Lymph node micrometastasis in stage II distal rectal cancer following neoadjuvant chemoradiation therapy

Objective The objective was to determine the presence and frequency of micrometastasis in lymph nodes of patients with rectal cancer treated by preoperative chemoradiation followed by curative resection.Patients and methods All 56 patients included were treated with 5-FU and leucovorin plus 5,040 cGy, followed by radical surgery and were diagnosed with stage II distal rectal adenocarcinoma after complete pathological examination (ypT3-4N0M0). Immunohistochemistry was assessed with cytokeratin monoclonal antibody AE1/AE3. Three 4-m paraffin sections were obtained from each lymph node, cut at 50 m apart from each other. The results were reviewed by two independent pathologists.Results Mean number of lymph nodes was 9.6 per patient. Four patients (7%) and seven lymph nodes (1.35%) were positive for micrometastasis. Three patients had pT3 and one a pT4 tumor. One of the patients had positive micrometastasis and the presence of mucinous deposits. One other patient had mucinous deposits without any micrometastasis. All four patients are alive with no evidence of recurrent disease. Fourteen patients negative for micrometastasis had recurrent disease (25%), eight systemic (14.7%) and six locoregional (10.3%). There were two cancer-related deaths. The mean follow-up period was 39 months.Conclusion Patients with rectal cancer treated by preoperative chemoradiation showed a surprisingly low rate of micrometastasis detection (7%), even in high-risk patients (T3 and T4 tumors). Lymph node micrometastasis was not associated with decreased overall or disease-free survival. The identification of mucinous deposits on lymph nodes with no viable tumor cells may be direct evidence of lymph node downstaging. The downstaging effect of preoperative chemoradiation therapy may be significant in reducing even micrometastasis detection in low rectal cancer managed by this treatment strategy.     

Lymph node involvement as a prognostic factor in pancreatic cancer

The finding of metastatic disease in lymph nodes predicts a poor outcome for patients with adenocarcinoma of the head of the pancreas. Nodal metastases occur in as many as one-half of the patients who currently undergo resection with small tumors (less than 2 cm in diameter). There is some evidence that a more extensive lymphatic and soft tissue resection than is commonly done could prolong survival. This possibility should be tested in a prospectively designed study.     

The prognostic value of lymph node ratio and updated TNM classification in rectal cancer patients with adequate versus inadequate lymph node dissection

Background

The aim of this study was to clarify whether the lymph node ratio (LNR) is superior to the updated TNM classification regarding the prognosis of stage III rectal cancer patients who have not undergone neoadjuvant therapy. The TNM system is based on the absolute number of lymph nodes involved, and the LNR takes into account involved and examined nodes.

Methods

In 237 patients with stage III rectal cancer, we evaluated prognostic factors for 5-year overall survival (OS), disease-free survival (DFS), and risk of distant metastases (DM) using the Kaplan–Meier method, with patients divided based on adequate versus inadequate lymph node dissection (≥12 vs. <12 lymph nodes examined). The updated TNM divides patients into four groups (1, 2–3, 4–6, and ≥7 involved nodes), while LNR divides patients into quartiles. Multivariate Cox regression analyses were performed.

Results

Among patients with adequate lymph node dissection, the distributions within the two systems were in agreement in 141/178 (79.2 %, kappa 0.721), and the predictive values for OS, DFS, and DM were similar. In patients with inadequate lymph node dissection, the classifications of both systems were concordant in only 13/59 (22 %, kappa 0.021). The pN system significantly under-staged patients, while the LNR classification was a better predictor of OS, DFS, and DM.

Conclusions

In patients with adequate lymph node dissection, LNR staging does not add substantial information to the predictions of updated TNM lymph node staging. However, in patients with inadequate lymph node harvesting, the LNR compensates for the under-staging of the TNM classification and provides a better estimation of prognosis than the updated TNM system.     

Metastatic lymph node ratio is a more precise predictor of prognosis than number of lymph node metastases in stage III colon cancer

Objective  

The objective of this study is to assess the value of metastatic lymph node ratio (LNR) in predicting disease-free survival (DFS) in patients with stage III adenocarcinoma of the colon.     

Metastatic lymph node ratio as an independent prognostic variable in colorectal cancer: study of 113 patients

Background  

In patients with colorectal cancer, involvement of the lymph nodes is one of the most important prognostic factors. The aim of this study was to determine the independent prognostic value of the lymph node ratio (LNR), that is the relationship between the involved and examined lymph nodes, in patients with colorectal cancer.     

Lymph node retrieval in colorectal cancer: determining factors and prognostic significance

Purpose

The study aimed to analyze clinicopathological factors that determine the extent of lymph node retrieval and to evaluate its prognostic impact in patients with colorectal cancer (CRC).

Methods

The number of retrieved lymph nodes was analyzed in 381 CRC specimens. Lymph node count was related to different clinicopathological variables by binary logistic regression. Progression-free survival (PFS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier method and Cox regression models.

Results

The median number of retrieved lymph nodes was 20 (mean 21 ± 10, range 1–65) in right-sided, 13 (16 ± 10, 1–66) in left-sided, and 15 (18 ± 11, 3–64) in rectal tumors. The number of retrieved lymph nodes was independently associated with T-classification (p < 0.001), N-classification (p = 0.014), and tumor size (p = 0.005) as well as right-sided tumor location (p = 0.012). There was no association with age, sex, tumor grade, mismatch-repair status, and lymph or blood vessel invasion. The longer the surgical specimen, the higher were the numbers of retrieved and positive lymph nodes (p < 0.001, respectively). In patients with locally advanced (T3/T4) tumors (n = 283), analysis of more than 12 lymph nodes was independently associated with PFS (HR = 0.63, p = 0.025) and CSS (HR = 0.54, p = 0.004). In the subset of T3/T4 N0 patients (n = 130), analysis of more than 12 lymph nodes similarly proved to be an independent predictor of outcome (PFS, HR = 0.48, p = 0.046; OS, HR = 0.41, p = 0.026).

Conclusion

The number of retrieved lymph nodes is associated with higher tumor stage, tumor size, and right-sided location. Low lymph node count indicates adverse outcome in patients with locally advanced (T3/T4) disease.

     

Esophageal cancer with distant lymph node metastasis: prognostic significance of metastatic lymph node ratio

The cervical and celiac lymph node metastases are defined as distant metastasis (Mlym) from thoracic esophageal carcinoma by TNM (primary tumor, regional lymph nodes, and distant metastasis) classification. The prognostic factors, however, of such distant node metastases are not fully understood. Of 85 patients with node-positive thoracic esophageal carcinoma who were treated with the same modalities of treatment, 31 (37%) had Mlym. Prognostic factors for long-term survival were analyzed by univariate and multivariate analyzes. Three patients are alive and free of cancer, and two patients survived over 5 years. Fifteen patients died of recurrent esophageal cancer and 11 patients succumbed to causes unrelated to esophageal cancer. Two patients with a single Mlym died without recurrence of esophageal cancer at 1.4 years and after more than 5 years, respectively. The 1-, 2-, 3-, and 5-year overall survival rates of all 31 patients were 64.5%, 24.8%, 17.0%, and 12.8%, respectively. The factors influencing survival rate were depth of invasion (pT1,2 vs. pT3,4) and metastatic lymph node ratio (< or =0.104 vs. > or =0.105). The survival rates were not influenced by number of lymph node metastasis, number of Mlym, or by metastatic lymph node ratio of Mlym. Among those two significant variables verified by univariate analysis, independent prognostic factor for survival determined by multivariate analysis was the metastatic lymph node ratio (risk ratio = 3.4, p = 0.0345). The results of this study indicate that a significant number of patients can be cured of esophageal carcinoma by extensive resection along with extended lymph node dissection even when the disease metastasizes to distant nodes.     

Feasibility and safety of lateral pelvic lymph node dissection for elderly patients with middle-low rectal cancer: results of a large multicenter lateral node collaborative group study in China

Techniques in Coloproctology - Lateral pelvic lymph node (LPN) dissection can improve local control in certain rectal cancer patients with LPN metastasis. However, the effects of this technically...     

The prognostic value of tumor/lymph node standardized uptake value max ratio and correlation with hematologic parameters in stage III nonsmall cell lung cancer

Stage III non-small cell lung cancer (NSCLC) is a highly heterogeneous subtype of lung cancer. There are still no widely accepted prognostic parameters for stage III NSCLC. In this study, we evaluated the prognostic value of the standardized uptake value (SUV) max ratio of primary tumor to lymph node (T/N SUV max) and its correlation with various hematological parameters.Patient data were reviewed from the hospital database retrospectively. The T/N SUV max ratio was calculated by dividing the SUV max of the primary tumor by the maximal SUV max of the lymph node. The cut-off value for T/N SUV max ratio was determined by receiver operating characteristic analysis. Survival analysis was performed by Kaplan–Meier method with the Long-rank test. P value < .05 was considered statistically significant.A total of 52 patients were included in this study. The optimal cut-off value for T/N SUV max was 1.96 (area under the curve: 0.74; 72.7% sensitivity and 73.7% specificity). Patients with T/N SUV max ≤1.96 were defined as high risk patients and those with >1.96 were defined as low risk patients. The median event (recurrence or progression) free survival was 24.3 months (95% confidence interval: 12.0–36.6) for low risk patients, and 9.2 months (95% confidence interval: 6.1–12.4) for high risk patients (P = .0015). There was an inverse correlation between T/N SUV max and hemoglobin concentration and mean corpuscular volume (rho: −0.349, P = .011; rho: −0.312, P = .025, respectively).Low risk patients had a more favorable prognosis compared to high risk patients. We demonstrated that T/N SUV max can be of prognostic value in stage III NSCLC. T/N SUV max correlated only with hemoglobin and mean corpuscular volume.     

Lymph node metastasis as a significant prognostic factor in gastric cancer: a multiple logistic regression analysis

BACKGROUND: In Japan, the standard treatment policy for all potentially curable patients with gastric cancer is radical resection including extensive lymphadenectomy. This treatment strategy has been used for both early and advanced gastric cancers, and substantial increases in survival time have been reported. In advanced gastric cancer, lymphatic spread is reported to be one of the most relevant prognostic factors for gastric cancer resected for cure. The purpose of this study was to determine the factors affecting lymph node involvement and to establish guidelines for the extent of lymph node dissection most appropriate for the treatment of gastric cancer. METHODS: The clinicopathological features of 926 patients with gastric cancer were reviewed. Information on the clinicopathological features was obtained from the database of gastric cancer at the Department of Gastroenterological Surgery, Sendai National Hospital. Univariate and multivariate analyses of data for patients with gastric cancer tumors were performed to evaluate the prognostic significance of clinicopathological features. The independent risk factors influencing lymph node metastasis were determined by multiple logistic regression analysis. RESULTS: The following clinicopathologic factors were found to be correlated with prognosis of gastric cancer: (1) macroscopic type, (2) depth of invasion, (3) cancer-stromal relationship, (4) histological growth pattern, (5) lymph node involvement, (6) lymphatic invasion, (7) vascular invasion and (8) tumor site. However, a multivariate analysis revealed that macroscopic type, depth of invasion, lymph node involvement and tumor site are independent risk factors for the prognosis of gastric cancer patients. Among these factors, the prognosis of patients with gastric cancer was most strongly influenced by lymph node involvement (odds ratio, 4.632). According to a multiple logistic regression model, depth of cancer invasion and lymphatic invasion was significantly correlated with lymph node metastases. CONCLUSIONS: Lymph node involvement has the strongest influence on the prognosis of gastric cancer. Among the clinicopathological factors, depth of invasion and microscopically lymphatic invasion are important factors in predicting lymph node metastases. Thus, the ability to perform gastrectomy with dissection of lymph nodes is a basic requirement for gastric cancer surgeons.     

Marked impact of tumor location on the appropriate cutoff values and the prognostic significance of the lymph node ratio in stage III colon cancer: a multi-institutional retrospective analysis

Journal of Gastroenterology - The prognostic significance of lymph node ratio (LNR) is not constant among studies. Exploration of appropriate location-specific cutoffs might be necessary because...     

Changes in modified Glasgow prognostic score after neoadjuvant chemotherapy is a prognostic factor in clinical stage II/III esophageal cancer

The inflammation‐based modified Glasgow prognostic score (mGPS) has been shown to be a prognostic factor for esophageal cancer, but its changes in relation to neoadjuvant chemotherapy (NAC) have never been discussed. The purpose of this study was to evaluate the potential prognostic role of mGPS with regard to NAC. mGPS was evaluated on the basis of admission blood samples taken before chemotherapy and before surgery. Patients with elevated C‐reactive protein (CRP) serum levels (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a score of 2, patients with elevated CRP serum levels without hypoalbuminemia were allocated a score of 1, and patients with normal CRP serum levels with or without hypoalbuminemia were allocated a score of 0. A total of 100 patients with clinical stage II/III squamous cell esophageal cancer, who underwent NAC and esophagectomy between January 2007 and August 2012, were investigated. From the multivariate analysis, the grade of response to chemotherapy and post‐NAC mGPS level was found to be independent prognostic factors. The overall survival rate was significantly higher in the conserved mGPS group than in the worse mGPS group (P = 0.030). Changes in mGPS during chemotherapy affected the prognosis of patients, and post‐NAC mGPS is an independent prognostic factor in patients with clinical stage II/III thoracic esophageal squamous cell cancer.     

Outcome of patients with clinical stage II or III rectal cancer treated without adjuvant radiotherapy

Background  To clarify the indications for preoperative adjuvant radiotherapy for rectal cancer, the outcome of patients who underwent curative surgery without adjuvant radiotherapy was investigated. Methods  A total of 817 consecutive patients who underwent curative surgery for clinical stage II or III rectal cancer without preoperative adjuvant radiotherapy between 1988 and 2002 were reviewed. Results  The actuarial 5-year local recurrence rate in the examined patients was 6.2%. Univariate analysis showed that sex, pathological T classification (pT), clinical N classification (cN), pathological N classification (pN), tumor site, distance from the anal verge, type of surgery, pathological stage, a positive radical margin, lymphatic invasion, and venous invasion were significantly correlated with local recurrence. Multivariate analysis of preoperative factors identified cN, distance from the anal verge, and sex as statistically significant risk factors for local recurrence. In patients with rectal cancer located less than 5 cm from the anal verge and with positive cN, the local recurrence rate was more than 10%. Conclusions  Patients with rectal cancer located less than 5 cm from the anal verge and with clinically positive lymph nodes should be given preoperative adjuvant radiotherapy.     

Yield of colonoscopy in patients with nonacute rectal bleeding: a multicenter database study of 1766 patients

OBJECTIVE: There are few data to guide the choice between colonoscopy and flexible sigmoidoscopy in patients with nonacute rectal bleeding, especially in younger age groups. Our aim was to determine the yield of colonoscopy for significant proximal large bowel disease in the absence of significant distal disease, with special reference to young patients. METHODS: This was a retrospective study of data collected prospectively in 1766 patients (median age 57 yr, 711 women). The endoscopic database (GI-Trac) contained 152 discrete fields for data input. Multiple logistic regression analysis was performed to identify variables independently associated with the presence of isolated significant proximal disease. RESULTS: Young patients had a higher percentage of normal examinations than did older patients. The incidence of diverticular disease, small polyps, large polyps, and cancer rose with increasing age. No patient aged <40 yr had an isolated proximal cancer, but 7% had other significant isolated proximal disease. There was no overall association between age and significant proximal disease in the absence of significant distal disease (p = 0.66). The only variable associated with isolated proximal disease was anemia (odds ratio = 1.81; 95% CI = 1.11-2.93; p = 0.02). CONCLUSION: The yield of colonoscopy (beyond the range of sigmoidoscopy) for neoplasia is low in patients aged <40 yr, but other significant disease may be missed if age is the only criterion determining colonoscopy use.     

Histologic prognostic markers in stage IIA colorectal cancer: a comparative study

Objective: pTNM stage IIA colorectal cancer (CRC) is not currently submitted to any adjuvant treatment due to its good prognosis. Nevertheless, a percentage of cases unexpectedly recur. The aim of this study was to assess and compare the prognostic value and inter-observer agreement of a novel histological grading system based on the counting of poorly differentiated clusters (PDC) of cancer cells and that of conventional histological grade, lymphatic, venous and perineural invasion (LVI, VI, PNI), tumour budding (TB) and tumor border configuration in stage IIA CRC.

Materials and methods: the afore mentioned histological parameters were assessed in 82 stage IIA CRCs. Inter-observer agreement and correlation with tumour relapse were analyzed by using Fleiss–Cohen’s weighted K statistics, Fisher exact test and Chi-squared test. The Mantel–Cox log-rank test was applied to assess the strength of association with disease-free interval (DFI).

Results: inter-observer agreement was very good/good in the assessment of PDC presence and grade, while it was moderate at best in the evaluation of the other parameters. The presence of PDC, high PDC grade, LVI and TB were significantly associated with disease progression (p?p?=?0.0012; p?=?0.0308; p?=?0.0002) and shorter DFI (p?=?0.0001; p?p?=?0.0129; p?=?0.0008). PDC presence (p?p?=?0.012) were independent prognostic factors in multivariate analysis.

Conclusions: our findings suggest that the assessment of PDC may be useful to stratify patients with stage IIA CRC for recurrence risk, and to identify high risk patients who could benefit from adjuvant chemotherapy.