The Impact of the Lymph Node Ratio is Greater than Traditional Lymph Node Status in Stage III Colorectal Cancer Patients

Background

The prognostic value of nodal status in colorectal cancer (CRC) patients may be influenced by the total number of lymph nodes (LNs) harvested. This study evaluates the impact of LN ratio (LNR) on CRC patients’ outcome.

Methods

A total of 612 stage III CRC patients who underwent curative-intent surgery between 2004 and 2008 were enrolled. The measured end point was postoperative disease-free survival (DFS) and overall survival (OS).

Results

The metastatic LN numbers were significantly higher in patients with more than 12 LN harvested (4.6 ± 5.81 vs. 2.7 ± 1.97, P < 0.001). The mean LNR was 22.9 ± 20 % (range = 2–100 %, median = 16.7 %). As the cutoff value of LNR was set above 17 %, the impact of the LNR on 5-year DFS became statistically significant. In univariate analysis, the 5-year DFS and OS for patients with high-LNR tumors was 54.4 and 57.3 %, respectively, significantly lower than those for patients with low-LNR tumors (72.8 and 76.4 %; P < 0.001). In multivariate analysis, the independent factors affecting the 5-year DFS and OS were tumor depth, carcinoembryonic antigen level, and LNR.

Conclusion

The LNR, set at the median value or 17 %, could be an independent prognostic factor for stage III CRC patients.     

Limitations of Lymph Node Ratio, Evidence-Based Benchmarks, and the Importance of a Thorough Lymph Node Dissection in Melanoma

Background

Stage III melanoma is currently stratified by number of lymph nodes (LNs) involved. However, given the variability of LN retrieval counts we hypothesize that lymph node ratio (LNR) may also provide prognostic information.

Methods

Retrospective cohort study of 411 patients with stage III melanoma were divided into two groups based on LNR (<0.15, n = 291 and ≥0.15, n = 120).

Results

In multivariate analysis N stage (N3 vs. N1, hazard ratio [HR] = 2.13, p < 0.001), extranodal extension (HR = 1.92, p = 0.002), macrometastasis (HR = 1.70, p = 0.005), non-SLN involvement (HR = 1.65, p = 0.005), risk of N2 disease exceeding 35 % (HR = 1.51, p = 0.03), and LNR ≥0.15 (HR = 1.46, p = 0.03) were associated with overall survival (OS). LNR failed to further stratify stage III melanoma; however, the number of LNs examined was an independent prognostic factor. Patients who had >8 inguinal, >15 axillary, or >20 cervical LNs examined had fewer same nodal basin recurrences (26 [8 %] vs. 20 [20 %], p = 0.0009) and for N1 patients an improved OS (3-year OS 84 % vs. 76 %, 10-year OS 53 % vs. 34 %, p = 0.06) compared with N1 patients who had fewer LNs examined.

Conclusions

LNR is an important prognostic factor in stage III melanoma; however, it was not independent over the current AJCC TNM staging system. Diligence by the surgeon and pathologist to retrieve and examine >8 inguinal, >15 axillary, or >20 cervical LNs is associated with fewer same nodal basin recurrences and improved survival and is critical to reliable prognostication.     

Lymph Node Harvest in Esophageal Cancer After Neoadjuvant Chemoradiotherapy

Background

This study was designed to determine the effects of lymph node (LN) harvest on survival in esophageal cancer after neoadjuvant chemoradiation (nCRT).

Methods

An analysis of surgically resected esophageal cancer patients after nCRT was performed to determine an association between the number of LNs resected and survival. Overall survival (OS) and disease-free survival (DFS) curves were calculated according to the Kaplan–Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model.

Results

We identified 358 patients with a mean follow-up of 27.3 months. The number of LN removed was not impacted by the type of surgical procedure. The number of LNs removed (<10 vs. ≥10, <12 vs. ≥12, and <15 vs. ≥15) did not impact OS or DFS. We found a significant difference in OS and DFS by pathologic response. The median and 5-year OS for patients with complete, partial, and no response was 65.6 months and 52.7 %, 29.7 months and 30.4 %, and 17.7 months and 25.4 % (p = 0.0002). However, the number of LN harvested did not impact OS and DFS when patients were stratified by pathologic response. MVA also revealed that the number of lymph nodes removed was not prognostic for OS or DFS. Higher age, higher stage, and less than a complete response were associated with a decreased OS. Higher stage and less than a complete response were prognostic for worse DFS.

Conclusions

The number of LNs harvested during esophagectomy does not impact survival after nCRT. Stage and pathologic response continue to be the strongest prognostic factors for survival in esophageal cancer after nCRT.     

The Prognostic Value of Lymph Node Ratio in Node-Positive Breast Cancer: A Dutch Nationwide Population-Based Study

Background

The absolute number of involved axillary lymph nodes (LNs) is considered the most important prognostic factor in breast cancer. Over the last decade, several studies indicated that the lymph node ratio (LNR) might predict outcome better than the number of positive LNs. In this study we test the applicability of earlier published LNR cutoff values and study the prognostic value of the LNR on a nationwide level.

Methods

A nationwide population-based study was performed, using data from the Netherlands Cancer Registry, including all women diagnosed with node-positive breast cancer between 1999 and 2005 (N = 25,315). Patients were divided into 3 LNR risk groups (low, ≤0.20; intermediate, 0.21–0.65; and high, >0.65). Kaplan–Meier survival analysis was performed. In order to evaluate whether LNR was associated with overall survival (OS), Cox proportional hazards modeling was used.

Results

For the entire cohort, 5- and 10-year OS rates were 78 % and 62 %, respectively. The number of positive LNs correlated with OS (5-year OS 84 %, 72 %, and 55 % for patients with 1–3, 4–9, and 10 or more positive LNs, respectively, P < .001). LNR also correlated with OS (5-year OS 86 %, 75 %, and 54 % for low-, intermediate-, and high-risk groups, respectively, P < .001). In the multivariable analysis, the risk of death increased with increasing LNR (P < .001).

Conclusions

The LNR has an important prognostic value in node-positive patients, independent of traditional clinicopathological factors. LNR should be added as an independent prognostic variable to the current staging system.     

Patterns and Prognostic Significance of Lymph Node Dissection for Surgical Treatment of Perihilar and Intrahepatic Cholangiocarcinoma

Introduction

The prognostic significance of lymph node dissection (LND), the number and status of harvested lymph nodes (LNs), and the lymph node ratio (LNR) are still under debate in intrahepatic (ICC) and perihilar (PCC) cholangiocarcinoma. The aims of this study were to evaluate the prognostic value of the extent of LN dissection, the number of positive LNs, the distribution of positive LNs along different LN stations, and the LNR in a cohort of patients with ICC and PCC who underwent surgical resection and to compare the different prognostic values of lymph node involvement.

Material and Methods

A retrospective analysis was done evaluating extent of LND, number, status, and location of harvested LNs in a cohort of 145 patients with cholangiocarcinoma submitted to surgical resection with curative intent from 1990 to 2012.

Results

Seventy patients had ICC and 75 had PCC. The median survival times of patients with N0 and N+ tumors were 42 and 19 months in ICC patients (p?=?0.05) and 42 and 22 months in PCC patients (p?=?0.01). In patients without LN metastases, the median survival times of patients with up to three LNs retrieved and with more than three LNs retrieved were 38 and 69 months in ICC patients (p?=?0.05) and 18 and 43 months in PCC patients (p?=?0.04), respectively. In N+ patients, the location of positive LNs (hepatoduodenal ligament or other regional stations) did not influence overall survival in ICC or PCC patients (p?=?0.6). The median survival times of patients with LNRs of 0 and >0.25 were 43 and 19 months in ICC patients (p?=?0.01); the 0–0.25 group did not reach the value. In PCC patients, median survival of 0, 0–0.25, and >0.25 groups of patients were 42, 23, and 11 months (p?=?0.01), respectively.

Conclusions

LN metastasis is a major prognostic factor after surgical resection of cholangiocarcinoma. The number of harvested LNs and the LNR showed a high prognostic value in ICC and PCC.     

Evaluation of Guanylyl Cyclase C Lymph Node Status for Colon Cancer Staging and Prognosis

Purpose

The prognostic significance of guanylyl cyclase C (GCC) gene expression in lymph nodes (LNs) was evaluated in patients with stage II colon cancer who were not treated with adjuvant chemotherapy. We report a planned analysis performed on 241 patients.

Methods

GCC mRNA was quantified by RT-qPCR using formalin-fixed LN tissues from patients with untreated stage II colon cancer who were diagnosed from 1999–2006 with at least ten LNs examined and blinded to clinical outcomes. Lymph node ratio (LNR) is the number of GCC-positive nodes divided by total number of informative LNs. Risk categories of low (0–0.1) and high (> 0.1) for LNR were chosen by significance using Cox regression models. The data were tested for association with time to recurrence.

Results

Twenty-nine patients (12%) had a disease recurrence or cancer death. The LNR significantly predicted higher recurrence risk for 84 patients (34.9%) classified as high risk (hazard ratio (HR), 2.38; P = 0.02). The estimated 5-year recurrence rates were 10% and 27% for the low- and high-risk groups, respectively. After adjusting for age, T stage, number of nodes assessed, and MMR status, a significant association remained (HR, 2.61; P = 0.02). In a subset of patients (n = 181) with T3 tumor, ≥ 12 nodes examined and negative margins, a significant association between the GCC LNR and recurrence risk also was observed (HR, 5.06; P = 0.003).

Conclusions

Our preliminary results suggest that detection of GCC mRNA in LNs is associated with risk of disease recurrence in patients with untreated stage II colon cancer. A larger validation study is ongoing.     

Prognostic impact of lymph node involvement and the extent of lymphadenectomy (LAD) in adenocarcinoma of the esophagogastric junction (AEG)

Background

The prognostic importance of lymph node (LN) involvement for patients with adenocarcinoma of the esophagogastric junction (AEG) is well-known. In the latest edition of the UICC staging system, the number of metastatic LNs was taken into account, while the extent of lymphadenectomy (LAD) remains unaddressed. Removal of at least six LNs is recommended, but there is no defined minimum number as to classify as (y)pN0. We examined the prognostic value of the number of positive LNs, number of LNs removed, and LN ratio (LNR) in order to determine the influence of an adequate LAD on overall survival (OS).

Methods

We analyzed data of 316 patients with AEG treated in our institution (2001–2011) regarding clinicopathological data, treatment, morbidity, mortality, and long-term prognosis. Univariate and multivariate analysis was performed using Cox regression to evaluate the prognostic impact of(y)pN category, number of LNs removed and LNR.

Results

OS decreased with higher count of positive LNs (p?<?0.001) and higher LNR (p?<?0.001). Whether >6, >15, or >30 LNs were removed did not influence OS, neither in the entire study population nor within individual (y)pT or (y)pN categories. Multivariate analysis revealed LNR (p?<?0.001) besides M category (p?=?0.015) and tracheotomy during the postoperative course (p?=?0.005) as independent predictors of OS.

Conclusion

The classification according to the number of involved LNs in the latest edition of the UICC staging system improves prognostication in patients with AEG. The importance of an adequate LAD is shown by the high prognostic relevance of the LNR rather than the absolute number of LNs removed.     

Validation of the prognostic value of lymph node ratio in patients with penile squamous cell carcinoma: a population-based study

Purpose

The aim of this study was to validate the prognostic value of lymph node ratio (LNR), the proportion of metastatic among removed lymph nodes, for patients with penile squamous cell carcinoma in a population-based database.

Methods

A total of 210 eligible patients with node-positive disease were identified from the surveillance epidemiology end results database. Cancer-specific survival (CSS) was the clinical outcome of interest. The prognostic ability of LNR was assessed by Cox regression analyses. Logrank test was used to compare CSS between low-risk and high-risk groups stratified by cutoff points of LNR.

Results

The median number of LNs removed was 16, and the median value of LNR was 0.20. First, LNR was a significant prognostic factor of CSS in univariate analysis (HR = 4.08). Second, LNR retained independent predictive ability (HR = 6.74) in the multivariate model including demographic data, disease characteristics and number-based LN variables. Addition of LNR remarkably improved the predictive accuracy and clinical usefulness of the survival model. Third, maximum stratification of CSS can be achieved at the cutoff point of 0.33.

Conclusion

In the population-based study, LNR outperformed number-based LN variables for predicting CSS of node-positive penile cancer. The ratio-based prognostic factor stresses the important role of adequate LND and identification of metastatic LNs in the community setting.     

Extracapsular Lymph Node Involvement is Associated With Colorectal Liver Metastases and Impact Outcome After Hepatectomy for Colorectal Metastases

Background

Hepatic resection of metastatic colorectal cancer (CRC) has become the treatment of choice for patients after resection of the primary CRC. However, some patients do not benefit from immediate resection because of rapidly progressive disease. The aim of this study was to examine the prognostic value of extracapsular invasion (ECI) of lymph node (LN) metastasis of CRC with liver metastases following liver resection.

Methods

All patients who underwent resection for CRC with liver metastases between 1995 and 2011 were reviewed. All of those with metastasis from primary CRC were included in this study. Preoperative, intraoperative, and postoperative data, including primary tumor pathology results, were retrospectively reviewed. All resected LNs from primary CRC were re-examined to assess ECI. Associations between clinicopathologic factors, survival, and the nodal findings were evaluated.

Results

ECI was identified in 47 (48 %) patients. ECI was correlated with the number of positive LNs (p = 0.0022), timing of liver metastasis (p = 0.0238), and number of liver metastases (p = 0.0001). Univariate analysis indicated that the number of positive LNs (p = 0.0014), ECI (p = 0.0203), and adjuvant chemotherapy (p = 0.0423) were significant prognostic factors. Patients with ECI had a significantly worse survival (p = 0.0024) after liver resection than patients with LN-negative and ECI-negative groups.

Conclusions

In patients with hepatic CRC metastases, ECI in regional LNs reflects a particularly aggressive behavior, such as a greater number of liver metastases. In CRC patients with liver metastases, ECI in regional LNs might be correlated with poor prognosis following liver resection.     

Lymph Node Ratio of the Central Compartment is a Significant Predictor for Locoregional Recurrence After Prophylactic Central Neck Dissection in Patients with Thyroid Papillary Carcinoma

Background

Lymph node ratio (LNR) is an important prognosis factor in many solid cancers, but there have been few reports of LNR in papillary thyroid carcinoma (PTC). This study investigated LNR of the central compartment to determine whether LNR has clinical significance as a prognostic predictor for recurrence after prophylactic central neck dissection (pCND) in patients with PTC.

Methods

The study includes 295 consecutive patients who underwent total thyroidectomy with bilateral pCND, which was pathologically diagnosed as N1a PTC. LNR was calculated as the ratio of positive LN to total LN removed.

Results

LNR of 0.65 was significantly meaningful for recurrence when three or more LNs were collected (P < 0.001). The 10-year estimated recurrence-free survival rates were 98.6 % for patients with LNR ≤0.65 and 75.4 % for patients with LNR >0.65 (P < 0.001). Univariate analysis revealed that increasing tumor size and LNR >0.65 were significantly associated with recurrence (P < 0.05 each). No significant association with recurrence was found for age ≥45 years, male gender, microscopic extrathyroidal extension, coexistent chronic lymphocytic thyroiditis, T classification, multicentricity, number of positive LN, and extranodal extension (P > 0.05 each). The only independent variable for recurrence identified by multivariate analysis was LNR >0.65 (P < 0.001).

Conclusions

LNR may be a useful predictor to stratify the likelihood of recurrence after pCND in patients with pathologic N1a PTC.     

Impact of Lymph Node Ratio on Survival in Papillary Thyroid Cancer

Background

In papillary thyroid cancer, the role of lymph node dissection remains controversial, and staging systems consider metastatic lymph nodes as a binary entity. The purpose of this study was to determine a threshold lymph node ratio (LNR) that impacted disease-specific mortality (DSM).

Methods

We utilized the surveillance, epidemiology, and end results (SEER) database to analyze adult patients who underwent thyroidectomy with lymph node dissection. A LNR (metastatic lymph nodes to total lymph nodes) was calculated after eliminating patients with less than three nodes collected. Kaplan–Meier estimates for DSM were plotted for LNRs and compared by the log rank test. The Cox proportional hazards model was used to evaluate LNR with other known clinical and pathologic determinants of prognosis.

Results

A total of 10,955 cases contained data on lymph nodes. Median follow-up time was 25 months (range 0–59 months), and the mean LNR was 0.28 ± 0.37. After comparing Kaplan–Meier survival estimates and overall DSM rates, we found that a LNR ≥0.42 best divided those with lymph node metastasis based on DSM (p < 0.01). Those with a LNR ≥0.42 experienced a DSM rate of 1.72 % while those with a LNR <0.42 had a DSM rate of 0.65 % (p < 0.01). In addition, patients with a LNR ≥0.42 experienced a 77 % higher DSM rate compared to those with metastatic lymph nodes as a whole. When considered with other known determinants of prognosis, we found that LNR was strongly associated with DSM (hazard ratio 4.33, 95 % confidence interval 1.68–11.18, p < 0.01).

Conclusions

LNR is a strong determinant of DSM, and a threshold LNR of 0.42 can be used to risk-stratify patients with metastatic lymph nodes.     

A Comparison of Five Competing Lymph Node Staging Schemes in a Cohort of Resectable Gastric Cancer Patients

Background

New classifications for lymph node (LN) staging have recently been proposed to improve upon the UICC/AJCC N category staging convention. Ratio-based systems and logarithmic odds (LODDS) scores are two families of novel competing staging systems. We compared UICC/AJCC staging with 5 ratio and LODDS systems in predicting overall survival (OS) in patients with resected gastric cancer.

Methods

Using a large population-based dataset, we identified 12,184 nonmetastatic resectable gastric cancer patients between 1988 and 2004. We compared each subject’s UICC/AJCC N stage with five novel staging schemes. We analyzed the OS for each method. Our comparison metric was the log-rank Chi squared statistic; larger Chi squared statistics indicate improvements in N stage discrimination.

Results

Median OS was 2.1 years (95 % CI 2.0–2.2 years), while median patient follow-up for surviving patients was 8.3 years (range, 1 month–22 years). Although all 5 staging systems were either comparable or superior to the UICC/AJCC convention, a LN ratio method outperformed others in N stage discrimination based on log-rank tests for OS. This trend was independent of the number of LNs examined.

Conclusions

Novel LN staging methods have a higher degree of discrimination utility than the UICC/AJCC N convention. These methods may have a role in reducing the prognostic impact of LN count variability. Of the systems assessed, the LN ratio system that assigns greater risk attribution to cases with <16 LNs was the best classification method to predict OS in patients with resectable gastric cancer.     

Prognostic Impact of Lymph Node Retrieval and Ratio in Gastric Cancer: a U.S. Single Center Experience

Introduction

Increased lymph node (LN) retrieval for gastric cancer has been associated with improved overall survival (OS). This study examines the impact of number of examined LN (eLN) and lymph node ratio.

Methods

Patients referred for surgical care of gastric cancer were stratified by number of eLN, positive LNs (LN+), and lymph node ratio (LN+/eLN). Clinicopathologic factors were compared; OS and disease-free survival (DFS) were the primary endpoints.

Results

From 1997 to 2012, 222 patients, median age 67 (range, 17–92)?years, were analyzed. Of 220 (99 %) explored, 164 (74 %) underwent resection. Median OS was 22 (range, 0.3–140)?months. Perineural and lymphovascular invasion and poor differentiation adversely affected OS, p?<?0.05. A median 14 eLN (range, 0–45), with median 1 LN+ (range, 0–31), was observed. There were no OS or DFS differences when comparing the eLN groups. Both OS and DFS were impacted by LN+. Lymph node ratio demonstrated worse median OS with increasing ratio: 49 months (0) to 37 months (0.01–0.2), 27 months (0.21–0.5), and 12 months (>0.5), p?<?0.0001. DFS was similar: 35 months (0), decreasing to 22 months (0.01–0.2), 13 months (0.21–0.5), and 7 months (>0.5), p?<?0.0001.

Conclusion

Number of eLN did not impact survival, while LN+ adversely affected survival. Lymph node ratio may predict prognosis better than number of eLN or LN+ in gastric cancer.     

Significance of Lymph Node Retrieval From the Terminal Ileum for Patients With Cecal and Ascending Colonic Cancers

Background

For patients with cecal and ascending colonic cancers, the significance of regional lymph node (LN) metastasis at the terminal ileum has not been elucidated. We analyzed its metastatic patterns and significance.

Methods

The records of patients with cecal and ascending colonic cancers receiving standard radical right hemicolectomy with D3 LN dissection between 2000 and 2010 were collected. The regional LNs were grouped according to the Japanese Classification of Colorectal Carcinoma. The regional LNs supplied by ileocolic vessels were further divided into 201-A (terminal ileal side) and 201-B (colonic side). The clinicopathologic characteristics of all cases showing positive for metastasis in 201-A LN were analyzed.

Results

Forty-seven cases of cecal and 56 cases of ascending colonic cancer were included. Seven cases had 201-A-positive LNs: five (10.6%) in cecal cancers and two (3.6%) in ascending colonic cancers. They all had distant metastases (P < 0.001), and the incidences were significantly correlated with the numbers of metastatic LNs (P < 0.05). There was no 201-A-positive LN noted among patients with stage I to III disease. Poor prognosis was noted for patients with a 201-A-positive LN.

Conclusions

Both cecal and ascending colonic cancers have a potential for LN metastasis at the terminal ileum. These cases are exclusively stage IV and have poor prognosis.     

Nodal Counts and Lymph Node Ratio Impact Survival After Distal Pancreatectomy for Pancreatic Adenocarcinoma

Background

The number of lymph nodes required for accurate staging after distal pancreatectomy for pancreatic adenocarcinoma is unknown.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 1,473 patients who underwent distal pancreatectomy for pancreatic adenocarcinoma from 1998 to 2010. We evaluated the influence of the total number of lymph nodes examined (NNE) and the lymph node ratio (LNR-positive nodes/total nodes examined) on survival.

Results

The median NNE was 8. No nodes were examined in 232 (16 %) of the patients, and 843 (57 %) had <10 NNE. Of the patients who had at least one node examined, 612 (49 %) were node positive. In the node-negative subset, the median and 5-year overall survival for patients with ≤10 NNE was significantly worse than patients with >10 NNE (16 vs. 20 months and 13 vs. 19 %, respectively, p?0.1 (17 vs. 6 %, p?=?0.002).

Discussion

Patients with pancreatic cancer undergoing distal pancreatectomy should ideally have at least 11 lymph nodes examined to avoid understaging. For node-positive patients, LNR may be a better prognostic indicator than the total number of positive nodes.     

Race and Correlations Between Lymph Node Number and Survival for Patients with Gastric Cancer

Background

There is ongoing debate whether extended lymphadenectomy improves survival in gastric cancer patients who undergo surgical resection. We previously observed that Korean–American patients had the highest overall survival in Los Angeles County. Our objective was to assess lymph node (LN) number and its impact on survival for Korean–American gastric cancer patients.

Methods

We utilized the National Cancer Institute’s Surveillance, Epidemiology, and End Results registry to identify Korean–Americans with gastric adenocarcinoma treated with curative-intent gastrectomy between 1988 and 2008. We grouped patients according to examined LN number (1–15 and 16+) and compared characteristics. We performed similar analysis for white patients.

Results

Out of 982 Korean–American patients with gastric adenocarcinoma, most patients had 1–15 examined LNs (60 %). When we compared LN groups, we observed higher overall survival in the 1–15 group than the 16+ group (5-year survival, 59 % vs 52 %, respectively; p?=?0.04). However, LN number was not prognostic of overall survival on stepwise Cox proportional hazards analysis. In contrast, LN number was prognostic for white patients.

Conclusions

Although examined LN number may impact survival for white patients, outcomes of Korean–American gastric cancer patients were independent of LN number. Our data suggest that survival of Korean–American gastric cancer patients are comparable with outcomes from East Asian hospitals and may be independent of surgical technique.     

Lymph Node Counts and Ratio in Axillary Dissections Following Neoadjuvant Chemotherapy for Breast Cancer: A Better Alternative to Traditional pN Staging

Background

Neoadjuvant chemotherapy (NCT) for breast cancer might change the number of involved and detected nodes in axillary lymph node dissections (ALND). In this study, we analyzed whether the number of dissected nodes and the lymph node ratio (LNR, defined as the proportion of involved nodes in dissected nodes) would have a better prognostic value than traditional pN staging.

Methods

A total of 569 patients with stage II, III breast cancer were included in this retrospective study. All patients underwent a median of three cycles of NCT followed by mastectomy and ALND. Clinical and pathological variables were investigated using univariate and multivariate survival analyses.

Results

In post-NCT node-negative (LN?) patients, those with 4–9 dissected nodes experienced a significantly lower relapse-free survival (RFS) compared with those with 10 or more dissected nodes (hazard ratio = 0.19, 0.41, for 10–19 nodes, 20+ nodes, respectively; 4–9 nodes as the reference; P = 0.002). In post-NCT node-positive (LN+) patients, a lower LNR was correlated with a better RFS on multivariate analysis, and pN staging failed to show independent prognostic significance when the LNR was included in the Cox regression model (hazard ratio = 4.2, 2.97, 2.24, and 1.68 for LNR 81–100, 61–80, 41–60; and 21–40 %, respectively; LNR 0–20 % as the reference. P < 0.001). In addition, there were significant differences in the estimated 5-year RFS for pN1 (P = 0.043) and pN3 patients (P = 0.03) among the different LNR subgroups.

Conclusions

Our study has provided new evidence that the number of dissected nodes (in LN? patients) and the LNR (in LN+ patients) might be a complementary or alternative method to traditional pN staging when evaluating disease after primary treatment.     

Prognostic Relevance of Number and Ratio of Metastatic Lymph Nodes in Resected Pancreatic, Ampullary, and Distal Bile Duct Carcinomas

Background

Lymph node ratio (LNR) may be more useful than nodal (N) status in prognostic subclassification of adenocarcinomas after pancreatoduodenectomy. Ampullary (AC), biliary (DBC), and pancreatic (PC) adenocarcinomas are biologically distinct, and nodal involvement may have different prognostic importance among these separate cancers.

Methods

We included 179 consecutive pancreatoduodenectomies for PC, AC, or DBC, and performed standardized histopathologic evaluation, including prospective registration and retrospective reevaluation of the cancer origin. Associations between histopathologic variables and LNR, N status, and number of metastatic nodes were evaluated. Unadjusted and adjusted survival analysis was performed.

Results

Overall 5 year survival was 6 % for PC (n = 72), 26 % for DBC (n = 46), and 46 % for AC (n = 61). Lymph node involvement was more frequent in PC (75 %) than in AC (48 %) and DBC (57 %). In PC, N status did not discriminate between prognostic groups (N1 vs. N0; p = 0.31). However, increasing LNR was associated with poorer survival in unadjusted analysis, as well as when adjusting for margin involvement, degree of differentiation, and tumor diameter (p = 0.032; hazard ratio 1.87, 95 % confidence interval 1.06–3.31). In AC and DBC, N status clearly discriminated between subgroups of patients with different long-term survival in unadjusted and adjusted survival analysis (N1 vs. N0; p < 0.001), whereas number of metastatic nodes and LNR did not predict survival among node-positive resections.

Conclusions

The predictive value of nodal involvement depends on the type of cancer within the pancreatic head. In AC and DBC, N status adequately discriminates between good and poor prognosis. In PC, LNR may be more powerful in prognostic subclassification.     

Modern Chemotherapy Mitigates Adverse Prognostic Effect of Regional Nodal Metastases in Stage IV Colorectal Cancer

Background

In colorectal cancer, the involvement of regional lymph nodes with metastasis is an established prognostic factor. The impact of the number of positive nodes on patient outcome with stage IV disease is not well defined.

Methods

A retrospective review was performed of 1,421 patients at two tertiary referral centers with stage IV colorectal cancer who underwent primary tumor resection. Associations between regional nodes, lymph node ratio (LNR), and overall survival (OS) from date of diagnosis were analyzed.

Results

The number of positive regional nodes and LNR correlated with multiple sites of metastases (p?<?0.001). Survival was significantly associated with the number of positive nodes and LNR, with a median OS of 43 months with negative nodes, compared to 20 months with ≥7 positive nodes (p?<?0.001). The number of regional nodal metastases correlated with OS among 400 patients undergoing resection of liver metastases (p?=?0.005) but lost prognostic significance in the subset of 223 patients who underwent hepatectomy with perioperative oxaliplatin- or irinotecan-based chemotherapy (p?=?0.48).

Conclusions

In stage IV colorectal cancer, an increasing number of positive regional nodes and LNR correlate with multiple sites of metastases and poorer survival. The number of metastatic regional lymph nodes loses prognostic significance with modern chemotherapy in patients undergoing resection of liver metastases.     

Japanese D3 Lymph Node Dissection in Low Rectal Cancer with Inferior Mesenteric Lymph Node Metastases

Background

There is currently no consensus on the significance of Japanese D3 lymph node dissection in low rectal cancer with inferior mesenteric lymph node (IMLN) metastasis. This is partly because, despite a number of studies on the subject, cases of IMLN metastasis are relatively rare, and there are few cases of curative resection because of metastasis to other organs. A retrospective study involving a large number of patients was conducted.

Methods

The subjects were 2,743 patients registered in the national registry of the Japanese Society for Cancer of the Colon and Rectum. The data were analyzed for (1) prognostic factors for IMLN metastasis, and (2) outcomes in R0 cases with IMLN metastasis.

Results

In the control group, 67 patients (2.7 %) were considered positive for IMLN metastasis. The outcomes in the 35 R0 cases with IMLN metastasis were 50.8 % for 5-year relapse-free survival (RFS) and 61.9 % for 5-year overall survival (OS), which were each better than for R1+R2 cases (5-year RFS 16.1 %, p = 0.0001; 5-year OS 26.7 %, p = 0.0002). The outcomes for R0 cases (total metastatic lymph nodes ≥7) with IMLN metastasis (5-year RFS 53.9 %, 5-year OS 68.8 %) did not differ significantly from those for IMLN(?) cases (5-year RFS 54.6 %, 5-year OS 57.1 %) (RFS: p = 0.9515, OS: p = 0.4621).

Conclusions

It was confirmed that cases of IMLN metastasis in low rectal cancer tend to have a large total number of metastatic lymph nodes, but if curative resection can be performed, a good prognosis can be expected. These results demonstrate the value of radical Japanese D3 lymph node dissection in low rectal cancer with IMLN metastasis.