Curative Surgery For Colon Cancer Research Articles

The Value of Preoperative C-Reactive Protein to Albumin Ratio as a Prognostic Biomarker in Colon Cancer Patients.

Inflammatory acute phase proteins have been reported to play a crucial role in cancer progression. Various hematologic and inflammatory markers and scores, such as the lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic inflammation score (SIS), prognostic nutritional index (PNI), Glasgow prognostic score, and, more recently, the Naples prognostic score, have been reported as significant prognostic markers. The aim of this prospective study was to evaluate the prognostic significance of the C reactive protein-to-albumin ratio (CAR) in patients with colon cancer. Materials and Methods: We conducted a prospective observational study on a series of patients who underwent curative surgery for colon cancer. The C reactive protein-to-albumin ratio was determined preoperatively, and we evaluated the correlations between the CAR and various clinical and pathological parameters, as well as the correlation with Overall and Relapse-free survival. Furthermore, we compared the accuracy of the CAR with that of the Naples score. Results: One hundred and ten patients were included in the study. We set 0.4927 as the cut-off value for the CAR according to a receiver operating characteristic curve analysis. Based on the cut-off value, patients were divided into a low CAR group and a high CAR group. The preoperative CAR exhibited statistically significant correlation with tumor volume, T and N stage, number of positive lymph nodes, and grade of tumor differentiation. We also demonstrated a positive correlation between high CAR values and a higher Naples score (p = 0.0005), even when a subgroup analysis was performed for each group individually. Conclusions: The preoperative CAR is a useful prognostic marker in patients with colon cancer. These results may help to design strategies to personalize targeted management approaches among colon cancer patients.

The incidence of venous thromboembolism after curative colon cancer surgery within an enhanced recovery after surgery programme

AimBased on three randomised controlled trials performed more than a decade ago, several national guidelines recommend prolonged venous thromboprophylaxis for 28 days following elective surgery for colon cancer. None of these studies were conducted within enhanced recovery after surgery setting. Newer studies indicate that prolonged prophylaxis might not be necessary with enhanced recovery after surgery. We aimed to provide further evidence to this unresolved discussion. MethodRetrospective study of patients undergoing elective surgery for colon cancer stage I-III with enhanced recovery after surgery in the Capital Region of Denmark from 2014 to 2017. Patients were excluded if discharged on postoperative day 28 or later, dying before discharge, undergoing concomitant rectum resection, or discharged with vitamin K antagonists, direct-oral anticoagulants, or low molecular weight heparin treatment. All patients received only low-dose low molecular weight heparin as prophylaxis during their admission.The primary endpoint was symptomatic lower limb deep venous thrombosis or pulmonary embolism diagnosed within 60 days postoperatively. ResultsOut of the included population of 1806 patients, only three experienced a symptomatic venous thromboembolic event; none was fatal. Two had pulmonary embolism associated with pneumonia, while one patient was diagnosed with lower limb deep venous thrombosis at postoperative day 15 after an uncomplicated course with first discharge at postoperative day 2. ConclusionThe risk of symptomatic venous thromboembolism after elective surgery for colon cancer with enhanced recovery after surgery seems negligible even without prolonged prophylaxis. The current guidelines need to be reconsidered.

Adverse Tumour and Host Biology May Explain the Poorer Outcomes Seen in Emergency Presentations of Colon Cancer.

To examine the association between tumor/host factors (including the systemic inflammatory response), mode of presentation, and short/long-term outcomes in patients undergoing curative resectional surgery for TNM I to III colon cancer. Emergency presentations of colon cancer are associated with worse long-term outcomes than elective presentations despite adjustment for TNM stage. A number of differences in tumor and host factors have been identified between elective and emergency presentations and it may be these factors that are associated with adverse outcomes. Patients undergoing curative surgery for TNM I to III colon cancer in the West of Scotland from 2011 to 2014 were identified. Tumor/host factors independently associated with the emergency presentation were identified and entered into a subsequent survival model to determine those that were independently associated with overall survival/cancer-specific survival (OS/CSS). A total of 2705 patients were identified. The emergency presentation was associated with a worse 3-year OS and CSS compared with elective presentations (70% vs 86% and 91% vs 75%). T stage, age, systemic inflammatory grade, anemia (all P < 0.001), N stage ( P = 0.077), extramural venous invasion ( P = 0.003), body mass index ( P = 0.001), and American Society of Anesthesiologists Classification classification ( P = 0.021) were independently associated with emergency presentation. Of these, body mass index [hazard ratio (HR), 0.82], American Society of Anesthesiologists Classification (HR, 1.45), anemia (HR, 1.29), systemic inflammatory grade (HR. 1.11), T stage (HR, 1.57), N stage (HR, 1.80), and adjuvant chemotherapy (HR, 0.47) were independently associated with OS. Similar results were observed for CSS. Within patients undergoing curative surgery for colon cancer, the emergency presentation was not independently associated with worse OS/CSS. Rather, a combination of tumor and host factors account for the worse outcomes observed.

Relationship between pre-operative glycated haemoglobin and surgical site infection in patients undergoing elective colon cancer surgery.

Surgical site infections remain a significant cause of morbidity following colon cancer surgery. Although diabetes has been recognised as a risk factor, patients with asymptomatic diabetes are likely underdiagnosed. The aim of the present study was to determine the relationship between preoperative glycated haemoglobin (HbA1C), clinicopathological characteristics and the influence on surgical site infection in a cohort of patients undergoing potentially curative colon cancer surgery. Patients who underwent elective, potentially curative colon cancer surgery between January 2011 and December 2014 were assessed for HbA1C levels (mmol/mol) measured within 3 months preoperatively. Clinicopathological data were recorded in a maintained database. A multivariate binary logistic regression model was used to assess the relationship between HbA1C, clinicopathological characteristics and surgical site infections. A total of 362 patients had HbA1C levels preoperatively recorded. HbA1C was significantly associated with body mass index (BMI), diabetes, smoking status, visceral fat area and skeletal muscle index. As determined by multivariate analysis, preoperative HbA1C levels remained independently associated with an increased risk of surgical site infections (OR 1.69, 95% CI 1.05-2.7; P=0.031) together with BMI (OR 1.91, 95% CI 1.36-2.67; P<0.001). Notably, in the present study, tumour-based factors, such as tumour location and TNM status, were not associated with infective complications. By contrast, host factors, such as BMI and pre-operative HbA1C were associated with surgical site infections suggesting that these factors were of more importance in determining short-term outcomes. In conclusion, objective measurements of BMI and HbA1C effectively stratified the risk of developing surgical site infection from 8 to 59%; therefore, HbA1C levels should be determined to allow for preoperative optimisation.

The association between preoperative CEA, the systemic inflammatory response and survival in colon cancer.

27 Background: Prior to curative surgery for colon cancer, carcinoembryonic antigen (CEA) has been reported to be a poor prognostic factor recommended for routine measurement, however the majority of studies evaluating this have not adjusted for the preoperative systemic inflammatory response (SIR) –widely shown to be associated with worse outcomes. The present study aims to analyse the association between preoperative CEA and long-term outcomes when adjusted for other factors including Systemic Inflammatory Grade (SIG). Methods: The effect on overall/cancer specific survival (OS/CSS) of preoperative CEA (&lt;5/5+) was examined in a regional cohort of patients undergoing surgery for colon cancer after adjustment for other clinicopathological factors including the SIR as measured by Systemic Inflammatory Grade (SIG). Results: 624 patients were identified undergoing curative surgery for colon cancer with a preoperative CEA available. For 3-year OS stratified by TNM Stage, CEA offered further prognostic value in patients with TNM Stage I (98% vs 75%, p=0.002), but not Stage II (p=0.444) or Stage III (p=0.351) disease. For 3-year OS stratified by SIG, CEA did not add further significant prognostic value for any SIG (all p&gt;0.05). On multivariate analysis, age (HR 1.65, p=0.020), sex (HR 0.53, p=0.001), mode of presentation (HR 1.93, p=0.008), TNM Stage (HR 1.83, p&lt;0.001) and SIG (HR 1.30, p&lt;0.001) remained significant for OS, but not CEA (p=0.620). Conclusions: The present results show that there is limited prognostic value of preoperative CEA. The SIR as measured by SIG should be routinely measured prior to curative colonic surgery. A mandatory reporting dataset is required in colorectal cancer and should include SIG. [Table: see text]

Long-term oncological outcomes in patients undergoing laparoscopic versus open surgery for colon cancer: A nationwide cohort study.

To estimate the effect of laparoscopy versus laparotomy on recurrence status in patients undergoing intended curative resection for stage I-III colon cancer using nationwide data. A retrospective cohort study using prospectively collected nationwide quality assurance data on all patients undergoing elective, intended curative surgery for UICC stage I-III colon cancer in Denmark from 1 January 2010, through 31 December 2013. The association between laparoscopic versus open surgery and recurrence status was investigated using cause-specific hazard and subdistribution hazard models with death from any cause as a competing event. In total, 4369 patients undergoing elective intended curative surgery for colon cancer were included in the analysis. Overall, 3243 (74.2%) patients underwent laparoscopic surgery. During a median follow-up time of 84months, 1191 (27.2%) patients experienced recurrence, and 1304 (29.8%) patients died. The cause-specific hazard of recurrence following laparoscopic versus open surgery was HRCS =1.08, 95% CI: 0.90-1.28, p=0.422. The subdistribution hazard of recurrence following laparoscopic versus open surgery was HRSD =0.99, 95% CI: 0.84-1.16, p=0.880. Elective laparoscopic resection for UICC stage I-III colon cancer is oncologically safe and comparable with open resection. These results confirm the external validity of previous RCTs in everyday clinical settings.

Recurrence Kinetics after Laparoscopic Versus Open Surgery in Colon Cancer. A Meta-Analysis.

Background: Colorectal cancer (CRC) is a leading cause of mortality worldwide and in the UK. Surgical resection is the main curative treatment modality available and using a laparoscopic vs. an open approach may have a direct influence on the inflammatory response, influencing cancer biology and potentially the recurrence kinetics by promoting cancer growth. Methods: This systematic review aims to compare laparoscopic with open surgery for the treatment of colon cancer with a specific focus on the moment of the recurrence. We included randomised controlled trials in intended curative surgery for colon cancer in adults. Interventions: Studies investigating laparoscopic vs. open resection as an intended curative treatment for patients with confirmed carcinoma of the colon. The two co-primary outcomes were the time to recurrence and the overall survival (OS) and disease-free survival (DFS) at three and five years. Meta-analyses were done on the mean differences. Results: After selection, we reviewed ten randomised controlled trials. Most of the trials did not display a statistically significant difference in either DFS or OS at three or at five years when comparing laparoscopic to open surgery. Groups did not differ for the OS and DFS, especially regarding the time needed to observe the median recurrence rate. The quality of evidence (GRADE) was moderate to very low. Conclusion: We observed no difference in the recurrence kinetics, OS or DFS at three or five years when comparing laparoscopic to open surgery in colon cancer.

Prognostic Factors Affecting Disease-Free Survival and Overall Survival in T4 Colon Cancer.

PurposeIt is known that as the T stage of a carcinoma progresses, the prognosis becomes poorer. However, there are few studies about factors that affect the prognosis of T4 advanced colon cancer. This study aimed to identify the prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in T4 colon cancer.MethodsPatients diagnosed with stage T4 on histopathology after undergoing curative surgery for colon cancer between March 2009 and March 2018 were retrospectively analyzed for factors related to postoperative survival. Primary outcomes were DFS and OS.ResultsEighty-two patients were included in the study. DFS and OS of the pathologic (p) T4b group were not inferior to that of the pT4a group. Multivariate analysis showed that differentiation (hazard ratio [HR], 4.994; P = 0.005), and laparoscopic surgery (HR, 0.323; P = 0.008) were significant prognostic factors for DFS, while differentiation (HR, 7.904; P ≤ 0.001) and chemotherapy (HR, 0.344; P = 0.038) were significant prognostic factors for OS.ConclusionTumor differentiation, laparoscopic surgery, and adjuvant chemotherapy were found to be significant prognostic factors in patients with T4 colon cancer. Adjuvant chemotherapy and curative resections by laparoscopy might improve the prognosis in these patients.

Usefulness of histological superstudy of sentinel lymph nodes detected with radioisotopes in colon cancer

IntroductionAdjuvant chemotherapy (CT) significally reduces the rate of relapse in +pN (stage III) colon cancer (CC) and in some pN0 (stage II) with risk factors such as pT4, vascular invasion V1, perineural invasion Pn1, and complicated tumors. However, unexpectedly, 20%–30% of pN0 present a relapse in the follow-up, which may suggest that the lymph node involvement was not discovered in the conventional histological study (CS), and its finding with a superstudy (SS) could increase the number of patients who would benefit from neoadjuvant CT. It is not possible to perform this SS in every lymph node (LN) from the specimen, but it is possible in a small group of LN which are representative of the N status (definition of sentinel node SN). The aim of our work is to state the representativeness of the SN and to analyze de number of patients who are suprastaged after the SS of the SN. Material and MethodsProspective study of a series of patients who have undergone curative surgery for CC, to whom we perform selective biopsy of sentinel node (SBDN). Identification of SN was carried out with in vivo injection of the radiotracer, with ex vivo isolation of SN. Once the specimen is out, we take pictures of the surgical bed to rule out the presence of aberrant drainage routes, out of the routine oncological resection area. We performed the histological CS (Hematoxilin-Eosin stain (H-E) in conventional sections) in the rest of the LN from the mesocolon. In the SN we performed the CS and a SS with H-E in serial sections, immunohistochemistry (IHC) and molecular study with OSNA® (One Step Nucleic Acid Amplification). Diagnostic validity study od SBSN was carried out, defining the false negative (FN) as the negativity of the SN while other LN are positive (N+), as well as a valuation of the suprastaging due to the SS of the SN. ResultsWe performed lymphatic map in 72 patients, finding the SN in 62 of them (87.3%). The 9 identification failures happened in the first 17 cases. We have not found aberrant drainage routes. A total of 1.164 LN were studied in the 62 patients (18.8 LN/patient), from which 145 are SN (2,34 SN/patient), having found 103 positive LN with the CS and 112 positive with the SS of SN (9+ LN more in 8 patients than detected with the CS). Positivity after CS in the SN group is 17.24% (25/145), while it is 8.53% in the rest (87/1.019) (P < .001). With the CS, 50% of the patients (31/62) were pN+ (4 are N+ exclusively in the SN), and after the SS of the SN, only 1 of the 31 pN0 patients (3.2%) becomes pN1a, with a definitive 51.6% of N+ in the whole series (32 N+ in the 62 patients) (5 are N+ exclusively in the SN).Exclusively with the SS of the SN, FN rate (“-SN, +others”, meaning patients who are N+ having -SN) is 54.8% (17/31). With the SS of the SN, 8 of the 62 patients (12.9%) increase their total number of +LN: apart from the patient who turns from pN0 to pN1a, suprastaging from IIA to IIIB (and therefore increasing the total number of pN+ to 32), 5 of the 17 FN in the CS turns into positive (2 change the pN subindex and one is suprastaged from IIIB to IIIC), decreasing FN to 37.5% (12/32 cases). Besides, 2 patients whose SN is already positive in the CS increase the number of +SN after the SS of the SN, therefore both changing their pN subindex and one of them suprastaging from IIIB to IIIC. In summary, 8 patients increase the total number of positive SN after the SS (8/62, 12.9%), 5 of them changing the pN subindex (5/62, 12.9%), even if only 3 of them get suprastaged (3/62, 4.8%), among them the one who turns from pN0 to pN1a. ConclusionTechnique is valid and reproducible, with a high detection rate even with a high learning curve. It globally increases the number of affected LN in 12.9% of patients, having prognostic implications in 4.8% (suprastaging rate). Only 3.2% of pN0 patients in the CS turn to be +pN after the SS of the SN, with its therapeutic implications (prescription of adjuvant CT), which could be relevant when extrapolated to a big number of patients. The high FN rate (37.5%) prevents us from accepting the representativeness of SN as the global N status, but it is not clinically relevant in CC, as its aim is not to avoid lymphadenectomy, which remains mandatory (opposite to breast cancer or melanoma in which SN detection decides upon whether to perform or not the lymphadenectomy), but to decide which patients would benefit from adjuvant CT.

The prognostic value of combined measures of the systemic inflammatory response in patients with colon cancer: an analysis of 1700 patients.

The pre-operative systemic inflammatory response (SIR) measured using an acute-phase-protein-based score (modified Glasgow Prognostic Score (mGPS)) or the differential white cell count (neutrophil-lymphocyte ratio (NLR)) demonstrates prognostic significance following curative resection of colon cancer. We investigate the complementary use of both measures to better stratify outcomes. The effect on survival of mGPS and NLR was examined using uni/multivariate analysis (UVA/MVA) in patients undergoing curative surgery for colon cancer. The synergistic effect of these scores in predicting OS/CSS was examined using a Systemic Inflammatory Grade (SIG). One thousand seven hundred and eight patients with TNM-I-III colon cancer were included. On MVA both mGPS and NLR were significant for OS (HR 1.16/1.21, respectively). Three-year survival stratified by mGPS was 83-58%(TNM-I-III), 87-65%(TNM-II) and 75-49%(TNM-III), and by NLR was 84-62%(TNM-I-III), 88-69%(TNM-II) and 77-49%(TNM-III). When mGPS and NLR were combined to form an overall SIG 0/1/2/3/4, this stratified 3-year OS 88%/84%/76%/65%/60% and CSS 93%/90%/82%/73%/70%, respectively (both p < 0.001). SIG stratified OS 93-68%/82-48% and CSS 97-80%/86-58% in TNM Stage II/III disease, respectively (all p < 0.001). The present study shows that the pre-operative SIR in patients undergoing curative surgery for colon cancer is best measured using a SIG utilising mGPS and NLR.

Utilidad del superestudio anatomopatológico de ganglio centinela detectado con radioisótopos en el cáncer de colon

IntroductionAdjuvant chemotherapy (CT) significally reduces the rate of relapse in +pN (stage III) colon cancer and in some pN0 (stage II) with risk factors such as pT4, vascular invasion V1, perineural invasion Pn1, and complicated tumors. However, unexpectedly, 20-30% of pN0 present a relapse in the follow-up, which may suggest that the lymph node involvement was not discovered in the conventional histological study (CS), and its finding with a superstudy (SS) could increase the number of patients who would benefit from neoadjuvant CT. It is not possible to perform this SS in every lymph node (LN) from the specimen, but it is possible in a small group of LN which are representative of the N status (definition of sentinel node SN). The aim of our work is to state the representativeness of the SN and to analyze de number of patients who are suprastaged after the SS of the SN. Material and methodsProspective study of a series of patients who have undergone curative surgery for colon cancer, to whom we perform selective biopsy of sentinel node. Identification of SN was carried out with in vivo injection of the radiotracer, with ex vivo isolation of SN. Once the specimen is out, we take pictures of the surgical bed to rule out the presence of aberrant drainage routes, out of the routine oncological resection area. We performed the histological CS (hematoxilin-eosin stain in conventional sections) in the rest of the LN from the mesocolon. In the SN we performed the CS and a SS with hematoxilin-eosin in serial sections, immunohistochemistry (IHC) and molecular study with One Step Nucleic Acid Amplification (OSNA®). Diagnostic validity study od selective biopsy of sentinel node was carried out, defining the false negative (FN) as the negativity of the SN while other LN are positive (N+), as well as a valuation of the suprastaging due to the SS of the SN. ResultsWe performed lymphatic map in 72 patients, finding the SN in 62 of them (87.3%). The 9 identification failures happened in the first 17 cases. We have not found aberrant drainage routes. A total of 1.164 LN were studied in the 62 patients (18.8 LN/ patient), from which 145 are SN (2,34 SN/ patient), having found 103 positive LN with the CS and 112 positive with the SS of SN (9 +LN more in 8 patients than detected with the CS). Positivity after CS in the SN group is 17.24% (25/145), while it is 8.53% in the rest (87/1.019) (p<.001). With the CS, 50% of the patients (31/62) were pN+ (4 are N+ exclusively in the SN), and after the SS of the SN, only 1 of the 31 pN0 patients (3.2%) becomes pN1a, with a definitive 51.6% of N+ in the whole series (32 N+ in the 62 patients) (5 are N+ exclusively in the SN).Exclusively with the SS of the SN, FN rate (“-SN, +others”, meaning patients who are N+ having -SN) is 54.8% (17/31). With the SS of the SN, 8 of the 62 patients (12.9%) increase their total number of +LN: apart from the patient who turns from pN0 to pN1a, suprastaging from IIA to IIIB (and therefore increasing the total number of pN+ to 32), 5 of the 17 FN in the CS turns into positive (2 change the pN subindex and one is suprastaged from IIIB to IIIC), decreasing FN to 37.5% (12/32 cases). Besides, 2 patients whose SN is already positive in the CS increase the number of +SN after the SS of the SN, therefore both changing their pN subindex and one of them suprastaging from IIIB to IIIC. In summary, 8 patients increase the total number of positive SN after the SS (8/62, 12.9%), 5 of them changing the pN subindex (5/62, 12.9%), even if only 3 of them get suprastaged (3/62, 4.8%), among them the one who turns from pN0 to pN1a. ConclusionTechnique is valid and reproducible, with a high detection rate even with a high learning curve. It globally increases the number of affected LN in 12.9% of patients, having prognostic implications in 4.8% (suprastaging rate). Only 3.2% of pN0 patients in the CS turn to be +pN after the SS of the SN, with its therapeutic implications (prescription of adjuvant CT), which could be relevant when extrapolated to a big number of patients. The high FN rate (37.5%) prevents us from accepting the representativeness of SN as the global N status, but it is not clinically relevant in colon cancer, as its aim is not to avoid lymphadenectomy, which remains mandatory (opposite to breast cancer or melanoma in which SN detection decides upon whether to perform or not the lymphadenectomy), but to decide which patients would benefit from adjuvant CT.

Sex and Adverse Events of Adjuvant Chemotherapy in Colon Cancer: An Analysis of 34 640 Patients in the ACCENT Database.

Adjuvant chemotherapy is a standard treatment option for patients with stage III and high-risk stage II colon cancer. Sex is one of several factors responsible for the wide inter-patient variability in drug responses. Amalgamated data on the effect of sex on the toxicity of current standard adjuvant treatment for colorectal cancer are missing. The objective of our study was to compare incidence and severity of major toxicities of fluoropyrimidine- (5FU or capecitabine) based adjuvant chemotherapy, with or without oxaliplatin, between male and female patients after curative surgery for colon cancer. Adult patients enrolled in 27 relevant randomized trials included in the ACCENT (Adjuvant Colon Cancer End Points) database, a large, multi-group, international data repository containing individual patient data, were included. Comparisons were conducted using logistic regression models (stratified by study and treatment arm) within each type of adjuvant chemotherapy (5FU, FOLFOX, capecitabine, CAPOX, and FOLFIRI). The following major toxicities were compared (grade III or IV and grade I-IV, according to National Cancer Institute Common Terminology Criteria [NCI-CTC] criteria, regardless of attribution): nausea, vomiting, nausea or vomiting, stomatitis, diarrhea, leukopenia, neutropenia, thrombocytopenia, anemia, and neuropathy (in patients treated with oxaliplatin). Data from 34 640 patients were analyzed. Statistically significant and clinically relevant differences in the occurrence of grade III or IV nonhematological {especially nausea (5FU: odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.90 to 2.87, P < .001; FOLFOX: OR = 2.34, 95% CI = 1.76 to 3.11, P < .001), vomiting (5FU: OR = 2.38, 95% CI = 1.86 to 3.04, P < .001; FOLFOX: OR = 2.00, 95% CI = 1.50 to 2.66, P < .001; CAPOX: OR = 2.32, 95% CI = 1.55 to 3.46, P < .001), and diarrhea (5FU: OR = 1.35, 95% CI = 1.21 to 1.51, P < .001; FOLFOX: OR = 1.60, 95% CI = 1.35 to 1.90, P < .001; FOLFIRI: OR = 1.57, 95% CI = 1.25 to 1.97, P < .001)} as well as hematological toxicities (neutropenia [5FU: OR = 1.55, 95% CI = 1.37 to 1.76, P < .001; FOLFOX: OR = 1.96, 95% CI = 1.71 to 2.25, P < .001; FOLFIRI: OR = 2.01, 95% CI = 1.66 to 2.43, P < .001; capecitabine: OR = 4.07, 95% CI = 1.84 to 8.99, P < .001] and leukopenia [5FU: OR = 1.74, 95% CI = 1.40 to 2.17, P < .001; FOLFIRI: OR = 1.75, 95% CI = 1.28 to 2.40, P < .001]) were observed, with women being consistently at increased risk. Our analysis confirms that women with colon cancer receiving adjuvant fluoropyrimidine-based chemotherapy are at increased risk of toxicity. Given the known sex differences in fluoropyrimidine pharmacokinetics, sex-specific dosing of fluoropyrimidines warrants further investigation.

Improved quality of colon cancer surveillance after implementation of a personalized surveillance schedule.

Early detection of recurrence through surveillance after curative surgery for primary colon cancer is recommended. We previously reported inadequate quality of surveillance among patients operated for colon cancer. These poor results led to the introduction of a personalized surveillance schedule. This study reassesses the quality of surveillance after the introduction of the personalized schedule. A total of 93 patients undergoing curative surgery for colon cancer between January 2009 and December 2014 (prospective data registration) were included in this retrospective single-center cohort study. Written informed consent was given by all patients. Compliance with surveillance was compared with national guidelines, as well as with the previous results and analyzed depending on where surveillance was conducted (general practitioner or outpatient clinic). Adherence to surveillance was higher when performed by oncologists compared to general practitioners with an odds ratio (OR), 6.03 (95%CI: 3.41-10.67, P = .001). Compared with the previous study, adherence to surveillance was significantly higher in the later cohort with an OR = 4.55 (95%CI: 2.50-8.33, P < 0.001). This study demonstrates that the implementation of a personalized surveillance schedule improves adherence to recommendations and that awareness can be increased with this simple measure.

Sociodemographic predictors of surgery refusal in patients with stage I-III colon cancer.

Over 104 000 cases of colon cancer are estimated to be diagnosed in 2020. Surgical resection is a critical part of colon cancer treatment and adequate resection impacts prognosis. However, some patients refuse potentially curative surgery. We aimed to identify the rate and predictors of surgery refusal among patients with colon cancer. The National Cancer Database (2004-2015) was queried for patients diagnosed with stage I-III colonic adenocarcinoma. Sociodemographic factors, clinical features, and treatment facility characteristics were collected. Patients who underwent surgery with curative intent were compared to those who refused surgery. Multivariable analysis was used to identify factors associated with surgery refusal. Adjusted survival analysis was performed on propensity-matched cohorts. A total of 151 020 patients were included and 1071 (0.71%) refused surgery. In multivariable analysis older age, Black race, higher Charlson comorbidity score, Medicaid, Medicare, or lack of insurance were predictive of refusing surgery. After propensity matching, there was a significant difference in 5-year survival for patients who refused surgery vs those who underwent surgery (P < .001). There are racial and socioeconomic disparities in the refusal of surgery for colon cancer. Further studies are needed to better understand the drivers behind differences in refusing curative surgery for colon cancer.

An investigation of the relationship between tumor location and survival following colon cancer resection.

255 Background: Both tumour location and systemic inflammation (SI) have been related to survival in patients undergoing curative surgery for colon cancer. Recently, right colon cancer (RCC) has been associated with pre-existing cardiovascular disease (CVD). Comorbidity scores such as the Lee Cardiac Risk Index (LCRI) capture symptomatic disease only. Imaging-based assessment of vascular calcification can be used to identify subclinical CVD. We explored the relationship between tumour location, systemic inflammation, cardiac comorbidity and survival in patients undergoing CC resection. Methods: Patients were identified from a prospective cancer database. Clinicopathological characteristics and survival data were abstracted. Aortic calcification (AC) was quantified visually on staging CT images. SI was measured using the modified Glasgow Prognostic Score (mGPS). Results: Of 418 patients, most were female (221, 53%), over 65 (282, 67%), ASA grade II or less (66%) with RCC (230, 55%) and TNM II-III disease (320, 77%). Compared with LCC, RCC was associated with increasing age (59% vs 41%, p = 0.039), greater AC (61% vs 39%, p = 0.013) but not SI (61% vs 39%, p = 0.139). There were no significant differences between LCC with respect to ASA, smoking status or LCRI. Univariate analysis revealed TNM stage (HR 3.55 (95%CI 1.51 - 8.39) p = 0.004) and degree of AC (HR 1.77 (1.04 - 3.00) p = 0.034) were associated with cancer-specific survival (CSS) in RCC while in LCC, only TNM stage was related to CSS (HR 2.30 (0.99 - 5.30) p = 0.05). Multivariate analysis in patients with RCC confirmed AC to be a stage-independent predictor of CSS (HR 1.94 (1.15 – 3.67) p = 0.013). Conclusions: AC is associated with RCC and confers an inferior prognosis, independent of stage. Investigation of underlying mechanisms is required, but impaired perfusion may limit mucosal function, potentiating the effect of carcinogens in the right colon.

Impact of perioperative transfusions and sepsis on long-term oncologic outcomes after curative colon cancer resection. A retrospective analysis of a prospective database

ObjectiveIntra-abdominal septic complications (IASC) affect short-term outcomes after surgery for colon cancer. Blood transfusions have been associated with worse short-term results. The role of IASC and blood transfusions on long-term oncologic results is still debated. This study aims to assess the impact of these two variables on survival after curative colon cancer resection. Patients and methodsRetrospective analysis of a prospectively maintained database of patients who underwent curative surgery for colon cancer at a university hospital, between 1993 and 2010. Cox regression was used to identify the role of IASC and transfusions (alone and combined) on local recurrence (LR), disease-free survival (DFS), and cancer-specific survival (CSS). ResultsOut of the 1686 patients analyzed, 1277 fit in the inclusion criteria. Colorectal surgeons performed the procedure in 82.2% of the patients. Blood transfusions were administered to 25.8% of the patients. Thirty-day complication and mortality rates were 34.5% and 6.1%. IASC occurred in 9.9%. The mean follow-up was 66 months. The 5-year rates of LR, DFS, and CSS were 7%, 79.8%, and 85.1%. The year of surgery and pT (Hazard ratio 9.35, 95% CI 1.23–70.9, for T4) and pN (Hazard ratio 2.57, 95% CI 1.39–4.72, for N2) stages were independent risk factors for LR. The same variables, bowel obstruction and surgeries performed by surgeons not specialized in colorectal surgery, were also associated with worse DFS and CSS. IASC and blood transfusions were not associated with LR, DFS, and CSS, whether alone or combined. ConclusionsIASC and transfusions were not associated with worse oncological outcomes after curative colon cancer surgery per se. Other factors were more important predictors of survival.

Potential image-based criteria of neoadjuvant chemotherapy for colon cancer: multireaders' diagnostic performance.

The objective was to assess which image-based criteria can be best accurately determined at MDCT and which results in least overtreatment. A total of 110 consecutive patients, who underwent curative surgery for colon cancer, were included in this retrospective study. Five radiologists independently assessed the longitudinal diameter of cancer as well as T- and N-categories. The five image-based criteria (T3cd/T4, T3/T4, T3/T4 or N+, T3cd/T4 or N2, and T3/T4 with ≥ 4cm) were evaluated in terms of diagnostic accuracy, interreader agreement, and overtreatment risk using pooled receiver-operating curve and Fleiss kappa analyses. Pathologic high-risk stage II or III was used as a reference standard for assessment of overtreatment risk. The diagnostic accuracy of multireaders was in the acceptable range (pooled area under curve (AUC): 0.751-0.829). T3/T4 showed the highest AUC (0.829) in terms of diagnostic accuracy. T3/T4 with ≥ 4cm showed the highest kappa value (κ = 0.695) followed by T3/T4 (κ = 0.623), indicating substantial agreement. The other three criteria revealed moderate agreement (κ = 0.558-0.577). In terms of overtreatment ratio, T3cd/T4 and T3cd/T4 or N2 showed relatively lower ratios (T3cd/T4, 2.2%; T3cd/T4 or N2, 2.9%), whereas T3/T4 and T3/T4 or N+ revealed higher ratios (T3/T4, 8.7%; T3/T4 or N+, 9.5%). T3/T4 was the best criterion in terms of diagnostic accuracy. However, in terms of interreader agreement and overtreatment risk, T3/T4 with ≥ 4cm and T3cd/T4 were better as potential image-based criteria of neoadjuvant chemotherapy for colon cancer.

The impact of major postoperative complications on long-term outcomes following curative resection of colon cancer

PurposeThe objective is to analyze the impact of severe postoperative complications in patients undergoing curative surgery for colon cancer. Material and methodsFrom a prospective database, we identified patients with stage I-III disease (AJCC) who underwent surgery between 2000 and 2014. Patients were selected with major complications (IIIb on the Clavien-Dindo classification) and with no major complications. Variables were analyzed in both groups. Local, peritoneal and distant recurrence together with overall survival and disease-free survival were analyzed. ResultsOf a total of 950 patients, 51 (5.3%) experienced major complications. Operative mortality was 2.6%. Age, ASA grade, urgent surgery, pre-operative hemoglobin, right-sided location, operative time, transfusion, conversion to open surgery, were all associated with major complications (all P < 0.05).With a median follow-up of 84.8 and 40 months in both groups, there was greater incidence of local recurrences in patients experiencing complications (2.4% vs 7.8%; P = 0.03 OR 3.39, 95% CI 1.12–10.24), being more marked in stage III patients (4.2% vs 21%; P = 0.005, OR 6.13 95% CI 1.74–21.56). In the stage III group, peritoneal recurrence was significantly greater in patients with complications (13.6% vs 31.6%; P = 0.04 OR 2.92 95% CI 1.04–8.18). Patients with major complications had a significantly lower overall survival (P = 0.024) than patients with no complications both at 5 years (78.9% vs 68.8%) and 10 years (74.6% vs 32.1%). The same trend was observed for disease-free survival (71.6% vs 48.3% and 69.8% vs 32.2%; P = 0.013). ConclusionThe development of major complications following colectomy for colon cancer has a negative impact on long-term oncologic outcomes, especially in stage III disease.

Preoperative platelet-lymphocyte ratio is an independent factor of poor prognosis after curative surgery for colon cancer.

Interaction between tumour and host triggers a systemic inflammatory response. This situation has been associated to cancer progression. Several peripheral blood inflammatory scores have been recently developed, as PLR. Data about the relationship between these scores and cancer prognosis are contradictory. Therefore, the aim of our work is to evaluate the capability of PLR to predict long-term outcomes (OS and RFS) in patients who underwent curative surgery for colon cancer. A retrospective study was designed with patients who underwent curative surgery for colon cancer between September 2008 and January 2012 at Rio Hortega University Hospital, Valladolid (Spain). We analysed the influence of PLR and other clinical variables on OS and RFS. Finally, 201 patients were analysed. Optimal cut-off value for PLR, established with ROC curves, was 153. 1-, 3- and 5-year OS were: 99.0, 90.4 and 82.3% for low PLR, and 93.8, 74.9 and 61.9% for high PLR, p<0.001. 1-, 3- and 5-year RFS were: 92.4, 84.7 and 77.6% for low PLR, and 83.3, 64.5 and 52.6% for high PLR, p<0.001. In MVA, high PLR was an independent negative prognostic factor for OS (HR=2.11; 95% CI 1.22-3.66; p=0.008) and RFS (HR=1.99; 95% CI 1.19-3.34; p=0.009). PLR represents an independent negative prognostic factor for OS and RFS in our sample of patients who underwent curative surgery for colon cancer. However, further studies with a larger sample size from different populations are necessary to confirm this conclusion.

The relationship between tumor location, tumor microenvironment, systemic inflammation, and cancer-specific survival in patients undergoing surgery for colon cancer.

689 Background: Evidence from clinical trials and cohort studies suggest primary tumour location is a prognostic factor in patients with advanced colorectal cancer and that right and left colonic tumours should be considered as distinct clinical and biological entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), and cancer-specific survival (CSS) in patients undergoing surgery for colon cancer. Methods: Clinicopathological characteristics were extracted from a prospective database of patients who underwent potentially curative surgery for colon cancer between 1997 and 2016, at a single centre. The tumour microenvironment was assessed retrospectively using routine H&amp;E pathological sections. Results: 722 patients were included. The majority of patients were over the age of 65 years (69%), were male (52%), had right-sided (RS) tumour location (63%), had TNM stage I/II disease (64%) and 25% received adjuvant chemotherapy. RS location was associated with poor tumour differentiation ( p =&lt; 0.001) and high venous invasion ( p =0.003) but not with TNM stage (p= 0.310), perineural invasion ( p= 0.286), tumour budding ( p= 0.568), margin involvement ( p= 0.424), peritoneal involvement ( p= 0.689), tumour necrosis ( p= 0.423) or tumour cell proliferation ( p= 0.605). RS location was not associated with tumour inflammatory cell infiltrate at the margin (CD3+ p= 0.103, CD8+ p= 0.620) or in the tumour (CD3+ p= 0.540, CD8+ p= 0.713) or with tumour stroma percentage ( p= 0.843). RS location was associated with high mGPS ( p =0.007) and neutrophil:platelet score ( p =0.001) but not NLR ( p= 0.387). Finally, there was no difference between RS and left sided tumour location in the administration of adjuvant chemotherapy (p= 0.901) or CSS ( p= 0.951). Conclusions: Few clinicopathological features were associated with tumour location in patients undergoing surgery for colon cancer. However, RS tumour location was consistently associated with a higher SIR. This may account for the poor prognosis associated with RS tumours in patients with advanced colon cancer.