Comment on ‘Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis’

No abstract available

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

Systemic neutrophil-to-lymphocyte ratio in colorectal cancer: the relationship to patient survival, tumour biology and local lymphocytic response to tumour

Background: Colorectal cancer (CRC) is a major cause of mortality and morbidity. The impact of inflammatory biomarkers (C-reactive protein etc.) on CRC is increasingly studied including systemic neutrophil-to-lymphocyte ratio (NLR) as they seem to predict outcome. Methods: All patients who underwent curative resection for CRC from 2000 to 2004 at Leeds Teaching Hospitals NHS Trust had pre-operative NLR calculated. Demographic, histopathological and survival data were collected. Tissue microarrays were created and stained to determine the mismatch repair (MMR) protein status of each tumour. Local lymphocytic response to the tumour was assessed and graded. Results: About 358 patients were eligible. Of these 88 had an NLR greater than or equal to5, which predicted lower overall survival and greater disease recurrence. A high NLR is associated with higher pT- and pN-stage and a greater incidence of extramural venous invasion. MMR protein status was not associated with NLR. A pronounced lymphocytic reaction at the invasive margin (IM) indicated a better prognosis and was associated with a lower NLR. Conclusion: Neutrophil-to-lymphocyte ratio predicts disease-free and overall survival and is associated with a more aggressive tumour phenotype. The lymphocytic response to tumour at the IM is associated with NLR however dMMR is not. Neutrophil-to-lymphocyte ratio is a cheap, easy-to-access test that predicts outcome in CRC

Inflammation and invasive margin in colorectal cancer

Abstract Prognostic features of colorectal cancer (CRC) are important for determining the optimal treatment for an individual patient. This study was carried out to evaluate the significance of the prognostic significance of inflammatory cell reaction and tumour budding at the invasive front of the tumour in CRC patients, to study the pattern of alterations in the serum cytokine levels of CRC patients compared to healthy controls, and to evaluate whether the patterns of the cytokine levels alter according to the stage of disease. Study material consists of a series of CRC patients operated in Oulu University Hospital (N=466, studies I-II, and N=148, study III). The intensities of inflammatory cell reaction and tumour budding were estimated and the association of these features with survival was analysed (I-II). Preoperative serum samples were collected from patients and age- and sex-matched controls, and concentrations of 13 cytokines and chemokines were analysed (III). Inflammatory cell reaction and tumour budding at the tumour invasive margin were independent prognostic markers in CRC. In patients with stage I-II disease, high-grade inflammation was associated with better 5-year survival (87.6%) than low-grade inflammation (47.0%). Tumour budding was present in 24.0% of cases and predicted worse 5-year survival (15.4% in contrast to 63.5%). Serum levels of PDGF, IL-6, IL-7, and IL-8 were higher, and levels of MCP-1 were lower in CRC patients compared to controls. A pattern of five most predictive cytokines reached an excellent capacity in discriminating patients from healthy controls and reached an AUC of 0.890 in the ROC analysis. High-stage CRC was associated with increased levels of IL-6, IL-8 and IL-1ra, and metastasised disease was accompanied by an orientation to Th2 cytokine milieu. According to this study, patients with CRC can be stratified into different prognostic groups by assessing inflammatory cell reaction and tumour budding at the invasive front of the tumour. Evaluation of these features may give additional information for making treatment decisions. Serum cytokine profile was shown to change during cancer progression and seems promising in separating CRC patients from healthy controls, but its clinical value is yet to be confirmed.Tiivistelmä Kasvaimen ennusteeseen vaikuttavien tekijöiden tunteminen on tärkeää syöpäpotilaan yksilöllisen hoidon suunnittelussa. Tässä tutkimuksessa selvitettiin kasvaimen tulehdusreaktion ja kasvaimen reunan silmuilevan kasvutavan merkitystä kolorektaalisyöpäpotilaiden ennusteeseen. Lisäksi tutkimuksessa mitattiin tulehdusreaktion välittäjäaineiden, seerumin sytokiinien, pitoisuuksia potilailla ja verrokeilla sekä näiden pitoisuuksien vaihtelua suhteessa syövän levinneisyyteen. Tutkimusaineisto koostui Oulun yliopistollisessa sairaalassa leikatuista kolorektaalisyöpäpotilaista (N=466, tutkimukset I–II, N=148, tutkimus III). Kasvainnäytteistä tutkittiin kasvaimen tulehdusreaktion ja silmuilevan kasvutavan voimakkuutta ja arvioitiin näitä piirteitä suhteessa potilaiden elinaikatietoihin (tutkimukset I–II). Potilaiden ja verrokkihenkilöiden seeruminäytteistä mitattiin 13 sytokiinin pitoisuudet (tutkimus III). Kasvaimen tulehdusreaktio ja silmuileva kasvutapa osoittautuivat itsenäisiksi ennustetekijöiksi. Potilailla oli parempi 5-vuotisennuste (87.6 %), jos kasvaimen tulehdusreaktio oli voimakas verrattuna tapauksiin, joissa tulehdusreaktio oli heikko (47.0 %). 24 %:ssa kasvaimista kasvutapa oli silmuileva, ja näillä 5-vuotisennuste oli huonompi kuin ei-silmuilevissa (15.4 % vs. 63.5 %). Potilailla todettiin korkeammat seerumin PDGF, IL-6, IL-7, ja IL-8 -pitoisuudet ja matalammat MCP-1 -pitoisuudet kuin verrokeilla. Mittaamalla viiden ennustearvoltaan merkitsevimmän sytokiinin pitoisuudet voitiin potilaat luotettavasti erottaa verrokeista ROC-analyysin avulla, kun ROC-käyrän alle jäävä pinta-ala oli 0.890 %. Pidemmälle levinneissä taudeissa todettiin korkeampia IL-6, IL-8 ja IL-1ra -pitoisuuksia, ja etäpesäkkeisissä taudeissa sytokiinipitoisuudet muuttuivat Th2 -profiilin suuntaiseksi. Tutkimuksen mukaan kasvaimen tulehdusreaktion ja silmuilevan kasvutavan arvioinnilla kolorektaalisyöpäpotilaat voidaan jakaa ennusteellisiin ryhmiin, mitä on mahdollista hyödyntää hoidon suunnittelussa. Seerumin sytokiiniprofiilin osoitettiin muuttuvan taudin edetessä, ja sytokiinien pitoisuudet poikkeavat kolorektaalisyöpäpotilailla verrattuna terveiltä verrokeilta mitattuihin arvoihin

Mechanical and oral antibiotic bowel preparation versus no bowel preparation in right and left colectomy: subgroup analysis of MOBILE trial

zrab011In retrospective series, mechanical and oral antibiotic bowel preparation (MOABP) has been reported to reduce surgical-site infections (SSIs) after colectomy compared with no bowel preparation (NBP).This was a subgroup analysis of a multicentre randomized trial that included patients scheduled for elective colectomy. The MOABP group underwent mechanical bowel preparation, and took 2 g neomycin and 2 g metronidazole orally during the day before surgery. The NBP group did not undergo bowel preparation. Patients were categorized according to the side of resection (right versus left colectomy), and these subgroups compared for postoperative outcomes.Among 217 patients undergoing right colectomy (106 in MOABP and 111 in NBP group), SSI was detected in seven (7 per cent) and 10 (9 per cent) patients (odds ratio (OR) 0.71, 95 per cent c.i. 0.26 to 1.95; P = 0.510), anastomotic dehiscence in two (2 per cent) and two (2 per cent) patients (OR 1.05, 0.15 to 7.58; P = 1.000), and the mean(s.d.) Comprehensive Complication Index (CCI) score was 9.4(12.9) and 10.5(18.0) (mean difference –1.09; 95 per cent c.i. –5.29 to 3.11; P = 0.608) in the MOABP and NBP groups respectively. Among 164 patients undergoing left colectomy (84 in MOABP and 80 in NBP group), SSI was detected in five (6 per cent) and eight (10 per cent) patients (OR 0.57, 0.18 to 1.82; P = 0.338), anastomotic dehiscence in four (5 per cent) and five (6 per cent) patients (OR 0.75, 0.19 to 2.90; P = 0.742), and the CCI score was 10.2(13.1) and 6.5(11.0) (mean difference 3.68, –0.06 to 7.42; P = 0.053) in the MOABP and NBP groups respectively.MOABP did not decrease the rate of SSI or complications in patients undergoing either right or left colectomy compared with NBP.Background: In retrospective series, mechanical and oral antibiotic bowel preparation (MOABP) has been reported to reduce surgical-site infections (SSIs) after colectomy compared with no bowel preparation (NBP). Method: This was a subgroup analysis of a multicentre randomized trial that included patients scheduled for elective colectomy. The MOABP group underwent mechanical bowel preparation, and took 2 g neomycin and 2 g metronidazole orally during the day before surgery. The NBP group did not undergo bowel preparation. Patients were categorized according to the side of resection (right versus left colectomy), and these subgroups compared for postoperative outcomes. Results: Among 217 patients undergoing right colectomy (106 in MOABP and 111 in NBP group), SSI was detected in seven (7 per cent) and 10 (9 per cent) patients (odds ratio (OR) 0.71, 95 per cent c.i. 0.26 to 1.95; P=0.510), anastomotic dehiscence in two (2 per cent) and two (2 per cent) patients (OR 1.05, 0.15 to 7.58; P=1.000), and the mean(s.d.) Comprehensive Complication Index (CCI) score was 9.4(12.9) and 10.5(18.0) (mean difference -1.09; 95 per cent c.i. -5.29 to 3.11; P=0.608) in the MOABP and NBP groups respectively. Among 164 patients undergoing left colectomy (84 in MOABP and 80 in NBP group), SSI was detected in five (6 per cent) and eight (10 per cent) patients (OR 0.57, 0.18 to 1.82; P=0.338), anastomotic dehiscence in four (5 per cent) and five (6 per cent) patients (OR 0.75, 0.19 to 2.90; P=0.742), and the CCI score was 10.2(13.1) and 6.5(11.0) (mean difference 3.68, -0.06 to 7.42; P=0.053) in the MOABP and NBP groups respectively. Conclusions: MOABP did not decrease the rate of SSI or complications in patients undergoing either right or left colectomy compared with NBP.Peer reviewe

Annual hospital volume and colorectal cancer survival in a population-based nationwide cohort study in Finland

Abstract Purpose: To examine the annual hospital volume of surgery in relation to survival in colorectal cancer. Previous studies on hospital volume and survival following colorectal cancer surgery are conflicting. Methods: All 49 032 patients who underwent resection for colorectal cancer in 1987–2016 in Finland were included, with complete follow-up until December 31, 2019. Primary outcome was 5-year mortality. Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) for quartiles of annual hospital volume for colorectal surgery, adjusted for calendar period, age, sex, comorbidity, stage, tumor location and oncological therapy. Additionally, colon and rectal cancer surgery were assessed separately. Sensitivity analysis of patients with confirmed curative intent was conducted. Results: Compared to highest quartile (≥108 resections annually), lowest hospital volume (≤37 resections annually) was associated with slightly increased 5-year all-cause mortality (adjusted HR 1.07, 95% CI 1.02–1.12). A pre-planned subgroup-analysis suggested a slightly improved 5-year survival in high-volume institutions for rectal cancer, but not colon cancer surgery. Sensitivity analysis including only those operated with confirmed curative intent suggested no differences between hospital volume groups in colorectal, colon or rectal cancer for 5-year all-cause mortality. Conclusions: Higher hospital volume is associated with slightly improved all-cause 5-year mortality in colorectal cancer surgery, but this effect may be limited to rectal cancer surgery only. Volume-outcome relationship in rectal cancer surgery should be investigated further using large datasets. These results do not support centralization of colon cancer surgery based on hospital volume only

Divergent expression of bacterial wall sensing toll-like receptors 2 and 4 in colorectal cancer

Abstract Aim: To characterize the expression of toll-like receptors (TLR) 2 and 4 in colorectal cancer (CRC) and in normal colorectal mucosa. Methods: We analysed tissue samples from a prospective series of 118 unselected surgically treated patients with CRC. Sections from formalin fixed, paraffin embedded specimens were analysed for TLR2 and TLR4 expression by immunohistochemistry. Two independent assessors evaluated separately expression at the normal mucosa, at the invasive front and the bulk of the carcinoma, and in the lymph node metastases when present. Expression levels in different locations were compared and their associations with clinicopathological features including TNM-stage and the grade of the tumour and 5-year follow-up observations were analysed. Results: Normal colorectal epithelium showed a gradient of expression of both TLR2 and TLR4 with low levels in the crypt bases and high levels in the surface. In CRC, expression of both TLRs was present in all cases and in the major proportion of tumour cells. Compared to normal epithelium, TLR4 expression was significantly weaker but TLR2 expression stronger in carcinoma cells. Weak TLR4 expression in the invasive front was associated with distant metastases and worse cancer-specific survival at 5 years. In tumours of the proximal colon the cancer-specific survival at 5 years was 36.9% better with strong TLR4 expression as compared with those with weak expression (P = 0.044). In contrast, TLR2 expression levels were not associated with prognosis. Tumour cells in the lymph node metastases showed higher TLR4 expression and lower TLR2 expression than cells in primary tumours. Conclusion: Tumour cells in CRC show downregulation of TLR4 and upregulation of TLR2. Low expression of TLR4 in the invasive front predicts poor prognosis and metastatic disease