Extranodal Tumor Deposits Research Articles

Comparison of age-stratified survival outcomes of gallbladder cancers in an Indian population

BackgroundGallbladder cancers (GBCs) occur a decade earlier in India in comparison to the global occurrence, limiting the applicability of existing literature on age adjusted outcomes. MethodsPatients who underwent surgery between 01.01.2010 and 31.12.2020 for GBC were analyzed. Patients were divided into three age groups: group 1(≤40 years), group 2(41–60 years), group 3(>60 years) and their outcomes were compared. ResultsTotal of 6190 patients were treated for suspected or diagnosed GBC with a median age of 57 years. Curative resection was performed in 749 (67.9%) patients, of whom 114 (16.2%), 471 (62.9%), and 164 (21.9%) patients were in groups 1, 2, and 3, respectively. 5-year disease-free survival (DFS) [46.8% vs. 58.5%, p = 0.031] and overall survival (OS)[53.5% vs. 66.6%, p = 0.05] of group 3 were significantly lower than group 1. Patient age (HR 1.021), AJCC stage (HR 6.413), pathologic residual disease in the gallbladder fossa (HR 2.44), and extranodal tumor deposits (HR 1.762) were identified as independent predictors of poor OS. ConclusionsGallbladder cancers in the Indian population show poorer outcomes with advancing age. Higher proportion of males in the elderly group with a more advanced stage at presentation are plausible reasons for poorer outcomes.

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.

Risk factors predict microscopic extranodal tumor deposits in advanced stage III colon cancer patients

Colorectal cancer is a frequent cause of cancer-related mortality in patients with lymph node or distant metastases. Pericolonic tumor deposits (TDs) are considered prognostically distinct from lymph node metastases. To investigate risk factors for extranodal TDs in stage III colon cancer. This was a retrospective cohort study. We selected 155 individuals diagnosed with stage III colon cancer from the database of the Cancer Registry of the Tri-Service General Hospital. The patients were allocated into the groups with/without N1c. Multivariate Cox regression analysis and Kaplan-Meier method were done. The primary outcomes investigate the association between the covariates and extranodal TDs, and prognostic significance of the covariates regarding the survival. There were 136 individuals in the non-N1c group and 19 individuals in the N1c group. Patients with lymphovascular invasion (LVI) had a higher risk of TDs. Overall survival rates of patients with and without LVI were 6.64 years and 8.61 years, respectively (P = 0.027). The N1c patients without LVI had higher overall survival than those who with LVI (7.73 years vs 4.42 years, P = 0.010). Patients having stage III colon cancer with LVI have a higher probability of having TDs than those with stage III colon cancer without LVI. Stage III colon cancer patients with TDs and LVI could have poor prognosis and outcome.

Diffusion-Weighted Magnetic Resonance Imaging of 103 Patients with Rectal Adenocarcinoma Identifies the Apparent Diffusion Coefficient as an Imaging Marker for Tumor Invasion and Regional Lymph Node Involvement.

BackgroundThis retrospective study included 103 patients diagnosed with rectal adenocarcinoma at a single center in Poland who underwent preoperative diffusion-weighted magnetic resonance imaging (DWI) and aimed to determine whether the apparent diffusion coefficient (ADC) was an imaging marker for tumor invasion and regional lymph node involvement.Material/MethodsWe analyzed primary staging magnetic resonance examinations of the rectum of 103 consecutive patients with histologically proven non-mucinous adenocarcinoma who underwent surgical treatment. In 85 patients, surgery was preceded by long-course chemoradiotherapy (n=18) or short-course radiotherapy (n=67). The following DWI parameters were measured: ADC mean, minimum, maximum, and standard deviation in the region of interest (ADC SD-in-ROI). Values were compared between subgroups based on histological parameters from the report: tumor stage, lymph node stage, differentiation grade, the presence of extranodal tumor deposits, angioinvasion, and perineural invasion. Statistical analysis was performed using the Mann-Whitney U test and the unilateral t test.ResultsADC mean values were lower for cases in which postoperative histopathological examination lymph node invasion (P=0.04) and tumor deposits were found (P=0.04). Minimal ADC value was higher in cases in which tumor deposits were not found (P=0.009). ADC SD-in-ROI values were lower in cases in which lymph nodes invasion was confirmed (P=0.014). There were no statistically significant differences for other parameters.ConclusionsThe ADC values in pre-treatment DWI in patients with rectal adenocarcinoma were correlated with tumor invasion and regional lymph node metastases. Therefore, ADC values from the pre-treatment MRI may help plan adjuvant therapy in patients with rectal adenocarcinoma.

Comparative analysis of clonal evolution among patients with right- and left-sided colon and rectal cancer

SummaryTumor multiregion sequencing reveals intratumor heterogeneity (ITH) and clonal evolution playing a key role in tumor progression and metastases. Large-scale high-depth multiregional sequencing of colorectal cancer, comparative analysis among patients with right-sided colon cancer (RCC), left-sided colon cancer (LCC), and rectal cancer (RC), as well as the study of lymph node metastasis (LN) with extranodal tumor deposits (ENTDs) from evolutionary perspective remain weakly explored. Here, we recruited 68 patients with RCC (18), LCC (20), and RC (30). We performed high-depth whole-exome sequencing of 206 tumor regions including 176 primary tumors, 19 LN, and 11 ENTD samples. Our results showed ITH with a Darwinian pattern of evolution and the evolution pattern of LCC and RC was more complex and divergent than RCC. Genetic and evolutionary evidences found that both LN and ENTD originated from different clones. Moreover, ENTD was a distinct entity from LN and evolved later.

Extranodal Tumor Deposits in the Axillary Fat Indicate the Need for Axillary Dissection Among T1-T2cN0 Patients with Positive Sentinel Nodes.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated the safety of omitting axillary lymph node dissection (ALND) in T1-T2cN0 patients with fewer than three positive sentinel nodes (SLNs) undergoing breast-conservation therapy. While microscopic extracapsular extension (mECE) > 2mm is associated with increased nodal burden, the significance of extranodal tumor deposits (ETDs) in the axillary fat is uncertain. Consecutive patients with T1-T2cN0 breast cancer undergoing sentinel node biopsy and ALND for SLN metastases from January 2010 to December 2018 were identified. ETDs were defined as intravascular tumor emboli or metastatic deposits in the axillary fat. Clinicopathologic characteristics and nodal burden were compared by ETD status. Among 1114 patients, 113 (10%) had ETDs: 81 (72%) were intravascular tumor emboli and 32 (28%) were soft tissue deposits. Patients with ETDs had larger tumors (median 2.2 vs. 2.1cm; p = 0.033) and more often had mECE (83% vs. 44%; p < 0.001). On univariable analysis, presence of ETDs (odds ratio [OR] 9.66, 95% confidence interval [CI] 6.36-14.68), larger tumors (OR 1.47, 95% CI 1.25-1.72), and mECE (OR 10.73, 95% CI 6.86-16.78) were associated with four or more additional positive non-SLNs (NSLNs; all p < 0.001). On multivariable analysis, ETDs remained associated with four or more positive NSLNs (OR 5.67, 95% CI 3.53-9.08; p < 0.001). ETDs were strongly associated with four or more positive NSLNs (OR 7.15, 95% CI 4.04-12.67) among patients with one to two positive SLNs (n = 925). Among T1-T2cN0 patients with SLN metastases, ETDs are strongly associated with four or more positive NSLNs at ALND. Even among those who may otherwise meet the criteria for omission of ALND, the presence of ETDs in axillary fat warrants consideration of ALND.

Impact of extranodal tumor deposits on prognosis and N stage in gastric cancer

BackgroundExtranodal tumor deposits have been reported to be associated with a poor prognosis in many malignancies and are also included in the tumor, node, and metastasis staging system for colorectal cancer. MethodsWe reviewed retrospectively a total of 2,344 gastric cancer patients who underwent gastrectomy with curative intent at the Tianjin Medical University Cancer Institute and Hospital (Hexi District, Tianjin, China) and the First Affiliated Hospital of Hainan Medical University (Longhua District, Haikou, China). Patients were categorized into 2 groups based on extranodal tumor deposit status: a positive group, including those with extranodal tumor deposits, and a negative group composed of those with no extranodal tumor deposits. Clinicopathologic factors were correlated with extranodal tumor deposits, and their individual prognoses were analyzed. In addition, a pathologically modified node classification system was proposed by incorporating the extranodal tumor deposit status into the 8th ed of the N staging system. The superiority of prognostic prediction between the modified node classification and node stage was compared. ResultsA total of 645 (27.5%) patients had extranodal tumor deposits. The presence of extranodal tumor deposits was associated with a larger tumor size, Borrmann type III and IV, a deeper depth of invasion, and an advanced node stage. In the multivariate analysis, extranodal tumor deposits were an independent prognostic factor for gastric cancer patients after curative resection. Gastric cancer patients with extranodal tumor deposits demonstrated a lesser 5-year overall survival than those with no extranodal tumor deposits (31.9% vs 61.4%, P < .001). With the strata analysis, statistically significant prognostic differences between the two groups were only observed in patients at the N0-N2 stage. The modified node classification was found to be more appropriate for predicting the overall survival of gastric cancer patients after curative resection than node stage, and the –2 log likelihood of the modified node classification (16,042.890) was smaller than the value of node stage (16,150.811). ConclusionExtranodal tumor deposits in gastric cancer patients indicate aggressive characteristics and a poorer prognosis of gastric cancer. We maintain that extranodal tumor deposits should be incorporated into the N staging system to enhance the accuracy of the prognostic prediction of patients with gastric cancer.

Prognostic Significance of Tumor Deposits in Stage III Colon Cancer.

The American Joint Committee on Cancer includes extranodal tumor deposits in the tumor-node-metastasis classification of colon cancer. However, it is unclear how tumor deposits compare with lymph node metastases in prognostic significance. This study evaluated the survival impact of tumor deposits relative to lymph node metastases in stage III colon cancer. The US National Cancer Database (2010-2012) was reviewed for resectable stage III adenocarcinoma of the colon, and stratified by presence of tumor deposits and lymph node metastases. Univariate and multivariate survival analyses were performed. Of 6424, 10.1% had both tumor deposits and lymph node metastases [5-year survival (5YS) 40.2%], 2.5% had tumor deposits alone (5YS 68.1%), and 87.4% had lymph node metastases alone (5YS 55.4%). Patients with lymph node metastases alone tended to have a greater number of lymph nodes retrieved (20.9 versus 18.8, p = 0.0126) and were more likely to receive adjuvant therapy (66.9 vs 58.0%, p = 0.003) than those with only tumor deposits. Patients with both had significantly worse survival at all T stages (p < 0.05, all). There was no significant difference in survival between tumor deposits alone and lymph node metastases alone at any T stage (p > 0.8, all). After controlling for patient, disease, and treatment characteristics, patients with tumor deposits alone [hazard ratio (HR) 0.56, p = 0.001] or only lymph node metastases (HR 0.64, p < 0.001) were associated with improved survival relative to patients with both. Concomitant presence of tumor deposits and lymph node invasion carries poor prognostic significance. Tumor deposits alone appear to have prognostic implications similar to lymph node invasion alone.

Clinicopathological features and prognosis of colorectal cancer with extranodal tumor deposits.

e15005 Background: The study discusses clinicopathological features of colorectal cancer with extranodal tumor deposits(ENTDs) and investigates whether ENTDs is a poor prognostic factor. Methods: 1. Clinicopathological data and follow-up of colorectal cancer with ENTDs who underwent surgery between June 2007 and June 2010 in seven hospitals in North China were collected retrospectively. Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used for multivariate analysis of prognostic factors. 2. The literatures on ENTDs and postoperative survival rate in colorectal cancer published from 1990 to 2016 were retrieved in English literature databases such as MEDLINE/PubMed, Web of Science and Chinese literature databases such as CNKI. Meta-analysis was conducted by Review Manager 5.3 software. Results: 1. A total of 253 cases of colorectal cancer with ENTDs were collected. The 5-year survival with only one ENTD was 49.2% (87/177), with median survival time 60 months. The 5-year survival with more than one ENTD was 17.1% (13/76), with median survival time 44 months. Cox regression analysis revealed that age, tumor size, number of ENTDs, N, m stage, surgical approach and adjuvant treatment were independent risk factors of prognosis of colorectal cancer with ENTDs. 2. The total sample size of the studies was 4731 cases with ENTDs (+) 917 cases. Meta analysis showed that: 5-year overall survival and 5-year relapse-free survival rate were significantly lower in ENTDs (+) group than ENTDs (-) group for colorectal cancer (OR:respectively 0.25,0.30; 95% CI:respectively 0.17-0.37,0.22-0.41; both P &lt; 0.00001); 5-year overall survival rates were both significantly lower in ENTDs (+) group than ENTDs (-) group for patients with N0 and N+ colorectal cancer (N0 group: P = 0.003; N+ group: P = 0.0008; both P &lt; 0.05). Conclusions: 1.Age, tumor size, number of ENTDs, N, m stage, surgical approach and adjuvant treatment were independent risk factors of prognosis of colorectal cancer with ENTDs. 2. ENTDs was a poor prognostic factor in colorectal cancer. The effect of ENTDs on postoperative survival rate might resemble that of between lymph node metastasis and distant metastasis.

481P - The correlation between tumor regression grade and retrieved lymph nodes status in locally advanced rectal cancer after neoadjuvant treatment: results from a prospective study

A paucity of lymph nodes harvested is common in rectal cancer after neoadjuvant treatment and the significance is still uncertain. We aimed to evaluate the correlation between tumor regression grade (TRG) and retrieved lymph nodes status in patients who underwent neoadjuvant treatment followed by total mesorectal excision (TME) for locally advanced rectal cancer. From Jan 2011 to Feb 2015, complete data was available for 447 patients with rectal cancer who received neoadjuvant treatment followed by TME enrolled in FOWARC study. According to the post-operative pathologic TRG of primary lesion, patients were categorized into 4 groups, TRG 0, 1, 2 and 3.The number of harvested lymph nodes, lymph node metastasis, and extranodal tumor deposits in each group were analyzed. Of the 447 patients, 77 (17.2%) patients were TRG 0, and 143 (32.0%) patients were TRG 1. Another 156 (34.9%) and 71 (15.9%) patients were TRG 2 and TRG 3, respectively. The median retrieved lymph node counts among the 4 groups were 8, 10, 11 and 13, respectively. The harvested lymph node in better TRG groups was less than that of poor TRG group (p = 0.001). The lymph node metastasis rates of the 4 groups were 7.8%, 14.7%, 21.8% and 38.0%, respectively. The differences were statistically significant (p < 0.001). And the extranodal tumor deposits rates of the 4 groups were 3.9%, 7.7%, 16.0% and 21.1%, respectively (p = 0.002).Tabled 1ItemsTRG 0 (N = 77)TRG 1 (N = 143)TRG 2 (N = 156)TRG 3 (N = 71)PHarvested lymph nodes (median)81011130.001LN metastasis (n,%)6(7.8)21(14.7)34(21.8)27(38.3)<0.001Extranodal TD (n,%)3(3.9)11(7.7)25(16.0)15(21.1)0.002 Open table in a new tab Lymph node metastasis and extranodal tumor deposits were correlated with TRG. The paucity of lymph nodes retrieved did not infer poor oncologic outcomes in rectal cancer after neoadjuvant treatment. The number of retrieved lymph nodes should be redefined according to the pathologic response to neoadjuvant treatment. Further analysis of optimal lymph node counts in different TRG group will be performed with survival data.

Meta-analysis of relationship between extranodal tumor deposits and prognosis in patients with colorectal cancer

To investigate the relationship between extranodal tumor deposits and prognosis in patients with colorectal cancer. The literatures on extranodal tumor deposits and postoperative survival rate in patients with colorectal cancer published at home and abroad from 1990 to 2014 were retrieved in 15 English literature databases such as MEDLINE/PubMed, Web of Science, Directory of Open Access Journals(DOAJ), SpringerLink and Chinese literature databases such as Chinese Biomedical Literature Database CD-ROM, China National Knowledge Infrastructure (CNKI) Database with the internet platform of Yonsei University Library. After screening for inclusion, data extraction and quality assessment, meta-analysis was conducted by the Review Manager 5.3 software. There were 10 studies meeting the inclusion criteria for meta-analysis. The total sample size of the studies was 4 068 cases with ENTD(+) 727 cases, while ENTD(-) 3 341 cases. Meta analysis showed that 5-year overall survival rate and 5-year relapse-free survival rate were significantly lower in ENTD(+) group than those in ENTD(-) group (OR 0.27, 0.23; 95% CI:0.18 to 0.43, 0.16 to 0.34 respectively, both P=0.000); the 5-year overall survival rates were both significantly lower in ENTD(+) group as compared to ENTD(-) group for patients with N0 and N(+) colorectal cancer (both P<0.05). Extranodal tumor deposits is a poor prognostic factor of patients with colorectal cancer.

Apparent Diffusion Coefficient (ADC) value: a potential imaging biomarker that reflects the biological features of rectal cancer.

ObjectiveWe elected to analyze the correlation between the pre-treatment apparent diffusion coefficient (ADC) and the clinical, histological, and immunohistochemical status of rectal cancers.Materials and MethodsForty-nine rectal cancer patients who received surgical resection without neoadjuvant therapy were selected that underwent primary MRI and diffusion-weighted imaging (DWI). Tumor ADC values were determined and analyzed to identify any correlations between these values and pre-treatment CEA or CA19-9 levels, and/or the histological and immunohistochemical properties of the tumor.ResultsInter-observer agreement of confidence levels from two separate observers was suitable for ADC measurement (k = 0.775). The pre-treatment ADC values of different T stage tumors were not equal (p = 0.003). The overall trend was that higher T stage values correlated with lower ADC values. ADC values were also significantly lower for the following conditions: tumors with the presence of extranodal tumor deposits (p = 0.006) and tumors with CA19-9 levels ≥ 35 g/ml (p = 0.006). There was a negative correlation between Ki-67 LI and the ADC value (r = −0.318, p = 0.026) and between the AgNOR count and the ADC value (r = −0.310, p = 0.030).ConclusionSignificant correlations were found between the pre-treatment ADC values and T stage, extranodal tumor deposits, CA19-9 levels, Ki-67 LI, and AgNOR counts in our study. Lower ADC values were associated with more aggressive tumor behavior. Therefore, the ADC value may represent a useful biomarker for assessing the biological features and possible relationship to the status of identified rectal cancers.

Tumor Deposit Is a Poor Prognostic Indicator for Patients Who Have Stage II and III Colorectal Cancer With Fewer Than 4 Lymph Node Metastases but not for Those With 4 or More

Extranodal tumor deposits are involved in TNM classification. However, it is uncertain whether a tumor deposit is a regular lymph node metastasis, and its prognostic significance in patients with stage II or III colorectal cancer remains to be established. This study aimed to determine the prognostic significance of tumor deposits for stage II and III colorectal cancer. This study is a retrospective review of clinicopathological data. This study was conducted at a tertiary care hospital/referral center in Japan. We reviewed the clinical course of 171 stage II and 173 stage III consecutive patients between January 1999 and December 2006. We examined the clinicopathological features of colorectal cancers with tumor deposits and calculated overall survival and recurrence-free survival of the patients according to the status of tumor deposits. The primary outcome was the impact of tumor deposits on patient survival. Thirty-five (10.2%) patients with colorectal cancers had tumor deposits in the pericolic and/or mesocolic region. Survival rates among the patients with tumor deposits were significantly lower than those without (5-year overall survival: 58.4% vs 81.0%, p < 0.0001; 5-year recurrence-free survival: 47.1% vs 73.4%, p < 0.0001). Tumor deposit was an independent prognostic factor for patients with colorectal cancer in multivariate analysis (overall survival: HR, 2.30; 95% CI, 1.26-4.04; p = 0.04; recurrence-free survival: HR, 2.42; 95% CI, 1.04-4.90; p = 0.04). Tumor deposit was an independent prognostic factor in N0 and N1 colorectal cancer, whereas N2 cancer had poor survival outcome regardless of tumor deposit. Our study was a single-institution retrospective study, and the numbers of patients were relatively small to draw firm conclusions. Tumor deposit may be an independent adverse prognostic factor for stage II and III N1 colorectal cancer.

側方領域再発切除後急激に骨・肝再発した直腸SM癌の1例

側方領域再発切除後急激に骨・肝再発した直腸SM癌の1例

Histopathology and mismatch repair status of 458 consecutive colorectal carcinomas.

Defects in the mismatch repair (MMR) genes hMLH1 and hMSH2 have been found in 10% to 20% of sporadic colorectal carcinomas and also many cases of hereditary nonpolyposis colorectal cancer syndrome. Patients with these tumors have an improved prognosis and may show greater sensitivity to chemotherapy. We examined 458 resected colorectal carcinomas from 430 consecutive patients and used immunohistochemistry to determine which tumors lacked expression of these genes (MMR-d). We correlated the status of MMR-d or "intact" expression with stage, site, and histology. Eighty-nine of 458 tumors (19.4%) were MMR-d, including 80 hMLH1 and 9 hMSH2 tumors. A total of 6% of patients had synchronous tumors, and 37.7% of these were MMR-d (P=0.0008). A high proportion of patients with previous breast cancer (4 of 6 patients) had hMLH1-defective colorectal carcinomas. MMR-d tumors presented at an earlier stage than intact tumors, and the node-positive MMR-d tumors were less likely than intact tumors to have pericolonic extranodal tumor deposits (18.2% vs. 44%). The proportion of tumors at each site that were MMR-d increased progressively from cecum (32%) to ascending (35%) to transverse colon, where 41% of all tumors were defective. The proportions then rapidly decreased, reaching the lowest rate (4.7%) in the rectum. Both types of MMR-d tumors more often had expansive borders, intraepithelial lymphocytosis, peritumoral lymphoid, and Crohn's-like lymphoid responses than the intact tumors; the frequencies of these features diminished with advancing stage. Tumor budding was less common in stage II and III MMR-d tumors than in intact tumors. Keloid and myxoid type stromas correlated with stage and vascular invasion and were not related to mismatch repair status. Significant differences existed between the hMLH1 and hMSH2 tumors. The reported right-sided preponderance of MMR-d tumors is due to most hMLH1, but not hMSH2, tumors being found there (87.5% vs. 44.4%). hMSH2 tumors were most common in the rectum (55.6%). Mucinous tumors were common in hMLH1 tumors (36.3%) but not in hMSH2 tumors (11.1%). hMLH1 tumors were most likely to be poorly differentiated (70%), which was uncommon with hMSH2 tumors (22.2%). hMSH2 tumors were more likely to be confined to the wall (66.7%) than hMLH1 (20%) or intact tumors (23%). We conclude that hMLH1 and hMSH2-defective tumors have distinctly differing histologic features from each other.

Histologic indices in biopsy specimens for estimating the probability of extended local spread in patients with rectal carcinoma.

Although precise preoperative assessment of the extent of local cancer spread is important to determine the appropriate treatment strategy, imaging modalities have not been sufficient. The aim of this study was to establish effective preoperative indices that would predict the degree of local spread in patients with rectal carcinoma. In specimens from 437 patients with advanced rectal carcinoma, the submucosal horizontal invasive frontal region was examined histologically with reference to three unfavorable characteristics: 1) tumor "budding", 2) poor differentiation, and 3) vascular invasion. In addition, a transanal submucosal biopsy, which targets the tumor edge, was performed on 85 patients to verify the utility of preoperative evaluation of these parameters. Multivariate logistic analysis showed that three unfavorable parameters had independent impact on the degree of nodal involvement. These parameters related significantly to the number of lymph nodes involved, the development of extranodal tumor deposits, circumferential surgical margin involvement, and lateral pelvic lymph node metastases. Regarding patients without unfavorable parameters as a standard, the odds ratio of pelvic recurrence was 1.8 (0.9-3.4) in patients with one unfavorable parameter and 5.3 (2.7-10.2) in patients with multiple unfavorable parameters. Based on the transanal biopsy, the submucosal invasive frontal region could be estimated in 73 patients (85.9%). Among these cases, the multiple unfavorable parameters were relevant to an increased risk of extensive local spread. In addition, pelvic recurrence developed in 36% of patients with multiple unfavorable parameters (no-risk patients, 5%; single-risk patients, 13%). Histology in the submucosal invasive frontal region reflects the extent of local spread and can be evaluated preoperatively by transanal biopsy, which should become a useful tool for therapy selection for patients with advanced rectal carcinoma.