Clinical implications of radiologic criteria and prognostic factors for lateral lymph node metastasis in low rectal cancer

To investigate the factors associated with lateral lymph node metastasis in middle and low rectal cancer. Clinical data of 203 patients with middle and low rectal cancer (within 10 cm from anal verge) undergoing lateral lymph node dissection in the Affiliated Cancer Hospital, Xinjiang Medical University between June 2004 to June 2010, were analyzed retrospectively. Logistic regression analysis was used to screen the associated factors. The total number of harvested lateral lymph node was 3349, and average number was 17 per case. The number of positive lateral lymph node was 221, and the lymph node metastasis ratio was 6.6%(221/3349). Univariate analysis showed that age, family history, tumor length, gross type of tumor, histological type, differentiation, depth of invasion, invasion of circumference, serum CEA, tumor thrombus and upper lymph node metastasis were associated with rectal cancer metastasis(P<0.05). Multivariate analysis showed that age, histological type, infiltration depth, gross type, differentiation degree and upper lymph node metastasis were the independent risk factors of the lateral lymph node metastasis in middle and low rectal cancer(P<0.05). For patients who is young, or with poorly differentiated cancers, infiltrative type, T4 cancer, or those with upper lymph node metastasis, lateral lymph resection may be indicated because of high risk of lateral node metastasis.

Identifying lateral pelvic lymph node (LPN) metastasis in low rectal cancer is crucial before treatment. Several risk factors and prediction models for LPN metastasis have been reported. However, there is no useful tool to accurately predict LPN metastasis. Therefore, we aimed to construct a nomogram for predicting LPN metastasis in rectal cancer. We analyzed the risk factors for potential LPN metastasis by logistic regression analysis in 705 patients who underwent primary resection of low rectal cancer. We included patients at 49 institutes of the Japan Society of Laparoscopic Colorectal Surgery between June 2010 and February 2012. Clinicopathological factors and magnetic resonance imaging findings were evaluated. The nomogram performance was assessed using the c-index and calibration plots, and the nomogram was validated using an external cohort. In the univariable logistic regression analysis, age, sex, carcinoembryonic antigen, tumor location, clinical T stage, tumor size, circumferential resection margin (CRM), extramural vascular invasion (EMVI), and the short and long axes of LPN and perirectal lymph node (PRLN) were nominated as risk factors for potential LPN metastasis. We identified a combination of the short axis of LPN, tumor location, EMVI, and short axis of PRLN as optimal for predicting potential LPN metastasis and developed a nomogram using these factors. This model had a c-index of 0.74 and was moderately calibrated and well-validated. This is the first study to construct a well-validated nomogram for predicting potential LPN metastasis in rectal cancer, and its performance was high.

Lateral lymph node (LLN) metastasis in T1 rectal cancer has an incidence of less than 1%. However, its clinical features are largely uncharted. We report a case of LLN metastasis in T1 rectal cancer and review the relevant literature. A 56-year-old female underwent rectal resection for lower rectal cancer 2 years previously (pT1bN0M0). During follow-up, an elevated tumor marker CA19-9 was documented. Enhanced CT and MRI showed a round shape nodule 2 cm in size on the left side of pelvic wall. PET-CT showed high accumulation of FDG in the same lesion, leading to a diagnosis of isolated LLN recurrence. Because no other site of recurrence was detected, surgical resection of the LLN was performed. Microscopic findings were consistent with metastatic lymph node originating from the recent rectal cancer. Adjuvant chemotherapy for six months was given, and patient remains free of recurrent disease seven months after LLN resection. Although LLN recurrence after surgery for T1 rectal cancer is rare, post-surgical follow-up should not be omitted. When LLN metastasis is suspected on CT, MRI and/or PET-CT will be recommended. Surgical resection of LLN metastasis in patients with T1 rectal cancer may lead to favorable outcomes, when recurrence in other areas is not observed.

The Significance of Lateral Lymph Node Metastasis in Low Rectal Cancer: a Propensity Score Matching Study

The lateral pelvic lymph node recurrence after curative resection in rectal cancer has been reported in more than 20% of cases and the lateral pelvic lymph node (LPLN) metastasis is an independent risk factor for local recurrence. A prospective cohort study with diagnosis of lower rectal cancer stages II and III performed to identify the factors with significant correlation with LPLN metastasis was categorised based on the number of positive factors and proposed a risk stratification model to uncover a possible benefit of LPLD in specific patient subgroups. Forty-three patients with lower rectal cancer underwent curative surgery, total mesorectal excision with bilateral lateral pelvic lymph node dissection. Pre-operative, female gender, raised serum CEA (> 5ng/mL), cT4, enlarged mesorectal lymph nodes, borderline enlarged LPLN on MRI, lower location (< 5cm from anal verge), large size (> 5cm) and non-circumferential lesion were significant predictors for LPLN metastasis. Histopathological, higher tumour grade, higher pT and pN stage, and the presence of LVI were significant factors. On cox-proportional hazard model analysis, female gender, large tumour, cT4, enlarged mesorectal lymph nodes, borderline enlarged LPLN, pN1 and positive LVI were associated with significant hazard. In conclusion, a specific group of patients with lower rectal cancer of stages II and III might be have treated with LPND in spite of concurrent chemo-radiation to achieve satisfactory oncological outcome. The proposed stratification grouping is strongly guiding the patient for lateral pelvic lymph node dissection. Further study to prove the oncological advantage of LPND is warranted at large scale.

To evaluate whether lateral pelvic lymph nodes (LNs) in low rectal cancer are metastatic disease or part of regional LNs that are amenable to curative resection. It is highly controversial whether lateral pelvic LNs should be considered as regional or distant disease, although the American Joint Committee on Cancer (AJCC) defines internal iliac LNs as regional LNs of rectal cancer. Data of patients with stage I to III low rectal cancer who underwent curative resection from 1978 to 1998 were extracted from the multi-institutional registry of large bowel cancer in Japan. Patients with only mesorectal LN metastasis were classified as the mesorectal-LN group. Patients with lateral pelvic LN metastasis localized to or extending beyond the internal iliac area were classified as the internal lateral pelvic lymph nodes (LPLN) group and external-LPLN group, respectively. Overall survival (OS) and cancer-specific survival (CSS) were compared between the groups. Lateral pelvic LN dissection was performed in 5789 (50%) of 11,567 patients. Overall, 3905 (34%), 411 (3.6%), and 244 (2.1%) patients were classified as the mesorectal-LN, internal-LPLN, and external-LPLN groups, respectively. When the mesorectal LN group was subdivided as defined by the AJCC, both 5-year OS and CSS were not significantly different between the N2a and internal-LPLN groups (OS: 45% vs 45%, P = 0.9585; CSS: 51% vs 49%, P = 0.5742), and the N2b and external-LPLN groups (OS: 32% vs 29%, P = 0.3342; CSS: 37% vs 34%, P = 0.4347). OS and CSS were significantly better in the external-LPLN group than in stage IV patients who underwent curative resection (OS: 29% vs 24%, P = 0.0240; CSS: 34% vs 27%, P = 0.0117). Lateral pelvic LNs can be considered as regional LNs in low rectal cancer, although metastasis extending beyond the internal iliac area is associated with poorer survival.

530 Background: The current Japanese Classification of Colorectal Carcinoma defines inferior mesenteric lymph nodes (IMLN) and lateral lymph nodes (LLN) as regional lymph nodes in rectal cancer. It states that these lymph nodes should be dissected when performing D3 dissection for rectal cancer. However, there is currently no consensus on the significance of Japanese D3 lymph node dissection in low rectal cancer. A retrospective study involving a large number of patients was conducted. Methods: The subjects were 2,743 patients registered in the multi-institutional registry of the Japanese Society for Cancer of the Colon and Rectum. The data were analyzed for outcomes in R0 cases with IMLN and/or LLN metastasis (IMLN(+)LLN(-) or IMLN(-)LLN(+) or IMLN(+)LLN(+)). Results: In the control group, 67 patients (2.7%) were considered positive for IMLN metastasis, 181 patients (7.4%) for LLN metastasis, and 34 patients (1.4%) for IMLN + LLN metastasis. The outcomes in the R0 cases with IMLN and/or LLN metastasis were 52.8% for 5-year RFS and 63.1% for 5-year OS, which were each better than for R1+R2 cases (5-year RFS 26.2%, p&lt;0.0001; 5-year OS 30.5%, p&lt;0.0001). Including only those with a total of seven or more metastatic lymph nodes, the outcomes in the R0 cases with IMLN and/or LLN metastasis were 53.6% for 5-year RFS and 64.9% for 5-year OS, which did not differ significantly from those for IMLN(-)LLN(-) cases (5-year RFS 54.4%, 5-year OS 55.2%) (RFS: p=0.9718, OS: p=0.4049). Conclusions: We confirmed that cases of IMLN and/or LLN metastasis in low rectal cancer tend to have a large total number of metastatic lymph nodes, but a good outcome can be expected if curative resection can be performed. These results demonstrate the value of radical Japanese D3 lymph node dissection in low rectal cancer with IMLN and/or LLN metastasis.

Accurate diagnosis of lateral lymph node metastasis is a major concern in rectal cancer. Metastasis is not only a poor prognostic factor, but it can also affect decisions about treatment options, such as preoperative chemoradiotherapy and lateral lymph node dissection. The purpose of this review was to assess the diagnostic performance of magnetic resonance imaging and computed tomography for lateral lymph node metastasis in rectal cancer. A literature search was systematically performed using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. All studies in which preoperative magnetic resonance imaging or computed tomography findings involving the lateral lymph nodes were compared with pathologic findings were included. Two authors independently assessed the literature and extracted the data, and any disagreement was resolved by discussion. Pooled sensitivity, specificity, and diagnostic odds ratios were estimated using hierarchical summary receiver-operating characteristic curve analysis. The methodologic quality of the included studies was assessed using the QUADAS-2 tool. Nine studies were included in the meta-analysis of magnetic resonance imaging. The pooled sensitivity, specificity, and diagnostic odds ratio for magnetic resonance imaging were 0.72 [95% confidence interval (CI) 0.66-0.78], 0.80 (95% CI 0.73-0.85), and 10.2 (95% CI 6.4-16.3), respectively. Pooled analyses were not conducted for computed tomography because of the small number of studies (only three could be identified) and the wide range in diagnostic performance between these studies. Magnetic resonance imaging was useful to diagnose lateral lymph node metastasis in rectal cancer, especially due to high specificity.

This study aimed to identify cases in which lateral lymph node (LLN) dissection (LLND) can be excluded by clarifying preoperative factors, including an evaluation of the middle rectal artery (MRA), associated with LLN metastasis. Fifty-five consecutive patients who underwent preoperative positron emission tomography-computed tomography (PET/CT) and total mesorectal excision with LLND for rectal cancer were included. We retrospectively investigated the preoperative clinical factors associated with pathological LLN (pLLN) metastasis. We analyzed the regions of pLLN metastasis using MRA. pLLN metastasis occurred in 13 (23.6%) patients. According to a multivariate analysis, clinical LLN (cLLN) metastasis based on short-axis size and LLN status based on PET/CT were independent preoperative factors of pLLN metastasis. The negative predictive value (NPV) was high (97.1%) in patients evaluated as negative based on PET/CT and cLLN short-axis size. MRA was detected in 24 patients (43.6%) using contrast-enhanced CT, and there was a significant relationship between pLLN metastasis and the presence of MRA. pLLN metastasis in the internal iliac region but not in the obturator region was significantly correlated with the presence of MRA. Combined cLLN metastasis based on short-axis size and PET/CT showed a higher NPV, suggesting this to be a useful method for identifying cases in which LLND can be excluded.

PurposeThis study attempted to establish a combined diagnostic model encompassing visualization of the middle rectal artery (MRA) and other imaging features to improve the diagnostic efficiency of lateral lymph node (LLN) metastasis, which is crucial for clinical decision-making in rectal cancer.MethodOne hundred eleven patients receiving bilateral or unilateral lymph node dissection were enrolled, and 140 cases of LLN status on a certain unilateral pelvic sidewall were selected. Enhanced computed tomography (CT) was used to determine whether MRA was visible. Multivariable regression was used to establish a diagnostic model combining MRA visualization with other imaging features to predict LLN metastasis. Receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to test the diagnostic efficacy for LLN metastasis. Ten-fold cross-validation was completed to internally validate the diagnostic model.ResultsOf the 140 LLNs harvested from 111 patients, 76 were positive and 64 were negative for metastases, respectively. The diagnostic model combining the MRA visualization and lymph node short diameter showed a greater efficiency than a single scale (AUC = 0.945, 95% confidence interval = 0.893–0.976, P < 0.001). The mean cross-validated AUC was 0.869 (95% confidence interval = 0.835–0.903).ConclusionOur results establish a combined diagnostic model with the help of MRA visualization to yield a high diagnostic efficiency of LLN metastasis in rectal cancer.

Lateral lymph node (LLN) metastasis in rectal cancer significantly affects patient treatment and prognosis. This study aimed to comprehensively compare the performance of various predictive models in predicting LLN metastasis. In this retrospective study, data from 152 rectal cancer patients who underwent lateral lymph node (LLN) dissection were collected. The cohort was divided into a training set (n=86) from Tianjin Union Medical Center (TUMC), and two testing cohorts: testing cohort (TUMC) (n=37) and testing cohort from Gansu Provincial Hospital (GSPH) (n=29). A clinical model was established using clinical data; deep transfer learning models and radiomics models were developed using MRI images of the primary tumor (PT) and largest short-axis LLN (LLLN), visible LLN (VLLN) areas, along with a fusion model that integrates features from both deep transfer learning and radiomics. The diagnostic value of these models for LLN metastasis was analyzed based on postoperative LLN pathology. Models based on LLLN image information generally outperformed those based on PT image information. Rradiomics models based on LLLN demonstrated improved robustness on external testing cohorts compared to those based on VLLN. Specifically, the radiomics model based on LLLN imaging achieved an AUC of 0.741 in the testing cohort (TUMC) and 0.713 in the testing cohort (GSPH) with the extra trees algorithm. Data from LLLN is a more reliable basis for predicting LLN metastasis in rectal cancer patients with suspicious LLN metastasis than data from PT. Among models performing adequately on the internal test set, all showed declines on the external test set, with LLLN_Rad_Models being less affected by scanning parameters and data sources.

3551 Background: The tumor-node-metastasis staging system by the American Joint Committee on Cancer defines internal iliac lymph nodes (LNs) as regional, and the other lateral pelvic LNs as distant in rectal cancer. However, the prognostic differences according to the extent of lateral pelvic LN metastasis are unknown. Methods: Data of all patients with stage I to III low rectal cancer who underwent curative resection from 1978 to 1998 were extracted from the Multi-Institutional Registry of Large-Bowel Cancer in Japan. Overall survival (OS) and cancer-specific survival (CSS) were compared between patients with only mesorectal LN metastasis (mesorectal-LN), lateral pelvic LN metastasis localized to the internal iliac area (internal-LPLN), and lateral pelvic LN metastasis extending beyond the internal iliac area (external-LPLN). Results: Among 11,567 patients, lateral pelvic LN dissection was performed in 5,789 (50%) patients. Mesorectal-LN, internal-LPLN, and external-LPLN were identified in 3,905 (34%), 411 (3.6%), and 244 (2.1%) patients, respectively. OS and CSS became significantly poorer with advancement of the LN metastatic level. When the mesorectal LN group was subdivided as defined by AJCC (N1a: 1 regional LN metastasis; N1b: 2–3 metastases; N2a: 4–6 metastases; N2b: ≥7 metastases), both OS and CSS were not significantly different between the N2a and internal-LPLN groups (p = 0.9585 for OS and 0.5742 for CSS), or the N2b and external-LPLN groups (p = 0.3342 for OS and 0.4347 for CSS). OS and CSS were significantly better in the external-LPLN group than in 260 patients with stage IV low rectal cancer who underwent curative resection (p = 0.0240 for OS and 0.0117 for CSS). Conclusions: Lateral pelvic LNs can be considered as regional LNs in low rectal cancer, although metastasis extending beyond the internal iliac area is associated with poorer survival.

In the surgical treatment for lower rectal cancer, preoperative selection of patients at high risk for lateral lymph node metastasis is important, since lateral lymph node dissection might impair genitourinary functions. We examined whether the status of lateral lymph node metastasis can be predicted from the lymph node size. The subjects were 533 (35 positive and 498 negative) lateral lymph nodes from 47 patients with lower rectal cancer who underwent curative resection with lateral lymph node dissection. The sizes of the lateral lymph nodes immediately after removal and those in paraffin-embedded sections were compared for 108 lateral lymph nodes from 13 patients. In addition, receiver-operating characteristic curves were generated for the 533 paraffin-embedded lateral lymph nodes from the 47 patients to determine the optimal cut-off size for discriminating between positive and negative lateral lymph nodes. Irrespective of the presence/absence of metastasis and the long-/short-axis diameter, a positive relationship was noted between the sizes of the lateral lymph nodes measured immediately after removal and those measured on paraffin-embedded sections (P< 0.01). The area under the curve for the short-axis diameter differed little from that for the long-axis diameter (0.77 vs. 0.76, P =0.80). The optimal cut-off values of the short- and long-axis diameter extrapolated to the living body were 5.4 and 8.4 mm, respectively, with an accuracy of 72.8% for the short-axis diameter and 71.9% for the long-axis diameter. Prediction of the status of lateral lymph node metastasis from the lymph node size (long-/short-axis diameter) may be a simple and reliable method. The optimal cut-off diameter should be validated in prospective imaging studies.

To evaluate the prognostic value of lateral pelvic lymph node metastasis on low rectal cancer. One hundred and seventy-six patients with low rectal cancer who underwent radical resection combined with lateral pelvic lymph node dissection between 1994 and 2005 were reviewed. The data of the cases was investigated to define the prognostic value of lateral pelvic lymph node metastasis on the patients. Lateral node metastasis occurred in 33 patients (18.8%), and 51.5% of the metastasis occurred in internal iliac nodes or nodes at middle rectal roots and 39.4% in obturator nodes. Age < or =40 years, infiltrative cancer, T34 tumor, upward lymph node metastasis were risk factors for lateral node metastasis in low rectal cancer (P < 0.05). The overall 5-year survival rate was 64.1%, and it was 94.1%, 79.1%, 42.1% for patients with TNM stage I, II, III cancer, respectively. Tumor size, depth of infiltration, upward lymph node metastasis, lateral node metastasis was correlated significantly with prognosis (P < 0.05). The 5-year survival rate of the patients without lateral metastasis was 73.6%, which was significant higher than that of patients with lateral metastasis (21.4%, P < 0.05). Lateral pelvic lymph node metastasis is an important prognostic factor for low rectal cancer.

The present study presented a 35-year-old female patient in whom fecal occult blood was detected in a medical check-up. Colonoscopy revealed a superficial elevated-type tumor with central depression in the lower rectum. The tumor was diagnosed as T1 deep invasive cancer. No swollen lymph nodes or distant metastasis were found on computed tomography or [18F]-fluorodeoxyglucose-positron emission tomography with computed tomography. However, a swollen right lateral pelvic lymph node (LPLN; short axis 4 mm) was revealed on magnetic resonance imaging (MRI). This lymph node exhibited high intensity on diffusion-weighted imaging (DWI), suggesting metastasis. Low anterior resection, regional lymph node dissection and right LPLN dissection (LPLD) were performed. Histological analysis revealed metastasis in the right LPLN, as suggested by the high DWI intensity. The indication for LPLD in the current Japanese guidelines is based on the tumor location and depth of invasion (≥T3), however, not on the status of LPLN metastasis in pre-operative evaluation. The present case was cT1, which is not included in this indication. DWI is sensitive for the diagnosis of lymph node metastasis of colorectal cancer, although inflammation-induced swelling of lymph nodes in advanced rectal cancer may cause a false-positive result, which is uncommon in T1 cases. Therefore, an LPLN with a high intensity DWI signal in T1 cases is likely to be metastasis-positive. Pre-operative DWI-MRI may be useful for identifying LPLN metastasis when planning the treatment strategy in these cases. The present study suggested reinvestigation of the indication for LPLD with inclusion of LPLN status on pre-operative imaging.