 0.001). On univariate survival analysis of patients with node-negative disease (Dukes A and B), age (P < 0.01), mGPS (P < 0.01), neutrophil count (P < 0.05), and Klintrup criteria (P < 0.05) were associated with cancer-specific survival. On multivariate survival analysis in node-negative disease, the mGPS (hazard ratio: 2.61, 95% CI: 1.27-5.35, P < 0.01) and Klintrup criteria (hazard ratio: 6.31, 95% CI: 1.40-28.44, P < 0.05) were independently associated with cancer-specific survival. <b>Conclusions</b>: The results of the present study suggest low peritumoral infiltrate (Klintrup criteria) and increased systemic inflammation (mGPS criteria) are linked through the cell-mediated immune system. Furthermore, both pathologic (Klintrup) and biochemical (mGPS) measures of the inflammatory response predict survival after colorectal cancer surgery

The relationship between pre-operative psoas and skeletal muscle parameters and survival following endovascular aneurysm repair: a systematic review and meta-analysis

Sarcopenia is characterised by chronically reduced skeletal muscle volume and function, and is determined radiologically by psoas and skeletal muscle measurement. The present systematic review and meta-analysis aims to examine the relationship between pre-operative CT-derived psoas and skeletal muscle parameters and outcomes in patients undergoing EVAR and F/B-EVAR for aortic aneurysm. The MEDLINE database was interrogated for studies investigating the effect of pre-operative CT-diagnosed sarcopenia on outcomes following EVAR and F/B-EVAR. The systematic review was carried out in accordance with PRISMA guidelines. The primary outcome was overall mortality. RevMan 5.4.1 was used to perform meta-analysis. PROSPERO Database Registration Number: CRD42021273085. Ten relevant studies were identified, one reporting skeletal muscle parameters, and the remaining nine reporting psoas muscle parameters, which were used for meta-analysis. There were a total of 2563 patients included (2062 EVAR, 501 F/B-EVAR), with mean follow-up ranging from 25 to 101 months. 836 patients (33%) were defined as radiologically sarcopenic. In all studies, the combined HR for all-cause mortality in sarcopenic versus non-sarcopenic patients was 2.61 (1.67–4.08), p < .001. Two studies reported outcomes on patients undergoing F/B-EVAR; the combined HR for all-cause mortality in sarcopenic versus non-sarcopenic patients was 3.08 (1.66–5.71), p = .004. Radiological sarcopenia defined by psoas or skeletal muscle parameters was associated with inferior survival in patients undergoing both EVAR and F/B-EVAR. Current evidence is limited by heterogeneity in assessment of body composition and lack of a consensus definition of radiological sarcopenia

The relationship between clinical frailty score, CT-derived body composition, systemic inflammation, and survival in patients with chronic limb threatening ischaemia

Introduction: Frailty is a chronic condition with complex aetiology and impaired functional performance, which has been associated altered body composition and chronic inflammation. Chronic Limb Threatening Ischaemia (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 centre with CLTI were included over a 12-month period. Frailty was diagnosed using the clinical frailty scale (CFS). Body composition was assessed using CT at the L3 vertebral level (CT-BC) to generate visceral and subcutaneous fat indices (VFI, SFI), skeletal muscle index (SMI), and skeletal muscle density (SMD). SMI and SMD 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 (IQR) follow-up of 22 (6) months (range 15-32 months), and 79 deaths during the follow-up period. 100 patients (53%) had a CFS > 4. CFS > 4 (HR 2.14, 95% 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 (OR 1.88, 95% CI 1.09 – 3.24, p < 0.01) was independently associated with CFS > 4. Patients with CT-SS 0 & CFS ≤4 had 90% (SE 5%) 1-year survival, compared with 35% (SE 9%) in patients with CT-SS 2 & CFS >4 (p <0.001). Patients with mGPS 0 & CFS ≤ 4 had 94% (SE 4%) 1-year survival compared with 44% (SE 6%) in the mGPS 2 & 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

The relationship between aortic calcification and anastomotic leak following gastrointestinal resection: a systematic review

Anastomotic leak (AL) is a significant complication of gastrointestinal (GI) surgery. Impaired perfusion of the anastomosis is thought to play an important role. The degree of aortic calcification (AC) visible on preoperative CT imaging may be associated with an increased risk of AL following GI resection. This review assessed the relationship between AC and AL in patients undergoing GI resection. MEDLINE, EMBASE and the Cochrane library were systematically searched between 1946 and 2019. Relevant keywords were grouped to form a sensitive search strategy: surgical procedure (e.g. digestive system surgical procedure), calcification (e.g. vascular calcification, calcium score) and outcome (e.g. anastomotic leak). Studies assessing the degree of AC on preoperative imaging in relation to AL in adult patients requiring resection and anastomosis were included. The quality of each study was assessed using the Newcastle-Ottawa scale. Bias was assessed using the RevMan risk of bias tool. Nine observational studies were included: four in patients undergoing oesophageal resection (n=1446) and five in patients undergoing colorectal resection (n=556). AL occurred in 20% of patients following oesophagectomy and 14% of patients following colorectal resection. Adjustment for relevant confounders was limited in most studies. Two studies reported a relationship between the degree of AC and AL in patients undergoing oesophagectomy, independent of age and comorbidity. One study reported an association between AC and AL following colorectal resection, while three studies reported higher calcium scores in the iliac arteries of patients who developed colorectal AL. Overall study quality was moderate to good using the Newcastle-Ottawa scale. Detection and reporting bias was evident in the studies examining AL following colorectal resection. The current evidence suggests that the degree of AC may be associated with the development of AL, in particular in patients undergoing oesophagectomy. Further prospective data with adequate adjustment for confounders is required

The prognostic value of pre-operative systemic inflammation-based scoring in patients undergoing endovascular repair of AAA

Objectives: Abdominal aortic aneurysm (AAA) is a common condition which is predominantly managed in the UK 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 systemic inflammatory response and survival in patients undergoing standard and complex endovascular aneurysm repair (EVAR and F/B-EVAR). Methods: Consecutive patients undergoing elective EVAR and F/B-EVAR were retrospectively identified from three tertiary vascular centres over a 5-year period. Neutrophil:lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) were calculated from pre-operative 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 sub-groups of SIG. Results: There were 506 patients included in the final study, with a median (IQR) follow-up of 68.0 (27.3) months, and there were 163 deaths during the follow-up period. Mean (95% CI) survival in the SIG 0 vs. SIG 1 vs. SIG 2 vs. SIG 3 vs. SIG 4 subgroups was 80.7 (76.5 – 85.0) vs. 78.7 (72.7 – 84.7) vs. 61.0 (51.1 - 70.8) vs. 65.1 (45.0 – 85.2) vs. 54.9 (34.4 – 75.3) months (p < 0.05). In the entire cohort, age (p < 0.001), BMI (p <0.05), high creatinine (p <0.05), and SIG (p < 0.05) were associated with survival on univariate analysis, with retained independent association for age (HR 1.72, 95% CI 1.29 – 2.31, p <0.001) and SIG (HR 1.20 95% CI 1.02 – 1.40, p <0.05) on multivariate analysis. Increasing SIG (AUC 0.68, 95% CI 0.58 – 0.78, p <0.01) predicted 1-year mortality. Conclusions: Markers of the systemic inflammatory response such the SIG may be used to identify patients at higher risk of adverse outcome in patients undergoing EVAR and F/B-EVAR for AAA. These findings warrant further investigation in large prospective cohort studies

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

Objectives: Patient selection and risk stratification for elective repair of abdominal aortic aneurysm (AAA), either by open surgical repair (OSR) or endovascular aneurysm repair (EVAR), remains challenging. 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 EVAR. The relationship between CT-BC, systemic inflammation, and prognosis has been explored in patients with cancer, but data in non-cancer 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: 611 consecutive patients undergoing elective intervention for AAA at three large tertiary referral centres were retrospectively recruited for inclusion into the study. CT-BC was performed and analysed using the CT-sarcopenia score (CT-SS). Subcutaneous and visceral fat indices (SFI, VFI) were also recorded. SIG was calculated from pre-operative blood tests. The outcomes of interest were overall and 5-year mortality. Results: Median (IQR) follow-up was 67.0 (32) months, and there were 194 (32%) deaths during the follow-up period. There were 122 (20%) OSR cases, 558 (91%) males, and a median (IQR) age of 73.0 (11.0) years. Age (HR 1.66, 95% CI 1.28 – 2.14, p <0.001), elevated CT-SS (HR 1.58, 95% CI 1.28 – 1.94, p <0.001), and elevated SIG (HR 1.29, 95% CI 1.07 – 1.55, p <0.01) were independently associated with increased hazard of mortality. Mean (95% CI) survival in the CT-SS 0 & SIG 0 sub-group was 92.6 (84.8 – 100.4) months, compared with 44.9 (30.6 – 59.2) months in the CT-SS 2 & SIG ≥ 2 sub-group (p <0.001). Patients with CT-SS 0 & SIG 0 had 90% (SE 4%) 5-year survival, compared with 34% (SE 9%) in patients with CT-SS 2 & SIG ≥ 2 (p <0.001). Conclusions: Combining measures of radiological sarcopenia and the SIR offers prognostic value in patients undergoing elective intervention for AAA and may contribute to future clinical risk predication strategies

The Glasgow Microenvironment Score and risk and site of recurrence in TNM I–III colorectal cancer

Background: Glasgow Microenvironment Score (GMS) stratifies long-term survival into three groups based on tumour phenotype: peritumoural inflammation (Klintrup–Mäkinen (KM)) and tumour stroma percentage (TSP). However, it is not known if the location of disease recurrence is influenced by the GMS category. Methods: Seven hundred and eighty-three TNM I–III colorectal cancers (CRC) were included. GMS (GMS0—high KM; GMS1—low KM, low TSP; GMS2—low KM, high TSP) and cancer-specific survival (CSS), overall survival (OS) and disease recurrence were assessed using Cox regression analysis. Results: Of the 783 patients, 221 developed CRC recurrence; 65 developed local recurrence + systemic disease. GMS was independent for CSS (HR 1.50, 95% CI 1.17–1.92, p < 0.001) and OS (HR 1.23, 1.05–1.44, p = 0.01). Higher GMS category was associated with T-stage, N-stage, emergency presentation and venous invasion. GMS was independent for local+systemic recurrence (HR 11.53, 95% CI 1.45–91.85, p = 0.04) and distant-only recurrence (HR 3.01, 95% CI 1.59–5.71, p = 0.002). GMS 2 disease did not appear to have statistically better outcomes with adjuvant chemotherapy in high-risk disease. Conclusion: Although confounded by a higher rate of T4 and node-positive disease, GMS 1 and 2 are associated with an increased risk of local and distant recurrence. GMS is an independent poor prognostic indicator for recurrent colorectal cancer. Higher GMS patients may benefit from enhanced postoperative surveillance

Changes in the multidisciplinary management of rectal cancer from 2009 to 2015 and associated improvements in short‐term outcomes

Aim: Significant recent changes in management of locally advanced rectal cancer include preoperative staging, use of extended neoadjuvant therapies, and minimally invasive surgery (MIS). This study was aimed at characterizing those changes and associated short‐term outcomes. Method: We retrospectively analysed treatment and outcome data from patients with T3/4 or N+ locally advanced rectal cancer ≤15 cm from the anal verge who were evaluated at a comprehensive cancer center in 2009–2015. Results: In total, 798 patients were identified and grouped into five cohorts based on treatment year: 2009‐2010, 2011, 2012, 2013, and 2014‐2015. Temporal changes included increased reliance on MRI staging, from 57% in 2009‐2010 to 98% in 2014‐2015 (p < 0.001); increased use of total neoadjuvant therapy, from 17% to 76% (p < 0.001); and increased use of MIS, from 33% to 70% (p < 0.001). Concurrently, median hospital stay decreased (from 7 to 5 days; p < 0.001), as did the rates of grade III‐V complications (from 13% to 7%; p < 0.05), surgical site infections (from 24% to 8%; p < 0.001), anastomotic leak (from 11% to 3%; p < 0.05), and positive circumferential resection margin (from 9% to 4%; p < 0.05). TNM downstaging increased from 62% to 74% (p = 0.002). Conclusion: Shifts toward MRI‐based staging, total neoadjuvant therapy, and MIS occurred between 2009 and 2015. Over the same period, treatment responses improved, and lengths of stay and the incidence of complications decreased

The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer

Background: The Glasgow Microenvironment Score (GMS) combines peritumoural inflammation and tumour stroma percentage to assess interactions between tumour and microenvironment. This was previously demonstrated to associate with colorectal cancer (CRC) prognosis, and now requires validation and assessment of interactions with adjuvant therapy. Methods: Two cohorts were utilised; 862 TNM I–III CRC validation cohort, and 2912 TNM II–III CRC adjuvant chemotherapy cohort (TransSCOT). Primary endpoints were disease-free survival (DFS) and relapse-free survival (RFS). Exploratory endpoint was adjuvant chemotherapy interaction. Results: GMS independently associated with DFS (p = 0.001) and RFS (p < 0.001). GMS significantly stratified RFS for both low risk (GMS 0 v GMS 2: HR 3.24 95% CI 1.85–5.68, p < 0.001) and high-risk disease (GMS 0 v GMS 2: HR 2.18 95% CI 1.39–3.41, p = 0.001). In TransSCOT, chemotherapy type (pinteraction = 0.013), but not duration (p = 0.64) was dependent on GMS. Furthermore, GMS 0 significantly associated with improved DFS in patients receiving FOLFOX compared with CAPOX (HR 2.23 95% CI 1.19–4.16, p = 0.012). Conclusions: This study validates the GMS as a prognostic tool for patients with stage I–III colorectal cancer, independent of TNM, with the ability to stratify both low- and high-risk disease. Furthermore, GMS 0 could be employed to identify a subset of patients that benefit from FOLFOX over CAPOX

Role of systemic inflammatory response in predicting survival in patients with primary operable cancer

Disease progression in cancer is dependent on the complex interaction between the tumor and the host inflammatory response. There is substantial evidence in advanced cancer that host factors, such as weight loss, poor performance status and the host systemic inflammatory response, are linked, and the latter is an important tumor-stage-independent predictor of outcome. Indeed, the systemic inflammatory response, as evidenced by an elevated level of C-reactive protein, is now included in the definition of cancer cachexia. This review examines the role of the systemic inflammatory response in predicting survival in patients with primary operable cancer. Approximately 80 studies have evaluated the role of the systemic inflammatory response using biochemical or hematological markers, such as elevated C-reactive protein levels, hypoalbuminemia or increased white cell, neutrophil and platelet counts. Combinations of such factors have been used to derive simple inflammation-based prognostic scores, such as the Glasgow Prognostic Score, the neutrophil:lymphocyte ratio and the platelet:lymphocyte ratio. This review demonstrates that there is now good evidence that preoperative measures of the systemic inflammatory response predict cancer survival, independent of tumor stage, in primary operable cancer. The evidence is particularly robust in colorectal (including liver metastases), gastro–esophageal and renal cancers. As described in this article, measurement of the systemic inflammatory response is simple, reliable and can be clinically incorporated into current staging algorithms. This will provide the clinician with a better prediction of outcome, and therefore better treatment allocation in patients with primary operable cancer. Furthermore, systemic inflammation-based markers and prognostic scores not only identify patients at risk, but also provide well-defined therapeutic targets for future clinical trials