Fifty-five cases of hepatic alveolar echinococcosis combined with lymph node metastasis:A retrospective study

BACKGROUND Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis(AE).Currently,there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of patients with hepatic AE combined with lymph node metastasis and its mechanism and management are still controversial.Radical hepatectomy combined with regional lymph node dissection is a better treatment.AIM To analyse the clinical features of hepatic AE combined with lymph node metastasis to explore its treatment and efficacy.METHODS A total of 623 patients with hepatic AE admitted to the First Affiliated Hospital of Xinjiang Medical University from 1 January 2012 to 1 January 2022 were retrospectively analysed.Fifty-five patients with combined lymph node metastasis were analysed for their clinical data,diagnosis and treatment methods,follow-up efficacy,and characteristics of lymph node metastasis.Finally,we comparatively analysed the lymph node metastasis rates at different sites.Categorical variables are expressed as frequencies and percentages,and the analysis of difference was performed using theχ2 test.The Bonferroni method was used for pairwise comparisons when statistical differences existed between multiple categorical variables.RESULTS A lymph node metastasis rate of 8.8%(55/623)was reported in patients with hepatic AE,with a female predilection(69.1%)and a statistically significant sex difference(χ2=8.018,P=0.005).Of the 55 patients with lymph node metastasis,72.7%had a parasite lesion,neighbouring organ invasion,and metastasis stage of P3N1M0 and above,of which 67.3%,78.2%,and 34.5%of hepatic AE lesions invaded the bile ducts,blood vessels,and distant metastases,respectively.Detection rates of lymph node metastasis of 16.4%,21.7%,and 34.2%were reported for a preoperative abdominal ultrasound,magnetic resonance imaging,and computed tomography examinations.All patients were intraoperatively suspected with enlarged lymph nodes and underwent radical hepatectomy combined with regional lymph node dissection.After surgery,a routine pathological examination was conducted on the resected lymph nodes.A total of 106 positive lymph nodes were detected in six groups at various sites,including 51 single-group metastasis cases and four multi-group metastasis cases.When the metastasis rates at different sites were statistically analysed,we observed that the metastasis rate in the para-hepatoduodenal ligament lymph nodes was significantly higher than that of the other sites(χ^(2)=128.089,P=0.000<0.05).No statistical difference was observed in the metastasis rate between the five other groups.Clavien-Dindo grade IIIa complication occurred in 14 cases,which improved after administering symptomatic treatment.Additionally,lymph node dissection-related complications were not observed.Recurrence after 2 years was observed in one patient.CONCLUSION Lymph node metastasis is a rare form of metastasis in hepatic AE,which is more frequent in women.Parahepatoduodenal ligament lymph nodes are commonly observed.Radical hepatectomy combined with regional lymph node dissection is a safe,effective,and feasible treatment for liver AE combined with lymph node metastasis.

Deep learning-based automatic pipeline system for predicting lateral cervical lymph node metastasis in patients with papillary thyroid carcinoma using computed tomography:A multi-center study

Objective:The assessment of lateral lymph node metastasis(LLNM)in patients with papillary thyroid carcinoma(PTC)holds great significance.This study aims to develop and evaluate a deep learning-based automatic pipeline system(DLAPS)for diagnosing LLNM in PTC using computed tomography(CT).Methods:A total of 1,266 lateral lymph nodes(LLNs)from 519 PTC patients who underwent CT examinations from January 2019 to November 2022 were included and divided into training and validation set,internal test set,pooled external test set,and prospective test set.The DLAPS consists of an auto-segmentation network based on RefineNet model and a classification network based on ensemble model(ResNet,Xception,and DenseNet).The performance of the DLAPS was compared with that of manually segmented DL models,the clinical model,and Node Reporting and Data System(Node-RADS).The improvement of radiologists’diagnostic performance under the DLAPS-assisted strategy was explored.In addition,bulk RNA-sequencing was conducted based on 12 LLNs to reveal the underlying biological basis of the DLAPS.Results:The DLAPS yielded good performance with area under the receiver operating characteristic curve(AUC)of 0.872,0.910,and 0.822 in the internal,pooled external,and prospective test sets,respectively.The DLAPS significantly outperformed clinical models(AUC 0.731,P<0.001)and Node-RADS(AUC 0.602,P<0.001)in the internal test set.Moreover,the performance of the DLAPS was comparable to that of the manually segmented deep learning(DL)model with AUCs ranging 0.814−0.901 in three test sets.Furthermore,the DLAPSassisted strategy improved the performance of radiologists and enhanced inter-observer consistency.In clinical situations,the rate of unnecessary LLN dissection decreased from 33.33%to 7.32%.Furthermore,the DLAPS was associated with the cell-cell conjunction in the microenvironment.Conclusions:Using CT images from PTC patients,the DLAPS could effectively segment and classify LLNs non-invasively,and this system had a good generalization ability and clinical applicability.

Risk factors for lymph node metastasis in superficial esophageal squamous cell carcinoma

In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.We focused on identifying risk factors for lymph node metastasis(LNM)in superficial esophageal squamous cell carcinoma(SESCC)patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients,thereby helping to guide the selection of an appropriate treatment plan.The current standard treatment for SESCC is radical esophagectomy with lymph node dissection.However,esophagectomy is associated with considerable morbidity and mortality.Endoscopic resection(ER)offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome.However,since ER is a localized treatment that does not allow for lymph node dissection,the risk of LNM in SESCC limits the effectiveness of ER.Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy.Previous studies have shown that tumor size,macroscopic type of tumor,degree of differentiation,depth of tumor invasion,and lymphovascular invasion are factors associated with LNM in patients with SESCC.In addition,tumor budding is commonly associated with LNM,recurrence,and distant metastasis,but this topic has been less covered in previous studies.By comprehensively evaluating the above risk factors for LNM,useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.

Histological Risk Factors for Lymph Node Metastasis in pT1 Colorectal Cancer:Does Submucosal Invasion Depth Really Matter?

Objective After endoscopic resection of colorectal cancer with submucosal invasion(pT1 CRC),additional surgical treatment is recommended if deep submucosal invasion(DSI)is present.This study aimed to further elucidate the risk factors for lymph node metastasis(LNM)in patients with pT1 CRC,especially the effect of DSI on LNM.Methods Patients with pT1 CRC who underwent lymph node dissection were selected.The Chi-square test and multivariate logistic regression were used to analyze the relationship between clinicopathological characteristics and LNM.The submucosal invasion depth(SID)was measured via 4 methods and analyzed with 3 cut-off values.Results Twenty-eight of the 239 patients presented with LNM(11.7%),and the independent risk factors for LNM included high histological grade(P=0.003),lymphovascular invasion(LVI)(P=0.004),intermediate to high budding(Bd 2/3)(P=0.008),and cancer gland rupture(CGR)(P=0.008).Moreover,the SID,width of submucosal invasion(WSI),and area of submucosal invasion(ASI)were not significantly different.When one,two,three or more risk factors were identified,the LNM rates were 1.1%(1/95),12.5%(7/56),and 48.8%(20/41),respectively.Conclusion Indicators such as the SID,WSI,and ASI are not risk factors for LNM and are subjective in their measurement,which renders them relatively inconvenient to apply in clinical practice.In contrast,histological grade,LVI,tumor budding and CGR are relatively straightforward to identify and have been demonstrated to be statistically significant.It would be prudent to focus on these histological factors rather than subjective measurements.

Magnetic resonance imaging-based lymph node radiomics for predicting the metastasis of evaluable lymph nodes in rectal cancer

BACKGROUND Lymph node(LN)staging in rectal cancer(RC)affects treatment decisions and patient prognosis.For radiologists,the traditional preoperative assessment of LN metastasis(LNM)using magnetic resonance imaging(MRI)poses a challenge.AIM To explore the value of a nomogram model that combines Conventional MRI and radiomics features from the LNs of RC in assessing the preoperative metastasis of evaluable LNs.METHODS In this retrospective study,270 LNs(158 nonmetastatic,112 metastatic)were randomly split into training(n=189)and validation sets(n=81).LNs were classified based on pathology-MRI matching.Conventional MRI features[size,shape,margin,T2-weighted imaging(T2WI)appearance,and CE-T1-weighted imaging(T1WI)enhancement]were evaluated.Three radiomics models used 3D features from T1WI and T2WI images.Additionally,a nomogram model combining conventional MRI and radiomics features was developed.The model used univariate analysis and multivariable logistic regression.Evaluation employed the receiver operating characteristic curve,with DeLong test for comparing diagnostic performance.Nomogram performance was assessed using calibration and decision curve analysis.RESULTS The nomogram model outperformed conventional MRI and single radiomics models in evaluating LNM.In the training set,the nomogram model achieved an area under the curve(AUC)of 0.92,which was significantly higher than the AUCs of 0.82(P<0.001)and 0.89(P<0.001)of the conventional MRI and radiomics models,respectively.In the validation set,the nomogram model achieved an AUC of 0.91,significantly surpassing 0.80(P<0.001)and 0.86(P<0.001),respectively.CONCLUSION The nomogram model showed the best performance in predicting metastasis of evaluable LNs.

Analysis of lymph node metastasis and survival prognosis in early gastric cancer patients: A retrospective study

BACKGROUND Early gastric cancer(EGC)is a common malignant tumor of the digestive system,and its lymph node metastasis and survival prognosis have been concerning.By retrospectively analyzing the clinical data of EGC patients,we can better under-stand the status of lymph node metastasis and its impact on survival and prog-nosis.AIM To evaluate the prognosis of EGC patients and the factors that affect lymph node METHODS The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort study.There were 561 males and 450 females.The mean age was 58±11 years.The patient underwent radical gastrectomy.The status of lymph node metastasis in each group was determined according to the pathological examination results of surgical specimens.The outcomes were as follows:(1)Lymph node metastasis in EGC patients;(2)Analysis of influencing factors of lymph node metastasis in EGC;and(3)Analysis of prognostic factors in patients with EGC.Normally distributed measurement data are expressed as mean±SD,and a t test was used for comparisons between groups.The data are expressed as absolute numbers or percentages,and the chi-square test was used for comparisons between groups.Rank data were compared using a nonparametric rank sum test.A log-rank test and a logistic regression model were used for univariate analysis.A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate analysis.The Kaplan-Meier method was used to calculate the survival rate and construct survival curves.A log-rank test was used for survival analysis.RESULTS Analysis of influencing factors of lymph node metastasis in EGC.The results of the multifactor analysis showed that tumor length and diameter,tumor site,tumor invasion depth,vascular thrombus,and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC(odds ratios=1.80,1.49,2.65,5.76,and 0.60;95%CI:1.29–2.50,1.11–2.00,1.81–3.88,3.87-8.59,and 0.48-0.76,respectively;P<0.05).Analysis of prognostic factors in patients with EGC.All 1011 patients with EGC were followed up for 43(0–13)months.The 3-year overall survival rate was 97.32%.Multivariate analysis revealed that age>60 years and lymph node metastasis were independent risk factors for prognosis in patients with EGC(hazard ratio=9.50,2.20;95%CI:3.31-27.29,1.00-4.87;P<0.05).Further analysis revealed that the 3-year overall survival rates of gastric cancer patients aged>60 years and≤60 years were 99.37%and 94.66%,respectively,and the difference was statistically significant(P<0.05).The 3-year overall survival rates of patients with and without lymph node metastasis were 95.42%and 97.92%,respectively,and the difference was statistically significant(P<0.05).CONCLUSION The lymph node metastasis rate of EGC patients was 23.64%.Tumor length,tumor site,tumor infiltration depth,vascular cancer thrombin,and tumor differentiation degree were found to be independent factors affecting lymph node metastasis in EGC patients.Age>60 years and lymph node metastasis are independent risk factors for EGC prognosis.

GLI1 and PTTG1 expression in colorectal carcinoma patients undergoing radical surgery and their correlation with lymph node metastasis

BACKGROUND Few studies have investigated the expression of GLI1 and PTTG1 in patients undergoing radical surgery for colorectal carcinoma(CRC)and their association with lymph node metastasis(LNM).Therefore,more relevant studies and analyses need to be conducted.AIM To explore GLI1 and PTTG1 expression in patients undergoing radical surgery for CRC and their correlation with LNM.METHODS This study selected 103 patients with CRC admitted to our hospital between April 2020 and April 2023.Sample specimens of CRC and adjacent tissues were collected to determine the positive rates and expression levels of GLI1 and PTTG1.The correlation of the two genes with patients’clinicopathological data(e.g.,LNM)was explored,and differences in GLI1 and PTTG1 expression between patients with LNM and those without were analyzed.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive potential of the two genes for LNM in patients with CRC.RESULTS Significantly higher positive rates and expression levels of GLI1 and PTTG1 wereobserved in CRC tissue samples compared with adjacent tissues.GLI1 and PTTG1 were strongly linked to LNM in patients undergoing radical surgery for CRC,with higher GLI1 and PTTG1 levels found in patients with LNM than in those without.The areas under the ROC curve of GLI1 and PTTG1 in assessing LNM in patients with CRC were 0.824 and 0.811,respectively.CONCLUSION GLI1 and PTTG1 expression was upregulated in patients undergoing radical surgery for CRC and are significantly related to LNM in these patients.Moreover,high GLI1 and PTTG1 expression can indicate LNM in patients with CRC undergoing radical surgery.The expression of both genes has certain diagnostic and therapeutic significance.

Predictive value of machine learning models for lymph node metastasis in gastric cancer: A two-center study

BACKGROUND Gastric cancer is one of the most common malignant tumors in the digestive system,ranking sixth in incidence and fourth in mortality worldwide.Since 42.5%of metastatic lymph nodes in gastric cancer belong to nodule type and peripheral type,the application of imaging diagnosis is restricted.AIM To establish models for predicting the risk of lymph node metastasis in gastric cancer patients using machine learning(ML)algorithms and to evaluate their pre-dictive performance in clinical practice.METHODS Data of a total of 369 patients who underwent radical gastrectomy at the Depart-ment of General Surgery of Affiliated Hospital of Xuzhou Medical University(Xuzhou,China)from March 2016 to November 2019 were collected and retro-spectively analyzed as the training group.In addition,data of 123 patients who underwent radical gastrectomy at the Department of General Surgery of Jining First People’s Hospital(Jining,China)were collected and analyzed as the verifi-cation group.Seven ML models,including decision tree,random forest,support vector machine(SVM),gradient boosting machine,naive Bayes,neural network,and logistic regression,were developed to evaluate the occurrence of lymph node metastasis in patients with gastric cancer.The ML models were established fo-llowing ten cross-validation iterations using the training dataset,and subsequently,each model was assessed using the test dataset.The models’performance was evaluated by comparing the area under the receiver operating characteristic curve of each model.RESULTS Among the seven ML models,except for SVM,the other ones exhibited higher accuracy and reliability,and the influences of various risk factors on the models are intuitive.CONCLUSION The ML models developed exhibit strong predictive capabilities for lymph node metastasis in gastric cancer,which can aid in personalized clinical diagnosis and treatment.

Vascular Endothelial Growth Factor C Expression in Gastric Carcinoma and Its Relationship with Lymph Node Metastasis

Objective: To study the expression of vascular endothelial growth factor C (VEGF-C) in gastric carcinoma and its relationship with lymph node metastasis. Methods: The expression of VEGF-C mRNA in 5 gastric carcinoma cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR). Simultaneously, the expression of VEGF-C protein in gastric carcinoma tissues, which were obtained from 63 patients who underwent radical gastrectomy, was detected by immunohistochemistry. Results: Three of the 5 gastric carcinoma cell lines, MKN-45, SGC-7901 and AGS, expressed VEGF-C mRNA. VEGF-C protein was expressed in 52.4% (33/63) of patients. VEGF-C protein expression was more frequently found in tumors with lymph node metastasis than in those without (P<0.01). VEGF-C protein expression was also closely related to lymphatic invasion (P<0.01) and TNM stage (P<0.01). However, there was no significant correlation between VEGF-C expression and the age, gender, tumor size, tumor location, Lauren classification, depth of invasion, and vascular invasion. Conclusion: The expression of VEGF-C is closely related to lymph node metastasis of gastric carcinoma, and lymphangiogenesis might be a new target for treatment of gastric carcinoma.

CXCR4/SDF-1 axis is involved in lymph node metastasis of gastric carcinoma

AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistric assay.SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration.RESULTS:Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243,P < 0.05).The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338,P < 0.05).CXCR4 expression was significantly related to poorly differentiated,high tumor stage and lymph node metastasis.Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601,P < 0.05).The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r=0.776,P < 0.01).Additionally,human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1.AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells.CONCLUSION:The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer.CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.

Progress in the Study of Lymph Node Metastasis in Early-stage Cervical Cancer

Spread into regional lymph node is the major route of metastasis in cervical cancer. Although lymph node status is not involved in the International Federation of Gynecology and Obstetrics staging system of uterine cervical cancer, the presence or absence of lymph node metastasis provides important information for prognosis and treatment. In this review, we have attempted to focus on the incidence and patterns of lymph node metastasis, and the issues surrounding surgical assessment of lymph nodes. In addition, the preoperative prediction of lymph node status, as well as the intraoperative assessment by sentinel nodes will be reviewed. Finally, lymph node micrometastasis also will be discussed.

Association of serum vascular endothelial growth factor-C and lymphatic vessel density with lymph node metastasis and prognosis of patients with gastric cancer

AIM： To investigate whether serum vascular endothelial growth factor-C （SVEGF-C）, VEGF-C, and lymphatic vessel density （LVD） in tumor tissues are related to lymph node metastasis （LNM） and prognosis in gastric cancer. METHODS： SVEGF-C levels of 80 gastric cancer patients and 20 healthy donors were examined using ELISA. VEGF-C expression and LVD were examined using immunohistochemical staining. Kaplan-Meier survival analysis was performed to determine their influence on the prognosis of the patients. RESULTS： The SVEGF-C level in gastric cancer patients （595.9 ± 201.0 ng/L） was significantly higher （P = 0.000） than controls （360.0 ± 97.4 ng/L）. Both SVEGF-C and LVD were significantly higher in poorly differentiated adenocarcinomas, T3 and T4, LNM, distant metastasis, and pTNM groups Ⅲ and Ⅳ （P = 0.000）. The sensitivity and specificity of SVEGF-C for predicting LNM were 82.8% and 81.8%, respectively （cut-off = 542.5 ng/L）. The positive expression rate of VEGF-C was significantly higher in cancerous than in normal tissues （65% vs 20%; P = 0.001）. VEGF-C expression up-regulation was significantly related to differentiation, depth of invasion, LNM, distant metastasis, and pTNM stage （P = 0.000）. LVD was 10.7 ± 3.1/200 HP in the experimental group vs 4.9 ± 1.3/200 HP in controls （P = 0.000）; LVD in cancerous tissues with and without LNM was 12.0 ± 2.7/200 HP vs 7.6 ± 0.5/200 HP, respectively （P = 0.000）. SVEGF-C and LVD were significantly higher in VEGF-C positive than in negative patients （P = 0.000）; SVEGF-C level was related to LVD （P = 0.000）. Kaplan-Meier survival analysis factors predicating poor prognosis were： SVEGF-C level （P = 0.001）, VEGF-C expression and LVD （both P = 0.000）. CONCLUSION： SVEGF-C level, VEGF-C and LVD are related to LNI and poor prognosis of patients with gastric cancer, SVEGF-C may be a biomarker for LNI in gastric cancer,

Analysis of factors related to non-sentinel lymph node metastasis in 296 sentinel lymph node-positive Chinese breast cancer patients

Objective: Axillary lymph node dissection(ALND) may be unnecessary in 20%–60% of breast cancer patients with sentinel lymph node(NSLN) metastasis. The aim of the present study was to review the medical records of Chinese patients with early-stage breast cancer and positive NSLN metastasis to identify clinicopathological characteristics as risk factors for non-NSLN metastasis.Methods: The medical records of 2008 early-stage breast cancer patients who received intraoperative sentinel lymph node biopsy(SLNB) between 2006 and 2016 were retrospectively reviewed. These patients were clinically and radiologically lymph nodenegative and had no prior history of receiving neoadjuvant chemotherapy or endocrinotherapy. The clinicopathological characteristics of patients with positive NSLN metastasis who underwent ALND were investigated.Results: In the present study, 296 patients with positive NSLN metastases underwent ALND. Positive non-NSLN metastases were confirmed in 95 patients(32.1%). On univariate analysis, ≥ 3 positive NSLN metastases(P <0.01), NSLN macrometastases(P =0.023), and lymphovascular invasion(P = 0.04) were associated with non-NSLN metastasis(P <0.05). In multivariate analysis, the number of positive SLNs was the most significant predictor of non-SLN metastasis. For patients with 0, 1, 2, or 3 associated risk factors, the non-SLN metastatic rates were 11.5%, 22.5%, 35.2%, and 73.1%, respectively.Conclusions: The number of positive NSLNs, NSLN macrometastases, and lymphovascular invasion were correlated with nonSLN metastasis. The number of positive SLNs was an independent predictor for non-NSLN metastasis. When 2 or 3 risk factors were present in one patient, the probability of non-NSLN was higher than that in the American College of Surgeons Oncology Group Z0011 trial(27.3%); thus, avoiding ALND should be considered carefully.

Anlotinib suppresses lymphangiogenesis and lymphatic metastasis in lung adenocarcinoma through a process potentially involving VEGFR-3 signaling

Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapies to block lymphangiogenesis are urgently required.Methods:Immunohistochemistry,immunofluorescence,Western blot,migration assays,and lymphangiogenesis and lymphatic metastasis assays were used.Results:Anlotinib,a receptor tyrosine kinase inhibitor,suppressed the rate of new metastatic lesions(31.82%in the placebo arm and 18.18%in the anlotinib arm)in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study.D2-40+-lymphatic vessel density was strongly correlated with disease stage,metastasis,and poor prognosis in 144 Chinese patients with lung adenocarcinoma.In mice bearing A549EGFP tumors,tumor lymphatic vessel density,tumor cell migration to lymph nodes,and the number of distant metastatic lesions were lower in the anlotinib group than in the controls.Anlotinib inhibited the growth and migration of human lymphatic endothelial cells(hLECs)and lymphangiogenesisin vitro andin vivo.Treatment of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3(VEGFR-3).Conclusions:Anlotinib inhibits lymphangiogenesis and lymphatic metastasis,probably through inactivating VEGFR-3 phosphorylation.The results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma.(Trial registration:ALTER0303;NCT02388919;March 17,2015.)

Construction and external validation of a nomogram that predicts lymph node metastasis in early gastric cancer patients using preoperative parameters

Objective: To create a nomogram to predict the incidence of lymph node metastasis(LNM) in early gastric cancer(EGC) patients and to externally validate the nomogram.Methods: To construct the nomogram,we retrospectively analyzed a primary cohort of 272 EGC patients.Univariate analysis and a binary logistic regression were performed.A nomogram predicting the incidence of LNM in EGC patients was created.The discrimination ability of the nomogram was measured using the concordance index(c-index),and the nomogram was also calibrated.Then,another prospective cohort of 81 patients was analyzed to validate the nomogram.Results: In the primary cohort,LNM was pathologically confirmed in 37(13.6%) patients.In multivariate analysis,the presence of an ulcer,the maximum lesion diameter observed via gastroscopy,the thickness of the lesion observed via endoscopic ultrasonography,and the presence of enlarged lymph nodes on computed tomography(CT) were independent risk factors for LNM.A nomogram was then created based on the regression model with the c-index of 0.905,and the calibration curve of the nomogram fell approximately on the ideal 45-degree line.The cut-off score of the nomogram was 110,and the sensitivity,specificity,positive predictive and negative predictive values of the nomogram in the primary cohort were 81.1%,86.0%,47.6% and 96.7%,respectively,and in the prospective validation cohort were 75.0%,91.0%,60.0% and 95.5%,respectively.The calibration curve of the external validation cohort was almost on the 45-degree line.Conclusions: We developed an effective nomogram predicting the incidence of LNM for EGC patients.

Metastasis of primary gallbladder carcinoma in lymph node and liver

AIM: To evaluate the patterns with metastasis of gallbladder carcinoma in lymph nodes and liver. METHODS: A total of 45 patients who had radical surgery were selected. The patterns with metastasis of primary gallbladder carcinoma in lymph nodes and liver were examined histopathologically and classified as TNM staging of the American Joint Committee on Cancer. RESULTS: Of the 45 patients, 29 (64.4%) had a lymph node positive disease and 20 (44.4%) had a direct invasion of the liver. The frequency of involvement of lymph nodes was strongly influenced by the depth of the primary tumor (P= 0.0001). The postoperative survival rate of patients with negative lymph node metastasis was significantly higher than that of patients with positive lymph node metastasis (P= 0.004), but the postoperative survival rate of patients with Nl lymph node metastasis was not significantly different from that of patients with N2 lymph node metastasis (P= 0.3874). The postoperative survival rate of patients without hepatic invasion was significantly better than that of patients with hepatic invasion (P= 0.0177). CONCLUSION: Complete resection of the regional lymph nodes is important in advanced primary gallbladder carcinoma (PGC). The initial sites of liver spread are located mostly in segments IV and V. It is necessary to achieve negative surgical margins 2 cm from the tumor. In patients with hepatic hilum invasion, extended right hepatectomy with or without bile duct resection or portal vein resection is necessary for curative resection.

STAT-3 correlates with lymph node metastasis and cell survival in gastric cancer

AIM:To investigate the correlation between gastric cancer growth and signal transducer and activator of transcription-3(STAT3) expression.METHODS:We assessed the expressions of STAT3,phosphor-STAT3(pSTAT3),suppressor of cytokine signaling-1(SOCS-1),survivin and Bcl-2 in gastric cancer patients after gastrectomy by immunohistochemical method.In addition,in situ hybridization was used to further demonstrate the mRNA expression of STAT3 in gastric cancer.RESULTS:With the univariate analysis,expressions of STAT3,pSTAT3,SOCS-1,survivin and Bcl-2,the size of primary tumor and the lymph node metastasis were found to be associated with the overall survival(OS) of gastric cancer patients.However,only pSTAT3 expression and the lymph node metastasis were identified as the independent factors of OS of gastric cancer with multivariate analysis.STAT3 expression was correlated with the lymph node metastasis.There were positive correlations between expressions of STAT3,survivin,Bcl-2 and pSTAT3 in gastric cancer,whereas there was negative correlation between STAT3 expression and SOCS-1 expression in gastric cancer.CONCLUSION:STAT3 can transform into pSTAT3 to promote the survival and inhibit the apoptosis of gastric cancer cells.SOCS-1 might be the valid molecular antagonist to inhibit the STAT3 expression in gastric cancer.

CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric carcinoma

AIM To investigate the role of CXC chemokine receptor (CXCR)-7 and CXCL12 in lymph node and liver metastasis of gastric carcinoma. METHODS In 160 cases of gastric cancer, the expression of CXCR7 and CXCL12 in tumor and matched tumoradjacent non-cancer tissues, in the lymph nodes around the stomach and in the liver was detected using immunohistochemistry to analyze the relationship between CXCR7/CXCL12 expression and clinicopathological features and to determine whether CXCR7 and CXCL12 constitute a biological axis to promote lymph node and liver metastasis of gastric cancer. Furthermore, the CXCR7 gene was silenced and overexpressed in human gastric cancer SGC-7901 cells, and cell proliferation, migration and invasiveness were measured by the MTT, wound healing and Transwell assays, respectively. RESULTS CXCR7 expression was up-regulated in gastric cancer tissues (P = 0.011). CXCR7/CXCL12 expression was significantly related to high tumor stage and lymph node (r = 0.338, P = 0.000) and liver metastasis (r = 0.629, P = 0.000). The expression of CXCL12 in lymph node and liver metastasis was higher than that in primary gastric cancer tissues (chi(2) = 6.669, P = 0.010; chi(2) = 25379, P = 0.000), and the expression of CXCL12 in lymph node and liver metastasis of gastric cancer was consistent with the positive expression of CXCR7 in primary gastric cancer (r = 0.338, P = 0.000; r = 0.629, P = 0.000). Overexpression of the CXCR7 gene promoted cell proliferation, migration and invasion. Silencing of the CXCR7 gene suppressed SGC-7901 cell proliferation, migration and invasion. Human gastric cancer cell lines expressed CXCR7 and showed vigorous proliferation and migratory responses to CXCL12. CONCLUSION The CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric cancer. CXCR7 is considered a potential therapeutic target for the treatment 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.

Unveiling lymph node metastasis in early gastric cancer

With respect to gastric cancer treatment,improvements in endoscopic techniques and novel therapeutic modalities[such as endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)]have been developed.Currently,EMR/ESD procedures are widely accepted treatment modalities for early gastric cancer(EGC).These procedures are most widely accepted in Asia,including in Korea and Japan.In the present era of endoscopic resection,accurate prediction of lymph node(LN)metastasis is a critical component of selecting suitable patients for EMR/ESD.Generally,indications for EMR/ESD are based on large Japanese datasets,which indicate that there is almost no risk of LN metastasis in the subgroup of EGC cases.However,there is some controversy among investigators regarding the validity of these criteria.Further,there are currently no accurate methods to predict LN metastasis in gastric cancer(for example,radiologic methods or methods based on molecular biomarkers).We recommend the use of a 2-step method for the management of early gastric cancer using endoscopic resection.The first step is the selection of suitable patients for endoscopic resection,based on endoscopic and histopathologic findings.After endoscopic resection,additional surgical intervention could be determined on the basis of a comprehensive review of the endoscopic mucosal resection/endoscopic submucosal dissection specimen,including lymphovascular tumor emboli,tumor size,histologic type,and depth of invasion.However,evaluation of clinical application data is essential for validating this recommendation.Moreover,gastroenterologists,surgeons,and pathologists should closely collaborate and communicate during these decisionmaking processes.