Prognostic significance of the preoperative C-reactive protein-to-albumin ratio in patients with colorectal cancer.

BACKGROUND: The aim of the present study was to determine the utility of the C-reactive protein-to-albumin ratio (CAR) for predicting the overall survival (OS) in locally advanced colorectal cancer (CRC) patients. PATIENTS AND METHODS: This retrospective multicenter study was performed using data from a prospectively maintained database of pathological Stage II or III patients undergoing CRC surgery at the Yokohama City University, Department of Surgery, and its affiliated institutions between April 2000 and March 2016. The risk factors for the OS were identified. RESULTS: A CAR of 0.03 was considered to be the optimal cutoff point for classification based on the 1-, 3-, and 5-year survival rates and receiver operating characteristic curve. The OS rates at 3 and 5 years after surgery were 92.4% and 85.7% in the CAR-low group, respectively, and 86.7% and 81.1% in the CAR-high group. A multivariate analysis showed that the CAR was a significant independent risk factor for the OS. When comparing the patients' demographic and clinical characteristics between the CAR ≤0.03 and >0.03 groups, the incidence of patients who received adjuvant chemotherapy and the incidence of postoperative complications were significantly different between the two groups. CONCLUSION: The present study showed that the preoperative CAR was a risk factor for the OS in patients who underwent surgery for CRC. To improve the patients' survival, CAR might be a useful tool for devising treatment strategies.

Lymphocyte-to-monocyte ratio combined with CA19-9 for predicting postoperative recurrence of colorectal cancer in patients with diabetes.

OBJECTIVE: To investigate the significance of lymphocyte-to-monocyte ratio (LMR) combined with carbohydrate antigen (CA) 19-9 for predicting postoperative recurrence of colorectal cancer (CRC) in patients with type II diabetes. METHODS: We conducted a retrospective analysis of 106 postoperative patients with stage II-III CRC and with type II diabetes. Their clinical indexes such as LMR and CA19-9 were collected, and the patients were followed up for 5 years. RESULTS: The CA19-9 level was 119.7 U/ml at baseline in the relapsed group, while this was 24.81 U/ml in non-relapsed group (p = 0.001). On the contrary, the LMR level was 5.10 and 2.57 for non-relapsed and relapsed group (p < 0.001), respectively. Kaplan-Meier survival curves stratified by CA19-9 and LMR suggested that patients with lower CA19-9 had higher survival probability (p < 0.001), while patients with high LMR level had higher survival probability (p < 0.001). The multivariable Cox proportional hazard regression analysis with CA19-9 and LMR indicated that although the baseline CA19-9 is significantly associated with increasing risk of disease recurrence, the HR (HR = 1.0, 95% CI 1.00-1.01) was small and close to 1, whereas the high baseline LMR (HR = 0.44, 95% CI 0.32-0.61) was associated with decrease in disease recurrence. Model with continuous CA19-9 and LMR was able to better predict (AUC 73.17%) the disease recurrence. CONCLUSION: LMR combined with CA19-9 may become a new index for predicting postoperative recurrence of CRC in patients with diabetes.

Influence of Muscle Mass Area and Visceral Obesity on 30-day Mortality After Colorectal Surgery with Primary Anastomosis.

BACKGROUND: Muscle mass and visceral fat may be assessed at the level of the third lumbar vertebra (L3) in computed tomography (CT). Both variables have been related with adverse surgical outcomes. OBJECTIVE: The objective of the study was to study the association of skeletal muscle index (SMI) and visceral fat area (VFA) with 30-day mortality in colorectal surgery. METHODS: This is a retrospective cohort study conducted at a tertiary referral hospital in Mexico City. Patients who underwent colorectal surgery with primary anastomosis from January 2007 to December 2018 were included in the study. Their preoperative CT scans were analyzed with the NIH ImageJ software at the level of the third lumbar vertebra to determine their SMI (L3-SMI) and the VFA. Logistic regression analysis (adjusted by surgery anatomical location) was used to determine the association between these variables and surgical 30-day mortality. RESULTS: A total of 548 patients were included; 30-day mortality was 4.18% (23 patients). On univariable analysis, L3-SMI, low SMI, anastomosis leak, pre-operative albumin, estimated blood loss, age, steroid use, Charlson comorbidity index score >2, and type of surgery were associated with 30-day mortality. On multivariable analysis, low SMI remained an independent risk factor with an odds ratio of 4.74, 95% confidence interval 1.22-18.36 (p = 0.02). CONCLUSION: Low SMI was found to be an independent risk factor for 30-day mortality in patients submitted to colorectal surgery with a primary anastomosis, whether for benign or malignant diagnosis. VFA was not associated with 30-day mortality.

The clinical impact of malnutrition on the postoperative outcomes of patients undergoing colorectal resection surgery for colon or rectal cancer: Propensity score matched analysis of 2011-2017 US hospitals.

BACKGROUND & AIMS: Malnutrition can be prevalently found in patients with significant-to-advanced colorectal cancer, who potential require colorectal resection procedures; to accurately describe the postoperative risks, we used a propensity-score matched comparison of national database to analyze the effects of malnutrition on post-colectomy outcomes. METHODS: 2011-2017 National inpatient Sample was used to isolate inpatient ceases of colorectal resection procedures, which were stratified using malnutrition into malnutrition-present cohort and malnutrition-absent controls; the controls were propensity-score matched with the study cohort using 1:1 ratio and compared to the following endpoints: mortality, length of stay, costs, postoperative complications. RESULTS: After matching, there were 11357 with and without malnutrition who underwent colorectal resection surgery; in comparison, malnourished patients had higher rates of in-hospital mortality (6.14 vs 3.22% p < 0.001, OR 1.96 95%CI 1.73-2.23), length of stay (15.4 vs 9.61d p < 0.001), costs ($163, 962 vs $102,709 p < 0.001), and were more likely to be discharged to non-routine discharges, including short term hospitals, skilled nursing facilities, and home healthcare. In terms of complications, malnourished patients had higher bleeding (2.87 vs 1.68% p < 0.001, OR 1.73 95%CI 1.44-2.07), wound complications (4.31 vs 1.34% p < 0.001, OR 3.32 95%CI 2.76-3.99), infection (6 vs 2.62% p < 0.001, OR 2.38 95%CI 2.07-2.73), and postoperative respiratory failure (7.27 vs 3.37% p < 0.001, OR 2.25 95%CI 1.99-2.54). CONCLUSION: This study demonstrates the presence of malnutrition to be associated with adverse postoperative outcomes including mortality and complications in patients undergoing colorectal resection surgery for colon cancer.

Comparative outcomes for older adults undergoing surgery for bladder and bowel dysfunction.

BACKGROUND/OBJECTIVES: To compare surgical outcomes between vulnerable nursing home (NH) residents and matched community-dwelling older adults undergoing surgery for bladder and bowel dysfunction. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 55,389 NH residents and propensity matched (based on procedure, age, sex, race, comorbidity, and year) community-dwelling older adults undergoing surgery for bladder and bowel dysfunction [female pelvic surgery, transurethral resection of the prostate, suprapubic tube placement, hemorrhoid surgery, rectal prolapse surgery]. Individuals were identified using Medicare claims and the Minimum Data Set (MDS) for NH residents between 2014 and 2016. MEASUREMENTS: Thirty-day complications, 1-year mortality, and weighted changes in healthcare resource utilization (hospital admissions, emergency room visits, office visits) in the year before and after surgery. RESULTS: NH residents demonstrated statistically significant increased risk of 30-day complications [60.1% v. 47.2%; RR 1.3 (95% CI 1.3-1.3)] and 1-year mortality [28.9% vs. 21.3%; RR 1.4 (95% CI 1.3-1.4)], compared to community-dwelling older adults. NH residents also demonstrated decreased healthcare resource utilization, compared to community-dwelling older adults, changing from 3.9 to 1.9 (vs.1.1 to 1.0) hospital admissions, 11 to 10.1 (vs. 9 to 9.7) office visits, and 3.4 to 2.2 (vs. 1.9 to 1.9) emergency room visits from the year before to after surgery. CONCLUSION: Despite matching on several important clinical characteristics, NH residents demonstrated increased rates of 30-day complications and 1-year mortality after surgery for bowel and bladder dysfunction, while demonstrating decreased healthcare resource utilization. These mixed findings suggest that outcomes may be more varied among vulnerable older adults and warrant further investigation.

Morbidity and Mortality in Patients with Perioperative COVID-19 Infection: Prospective Cohort in General, Gastroesophagic, Hepatobiliary, and Colorectal Surgery.

BACKGROUND: Severe acute respiratory syndrome due to coronavirus 2 has rapidly spread worldwide in an unprecedented pandemic. Patients with an ongoing COVID-19 infection requiring surgery have higher risk of mortality and complications. This study describes the mortality and morbidity in patients with perioperative COVID-19 infection undergoing elective and emergency surgeries. METHODS: Prospective cohort of consecutive patients who required a general, gastroesophageal, hepatobiliary, colorectal, or emergency surgery during COVID-19 pandemic at an academic teaching hospital. The primary outcome was 30-day mortality and major complications. Secondary outcomes were specific respiratory mortality and complications. RESULTS: A total of 701 patients underwent surgery, 39 (5.6%) with a perioperative COVID-19 infection. 30-day mortality was 12.8% and 1.4% in patients with and without COVID-19 infection, respectively (p < 0.001). Major surgical complications occurred in 25.6% and 6.8% in patients with and without COVID-19 infection, respectively (p < 0.001). Respiratory complications occurred in 30.8% and 1.4% in patients with and without COVID-19 infection, respectively (p < 0.001). Mortality due to a respiratory complication was 100% and 11.1% in patients with and without COVID-19 infection, respectively (p < 0.006). CONCLUSIONS: 30-day mortality and surgical complications are higher in patients with perioperative COVID-19 infection. Indications for elective surgery need to be reserved for non-deferrable procedures in order to avoid unnecessary risks of non-urgent procedures.

Robotic-assisted versus conventional laparoscopic surgery for colorectal cancer: Short-term outcomes at a single center.

BACKGROUND: The robotic technique has been established as an alternative approach to laparoscopy for colorectal surgery. The aim of this study was to compare the short-term outcomes of robot-assisted and laparoscopic surgery in colorectal cancer. METHODS: The cases of robot-assisted or laparoscopic colorectal resection were collected retrospectively between July 2015 and September 2018. We evaluated patient demographics, perioperative characteristics, and pathologic examinations. Short-term outcomes included time to passage of flatus and length of postoperative hospital stay. RESULTS: A total of 580 patients were included in the study. There were 271 patients in the robotic colorectal surgery (RCS) group and 309 in the laparoscopic colorectal surgery (LCS) group. The time to passage of flatus in the RCS group was 3.62 days shorter than the LCS group. The total costs were increased by 2,258.8 USD in the RCS group compared to the LCS group (P < 0.001). CONCLUSION: The present study suggests that colorectal cancer robotic surgery was more beneficial to patients because of a shorter postoperative recovery time of bowel function and shorter hospital stays.

Prognostic significance of interleukin-17A-producing colorectal tumour antigen-specific T cells.

BACKGROUND: The T cell cytokine profile is a key prognostic indicator of post-surgical outcome for colorectal cancer (CRC). Whilst TH1 (IFN-γ+) cell-mediated responses generated in CRC are well documented and are associated with improved survival, antigen-specific TH17 (IL-17A+) responses have not been similarly measured. METHODS: We sought to determine the cytokine profile of circulating tumour antigen-(5T4/CEA) specific T cells of 34 CRC patients to address whether antigen-specific IL-17A responses were detectable and whether these were distinct to IFN-γ responses. RESULTS: As with IFN-γ-producing T cells, anti-5T4/CEA TH17 responses were detectable predominantly in early stage (TNM I/II) CRC patients. Moreover, whilst IL-17A was always produced in association with IFN-γ, this release was mainly from two distinct T cell populations rather than by 'dual producing' T cells. Patients mounting both tumour-specific TH1+/TH17+ responses exhibited prolonged relapse-free survival. CONCLUSIONS: Tumour antigen-specific TH17 responses play a beneficial role in preventing post-operative colorectal tumour recurrence.

Frequent post-operative monitoring of colorectal cancer using individualised ctDNA validated by multiregional molecular profiling.

BACKGROUND: Circulating tumour DNA (ctDNA) is known as a tumour-specific personalised biomarker, but the mutation-selection criteria from heterogeneous tumours remain a challenge. METHODS: We conducted multiregional sequencing of 42 specimens from 14 colorectal tumours of 12 patients, including two double-cancer cases, to identify mutational heterogeneity to develop personalised ctDNA assays using 175 plasma samples. RESULTS: "Founder" mutations, defined as a mutation that is present in all regions of the tumour in a binary manner (i.e., present or absent), were identified in 12/14 tumours. In contrast, "truncal" mutations, which are the first mutation that occurs prior to the divergence of branches in the phylogenetic tree using variant allele frequency (VAF) as continuous variables, were identified in 12/14 tumours. Two tumours without founder and truncal mutations were hypermutators. Most founder and truncal mutations exhibited higher VAFs than "non-founder" and "branch" mutations, resulting in a high chance to be detected in ctDNA. In post-operative long-term observation for 10/12 patients, early relapse prediction, treatment efficacy and non-relapse corroboration were achievable from frequent ctDNA monitoring. CONCLUSIONS: A single biopsy is sufficient to develop custom dPCR probes for monitoring tumour burden in most CRC patients. However, it may not be effective for those with hypermutated tumours.

An Oxidative Stress Index-Based Score for Prognostic Prediction in Colorectal Cancer Patients Undergoing Surgery.

Oxidative stress plays an important role in the development of colorectal cancer (CRC). This study is aimed at developing and validating a novel scoring system, based on oxidative stress indexes, for prognostic prediction in CRC patients. A retrospective analysis of 1422 CRC patients who underwent surgical resection between January 2013 and December 2017 was performed. These patients were randomly assigned to the training set (n = 1022) or the validation set (n = 400). Cox regression model was used to analyze the laboratory parameters. The CRC-Integrated Oxidative Stress Score (CIOSS) was developed from albumin (ALB), direct bilirubin (DBIL), and blood urea nitrogen (BUN), which were significantly associated with survival in CRC patients. Furthermore, a survival nomogram was generated by combining the CIOSS with other beneficial clinical characteristics. The CIOSS generated was as follows: 0.074 × albumin (g/L), -0.094 × bilirubin (µmol/L), and -0.099 × blood urea nitrogen (mmol/L), based on the multivariable Cox regression analysis. Using 50% (0.1025) and 85% (0.481) of CIOSS as cutoff values, three prognostically distinct groups were formed. Patients with high CIOSS experienced worse overall survival (OS) (hazard ratio [HR] = 4.33; 95% confidence interval [CI], 2.80-6.68; P < 0.001) and worse disease-free survival (DFS) (HR = 3.02; 95% CI, 1.96-4.64; P < 0.001) compared to those with low CIOSS. This predictive nomogram had good calibration and discrimination. ROC analyses showed that the CIOSS possessed excellent performance (AUC = 0.818) in predicting DFS. The AUC of the OS nomogram based on CIOSS, TNM stage, T stage, and chemotherapy was 0.812, while that of the DFS nomogram based on CIOSS, T stage, and TNM stage was 0.855. Decision curve analysis showed that these two prediction models were clinically useful. CIOSS is a CRC-specific prognostic index based on the combination of available oxidative stress indexes. High CIOSS is a powerful indicator of poor prognosis. The CIOSS also showed better predictive performance compared to TNM stage in CRC patients.

A nomogram based on pretreatment levels of serum bilirubin and total bile acid levels predicts survival in colorectal cancer patients.

BACKGROUND: Serum bilirubin and total bile acid (TBA) levels have been reported to be strongly associated with the risk and prognosis of certain cancers. Here, we aimed to investigate the effects of pretreatment levels of serum bilirubin and bile acids on the prognosis of patients with colorectal cancer (CRC). METHODS: A retrospective cohort of 1474 patients with CRC who underwent surgical resection between January 2015 and December 2017 was included in the study. Survival analysis was used to evaluate the predictive value of pretreatment levels of bilirubin and bile acids. X-Tile software was used to identify optimal cut-off values for total bilirubin (TBIL), direct bilirubin (DBIL) and TBA in terms of overall survival (OS) and disease-free survival (DFS). RESULTS: DBIL, TBIL, and TBA were validated as significant prognostic factors by univariate Cox regression analysis for both 3-year OS and DFS. Multivariate Cox regression analyses confirmed that high DBIL, TBIL and TBA levels were independent prognostic factors for both OS (HR: 0.435, 95% CI: 0.299-0.637, P < 0.001; HR: 0.436, 95% CI: 0.329-0.578, P < 0.001; HR: 0.206, 95% CI: 0.124-0.341, P < 0.001, respectively) and DFS (HR: 0.583, 95% CI: 0.391-0.871, P = 0.008; HR:0.437,95% CI: 0.292-0.655, P <0.001; HR: 0.634, 95% CI: 0.465-0.865, P = 0.004, respectively). In addition, nomograms for OS and DFS were established according to all significant factors, and the c-indexes were 0.819 (95% CI: 0.806-0.832) and 0.835 (95% CI: 0.822-0.849), respectively. CONCLUSIONS: TBIL, DBIL and TBA levels are independent prognostic factors in colorectal cancer patients. The nomograms based on OS and DFS can be used as a practical model for evaluating the prognosis of CRC patients.

Hazard function analysis of metastatic recurrence after colorectal cancer surgery-A nationwide retrospective study.

BACKGROUND AND OBJECTIVES: An optimal postoperative surveillance protocol for colorectal cancer (CRC) is dependent on understanding the time line of recurrence. By hazard function analysis, this study aimed at evaluating the time of occurrence of metastasis. METHODS: A total of 21,671 Stage I-III colon cancer patients were retrospectively included from the Japanese study group for postoperative follow-up of colorectal cancer database. RESULTS: The 5-year incidence by metastasized organ was 6.3% for liver (right:left = 5.5%:7.0%, p = .0067), 6.0% for lung (right:left:rectum = 3.7%:4.4%:8.8%, p = 7.05E-45), and 2.0% for peritoneal (right:left:rectum = 3.1%:2.0%:1.2%, p = 1.29E-12). The peak of liver metastasis hazard rate (HR) (0.67 years) was earlier and higher than those of other metastases. The peak HR tended to be delayed in early stage CRCs (0.91, 0.76, and 0.52 years; for Stages I, II, and III, respectively). When analyzed as per the primary tumor location (right-sided, left-sided, and rectum), the peak HR for lung metastasis was twice as high for rectal cancer than for colon cancer, and peritoneal metastasis had a high HR in right-sided colon cancers. CONCLUSION: The time course for the risk of recurrence in various metastatic organs based on the primary tumor site was clearly visualized in this study. This will aid in individualizing postoperative surveillance schedules.

The interplay of KRAS mutational status with tumor laterality in non-metastatic colorectal cancer: An international, multi-institutional study in patients with known KRAS, BRAF, and MSI status.

BACKGROUND: Although the prognostic relevance of KRAS status in metastatic colorectal cancer (CRC) depends on tumor laterality, this relationship is largely unknown in non-metastatic CRC. METHODS: Patients who underwent resection for non-metastatic CRC between 2000 and 2018 were identified from institutional databases at six academic tertiary centers in Europe and Japan. The prognostic relevance of KRAS status in patients with right-sided (RS), left-sided (LS), and rectal cancers was assessed. RESULTS: Of the 1093 eligible patients, 378 had right-sided tumors and 715 had left-sided tumors. Among patients with RS tumors, the 5-year overall (OS) and recurrence-free survival (RFS) for patients with KRASmut versus wild-type tumors was not shown to differ significantly (82.2% vs. 83.2% and 72.1% vs. 76.7%, respectively, all p > .05). Among those with LS tumors, KRAS mutation was associated with shorter 5-year OS and RFS on both the univariable (OS: 79.4% vs. 86.1%, p = .004; RFS: 68.8% vs. 77.3%, p = .005) and multivariable analysis (OS: HR: 1.52, p = .019; RFS: HR: 1.32, p = .05). CONCLUSIONS: KRAS mutation status was independently prognostic among patients with LS tumors, but this association failed to reach statistical significance in RS and rectal tumors. These findings confirm reports in metastatic CRC and underline the possible biologic importance of tumor location.

Preoperative neutrophil-to-lymphocyte ratio as a predictive factor for survival in nonmetastatic colorectal cancer.

BACKGROUND: The pretreatment ratio of neutrophils to lymphocytes (NLR) has been suggested as an indicator of poor outcome in various cancers. This study aimed to determine whether the preoperative NLR may be a predictor of survival in patients who underwent curative resection for colorectal cancer (CRC). MATERIALS AND METHODS: The records of 219 CRC patients underwent curative resection between 2008 and 2014 were retrospectively evaluated. NLR was calculated by preoperative complete blood counts. The effects of age, gender, anatomic location, histologic grade, lymphovascular invasion, pathological T, pathological N, and tumor-node-metastasis stages and NLR on disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate analyses. The optimal cutoff value for NLR was determined using receiver operating characteristic curve analysis. RESULTS: The best cutoff value of NLR was 2.8. Multivariate analysis showed that NLR was not a predictor of DFS. However, NLR was found as an independent prognostic factor for OS (Hazard ratio, 5.4; 95% confidence interval, 2.3-12.5; P = 0.0001). CONCLUSION: A preoperative NLR of more than 2.8 might be an independent predictor for OS in patients with CRC. This simple and routinely available laboratory parameter may be used as a useful marker for identifying patients with a worse prognosis.

Uptake of minimally invasive surgery for early stage colorectal cancer and its effect on survival: A population-based study.

PURPOSE: The uptake of minimally invasive surgery (MIS) for colorectal cancer (CRC) varies between jurisdictions. We aimed to identify the factors associated with the uptake of MIS for early-stage CRC and its oncologic outcomes in the Canadian province of Ontario. METHODS: This study includes all patients with CRC in Ontario from 2007 to 2017. A logistic regression analysis was used to identify the predictors of MIS and a flexible parametric survival model to estimate survival rates based on MIS versus open surgery. RESULTS: In total, 14,675 patients with CRC were identified of which 29.5% had MIS resections. The likelihood of undergoing MIS decreased with age, disease stage, and distance to the regional cancer center, and increased with year of diagnosis. The likelihood of mortality for MIS was significantly lower compared to open surgery (p < 0.001). In terms of survival, MIS was most beneficial to older patients with stage II disease, despite their lower likelihood of receiving MIS. CONCLUSIONS: Despite the lower uptake of MIS among older patients and patients with stage II disease, these patients had the greatest long-term survival benefit from MIS. This suggests further use of laparoscopy to patient populations that are often excluded.

Impact of ASA-score, age and learning curve on early outcome in the initiation phase of an oncological robotic colorectal program.

The ASA score is known to be an independent predictor of complications and mortality following colorectal surgery. We evaluated early outcome in the initiation phase of a robotic oncological colorectal resection program in dependence of comorbidity and learning curve. 43 consecutive colorectal cancer patients (median age: 74 years) who underwent robotic surgery were firstly analysed defined by physical status (group A = ASA1 + 2; group B = ASA3). Secondly, outcome was evaluated relating to surgery date (group E: early phase; group L: late phase). There were no differences among groups A and B with regard to gender, BMI, skin-to-skin operative times (STS), N- and M-status, hospital-stay as well as overall rate of complications according to Dindo-Clavien and no one-year mortality. GroupA when compared to group B demonstrated significantly lower mean age (65.5 years ± 11.4 years vs 75.8 years ± 8.9 years), T-stage and ICU-stay. When separately analyzed for patients age ICU-stay was comparable (> 75 years vs. < 75 years). Group E and L demonstrated comparable characteristics and early outcome except more frequent lymphatic fistulas in group E. STS was reduced in group L compared to group E. Beyond learning curve aspects in our series, we could demonstrate that patient's physical condition according to ASA rather than age may have an impact on early outcome in the initial phase of a robotic oncological colorectal program.

The impact of multidisciplinary team management on outcome of hepatic resection in liver-limited colorectal metastases.

Hepatic resection is the gold standard treatment for patients affected by liver-limited colorectal metastases. Reports addressing the impact of multidisciplinary team (MDT) evaluation on survival are controversial. The aim of this study was to evaluate the benefit of MDT management in these patients in our Institution experience. The objective of the analysis was to compare survivals of patients managed within our MDT (MDT cohort) to those of patients referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Of the 523 patients, 229 were included in the MDT cohort and 294 in the non-MDT cohort. No difference between the two groups was found in terms of median overall survival (52.5 vs 53.6 months; HR 1.13; 95% CI, 0.88-1.45; p = 0.344). In the MDT cohort there was a higher number of metastases (4.5 vs 2.7; p < 0.0001). The median duration of chemotherapy was lower in MDT patients (8 vs 10 cycles; p < 0.001). Post-operative morbidity was lower in the MDT cohort (6.2 vs 21.5%; p < 0.001). One hundred and ninety-seven patients in each group were matched by propensity score and no significant difference was observed between the two groups in terms of OS and DFS. Our study does not demonstrate a survival benefit from MDT management, but it allows surgery to patients with a more advanced disease. MDT assessment reduces the median duration of chemotherapy and post-operative morbidities.

TRF2 and VEGF-A: an unknown relationship with prognostic impact on survival of colorectal cancer patients.

BACKGROUND: Colorectal cancer is one of most common tumors in developed countries and, despite improvements in treatment and diagnosis, mortality rate of patients remains high, evidencing the urgent need of novel biomarkers to properly identify colorectal cancer high-risk patients that would benefit of specific treatments. Recent works have demonstrated that the telomeric protein TRF2 is over-expressed in colorectal cancer and it promotes tumor formation and progression through extra-telomeric functions. Moreover, we and other groups evidenced, both in vitro on established cell lines and in vivo on tumor bearing mice, that TRF2 regulates the vascularization mediated by VEGF-A. In the present paper, our data evidence a tight correlation between TRF2 and VEGF-A with prognostic relevance in colorectal cancer patients. METHODS: For this study we sampled 185 colorectal cancer patients surgically treated and diagnosed at the Regina Elena National Cancer Institute of Rome and investigated the association between the survival outcome and the levels of VEGF-A and TRF2. RESULTS: Tissue microarray immunohistochemical analyses revealed that TRF2 positively correlates with VEGF-A expression in our cohort of patients. Moreover, analysis of patients' survival, confirmed in a larger dataset of patients from TCGA, demonstrated that co-expression of TRF2 and VEGF-A correlate with a poor clinical outcome in stage I-III colorectal cancer patients, regardless the mutational state of driver oncogenes. CONCLUSIONS: Our results permitted to identify the positive correlation between high levels of TRF2 and VEGF-A as a novel prognostic biomarker for identifying the subset of high-risk colorectal cancer patients that could benefit of specific therapeutic regimens.

Development and validation of a nomogram to predict survival after curative resection of nonmetastatic colorectal cancer.

BACKGROUND: We aimed to develop a clinical applicable nomogram to predict overall survival (OS) for patients with curatively resected nonmetastatic colorectal cancer. METHODS: Records from a retrospective cohort of 846 patients with complete information were used to construct the nomogram. The nomogram was validated in a prospective cohort of 379 patients. The performance of the nomogram was evaluated with concordance index (c-index), time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analyses for discrimination, accuracy, calibration ability, and clinical net benefits respectively, and further compared with AJCC 8th TNM staging and the MSKCC nomogram. Risk stratification based on nomogram scores was performed with recursive partitioning analysis. RESULTS: The nomogram incorporated age, Glasgow prognostic score, pretreatment carcinoembryonic antigen levels, T staging, N staging, number of harvested lymph nodes, and histological grade. Compared with the 8th AJCC staging and MSKCC model, the nomogram had a statistically higher c-index (0.77, 95% CI: 0.73-0.80), bigger areas under the time-dependent ROC curves (AUC at 3 years: 79; at 5 years: 79), and improved clinical net benefits. Calibration plots revealed no deviations from reference lines. All results were reproducible in the validation cohort. Nomogram-based risk stratification successfully discriminated patients within each AJCC stage (all log-rank P < .05). CONCLUSION: We established an accurate, reliable, and easy-to-use nomogram to predict OS after curative resection for nonmetastatic colorectal cancer (CRC). The nomogram outperformed the 8th AJCC staging and the MSKCC model and could aid in personalized treatment and follow-up strategy for CRC patients.

Clinical Implication of Concordant or Discordant Genomic Profiling between Primary and Matched Metastatic Tissues in Patients with Colorectal Cancer.

PURPOSE: The purpose of this study was to identify the concordant or discordant genomic profiling between primary and matched metastatic tumors in patients with colorectal cancer (CRC) and to explore the clinical implication. MATERIALS AND METHODS: Surgical samples of primary and matched metastatic tissues from 158 patients (335 samples) with CRC at Korea University Anam Hospital were evaluated using the Ion AmpliSeq Cancer Hotspot Panel. We compared genetic variants and classified them as concordant, primary-specific, and metastasis-specific variants. We used a combination of principal components analysis and clustering to find genomic groups. Kaplan-Meier curves were used to appraise survival between genomic groups. We used machine learning to confirm the correlation between genetic variants and metastatic sites. RESULTS: A total of 282 types of deleterious non-synonymous variants were selected for analysis. Of a total of 897 variants, an average of 40% was discordant. Three genomic groups were yielded based on the genomic discrepancy patterns. Overall survival differed significantly between the genomic groups. The poorest group had the highest proportion of concordant KRAS G12V and additional metastasis-specific SMAD4. Correlation analysis between genetic variants and metastatic sites suggested that concordant KRAS mutations would have more disseminated metastases. CONCLUSION: Driver gene mutations were mostly concordant; however, discordant or metastasis-specific mutations were present. Clinically, the concordant driver genetic changes with additional metastasis-specific variants can predict poor prognosis for patients with CRC.