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.

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.

Route to diagnosis of colorectal cancer and association with survival within the context of a bowel screening programme.

OBJECTIVES: Bowel cancer screening has been introduced to improve colorectal cancer outcomes; however, a significant proportion of cases continue to present with TNM Stage III-IV disease and/or emergently. This study analyses the prior interaction with screening of patients diagnosed with colorectal cancer and factors associated with non-screening diagnosis. STUDY DESIGN: This was a retrospective observational study. METHODS: All patients diagnosed with colorectal cancer in the West of Scotland from 2011 to 2014 were identified. Through data linkage to the Scottish Bowel Cancer Screening Programme, we analysed patient interaction with screening within 2 years before cancer diagnosis. RESULTS: In total, 6549 patients were diagnosed with colorectal cancer, 1217 (19%) via screening. Screening participation was associated with earlier TNM stage, reduced emergency presentations and improved 3-year survival (all P < 0.001). Failure to diagnose through screening was predominantly due to non-invitation (37%), non-return of screening test (29%) or negative test (13%). Three hundred fifty-one patients were below screening age, 79% of whom were aged 40-49 years and 2035 patients were above screening age. Factors associated with non-return of screening test included age, sex, SIMD (all P < 0.001) and raised Charlson score (P = 0.030). Factors associated with negative screening result included sex, anaemia, differentiation, right-sided tumours and venous invasion (P < 0.001). CONCLUSION: Within Scotland, <20% of colorectal cancer is diagnosed through screening despite the existence of a population screening programme. Measures must be taken to improve screening participation including encouragement of those of routine screening age and those age ≥75 years in good health to participate in screening with consideration given to extending screening to under 50s. A significant false-negative rate of testing was observed in the present study and this requires further investigation within a population undergoing screening through faecal immunochemical testing.

The Influence of Systemic Inflammation on Treatment Response and Survival in Anal Squamous Cell Cancer.

AIMS: The incidence of anal squamous cell cancer (SCCA) is rising. Although chemoradiotherapy (CRT) provides a chance of cure, a proportion of patients have an incomplete response or develop recurrence. This study assessed the value of inflammation-based prognostic indicators, including the modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR), in patients with SCCA treated by CRT with curative intent. MATERIAL AND METHODS: Patients with histologically confirmed SCCA were identified from pathology records. Medical records were retrospectively reviewed and clinical, pathological and treatment characteristics were abstracted. The mGPS (0 = normal C-reactive protein [CRP] and albumin, 1 = CRP >10 mg/l and 2 = CRP >10 mg/l and albumin <35 mg/l) and NLR were calculated from routine blood tests obtained prior to CRT. RESULTS: In total, 118 patients underwent CRT for SCCA between December 2007 and February 2018. Of these, 99 patients had appropriate pretreatment blood results available. Systemic inflammation as indicated by NLR >3 and mGPS >0 was present in 41% and 39% of patients, respectively. Most patients had T2 or larger tumours (n = 85, 86%) without nodal involvement (n = 64, 65%). An elevated mGPS was associated with more advanced T-stage (56% versus 35%, P = 0.036). NLR >5 was associated with nodal positivity (56% versus 31%, P = 0.047). On multivariate analysis, more advanced T-stage (odds ratio 7.49, 95% confidence interval 1.51-37.20, P = 0.014) and a raised mGPS (odds ratio 5.13, 95% confidence interval 1.25-21.14, P = 0.024) were independently related to incomplete CRT response. An elevated mGPS was prognostic of inferior survival (hazard ratio 3.09, 95% confidence interval 1.47-6.50, P = 0.003) and cancer-specific survival (hazard ratio 4.32, 95% confidence interval 1.54-12.15, P = 0.006), independent of TNM stage. CONCLUSION: Systemic inflammation, as measured by the mGPS, is associated with an incomplete CRT response and is independently prognostic of inferior survival in patients with SCCA. The mGPS may offer a simple marker of inferior outcome that could be used to identify high-risk patients.

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

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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 are required. PROSPERO REGISTRATION NUMBER: CRD42018081128.

Effect of preoperative oral antibiotics in combination with mechanical bowel preparation on inflammatory response and short-term outcomes following left-sided colonic and rectal resections.

Background: Preoperative oral antibiotics in addition to intravenous antibiotics and mechanical bowel preparation (MBP) may influence the gut microbiome and reduce both the postoperative systemic inflammatory response to surgery and postoperative infective complications following colorectal resection. This propensity score-matched study compared outcomes of patients undergoing left-sided colonic or rectal resection with or without a combination of oral antibiotics and MBP. Methods: The addition of oral antibiotics and MBP to prophylactic intravenous antibiotics in left-sided colonic and rectal resections was introduced in 2015-2016 at a single institution. Propensity score matching was undertaken to compare the effects of oral antibiotics plus MBP versus neither oral antibiotics nor MBP on the postoperative systemic inflammatory response and short-term outcomes in patients undergoing left-sided colonic or rectal resection between 2013 and 2018. Results: Of 396 patients who had propensity score matching for host, anaesthetic and operative factors, 204 matched patients were identified. The addition of oral antibiotics and MBP was associated with a significantly reduced postoperative inflammatory response (reduced postoperative Glasgow Prognostic Score) on day 3 (odds ratio (OR) 0·66, 95 per cent c.i. 0·44 to 0·99; P = 0·013) and day 4 (OR 0·46, 0·30 to 0·71; P = 0·001). Significantly reduced overall complications (OR 0·31, 0·17 to 0·56; P < 0·001), infective complications (OR 0·41, 0·22 to 0·77; P = 0·011), surgical-site infection (OR 0·37, 0·17 to 0·83; P = 0·024) and postoperative length of hospital stay (median 7 days versus 8 days in patients who had intravenous antibiotics alone; P = 0·050) were also observed. Conclusion: Preoperative oral antibiotics and MBP in addition to prophylactic intravenous antibiotics were associated with a reduction in the postoperative systemic inflammatory response and postoperative complications in patients undergoing resectional left-sided colonic or rectal surgery.

Antecedentes: La administración preoperatoria de antibióticos por vía oral (preoperative oral antibiotics, OAB), además de por vía intravenosa y de la preparación mecánica del colon (mechanical bowel preparation, MBP) puede afectar al microbioma intestinal y disminuir tanto la respuesta postoperatoria sistémica inflamatoria a la cirugía, como las complicaciones infecciosas postoperatorias tras una resección colorrectal. Este estudio emparejado por puntaje de propensión comparó los resultados de pacientes sometidos a resección del colon izquierdo o resección rectal con y sin una combinación de OAB y MBP. Métodos: La adición de OAB y MBP a la administración profiláctica de antibióticos por vía intravenosa fue introducida en 2015­2016 en un centro médico. Se llevó a cabo un estudio emparejado por puntaje de propensión para comparar los efectos de OAB con MBP versus la no administración de OAB ni el uso de MBP sobre la respuesta postoperatoria sistémica inflamatoria a la cirugía y los resultados a corto plazo en pacientes sometidos a resección del colon izquierdo o resección rectal desde el 2013 al 2018. Resultados: De los 396 pacientes incluidos en el emparejamiento por puntaje de propensión relativo a factores relacionados con el huésped, anestésicos y operatorios, se identificaron 204 pacientes emparejados. La adición de OAB y MBP se asoció con una disminución significativa de la respuesta inflamatoria postoperatoria (disminución postoperatoria de la puntuación pronóstica de Glasgow el día 3 (razón de oportunidades, odds ratio, OR 0,66, i.c. del 95% 0,44­0,99, P = 0,013) y el día 4 (OR 0,46, i.c. del 95% 0,30­0,71, P = 0,001). También se observaron reducciones significativas de las complicaciones globales (OR 0,31, i.c. del 95% 0,17­0,56, P < 0,001), complicaciones infecciosas (OR 0,41, i.c. del 95% 0,17­0,83, P = 0,011), infecciones del sitio quirúrgico (OR 0,37, i.c. del 95% 0,17­0,83, P = 0,024) y duración de la estancia hospitalaria postoperatoria (mediana 8 versus 7 días, P = 0,05). Conclusión: La adición preoperatoria de OAB y MBP a la administración profiláctica de antibióticos intravenosos se han asociado con una disminución de la respuesta inflamatoria sistémica postoperatoria y de las complicaciones postoperatorias en pacientes sometidos a resección del colon izquierdo o cirugía rectal.

A novel tumor-based epithelial-to-mesenchymal transition score that associates with prognosis and metastasis in patients with Stage II/III colorectal cancer.

It is increasingly appreciated that host factors within the tumor center and microenvironment play a key role in dictating colorectal cancer (CRC) outcomes. As a result, the metastatic process has now been defined as a result of epithelial-mesenchymal transition (EMT). Establishment of the role of EMT within the tumor center and its effect on the tumor microenvironment would be beneficial for prognosis and therapeutic intervention in CRC. The present study assessed five immunohistochemical EMT markers within the tumor center on a 185 Stage II/III CRC patient tissue microarray. In 185 patients with CRC, cytoplasmic snail (HR 1.94 95% confidence interval [CI] 1.15-3.29, p = 0.012) and a novel combined EMT score (HR 3.86 95% CI 2.17-6.86, p < 0.001) were associated with decreased cancer-specific survival. The combined EMT score was also associated with increased tumor budding (p = 0.046), and systemic inflammation (p = 0.007), as well as decreased memory T-cells within the stroma (p = 0.030) and at the invasive margin (p = 0.035). Furthermore, the combined EMT score was associated with cancer-specific survival independent of TNM-stage (HR 4.12 95% CI 2.30-7.39, p < 0.001). In conclusion, a novel combined EMT score stratifies patient's survival in Stage II/III CRC and associates with key factors of tumor metastasis. Therefore, the combined EMT score could be used to identify patients at risk of micrometastases and who may benefit from standard adjuvant therapy, potentially in combination with EMT blockade.

The relationship between 18 F-FDG-PETCT-derived markers of tumour metabolism and systemic inflammation in patients with recurrent disease following surgery for colorectal cancer.

AIM: 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG-PETCT)-derived markers of tumour metabolism have been reported to have prognostic significance in a variety of tumours. Host inflammation is also recognized to have prognostic significance. The aim of the present study was to investigate the relationship between these markers and host systemic inflammation in patients undergoing elective surgery for colorectal cancer. METHOD: Patients with histologically confirmed colorectal cancer who underwent elective surgery between 2008 and 2015 and also underwent 18 F-FDG-PETCT at a single centre were included (n = 103). The neutrophil-lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) were derived from routine blood tests. The maximum standardized uptake (SUVmax), peak standardized uptake (SUVpeak), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured. RESULTS: There was no association between 18 F-FDG-PETCT measures of tumour metabolism and systemic inflammation in the 33 patients who underwent preoperative imaging. Of the 70 patients with recurrent disease who underwent 18 F-FDG-PETCT during follow-up, patients with NLR ≥ 5 had a significantly higher SUVmax (20 vs 7, P = 0.002), SUVpeak (14 vs 5, P < 0.001), MTV (29 g vs 2 g, P = 0.001) and TLG (338 g vs 9 g, P < 0.001). Similarly, patients with a mGPS of 1-2 at the time of 18 F-FDG-PETCT had a significantly higher median SUVmax (11 vs 6, P = 0.048), SUVpeak (8 vs 4, P = 0.046), MTV (13 ml vs 2 ml, P = 0.005) and TLG (146 g vs 10 g, P = 0.004). CONCLUSION: The present study reports a direct association between 18 F-FDG-PETCT-derived measures of tumour metabolism and systemic inflammation in patients with recurrent colorectal cancer.

ESPEN expert group recommendations for action against cancer-related malnutrition.

Patients with cancer are at particularly high risk for malnutrition because both the disease and its treatments threaten their nutritional status. Yet cancer-related nutritional risk is sometimes overlooked or under-treated by clinicians, patients, and their families. The European Society for Clinical Nutrition and Metabolism (ESPEN) recently published evidence-based guidelines for nutritional care in patients with cancer. In further support of these guidelines, an ESPEN oncology expert group met for a Cancer and Nutrition Workshop in Berlin on October 24 and 25, 2016. The group examined the causes and consequences of cancer-related malnutrition, reviewed treatment approaches currently available, and built the rationale and impetus for clinicians involved with care of patients with cancer to take actions that facilitate nutrition support in practice. The content of this position paper is based on presentations and discussions at the Berlin meeting. The expert group emphasized 3 key steps to update nutritional care for people with cancer: (1) screen all patients with cancer for nutritional risk early in the course of their care, regardless of body mass index and weight history; (2) expand nutrition-related assessment practices to include measures of anorexia, body composition, inflammatory biomarkers, resting energy expenditure, and physical function; (3) use multimodal nutritional interventions with individualized plans, including care focused on increasing nutritional intake, lessening inflammation and hypermetabolic stress, and increasing physical activity.

Tumour invasiveness, the local and systemic environment and the basis of staging systems in colorectal cancer.

BACKGROUND: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. METHODS: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR). A 5-year CSS was examined. RESULTS: A total of 331 patients were included. Increasing T stage was associated with colonic primary, N stage, poor differentiation, margin involvement and venous invasion (P<0.05). T stage was significantly associated with KM grade (P=0.001), Immunoscore (P=0.016), TSP (P=0.006), tumour budding (P<0.001), and elevated mGPS and NLR (both P<0.05). In patients with T3 cancer, N stage stratified survival from 88 to 64%, whereas Immunoscore and budding stratified survival from 100 to 70% and from 91 to 56%, respectively. The Glasgow Microenvironment Score, a score based on KM grade and TSP, stratified survival from 93 to 58%. CONCLUSIONS: Although associated with increasing T stage, local and systemic tumour environment characteristics, and in particular Immunoscore, budding, TSP and mGPS, are stage-independent determinants of survival and may be utilised in the staging of patients with primary operable colorectal cancer.

The role of dietary polyphenols in the moderation of the inflammatory response in early stage colorectal cancer.

Current focus in colorectal cancer (CRC) management is on reducing overall mortality by increasing the number of early-stage cancers diagnosed and treated with curative intent. Despite the success of screening programs in down-staging CRC, interval cancer rates are substantial and other strategies are desirable. Sporadic CRC is largely associated with lifestyle factors including diet. Polyphenols are phytochemicals ingested as part of a normal diet, which are abundant in plant foods including fruits/berries and vegetables. These may exert their anti-carcinogenic effects via the modulation of inflammatory pathways. Key signal transduction pathways are fundamental to the association of inflammation and disease progression including those mediated by NF-κB and STAT, PI3K and COX. Our aim was to examine the evidence for the effect of dietary polyphenols intake on tumor and host inflammatory responses to determine if polyphenols may be effective as part of a dietary intervention. There is good epidemiological evidence of a reduction in CRC risk from case-control and cohort studies assessing polyphenol intake. It would be premature to suggest a major public health intervention to promote their consumption; however, dietary change is safe and feasible, emphasizing the need for further investigation of polyphenols and CRC risk.

Comparison of the prognostic value of measures of the tumor inflammatory cell infiltrate and tumor-associated stroma in patients with primary operable colorectal cancer.

The aim of the present study was to compare the clinical utility of two measures of the inflammatory cell infiltrate - a H&E-based assessment of the generalized inflammatory cell infiltrate (the Klintrup-Mäkinen (KM) grade), and an immunohistochemistry-based assessment of combined CD3+ and CD8+ T-cell density (the "Immunoscore"), in conjunction with assessment of the tumor stroma percentage (TSP) in patients undergoing resection of stage I-III colorectal cancer (CRC). Two hundred and forty-six patients were identified from a prospectively maintained database of CRC resections in a single surgical unit. Assessment of KM grade and TSP was performed using full H&E sections. CD3+ and CD8+ T-cell density was assessed on full sections and the Immunoscore calculated. KM grade and Immunoscore were strongly associated (p < 0.001). KM grade stratified cancer-specific survival (CSS) from 88% to 66% (p = 0.002) and Immunoscore from 93% to 61% (p < 0.001). Immunoscore further stratified survival of patients independent of KM grade from 94% (high KM, Im4) to 60% (low KM, Im0/1). Furthermore, TSP stratified survival of patients with a weak inflammatory cell infiltrate (low KM: from 75% to 47%; Im0/1: from 71% to 38%, both p < 0.001) but not those with a strong inflammatory infiltrate. On multivariate analysis, only Immunoscore (HR 0.44, p < 0.001) and TSP (HR 2.04, p < 0.001) were independently associated with CSS. These results suggest that the prognostic value of an immunohistochemistry-based assessment of the inflammatory cell infiltrate is superior to H&E-based assessment in patients undergoing resection of stage I-III CRC. Furthermore, assessment of the tumor-associated stroma, using TSP, further improves prediction of outcome.

Serum amylase and C-reactive protein in risk stratification of pancreas-specific complications after pancreaticoduodenectomy.

BACKGROUND: Pancreas-specific complications (PSCs), comprising postoperative pancreatic fistula, haemorrhage and intra-abdominal collections, are drivers of morbidity and mortality after pancreaticoduodenectomy (PD). A serum amylase concentration of 130 units/l or more on postoperative day (POD) 0 has been shown to be an objective surrogate of pancreatic texture, a determinant of PSCs. This study evaluated serial measurements of C-reactive protein (CRP) to refine PSC risk stratification. METHODS: Consecutive patients undergoing PD between 2008 and 2014, with vascular resection if required and without preoperative chemoradiotherapy, had serum investigations from the day before operation until discharge. Receiver operating characteristic (ROC) curve analysis was used to identify a threshold value of serum CRP with clinically relevant PSCs for up to 30 days after discharge as outcome measure. RESULTS: Of 230 patients, 95 (41·3 per cent) experienced a clinically relevant PSC. A serum CRP level of 180 mg/l or higher on POD 2 was associated with PSCs, prolonged critical care stay and relaparotomy (all P < 0·050). Patients with a serum amylase concentration of 130 units/l or more on POD 0 who developed a serum CRP level of at least 180 mg/l on POD 2 had a higher incidence of morbidity. Patients were stratified into high-, intermediate- and low-risk groups using these markers. The low-risk category was associated with a negative predictive value of 86·5 per cent for development of clinically relevant PSCs. There were no deaths among 52 patients in the low-risk group, but seven deaths among 79 (9 per cent) in the high-risk group. CONCLUSION: A serum amylase level below 130 units/l on POD 0 combined with a serum CRP level under 180 mg/l on POD 2 constitutes a low-risk profile following PD, and may help identify patients suitable for early discharge.

A comparison of tumour and host prognostic factors in screen-detected vs nonscreen-detected colorectal cancer: a contemporaneous study.

AIM: In addition to TNM stage there are adverse tumour and host factors, such as venous invasion and the presence of an elevated systemic inflammatory response (SIR), that influence the outcome in colorectal cancer. The present study aimed to examine how these factors varied in screen-detected (SD) and nonscreen-detected (NSD) tumours. METHOD: Prospectively maintained databases of the prevalence round of a biennial population faecal occult blood test screening programme and a regional cancer audit database were analysed. Interval cancers (INT) were defined as cancers identified within 2 years of a negative screening test. RESULTS: Of the 395 097 people invited, 204 535 (52%) responded, 6159 (3%) tested positive and 421 (9%) had cancer detected. A further 708 NSD patients were identified [468 (65%) nonresponders, 182 (25%) INT cancers and 58 (10%) who did not attend or did not have cancer diagnosed at colonoscopy]. Comparing SD and NSD patients, SD patients were more likely to be male, and have a tumour with a lower TNM stage (both P < 0.05). On stage-by-stage analysis, SD patients had less evidence of an elevated SIR (P < 0.05). Both the presence of venous invasion (P = 0.761) and an elevated SIR (P = 0.059) were similar in those with INT cancers and in those that arose in nonresponders. CONCLUSION: Independent of TNM stage, SD tumours have more favourable host prognostic factors than NSD tumours. There is no evidence that INT cancers are biologically more aggressive than those that develop in the rest of the population and are hence likely to be due to limitations of screening in its current format.

The relationship between tumour budding, the tumour microenvironment and survival in patients with invasive ductal breast cancer.

BACKGROUND: Tumour budding has previously been reported to predict survival in several solid organ tumours, including breast; however, whether this is independent of other aspects of the tumour microenvironment is unknown. In the present study, the relationship between tumour budding, the tumour microenvironment and survival was examined in patients with invasive ductal breast cancer. METHODS: Patients presenting between 1995 and 1998 were studied (n=474). Using routine pathological sections, tumour budding was measured at the invasive margin and its association with clinicopathological characteristics and cancer-specific survival (CSS) was examined. RESULTS: Tumour budding was associated with several adverse pathological characteristics, including lymph node involvement, lymph vessel invasion (LVI), increased tumour stroma percentage (TSP) and weaker local inflammatory infiltrative. Tumour budding was associated with reduced CSS (hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.14-3.09, P=0.004), independent of nodal status, molecular subtypes, tumour necrosis, CD8+, CD138+, LVI, blood vessel invasion and TSP. Further, tumour budding was independently associated with reduced CSS in node-negative patients (HR 2.63, 95% CI 1.16-5.92, P=0.020) and those who have low TSP (HR 1.98, 95% CI 1.09-3.57, P=0.024) and high-grade local inflammatory infiltrative (HR 2.27, 95% CI 1.35-5.36, P=0.014). CONCLUSIONS: Tumour budding was a significant predictor of survival in patients with invasive ductal breast cancer, independent of adverse pathological characteristics and components of tumour microenvironment. The present study further confirms the clinical utility of both tumour and host-based factors of tumour microenvironment.

Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland.

BACKGROUND: Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. METHODS: Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. RESULTS: In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P⩽0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P⩽0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P⩽0.001). CONCLUSIONS: Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer.

The relationship between acute changes in the systemic inflammatory response and plasma ascorbic acid, alpha-tocopherol and lipid peroxidation after elective hip arthroplasty.

BACKGROUND & AIMS: Vitamin C (ascorbic acid, AA) is a water soluble vitamin with many functions including antioxidative properties, haemostasis, hormone synthesis, collagen synthesis, carnitine synthesis, bile salt production and enhancing iron absorption. There is some evidence that there is a negative inverse relationship between plasma vitamin C concentration and the systemic inflammatory response as measured by C-reactive protein (CRP). The aim of the present study was to examine, in the context of a longitudinal study, the change in plasma concentrations of ascorbic acid (AA) and Vitamin E (α-tocopherol, AT) and their relationship to free radical damage during the evolution of the systemic inflammatory response. METHODS: Venous blood samples were obtained pre-operatively and at 1, 2, 3 and 90 days post-operatively from 11 patients undergoing elective hip arthroplasty at Glasgow Royal Infirmary. AA, AT, cholesterol, MDA (marker of free radical damage), CRP and albumin were measured in plasma. RESULTS: Plasma AA fell significantly by 74% (P < 0.01), AT fell by 36% (P < 0.01), cholesterol by 40% (P < 0.01), MDA by 38% (P < 0.01), albumin by 29% (P < 0.01) and CRP increased significantly by 160 fold (P < 0.01) during the systemic inflammatory response. The fall in plasma AA remained significant when adjusted for albumin (P < 0.01). Plasma AT adjusted for cholesterol did not change significantly during the study period. The fall in plasma MDA remained significant when adjusted for albumin (P 0.01). At 3 months post-operatively, all measurements (including AA) except albumin had returned to baseline values. CONCLUSIONS: Plasma AA levels are unlikely to be a reliable measurement of Vitamin C where there is evidence of a systemic inflammatory response. The decrease in plasma AA concentration is likely to be secondary to increased consumption, increased usage neutralising free radicals, increased utilisation in supporting AT regeneration and increased urinary excretion.

Systemic inflammatory response and survival in patients undergoing curative resection of oral squamous cell carcinoma.

Prognostic stratification in squamous cell carcinoma (SCC) of the head and neck has traditionally relied on the pathological staging of a tumour, but it is increasingly being recognised that host-related factors have an important role in the assessment of survival and recurrence. We aimed to evaluate the prognostic value of systemic inflammation scores including the modified Glasgow Prognostic Score (mGPS) in patients undergoing potentially curative resection for oral SCC. We retrospectively identified 178 patients who had curative operations for cancer of the oral cavity and soft palate between January 2006 and April 2011. Among the inclusion criteria were preoperative estimates of C-reactive protein and serum albumin. We analysed established pathological prognostic factors and scores for systemic inflammation as predictors of cancer-specific and overall survival. On univariate analysis, the mGPS was a significant predictor of both cancer-specific (p<0.001) and overall survival (p<0.001), and it remained an independent predictor of cancer-specific (HR: 2.12, 95% CI 1.49 to 3.00; p<0.001) and overall survival (HR: 1.69, 95% CI 1.23 to 2.31; p=0.001) on Cox regression analysis. The mGPS of activated systemic inflammation seems to be a powerful adverse prognostic indicator in resectable oral SCC.