Extramural Venous Invasion Research Articles

Upfront surgery, neoadjuvant chemoradiotherapy, or neoadjuvant chemotherapy for rectal cancer with lateral lymph node metastasis: A multicenter MRI and lateral lymph node dissection study

AbstractAimThe purpose was to clarify the oncological outcomes of rectal cancer (RC) with lateral lymph node metastasis (LLNM) on high‐resolution MRI (HRMRI), considering preoperative treatments.MethodsTwo hundred and twelve patients, from 13 hospitals, diagnosed with RC with lateral lymph node dissection (LLND), between 2017 and 2019, were prospectively registered. LLNM was defined as a short‐axis size ≥5 mm. Ultimately, this study included 102 patients. Upfront surgery (Upfront), chemoradiotherapy (CRT), and neoadjuvant chemotherapy (NAC) were performed at each institution's discretion.ResultsSixty‐six (64.7%) had mesorectal fascia (MRF) involvement, 35 (34.3%) had extramural venous invasion, and 33 (32.4%) had bilateral LLNMs. A positive radial margin (RM1) was observed in nine patients (8.8%), and 35 (34.3%) had pathological LLNM (pLLNM). Overall, 3‐year relapse‐free survival (3yRFS) and local recurrence‐free survival (3yLRFS) were 69.6% and 92.9%. Upfront 3yRFS (N = 54), CRT (N = 23) and NAC (N = 25) constituted 62.9%, 82.6%, and 72.0%; 3yLRFS was 92.4%, 100%, and 88.0%. RM1 and pLLNM were significantly associated with LRFS (RM0 vs. RM1, 3yLRFS 96.7% vs. 50.0%; pLLNM negative vs. positive, 97.0% vs. 84.7%). 3yRFS Upfront non‐MRF (N = 21), post CRT non‐MRF (N = 15), and post NAC non‐MRF (N = 14) were 61.9%, 86.7%, and 100%; 3yLRFS was 90.2%, 100%, and 100%.ConclusionsGood local control of Upfront LLND for RC with LLNM was shown, but multidisciplinary treatments were required. CRT followed by surgery was preferable for RC with LLNM, but a radiation‐sparing strategy is promising for post NAC non‐MRF.

Outcomes and failure patterns after chemoradiotherapy for locally advanced rectal cancer with positive lateral pelvic lymph nodes: a propensity score-matched analysis

PurposeThis study aimed to use propensity score matching (PSM) to explore the long-term outcomes and failure patterns in locally advanced rectal cancer (LARC) patients with positive versus negative lateral pelvic lymph node (LPLN).Materials and methodsPatients with LARC were retrospectively divided into LPLN-positive and LPLN-negative groups. Clinical characteristics were compared between the groups using the chi-square test. PSM was applied to balance these differences. Progression-free survival (PFS) and overall survival (OS), and local–regional recurrence (LRR) and distant metastasis (DM) rates were compared between the groups using the Kaplan–Meier method and log-rank tests.ResultsA total of 651 LARC patients were included, 160 (24.6%) of whom had positive LPLN and 491 (75.4%) had negative LPLN. Before PSM, the LPLN-positive group had higher rates of lower location (53.1% vs. 43.0%, P = 0.025), T4 stage (37.5% vs. 23.2%, P = 0.002), mesorectal fascia (MRF)-positive (53.9% vs. 35.4%, P < 0.001) and extramural venous invasion (EMVI)-positive (51.2% vs. 27.2%, P < 0.001) disease than the LPLN-negative group. After PSM, there were 114 patients for each group along with the balanced clinical factors, and both groups had comparable surgery, pathologic complete response (pCR), and ypN stage rates. The median follow-up was 45.9 months, 3-year OS (88.3% vs. 92.1%, P = 0.276) and LRR (5.7% vs. 2.8%, P = 0.172) rates were comparable between LPLN-positive and LPLN-negative groups. Meanwhile, despite no statistical difference, 3-year PFS (78.8% vs. 85.9%, P = 0.065) and DM (20.4% vs. 13.3%, P = 0.061) rates slightly differed between the groups. 45 patients were diagnosed with DM, 11 (39.3%) LPLN-positive and 3 (17.6%) LPLN-negative patients were diagnosed with oligometastases (P = 0.109).ConclusionsOur study indicates that for LPLN-positive patients, there is a tendency of worse PFS and DM than LPLN-negative patients, and for this group patients, large samples are needed to further confirm our conclusion.

Comparative effectiveness of two abbreviated rectal MRI protocols in assessing tumor response to neoadjuvant chemoradiotherapy in patients with rectal cancer.

The present study aimed to compare the effectiveness of two abbreviated magnetic resonance imaging (MRI) protocols in assessing the response to neoadjuvant chemoradiotherapy (CRT) in patients with rectal cancer. Data from the examinations of 62 patients with rectal cancer who underwent neoadjuvant CRT and standard contrast-enhanced rectal MRI were retrospectively evaluated. Standard contrast-enhanced T2-weighted imaging (T2-WI), post-contrast T1-weighted imaging (T1-WI) and diffusion-weighted imaging (DWI) MRI, as well as two abbreviated protocols derived from these images, namely protocol AB1 (T2-WI and DWI) and protocol AB2 (post-contrast fat-suppressed (FS) T1-WI and DWI), were assessed. Measurements of lesion length and width, lymph node short-axis length, tumor staging, circumferential resection margin (CRM), presence of extramural venous invasion (EMVI), luminal mucin accumulation (MAIN), mucinous response, mesorectal fascia (MRF) involvement, and MRI-based tumor regression grade (mrTRG) were obtained. The reliability and compatibility of the AB1 and AB2 protocols in the evaluation of tumor response were analyzed. The imaging performed according to the AB1 and AB2 protocols revealed significant decreases in lesion length, width and lymph node size after CRT. These protocols also showed reductions in lymph node positivity, CRM, MRF, EMVI.Furthermore, both protocols were found to be reliable in determining lesion length and width. Additionally, compliance was observed between the protocols in determining lymph node size and positivity, CRM involvement, and EMVI after CRT. In conclusion, the use of abbreviated MRI protocols, specifically T2-WI with DWI sequences or post-contrast FS T1-WI with DWI sequences, is effective for evaluating tumor response in patients with rectal cancer following neoadjuvant CRT. The AB protocols examined in this study yielded similar results in terms of lesion length and width, lymph node positivity, CRM involvement, EMVI, MAIN, and MRF involvement.

Overall survival prediction of gastric cancer using the gene signature of CT-detected extramural venous invasion combined with M2 macrophages infiltration

BackgroundCT-detected Extramural venous invasion (EMVI) is known as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). However, the molecular basis is not clear. In colorectal cancer, M2 macrophages plays a vital role in determining EMVI. This study aimed to investigate the relationship between CT-detected EMVI and the M2 macrophages as well as prognosis predictionusing a radiogenomic approach.MethodWe utilized EMVI-related genes (from mRNA sequencing of 13 GC samples correlated with EMVI score by spearman analysis, P < 0.01) to overlap the co-expression genes of WGCNA module and M2 macrophages related genes (from mRNA data of 371 GC patients in TCGA database), generating a total of 136 genes. An EMVI-M2-prognosis-related hub gene signature was constructed by COX and least absolute shrinkage and selection operator (LASSO) analysis from a training cohort TCGA database (n = 371) and validated it in a validation cohort from GEO database (n = 357). High- and low-risk groups were divided by hub gene (EGFLAM and GNG11) signature-derived risk scores. We assessed its predictive ability through Kaplan-Meier (K-M) curve and COX analysis. Furthermore, we utilized ESTIMATE to detect tumor mutation burden (TMB) and evaluate sensitivity to immune checkpoint inhibitors (ICIs). Expression of hub genes was tested using western blotting and immunohistochemistry (IHC) analysis.ResultsThe overall survival (OS) was significantly reduced in the high-risk group (Training/Validation: AUC = 0.701/0.620; P < 0.001/0.003). Furthermore, the risk score was identified as an independent predictor of OS in multivariate COX regression analyses (Training/Validation: HR = 1.909/1.928; 95% CI: 1.225–2.974/1.308–2.844). The low-risk group exhibited significantly higher TMB levels (P = 1.6e− 07) and greater sensitivity to ICIs. Significant higher expression of hub-genes was identified on multiple GC cell lines and original samples. Hub-genes knockdown in gastric cancer cell lines inhibited their proliferation, metastatic and invasive capacity to varying degrees. In vivo experiments indicate that EGFLAM, as one of the hub genes, its high expression can serve as a biomarker for low response to immunotherapy.ConclusionOur study demonstrated EMVI-M2 gene signature could effectively predict the prognosis of GC tissue, reflecting the relationship between EMVI and M2 macrophages.

FP4.10 - Oncosurgical Outcome Differences of Left and Right Colonic Cancer Resections Still a Colorectal Enigma

Abstract Aims The study aimed to compare surgical outcomes between right (RCC) and left colonic cancer (LCC) resections at a single centre (DGH) with special reference to 3 and 5-year survival rates. Methods 100 colonic resections (2017-2021) were included. Length of stay (LOS), pathology results and 3 and 5-year survival rates were analysed. The Kaplan-Meier estimate was used for patients within 5 years post-operative. Results 68 RCC and 32 LCC noted. RCC: 37 female, 31 male, median age of 73. 66 R0 resections, 2 R1, none R2. TNM: 52 (86.1%) had T3/4, 26 (38.2%) had N1/2. 20 had extramural venous invasion (EMVI), 26 intramural venous invasion (IMVI), 8 mucinous, 11 perineural invasion. Estimated 3-year survival rate 0.8530, 5-year 0.7766. No local recurrences, 4 subsequent distant metastases within 5 years. LCC: 11 female, 21 male, median age of 67. 23 R0, 2 R1, 2 R2 resections. TNM: 28 (87.5%) had T3/4, 15 (46.9%) had N1/2. 18 EMVI, 11 IMVI, 1 mucinous, 9 perineural invasion. Estimated 3-year survival rate 0.7498, 5-year 0.5965. No local recurrences, 9 subsequent distant metastases within 5 years. Both cohorts’ median LOS similar (6 days). Discussion This study shows higher survival rates in RCC, contradicting acclaimed superiority of LCC survival in literature(1-5). The limited LCCs in this study (during Covid pandemic) being pathologically more advanced, possibly accounts for the statistically significant mortality. A prospective audit of tumour biology and oncological outcome is ongoing with intentions to validate our early observation.

The Role of Predictive and Prognostic MRI-Based Biomarkers in the Era of Total Neoadjuvant Treatment in Rectal Cancer.

The role of magnetic resonance imaging (MRI) in rectal cancer management has significantly increased over the last decade, in line with more personalized treatment approaches. Total neoadjuvant treatment (TNT) plays a pivotal role in the shift from traditional surgical approach to non-surgical approaches such as 'watch-and-wait'. MRI plays a central role in this evolving landscape, providing essential morphological and functional data that support clinical decision-making. Key MRI-based biomarkers, including circumferential resection margin (CRM), extramural venous invasion (EMVI), tumour deposits, diffusion-weighted imaging (DWI), and MRI tumour regression grade (mrTRG), have proven valuable for staging, response assessment, and patient prognosis. Functional imaging techniques, such as dynamic contrast-enhanced MRI (DCE-MRI), alongside emerging biomarkers derived from radiomics and artificial intelligence (AI) have the potential to transform rectal cancer management offering data that enhance T and N staging, histopathological characterization, prediction of treatment response, recurrence detection, and identification of genomic features. This review outlines validated morphological and functional MRI-derived biomarkers with both prognostic and predictive significance, while also exploring the potential of radiomics and artificial intelligence in rectal cancer management. Furthermore, we discuss the role of rectal MRI in the 'watch-and-wait' approach, highlighting important practical aspects in selecting patients for non-surgical management.

Baseline MRI predictors of successful organ preservation in the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial.

Prospective randomized trials have not yet identified baseline features predictive of organ preservation in locally advanced rectal cancers treated with total neoadjuvant therapy and a selective watch-and-wait strategy. This was a secondary analysis of the OPRA trial, which randomized patients with stage II-III rectal adenocarcinoma to receive either induction or consolidation total neoadjuvant therapy. Patients were recommended for total mesorectal excision, or watch and wait based on clinical response at 8 ± 4 weeks after completing treatment. Standardized baseline clinical and radiological variables were collected prospectively. Survival outcomes, including total mesorectal excision-free survival, disease-free survival, and overall survival, were assessed by intention-to-treat analysis. Cox proportional hazards models were used to evaluate associations between baseline variables and survival outcomes. Of the 324 patients randomized for the OPRA trial, 38 (11.7%) had cT4 tumours, 230 (71.0%) cN-positive disease, 101 (32.5%) mesorectal fascia involvement, and 64 (19.8%) extramural venous invasion. Several baseline features were independently associated with recommendation for total mesorectal excision on multivariable analysis: nodal disease (HR 1.66, 95% c.i. 1.12 to 2.48), extramural venous invasion (HR 1.57, 1.07 to 2.29), mesorectal fascia involvement (HR 1.45, 1.01 to 2.09), and tumour length (HR 1.11, 1.00 to 1.22). Of these, nodal disease (HR 2.02, 1.15 to 3.53) and mesorectal fascia involvement (HR 2.02, 1.26 to 3.26) also predicted worse disease-free survival. Age (HR 1.03, 1.00 to 1.06) was associated with overall survival. Baseline MRI features, including nodal disease, extramural venous invasion, mesorectal fascia involvement, and tumour length, independently predict the likelihood of organ preservation after completion of total neoadjuvant therapy. Mesorectal fascia involvement and nodal disease are associated with disease-free survival.

Early-Stage Colon Cancer Surveillance: Pattern and Timing of Recurrence and the Role of 5-Year Surveillance

Introduction: Colorectal cancer is the third most prevalent cancer among both men and women with 80% of patients having localized disease enabling curative treatments. Given the low recurrence rate in early-stage disease, there is a growing interest in reviewing follow-up protocols. The aim of this study was to assess the frequency and timing of recurrence in early-stage colon cancer, as well as recurrence patterns. Methods: The data from all patients with colon adenocarcinoma consecutively treated with surgery at the Instituto Português de Oncologia do Porto, EPE, between January 2013 and December 2016, were retrospectively reviewed. Results: A total of 1,372 patients with colon cancer were submitted to surgery during the study period. From this group, 51.4% (n = 705) were early-stage colon cancers. Regarding the pathological stage, 3.5% were stage 0, 37.4% were stage I and 59.1% were stage II. The overall recurrence rate was 6.7%. When considering the group of patients without risk factors, the recurrence rate was 5.6%. The majority of recurrences occurred in the first 3 years of follow-up. The recurrence was diagnosed in the majority of patients through carcinoembryonic antigen elevation, followed by imaging exams. The presence of one or more risk factors (high nuclear grade, vascular invasion, extramural venous invasion, and perineural invasion) showed a statistically significant association with recurrence rate. Conclusion: The recurrence rate was low in early-stage colon cancer, with the majority of recurrences occurring in the first 3 years. Our study results show that surveillance should be tailored according to individual risk factors.

Implications of pretreatment extramural venous invasion in rectal cancer patients: A population-based study.

Extramural venous invasion detected by MRI (mrEMVI) has in several expert centre studies been identified as an important prognostic factor in rectal cancer, and in guiding neoadjuvant therapy. However, population-based evidence for mrEMVI as a predictor for recurrent disease is lacking. This was a multicentre retrospective study based on the Swedish Colorectal Cancer Registry. The study period encompassed patients operated with abdominal resection for rectal cancer 2017-2021, with follow-up until January 2023. Patients diagnosed at hospitals with radiological registry data coverage <90% or with metastatic disease were excluded. Pretreatment mrEMVI constituted exposure, while recurrence-free survival was the main outcome. Distant and local recurrence, and overall survival were secondary outcomes, and pretreatment and postoperative scenarios were explored using multivariable Cox regression with multiple imputation. Hazard ratios (HRs) with 95% confidence intervals (CIs) were reported. A total of 2737 patients from 13 hospitals were eligible for analysis. Pretreatment mrEMVI was reported in 14.5% of patients, while 71.9% had negative findings and 13.6% had missing data. In the pretreatment scenario, mrEMVI was an independent predictor for worse recurrence-free survival with an adjusted HR of 1.64 (95% CI: 1.31-2.06). In the postoperative MDT setting, the influence of mrEMVI on recurrence-free survival decreased with an adjusted HR of 1.27 (95% CI: 1.00-1.61). mrEMVI at diagnosis is an independent predictor of recurrence-free survival in an unselected population of rectal cancer patients undergoing abdominal resection.

β2-microglobulin expression is associated with aggressive histology, activated tumor immune milieu, and outcome in colon carcinoma.

We sought to assess the expression of human leukocyte antigen (HLA) proteins and β2-microglobulin (B2M) in tumor cells and the relationship with immune microenvironment and outcome in colorectal cancer (CRC). A total of 953 CRC cases were evaluated by immunohistochemistry for HLA class I, HLA class II, and B2M. The expression level of these biomarkers was correlated with clinicopathologic information, BRAF V600E and mismatch repair (MMR) proteins, and the quantitated expression levels of immune cells (CD8 and CD163) and immune regulatory proteins (FoxP3, programmed cell death 1 ligand 1 [PD-L1], and LAG3). We found that B2M-low tumors were statistically correlated with aggressive histologic features, including higher stage, higher grade, extramural venous invasion, perineural invasion, and distant metastasis. Expression of B2M was positively correlated (R2=0.3) and significantly associated with MMR-deficient tumors (P<.001); B2M-low tumors were also associated with an "immune cold"' microenvironment, including a reduced number of immune cells (CD8 and CD163), reduced expression of immune regulatory proteins by immune cells (PD-L1, FoxP3, and LAG3), and reduced tumor cell expression of PD-L1. These B2M-low tumors correlated with lower disease-specific survival (P=.018), a finding that maintained significance only for the proficient MMR cohort (P=.037). Our findings suggest that B2M expression may support predictive models for both outcome and checkpoint inhibitor therapy treatment response for colorectal adenocarcinoma.

Multivariable prognostic modelling to improve prediction of colorectal cancer recurrence: the PROSPeCT trial

ObjectiveImproving prognostication to direct personalised therapy remains an unmet need. This study prospectively investigated promising CT, genetic, and immunohistochemical markers to improve the prediction of colorectal cancer recurrence.Material and methodsThis multicentre trial (ISRCTN 95037515) recruited patients with primary colorectal cancer undergoing CT staging from 13 hospitals. Follow-up identified cancer recurrence and death. A baseline model for cancer recurrence at 3 years was developed from pre-specified clinicopathological variables (age, sex, tumour-node stage, tumour size, location, extramural venous invasion, and treatment). Then, CT perfusion (blood flow, blood volume, transit time and permeability), genetic (RAS, RAF, and DNA mismatch repair), and immunohistochemical markers of angiogenesis and hypoxia (CD105, vascular endothelial growth factor, glucose transporter protein, and hypoxia-inducible factor) were added to assess whether prediction improved over tumour-node staging alone as the main outcome measure.ResultsThree hundred twenty-six of 448 participants formed the final cohort (226 male; mean 66 ± 10 years. 227 (70%) had ≥ T3 stage cancers; 151 (46%) were node-positive; 81 (25%) developed subsequent recurrence. The sensitivity and specificity of staging alone for recurrence were 0.56 [95% CI: 0.44, 0.67] and 0.58 [0.51, 0.64], respectively. The baseline clinicopathologic model improved specificity (0.74 [0.68, 0.79], with equivalent sensitivity of 0.57 [0.45, 0.68] for high vs medium/low-risk participants. The addition of prespecified CT perfusion, genetic, and immunohistochemical markers did not improve prediction over and above the clinicopathologic model (sensitivity, 0.58–0.68; specificity, 0.75–0.76).ConclusionA multivariable clinicopathological model outperformed staging in identifying patients at high risk of recurrence. Promising CT, genetic, and immunohistochemical markers investigated did not further improve prognostication in rigorous prospective evaluation.Clinical relevance statementA prognostic model based on clinicopathological variables including age, sex, tumour-node stage, size, location, and extramural venous invasion better identifies colorectal cancer patients at high risk of recurrence for neoadjuvant/adjuvant therapy than stage alone.Key PointsIdentification of colorectal cancer patients at high risk of recurrence is an unmet need for treatment personalisation.This model for recurrence, incorporating many patient variables, had higher specificity than staging alone.Continued optimisation of risk stratification schema will help individualise treatment plans and follow-up schedules.

Three-year survival data from a phase 2 trial of neoadjuvant short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer.

e15611 Background: For locally advanced rectal cancer (LARC), short-course radiotherapy (SCRT) or long-course chemoradiotherapy combined with chemotherapy have been the established neoadjuvant treatment, but the optimal therapeutic modality is still under exploration. We previously reported the short-term results of neoadjuvant SCRT followed by chemotherapy and camrelizumab (a PD-1 inhibitor), encouragingly noting pathological complete response (pCR) in 48.1% of LARC patients (Lin Z et al. J Immunother Cancer 2021;9:e003554). Here, we report the further 3-year follow-up results. Methods: Adult patients with histologically confirmed T3-4N0M0 or T1-4N+M0 rectal adenocarcinoma were enrolled. Prior to surgery, eligible patients received 5×5 Gy SCRT, and after one week, they were treated with camrelizumab (200 mg, i.v., on day 1) plus CAPOX chemotherapy (oxaliplatin 130 mg/m2, i.v., on day 1 and capecitabine 1000 mg/m2, orally, bid, on days 1-14) in 21-day cycles for 2 cycles. Radical surgery was performed one week after the last neoadjuvant cycle. For this updated analysis, disease-free survival (DFS) and overall survival (OS) at 3 years are reported. Results: Thirty patients were enrolled and received SCRT, and all of these patients were included in this OS analysis. Among them, 27 patients received camrelizumab plus CAPOX chemotherapy, all of whom underwent surgery and were included in this DFS analysis. Of the 27 patients, 21 patients (77.8%) received at least one cycle of postoperative adjuvant chemotherapy with CAPOX regimen. With a median follow-up of 40.8 months (IQR 40.3-44.3), disease recurrence or death occurred in six (22.2%) patients. The median DFS and OS were both not reached, with the 3-year DFS and OS rates of 80.2% (95% CI 58.6-91.3) and 93.3% (95% CI 75.9-98.3), respectively. Subgroup analysis showed that patients with pCR, postoperative pathological node-negative status, PD-L1 combined positive score ≥ 1, and negative circumferential resection margin and negative extramural venous invasion by MRI at baseline had a tendency towards improved 3-year DFS and OS compared to those without these characteristics. No new or long-term safety signals were identified. Conclusions: With 3 years of extended follow-up, a favorable survival benefit was observed with neoadjuvant SCRT combined with subsequent CAPOX plus camrelizumab followed by delayed surgery in LARC patients. A randomized phase 3 trial (NCT04928807) is ongoing to confirm these results. Clinical trial information: NCT04231552 .

MRI-based radiomics feature combined with tumor markers to predict TN staging of rectal cancer.

The aim of this study is to evaluate the predictive ability of MRI-based radiomics combined with tumor markers for TN staging in patients with rectal cancer and to develop a prediction model for TN staging. A total of 190 patients with rectal adenocarcinoma who underwent total mesorectal excision at the First Affiliated Hospital of the Air Force Medical University between January 2016 and December 2020 were included in the study. An additional 54 patients from a prospective validation cohort were included between August 2022 and August 2023. Preoperative tumor markers and MRI imaging data were collected from all enrolled patients. The 190 patients were divided into a training cohort (n = 133) and a validation cohort (n = 57). Radiomics features were extracted by outlining the region of interest (ROI) on T2WI sequence images. Feature selection and radiomics score (Rad-score) construction were performed using least absolute shrinkage and selection operator regression analysis (LASSO). The postoperative pathology TNM stage was used to differentiate locally advanced rectal cancer (T3/4 or N1/2) from locally early rectal cancer (T1/2, N0). Logistic regression was used to construct separate prediction models for T stage and N stage. The models' predictive performance was evaluated using DCA curves and calibration curves. The T staging model showed that Rad-score, based on 8 radiomics features, was an independent predictor of T staging. When combined with CEA, tumor diameter, mesoretal fascia (MRF), and extramural venous invasion (EMVI), it effectively differentiated between T1/2 and T3/4 stage rectal cancers in the training cohort (AUC 0.87 [95% CI: 0.81-0.93]). The N-staging model found that Rad-score, based on 10 radiomics features, was an independent predictor of N-staging. When combined with CA19.9, degree of differentiation, and EMVI, it effectively differentiated between N0 and N1/2 stage rectal cancers. The training cohort had an AUC of 0.84 (95% CI: 0.77-0.91). The calibration curves demonstrated good precision between the predicted and actual results. The DCA curves indicated that both sets of predictive models could provide net clinical benefits for diagnosis. MRI-based radiomics features are independent predictors of T staging and N staging. When combined with tumor markers, they have good predictive efficacy for TN staging of rectal cancer.

Pathological Extramural Venous Invasion in High-stage Urothelial Carcinoma of the Bladder has Shorter Locoregional Recurrence-free Survival.

Extramural venous invasion is an independent prognostic factor in colorectal cancers; the pathological identification of extramural venous invasion in bladder cancer remains unclear. By focusing on high-stage urothelial carcinoma of the bladder, we provide insights into the pathological identification of extramural venous invasion in this particular clinical context. Clinical and demographic details and pathological reports were extracted from electronic medical records. Histological sections were reviewed for the pathological identification of extramural venous invasion. Statistical analysis was done using SPSS version 23 software. Survival analysis was done using Kaplan-Meier method. In patients with available follow-up data, 62% (n = 21) exhibited pathologically evidenced extramural venous invasion, whereas 38% (n = 13) did not. The extramural venous invasion positive group showed trends toward more advanced and pathological staging and a higher occurrence of extra-nodal extension. Positive margins were more frequent in the extramural venous invasion positive group (33%) compared to the extramural venous invasion negative group (8%). However, these differences were not statistically significant. Notably, all instances of recurrence were in the extramural venous invasion positive group of patients. The extramural venous invasion positive group of patients showed a significantly shorter locoregional recurrence-free survival (P-value of 0.045). However, extramural venous invasion did not emerge as a significant factor in univariate analyses for recurrence-free survival. These findings highlight the potential role of extramural venous invasion as a prognostic factor in bladder cancer but underscore the need for further research with larger cohorts to confirm its significance.

Clinical, pathological, genetics and intratumoural immune milieu of micropapillary carcinoma of the colon

AimMicropapillary carcinoma (MPC) is a recognised WHO variant of colonic carcinoma (CC), although little is known about its prognosis, immune microenvironment and molecular alterations. We investigated its clinical, pathological and...

Impact of mesorectal extranodal tumor deposits in magnetic resonance imaging on outcome of rectal cancer patients

AimMesorectal extranodal tumor deposits (TDs) are identified in many rectal cancers. Their radiological features differ from metastatic lymph nodes, and they can be detected with magnetic resonance imaging (MRI). The purpose of this study was to determine the prevalence of rectal cancer TDs detected with MRI and their impact on overall (OS), cancer-specific (CSS), and disease-free survival (DFS) and the local recurrence rate. MethodIn this retrospective cohort study, we screened all 525 consecutive rectal cancer patients who underwent surgery during 2017–2018 in a tertiary center. Patients with synchronous metastases or who had not undergone MRI were excluded. We analyzed the OS, CSS, and DFS as well as local recurrences. ResultsOf the 480 included patients, TDs were detected in the images of 81 (16.9 %). Extramural venous invasion (EMVI) and TDs were frequently found together (n = 50, 61.7 % of all cases with TDs). The presence of TDs alone [hazard ratio (HR) 1.66 (1.03–2.68)] or TDs and/or EMVI [HR 1.63 (1.01–2.62)] were risk factors for adverse DFS in multivariate Cox regression analysis. The OS and CSS rates were poorer among patients with TDs compared to those without, p = 0.009 and p < 0.001, respectively. TDs were also a risk factor for local recurrence in the univariate analysis. ConclusionsTDs detected with imaging are a risk factor for impaired DFS and associated with impaired CSS and OS of rectal cancer patients and should be taken into consideration in clinical decision-making.

Prognostic significance of MRI-detected extramural venous invasion according to grade and response to neo-adjuvant treatment in locally advanced rectal cancer A national cohort study after radiologic training and reassessment

BackgroundDetection of grade 3–4 extra mural venous invasion (mrEMVI) on magnetic resonance imaging (MRI) is associated with an increased distant metastases (DM)-rate. This study aimed to determine the impact of different grades of mrEMVI and their disappearance after neoadjuvant therapy. MethodsA Dutch national retrospective cross-sectional study was conducted, including patients who underwent resection for rectal cancer in 2016 from 60/69 hospitals performing rectal surgery. Patients with a cT3-4 tumour ≤8 cm from the anorectal junction were selected and their MRI-scans were reassessed by trained abdominal radiologists. Positive mrEMVI grades (3 and 4) were analyzed in regard to 4-year local recurrence (LR), DM, disease-free survival (DFS) and overall survival (OS). ResultsThe 1213 included patients had a median follow-up of 48 months (IQR 30–54). Positive mrEMVI was present in 324 patients (27%); 161 had grade 3 and 163 had grade 4. A higher mrEMVI stage (grade 4 vs grade 3 vs no mrEMVI) increased LR-risk (21% vs 18% vs 7%, <0.001) and DM-risk (49% vs 30% vs 21%, p < 0.001) and decreased DFS (42% vs 55% vs 69%, p < 0.001) and OS (62% vs 76% vs 81%, p < 0.001), which remained independently associated in multivariable analysis. When mrEMVI had disappeared on restaging MRI, DM-rate was comparable to initial absence of mrEMVI (both 26%), whereas LR-rate remained high (22% vs 9%, p = 0.006). ConclusionThe negative oncological impact of mrEMVI on recurrence and survival rates was dependent on grading. Disappearance of mrEMVI on restaging MRI decreased the risk of DM, but not of LR.

Performance of CT in the locoregional staging of colon cancer: detailed radiology-pathology correlation with special emphasis on tumor deposits, extramural venous invasion and T staging.

To investigate the performance of computed tomography (CT) in the local staging of colon cancer in different segments, with emphasis on parameters that have been found to be significant for rectal cancer, namely, extramural venous invasion (EMVI) and tumor deposits (TDs). CT and pathology data from 137 patients were independently reviewed by radiology and pathology teams. The performance of CT in categorizing a given patient into good, versus poor prognostic groups was assessed for each segment, as well as the presence of lymph nodes (LNs), TDs and EMVIs. Discordant cases were re-evaluated to determine potential sources of error. Elastic stain was applied for EMVI discordance. The T staging accuracy was 80.2%. For T stage stratification, CT performed slightly better in the left colon, and the lowest accuracy was in the transverse colon. Under-staging was more common (in 12.4%), and most of the mis-staged cases were in sigmoid colon. According to the first comprehensive correlative analysis, the sensitivity, specificity, and accuracy of CT for detecting TDs were found to be 57.9%, 92.4%, 87.6%, respectively. These figures were 44.7%, 72.7%, and 63.5% for LN, and 58.5%, 82.1% and 73% for EMVI. The detection rate was better for multifocal EMVI. The detection rate was also comparable (although substantially underestimated) for LNs, with the half of the LNs missed by CT being < 5mm. Four patients that were classified as TD by CT, disclosed to be LNs by pathology. Correlative analysis led to refinement of the pathology criteria, with subsequent modifications of the initial reports in 13 (9.5%) patients. Overall, CT performed well in the evaluation of colon cancer, as did TD and EMVI. It is advisable to include these parameters in CT-based staging. Radiologists should be aware of the pitfalls that occur more commonly in different segments.

Double Negativity of MRI-Detected and Pathologically-Diagnosed Extramural Venous Invasion is a Favorable Prognostic Factor for Rectal Cancer.

Extramural venous invasion (EMVI) is a prognostic factor in rectal cancer. There are two types: EMVI detected by magnetic resonance imaging (MRI) (mr-EMVI) and EMVI detected by pathology (p-EMVI). They have been separately evaluated, but they have not yet been concurrently evaluated. We therefore evaluate both mr-EMVI and p-EMVI in rectal cancer at the same time and clarify their association with prognosis. Included were the 186 consecutive patients who underwent complete radical resection of tumors ≤ stage III at Wakayama Medical University Hospital, Japan, between 2010 and 2018. All underwent preoperative MRI examination, and were reassessed for EMVI by a radiologist. Surgically resected specimens were then reassessed for EMVI by a pathologist. We assessed the correlation between positivity of mr-EMVI and p-EMVI and prognosis, and the clinicopathological background behind them. Patients with double negativity for mr-EMVI and p-EMVI had better prognosis than patients with mr-EMVI or p-EMVI positivity (p < 0.0001). Positivity for mr-EMVI or p-EMVI was a poor independent prognostic factor in multivariate analysis. Combined analysis of mr-EMVI and p-EMVI may enable prediction of postoperative prognosis of rectal cancer. Patients with double negativity of mr-EMVI and p-EMVI had better prognosis than patients with some form of positivity. Stated differently, patients with positivity of mr-EMVI, p-EMVI, or both had a poorer prognosis than those with double negativity. Postoperative adjuvant chemotherapy may improve poor prognosis. Combined evaluation of mr-EMVI and p-EMVI may be used to predict clinical outcomes and may be an effective prognostic predictor of rectal cancer.

The prognostic significance of extramural venous invasion detected via contrast-enhanced computed tomography colonography in colon cancer.

167 Background: The precise effects of extramural venous invasion (EMVI) and Spiculation on colon cancer recurrence remain poorly understood. This study investigated the clinical significance of ctEMVI and ctSpiculation as diagnosed via preoperative contrast-enhanced CT colonography (CTC) using three-dimensional multiplanar reconstruction (3D MPR) images. Methods: Patients with stage I–Ⅲ colon cancer (T2 or deeper) diagnosed via CTC at the National Cancer Center Hospital in Japan between 2013 and 2018 were retrospectively evaluated for ctEMVI and ctSpiculation, diagnosed by two observers using 3D MPR images of slices 0.5 mm thick. The interobserver reliability was assessed with Cohen’s kappa statistic, and recurrence-free survival (RFS) was analyzed using Kaplan–Meier curves. Preoperative clinical factors were subjected to Cox regression analysis in relation to RFS. Results: Of 922 patients, 544 eligible cases were analyzed. There were 50 (9.2%) ctEMVI-positive cases and 494 (90.8%) ctEMVI-negative cases, along with 186 (34.2%) ctSpiculation-positive cases and 358 (65.8%) with negative findings. Kappa coefficients for ctEMVI and ctSpiculation were 0.830 and 0.718, respectively. Kaplan–Meier analysis and log-rank tests demonstrated lower RFS in ctEMVI- and ctSpiculation-positive cases (p&lt;0.001). In multivariable analysis, ctT4 (HR 2.95, 95% CI 1.73–5.02) and ctEMVI (2.97, 1.81–4.87) were independent factors associated with RFS. When stratifying TNM stages based on ctEMVI status, in N(+) (i.e., Stage III), ctEMVI-positive group had worse prognoses than negative group (5-year RFS rates; 52.0% vs. 78.5%, p=0.003). Similarly, in N(–) (i.e., Stage I and II), T3N0EMVI(+) cases had significantly worse prognoses than T3N0EMVI(–) and Stage I cases (50.6% vs. 89.3% and 90.1%) and were comparable to the T4N0 group (50.6% vs. 46.7%, p=0.844). Conclusions: Both ctEMVI and ctSpiculation are associated with RFS. ctEMVI is an independent predictor of recurrence and may be valuable in combination with preoperative TNM staging to identify patients at high risk for recurrence. [Table: see text]