A DNA damage response-like phenotype defines a third of colon cancers at onset.

Colon adenocarcinoma (COAD) has a limited range of diversified, personalized therapeutic opportunities, besides DNA hypermutating cases; thus, both new targets or broadening existing strategies for personalized intervention are of interest. Routinely processed material from 246 untreated COADs with clinical follow-up was probed for evidence of DNA damage response (DDR), that is, the gathering of DDR-associated molecules at discrete nuclear spots, by multiplex immunofluorescence and immunohistochemical staining for DDR complex proteins (γH2AX, pCHK2, and pNBS1). We also tested the cases for type I interferon response, T-lymphocyte infiltration (TILs), and mutation mismatch repair defects (MMRd), known to be associated with defects of DNA repair. FISH analysis for chromosome 20q copy number variations was obtained. A total of 33.7% of COAD display a coordinated DDR on quiescent, non-senescent, non-apoptotic glands, irrespective of TP53 status, chromosome 20q abnormalities, and type I IFN response. Clinicopathological parameters did not differentiate DDR+ cases from the other cases. TILs were equally present in DDR and non-DDR cases. DDR+ MMRd cases were preferentially retaining wild-type MLH1. The outcome after 5FU-based chemotherapy was not different in the two groups. DDR+ COAD represents a subgroup not aligned with known diagnostic, prognostic, or therapeutic categories, with potential new targeted treatment opportunities, exploiting the DNA damage repair pathways.

Small arteriole sign: an imaging feature for staging T4a colon cancer.

OBJECTIVES: By analyzing the distribution of existing and newly proposed staging imaging features in pT1-3 and pT4a tumors, we searched for a salient feature and validated its diagnostic performance. METHODS: Preoperative multiphase contrast-enhanced CT images of the training cohort were retrospectively collected at three centers from January 2016 to December 2017. We used the chi-square test to analyze the distribution of several stage-related imaging features in pT1-3 and pT4a tumors, including small arteriole sign (SAS), outer edge of the intestine, tumor invasion range, and peritumoral adipose tissue. Preoperative multiphase contrast-enhanced CT images of the validation cohort were retrospectively collected at Beijing Cancer Hospital from January 2018 to December 2018. The diagnostic performance of the selected imaging feature, including accuracy, sensitivity, and specificity, was validated and compared with the conventional clinical tumor stage (cT) by the McNemar test. RESULTS: In the training cohort, a total of 268 patients were enrolled, and only SAS was significantly different between pT1-3 and pT4a tumors. The accuracy, sensitivity, and specificity of the SAS and conventional cT in differentiating T1-3 and T4a tumors were 94.4%, 81.6%, and 97.3% and 53.7%, 32.7%, and 58.4%, respectively (all p < 0.001). In the validation cohort, a total of 135 patients were collected. The accuracy, sensitivity, and specificity of the SAS and the conventional cT were 93.3%, 76.2%, and 96.5% and 62.2%, 38.1%, and 66.7%, respectively (p < 0.001, p = 0.021, p < 0.001). CONCLUSION: Small arteriole sign positivity, an indirect imaging feature of serosa invasion, may improve the accuracy of identifying T4a colon cancer. CLINICAL RELEVANCE STATEMENT: Small arteriole sign helps to distinguish T1-3 and T4a colon cancer and further improves the accuracy of preoperative CT staging of colon cancer. KEY POINTS: • The accuracy of preoperative CT staging of colon cancer is not ideal, especially for T4a tumors. • Small arteriole sign (SAS) is a newly defined imaging feature that shows the appearance of tumor-supplying arterioles at the site where they penetrate the intestine wall. • SAS is an indirect imaging marker of tumor invasion into the serosa with a great value in distinguishing between T1-3 and T4a colon cancer.

Gastrointestinal functions after laparoscopic right colectomy with intracorporeal anastomosis: a pilot randomized clinical trial on effects of abdominal drain, prolonged antibiotic prophylaxis, and D3 lymphadenectomy with complete mesocolic excision.

PURPOSE: Routine use of abdominal drain or prolonged antibiotic prophylaxis is no longer part of current clinical practice in colorectal surgery. Nevertheless, in patients undergoing laparoscopic right hemicolectomy with intracorporeal anastomosis (ICA), it may reduce perioperative abdominal contamination. Furthermore, in cancer patients, prolonged surgery with extensive dissection such as central vascular ligation and complete mesocolon excision with D3 lymphadenectomy (altogether radical right colectomy RRC) is called responsible for affecting postoperative ileus. The aim was to evaluate postoperative resumption of gastrointestinal functions in patients undergoing right hemicolectomy for cancer with ICA and standard D2 dissection or RRC, with or without abdominal drain and prolonged antibiotic prophylaxis. METHODS: Monocentric factorial parallel arm randomized pilot trial including all consecutive patients undergoing laparoscopic right hemicolectomy and ICA for cancer, in 20 months. Patients were randomized on a 1:1:1 ratio to receive abdominal drain, prolonged antibiotic prophylaxis or neither (I level), and 1:1 to receive RRC or D2 colectomy (II level). Patients were not blinded. The primary aim was the resumption of gastrointestinal functions (time to first gas and stool, time to tolerated fluids and food). Secondary aims were length of stay and complications' rate. CLINICALTRIALS: gov no. NCT04977882. RESULTS: Fifty-seven patients were screened; according to sample size, 36 were randomized, 12 for each arm for postoperative management, and 18 for each arm according to surgical techniques. A difference in time to solid diet favored the group without drain or antibiotic independently from standard or RRC. Furthermore, when patients were divided with respect to surgical technique and into matched cohorts, no differences were seen for primary and secondary outcomes. CONCLUSION: Abdominal drainage and prolonged antibiotic prophylaxis in patients undergoing right hemicolectomy for cancer with ICA seem to negatively affect the resumption of a solid diet after laparoscopic right hemicolectomy with ICA for cancer. RRC does not seem to influence gastrointestinal function recovery.

Influence of proficiency in conventional laparoscopic surgery in colorectal cancer on the introduction of robotic surgery.

PURPOSE: Although there have been many reports on learning curves for robotic surgery, it is unclear how surgeons' conventional laparoscopic surgical skills influence their ability in performing robotic surgery for colorectal cancer (CRC). The aim of this study was to determine the surgical outcomes of robotic surgery for CRC during the induction phase by skilled laparoscopic surgeons. METHODS: Surgical outcomes of consecutive CRC cases between January 2021 and March 2023 following the skilled phase of laparoscopic surgery and introductory phase of robotic surgery performed by three skilled laparoscopic surgeons were compared. RESULTS: Overall, 77 consecutive patients diagnosed with sigmoid colon or rectosigmoid cancer were analysed, including 50 in the laparoscopy group (LAP) and 27 in the robotic group (Ro). Patient characteristics, including age, sex, body mass index, and tumour progression, did not differ between the groups. The median operation time was 204 min in the robotic group and 170 min in the laparoscopic group (p < 0.001). Blood loss was significantly lower in the robotic group (p = 0.0059). The incidence of grade 2 or higher complications did not differ between the two groups (LAP, 10.0% vs. Ro, 7.4%, p = 1). In the robotic group, the time required for lymph node dissection had a greater impact on operative duration. CONCLUSION: Skills acquired from performing conventional laparoscopic surgery may contribute to the safe and reliable performance of robotic surgery for CRC. TRIAL REGISTRATION: UMIN000050923.

Clinical utility of the carcinoembryonic antigen level in patients with stage III colon cancer after surgery and adjuvant chemotherapy.

PURPOSE: The association between perioperative and post-adjuvant carcinoembryonic antigen (CEA) levels and recurrence and prognosis remains unclear. We aimed to evaluate whether perioperative CEA levels are an integral component of the assessment of recurrence and prognosis of patients with stage III colon cancer (CC). METHODS: This retrospective study was conducted at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 2005 to 2013. We enrolled patients with stage III CC who underwent complete resection of a primary tumor and received adjuvant chemotherapy. We analyzed the association between perioperative and post-adjuvant CEA levels and recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 564 consecutive patients were included in the analysis. The RFS and OS of patients with high postoperative CEA levels were significantly worse than those of patients with normal postoperative CEA levels. In the multivariate analysis, high postoperative CEA levels were associated with shorter RFS and OS. The number of risk factors, postoperative CEA levels, and T/N-stage all had a cumulative effect on RFS and OS. CONCLUSIONS: High postoperative CEA levels and the number of risk factors are associated with recurrence and worse prognosis for patients with stage III CC.

Proposal for standardization of laparoscopic D3 lymphadenectomy for right colon cancer.

BACKGROUND: This study presents a laparoscopic surgical protocol for right hemicolectomy and D3 lymphadenectomy (R-D3L) in right colon cancer and reports the oncological outcomes based on a prospective series. METHODS: The study comprises two phases. In the first phase, a dynamic demonstration of the R-D3L surgical protocol is provided through textual explanation, illustrations, and edited surgical videos. The protocol emphasizes technical steps such as dissection of the embryological plane of the right mesocolon, high tie of ileocolic vessels, surgical trunk of Gillot dissection, and high tie of superior right colic vein (SRCV). In the second phase, a prospective observational study was conducted involving patients undergoing R-D3L surgery with this protocol between July 2015 and July 2021. Demographic, perioperative, and postoperative variables are analyzed, along with anatomopathological variables and oncological outcomes. RESULTS: A total of 33 patients were analyzed. Median operative time was 202 min. Perioperative bleeding occurred in 6%. Postoperative complications were mild (Clavien-Dindo III in 2%). Postoperative ileus was observed in 15%. No anastomotic dehiscence was reported. The median postoperative stay was 7 days. The median number of resected lymph nodes was 26, with 27% having positive nodes and 70% were classified as stage T3 or T4. After a median follow-up of 45 months, local recurrence, distant recurrence, and carcinomatosis rates were 0%. Mortality rate from other causes was 9%. CONCLUSION: The surgical protocol shown in the present study could help in the implementation of this technique in those units that consider it appropriate.

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer.

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. MATERIALS AND METHODS: Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. RESULTS: The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). CONCLUSION: These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.

Impact of Patient Comorbidities on Presentation Stage of Breast and Colon Cancers.

BACKGROUND: While patients with multiple comorbidities may have frequent contact with medical providers, it is unclear whether their healthcare visits translate into earlier detection of cancers, specifically breast and colon cancers. METHODS: Patients diagnosed with stage I-IV breast ductal carcinoma and colon adenocarcinoma were identified from the National Cancer Database and stratified by comorbidity burden, dichotomized as a Charlson Comorbidity Index (CCI) Score of <2 or ≥2. Characteristics associated with comorbidities were analyzed by univariate and multivariate logistic regression. Propensity-score matching was performed to determine the impact of CCI on stage at cancer diagnosis, dichotomized as early (I-II) or late (III-IV). RESULTS: A total of 672,032 patients with colon adenocarcinoma and 2,132,889 with breast ductal carcinoma were included. Patients with colon adenocarcinoma who had a CCI ≥ 2 (11%, n = 72,620) were more likely to be diagnosed with early-stage disease (53% vs. 47%; odds ratio [OR] 1.02, p = 0.017), and this finding persisted after propensity matching (CCI ≥ 2 55% vs. CCI < 2 53%, p < 0.001). Patients with breast ductal carcinoma who had a CCI ≥ 2 (4%, n = 85,069) were more likely to be diagnosed with late-stage disease (15% vs. 12%; OR 1.35, p < 0.001). This finding also persisted after propensity matching (CCI ≥ 2 14% vs. CCI < 2 10%, p < 0.001). CONCLUSIONS: Patients with more comorbidities are more likely to present with early-stage colon cancers but late-stage breast cancers. This finding may reflect differences in practice patterns for routine screening in these patients. Providers should continue guideline directed screenings to detect cancers at an earlier stage and optimize outcomes.

Staging Chest CT in Patients With Early-Stage Colon Cancer: Analysis of Impact on Survival Using Inverse Probability Weighting and Causal Diagram.

BACKGROUND. Staging chest CT has been shown to have negligible diagnostic yield for detecting lung metastases in patients with early-stage colon cancer. Nonetheless, staging chest CT may have potential survival benefits, including opportunistic screening of comorbidity and provision of a baseline examination for future comparisons. Evidence is lacking regarding the impact of staging chest CT on survival in patients with early-stage colon cancer. OBJECTIVE. The purpose of this study was to determine whether the performance of staging chest CT affects survival in patients with early-stage colon cancer. METHODS. This retrospective study included patients with early-stage colon cancer (defined as clinical stage 0 or I on staging abdominal CT) at a single tertiary hospital between January 2009 and December 2015. Patients were divided into two groups according to the presence of a staging chest CT examination. To ensure comparability between the two groups, inverse probability weighting was applied to adjust for the confounders derived from a causal diagram. The between-group differences in adjusted restricted mean survival time at 5 years were measured for overall survival, relapse-free survival, and thoracic metastasis-free survival. Sensitivity analyses were performed. RESULTS. A total of 991 patients (618 men and 373 women; median age, 64 years [IQR, 55-71 years]) were included: 606 patients (61.2%) had staging chest CT. For overall survival, the difference between groups in restricted mean survival time at 5 years was not significant (0.4 months [95% CI, -0.8 to 2.1 months]). The differences between groups in restricted mean survival at 5 years were also not significant for relapse-free survival (0.4 months [95% CI, -1.1 to 2.3 months]) and for thoracic metastasis-free survival (0.6 months [95% CI, -0.8 to 2.4 months]). Similar results were observed in sensitivity analyses that tested 3- and 10-year RMST differences, excluded patients who underwent FDG PET/CT during staging workup, and added treatment decision (surgery vs no surgery) to the causal diagram. CONCLUSION. The use of staging chest CT did not affect survival in patients with early-stage colon cancer. CLINICAL IMPACT. Staging chest CT may be omitted from the staging workup for patients with colon cancer of clinical stage 0 or I.

The effect of preoperative endoscopic tattooing using India ink on lymph node yield in laparoscopic colectomy for stage I right-sided colon cancer.

PURPOSE: The purpose of this study is to evaluate the effect of preoperative endoscopic tattooing using India ink (ETI) on the number of retrieved lymph nodes (LNs) dissected during laparoscopic surgery for stage I right-sided colon cancer (RCC). METHODS: This single-center, retrospective study included stage I RCC patients who underwent laparoscopic surgery between January 2010 and December 2021. The clinicopathological background and number of LNs retrieved were compared between patients managed with and without ETI. A multiple linear regression analysis was used to examine the effect of independent variables on the LN yield. RESULTS: A total of 169 patients were enrolled. Of these, 89 patients (52.7%) were classified into the ETI group, and 80 (47.3%) were classified into the no-ETI group. There were no significant differences in age, sex, body mass index, or tumor progression between the two groups. A univariate analysis showed that the number of LNs retrieved was significantly higher in female (26 vs. 24, p = 0.026), with tumor localization in the ascending or transverse colon (20 in the cecum, 26 in the ascending colon, 27 in the transverse colon, p < 0.001), and with preoperative ETI (28 vs. 21, p < 0.001). In a multivariate linear regression analysis, female sex (p = 0.0011), D3 lymphadenectomy (p = 0.046), and preoperative ETI (p = 0.012) were independently associated with the LN yield. CONCLUSION: In laparoscopic surgery for stage I RCC, preoperative ETI increased the number of LNs retrieved and allowed for appropriate staging.

The usefulness of indocyanine green fluorescence imaging for intestinal perfusion assessment of intracorporeal anastomosis in laparoscopic colon cancer surgery.

PURPOSE: The purpose of this study was to clarify the usefulness of indocyanine green fluorescence imaging (ICG-FI) in the assessment of intestinal vascular perfusion in patients who receive intracorporeal anastomosis (IA) in colon cancer surgery. METHODS: This was a single-center, retrospective study using propensity score matching. We compared the surgical outcomes of colon cancer patients who underwent laparoscopic colonic resection with IA or external anastomosis (EA) with the intraoperative evaluation of anastomotic perfusion using ICG-FI from January 2019 to July 2021. The detection rate of poor anastomotic perfusion by ICG-FI was examined. RESULTS: A total of 223 patients were enrolled. After matching, 69 patients each were classified into the IA and EA groups. There were no significant differences in age, sex, body mass index, tumor localization, or progression between the two groups. The operation time was similar (172 min vs. 171 min, p = 0.62) and the amount of bleeding was significantly lower (0 ml vs. 2 ml, p = 0.0023) in the IA group. The complication rates (grade ≥ 2) of the two groups were similar (14.5% vs. 11.6%, p = 0.59). ICG-FI identified four patients (5.8%) with poor anastomotic perfusion in the IA group, but none in the EA group (p = 0.046). All four patients with poor perfusion in the IA group underwent additional resection; none of these patients developed postoperative complications. CONCLUSION: Poor anastomotic perfusion was detected in 5.8% of cases who underwent laparoscopic colon cancer surgery with IA. ICG-FI is useful for evaluating anastomotic perfusion in IA in order to prevent AL.

α-SMA+ cancer-associated fibroblasts increased tumor enhancement ratio on contrast-enhanced multidetector-row computed tomography in stages I-III colon cancer.

BACKGROUND AND AIM: Our prior research revealed that the tumor enhancement ratio (TER) on triphasic abdominal contrast-enhanced MDCT (CE-MDCT) scans was a prognostic factor for patients with stages I-III colon cancer. Building upon this finding, the present study aims to investigate the proteomic changes in colon cancer patients with varying TER values. METHODS: TER was analyzed on preoperative triphasic CE-MDCT scans of 160 stages I-III colon cancer patients. The survival outcomes of those in the low-TER and high-TER groups were compared. Proteomic analysis on colon cancer tissues was performed by mass spectrometry (MS) and verified by immune-histological chemistry (IHC) assays. In vivo, mouse xenograft models were employed to test the function of target proteins identified through the MS. CE-MDCT scans were conducted on mice xenografts, and the TER values were compared. RESULTS: Patients in the high-TER group had a significantly worse prognosis than those in the low-TER group. Proteomic analysis of colon cancer tissues revealed 153 differentially expressed proteins between the two groups. A correlation between TER and the abundance of α-SMA protein in tumor tissue was observed. IHC assays further confirmed that α-SMA protein expression was significantly increased in high-TER colon cancer, predominantly in cancer-associated fibroblasts (CAFs) within the cancer stroma. Moreover, CAFs promoted the growth of CRC xenografts in vivo and increased TER. CONCLUSIONS: Our study identified the distinct protein changes in colon cancer with low and high TER for the first time. The presence of CAFs may promote the growth of colon cancer and contribute to an increased TER.

Novel approach toward minimally invasive surgery for mid-transverse colon cancer: 'moving the left colon' technique.

AIM: During surgery for mid-transverse colon cancer (MTC), surgeons often face the dilemma of whether to mobilize the hepatic or splenic flexure. There is no established optimal minimally invasive surgical procedure for MTC. METHODS: We present our novel minimally invasive surgical technique, called the 'moving the left colon' technique for MTC, along with a video demonstration. The procedure involves four main steps: (i) mobilization of the splenic flexure using a medial-to-lateral approach, (ii) dissection of lymph nodes around the middle colic artery from the left side of the superior mesenteric artery approach, (iii) separation of the pancreas and transverse mesocolon and (iv) 'moving the left colon' and performing an intracorporeal anastomosis. By mobilizing the splenic flexure, anatomical landmarks are revealed, which enables safer dissection. Combining this technique with intracorporeal anastomosis allows for a safe and easy anastomosis. RESULTS: Between April 2021 and January 2023, a single-skilled colorectal surgeon performed laparoscopic transverse colectomies using our new approach on three consecutive patients with MTC. The patients had a median age of 75 years (range 46-89 years). The median operative time was 194 min (range 193-228 min) and blood loss was 8 mL (range 0-20 mL). None of the patients experienced any perioperative complications and the median postoperative hospital stay was 6 days. CONCLUSION: We introduced a novel approach for laparoscopic surgery for MTC. This technique can be performed safely and may help standardize minimally invasive surgery for MTC.

Pancreaticoduodenectomy with right hemicolectomy for advanced malignancy: a single UK hepatopancreaticobiliary centre experience.

AIM: Locally advanced intestinal neoplasms including colon cancer may require radical en bloc pancreaticoduodenectomy and right hemicolectomy (PD-RC) to achieve curative, margin-negative resection, but the safety and benefit of this uncommon procedure has not been established. The Association of Coloproctology of Great Britain and Ireland IMPACT initiative has also highlighted a lack of awareness about current services available within the UK for patients with advanced colorectal cancer and concerns about low-volume centres managing complex cases. Thus, we aimed to review the feasibility, safety and long-term outcomes of this procedure at a single high-volume hepatopancreaticobiliary surgery unit in the UK. METHOD: A retrospective cohort study was performed using a database of all consecutive patients with intestinal cancer who had been referred to our regional advanced multidisciplinary team and undergone PD-RC in a 7-year period (2013-2020). Clinico-pathological and outcome data were reviewed. RESULTS: Ten patients (mean age 54 ± 13, 8/10 men) were identified. Final histology revealed the primary tumour sites were colon (n = 7) and duodenum (n = 3). R0 resection was achieved in all cases. The major complication rate (Clavien-Dindo ≥ 3) was 10% (1/10) with no deaths within 90 days of surgery. The Kaplan-Meier estimated 5-year overall survival was 83.3% (95% CI 58.3%-100%). Univariate survival analysis identified perineural invasion and extra-colonic origin as predictors of poor survival (log-rank P < 0.05). CONCLUSION: En bloc PD-RC for locally advanced intestinal cancer can be performed safely with a high proportion of margin-negative resections and resultant long-term survival in carefully selected patients.

Virtual monoenergetic dual-layer dual-energy CT images in colorectal cancer: CT diagnosis could be improved?

PURPOSE: To compare conventional CT images and virtual monoenergetic images (VMI) at dual-layer dual-energy CT (dlDECT) in patients with colorectal cancer (CRC) through quantitative analysis and to investigate the added value of VMI. MATERIAL AND METHODS: Sixty-six consecutive patients with histologically documented CRC and available VMI reconstructions were retrospectively investigated. Subsequently, forty-two patients, without any colonic disease at colonoscopy, were selected as control group. Conventional CT images and VMI reconstructions at energy levels ranging from 40 (VMI40) to 100 keV (VMI100) in 10 keV increments, were obtained from the late arterial phase. First, signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were obtained to select the best VMI reconstruction. Finally, the diagnostic accuracy of conventional CT and VMI40 in late arterial phase was evaluated. RESULTS: On quantitative analysis, SNR and CNR were higher for VMI40 (19.5 ± 7.7 and 11.8 ± 6.2, respectively) with statistically significant differences compared to conventional CT (P < 0.05) and all the other VMI reconstructions (P < 0.05), except for VMI50 (P > 0.05). The addition of VMI40 to conventional CT images significantly improved the area under the curve (AUC) for the diagnosis of CRC, increasing it from 0.875 to 0.943 for reader 1 (P < 0.05) and from 0.916 to 0.954 for reader 2 (P < 0.05). The improvement was greater in the less experienced radiologist (0.068) compared to the more experienced one (0.037). CONCLUSION: VMI40 has showed the highest quantitative image parameters. Furthermore, the use of VMI40 can lead to a significant improvement in the diagnostic performance for detecting CRC.

Multivariate Prognostic Models for Patients with Stages I and Ii Colon Carcinoma: a Strobe-Compliant Retrospective Cohort Study.

Background: Colorectal cancer is the most frequent gastrointestinal malignancy worldwide. The value of adjuvant treatment is controversial in Stages I and II. Objective: The aim of this study was to construct post-operative prognostic models applicable to patients with stages I-II colon carcinoma (CC). Methods: This is a retrospective cohort study of patients with Stage I-II CC treated over a 25-year period. Exposure was defined as clinical, histopathological, and immunohistochemical factors (including CDX2 and MUC2 expression). Patients were randomly allocated to either a "modeling set" or a "validation set". Factors associated with recurrence, disease-free survival (DFS), and overall survival (OS) were defined in the "modeling set". Their performances were tested in the "validation set". Results: From a total of 556 recruited patients, 339 (61%) were allocated to the "modeling set" and 217 (39%) to the "validation set". Three models explaining recurrence, DFS, and OS were described. Tumor location in the left colon (Hazards ratio [HR] = 1.57; 95% Confidence interval [CI] 0.99-2.48), lymphocyte (HR = 0.46; 96% CI 0.27-0.88) and monocyte (HR = 0.99; 95% CI 0.99-1) counts, neutrophil/platelet ratio (HR = 1.3; 95% CI 0.74-2.3, and HR = 2.3; 95% CI 1.3-4.1; for second and third category, respectively), albumin/monocyte ratio (HR = 0.43; 95% CI 0.21-0.87), and microscopic residual disease after surgery (HR = 8.7; 95% CI 3.1-24) were independently associated with OS. T classification and expression of CDX2 and/or MUC2 were not independently associated with recurrence or prognosis. Conclusion: These models are simple and readily available, and distinguish the risk and prognosis in patients with CC stages I and II; these models require cheaper processes than the use of more sophisticated molecular biology techniques. They may guide either the need for adjuvant therapy versus post-operative surveillance only, as well as aid in the design of clinical trials.

Oncological outcomes after piecemeal endoscopic mucosal resection of large non-pedunculated colorectal polyps with covert submucosal invasive cancer.

OBJECTIVE: Management of covert submucosal invasive cancer (SMIC) discovered after piecemeal endoscopic mucosal resection (pEMR) of large (>20 mm) non-pedunculated colorectal polyps is challenging. The residual cancer risk is largely unknown. We sought to evaluate this in a large tertiary referral cohort. DESIGN: Cases of covert SMIC following pEMR were identified and followed. Oncological outcomes after surgery were divided based on residual intramural cancer, lymph node metastases (LNM) or both. Risk factors for residual intramural cancer and LNM were analysed based on the original pEMR histological variables. Risk parameters were analysed with respect to low and high-risk variables for residual intramural cancer and LNM. RESULTS: Among 3372 cases of large non-pedunculated colorectal polyps, 143 cases of covert SMIC (4.2%) were identified. 109 underwent surgical resection. Histological analysis of pEMR histology was available in 98 of 109 (90%) cases. 62 cases (63%) had no residual malignancy. 36 cases had residual malignancy (residual intramural cancer n=24; LNM n=5; both n=7). All cases of residual intramural cancer could be identified by a R1 histological deep margin. Cases with poor differentiation (PD) and/or lymphovascular invasion (LVI) had a high risk of LNM (12/33), with a very low risk without these criteria (<1%; 0/65). Cases at low risk for LNM with R0 deep margin have a low risk of residual intramural cancer (<1%; 0/35). CONCLUSION: The majority of cases of large non-pedunculated colorectal polyps with covert SMIC following pEMR will have no residual malignancy. The risk of residual malignancy can be ascertained from three key variables: PD, LVI and R1 deep margin.

Development of population-level colon cancer pathway concordance measures and association with survival.

Clinical cancer pathways help standardize healthcare delivery to optimize patient outcomes and health system costs. However, population-level measurement of concordance between standardized pathways and actual care received is lacking. Two measures of pathway concordance were developed for a simplified colon cancer pathway map for Stage II-III colon cancer patients in Ontario, Canada: a cumulative count of concordant events (CCCE) and the Levenshtein algorithm. Associations of concordance with patient survival were estimated using Cox proportional hazards models adjusted for patient characteristics and time-dependent cancer-related activities. Models were compared and the impact of including concordance scores was quantified using the likelihood ratio chi-squared test. The ability of the measures to discriminate between survivors and decedents was compared using the C-index. Normalized concordance scores were significantly associated with patient survival in models for cancer stage-a 10% increase in concordance for Stage II patients resulted in a CCCE score adjusted hazard ratio (aHR) of death of 0.93, 95% CI 0.88-0.98 and a Levenshtein score aHR of 0.64, 95% CI 0.60-0.67. A similar relationship was found for Stage III patients-a 10% increase in concordance resulted in a CCCE aHR of 0.85, 95% CI 0.81-0.88 and a Levenshtein aHR of 0.78, 95% CI, 0.74-0.81. Pathway concordance can be used as a tool for health systems to monitor deviations from established clinical pathways. The Levenshtein score better characterized differences between actual care and clinical pathways in a population, was more strongly associated with survival and demonstrated better patient discrimination.

Marital Status, Living Arrangement, and Cancer Recurrence and Survival in Patients with Stage III Colon Cancer: Findings from CALGB 89803 (Alliance).

BACKGROUND: Limited and conflicting findings have been reported regarding the association between social support and colorectal cancer (CRC) outcomes. We sought to assess the influences of marital status and living arrangement on survival outcomes among patients with stage III colon cancer. PATIENTS AND METHODS: We conducted a secondary analysis of 1082 patients with stage III colon cancer prospectively followed in the CALGB 89803 randomized adjuvant chemotherapy trial. Marital status and living arrangement were both self-reported at the time of enrollment as, respectively, married, divorced, separated, widowed, or never-married, and living alone, with a spouse or partner, with other family, in a nursing home, or other. RESULTS: Over a median follow-up of 7.6 years, divorced/separated/widowed patients experienced worse outcomes relative to those married regarding disease free-survival (DFS) (hazards ratio (HR), 1.44 (95% CI, 1.14-1.81); P =.002), recurrence-free survival (RFS) (HR, 1.35 (95% CI, 1.05-1.73); P = .02), and overall survival (OS) (HR, 1.40 (95% CI, 1.08-1.82); P =.01); outcomes were not significantly different for never-married patients. Compared to patients living with a spouse/partner, those living with other family experienced a DFS of 1.47 (95% CI, 1.02-2.11; P = .04), RFS of 1.34 (95% CI, 0.91-1.98; P = .14), and OS of 1.50 (95% CI, 1.00-2.25; P =.05); patients living alone did not experience significantly different outcomes. CONCLUSION: Among patients with stage III colon cancer who received uniform treatment and follow-up within a nationwide randomized clinical trial, being divorced/separated/widowed and living with other family were significantly associated with greater colon cancer mortality. Interventions enhancing social support services may be clinically relevant for this patient population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00003835.

Association of tumor-infiltrating lymphocytes with survival depends on primary tumor sidedness in stage III colon cancers (NCCTG N0147) [Alliance].

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are a robust and independent prognostic variable in localized colon cancer. Given reported differences in molecular features and prognosis of right- versus left-sided tumors, we examined the association of TIL densities with patient survival by primary tumor sidedness in stage III cancers, including clinical low- (T1-3, N1) and high-risk (T4 and/or N2) groups. PATIENTS AND METHODS: In a phase III trial of FOLFOX-based adjuvant chemotherapy, TIL densities were analyzed and dichotomized in colon carcinomas (N = 1532) based on a previously determined cut point optimized for disease-free survival (DFS). Right-sided tumors were defined as proximal to the splenic flexure. Associations of TILs and sidedness with 5-year DFS were examined using Kaplan-Meier methodology along with multivariable modeling and relative contribution analysis by Cox regression. RESULTS: Lower TIL densities were found in left- versus right-sided tumors (P < 0.0001). The association of TIL densities with DFS differed significantly by tumor sidedness (Pinteraction = 0.045). Overall, patient tumors with low (versus high) TILs had significantly poorer DFS in right-sided (hazard ratio 2.02, 95% confidence interval 1.45-2.82; Padj < 0.0001), but not left-sided tumors (Padj = 0.1731). Among clinical low-risk patients, low (versus high) TILs were adversely prognostic only in right-sided tumors (Padj = 0.0058). Among high-risk patients, low TILs were prognostic independent of sidedness (Padj < 0.025). The relative contribution of TILs to DFS was substantially greater in right- versus left-sided tumors (24% versus 1.5%). In high-risk tumors, TILs had the highest relative contribution to DFS (42%) of all variables. In low-risk tumors, the contribution of TILs (16%) to DFS was second to KRAS. CONCLUSIONS: The association of TIL densities with patient survival differed by primary tumor sidedness and clinical risk group, suggesting that TILs should be interpreted in this context among stage III colon cancers. GOV IDENTIFIER: NCT00079274; https://clinicaltrials.gov/ct2/show/NCT00079274.