Prognostic assessment of different metastatic lymph node staging methods for gastric cancer after D2 resection

AIM: To compare the prognostic assessment of lymph node ratio and absolute number based staging system for gastric cancer after D2 resection. METHODS: The clinical, pathologic, and long-term follow-up data of 427 patients with gastric cancer that underwent D2 curative gastrectomy were retrospectively analyzed. The relationships between the metastatic lymph node ratio (MLR), log odds of positive lymph nodes (LODDS), and positive lymph nodes (pN) staging methods and the long-term prognoses of the patients were compared. In addition, the survival curves, accuracy, and homogeneity were compared with stratification to evaluate the prognostic assessment of the 3 methods when the number of tested lymph nodes was insufficient (< 10 and 10-15). RESULTS: MLR [hazard ratio (HR) = 1.401, P = 0.012], LODDS (HR = 1.012,P = 0.034), and pN (HR = 1.376, P = 0.005) were independent risk factors for gastric cancer patients. The receiver operating characteristic (ROC) curves showed that the prognostic accuracy of the 3 methods was comparable (P > 0.05). Spearman correlation analysis confirmed that MLR, LODDS, and pN were all positively correlated with the total number of tested lymph nodes. When the number of tested lymph node was < 10, the value of survival curves staged by MLR and LODDS was superior to those of pN staging. However, the difference in survival curves between adjacent stages was not significant. In addition, the survival rate of stage 4 patients using the MLR and LODDS staging methods was 26.7% and 27.3% with < 10 lymph node, respectively which were significantly higher than the survival rate of patients with > 15 tested lymph nodes (< 4%). The ROC curve showed that the accuracy of the prognostic assessment of MLR, LODDS, and pN staging methods was comparable (P > 0.05), and the area under the ROC curve of all 3 methods were increased progressively with the enhanced levels of examined lymph nodes. In addition, the homogeneity of the 3 methods in patients with ≤ 15 tested lymph nodes also showe     

Original study: The rescue staging for pancreatic ductal adenocarcinoma with inadequate examined lymph nodes

BackgroundIn previous studies, it’s recommended that the lymph node involvement should be evaluated with enough examined lymph nodes (eLNs) in the 8th American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer. This study aims to put forward a rescue staging system for pancreatic ductal adenocarcinoma (PDAC) patients with inadequate eLNs after pancreatoduodenectomy (PD).Method11,224 PDAC patients undergoing PD in The Surveillance, Epidemiology, and End Results (SEER) database were included. Another Ruijin Pancreatic Disease Center (RJPDC) database consisted of 821 patients was utilized for external validation.ResultsThe proportions of patients with eLNs≥15 were 44.7% and 32.8% in SEER and RJPDC database separately. The rescue staging system was put forward relying on LNR (HR = 1.83, 95% CI 1.74–1.92, P < 0.001) for N staging of eLNs<15 population and pLNs for the rest. The TNM modalities were also rearranged in the rescue system for better survival coordination. The C-index of rescue staging system was 0.638 while that of AJCC 8th staging system was 0.613 in SEER database. Similar phenomena were observed in RJPDC database. Kaplan-Meier analyses revealed reliable internal coherences (SEER: Ib: P = 0.26; IIa: P = 0.063; IIb: P = 0.53; IIIa: P = 0.11. RJPDC: Ib: P = 0.32; IIa: P = 0.66; IIb: P = 0.76; IIIa: P = 0.66) and significant staging efficiency (SEER: P < 0.001; RJPDC: P = 0.002).ConclusionA rescue staging system was put forward regardless of the eLNs number. And the novel system manifested better predictive capacity than 8th AJCC staging system.     

Prognostic significance of perigastric lymph nodes metastases on survival in patients with thoracic esophageal cancer

Several publications have showed that the number of metastatic lymph node (LN) should be taken into consideration in nodal category of esophageal cancer, but seldom considered extent of involved regional LNs. The aim of this study is to evaluate the significance of the extent of regional LN metastasis on survival in patients with esophageal cancer. A total of 245 thoracic esophageal cancer patients underwent transthoracic esophagectomy with standard lymphadenectomy between January 2000 and December 2006 were included in the study. Data including demographic factors, pathologic findings, LN parameters and survival outcomes were collected. The survival experience was depicted using Kaplan‐Meier method. A multivariate Cox proportional hazard model was used to screen the significant prognostic factors. The univariate analysis to further explore the significant prognostic factor was done by log‐rank test. After a median follow‐up of 53.2 months, the 5‐year survival rate was 46.3% for the entire cohort. Cox model regression indicated that the LN status and perigastric nodal status, aside from residual tumor status, histological tumor type and depth of invasion, were the independent prognostic factors. Patients without LN metastasis had better 5‐year survival than those with positive nodes (64.2% vs. 18.9%, X²= 35.875, P < 0.001). However, For those patients with nodal involvement, there was no difference in 5‐year survival between patients with involved nodes <3 and ≥3 (27.8% vs. 0%, X²= 0.925, P= 0.336). When considering the location of LN metastasis, patients could be further stratified according to whether the perigastric nodes were involved or not (37.5% vs. 10.0%, X²= 4.295, P= 0.038). In conclusion, involved LN number had no prognostic implication in nodal involved patients based on our data. Whereas, perigastric nodal involvement should be used to refine the N category (N0, no nodal metastasis, N1, non‐perigastric node metastasis, N2, perigastric node metastasis) for the future esophageal cancer staging criteria.     

Anatomical location of metastatic lymph nodes: an indispensable prognostic factor for gastric cancer patients who underwent curative resection

Background: Although the numeric-based lymph node (LN) staging was widely used in the worldwide, it did not represent the anatomical location of metastatic lymph nodes (MLNs) and not reflect extent of LN dissection. Therefore, in the present study, we investigated whether the anatomical location of MLNs was still necessary to evaluate the prognosis of node-positive gastric cancer (GC) patients.

Methods: We reviewed 1451 GC patients who underwent radical gastrectomy in our institution between January 1986 and January 2008. All patients were reclassified into several groups according to the anatomical location of MLNs and the number of MLNs. The prognostic differences between different patient groups were compared and clinicopathologic features were analyzed.

Results: In the present study, both anatomical location of MLNs and the number of MLNs were identified as the independent prognostic factors (p?p?p?p?Conclusion: The anatomical location of MLNs was an important factor influencing the prognostic outcome of GC patients. To provide more accurate prognostic information for GC patients, the anatomical location of MLNs should not be ignored.     

Lymph node staging in colorectal cancer:Old controversies and recent advances

Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC)tumor node metastasis(TNM)system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer.For affected patients,the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis.In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen,several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging.These include changing definitions of lymph nodes,involved lymph nodes,and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected.Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression.Outcome prediction based on the lymph node ratio,defined as the number of positive lymph nodes divided by the total number of retrieved nodes,may be superior to the absolute numbers of involved nodes.Extracapsular invasion has been identified as additional prognostic factor.Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis.The clinical value of more recent technical advances,such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined.     

Prognostic evaluation and review of immunohistochemically detected disseminated tumor cells in peritumoral lymph nodes of patients with pN0 colorectal cancer

Background The value of immunohistochemical detection of disseminated tumor cells in histopathologically tumor-free lymph nodes (pN0) of patients with colorectal cancer is still of uncertain prognostic value. We therefore evaluated the immunohistochemical detection rates and their prognostic value comparing three different monoclonal antibodies.Methods A total of 170 lymph nodes of 85 patients with curatively resected colorectal carcinoma at UICC stage I or II were evaluated for disseminated tumor cells. Frozen sections of each lymph node were immunohistochemically stained using three antibodies directed against CEA, CK20, and Ber-EP4. The detection rates were compared with histopathological tumor parameters and with the patients survival. The median follow-up time was 86 months.Results CEA-, CK20-, and Ber-EP4-positive disseminated tumor cells were identified microscopically in lymph nodes of 23 patients (27%), 24 patients (28%), and 23 patients (27%), respectively. In 18 patients (21%) disseminated tumor cells were found in consecutive sections and stained positive for all three monoclonal antibodies. The lymph nodes of 10 of 18 patients (56%), which developed tumor recurrence, contained CEA- and CK20-positive disseminated tumor cells. Ber-EP4-positive cells were present in lymph nodes of 9 of 18 patients (50%) with tumor recurrence. The 5-year overall survival of the 23 patients with CEA-positive disseminated tumor cells was 72% compared to 91% of the patients without immunohistochemical evidence of tumor cells (p<0.01). While the identification of CK20-positive tumor cells was also correlated significantly with a worse overall patient survival (p<0.01), the application of Ber-EP4 failed to reach significance (p=0.057). Multivariate analysis identified the tumor site (colon versus rectal cancer) (p<0.006) and the presence of CEA-positive disseminated tumor cells (p<0.03) as independent prognostic factors.Conclusion In colorectal carcinoma, the immunohistochemical detection of disseminated tumor cells in histopathologically pN0 peritumoral lymph nodes allows the identification of a subgroup with a significantly worse prognosis. Nevertheless, the prognostic value of immunohistochemically detected disseminated tumor cells remains controversial due to the nonuniform data in the literature.     

Ratio of metastatic lymph nodes is more important for rectal cancer patients treated with preoperative chemoradiotherapy

AIM:To evaluate the predictive value of the lymph node(LN) ratio(LNR,number of metastatic LNs/ examined LNs) for recurrence in patients with rectal cancer and to compare its applicability according to preoperative chemoradiotherapy(PCRT).METHODS:From 2000 to 2009,967 patients with metastatic LNs after curative resection for locally advanced rectal cancer were identified.Patients were categorized according to PCRT(PCRT vs No PCRT).The cut-off LNR was determined based on the p N1 vs p N2 when the recommended number of LNs was harvested.The 5-year recurrence-free survival(RFS) rates using the Kaplan-Meier method were compared according to p/yp N stage and the LNR in each group.RESULTS:Among patients with the same p/yp N stage,the 5-year RFS rate differed according to the LNR.In addition,the 5-year RFS rate was significantly different between p N and LNR groups in patients with No PCRT.In PCRT group,however,only LNR was associated with prognosis.On multivariate analysis,both p N and LNR were significant independent prognostic factors for 5-year RFS in the No PCRT group.In the PCRT group,only LNR category was found to be associated with RFS(HR = 2.36,95%CI:1.31-3.84,and P = 0.001).CONCLUSION:The LNR is an important prognostic predictor of RFS in rectal cancer patients especially treated with PCRT.Current p N categories could not discriminate between prognostic groups of RFS after PCRT.     

Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer

Accurate prediction of lymph node (LN) status is crucially important for appropriate treatment planning in patients with early gastric cancer (EGC). However, consensus on patient and tumor characteristics associated with LN metastasis are yet to be reached. Through systematic search, we identified several independent variables associated with LN metastasis in EGC, which should be included in future research to assess which of these variables remain as significant predictors of LN metastasis. On the other hand, even if we use these promising parameters, we should realize the limitation and the difficulty of predicting LN metastasis accurately. The sentinel LN (SLN) is defined as first possible site to receive cancer cells along the route of lymphatic drainage from the primary tumor. The absence of metastasis in SLN is believed to correlate with the absence of metastasis in downstream LNs. In this review, we have attempted to focus on several independent parameters which have close relationship between tumor and LN metastasis in EGC. In addition, we evaluated the history of sentinel node navigation surgery and the usefulness for EGC.     

Cervical lymph node metastases in papillary thyroid cancer: Preoperative staging with ultrasound and/or computed tomography

Preoperative screening of potential risk of lymph node metastasis is necessary for thyroidectomy plus lymph node dissection. The 2015 American thyroid association management guidelines do not recommend prophylactic cervical lymph node resection without clinical evidence of metastasis. Ultrasound is recommended imaging method and routine computed tomography is not recommended by the 2015 American thyroid association management guidelines for screening of lymph node metastasis. The objective of the study was to compare the diagnostic performance of ultrasound against that of computed tomography for screening cervical lymph node metastasis of patients with papillary thyroid cancer before thyroidectomy plus lymph node dissection.Data regarding preoperative neck ultrasound, neck computed tomography, and physical examination of the head and neck and postoperative pathological results of a total of 185 patients (age > 18 years) with a diagnosis of papillary thyroid cancer who had suspicious lymph nodes on preoperative imaging and treated by thyroidectomy plus lymph node dissection for the therapeutic purpose were collected and analyzed.Sensitivity (78.09% vs 75.28%, P < .0001) and accuracy (77.29% vs 75.13%, P = .0004) of neck computed tomography scanning to detect cervical lymph node metastasis were higher than those of neck ultrasound scanning. Sensitivity, accuracy, positive clinical utility, and negative clinical utility for neck ultrasound scanning plus neck computed tomography scanning to detect cervical lymph node metastasis were higher among all index tests (P < .05 for all) and were statistically the same as those of surgical pathology (P > .05 for all). The working areas for decision-making of thyroidectomy plus lymph node dissection of the physical examination, neck ultrasound, the neck computed tomography, and the neck ultrasound scanning plus the neck computed tomography scanning were 0 to 0.691 diagnostic confidence/lesion, 0 to 0.961 diagnostic confidence/lesion, 0 to 0.944 diagnostic confidence/lesion, and 0 to 0.981 diagnostic confidence/lesion, respectively.Besides the neck ultrasound, the neck computed tomography scanning can be used as a complementary imaging method to detect cervical lymph node metastasis of patients with papillary thyroid cancer before thyroidectomy plus lymph node dissection.Level of evidence: III.Technical efficacy stage: 2.     

Effect of 3A lymph node resection on survival in patients with right-sided NSCLC: a retrospective,multicentre, propensity-score matching study

BackgroundWe aimed to assess the clinical significance and impact on survival of prevascular mediastinal lymph nodes (3A) in patients with right-sided lung cancer.MethodsProspective data of 6,348 patients, who underwent lung resection from 2005 to 2015, were retrospectively analysed. There were 221 patients who underwent 3A dissection (3ALN+), while 6,127 did not (3ALN−). We performed propensity score matching (PSM) to decrease selection bias (221 vs. 221).ResultsThe incidence of 3A metastasis was 8%, and it elevated with pT stage. Between pT1c and pT2a, there was a significant increase in the 3A metastasis incidence, which doubled from 4% to 9%. For pT4, the incidence was 15%. The highest incidence was found among patients undergoing pneumonectomy (10%) and in the N2b1 and N2b2 subgroups (33% and 64%). In univariable analysis, we found no differences in 5-year survival between 3ALN+ and 3ALN− (51% vs. 51%, P=0.74). But, non-metastatic 3ALN+, 3ALN−, and metastatic 3ALN+ differed significantly (P<0.0001). pN2 subgroups (pN2a1, pN2a2, pN2b1, pN2b2) within PSM analysis did not differ significantly in terms of survival. 3A metastasis failed to be an independent prognostic factor in the multivariable analysis of matched pN2 subgroups.ConclusionsRegardless of 3A lymph nodes failing to be an independent prognostic factor in our cohort, the incidence of metastases in lymph nodes increases notably in advanced stages. 3A metastasis rate is comparable to other lymph node stations. Therefore, superior mediastinal lymphadenectomy in advanced cancers may improve from resections of the 3A lymph node station.     

Size analysis of lymph node metastasis in esophageal cancer: diameter distribution and assessment of accuracy of preoperative diagnosis

Background In esophageal cancer, lymphatic spread occurs more frequently and at an earlier stage than in other gastrointestinal cancers, and both preoperative and intraoperative diagnoses of lymph nodes metastases are sometimes incorrect. Our objective was to measure the sizes of lymphatic metastases and to examine the accuracy of clinical diagnosis of lymphatic spread in patients with squamous cell carcinoma of the esophagus. Methods The sizes of 320 metastatic lymph nodes of 9254 dissected nodes from 92 consecutive esophagectomy patients over 1 year were measured and compared with the sizes of the actual metastases within the nodes. These data allowed investigation of the correct rate of preoperative diagnosis of lymph node metastasis. Results The mean diameter of the metastases was 4.8 mm, which was significantly smaller than that of the involved lymph nodes. Among the metastatic lymph nodes, 37.2% were less than 5 mm in diameter, and 63.1% of the metastases were less than 5 mm in diameter. The true-positive and true-negative diagnosis rate for all lymph node stations in three fields (neck, thorax, and abdomen) was only 23.2%, and the false-negative rate for diagnosis of lymph node metastasis was 53.7%. Conclusions Two-thirds of involved lymph nodes had very small metastases (<5 mm), suggesting that limited confidence should be placed in the preoperative diagnosis of lymphatic spread. Therefore, extensive lymph node dissection appears appropriate in esophageal cancer surgery, given the small sizes of many metastases and the difficulty with preoperative diagnosis.     

Clinicopathological study of lymph-node metastasis in 1,389 patients with early gastric cancer: assessment of indications for endoscopic resection

BACKGROUND: The endoscopic resection of early gastric cancers (EGC) is a standard technique in Japan and is increasingly used throughout the world. Further experience in the treatment of EGC and a clearer delineation of the factors related to lymph‐node metastasis would permit a more accurate assessment of endoscopic resection. METHODS: The study group comprised 1389 patients with EGC who underwent gastrectomy with lymph‐node dissection. We evaluated the relations of lymph‐node metastasis to clinicopathological factors. RESULTS: Of the 718 patients with intramucosal carcinomas, 14 (1.9%) had lymph‐node metastasis. All cases of lymph‐node metastasis were associated with ulceration. No lymph‐node metastasis was found in patients with intramucosal carcinomas without ulceration, irrespective of tumor size and histological type. Lymph‐node metastasis was present in 14 (4.7%) of the 296 patients who had cancer with a submucosal invasion depth of less than 500 μm (sm1). Significantly increased rates of lymph‐node metastasis were associated with undifferentiated types, ulcerated lesions and lymphatic invasion. No lymph‐node metastasis was found in patients with differentiated sm1 carcinomas 30 mm or less in diameter without ulceration. Lymph‐node metastasis occurred in 29% of the patients who had cancer with a submucosal invasion depth of 500 μm or more (sm2). CONCLUSION: This large series of patients with EGC provides further evidence supporting the expansion of indications for endoscopic treatment, as well as warns against potential risks.     

Use of Magnetic Resonance Imaging for N-Staging in Patients with Non-Small Cell Lung Cancer. A Systematic Review

Introduction

The aim of this study is to assess the diagnostic value of the magnetic resonance imaging (MRI) in differentiating metastasic from non-metastatic lymph nodes in NSCLC patients compared with computed tomography (CT) and fluorodeoxyglucose (FDG) - positron emission tomography (PET) or both combined.