Mesorectal Extension Research Articles

A comparison of whole-mount and conventional sections for pathological mesorectal extension and circumferential resection margin assessment after total mesorectal excision

IntroductionThe objective of the study is to compare 2 techniques for histological handling of rectal cancer specimens, namely whole-mount in a large block vs conventional sampling using small blocks, for mesorectal pathological assessment of circumferential resection margin status and depth of tumor invasion into the mesorectal fat. MethodsThis is a prospective study including 27 total mesorectal excision specimens of rectal cancer from patients treated for primary rectal carcinoma between 2020 and 2022 in a specialized multidisciplinary Colorectal Unit. For each total mesorectal excision specimen, 2 contiguous representative tumoral slices were selected and comparatively analyzed with whole-mount and small blocks macroscopic dissection techniques, enabling comparison between them in the same surgical specimen. The agreement between the 2 techniques to assess the distance of the tumor from the circumferential resection margin as well as the depth of tumor invasion was evaluated with the Student’s t-test for paired samples, Pearson’s correlation coefficient, and the Bland-Altman method comparison analysis. ResultsComplete mesorectal excision was observed in 8% of cases. Circumferential resection margin involvement was observed in only one case (4 %). The whole-mount and small block techniques obtained similar results when we assessed the distance to the circumferential resection margin (t-test P = 0.8, r = 0.92) and the depth of mesorectal infiltration (t-test P = 0.6, r = 0.95). ConclusionsBoth gross dissection techniques (whole-mount vs multiple small cassettes) are equivalent and reliable to assess the distance to circumferential resection margin and the depth of mesorectal infiltration in the mesorectal fat in rectal cancer staging.

A comparison of whole-mount and conventional sections for pathological mesorectal extension and circumferential resection margin assessment after total mesorectal excision

IntroductionThe objective of the study is to compare 2 techniques for histological handling of rectal cancer specimens, namely whole-mount in a large block vs conventional sampling using small blocks, for mesorectal pathological assessment of circumferential resection margin status and depth of tumor invasion into the mesorectal fat. MethodsThis is a prospective study including 27 total mesorectal excision specimens of rectal cancer from patients treated for primary rectal carcinoma between 2020 and 2022 in a specialized multidisciplinary Colorectal Unit. For each total mesorectal excision specimen, 2 contiguous representative tumoral slices were selected and comparatively analyzed with whole-mount and small blocks macroscopic dissection techniques, enabling comparison between them in the same surgical specimen. The agreement between the 2 techniques to assess the distance of the tumor from the circumferential resection margin as well as the depth of tumor invasion was evaluated with the Student’s t-test for paired samples, Pearson’s correlation coefficient, and the Bland-Altman method comparison analysis. ResultsComplete mesorectal excision was observed in 8% of cases. Circumferential resection margin involvement was observed in only one case (4 %). The whole-mount and small block techniques obtained similar results when we assessed the distance to the circumferential resection margin (t-test P = 0.8, r = 0.92) and the depth of mesorectal infiltration (t-test P = 0.6, r = 0.95). ConclusionsBoth gross dissection techniques (whole-mount vs multiple small cassettes) are equivalent and reliable to assess the distance to circumferential resection margin and the depth of mesorectal infiltration in the mesorectal fat in rectal cancer staging.

Comparative study of radiomics, tumor morphology, and clinicopathological factors in predicting overall survival of patients with rectal cancer before surgery

We compared the ability of a radiomics model, morphological imaging model, and clinicopathological risk model to predict 3-year overall survival (OS) in 206 patients with rectal cancer who underwent radical surgery and had magnetic resonance imaging, clinicopathological, and OS data available. The patients were randomized to a training cohort (n = 146) and a verification cohort (n = 60). Radiomics features were extracted from preoperative T2-weighted images, and a radiomics score model was constructed. Factors that were significant in the Cox multivariate analysis were used to construct the final morphological tumor model and clinicopathological model. A comprehensive model in the form of a line chart was established by combining the three models. Ten radiomics features significantly related to OS were selected to construct the radiomics feature model and calculate the radiomics score. In the morphological model, mesorectal extension depth and distance between the lower tumor margin and the anal margin were significant prognostic factors. N stage was the only significant clinicopathological factor. The comprehensive model combined with the above factors had the best prediction performance for OS. The C-index had a predictive performance of 0.872 (95% confidence interval [CI]: 0.832–0.912) in the training cohort and 0.944 (95% CI: 0.890–0.990) in the verification cohort, which was better than for any single model. The comprehensive model was divided into high-risk and low-risk groups. Kaplan-Meier curve analysis showed that all factors were significantly correlated with poor OS in the high-risk group. A comprehensive nomogram based on multi-model radiomics features can predict 3-year OS after rectal cancer surgery.

When a rare simultaneous infection simulates a local extension of a rectal cancer: a case report

BackgroundActinomycosis is a rare chronic infection caused by Actinomyces. The abdominopelvic localization of this pathology makes preoperative diagnosis extremely exceptional. The following report is the case of a patient treated for adenocarcinoma of the middle rectum associated with mesorectal actinomycosis. The diagnosis of actinomycosis was made postoperatively.Case presentationA 69-year-old Caucasian male patient was admitted for rectal bleeding. Clinical and paraclinical assessment revealed a middle rectum adenocarcinoma with local extension in the mesorectum. The patient underwent an anterior resection of the rectum by laparotomy after neoadjuvant chemoradiotherapy. Postoperative follow-up was simple. Pathological study of the specimen noted complete sterilization of the rectal adenocarcinoma and the presence of large foci of suppurative necrosis containing actinomycotic grains in the mesorectum.ConclusionAbdominopelvic actinomycosis is a rare pathology and has therefore rarely been dealt with. This issue can lead to unnecessary and mutilating surgery. We report an exceptional coincidence of rectal adenocarcinoma and mesorectal actinomycosis mistaken for mesorectal extension of the cancer.

Additional value of MRI-detected EMVI scoring system in rectal cancer: applicability in predicting synchronous metastasis.

Extramural vascular invasion (EMVI) has been recommended as an independent prognostic factor for poor overall survival rate in rectal cancer and can be used as a potential biomarker. Early prediction of prevalence of synchronous metastasis can elevate the disease-free survival rate. We aimed to evaluate the magnetic resonance imaging (MRI)-detected EMVI (mrEMVI) scoring system in predicting distant metastasis in T3 rectal cancer. Patients with postoperative histopathologically confirmed T3 rectal cancer without previous treatment from July 2014 to December 2015 were enrolled in this study. Two blinded radiologists evaluated mrEMVI status. mrEMVI was categorized as EMVI-positive or EMVI-negative in T2-weighted images using an mrEMVI scoring system. The results, along with other clinical characteristics (age, sex, tumor location, MRI-detected distance of mesorectal extension, lymphatic invasion, perineural invasion, mrEMVI score, and carcinoembryonic antigen [CEA]), were then correlated with synchronous metastases to determine the risk factors using univariate and multivariate analysis. Of 180 patients, 38 were confirmed to be mrEMVI-positive, 142 mrEMVI-negative. There were 34 patients with synchronous metastasis, of whom 25 were mrEMVI-positive and 9 were mrEMVI-negative. Three factors were significantly associated with synchronous metastasis: mrEMVI (p = 0.001; odds ratio = 8.665), histopathologic lymphatic invasion (p = 0.001; odds ratio = 12.940), and preoperative CEA (p = 0.026; odds ratio = 4.124). mrEMVI score 4 was more likely for synchronous metastasis (p = 0.044; odds ratio = 9.429) than mrEMVI score 3 in rectal cancer. mrEMVI positivity is an independent risk factor for synchronous distant metastasis in rectal cancer. mrEMVI score 4 is a stronger risk factor for synchronous metastasis than mrEMVI score 3 in rectal cancer.

The prognostic significance of MRI-detected extramural venous invasion, mesorectal extension, and lymph node status in clinical T3 mid-low rectal cancer

The purpose of this study was to evaluate the prognostic significance of the magnetic resonance imaging-detected extramural venous invasion (MR-EMVI), the depth of mesorectal extension (MR-DME), and lymph node status (MR-LN) in clinical T3 mid-low rectal cancer. One hundred and forty-six patients with clinical T3 mid-low rectal cancer underwent curative surgery were identified. Pretreatment high-resolution MRI was independently reviewed by two experienced radiologists to evaluate MR-EMVI score (0–4), MR-DME (≤4 mm or >4 mm), and MR-LN (positive or negative). The Cox-multivariate regression analysis revealed that the MR-EMVI was the only independent prognostic factor that correlated with overall 3-year disease-free survival (DFS) (p = 0.01). The survival analysis showed that patients with positive MR-EMVI, MR-DME > 4 mm, and positive MR-LN had a poorer prognosis in the overall 3-year DFS (HR 3.557, 95% CI 2.028 to 13.32, p < 0.01; HR 3.744, 95% CI:1.165 to 5.992, p = 0.002; HR 2.946, 95% CI: 1.386 to 6.699, p < 0.01). By combining MR-EMVI with MR-DME or MR-LN, the prognostic significance was more remarkable. Our study suggested that the MR-EMVI, MR-DME, and MR-LN were the important prognostic factors for patients with clinical T3 mid-low rectal cancer and the MR-EMVI was an independent prognostic factor.

Clinical Feasibility Assessment of T3 Sub-Stage in Rectal Cancer Using MRI

Background: MRI predicted distance of mesorectal extension (mrDME) in rectal cancer is one of the independent risk factors for recurrence and poor overall survival. In T3 rectal cancer, if no lymph node or distant metastasis is seen, the selection of optimum treatment is based on the distance of mesorectal extension. Therefore, it is very crucial to investigate the reproducibility of DME in T3 rectal cancer. Objectives: To investigate the reproducibility of the distance of mesorectal extension by tumor invasion in T3 stage rectal cancer by evaluating sub-stages T3a, T3b T3c and T3d individually versus T3a, T3b (T3ab) and T3c, T3d (T3cd) combined together using MRI. Patients and Methods: From July 2014 to December 2015, 188 patients with surgically and histologically confirmed T3 rectal cancer who underwent preoperative MRI were enrolled into this study. Two blinded radiologists evaluated the maximum distance of mesorectal extension (mrDME) in T2 weighted image in MRI. The study population was sub classified into T3a ( 15 mm) according to the distance of mesorectal extension by tumor invasion. The inter-observer and intra-observer agreements were then assessed using kappa (k) coefficient of agreement and intraclass correlation coefficient (ICC). Results: Difference in the value of inter-/intra-observer kappa, and inter-/intra-observer ICC between the two groups was very distinct. In the individual group (T3a, T3b, T3c and T3d), the inter-observer and intra-observer (k) for the mrDME was 0.700 and 0.718 respectively; the inter-observer and intra-observer ICC was 0.772 and 0.786 respectively. In the combined group (T3ab and T3cd), the inter-observer and intra-observer kappa (k) for the mrDME was 0.819 and 0.883 respectively; the inter-observer and intra-observer ICC was 0.829 and 0.796 respectively. Conclusion: There was a distinct increase in the kappa and ICC value in the combined group compared with the individual group. This high reproducibility result suggested that it is more reliable to measure T3ab and T3cd combined together than individually. This finding can play a crucial role in the management of rectal cancer and clinical decision making for non-expert radiologists in non-academic setting.

Mesorectal Invasion Depth in Rectal Carcinoma Is Associated With Low Survival

BackgroundMost cases of rectal cancer (RC) in our institution are in pathologic stage T3. They are a heterogeneous group but have been classified in a single-stage category. We performed the present study to validate the prognostic significance of the mesorectal extension depth (MED) in T3 RC measured in millimeters beyond the muscularis propria plane. Materials and MethodsWe performed a retrospective analysis of 104 patients with T3 RC who had undergone curative surgery after a course of preoperative chemoradiotherapy at a tertiary referral cancer hospital. The patients were grouped by MED (T3a, < 1 mm; T3b, 1-5 mm; T3c > 5-10 mm; and T3d > 10 mm). The clinicopathologic data and disease-free survival were analyzed. ResultsThe 5-year disease-free survival rate according to the T3 subclassification was 87.5% for those with T3a, 57.9% for T3b, 38.7% for T3c, and 40.3% for those with T3d tumors (P = .050). On univariate and multivariate analysis, the prognostic factors affecting survival were overall recurrence (hazard ratio [HR], 3.670; 95% confidence interval [CI], 1.710-7.837; P = .001), histologic grade (HR, 2.204; 95% CI, 1.156-4.199; P = .016), mesorectal invasion depth (HR, 1.885; 95% CI, 1.164-3.052; P = .010), and lymph node metastasis (HR, 1.211; 95% CI, 1.015-1.444; P = .033). ConclusionMED is a significant prognostic factor in patients with T3 RC who have undergone neoadjuvant chemoradiotherapy, especially when the MED is > 5 mm. The MED could be as important as other clinicopathologic factors in predicting disease-specific survival.

Prognostic significance of a preoperative magnetic resonance imaging assessment of the distance of mesorectal extension in clinical T3 lower rectal cancer.

The aim of this study was to evaluate the association between the mesorectal extensions on high-resolution magnetic resonance imaging (MRI) and the prognosis of patients with clinical T3 lower rectal cancer. Fifty-eight patients with clinical T3 lower rectal cancer were investigated using high-resolution MRI. One radiologist who was blinded to the clinicopathological findings retrospectively examined the MRI-predicted circumferential resection margin (mrCRM) and the distance of mesorectal extension (mrDME) on the scans. If the imaging showed a tumor ≤1mm from the mesorectal fascia, then the mrCRM involvement was defined as potentially present. The tumors were divided into two groups: mrDME ≤4mm and mrDME >4mm. A survival analysis showed that mrCRM-positive patients had a significantly poorer prognosis in the RFS (p<0.01) and LRFS (p<0.01). Patients with mrDME >4mm revealed a significantly poorer prognosis than those with mrDME ≤4mm in the OS (p=0.04), RFS (p<0.01), and LRFS (p=0.04). A multivariate analysis revealed that both mrCRM and mrDME on MRI had a significant impact on the RFS (p=0.01 and 0.03, respectively). The mrDME, as well as the mrCRM, may be an important preoperative prognostic factor for patients with clinical T3 lower rectal cancer.

Histopathological predictors for local recurrence in patients with T3 and T4 rectal cancers without preoperative chemoradiotherapy.

Identification of suitable predictors of local recurrence (LR) in patients with rectal cancer would be of clinical benefit. The aim of this study was to identify histopathological factors that could predict LR. A total of 796 stage II/III patients with pT3 and pT4 rectal cancer who did not undergo preoperative chemoradiation were enrolled. LR was defined as intra-pelvic recurrence only. Histopathological factors related to LR were investigated. LR was found in 25 patients (6.1%) with stage II and 54 patients (13.9%) with stage IIIB/IIIC. In patients with stage II, distance of mesorectal extension (DME) >4 mm (P = 0.011) and positive venous invasion (P = 0.035) were independent factors that predicted LR. In patients with stage IIIB/IIIC, circumferential resection margin (CRM) ≤1 mm (P = 0.003) and positive lymphatic invasion (P = 0.006) were independent factors. The cumulative 5-year LR rate was higher (11.9%) in patients with a combination of DME > 4 mm and/or positive venous invasion for stage II (P < 0.001), and was also higher in patients with a combination of CRM≤1 mm and/or positive lymphatic invasion for stage IIIB and IIIC (22.2%; P < 0.002, and 34.3%; P < 0.006, respectively). Important histopathological predictors for LR in patients with pT3 and pT4 rectal cancer were different at each stage.

Clinical Significance of the Mesorectal Extension as the Prognostic Predictor in Rectal Cancer

Clinical Significance of the Mesorectal Extension as the Prognostic Predictor in Rectal Cancer

Safe Distal Resection Margin in Patients With T3 Mid and Distal Rectal Cancer Who Underwent a Sphincter-Saving Resection Without Preoperative Radiotherapy

See Article on Page 231-237 The Korean Clinical Practice Guideline for Colon and Rectal Cancer v.1.0 (2012) recommends preoperative chemoradiation as an initial treatment for patients with clinical stage II and III (cT3+ or cN+) rectal cancer [1]. The National Comprehensive Cancer Network guideline v.4. (2013) for rectal cancer also recommends preoperative chemoradiation as an initial treatment for T3N0 or TanyN1-2 rectal cancer. Preoperative chemoradiotherapy significantly decreases the local recurrence rate after a total mesorectal excision (TME) curative resection for rectal cancer, but the functional disability of the anal sphincter after radiation therapy cannot be neglected. In Japan, a major trend in the treatment of rectal cancer has been the radical low anterior resection including lateral node dissection without adjuvant radiotherapy. The Study Group of the Japanese Society for Cancer of the Colon and Rectum reported on the Clinical Significance of the Mesorectal Extension of Rectal Cancer that the distance of mesorectal extension (DME), which was measured with histology after fixation in 20% formalin, was a significant prognostic factor for recurrence-free survival (cut off point, 4 mm) [2]. The multivariate Cox regression analysis showed that the recurrence-free five-year survival rate was significantly higher in patients with a DME ≤4 mm than in patients with DME >4 mm in stage IIA and IIIA cancer, but not in stage IIIC cancer (P = 0.00015, P = 0.0001, and P = 0.2697, respectively). The reports suggested that local recurrences were increased by the status of cancer-positive lymph nodes even in the same category of T3 cancer in patients without radiation therapy. The distal resection margin (DRM) means the length of the tumor-free normal mucosa and rectal wall. Han et al. [3] published the manuscript, 'Association between a close distal resection margin and recurrence after sphincter-saving resections for T3 midor low-rectal cancer without radiotherapy.' With retrospective data, they described the 5-year local recurrence rates as 6.69% in patient with DRM ≤10 mm and 9.52% in patients with DRM >10 mm, respectively (DRM cut off point, 1 cm; P = 0.3981). However, they gave no descriptions of cancer-positive lymph nodes in the groups with stage IIA, IIIB, and IIIC cancer. The local recurrence may be influenced not only by DRM but also by the status of lymph nodes. A Norwegian national study recommended a DRM of >10 mm for rectal cancer patients treated without radiotherapy [4]. The 5-year local recurrence rate was 14.5% for patients with DRM of 0-10 mm compared to 8.66% for patients with DRM >11 mm (P < 0.001). The proportions of T3 cancer were 48% and 63%, respectively, in those two groups. Current Japanese guidelines state a 2-cm DRM is needed for rectal cancer with a distal edge below the peritoneal reflection. Intramural and extramural distal spread prevents local control and promotes systemic metastasis. If the specimen is not pinned, the length of the DRM can shrink by 50% in a nonradiated rectum after formalin fixation. A gross determination of a safe distal resection margin is difficult in the operating room. The frozen-section result for the DRM may be falsely negative in 12% of all cases. A systemic review supported the practice of sphincter preservation in selected settings of close distal resection margins (≤1 cm) after mesorectal excision for distal rectal cancer [5]. A further subgroup study suggested that margins as close as ≤5 mm, if they were indeed negative, might be acceptable. However, the importance of patient and tumor selection for this approach must be emphasized. In distal rectal cancer, the mesorectal fascia does not extend beyond the puborectalis level, and the anal sphincter is another barrier for safe distal resection margins. Local recurrence may develop with uninvolved margins related to lymphatic spread from the DRM. In preoperative radiation cases, a distal clearance margin of 1 cm or less may a safe distance in patients who undergo lower rectum cancer surgery [6]. We would like to conclude with the following remark. Although reduction of the DRM to less than 10 mm does not increase local recurrences in many low-risk patients, a DRM >10 mm is safe in cases of rectal cancer with lymphovascular invasion, perineural invasion and multiple lymph-node metastases.

Benefit of the measurement of mesorectal extension in patients with pT3N1-2 rectal cancer without pre-operative chemoradiotherapy: Post-operative treatment strategy

A treatment strategy based on the distance of mesorectal extension (DME) for pT3N1-2 rectal cancer patients without pre-operative chemoradiotherapy has not yet been defined. The present study aimed to describe the benefit of the measurement of mesorectal extension in stratifying treatment for pT3N1-2 rectal cancer patients. Data from 512 patients with pT3N1-2 rectal cancer undergoing curative surgery at 28 institutes were analyzed in this study. DME was measured histologically, and the optimal prognostic cut-off point of the DME was determined using Cox regression analyses. Survival was calculated using the Kaplan-Meier method. The patients were subdivided into two groups based on the optimal prognostic cut-off point: DME ≤4 mm and DME >4 mm. The DME was found to be a powerful independent risk factor for predicting distant and local recurrences. The recurrence-free 5-year survival rates of patients with DME >4 mm were significantly poorer for Stages IIIB (53.3%; p=0.0015; HR, 1.76; 95% CI, 1.233–2.501) and IIIC (32.9%; p=0.0095; HR, 1.64; 95% CI, 1.119–2.407) than for patients with DME ≤4 mm (69.7 and 50.4%, respectively). The cancer-specific survival rates of patients with DME >4 mm were also significantly worse than those with DME ≤4 mm. A value of 4 mm provides the best cut-off point for subdividing the mesorectal extension to predict oncologic outcomes. Measurement of mesorectal extension appears to be of benefit in stratifying patients for post-operative adjuvant treatments.

Depth of Mesorectal Extension Has Prognostic Significance in Patients With T3 Rectal Cancer

More than half of all rectal cancers are T3 lesions, but they are classified as a single-stage category. The aim of this study was to validate prognostic significance of mesorectal extension depth in T3 rectal cancer. This study is a retrospective analysis of oncologic outcomes of patients with T3 rectal cancer grouped by mesorectal extension depth (T3a, <1 mm; T3b, 1-5 mm; T3c, 5-15 mm; T3d, >15 mm). This study was conducted at a tertiary referral cancer hospital. From 2003 to 2009, 291 patients who underwent a curative surgery were included. Oncologic outcomes in terms of disease-free survival were analyzed. The 5-year disease-free survival rate according to T3 subclassification was 86.5% for T3a, 74.2% for T3b, 58.3% for T3c, and 29.0% for T3d. It was significantly higher in T3a,b tumors than that in T3c,d tumors (77.6% vs 55.2%, p < 0.001). On univariate and multivariate analysis, prognostic factors affecting recurrence were preoperative CEA level ≥ 5 ng/mL (HR 2.617, 95% CI 1.620-4.226), lymph node metastasis (HR 3.347, 95% CI 1.834-6.566), and mesorectal extension depth >5 mm (HR 1.661, 95% CI 1.013-2.725). In subgroup analysis, independent prognostic factors were preoperative CEA level and mesorectal extension depth >5 mm for 200 patients with ypT3 rectal cancer and preoperative CEA level and lymph node metastasis for 91 patients with pT3 rectal cancer. This study lacks quality of surgery plane evaluation because of its retrospective nature. Moreover, pathologic examination was not done with a whole-mount section. Depth of mesorectal extension >5 mm is a significant prognostic factor in patients with T3 rectal cancer. Depth of mesorectal extension especially may be more important than the nodal status in predicting the oncologic outcome for patients who had received preoperative chemoradiotherapy.

Predicting oncologic outcomes by stratifying mesorectal extension in patients with pT3 rectal cancer: A Japanese multi‐institutional study

The goal of this study was to clarify the clinical significance of mesorectal extension in pT3 rectal cancer. This currently remains unclear. Data from 975 consecutive patients with pT3 rectal cancer that underwent curative surgery at 28 institutes were reviewed. The distance of the mesorectal extension (DME) was measured histologically. The optimal prognostic cut-off point of the DME for oncologic outcomes was determined using the receiver operating characteristic curve and Cox regression analysis. When patients were subdivided into two groups according to the optimal cut-off point, DME≤4 mm and DME>4 mm, DME was found to be a powerful independent risk factor for postoperative recurrence. A DME>4 mm was significantly correlated with distant and local recurrences at Stage IIA and IIIB diseases. The recurrence-free 5-year-survival rate was significantly higher in patients with a DME≤4 mm [86.6% at Stage IIA (p=0.00015), and 68.7% at Stage IIIB (p<0.0001)] than in patients with a DME>4 mm (71.3% at Stage IIA and 49.1% at Stage IIIB). No significant difference was noted in the oncologic outcomes between the two groups at Stage IIIC. A value of 4 mm provides the best prognostic cut-off point for patient stratification and for the prediction of oncologic outcomes. A subclassification based on a 4-mm cut-off point may improve the utility of the TNM 7th staging system except for Stage IIIC. These findings warrant further prospective studies to determine the reliability and validity of this cut-off point.

Clinical Significance of the Mesorectal Extension of Rectal Cancer

The aim of this study was to emphasize the importance of a subclassification in the TNM staging system of rectal cancer. The clinical significance of the mesorectal extension of rectal cancer is unclear. Data from 463 consecutive patients with stage IIa disease (T3N0) undergoing curative surgery at 28 institutes were analyzed. The measurement of the distance of the mesorectal extension (DME) was histologically evaluated. Risk factors for recurrence, for the optimal cutoff point of the DME, independent prognostic factors, and for survivals were studied using receiver operating characteristic curve and logistic and Cox regression analyses. Survivals were calculated using the Kaplan-Meier method. A value of 4 mm was determined as the optimal cutoff point. The patients were subdivided into 2 groups: DME ≤ 4 mm and DME > 4 mm at the optimal cutoff point. DME > 4 mm had the greatest impact on recurrence-free survival [P = 0.00023, hazard ratio (HR): 2.26, 95% confidence interval (95% CI): 1.465-3.492, L/U ratio: 0.420] and was an independent adverse prognostic factor (P = 0.00323, HR: 1.97, 95% CI: 1.254-3.091). The distant metastasis rate in DME > 4 mm was higher 16.7% than that in DME ≤ 4 mm (P = 0.00177, OR: 2.61, 95% CI: 1.430-4.761). The incidence of local recurrence was not influenced by DME. The recurrence-free 5-year survival rate in DME ≤ 4 mm was significantly better than that in DME > 4 mm (86.6% vs 71.3%, P = 0.00015, HR: 0.44, 95% CI: 0.286-0.683). The cancer-specific survival rate in DME ≤ 4 mm was also significantly better than that in DME > 4 mm (91.3% vs 82.2%, P = 0.000664, HR: 0.52, 95% CI: 0.325-0.843). A subclassification according to mesorectal extension based on a 4-mm cutoff point is needed for the TNM staging system. However, further prospective study is necessary to prove reproducibility and validity of the cutoff point.

Challenges in Staging Systems for Colorectal Cancer: Clinical Significance of Metastatic Lymph Node Number in Colorectal Cancer and Mesorectal Extension in Rectal Cancer

In many countries, treatment for cancer is performed based on staging systems in which the degree of cancer development is defined objectively. A common staging system is thus needed to compare outcomes. The staging system for colorectal cancer in Japan has been made to enhance consistency with the TNM classification, and the categorization of metastatic lymph nodes and depth of invasion have been revised in recent years. Although these are important factors that determine disease stage, relationships between each factor and recurrence have shown differing prognoses. In our retrospective study, the prognosis of a group with only one metastatic lymph node was significantly better compared to a group with ≧2 metastatic lymph nodes. In addition, rectal cancer with mesorectal extension >5 mm showed low relapse-free survival rates and high recurrence rates. The validity of staging systems should thus be inspected from various perspectives.