Current clinical guidelines recommend the removal of at least 12 lymph nodes (LNs) in resectable colorectal cancer (CRC). With advancements in lymphadenectomy technologies, the number of retrieved lymph nodes (rLNs) has markedly increased. This study aimed to investigate the lowest number of rLNs in node-negative patients.

A total of 1103 N0 and 208 N1a stage patients were enrolled in our cohort, while 8503 N0 and 1276 N1a patients from the Surveillance, Epidemiology, and End Results CRC database were included. Propensity score matching and multivariate Cox regression analyses were performed to mitigate the influence of selection bias and control for potential confounding variables.

The median number of rLNs in N0 patients increased from 13.5 (interquartile range [IQR]: 9-18) in 2013 to 17 (IQR: 15-20) in 2019. The restrictive cubic spline illustrated a nonlinear relationship between rLNs and prognosis (nonlinearity, P =0.009), with a threshold ( N =16) influencing clinical outcomes. Patients at either N0 or N1a stage with sufficient rLNs (≥16) demonstrated superior prognoses to those with a limited rLNs (<16). After adjusting for clinical confounders, similar prognoses were observed in N0 limited and N1a adequate populations. Furthermore, Kaplan-Meier curves revealed that N0 limited patients who received chemotherapy exhibited better outcomes than those who did not.

Among patients with node-negative CRC, it is crucial to remove 16 or more LNs effectively. Fewer than 16 rLNs should be regarded as an independent risk factor, implying the need for adjuvant chemotherapy.

Lymph node dissection is a crucial element of oncologic rectal surgery. Many guidelines regard the removal of at least 12 lymph nodes as the quality criterion in rectal cancer. However, this recommendation remains controversial. This study examines the factors influencing the lymph node yield and the validity of the 12-lymph node limit. Patients with rectal cancer who underwent low anterior resection or abdominoperineal amputation between 2000 and 2010 were analyzed. In total, 20,966 patients from 381 hospitals were included. Less than 12 lymph nodes were found in 20.53% of men and 19.31% of women (p = 0.03). The number of lymph nodes yielded increased significantly from 2000, 2005 and 2010 within the quality assurance program for all procedures. The univariate analysis indicated a significant (p < 0.001) correlation between lymph node yield and gender, age, pre-therapeutic T-stage, risk factors and neoadjuvant therapy. The multivariate analyses found T3 stage, female sex, the presence of at least one risk factor and neoadjuvant therapy to have a significant influence on yield. The probability of finding a positive lymph node was proportional to the number of examined nodes with no plateau. There is a proportional relationship between the number of examined lymph nodes and the probability of finding an infiltrated node. Optimal surgical technique and pathological evaluation of the specimen cannot be replaced by a numeric cut-off value.

The lymph node status plays an important role in rectal cancer, which depends on adequate lymph node harvest. Lymph node stain techniques increase the lymph node harvest. The aim of this prospective study is to investigate which subgroups of lymph nodes harvested were increased mostly.

From May 2020 to May 2022, 172 stage II-III rectal cancer patients were randomized to methylene blue (MB) stained group or unstained group to retrieve the lymph nodes. Methylene blue solution was injected into the inferior mesenteric artery, we dissected lymph nodes by palpation and sight. The lymph nodes were divided into 3 groups depending on the anatomy (main lymph nodes, superior rectal and perirectal lymph nodes (SPLNs), and pericolic lymph nodes located beyond 10 cm proximal to the tumor), and 3 groups depending on the short diameter of the nodes (big: ≥ 5 mm, small: 5-2 mm, mini: ≤ 2 mm).

The number of lymph nodes harvested with MB was significantly higher (22.0 (14.8, 32.0) vs 14.5 (11.0, 22.0); p < 0.001) without difference in positive patients or number of positive nodes. The positive rate of the big node was 3.5%, the small node was 1.9%, and the mini node was 0.2%. In the subgroup analysis, the median number of mini lymph nodes in the MB-stained group was significantly more than that of the unstained group (median (IQR): 9.0 (6.0, 14.0) vs 4.0 (2.0,6.0), p < 0.001); and the median number of SPLNs in the MB-stained group were significantly more than that of the unstained group (median (IQR): 15.0 (9.0, 19.0) vs 10.0 (6.0, 13.3), p < 0.001); these differences were existing in both patients with and without neoadjuvant treatments.

Intra-arterial injection of MB can significantly increase the number of lymph nodes harvested in rectal cancers, especially those mini lymph nodes. However, methylene blue staining did not significantly increase the number of positive lymph nodes and the proportion of patients with more than 12 lymph nodes, or affect lymph node staging accuracy after radical resection of rectal cancer.

Preoperative endoscopic tattooing is an effective tool for intraoperative tumor localization in colon cancer. Endoscopic tattooing in rectal cancer may have unidentified benefits on lymph node yield, making it easier for pathologists to identify nodes during histopathologic assessment. There remains concern that tattoo ink may alter anatomical planes, increasing surgical difficulty.

Retrospective chart reviews from 2016 to 2021 of n = 170 patients presenting with rectal cancer were divided into two groups: with (n = 79) and without (n = 91) endoscopic tattoos. Demographics, operative details, tumor characteristics, prior chemoradiation, and pathologic details were collected. Primary outcome was total lymph node yield. Secondary outcomes were rates of adequate (> 12) nodes, margin status, and operative variables including operative time.

No differences between pathologic stage, tumor height, high inferior mesenteric artery ligation, operative times, conversion rate, or surgical approach (open versus minimally invasive) were noted between groups. Receipt of neoadjuvant chemoradiation was less frequent in the endoscopic tattooing group (53.2% versus 76.9%, P ≤ 0.001). Total node number and rate of adequate lymph node yield were higher with endoscopic tattooing (20.5 ± 7.6 versus 16.8 ± 6.6 lymph nodes and 100.0% versus 83.5% adequate lymph node harvest, both P ≤ 0.001). Rates of positive circumferential and distal margins and complete total mesorectal excision were also similar. Regression analysis identified endoscopic tattooing (Incidence Risk Ratio 1.17, 95% confidence interval 1.04-1.31) and operative time more than 300 min (Incidence Risk Ratio 0.88, 95% confidence interval 0.77-0.99) had significant effects on lymph node harvest. Removal of patients with inadequate lymph node yield resulted in similar rates of total and positive lymph nodes.

Endoscopic rectal tattooing is associated with increased lymph node yield (including after neoadjuvant chemoradiotherapy) without sacrificing oncologic or perioperative outcomes, although this effect is inconsistent when only considering patients with an adequate lymph node yield.

Previous studies have confirmed that neoadjuvant chemoradiotherapy (nCRT) may reduce the number of lymph nodes retrieved in rectal cancer. However, it is still controversial whether it is necessary to harvest at least 12 lymph nodes for locally advanced rectal cancer (LARC) patients who underwent nCRT regardless of open or laparoscopic surgery. This study was designed to evaluate the relationship between lymph node yield (LNY) and survival in LARC patients who underwent laparoscopic TME following nCRT.

Patients with LARC who underwent nCRT followed by laparoscopic TME were retrospectively analyzed. The relationship between LNY and survival of patients was evaluated, and the related factors affecting LNY were explored. To further eliminate the influence of imbalance of clinicopathological features on prognosis between groups, propensity score matching was conducted.

A total of 257 consecutive patients were included in our study. The median number of LNY was 10 (7 to 13) in the total cohort. There were 98 (38.1%) patients with 12 or more lymph nodes harvested (LNY ≥12 group), and 159 (61.9%) patients with fewer than 12 lymph nodes retrieved (LNY <12 group). There was nearly no significant difference between the two groups in clinicopathologic characteristics and surgical outcomes except that the age of LNY <12 group was older (P<0.001), and LNY <12 group tended to have more TRG 0 cases (P<0.060). However, after matching, when 87 pairs of patients obtained, the clinicopathological features were almost balanced between the two groups. After a median follow-up of 65 (54 to 75) months, the 5-year OS was 83.9% for the LNY ≥12 group and 83.6% for the LNY <12 group (P=0.893), the 5-year DFS was 78.8% and 73.4%, respectively (P=0.621). Multivariate analysis showed that only patient age, TRG score and ypN stage were independent factors affecting the number of LNY (all P<0.05). However, no association was found between LNY and laparoscopic surgery-related factors.

For LARC patients who underwent nCRT followed by laparoscopic TME, the number of LNY less than 12 has not been proved to be an adverse predictor for long-term survival. There was no correlation between LNY and laparoscopic surgery-related factors.

Endoscopic tattooing in rectal cancer is infrequently utilized for fear of tattoo ink obscuring anatomical planes, increasing the difficulty of surgical excision. Colon cancer tattooing has demonstrated increased lymph node yields and increased accuracy in establishing adequate margins. Rectal cancer tattooing may be especially helpful after neoadjuvant chemoradiation, where complete clinical responses could limit lesion identification and lymph node yields are typically less robust. We seek to review and identify the effects of tattooing in rectal cancer.

A systematic literature search was performed in PubMed, Embase, and SCOPUS. Studies on endoscopic tattooing with cohorts consisting of at least ≥ 25% of rectal cancer patients were selected. Studies focusing solely on rectal cancer were also reviewed separately.

Of 416 studies identified, 10 studies encompassing 2460 patients were evaluated. Seven studies evaluated lymph node yields; five reported beneficial effects of endoscopic tattooing, while two reported no significant difference. Among four studies reporting lesion localization, successful localization rates were between 63 and 100%. Rates of intraoperative endoscopy performed to reevaluate lesion location ranged from 5.7 to 20%. The distal margin was evaluated in two studies, which reported more accurate placement of the distal resection margin after tattooing. When complications of tattooing were documented (7 studies with 889 patients), only five direct complications of endoscopic tattooing were observed (0.6%).

Although the data is heterogenous, it suggests that endoscopic tattooing in rectal cancer may improve lymph node yields and assist in determining accurate distal margins without high rates of complication. Further research must be completed before practice management guidelines can change.

No. CRD42021271784.

At least 12 lymph nodes (LNs) should be examined following surgical resection of colon cancer. As it is difficult to find small LNs, fat clearing fixatives have been proposed, but there is no consensus about the best option. The objective of this study was to verify if Carnoy's solution (CS) increases the LN count in left colon cancer specimens.

A prospective randomized trial (clinicaltrials.gov registration: NCT02629315) with 60 patients with left colon adenocarcinoma who underwent rectosigmoidectomy. Specimens were randomized for fixation with CS or 10% neutral buffered formalin (NBF). After dissection, the pericolic fat from the NBF group was immersed in CS and re-dissected (Revision). The primary endpoint was the total number of LNs retrieved.

Mean LN count was 36.6 and 26.8 for CS and NBF groups, respectively (p=0.004). The number of cases with <12 LNs was 0 (CS) and 3 (NBF, p=0.237). The duration of dissection was similar. LNs were retrieved in all cases during the revision (mean: 19, range: 4-37), accounting for nearly 40% of the LNs of this arm of the study. After the revision, no case was found in the NBF arm with <12 LNs. Two patients had metastatic LNs during the revision (no upstaging occurred).

Compared to NBF, CS increases LN count in colon cancer specimens. After conventional pathologic analysis, fixing the pericolic fat with CS and performing a second dissection substantially increased the number of LNs.

A number of randomized controlled trials (RCT) have compared different techniques to improve lymph node yield (LNY) in colorectal cancer specimens but data on comparative effectiveness are sparse. Our aim was to compare the relative effectiveness and rank all available techniques.

A systematic search of Embase, Cochrane, PubMed and Scopus was performed for randomized trials. Pairwise meta-analysis performed if more than two homogeneous studies were available for each comparison. Network meta-analysis was used to rank and compare all available techniques.

Fifteen studies fulfilled the inclusion criteria. Techniques that were compared included methylene blue (MB), GEWF, Carnoy solution (CS), patent blue (PB), formalin, fat clearing (FC) and their combinations. The overall quality of studies was found to be fair. In pairwise meta-analysis MB had a higher lymph node yield weighted mean difference [WMD] 13.67 [4.83-22.51], P<0.01, lower number of specimens with less than 12 lymph nodes log Odds Ratio= -1.88(-2.8, -0.91), P<0.01 and higher LNY in patients with prior chemoradiotherapy (WMD 9.11 [3.15,15.08], p=0.02) as compared to formalin. Evaluation of the network plot revealed a well-connected network. In network meta-analysis MBFC had a higher LNY with [Mean Difference (MD) 13 and 95% credible interval (CI) (2.09- 23.91)] as compared to formalin. MBFC probability of being the best technique for LNY was 91.4%. In network meta-analysis MB did not have a statistically significant difference when compared to formalin.

MBFCS seems to be the most effective technique for LNY. Further studies are required to make safe conclusions for outcomes such positive lymph nodes and upstaging.

The aim of this study was to determine the prognostic value of lymph node count (LNC) and lymph node ratio (LNR) in rectal cancer after neoadjuvant chemoradiotherapy (CRT).

Patients who underwent neoadjuvant CRT and total mesorectal excision (TME) for Stage I-III rectal cancer were selected from a cross-sectional study including 71 Dutch centres. Primary outcome parameters were disease-free survival (DFS) and overall survival (OS). Prognostic significance of LNC and LNR (cut-off values 0.15, 0.20, 0.30) was tested for different (sub)groups.

From 2095 registered patients, 458 were included, of which 240 patients with LNC < 12 and 218 patients with LNC ≥ 12. LNC was not significantly associated with DFS (p = 0.35) and OS (p = 0.59). In univariable analysis, LNR was significantly associated with DFS and OS in the whole cohort and LNC subgroups, but not in multivariable analysis.

LNC was not associated with long-term oncological outcome in rectal cancer patients treated with CRT, nor was LNR when corrected for N-stage. However, LNR might be used to identify subgroups of node-positive patients with a favourable outcome.

Conventional clinical guidelines recommend that at least 12 lymph nodes should be removed during radical rectal cancer surgery to achieve accurate staging. The current application of neoadjuvant therapy has changed the number of lymph node dissection.

To investigate factors affecting the number of lymph nodes dissected after neoadjuvant chemoradiotherapy in locally advanced rectal cancer and to evaluate the relationship of the total number of retrieved lymph nodes (TLN) with disease-free survival (DFS) and overall survival (OS).

A total of 231 patients with locally advanced rectal cancer from 2015 to 2017 were included in this study. According to the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) classification system and the NCCN guidelines for rectal cancer, the patients were divided into two groups: group A (TLN ≥ 12, n = 177) and group B (TLN < 12, n = 54). Factors influencing lymph node retrieval were analyzed by univariate and binary logistic regression analysis. DFS and OS were evaluated by Kaplan-Meier curves and Cox regression models.

The median number of lymph nodes dissected was 18 (range, 12-45) in group A and 8 (range, 2-11) in group B. The lymph node ratio (number of positive lymph nodes/total number of lymph nodes) (P = 0.039) and the interval between neoadjuvant therapy and radical surgery (P = 0.002) were independent factors of the TLN. However,TLN was not associated with sex, age, ASA score, clinical T or N stage, pathological T stage, tumor response grade (Dworak), downstaging, pathological complete response, radiotherapy dose, preoperative concurrent chemotherapy regimen, tumor distance from anal verge, multivisceral resection, preoperative carcinoembryonic antigen level, perineural invasion, intravascular tumor embolus or degree of differentiation. The pathological T stage (P < 0.001) and TLN (P < 0.001) were independent factors of DFS, and pathological T stage (P = 0.011) and perineural invasion (P = 0.002) were independent factors of OS. In addition, the risk of distant recurrence was greater for TLN < 12 (P = 0.009).

A shorter interval to surgery after neoadjuvant chemoradiotherapy for rectal cancer under indications may cause increased number of lymph nodes harvested. Tumor shrinkage and more extensive lymph node retrieval may lead to a more favorable prognosis.

To clarify the usefulness of chemoradiotherapy (CRT) for low rectal cancer, we investigated the current status of CRT in Japan and its short- and long-term outcomes versus surgery alone for low rectal cancer in a large multicenter cohort study.

Between January 2010 and December 2011, data from 1608 patients with clinical Stage II-III rectal adenocarcinoma were collected from 69 specialized centers. Of these 1608 patients, 923 were diagnosed with clinical stage III low rectal cancer, 838 were enrolled in this study, divided into the surgery-alone group (n = 649) and preoperative CRT group (n = 189), and analyzed.

The following parameters were significantly lower in the CRT versus surgery-alone group: blood loss (210 vs. 431.5 mL), postoperative complications (27.5% vs 39.0%), and the incidence of anastomotic leakage (3.7% vs. 8.8%). The 3-year overall survival, relapse-free and local recurrence-free survival rates did not between the two groups to a statistically significant extent (91.2% vs. 87.4%, 68.8% vs. 66.4%, and 88.2% vs. 88.4%, respectively).

The present study revealed the current status of CRT for low rectal cancer in Japan. The results showed that CRT could be safely performed for advanced low rectal cancer in comparison to surgery alone.

Neoadjuvant chemotherapy (nCMT) has been increasingly used in advanced gastric cancer (GC). However, the prognostic impact of tumor response remains unclear. This study aimed to evaluate if tumor response at the primary site and lymph nodes (LN) correlate with survival in GC patients after nCMT.

Patients with gastric adenocarcinoma treated with nCMT followed by gastrectomy were evaluated. Residual tumor was graded from 0% to 100%, defining two groups: poor (PR) and major response (MR). LN regression rate (LNRR) was determined based on tumor/fibrosis examination at each LN and a cutoff value established by receiver operating characteristic curve.

Among 62 cases, 20 (32.2%) had MR and 42 (67.7%) PR. Smaller size, diffuse histology, lower ypT status and less advanced stage were associated with the MR group. Based on cutoff value of 57, 45.6% and 54.4% patients were classified as low-LNRR and high-LNRR. High-LNRR correlated with absence of venous, lymphatic and perineural invasion, and less advanced stage. Survival was equivalent between MR and PR (P = .956). High-LNRR had better disease-free survival (DFS) than low-LNRR (P < .001). In multivariate analysis, only LNRR associated with DFS.

High-LNRR associates with DFS in GC treated with nCMT. Response at the primary site does not correlate with survival.

This study aimed to compare the performance of two lymph node revealing solutions.

This randomized clinical trial (NTC02704988) investigated patients with colon or rectal cancer who underwent surgical resection with D2 lymphadenectomy. Specimens submitted for conventional pathological examination were randomly assigned for additional fixation with Carnoy or GEWF solution, and dissection was performed to examine the missed lymph nodes. The number of lymph nodes retrieved, additional identified metastatic lymph nodes, lymph node upstaging, and complementary indication of adjuvant therapy were investigated.

The number of lymph nodes retrieved was significantly higher with the use of lymph node revealing solutions than with the conventional method in colon cancer (GEWF: 29.5 vs 27; p < 0.001; Carnoy: 27.7 vs 25.2; p < 0.001) and rectal cancer (GEWF: 25.8 vs 23.6; p < 0.001; Carnoy: 23.1 vs 20.8; p < 0.001). There were no differences between the solutions and conventional examination with respect to the median number of additional metastatic lymph nodes identified (0 in all arms), the number of patients with lymph node upstaging (colon cancer: 1 in the Carnoy arm, 0 in the GEWF arm; rectal cancer: 1 in the GEWF arm, 0 in the Carnoy arm), or the number of patients with complementary indication of adjuvant therapy (colon cancer: 1 in the Carnoy arm, 0 in the GEWF arm; rectal cancer: 0 in both arms).

Despite the higher number of lymph nodes retrieved, neither solution resulted in significant changes in patient staging or treatment. Both solutions exhibited equal performance with respect to all outcomes.

NTC02704988.

It is recommended for colorectal cancer to harvest at least 12 lymph nodes (LNs) during surgery to avoid understaging of the disease. However, it is still controversial whether it is necessary to harvest from locally advanced rectal cancer (LARC) patients who underwent neoadjuvant chemoradiotherapy (neo-CRT). The impact of lymph node yield (LNY) on prognosis in LARC patients was analyzed.

In total, 495 LARC patients who underwent neo-CRT in 2006-2015 were analyzed. After examining clinicopathological distribution differences between the LNY subgroups (with the threshold of 12), univariate and multivariate Cox survival analyses were performed. Survival plots were obtained from Kaplan-Meier analyses. Similar subgroup analyses were performed according to the tumor regression grade (TRG) and metastatic status of post-operational LNs.

Of the 495 patients, 287 (57.98%) had an LNY of less than 12. Nearly no significant clinicopathological difference was found between the LNY subgroups, including the TRG scores. Multivariate survival analysis demonstrated that at least 12 LNs examined was an independent prognostic feature of good overall survival (OS), disease-free survival (DFS), and distant metastasis free survival (DMFS), but not local recurrence free survival (LRFS). However, in the subgroup analyses, no association was found between LNY and prognosis in patients with good TRG scores (0-1) or negative LNs.

For LARC patients treated with neo-CRT, an LNY of at least 12 indicated an improved survival. Decreased LNY was not related to better tumor regression. It suggests that a sufficiently high LNY is still required, especially in those with a potentially poor tumor response.