Different lymph node staging systems for predicting the prognosis of colorectal neuroendocrine neoplasms

BACKGROUND Colorectal neuroendocrine neoplasms(NENs)are a rare malignancy that primarily arises from the diffuse distribution of neuroendocrine cells in the colon and rectum.Previous studies have pointed out that the status of lymph node may be used to predict the prognosis.AIM To investigate the predictive values of lymph node ratio(LNR),positive lymph node(PLN),and log odds of PLNs(LODDS)staging systems on the prognosis of colorectal NENs treated surgically,and compare their predictive values.METHODS This cohort study included 895 patients with colorectal NENs treated surgically from the Surveillance,Epidemiology,and End Results database.The endpoint was mortality of patients with colorectal NENs treated surgically.X-tile software was utilized to identify most suitable thresholds for categorizing the LNR,PLN,and LODDS.Participants were selected in a random manner to form training and testing sets.The prognosis of surgically treating colorectal NENs was examined using multivariate cox analysis to assess the associations of LNR,PLN,and LODDS with the prognosis of colorectal NENs.C-index was used for assessing the predictive effectiveness.We conducted a subgroup analysis to explore the different lymph node staging systems’predictive values.RESULTS After adjusting all confounding factors,PLN,LNR and LODDS staging systems were linked with mortality in patients with colorectal NENs treated surgically(P<0.05).We found that LODDS staging had a higher prognostic value for patients with colorectal NENs treated surgically than PLN and LNR staging systems.Similar results were obtained in the different G staging subgroup analyses.Furthermore,the area under the receiver operating characteristic curve values for LODDS staging system remained consistently higher than those of PLN or LNR,even at the 1-,2-,3-,4-,5-and 6-year follow-up periods.CONCLUSION LNR,PLN,and LODDS were found to significantly predict the prognosis of patients with colorectal NENs treated surgically.

Risk factors for lymph node metastasis in patients with pancreatic neuroendocrine neoplasms

BACKGROUND Although PNENs generally have a better prognosis than pancreatic cancers,some PNENs display malignant behavior including lymph node(LN)metastasis.Complete tumor resection can be the only potentially curative treatment for patients with resectable PNENs.However,the indications for LN dissection are still controversial.Over the last decade,minimally invasive surgery such as laparoscopic pancreatic surgery(LPS)has been increasingly performed for pancreatic tumors including PNENs.AIM To investigate the risk factors for LN metastasis in PNENs and to select appropriate patients for limited surgery by LPS.METHODS From April 2001 to December 2019,92 patients underwent pancreatic resection for PNENs at Kumamoto University Hospital.Finally,82 patients were enrolled in this study.Using perioperative factors,we examined the predictive factors for LN metastasis in PNENs.RESULTS Among the 82 patients,the percentage of LN metastasis according to the pathological findings was 12%(10/82 cases).The median tumor size was 12 mm(range:5-90 mm).The median tumor size in the LN-positive group(37 mm)was significantly larger than that in the LN-negative group(12 mm)(P=0.0001).Multivariate analyses revealed that larger tumor size(≥20 mm)was an independent risk factor for LN metastasis(odds ratio 16.8,P=0.0062).In patients with small tumors(≤10 mm),LN metastasis was not found.CONCLUSION Larger tumor size(≥20 mm)is an independent risk factor for LN metastasis in PNENs.In smaller PNENs(≤10 mm),we may be able to choose limited surgery without LN dissection.

Synaptophysin-like 2 expression correlates with lymph node metastasis and poor prognosis in colorectal cancer patients

BACKGROUND Colorectal cancer(CRC)is one of the most common and fatal cancers worldwide.Synaptophysin-like 2(SYPL2)is a neuroendocrine-related protein highly expressed in skeletal muscle and the tongue.The involvement of SYPL2 in CRC,including its level of expression and function,has not been evaluated.AIM To evaluate the correlations of SYPL2 expression with lymph node metastasis(LNM)and prognosis in patients with CRC.METHODS The levels of expression of SYPL2 in CRC and normal colorectal tissues were analyzed in multiple public and online databases.The associations between clinical variables and SYPL2 expression were evaluated statistically,and the associations between SYPL2 expression and prognosis in patients with CRC were analyzed using the Kaplan-Meier method and univariate/multivariate Cox regression analyses.SYPL2 expression was assessed in 20 paired CRC tissue and adjacent normal colorectal tissue samples obtained from Fuyang People’s Hospital,and the associations between SYPL2 expression and the clinical characteristics of these patients were investigated.Correlations between the levels of expression of SYPL2 and key targeted genes were determined by Pearson’s correlation analysis.The distribution of immune cells in these samples was calculated using the CIBERSORT algorithm.Gene set enrichment analysis(GSEA)was performed to evaluate the biofunction and pathways of SYPL2 in CRC.RESULTS SYPL2 expression was significantly lower in CRC tissue samples than in normal colorectal tissue samples(P<0.05).High SYPL2 levels in CRC tissues correlated significantly with LNM(P<0.05)and a poorer patient prognosis,including significantly shorter overall survival(OS)[hazard ratio(HR)=1.9,P<0.05]and disease-free survival(HR=1.6,P<0.05).High SYPL2 expression was an independent risk factor for OS in both univariate(HR=2.078,P=0.014)and multivariate(HR=1.754,P=0.018)Cox regression analyses.In addition,SYPL2 expression correlated significantly with the expression of KDR(P<0.0001,r=0.47)and the BRAFV600E mutation(P<0.05).Higher SYPL2 expression was associated with the enrichment of CD8 T-cells and M0 macrophages in the tumor microenvironment.GSEA revealed that SYPL2 was associated with the regulation of epithelial cell migration,vasculature development,pathways in cancer,and several vital tumor-related pathways.CONCLUSION SYPL2 expression was lower in CRC tissue than in normal colorectal tissue.Higher SYPL2 expression in CRC was significantly associated with LNM and poorer survival.

S100A4 over-expression underlies lymph node metastasis and poor prognosis in colorectal cancer

AIM:To develop lymph node metastasis(LNM)-associated biomarkers for colorectal cancer(CRC) using quantitative proteome analysis.METHODS:Differences in protein expression between primary CRC with LNM(LNM CRC) and without LNM(non-LNM CRC) were assessed using methyl esterification stable isotope labeling coupled with 2D liquid chromatography followed by tandem mass spectrometry(2D-LC-MS/MS).The relationship to clinicopathological parameters and prognosis of candidate biomarkers was examined using an independent sample set.RESULTS:Forty-three proteins were found to be differentially expressed by at least 2.5-fold in two types of CRC.S100A4 was significantly upregulated in LNM CRC compared with non-LNM CRC,which was confirmed by Western blotting,immunohistochemistry and real-time quantitative polymerase chain reaction.Further immunohistochemistry on another 112 CRC cases showed that overexpression of S100A4 frequently existed in LNM CRC compared with non-LNM CRC(P < 0.001).Overexpression of S100A4 was significantly associated with LNM(P < 0.001),advanced TNM stage(P < 0.001),increased 5-year recurrence rate(P < 0.001) and decreased 5-year overall survival rate(P < 0.001).Univariate and multivariate analyses indicated that S100A4 expression was an independent prognostic factor for recurrence and survival of CRC patients(P < 0.05).CONCLUSION:S100A4 might serve as a powerful biomarker for LNM and a prognostic factor in CRC.

Downregulation of miR-193a-5p correlates with lymph node metastasis and poor prognosis in colorectal cancer

AIM:To investigate the correlation of miR-193a-5p with lymph node metastasis and postoperative survival of colorectal cancer(CRC)patients.METHODS:A total of 304 formalin-fixed,paraffinembedded specimens(69 paired cancer and normal tissues,55 primary tumors of stageⅢCRC and matched lymph nodes,and 56 primary tumors of stageⅡCRC)were included in this study.The relative expression lev-els of miR-193a-5p in the normal mucosa,primary cancer,and metastatic lymph node lesions were measured by quantitative real-time reverse transcriptase polymerase chain reaction.We evaluated the association of its expression with colorectal cancer lymph node metastasis,clinicopathological factors,and patient survival.RESULTS:The relative expression level of miR-193a-5p was significantly lower in CRC tissues than in the normal mucosa(P=0.0060).The expression levels of miR-193a-5p were lower in primary CRC tissues with lymph node metastases than in those without metastases(P=0.0006),and decreased expression of miR-193a-5p correlated with advanced lymph node metastatic stage(P=0.0007).Kaplan-Meier analysis showed that patients with low miR-193a-5p expression had decreased disease-free survival(DFS)(P=0.0026)and poor overall survival(OS)(P=0.0003).Interestingly,for the group of patients with lymph node metastases,miR-193a-5p expression was also related to survival.Patients with low miR-193a-5p expression had decreased DFS(P=0.0262)and poor OS(P=0.0230).Moreover,multivariate analysis indicated that downregulation of miR-193a-5p was an independent predictor of poor OS.CONCLUSION:Downregulation of miR-193a-5p correlates with lymph node metastasis and poor survival of CRC.miR-193a-5p may be a useful biomarker for CRC diagnosis,metastasis and prognosis prediction.

Lymph Node Mapping with Carbon Nanoparticles and the Risk Factors of Lymph Node Metastasis in Gastric Cancer

The study aimed to examine the applicability of carbon nanoparticles as a tracer for lymph node mapping and the related factors of lymph node and No.8p subgroup metastasis in patients with gastric cancer.Clinical data of 50 patients with gastric cancer,who had not received treatment preoperatively and underwent gastrectomy in Department of Gastrointestinal Surgery,Wuhan Union Hospital,between October 2014 and August 2015,were retrospectively analyzed.These patients were found to have no distant metastasis preoperatively.Thirty-five out of 50 patients were subjected to lymphatic mapping technique using carbon nanoparticles as the tracer,and the rest 15 cases did not experience the lymphatic mapping and served as controls.The sensitivity,specificity,false positive rate and false negative rate were calculated according to the number of lymph nodes,and the staining and metastasis condition of lymph nodes.The diagnostic value of carbon nanoparticles on metastatic lymph nodes was evaluated.The relationship between the metastasis of lymph nodes or subgroup No.8p lymph nodes and clinicopathologic features was analyzed by χ^2-test or Fisher＇s exact test.All patients underwent D2 surgery（lymph node dissection including all the group 1 and group 2 nodes） plus the dissection of the subgroup No.8p lymph nodes.It was found that the average number of harvested lymph nodes in lymphatic mapping technique group（45.7±14.5） was greater than that in control group（39.2±11.7）,but the difference was not significantly different（P=0.138〉0.05）.The success rate,the accuracy,sensitivity,specificity and false negative rate was 97%,57%,28%,62% and 72% respectively.The metastasis of lymph nodes was correlated to the depth of cancer invasion（T stage）（P=0.004〈0.05）,and the metastasis of No.8p lymph nodes was correlated to the extent of lymph node involvement（N stage）（P=0.007〈0.05）.Six cases had lymph node metastasis in subgroup No.8p,and their TNM stages and clinical stages were as follows：T1N2M0 ⅡA,T3N3M0 ⅢB,T4 a N3M0 ⅢC,T4 a N3M0 ⅢC,T4 a N3M0 ⅢC,and T4 b N3M0 ⅢC.In conclusion,our study indicated that carbon nanoparticles failed to show good selectivity for metastatic lymph nodes;the result of lymphatic mapping does not achieve a satisfactory performance;the incidence of lymph node metastasis may increase,accompanying with the increase of the depth of cancer invasion;No.8p lymph node metastasis tends to occur for gastric carcinoma patients with the extent of lymph node metastasis over N2 stage.

Separate lateral parametrial lymph node dissection improves detection rate of parametrial lymph node metastasis in early-stage cervical cancer: 10-year clinical evaluation in a single center in China

Objective: To investigate the clinical significance of separate lateral parametrial lymph node dissection(LPLND) in improving parametrial lymph node(PLN) and its metastasis detection rate during radical hysterectomy for early-stage cervical cancer.Methods: From July 2007 to August 2017, 2,695 patients with cervical cancer in stage IB1-IIA2 underwent radical hysterectomy were included. Of these patients, 368 underwent separate dissection of PLNs using the LPLND method, and 2,327 patients underwent conventional radical hysterectomy(CRH). We compared the surgical parameters, PLN detection rate and PLN metastasis rate between the two groups.Results: Compared with CRH group, the rate of laparoscopic surgery was higher(60.3% vs. 15.9%, P<0.001),and the blood transfusion rate was lower(19.0% vs. 29.0%, P<0.001) in the LPLND group. PLNs were detected in 356 cases(96.7%) in the LPLND group, and 270 cases(11.6%) in the CRH group(P<0.001), respectively. The number of PLNs detected in the LPLND group was higher than that in the CRH group(median 3 vs. 1, P<0.001).The PLN metastases were detected in 25 cases(6.8%) in the LPLND group, and 18 cases(0.8%) in the CRH group(P<0.001), respectively. In multivariable analysis, LPLND is an independent factor not only for PLN detection [odds ratio(OR)=228.999, 95% confidence interval(95% CI): 124.661-420.664;P<0.001], but also for PLN metastasis identification(OR=10.867, 95% CI: 5.381-21.946;P<0.001).Conclusions: LPLND is feasible and safe. The surgical method significantly improves the detection rate of PLN and avoids omission of PLN metastasis during radical hysterectomy for early-stage cervical cancer.

Relationship between Preoperative Clinicopathologic Characteristics and Lymph Node Metastasis in Early Gastric Cancer

Objective： To investigate the features of the preoperative clinicopathologic characteristics in correlation with lymph node metastasis. Methods： The preoperative clinicopathologic characteristics and lymph node metastasis of 265 patients with early gastric carcinoma were analyzed retrospectively. Results： The three clinicopathologic characteristics, maximum cancer diameter 〉2cm under endoscope, poor differentiation and excavated type were significant high risk independent preoperative clinicopathologic characteristics （P〈0.05） . The patients who had none of the three preoperative clinicopathologic characteristics had no lymph node metastasis, while 27.27% of the patients who had all the three preoperative clinicopathologic characteristics had N2 lymph node metastasis. Conclusion： The three preoperative clinicopathologic charaeteristics, maximum cancer diameter under endoscope, cell differentiation and gross type were very useful to evaluate the extent of lymph node metastasis.

Significance of the lymph nodes in the 7th station in rational dissection for metastasis of distal gastric cancer with different T categories

Objective： To determine the clinicopathological characteristics, and evaluate the appropriate extent of lymph node dissection in distal gastric cancer patients with comparable T category. Methods： A retrospective study was conducted on 570 distal gastric cancer patients, who underwent gastric resection with D2 nodal dissection, which was performed by the same surgical team from January 1997 to January 2011. We compared the differences in lymph node metastasis rates and metastatic lymph node ratios between different T categories. Additionally, we investigated the impact of lymph node metastasis in the 7th station on survival rate of distal gastric cancer patients with the same TNM staging. Results： Among the 570 patients, the overall lymph node metastasis rate of advanced distal gastric cancer was 78.1%, and the metastatic lymph node ratio was 27%. The lymph node metastasis rate in the 7th station was similar to that of perigastric lymph nodes. There was no statistical significance in patients with the same TNM stage （stage Ⅱ and Ⅲ）, irrespective of the metastatic status in the 7th station. Conclusions： Our results suggest that to a certain extent, it is reasonable to include lymph nodes in the 7th station in the D 1 lymph node dissection.

Factors contributing to lymph node occult metastasis in supraglottic laryngeal carcinoma cT2-T4 N0M0 and metastasis predictive equation

Objective： To investigate factors that contribute to lymph node metastasis（LNM） from clinical cT2-T4 N0M0（cN0） supraglottic laryngeal carcinoma（SLC）, and to predict the risk of occult metastasis before surgery.Methods： A total of 121 patients who received surgery were retrospectively analyzed. Relevant factors regarding cervical LNM were analyzed. Multivariate analyses were conducted to predict the region where the metastasis occurred and prognosis. Results： The overall metastatic rate of c N0 SLC was 28.1%. Metastatic rates were 15.4%, 32.5% and 35.7% for T2, T3 and T4, respectively. Metastatic rates for SLC levels II, III and IV were 19.6%, 17.2% and 3.6%, respectively. A regression equation was formulated to predict the probability of metastasis in cN0 SLC as follows： Pn=e（–3.874＋0.749T3＋1.154T4＋1.935P1＋1.750P2）/[1＋e（–3.874＋0.749T3＋1.154T4＋1.935P1＋1.750P2）]. Approximately 0.2% of patients experienced LNM with no recurrence of laryngeal cancer. Comparison of the intergroup survival curves between patients with and without LNM indicated a statistically significant difference（P=0.029）.Conclusions： Cervical lymph node metastatic rates tended to increase in tandem with T stage in patients with LNM in cN0 SLC, and neck dissection is advised for these patients. Moreover, cervical LNM in cN0 SLC showed a sequential pattern and may be predicted.

A CLINICOPATHOLOGICAL STUDY OF MEDIASTINAL LYMPH NODE METASTASIS OF LUNG CANCER

Objective: To investigate pathologically the characteristics of lung cancer metastasis by mediastinal lymph node ways (N2). Methods: Of 398 lung cancer patients who underwent radical pulmonectomy and extensive lymph node dissection, 160 patients were diagnosed as with N2 metastasis, their 352 groups of mediastinal lymph nodes invaded were subject to the pathological study. Results: Evidences showed that the N2 metastasis of lung cancer was very active. It appears as single group or multi-group or jumping-form metastasis, rating 41.2%, 58.8% and 29.3% respectively. In addition, the extension of N2 metastasis was large, the most concentrated site was the 7th group lymph node (48.8%), then the 4th, 3rd and 5th group, rating 45.6%, 31.3% and 25.6% respectively. The occurrence of N2 metastasis was highly correlated with the site, size, histopathological type and the grade of differentiation of the cancer. An another feature of N2 metastasis was the invasion of metastasized lymph node into the bronchial wall, especially in adenocarcinoma. Conclusion: In order to achieve the radical removal of tumor, it is necessary to dissect the lymph nodes of the hilar and upper and lower mediastinum at the homolateral thoracic cavity actively and completely; beside, attention may be paid to the bronchial wall invasion caused by the lymph nodes metastasized.

Clinical significance of lymph node metastasis in gastric cancer

Gastric cancer,one of the most common malignancies in the world,frequently reveals lymph node,peritoneum,and liver metastases.Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection,which results in poor prognosis.Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer.Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials,it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year followup study.Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide,but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis.It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer.Besides,the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer.

Prognostic role of lymph node metastasis in early gastric cancer

Objective： To clarify the relationship between clinicopathological features and lymph node metastasis and to propose the potential indications of lymph node metastasis for prognosis in early gaswic cancer （EGC） patients. Methods： We retrospectively observed 226 EGC patients with lymph node resection, and analyzed the associations between lymph node metastasis and clinicopathological parameters using the chi-square test in univariate analysis and logistic regression analysis in multivariate analysis. Overall survival analysis was determined using the Kaplan-Meier and log-rank test. We conducted multivariate prognosis analysis using the Cox proportional hazards model. Results： Of all the EGC patients, 7.5% （17/226） were histologically shown to have lymph node metastasis. The differentiation, lymphovascular invasion and depth of invasion were independent risk factors for lymph node metastasis in EGC. The 5- and 10-year survival rates were significantly lower in patients with lymph node metastasis than in those without and the patients also had shorter progress-free survival time. Lymph node metastasis and tumor size were independent prognostic factors for EGC. The status of the lymph nodes was a significant factor in predicting recurrence or metastasis after surgery. Conclusions： The undifferentiated carcinoma and lymphovascular and/or submucosal invasion were associated with a higher incidence of lymph node metastasis in EGC patients, whom need to perform subsequent D2 lymphadenectomy or laparoscopic lymph node dissection and more rigorous follow-up or additional chemotherapy/radiation after D2 gastrectomy for poor prognosis and high recurrence/metastasis rate.

Comparison of different lymph node staging systems in prognosis of gastric cancer:a bi-institutional study from Hungary

Objective： The Union for International Cancer Control （UICC） Node （N） classification is the most common used staging method for the prognosis of gastric cancer. It demands adequate, at least 16 lymph nodes （LNs） to be dissected; therefore different staging systems were invented. Methods： Between March 2005 and March 2010, 164 patients were evaluated at the Department of General Surgery in the Ken^zy Gyula Hospital and at the Department of General, Thoracic and Vascular Surgery in the Kaposi M6r Hospital. The 6th, 7th and 8th UICC N-staging systems, the number of examined LNs, the number of harvested negative LNs, the metastatic lymph node ratio （MLR） and the log odds of positive LNs （LODDS） were determined to measure their 5-year survival rates and to compare them to each other. Results： The overall 5year survival rate for all patients was 55.5% with a median overall survival time of 102 months. The tumor stage, gender, UICC N-stages, MLR and the LODDS were significant prognostic factors for the 5-year survival with univariate analysis. The 6th UICC N-stage did not follow the adequate risk in comparing N2 vs. NO and N3 vs. NO with multivariate investigation. Comparison of performances of the residual N classifications proved that the LODDS system was first in the prediction of prognosis during the evaluation of all patients and in cases with less than 16 harvested LNs. The MLR gave the best prognostic prediction when adequate （more than or equal to 16） lymphadenectomy was performed. Conclusions： We suggest the application of LODDS system routinely in western patients and the usage of MLR classification in cases with extended lymphadenectomy.

A new radiomics approach combining the tumor and peri-tumor regions to predict lymph node metastasis and prognosis in gastric cancer

Objective The development of non-invasive methods for evaluating lymph node metastasis(LNM)preoperatively in gastric cancer(GC)is necessary.In this study,we developed a new radiomics model combining features from the tumor and peritumor regions for predicting LNM and prognoses.Methods This was a retrospective observational study.In this study,two cohorts of patients with GC treated in Zhongshan Hospital Fudan University(Shanghai,China)were included.In total,193 patients were assigned to the internal training/validation cohort;another 98 patients were assigned to the independent testing cohort.The radiomics features were extracted from venous phase computerized tomography(CT)images.The radiomics model was constructed and the output was defined as the radiomics score(RS).The performance of the RS and CT-defined N status(ctN)for predicting LNM was compared using the area under the curve(AUC).The 5-year overall survival and progression-free survival were compared between different subgroups using Kaplan–Meier curves.Results In both cohorts,the RS was significantly higher in the LNM-positive group than that in the LNM-negative group(all P<0.001).The radiomics model combining features from the tumor and peri-tumor regions achieved the highest AUC in predicting LNM(AUC,0.779 and 0.724,respectively),which performed better than the radiomics model based only on the tumor region and ctN(AUC,0.717,0.622 and 0.710,0.603,respectively).The differences in 5-year overall survival and progression-free survival between high-risk and low-risk groups were significant(both P<0.001).Conclusions The radiomics model combining features from the tumor and peri-tumor regions could effectively predict the LNM in GC.Risk stratification based on the RS was capable of distinguishing patients with poor prognoses.

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.METHODS We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy.PD-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive score.All PD-L1+PT staged as pN+were also tested for PD-L1 expression in their LNM.PD-L1(-)GC with pN+served as the comparison group.RESULTS Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the LNM.Regarding PD-L1(-)PT,9.1%(4/44)had PD-L1+in the LNM.The agreement between PT and LNM had a kappa value of 0.483.Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites.There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM.This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

Prediction of risk factors for lymph node metastasis in early gastric cancer

AIM:To explore risk factors for lymph node metastases in early gastric cancer(EGC) and to confirm the appropriate range of lymph node dissection.METHODS:A total of 202 patients with EGC who underwent curative gastrectomy with lymphadenectomy in the Department of Surgery,Xinhua Hospital and Ruijin Hospital of Shanghai Jiaotong University Medical School between November 2003 and July 2009,were retrospectively reviewed.Both the surgical procedure and the extent of lymph node dissection were based on the recommendations of the Japanese gastric cancer treatment guidelines.The macroscopic type was classified as elevated(type Ⅰ or Ⅱa),flat(Ⅱb),or depressed(Ⅱc or Ⅲ).Histopathologically,papillary and tubular adenocarcinomas were grouped together as differentiated adenocarcinomas,and poorly differentiated and signet-ring cell adenocarcinomas were regarded as undifferentiated adenocarcinomas.Univariate and multivariate analyses of lymph node metastases and patient and tumor characteristics were undertaken.RESULTS:The lymph node metastases rate in patients with EGC was 14.4%.Among these,the rate for mucosal cancer was 5.4%,and 8.9% for submucosal cancer.Univariate analysis showed an obvious correlation between lymph node metastases and tumor location,depth of invasion,morphological classification and venous invasion(χ 2 = 122.901,P = 0.001;χ 2 = 7.14,P = 0.008;χ 2 = 79.523,P = 0.001;χ 2 = 8.687,P = 0.003,respectively).In patients with submucosal cancers,the lymph node metastases rate in patients with venous invasion(60%,3/5) was higher than in those without invasion(20%,15/75)(χ 2 = 4.301,P = 0.038).Multivariate logistic regression analysis revealed that the depth of invasion was the only independent risk factor for lymph node metastases in EGC [P = 0.018,Exp(B) = 2.744].Among the patients with lymph node metastases,29 cases(14.4%) were at N1,seven cases were at N2(3.5%),and two cases were at N3(1.0%).Univariate analysis of variance revealed a close relationship between the depth of invasion and lymph node metastases at pN 1(P = 0.008).CONCLUSION:The depth of invasion was the only independent risk factor for lymph node metastases.Risk factors for metastases should be considered when choosing surgery for EGC.

Radical lymph node dissection and assessment:Impact on gallbladder cancer prognosis

AIM: To investigate the lymph node metastasis patterns of gallbladder cancer(GBC) and evaluate the optimal categorization of nodal status as a critical prognostic factor.METHODS: From May 1995 to December 2010,a total of 78 consecutive patients with GBC underwent a radical resection at Liaocheng People's Hospital.A radical resection was defined as removing both the primary tumor and the regional lymph nodes of the gallbladder.Demographic,operative and pathologic data were recorded.The lymph nodes retrieved were examined histologically for metastases routinely from each node.The positive lymph node count(PLNC) as well as the total lymph node count(TLNC) was recorded for each patient.Then the metastatic to examined lymph nodes ratio(LNR) was calculated.Disease-specific survival(DSS) and predictors of outcome were analyzed.RESULTS: With a median follow-up time of 26.50 mo(range,2-132 mo),median DSS was 29.00 ± 3.92 mo(5-year survival rate,20.51%).Nodal disease was found in 37 patients(47.44%).DSS of node-negative patients was significantly better than that of nodepositive patients(median DSS,40 mo vs 17 mo,χ2= 14.814,P < 0.001),while there was no significant difference between N1 patients and N2 patients(median DSS,18 mo vs 13 mo,χ2= 0.741,P = 0.389).Optimal TLNC was determined to be four.When node-negative patients were divided according to TLNC,there was no difference in DSS between TLNC < 4 subgroup and TLNC ≥ 4 subgroup(median DSS,37 mo vs 54 mo,χ2 = 0.715,P = 0.398).For node-positive patients,DSS of TLNC < 4 subgroup was worse than that of TLNC ≥ 4 subgroup(median DSS,13 mo vs 21 mo,χ2= 11.035,P < 0.001).Moreover,for node-positive patients,a new cut-off value of six nodes was identified for the number of TLNC that clearly stratified them into 2 separate survival groups(< 6 or ≥ 6,respectively;median DSS,15 mo vs 33 mo,χ2= 11.820,P < 0.001).DSS progressively worsened with increasing PLNC and LNR,but no definite cut-off value could be identified.Multivariate analysis revealed histological grade,tumor node metastasis staging,TNLC and LNR to be independent predictors of DSS.Neither location of positive lymph nodes nor PNLC were identified as an independent variable by multivariate analysis.CONCLUSION: Both TLNC and LNR are strong predictors of outcome after curative resection for GBC.The retrieval and examination of at least 6 nodes can influence staging quality and DSS,especially in nodepositive patients.

Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients

AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis(LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded.METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health(Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM(49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012.RESULTS: The baseline serum direct bilirubin concentration was(median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin(2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin wasindependently associated with LNM(OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that:(1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification;(2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and(3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis.CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers.

Patterns of lymph node metastasis are different in colon and rectal carcinomas

AIM:To describe patterns of lymph node metastasis in invasive colon and rectal carcinomas.METHODS:Clinical data of 2340 patients with colorectal carcinoma(stageⅠ to Ⅲ) who received radical resection,was retrospectively reviewed.Of the 2340 patients,1314 patients suffered from rectal carcinoma and 1026 from colon carcinoma.Patients with rectal cancer who received neoadjuvant chemoradiation therapy were excluded.Statistical analysis was performed using MannWhitney,χ 2 and Cochran's and Mantel-Haenszel tests(SPSS 15.0).A two-tailed P < 0.05 was considered statistically significant.RESULTS:Lymph node retrieval in the rectal carcinoma group was significantly lower than that in the colon carcinoma group(P < 0.001),while positive lymph node retrieval in the rectal carcinoma group was significantly higher than that in the colon carcinoma group(P < 0.001).The proportion of lymph node positive(N+) cases was higher(patients with one or more positive lymph nodes) in the rectal carcinoma group(P = 0.004).The number of N+ cases was compared at different T stages(T1-T4) to eliminate background bias and the results were confirmed(P < 0.001).In addition,the lymph node ratio(the ratio of number of positive lymph nodes over the number of lymph nodes examined) of stage Ⅲ cases in the rectal carcinoma group was significantly higher than that in the colon carcinoma group(P < 0.001).CONCLUSION:Rectal carcinomas seem more prone to metastasize to the lymph nodes than colon carcinomas,which may be of potential clinical significance.