• colon cancer
• surgical oncology

• Humans
• Colonic Neoplasms/pathology
• Colonic Neoplasms/mortality
• Colonic Neoplasms/surgery
• Female
• Male
• Prognosis
• Lymph Nodes/pathology
• Aged
• Middle Aged
• Lymphatic Metastasis/pathology
• Retrospective Studies
• SEER Program
• Adenocarcinoma/pathology
• Adenocarcinoma/mortality
• Lymph Node Excision
• Neoplasm Staging
• Aged, 80 and over
• Biomarkers, Tumor
• Adult

• C14094/A27178 Cancer Research UK (CRUK)

• Colonic neoplasms
• Lymph node ratio
• Lymph nodes
• Neoplasm staging
• Prognosis

• Colonic neoplasms
• Diagnosis
• Genetics
• Humans
• Therapy

• Colorectal carcinoma
• Lymph node harvesting
• Nodal staging

• Humans
• Methylene Blue
• Lymph Nodes/surgery
• Elective Surgical Procedures
• Neoadjuvant Therapy
• Transforming Growth Factor beta
• Colorectal Neoplasms/surgery

• colon cancer
• five-year overall survival
• lymph node ratio
• lymph node yield
• lymph nodes

• cancer microenvironment
• immunoediting

• Humans
• Lymph Nodes/pathology
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/surgery
• Colonic Neoplasms/pathology
• Prognosis
• Lymph Node Excision
• Tumor Microenvironment
• Neoplasm Staging

• P30 DK043351 NIDDK NIH HHS

• Age
• Colectomy
• Colon cancer
• Lymph node
• Obesity

• Humans
• Aged
• Middle Aged
• Robotic Surgical Procedures/methods
• Colonic Neoplasms/surgery
• Colectomy
• Laparoscopy
• Retrospective Studies
• Obesity/complications
• Obesity/surgery
• Treatment Outcome

• Colorectal cancer
• lymph node yield
• pathological staging

• Humans
• Male
• Middle Aged
• Female
• Lymph Node Excision/methods
• Neoplasm Staging
• Lymphatic Metastasis/pathology
• Lymph Nodes/surgery
• Lymph Nodes/pathology
• Colorectal Neoplasms/surgery
• Colorectal Neoplasms/pathology
• Retrospective Studies

• colon cancer
• immune response
• lymph node harvest
• lymph node ratio
• total positive lymph nodes

• U54 GM104938 NIGMS NIH HHS

• Colon cancer
• Complete mesocolic excision
• D2 standard lymphadenectomy
• D3 lymphadenectomy
• Right colectomy
• Surgery

• Carcinoma, Renal Cell/surgery
• Colectomy
• Colonic Neoplasms
• Humans
• Kidney Neoplasms/surgery
• Laparoscopy
• Lymph Node Excision
• Lymphatic Metastasis
• Neoplasm Recurrence, Local/surgery
• Retrospective Studies

• Università di Pisa

• Colonic neoplasms
• Cutoff value
• Lymph node yield
• Prognosis
• Survival

• colorectal cancer
• molecular markers
• pathological features
• prognosis
• survival

• Colorectal Neoplasms/pathology
• Humans
• Lymph Nodes/pathology
• Neoplasm Staging
• Prognosis

• Lymph node ratio
• Penile squamous cell carcinoma
• Positive lymph node count
• SEER

• Carcinoma, Squamous Cell/pathology
• Humans
• Lymph Node Ratio
• Lymph Nodes/pathology
• Male
• Middle Aged
• Neoplasm Staging
• Penile Neoplasms/pathology
• Prognosis
• SEER Program

• cancer-specific survival
• colon cancer
• mediation analysis
• overall survival
• propensity score analysis
• sentinel lymph node

• adjuvant therapy
• colon cancer
• microsatellite instability (MSI)
• prognostic and predictive value
• tumor-infiltrating lymphocytes (TILs)

• Animals
• Colonic Neoplasms/genetics
• Colonic Neoplasms/immunology
• Colonic Neoplasms/pathology
• Humans
• Immunity/immunology
• Lymphocytes, Tumor-Infiltrating/immunology
• Microsatellite Instability

• AIRC IG 2014 Id.16092 AIRC Associazione Italiana Ricerca sul Cancro

Assessing lymph node (LN) status during tumor resection is fundamental for the staging of colorectal cancer. Current guidelines require a minimum of 12 LNs to be harvested during resection and ultra-staging regional lymph nodes by sentinel lymph node (SLN) assessment is being extensively investigated. The current study presents novel near-infrared (NIR) fluorescent dyes for simultaneous pan lymph node (PanLN; regional) and SLN mapping. PanLN-Forte was intravenously injected in mice and assessed for accumulation in regional LNs. SLN800 was injected intradermally in mice, after which the collection and retention of fluorescence in SLNs were measured using indocyanine green (ICG) and its precursor, SLN700, as references. LNs in the cervical, inguinal, jejunal, iliac, and thoracic basins could clearly be distinguished after a low dose intravenous injection of PanLN-Forte. Background fluorescence was significantly lower compared to the parent compound ZW800-3A (p < 0.001). SLN700 and SLN800 specifically targeted SLNs with fluorescence being retained over 40-fold longer than the current clinically used agent ICG. Using SLN700 and SLN800, absolute fluorescence in SLN was at least 10 times higher than ICG in second-tier nodes, even at 1 hour post-injection. Histologically, the fluorescent signal localized in the LN medulla (PanLN-Forte) or sinus entry (SLN700/SLN800). PanLN-Forte and SLN800 appear to be optimal for real-time NIR fluorescence imaging of regional and SLNs, respectively.

• ZW800
• cancer staging
• fluorescence
• image-guided surgery
• indocyanine green

• Lymph node yield
• Nodal staging
• Right-sided colon cancer
• SEER database
• Survival

Supplemental digital content is available in the text.

The aim of this study was to use 7 T ex vivo magnetic resonance imaging (MRI) scans to determine the size of lymph nodes (LNs) in total mesorectal excision (TME) specimens and to increase the pathological yield of LNs with MR-guided pathology.

This study aimed to identify possible patient- and tumor-related factors associated with risk of TNM stage III disease in nonmetastatic colon cancer.

The associations between stage III disease and age, sex, lymph node yield, pathological tumor (pT) stage, tumor subsite, type of surgery, and priority of surgery were assessed in a nationwide cohort of 13,766 patients treated with curative resection of colon cancer. Each level of age, lymph node yield, and pT stage was compared to the preceding level.

Age, lymph node yield, pT stage, tumor subsite, and priority of surgery were associated with stage III disease. Odds ratios (95% confidence interval [CI]) were as follows: age < 65/65–75 years: 1.28 (95% CI, 1.15–1.43) and 65–75/ > 75 years: 1.22 (95% CI, 1.13–1.32); lymph node yield 0–5/6–11: 0.60 (95% CI, 0.50–0.72), lymph node yield 6–11/12–17: 0.84 (95% CI, 0.76–0.93), and lymph node yield 12–17/ ≥ 18: 0.97 (95% CI, 0.89–1.05); pT1/pT2: 0.74 (95% CI, 0.57–0.95), pT2/pT3: 0.35 (95% CI, 0.30–0.40), and pT3/pT4: 0.49 (95% CI, 0.47–0.54). Only tumors of the transverse colon were independently associated with lower risk of stage III disease than tumors in the sigmoid colon (sigmoid colon: 1, transverse colon: 0.84 [95% CI, 0.73–0.96]; elective surgery: 1, acute surgery: 1.43 [95% CI, 1.29–1.60]).

In this study, stage III disease in colon cancer was significantly associated with age, lymph node yield, pT stage, tumor subsite, and priority of surgery but was not associated with right-sided location compared with stage I and II cancers.

• Colonic neoplasms
• Lymph nodes
• Neoplasm staging
• Tumor subsite

• Adequacy of lymphadenectomy
• CME
• Cancer
• Cancer staging
• Colectomy
• Colorectal
• Colorectal cancer surgery
• Colorectal malignancy
• Lymphadenectomy
• Prognostic factors
• Surgical oncology

• Aged, 80 and over
• Colectomy/methods
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/secondary
• Colorectal Neoplasms/surgery
• Female
• Humans
• Lymph Node Excision/methods
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Male
• Neoplasm Staging
• Postoperative Period
• Prognosis
• Prospective Studies

According to the American Joint Committee on Cancer staging for cancer of the colon, a minimum of 12 lymph nodes (LN) has to be sampled for accurate staging. This has bearing on the long-term prognosis and the need for adjuvant chemotherapy. The aim of this study was to revisit the association of lymph node yield and the long-term survival in patients with stages I and II, i.e. node-negative, colon cancer.

Consecutive patients who underwent elective or emergency curative resections for cancer of colon between the years 2003 and 2012 were retrospectively reviewed. Only patients with stage I or II diseases (AJCC 8th edition) were included. They were analysed in three groups, LN<12, LN12-19 and LN≥20. Their clinic-pathological characteristics were compared. The disease-free (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with the log-rank test.

There was a total of 659 patients included in the analysis. Twelve or more LN were found in 65.6% of the specimens. The mean follow-up was 83.9 months. LN≥20 had significantly better DFS (p = 0.015) and OS (p = 0.036), whereas LN<12 had similar DFS and OS when compared to LN12-19. The advantage in DFS and OS were mainly seen in those with stage II diseases. A lymph node yield of greater than 20 was one of the predictors of favourable DFS, hazard ratio 0.358; 95% CI 0.170–.756, p = 0.007.

The lymph node yield had a significant association with survival outcomes. A lymph node yield of 20 or more was associated with better survival outcomes. On the other hand, lymph node yield less than 12 was not shown to have inferior survival outcomes when compared to those between 12 and 19.

• Colon cancer
• Lymph node
• Survival

• Deep cervical fascia
• Head and neck surgery
• Lingual lymph node
• Neck dissection
• Oral cancer

• Central lymph node
• Colon cancer
• Location of lymph node
• Lymph node ratio

• Aged
• Colonic Neoplasms/diagnosis
• Colonic Neoplasms/secondary
• Colonic Neoplasms/surgery
• Disease-Free Survival
• Female
• Humans
• Lymph Node Excision
• Lymph Nodes/pathology
• Lymph Nodes/surgery
• Lymphatic Metastasis
• Male
• Mesentery
• Neoplasm Staging/methods
• Prognosis
• Retrospective Studies

Lymph node yield (LNY) of 12 or more in resection of colorectal cancer is recommended in current international guidelines. Although a low LNY (less than 12) is associated with poorer outcome in some studies, its prognostic value is unclear in patients with early‐stage colorectal or rectal cancer with a complete pathological response following neoadjuvant therapy. Lymph node ratio (LNR), which reflects the proportion of positive to total nodes obtained, may be more accurate in predicting outcome in stage III colorectal cancer. This study aimed to identify factors correlating with LNY and evaluate the prognostic role of LNY and LNR in colorectal cancer.

An observational study was performed on patients with colorectal cancer treated at three hospitals in Melbourne, Australia, from January 2010 to March 2016. Association of LNY and LNR with clinical variables was analysed using linear regression. Disease‐free (DFS) and overall (OS) survival were investigated with Cox regression and Kaplan–Meier survival analyses.

Some 1585 resections were analysed. Median follow‐up was 27·1 (range 0·1–71) months. Median LNY was 16 (range 0–86), and was lower for rectal cancers, decreased with increasing age, and increased with increasing stage. High LNY (12 or more) was associated with better DFS in colorectal cancer. Subgroup analysis indicated that low LNY was associated with poorer DFS and OS in stage III colonic cancer, but had no effect on DFS and OS in rectal cancer (stages I–III). Higher LNR was predictive of poorer DFS and OS.

Low LNY (less than 12) was predictive of poor DFS in stage III colonic cancer, but was not a factor for stage I or II colonic disease or any rectal cancer. LNR was a predictive factor in DFS and OS in stage III colonic cancer, but influenced DFS only in rectal cancer.

• Colon cancer
• lymph nodes
• mesocolic excision
• robotic surgery

• Colon cancer
• lymph node yield
• population studies
• survival factors

Increased lymph node count (LNC) has been associated with prolonged survival in colorectal cancer (CRC), but the underlying mechanisms are still poorly understood. The study aims to identify new predictors and develop a preoperative nomogram for predicting the probability of adequate LNC (≥ 12). 501 eligible patients were retrospectively selected to identify clinical-pathological factors associated with LNC ≥ 12 through univariate and multivariate logistic regression analyses. The nomogram was built according to multivariate analyses of preoperative factors. Model performance was assessed with concordance index (c-index) and area under the receiver operating characteristic curve (AUC), followed by internal validation and calibration using 1000-resample bootstrapping. Clinical validity of the nomogram and LNC impact on stage migration were also evaluated. Multivariate analyses showed patient age, CA19-9, circulating lymphocytes, neutrophils, platelets, tumor diameter, histology and deposit significantly correlated with LNC (P < 0.05). The effects were marginal for CEA, anemia and CRC location (0.05 < P < 0.1). The multivariate analyses of preoperative factors suggested decreased age, CEA, CA19-9, neutrophils, proximal location, and increased platelets and diameter were significantly associated with increased probability of LNC ≥ 12 (P < 0.05). The nomogram achieved c-indexes of 0.75 and 0.73 before and after correction for overfitting. The AUC was 0.75 (95% CI, 0.70–0.79) and the clinically valid threshold probabilities were between 10% and 60% for the nomogram to predict LNC < 12. Additionally, increased probability of adequate LNC before surgery was associated with increased LNC and negative lymph nodes rather than increased positive lymph nodes, lymph node ratio, pN stages or AJCC stages. Collectively, the results indicate the LNC is multifactorial and irrelevant to stage migration. The significant correlations with preoperative circulating markers may provide new explanations for LNC-related survival advantage which is reflected by the implication of regional and systemic antitumor immune responses.

• SEER
• colon cancer
• lymph nodes
• patient features
• tumor features

• Adenocarcinoma/mortality
• Adenocarcinoma/surgery
• Adult
• Aged
• Aged, 80 and over
• Cell Differentiation
• Colonic Neoplasms/mortality
• Colonic Neoplasms/surgery
• Female
• Humans
• Kaplan-Meier Estimate
• Lymph Node Excision
• Lymph Nodes/pathology
• Lymphatic Metastasis/pathology
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• SEER Program
• Sex Factors
• Treatment Outcome
• Young Adult

• Colon cancer
• Lymph node yield
• Lymph nodes
• National guidelines

• Age Factors
• Aged
• Colonic Neoplasms/pathology
• Colonic Neoplasms/surgery
• Denmark
• Female
• Humans
• Logistic Models
• Lymph Nodes/pathology
• Male
• Middle Aged
• Neoplasm Staging
• Prospective Studies

Improvement in survival of patients with colon cancer is reduced in elderly patients compared to younger patients. The aim of this study was to investigate whether the removal of ≥ 12 lymph nodes can explain differences in survival rates between elderly and younger patients diagnosed with colon cancer.

In a population-based cohort study, all patients (N = 41,074) diagnosed with colon cancer stage I to III from 2003 through 2010 from the Netherlands Cancer Registry were included. Age groups were defined as < 66, 66–75 and > 75 years of age. Main outcome measures were overall and relative survival, the latter as a proxy for disease specific survival.

Over an eight years time period there was a 41.2% increase in patients with ≥ 12 lymph nodes removed, whereas the percentage of patients with the presence of lymph node metastases remained stable (35.7% to 37.5%). After adjustment for patient and tumour characteristics and adjuvant chemotherapy, it was found that for patients in which ≥ 12 lymph nodes were removed compared to patients with < 12 lymph nodes removed, there was a statistically significant higher overall survival (< 66: HR: 0.858 (95% CI, 0.789–0.933); 66–75: HR: 0.763 (95% CI, 0.714–0.814); > 75: HR: 0.734 (95% CI, 0.700–0.771)) and relative survival (< 66: RER: 0.783 (95% CI, 0.708–0.865); 66–75: RER: 0.672 (95% CI, 0.611–0.739); > 75: RER: 0.621 (95% CI, 0.567–0.681)) in all three age groups.

The removal of ≥ 12 lymph nodes is associated with an improvement in both overall and relative survival in all patients. This association was stronger in the elderly patient. The biology of this association needs further clarification.

• Colorectal cancer
• Disease-free survival
• Impact of examining lymph nodes
• Lymph nodes harvested
• Overall survival

• Adult
• Aged
• Colonic Neoplasms/mortality
• Colonic Neoplasms/pathology
• Colonic Neoplasms/surgery
• Disease-Free Survival
• Female
• Humans
• Lymph Node Excision
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Staging
• Rectal Neoplasms/mortality
• Rectal Neoplasms/pathology
• Rectal Neoplasms/surgery
• Retrospective Studies

• R56 DK105001 NIDDK NIH HHS

• Colon cancer
• Disease-free survival
• Lymph node ratio
• Outcomes
• Resection length
• Survival

Lymph node metastasis informs prognosis and is a key factor in deciding further management, particularly adjuvant chemotherapy. It is core to all contemporary staging systems, including the widely used tumor node metastasis staging system. Patients with node-negative disease have 5-year survival rates of 70%-80%, implying a significant minority of patients with occult lymph node metastases will succumb to disease recurrence. Enhanced staging techniques may help to identify this subset of patients, who might benefit from further treatment. Obtaining adequate numbers of lymph nodes is essential for accurate staging. Lymph node yields are affected by numerous factors, many inherent to the patient and the tumour, but others related to surgical and histopathological practice. Good lymph node recovery relies on close collaboration between surgeon and pathologist. The optimal extent of surgical resection remains a subject of debate. Extended lymphadenectomy, extra-mesenteric lymph node dissection, high arterial ligation and complete mesocolic excision are amongst the surgical techniques with plausible oncological bases, but which are not supported by the highest levels of evidence. With further development and refinement, intra-operative lymphatic mapping and sentinel lymph node biopsy may provide a guide to the optimum extent of lymphadenectomy, but in its present form, it is beset by false negatives, skip lesions and failures to identify a sentinel node. Once resected, histopathological assessment of the surgical specimen can be improved by thorough dissection techniques, step-sectioning of tissue blocks and immunohistochemistry. More recently, molecular methods have been employed. In this review, we consider the numerous factors that affect lymph node yields, including the impact of the surgical and histopathological techniques. Potential future strategies, including the use of evolving technologies, are also discussed.

• Colorectal cancer
• Lymphatic metastases
• Lymph node metastasis
• Neoplasm staging
• Tumor node metastasis classification
• Sentinel lymph node biopsy
• Lymph node excision
• Histopathological assessment
• Surgery

Lymph nodes’ examination in colorectal cancer (CRC) resection specimens is an important determinant that aids in the accuracy of CRC staging and treatment outcomes. Current guidelines call for the examination of at least 12 lymph nodes (LN) in resected specimens in order to establish accurate staging.

To investigate lymph nodes’ examination protocol as it relates to accurate CRC staging.

We reviewed 216 African American CRC patients from 1996–2013 who underwent CRC resection and met inclusion criteria for this study. The number of retrieved LNs, length of resected specimens, tumor grade, stage, location, size and histology were examined.

The cohort study was made of 49 % males, median age was 63 years and 45 % of patients were at stage III and IV. The median (IQR) number of examined LNs was 15 (10–22) and the rate of patients with more than 12 examined LNs was 64 %. There was a gradual increase in the percentage of patients with adequate number (>12) of examined LNs during the study period (from 60 % in 1996–2000 to 84 % in 2010–2013 period, P = 0.014). Adequate LNs resection was neither associated with shift of stage from II to III (P = 0.3) nor with the changes from stage IIIa to IIIc (P = 0.9). Metastatic LNs were observed in 8 % of samples with LNs (>12) vs. 13 % of samples with <12 examined LNs (P = 0.1). Patients that had pre-surgical treatment (chemotherapy and radiotherapy) before surgery had <12 LNs examined. There was also a trend of having more examined lymph nodes in large tumors.

Our study shows that there has been an increase in the number of lymph nodes examined in CRC resections since the advent of the current quality initiative. However this increase does not seem to affect the stage or percentage of metastatic lymph nodes’ detection in CRC patients.

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

Increasing lymph node ratio (LNR) (ratio of metastatic lymph nodes to the total number of harvested lymph nodes) and extramural vascular invasion (EMVI) have been proposed as adverse prognostic indicators in colorectal cancer, although their use remains variable and controversial. The aim of the present study was to assess the prognostic value of LNR and EMVI in predicting survival for patients undergoing curative colon cancer resection.

Between 2006 and 2012, 922 patients underwent curative colon cancer resection. Surgical technique and pathological assessment did not change during the study period. Clinical and pathological data were collected from a prospectively maintained database. The primary outcome measure was overall survival and disease-free survival. LNR was separated into five categories based on three previously calculated cutoff values: LNR 0 (no lymph nodes involved), LNR 1 (ratio 0.01<0.17), LNR 2 (ratio 0.18–0.41), LNR 3 (ratio 0.42–0.69), and LNR 4 (ratio >0.70).

Nine hundred and twenty-two patients underwent colon cancer resection. The median follow-up for survivors was 52.8 months (IQR 34.6–77.6). The median total number of lymph nodes harvested was 16 (IQR13-22). On multivariate analysis, both pN and LNR were strongly associated with overall and disease-free survival. Using the Akaike information criterion (AIC), LNR had greater prognostic value compared with pN. For overall survival, compared with patients in LNR category 0, hazard ratios (95% CI) for those in categories 1, 2, 3 and 4 were 1.37 (1.03,1.82), 2.37 (1.70,3.30), 2.40 (1.57,3.65) and 5.51 (3.16,9.58), respectively. For disease-free survival, patients had hazard ratios (95% CI) of 1.78 (1.25,2.52), 3.79 (2.56,5.61), 2.60 (1.50,4.48) and 4.76 (2.21,10.27), respectively. The presence of EMVI was a significant predictor of decreased overall and disease-free survival (P<0.001).

This study demonstrated, in the presence of high surgical, oncology and pathological standards, EMVI and increasing LNR were independent predictors of decreased overall and disease-free survival for patients undergoing curative colon cancer resection. LNR was superior to pN stage in predicting overall and disease-free survival.

• colorectal cancer
• lymph nodes
• prognosis

• Aged
• Colon/pathology
• Colorectal Neoplasms/pathology
• Female
• Humans
• Lymph Node Excision
• Lymph Nodes/pathology
• Lymphatic Metastasis/pathology
• Male
• Neoplasm Staging
• Rectum/pathology