• biomarkers
• molecular targeted treatment
• predictive markers
• prognostic marker

• Colorectal cancer
• Cox regression analyses
• Lymph nodes
• Overall survival
• T stage

• Anastomosis stricture
• Minimally invasive
• Rectal surgery
• Robotic surgery
• Splenic flexure mobilization
• Surgical technique

• Humans
• Anastomosis, Surgical/adverse effects
• Anastomosis, Surgical/methods
• Cohort Studies
• Colon, Transverse/surgery
• Constriction, Pathologic/surgery
• Laparoscopy/methods
• Rectal Neoplasms/surgery
• Retrospective Studies
• Robotic Surgical Procedures/methods

• Delphi
• colorectal neoplasms
• quality indicators
• quality of care
• systematic review

• Humans
• Colorectal Neoplasms/therapy
• Delphi Technique
• Quality Indicators, Health Care
• Patient Care Team/standards
• Australia

• Radiation Oncology Network, Western Sydney Local Health District
• 15/TRC/1-01 Sydney West Translational Cancer Research Centre, The Cancer Institute NSW, Translational Cancer Research Centres

• abdominoperineal amputation
• low anterior resection
• lymph nodes
• rectal cancer

• Gastrectomy
• Gastric carcinoma
• Lymphadenectomy
• Micro lymph node metastasis
• Prognosis

• 2019012 The Cultivating Outstanding Talents Project of Hebei Provincial Government Fund
• 2019024 Hebei public health committee county-level public hospitals suitable health technology promotion and storage project
• 2020CGPY-12,2020CHYB-23 Hebei Medical University Education and Teaching Research Project
• ZD2019139 Hebei University Science and Technology Research Project

• Nomogram
• Non-metastatic
• Prediction
• Rectal adenocarcinoma
• Survival prediction

Neoadjuvant chemoradiotherapy (nCRT) and total rectal mesenteric excision are the main standards of treatment for locally advanced rectal cancer (LARC). Lymph node regression grade (LRG) is an indicator of prognosis and response to preoperative nCRT based on postsurgical metastatic lymph node pathology. Common histopathological findings in metastatic lymph nodes after nCRT include necrosis, hemorrhage, nodular fibrosis, foamy histiocytes, cystic cell reactions, areas of hyalinosis, residual cancer cells, and pools of mucin. A number of LRG systems designed to classify the amount of lymph node regression after nCRT is mainly concerned with the relationship between residual cancer cells and regressive fibrosis and with estimating the number of lymph nodes existing with residual cancer cells. LRG offers significant prognostic information, and in most cases, LRG after nCRT correlates with patient outcomes. In this review, we describe the systematic classification of LRG after nCRT, patient prognosis, the correlation with tumor regression grade, and the typical histopathological findings of lymph nodes. This work may serve as a reference to help predict the clinical complete response and determine lymph node regression in patients based on preservation strategies, allowing for the formulation of more accurate treatment strategies for LARC patients, which has important clinical significance and scientific value.

• Lymph node regression grade
• Histopathological
• Rectal cancer
• Chemoradiotherapy
• Treatment response
• Neoadjuvant therapy

• Disease-free survival
• Lymph node ratio
• Overall survival
• Preoperative radiotherapy
• Rectal cancer

• lymph node yield
• neoadjuvant therapy
• quality
• rectal cancer
• survival

• chemoradiotherapy
• disease-free survival
• lymph nodes
• rectal cancer
• survival

Neoadjuvant chemoradiotherapy (NCRT) results in fewer lymph nodes harvested and causes staging migration. Therefore, we compared the prognostic value of the logarithmic odds of positive lymph nodes (LODDS) with the lymph node ratio (LNR) and the American Joint Committee on Cancer (AJCC) ypN stage in patients with locally advanced rectal cancer (LARC) after NCRT.

A total of 445 patients with LARC who received NCRT and underwent radical surgery between January 2004 and December 2015 were recruited, and data from 4881 patients included in the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2013 were analyzed to verify our results. The time-dependent area under the receiver operating characteristic curve (TimeROC) was used to evaluate the discriminative ability of the different lymph node staging systems.

ypN staging failed to satisfactorily stratify the patients treated with NCRT [the 3-year disease-free survival (DFS) rates were 65.7% and 55.4% for the ypN1 and ypN2 groups, respectively, P=0.252]. The LODDS classification was significantly associated with DFS, and the 3-year DFS rates for the LODDS0, LODDS1, and LODDS2 groups were 89.9%, 72.4%, and 53.9%, respectively (P<0.05 across all groups). Furthermore, the LODDS classification system was able to subclassify patients with ypN0 stage tumors regardless of whether ≥12 or <12 total lymph nodes (TLNs) were harvested. TimeROC analysis showed that the LODDS classification (AUC, median: 0.722, range: 0.692–0.754) had a higher accuracy for determining the prognosis than the ypN stage (AUC, median: 0.691, range: 0.684–0.712) or the LNR (AUC, median: 0.703, range: 0.685–0.730) classification, regardless of lymph node status. These results were verified using the SEER database.

The LODDS was a better prognostic factor for DFS than ypN staging or the LNR-based approach in patients with LARC after NCRT, particularly those with <12 TLNs harvested or ypN0 stage disease.

• Logarithmic odds of positive lymph nodes (LODDS)
• lymph node ratio (LNR)
• neoadjuvant chemoradiotherapy (NCRT)
• staging

Nomograms for prognosis prediction in colorectal cancer patients are few, and prognostic indicators differ with age.

To construct a new nomogram survival prediction tool for middle-aged and elderly patients with stage III rectal adenocarcinoma.

A total of 2773 eligible patients were divided into the training cohort (70%) and the validation cohort (30%). Optimal cutoff values were calculated using the X-tile software for continuous variables. Univariate and multivariate Cox proportional hazards regression analyses were used to determine overall survival (OS) and cancer-specific survival (CSS)-related prognostic factors. Two nomograms were successfully constructed. The discriminant and predictive ability and clinical usefulness of the model were also assessed by multiple methods of analysis.

The 95%CI in the training group was 0.719 (0.690-0.749) and 0.733 (0.702-0.74), while that in the validation group was 0.739 (0.696-0.782) and 0.750 (0.701-0.800) for the OS and CSS nomogram prediction models, respectively. In the validation group, the AUC of the three-year survival rate was 0.762 and 0.770, while the AUC of the five-year survival rate was 0.722 and 0.744 for the OS and CSS nomograms, respectively. The nomogram distinguishes all-cause mortality from cancer-specific mortality in patients with different risk grades. The time-dependent AUC and decision curve analysis showed that the nomogram had good clinical predictive ability and decision efficacy and was significantly better than the tumor-node-metastases staging system.

The survival prediction model constructed in this study is helpful in evaluating the prognosis of patients and can aid physicians in clinical diagnosis and treatment.

• Rectal adenocarcinoma
• Lymph node positive rate
• Nomogram
• Prognostic model
• Predictive model
• Survival time

• lymph node
• neoadjuvant chemoradiotherapy
• prognostic factor
• rectal cancer
• ypT0

• Lymph node retrieval
• Neoadjuvant therapy
• Prognosis
• Rectal cancer
• Survival analysis
• Tumor-node-metastasis stage

The current TNM staging system uses the same category definitions for both rectal cancer patients with and without neoadjuvant chemoradiotherapy (NCRT). However, ypTNM stage, especially ypN stage does not predict patient survival after NCRT well. Whether tumor regression in lymph nodes (LRG) may improve the prediction has not been well studied. In total, 358 patients with rectal cancer who received NCRT followed by radical resection were recruited from 2004 to 2015, and the median follow‐up time was 57.5 months. The main outcome measure was disease‐free survival (DFS). In univariate analysis, factors associated with DFS were ypT stage, ypN stage, number of negative lymph nodes (NLN), lymph node ratio (LNR), tumor regression grade (TRG), M‐TTRG (modified ypT stage by combining ypT stage and TRG), maximum LRG (LRGmax), sum score of LRG (LRGsum), LRG ratio (average value of LRGsum), and M‐NLRG (modified ypN stage by combining LRGmax and LNR). In the multivariate Cox regression analysis, M‐TTRG and M‐NLRG (p < 0.001 and p = 0.030, respectively) were significantly associated with DFS. The estimated 5‐year DFS rates were 86.6%, 60.3%, and 36.4% for patients with M‐NLRG‐0, M‐NLRG‐1, and M‐NLRG‐2, respectively (p < 0.001). A significant difference in survival was observed among patients with NCRT after incorporating TRG and LRG simultaneously into the current ypTNM staging system (p < 0.001). LRG was an important prognostic factor in rectal cancer patients treated with NCRT and could refine the ypTNM staging system. The modified ypTNM staging system in combination with LRGmax, LNR, and TRG could improve the DFS prediction in each subset of patients.

• lymph node regression
• neoadjuvant chemoradiotherapy
• prognosis
• rectal cancer
• tumor regression grade

• Adult
• Aged
• Aged, 80 and over
• Carcinoma/mortality
• Carcinoma/pathology
• Carcinoma/therapy
• Chemoradiotherapy, Adjuvant
• Female
• Follow-Up Studies
• Humans
• Kaplan-Meier Estimate
• Lymph Node Excision
• Lymph Nodes/pathology
• Lymph Nodes/surgery
• Male
• Middle Aged
• Morocco
• Neoadjuvant Therapy
• Proctectomy
• Prognosis
• Rectal Neoplasms/mortality
• Rectal Neoplasms/pathology
• Rectal Neoplasms/therapy
• Retrospective Studies
• Survival Analysis
• Young Adult

Lymph node status can predict the prognosis of patients with rectal cancer treated with surgery. Thus, we sought to establish a standard for the minimum number of lymph nodes (LNs) examined in patients with rectal cancer by evaluating the probability that pathologically negative LNs prove positive during surgery.

We extracted information of 31,853 patients with stage I–III rectal carcinoma registered between 2004 and 2013 from the Surveillance, Epidemiology, and End Results database and divided them into two groups: the first group was SURG, including patients receiving surgery directly and the other group was NEO, encompassing those underwent neo-adjuvant therapy. Using a beta-binomial model, we developed nodal staging score (NSS) based on pT/ypT stage and the number of LNs retrieved.

In both cohorts, the false-negative rate was estimated to be 16% when 12 LNs were examined, but it dropped to 10% when 20 LNs were evaluated. In the SURG cohort, to rule out 90% possibility of false staging, 3, 7, 28, and 32 LNs would be necessarily examined in patients with pT1–4 disease, respectively. While in the NEO cohort, 4, 7, 12, and 16 LNs would be included for examination in patients with ypT1–4 disease to guarantee an NSS of 90%.

By determining whether a rectal cancer patient with negative LNs was appropriately staged, the NSS model we developed in this study may assist in tailoring postoperative management.

• beta-binomial model
• lymph node
• neoadjuvant therapy
• nodal staging score
• rectal cancer

• Irradiated rectal cancer
• Lymph node yeld
• Neoadjuvant radiation therapy
• Rectal cancer

• Adenocarcinoma/diagnosis
• Adenocarcinoma/surgery
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Digestive System Surgical Procedures/methods
• Female
• Follow-Up Studies
• Humans
• Lymph Nodes/pathology
• Lymph Nodes/surgery
• Male
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Staging
• Prognosis
• Rectal Neoplasms/diagnosis
• Rectal Neoplasms/therapy
• Retrospective Studies
• Societies, Medical
• Surgical Oncology
• Young Adult

• false-negative rate
• lymph node
• rectal cancer
• tumour stage

• Colorectal cancer staging
• Neoadjuvant
• Prognostic features
• TNM

• Colon/pathology
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/pathology
• Humans
• Lymphatic Metastasis
• Neoplasm Invasiveness
• Neoplasm Staging

• Lymph node yield
• Lymphadenectomy
• Neoadjuvant chemoradiation
• Rectal adenocarcinoma
• Total mesorectal excision

According to the current official guidelines, at least 12 lymph nodes (LNs) are qualified as an adequate sampling for colon cancer patients. However, patients evaluated with less nodes were still common in the United States, and the prevalence of positive nodal disease may be under-estimated because of the false-negative assessment. In this study, we present a statistical model that allows preoperative determination of the minimum number of lymph nodes needed to confirm a node-negative disease with certain confidence.

Adenocarcinoma colon cancer patients with stage T1-T3, diagnosed between 2004 and 2013, who did not receive neoadjuvant therapies and had at least one lymph node pathologically examined, were extracted from the Surveillance, Epidemiology and End Results (SEER) database. A beta binomial distribution was used to estimate the probability of an occult nodal disease is truly node-negative as a function of total number of LNs examined and T stage.

A total of 125,306 patients met study criteria; and 47,788 of those were node-positive. The probability of falsely identifying a patient as node-negative decreased with an increasing number of nodes examined for each stage, and was estimated to be 72% for T1 and T2 patients with a single node examined and 57% for T3 patients with a single node examined. To confirm an occult nodal disease with 90% confidence, 3, 8, and 24 nodes need to be examined for patients from stage T1, T2, and T3, respectively.

The false-negative rate of diagnosed node negative, together with the minimum number of examined nodes for adequate staging, depend preoperatively on the clinical T stage. Predictive tools can recommend a threshold on the minimum number of examined nodes regarding to the favored level of confidence for each T stage.

The online version of this article (doi:10.1186/s12885-017-3491-2) contains supplementary material, which is available to authorized users.

• Colon cancer
• False-negative rate
• Lymph node
• Tumor stage

• Chemoradiotherapy
• Lymph node
• Rectal cancer
• Tattooing

• Chemoradiotherapy
• Neoadjuvant therapy
• Rectal cancer
• Recurrence

• Colon cancer
• Lymph node
• Multivariate analysis
• Prognostic factor
• Rectum cancer

• HEALTH SERVICES RES
• LYMPH NODES
• RECTAL CANCER
• SURGERY
• SURGICAL PATHOLOGY

• Rectal carcinoma
• lymph node yield
• mesorectal excision
• pre-operative chemo-radiotherapy
• tumor regression

• Local recurrence
• Oncologic outcome
• Rectal cancer
• Survival

• Circumferential resection margins
• Minimally invasive surgery
• Rectal cancer
• Robotic surgery
• Total mesorectal excision

• chemoradiotherapy
• outcome prediction
• pathologic stage
• rectal cancer

• Lymph nodes metastases
• Mesorectum
• Radiochemotherapy
• Rectal cancer
• Tumor deposits

Lymph node staging is of crucial importance for the therapy stratification and prognosis estimation in colon cancer. Beside the detection of metastases, the number of harvested lymph nodes itself has prognostic relevance in stage II/III cancers. A stage migration effect caused by missed lymph node metastases has been postulated as most likely explanation for that. In order to avoid false negative node staging reporting of at least 12 lymph nodes is recommended. However, this threshold is met only in a minority of cases in daily practice. Due to quality initiatives the situation has improved in the past. This, however, had no influence on staging in several studies. While the numbers of evaluated lymph nodes increased continuously during the last decades the rate of node positive cases remained relatively constant. This fact together with other indications raised doubts that understaging is indeed the correct explanation for the prognostic impact of lymph node harvest. Several authors assume that immune response could play a major role in this context influencing both the lymph node detectability and the tumor’s behavior. Further studies addressing this issue are need. Based on the findings the recommendations concerning minimal lymph node numbers and adjuvant chemotherapy should be reconsidered.

• Colon cancer
• Lymph node harvest
• Stage migration
• Understaging
• Will Rogers
• Immune response

• Colonic Neoplasms/immunology
• Colonic Neoplasms/pathology
• Colonic Neoplasms/surgery
• Humans
• Lymph Node Excision/trends
• Lymph Nodes/immunology
• Lymph Nodes/pathology
• Lymph Nodes/surgery
• Lymphatic Metastasis
• Neoplasm Staging/methods
• Neoplasm Staging/trends
• Observer Variation
• Practice Patterns, Physicians'/trends
• Predictive Value of Tests
• Reproducibility of Results

AIM: To establish the association between lymph node involvement and the response to neoadjuvant therapy in locally advanced rectal cancer.

METHODS: Data of 130 patients with mid and low locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation followed by radical surgery over a 5-year period were reviewed. Tumor staging was done by endorectal ultrasound and/or magnetic resonance imaging. Tumor response to neoadjuvant therapy was determined by T-downstaging and tumor regression grading (TRG). Pathologic complete response (pCR) is defined as the absence of tumor cells in the surgical specimen (ypT0N0). The varying degrees TRG were classified according to Mandard’s scoring system. The evaluation of the response is based on the comparison between previous clinico-radiological staging and the results of pathological evaluation. χ² and Spearman’s correlation tests were used for the comparison of variables.

RESULTS: Pathologic complete response (pCR, ypT0N0, TRG1) was observed in 19 cases (14.6%), and other 18 (13.8%) had only very few residual malignant cells in the rectal wall (TRG2). T-downstaging was found in 63 (48.5%). Mean lymph node retrieval was 9.4 (range 0-38). In 37 cases (28.5%) more than 12 nodes were identified in the surgical specimen. Preoperative lymph node involvement was seen in 77 patients (59.2%), 71 N1 and 6 N2. Postoperative lymph node involvement was observed in 41 patients (31.5%), 29 N1 and 12 N2, while the remaining 89 were N0 (68.5%). In relation to ypT stage, we found nodal involvement of 9.4% in ypT0-1, 22.2% in ypT2 and 43.7% in ypT3-4. Of the 37 patients considered “responders” to neoadjuvant therapy (TRG1 and 2), there were only 4 N+ (10.8%) and the remainder N0 (89.2%). In the “non responders” group (TRG 3, 4 and 5), 37 cases were N+ (39.8%) and 56 (60.2%) were N0 (P < 0.001).

CONCLUSION: Response to neoadjuvant chemoradiation in rectal cancer is associated with lymph node involvement.

• Response to treatment
• Neoadjuvant therapy
• Rectal cancer
• Chemoradiotherapy
• Lymph node involvement

• Adult
• Aged
• Chemoradiotherapy
• Digestive System Surgical Procedures/standards
• Digestive System Surgical Procedures/statistics & numerical data
• Female
• Humans
• Lymph Node Excision/standards
• Lymph Node Excision/statistics & numerical data
• Lymph Nodes/pathology
• Male
• Middle Aged
• Neoadjuvant Therapy
• Rectal Neoplasms/drug therapy
• Rectal Neoplasms/pathology
• Rectal Neoplasms/surgery
• Retrospective Studies