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...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.展开更多
Objective: To study the correlation of Slug gene expression with lymph node metastasis and invasion molecule expression in oral squamous cell carcinoma tissue. Methods: Oral squamous cell carcinoma tissue surgical rem...Objective: To study the correlation of Slug gene expression with lymph node metastasis and invasion molecule expression in oral squamous cell carcinoma tissue. Methods: Oral squamous cell carcinoma tissue surgical removed in Affiliated Stomatological Hospital of Nanjing Medical University between March 2015 and April 2017 was selected and divided into the oral squamous cell carcinoma tissue with neck lymph node metastasis and the oral squamous cell carcinoma tissues without lymph node metastasis according to the condition of lymph node metastasis. The expression of Slug, epithelial-mesenchymal transition molecules and invasion molecules in the oral squamous cell carcinoma tissue were detected. Results:Slug, N-cadherin, Vimentin, CD147, OPN, GRP78, SDF-1 and CXCR4 protein expression in oral squamous cell carcinoma tissue with neck lymph node metastasis were significantly higher than those in oral squamous cell carcinoma tissue without lymph node metastasis while E-cadherin, P120ctn and ZO-1 protein expression were significantly lower than those in oral squamous cell carcinoma tissue without lymph node metastasis;N-cadherin, Vimentin, CD147, OPN, GRP78, SDF-1 and CXCR4 protein expression in oral squamous cell carcinoma tissue with high Slug expression were significantly higher than those in oral squamous cell carcinoma tissue with low Slug expression while E-cadherin, P120ctn and ZO-1 protein expression were significantly lower than those in oral squamous cell carcinoma tissue with low Slug expression. Conclusion: The highly expressed Slug in oral squamous cell carcinoma tissue can promote the epithelial-mesenchymal transition and invasion of the cells to participate in the lymph node metastasis of tumor cells.展开更多
AIM To investigate the relationship between histological mixed-type of early gastric cancer(EGC) in the mucosa and submucosa and lymph node metastasis(LNM).METHODS This study included 298 patients who underwent gastre...AIM To investigate the relationship between histological mixed-type of early gastric cancer(EGC) in the mucosa and submucosa and lymph node metastasis(LNM).METHODS This study included 298 patients who underwent gastrectomy for EGC between 2005 and 2012. Enrolled lesions were divided into groups of pure differentiated(pure D), pure undifferentiated(pure U), and mixed-type according to the proportion of the differentiated and undifferentiated components observed under a microscope. We reviewed the clinicopathological features, including age, sex, location, size, gross type, lymphovascular invasion, ulceration, and LNM, among the three groups. furthermore, we evaluated the predictors of LNM in the mucosa-confined EGC.RESULTS Of the 298 patients, 165(55.4%) had mucosa-confined EGC and 133(44.6%) had submucosa-invasive EGC. Only 13(7.9%) cases of mucosa-confined EGC and 30(22.6%) cases of submucosa-invasive EGC were observed to have LNM. The submucosal invasion(OR = 4.58, 95%CI: 1.23-16.97, P = 0.023), pure U type(OR = 4.97, 95%CI: 1.21-20.39, P = 0.026), and mixedtype(OR = 5.84, 95%CI: 1.05-32.61, P = 0.044) were independent risk factors for LNM in EGC. The rate of LNM in mucosa-confined EGC was higher in the mixedtype group(P = 0.012) and pure U group(P = 0.010) than in the pure D group, but no significant difference was found between the mixed-type group and pure U group(P = 0.739). Similarly, the rate of LNM in the submucosa-invasive EGC was higher in the mixedtype(P = 0.012) and pure U group(P = 0.009) than in the pure D group but was not significantly different between the mixed-type and pure U group(P = 0.375). Multivariate logistic analysis showed that only female sex(OR = 5.83, 95%CI: 1.64-20.70, P = 0.028) and presence of lymphovascular invasion(OR = 13.18, 95%CI: 1.39-125.30, P = 0.020) were independent risk factors for LNM in mucosa-confined EGC, while histological type was not an independent risk factor for LNM in mucosa-confined EGC(P = 0.106).CONCLUSION for mucosal EGC, histological mixed-type is not an independent risk factor for LNM and could be managed in the same way as the undifferentiated type.展开更多
AIM:To explore the feasibility of pertorming minimally invasive surgery(MIS)on subsets of submucosal gastric cancers that are unlikely to have regional lymph node metastasis. METHODS:A total of 105 patients underwent ...AIM:To explore the feasibility of pertorming minimally invasive surgery(MIS)on subsets of submucosal gastric cancers that are unlikely to have regional lymph node metastasis. METHODS:A total of 105 patients underwent radical gastrectomy with lymph node dissection for submucosal gastric cancer at our hospital from January 1995 to December 1995.Besides investigating many clinicopathological features such as tumor size,gross appearance,and differentiation, we measured the depth of invasion into submucosa minutely and analyzed the clinicopathologic features of these patients regarding lymph node metastasis. RESULTS:The rate of lymph node metastasis in cases where the depth of invasion was<500 μm,500-2 000 μm,or >2 000 μm was 9%(2/23),19%(7136),and 33%(15/46), respectively(P<0.05).In univariate analysis,no significant correlation was found between lymph node metastasis and clinicopathological characteristics such as age,sex,tumor location,gross appearance,tumor differentiation,Lauren's classification,and lymphatic invasion.In multivariate analysis, tumor size(>4 cm vs≤2 cm,odds ratio=4.80, P=0.04)and depth of invasion(>2 000 μm vs ≤500 μm, odds ratio=6.81,P=0.02)were significantly correlated with lymph node metastasis.Combining the depth and size in cases where the depth of invasion was less than 500 μm, we found that lymph node metastasis occurred where the tumor size was greater than 4 cm.In cases where the tumor size was less than 2 cm,lymph node metastasis was found only where the depth of tumor invasion was more than 2 000 μm. CONCLUSION:MIS can be applied to submucosal gastric cancer that is less than 2 cm in size and 500 μm in depth.展开更多
OBJECTIVE To investigate the relationship between lymphatic vessel density and lymph node metastasis of invasive micropapillary carcinoma (IMPC) of the breast. METHODS The immunohistochemical study for vascular endoth...OBJECTIVE To investigate the relationship between lymphatic vessel density and lymph node metastasis of invasive micropapillary carcinoma (IMPC) of the breast. METHODS The immunohistochemical study for vascular endothelial growth factor-c (VEGF-C), VEGF Receptor-3 (VEGFR-3) and lymphatic vessel density of 51 cases of IMPC were performed, and lymph node metastases were examined by microscopic analysis of these cases. RESULTS In IMPC, VEGF-C was expressed in the cytoplasm and/or on the membrane of the tumor cells, and the expression of VEGF-C showed a positive correlation with lymph node metastasis (P<0.01). Lymphatic vessel density was determined by the number of micro-lymphatic vessels with VEGFR-3 positive staining. Lymphatic vessel density was positively correlated with VEGF-C expression (P<0.01) and lymph node metastasis (P<0.01). The percentage of IMPC in the tumor was not associated with the incidence of lymph node metastasis. The metastatic foci in lymph nodes were either pure or predominant micropapillary carcinoma. CONCLUSION The results suggested that VEGF-C overexpression stimulated tumor lymphangiogenesis, and the increased lymphatic vessel density may be the key factor that influenced lymph node metastasis of IMPC.展开更多
Objective: This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion (LVI) labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma (ESCC). Methods: Immunoh...Objective: This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion (LVI) labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma (ESCC). Methods: Immunohistochemical assay was used to detect the expression of D2-40 and LVI in 107 ESCC patients. Then, the correlation between the clinicopathologic feature and the overall survival time of the patients was analyzed. Results: The lymph node metastasis rates were 70% and 21% in the LVI-positive and LVI-negative groups, respectively. The nodal metastasis rate was higher in the LVI-positive group than in the LVI-negative group. Multivariate regression analysis showed that LVI was related to nodal metastasis (P〈0.001). The median survival time of the patients was 26 and 43 months in the LVI-positive and LVI-negative groups, respectively. Mthough univariate regression analysis showed significant difference between the two groups (P=0.014), multivariate regression analysis revealed that LVI was not an independent prognostic factor for overall survival in the ESCC patients (P=0.062). Lymphatic node metastasis (P=0.031), clinical stage (P=0.019), and residual tumor (P=0.026) were the independent prognostic factors. Conclusion: LVI labeled by D2-40 monoclonal antibody is a risk factor predictive of lymph node metastasis in ESCC patients.展开更多
AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal ...AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan (Trp) and kynurenine (Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologically and were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies.RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups (both P > 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp (r = 0.450, P < 0.01). Urinary biopterin was significantly higher in cancer cases (P < 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients (P < 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group (44.56% ± 6.11%) than negative colorectal cancer patients (24.04% ± 6.90%), (P < 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis (P < 0.01 and P < 0.05, respectively). A significant difference between the accuracy of diagnosis by using either total indoleamine-2,3-dioxygenase immunostaining score or of lymph node metastasis was found during the evaluation of cancer patients.CONCLUSION: Indoleamine-2,3-dioxygenase expression may predict the presence of unrecognized LI and lymph node metastasis and may be included in the histopathological evaluation of colorectal carcinoma cases.展开更多
Purpose: Submucosal invasive colorectal carcinoma (SICC) exhibits lymph node metastasis in about 10% of patients. Therefore, endoscopic resection is insufficient for cases of SICC at risk of lymph node metastasis, and...Purpose: Submucosal invasive colorectal carcinoma (SICC) exhibits lymph node metastasis in about 10% of patients. Therefore, endoscopic resection is insufficient for cases of SICC at risk of lymph node metastasis, and surgical resection accompanied with lymph node dissection is necessary. However, because additional intestinal resection is unnecessary for cases without lymph node metastasis, more rigid criteria are required in order to decrease the incidence of unnecessary further intestinal resection. We retrospectively identified predictive factors for lymph node metastasis in submucosal invasive colorectal carcinoma. Methods: One hundred and two patients who underwent intestinal resection as the first treatment or additional intestinal resection after endoscopic resection at our department between 1999 and 2012 were enrolled in the present study. Clinicopathological factors were analyzed to determine predictive factors related to lymph node metastasis. Results: The multivariate analysis revealing only depth of submucosal invasion (≤2700 μm) was found to be a significant, independent predictive factor of lymph node metastasis (P = 0.04, Odds ratio: 4.18, 95% CI: 1.06 - 16.40). Conclusion: It is considered that the refinement of the criteria in the present study will be very useful, especially in the patients for whom careful judgment is required when considering additional intestinal resection.展开更多
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 pro...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.展开更多
AIM To evaluate a novel grading system to predict lymph node metastasis(LNM) in patients with submucosal invasive colorectal carcinoma(SICRC).METHODS We analyzed the associations between LNM and various clinicopatholo...AIM To evaluate a novel grading system to predict lymph node metastasis(LNM) in patients with submucosal invasive colorectal carcinoma(SICRC).METHODS We analyzed the associations between LNM and various clinicopathological features in 252 patients with SICRC who had undergone radical surgery at the Seoul Saint Mary's hospital between 2000 and 2015.RESULTS LNM was observed in 31 patients(12.3%). The depth and width of the submucosal invasion, lymphatic invasion, tumor budding, and the presence of poorly differentiated clusters(PDCs) were significantly associated with the incidence of LNM. Using multivariate analysis, the receiver operating characteristic curvewas calculated and the area under curve(AUC) was used to compare the ability of the different parameters to identify the risk of LNM. The most powerful clinicopathological parameter for predicting LNM was lymphatic invasion(difference AUC = 0.204), followed by the presence or absence of tumor budding(difference AUC = 0.190), presence of PDCs(difference AUC = 0.172) and tumor budding graded by the Ueno method(difference AUC = 0.128). CONCLUSION Our results indicate that the tumor budding and the depth multiplied by the width measurements of submucosal invasion can provide important information for patients with SICRC.展开更多
AIM To assess clinical outcomes for submucosal (T1b) oesophageal adenocarcinoma (OAC) patients managed with either surgery or endoscopic eradication therapy.METHODS Patients found to have T1b OAC following endoscopic ...AIM To assess clinical outcomes for submucosal (T1b) oesophageal adenocarcinoma (OAC) patients managed with either surgery or endoscopic eradication therapy.METHODS Patients found to have T1b OAC following endoscopic resection between January 2008 to February 2016 at University College London Hospital were retrospectively analysed. Patients were split into low-risk and high-risk groups according to established histopathological criteria and were then further categorised according to whether they underwent surgical resection or conservative management. Study outcomes include the presence of lymphnode metastases, disease-specific mortality and overall survival. RESULTS A total of 60 patients were included; 22 patients were surgically managed (1 low-risk and 21 high-risk patients) whilst 38 patients were treated conservatively (12 low-risk and 26 high-risk). Overall, lymph node metastases (LNM) were detected in 10 patients (17%); six of these patients had undergone conservative management and LNM were detected at a median of 4 mo after endoscopic mucosal resection (EMR). All LNM occurred in patients with highrisk lesions and this represented 21% of the total high-risk lesions. Importantly, there was no statistically significant difference in tumor-related deaths between those treated surgically or conservatively (P = 0.636) and disease-specific survival time was also comparable between the two treatment strategies (P = 0.376).CONCLUSION T1b tumours without histopathological high-risk markers of LNM can be treated endoscopically with good outcomes. In selected patients, endoscopic therapy may be appropriate for high-risk lesions.展开更多
AIM: To evaluate and compare detection of lymphatic and blood vessel invasion (LVI and BVI) by hematox-ylin-eosin (HE) and immunohistochemistry (IHC) in gastric cancer specimens, and to correlate with lymph node statu...AIM: To evaluate and compare detection of lymphatic and blood vessel invasion (LVI and BVI) by hematox-ylin-eosin (HE) and immunohistochemistry (IHC) in gastric cancer specimens, and to correlate with lymph node status. METHODS: IHC using D2-40 (a lymphatic endothelial marker) and CD34 (a pan-endothelial marker) was performed to study LVI and BVI in surgical specimens froma consecutive series of 95 primary gastric cancer cases. The results of the IHC study were compared with the detection by HE using McNemar test and kappa index. The morphologic features of the tumors and the presence of LVI and BVI were related to the presence of lymph node metastasis. A χ2 test was performed to obtain associations between LVI and BVI and other prognostic factors for gastric cancer. RESULTS: The detection rate of LVI was considerably higher than that of BVI. The IHC study identified eight false-positive cases and 13 false-negative cases for LVI, and 24 false-positive cases and 10 false-negative cases for BVI. The average Kappa value determined was moderate for LVI (k=0.50) and low for BVI (k=0.20). Both LVI and BVI were statistically associated with the presence of lymph node metastasis (HE: P=0.001, P=0.013, and IHC: P=0.001, P=0.019). The mor-phologic features associated with LVI were location of the tumor in the distal third of the stomach (P=0.039), Borrmann's macroscopic type (P=0.001), organ inva-sion (P=0.03) and the depth of tumor invasion (P=0.001). The presence of BVI was related only to the depth of tumor invasion (P=0.003). CONCLUSION: The immunohistochemical identification of lymphatic and blood vessels is useful for increasing the accuracy of the diagnosis of vessel invasion and for predicting lymph node metastasis.展开更多
Objective: T-stage and N-stage have been proven to be the most important factors influencing survival in gastric cancer patients, and have been accepted for use in the Japanese Classification of Gastric Carcinoma(J...Objective: T-stage and N-stage have been proven to be the most important factors influencing survival in gastric cancer patients, and have been accepted for use in the Japanese Classification of Gastric Carcinoma(JCGC) and the Union International Cancer Control(UICC-TNM) staging systems. The purpose of this study was to compare the prognostic values of the different N classification systems in gastric cancer patients without serosal invasion.Methods: We retrospectively compared the clinicopathological results of 1,115 patients with primary gastric cancer who underwent curative gastric resection.Results: Serosal invasion was identified in 212 of 1,115 patients(19.0%), and it was associated with lymph node metastasis according to the JCGC^13th(P〈0.001) and TNM^7th(P〈0.001) systems. The 5-year survival rate for the serosal invasion-negative patients(78.2%) was significantly higher than that for the serosal invasion-positive patients(31.1%)(P〈0.001). Multivariate Cox regression survival analysis showed that depth of invasion(P=0.013), 13 th JCGC PN stage(P〈0.001), and 7th TNM PN stage(P〈0.001) were independent prognostic factors for serosal invasion-negative gastric cancer patients.Conclusions: The prognosis of gastric cancer patients with serosal invasion is very poor. Both the 13 th JCGC and 7th TNM N-staging systems were able to accurately estimate the prognosis of gastric cancer patients, but the 7th TNM system was simpler and easier to use.展开更多
BACKGROUND Accurate preoperative staging of gastric cancer(GC),a common malignant tumor worldwide,is critical for appropriate treatment plans and prognosis.Dynamic three-phase enhanced computed tomography(CT)scanning ...BACKGROUND Accurate preoperative staging of gastric cancer(GC),a common malignant tumor worldwide,is critical for appropriate treatment plans and prognosis.Dynamic three-phase enhanced computed tomography(CT)scanning for preoperative staging of GC has limitations in evaluating tumor angiogenesis.CD34,a marker on vascular endothelial cell surfaces,is promising in evaluating tumor angiogenesis.We explored the value of their combination for preoperative staging of GC to improve the efficacy and prognosis of patients with GC.Medical records of 106 patients with GC treated at the First People's Hospital of Lianyungang between February 2021 and January 2023 were retrospectively studied.All patients underwent three-phase dynamic contrast-enhanced CT scanning before surgery,and CD34 was detected in gastroscopic biopsy specimens.Using surgical and pathological results as the gold standard,the diagnostic results of three-phase dynamic contrast-enhanced CT scanning at different T and N stages were analyzed,and the expression of CD34-marked microvessel density(MVD)at different T and N stages was determined.The specificity and sensitivity of three-phase dynamic contrast-enhanced CT and CD34 in T and N staging were calculated;those of the combined diagnosis of the two were evaluated in parallel.Independent factors affecting lymph node metastasis were analyzed using multiple logistic regression.RESULTS The accuracy of three-phase dynamic contrast-enhanced CT scanning in diagnosing stages T1,T2,T3 and T4 were 68.00%,75.00%,79.41%,and 73.68%,respectively,and for diagnosing stages N0,N1,N2,and N3 were 75.68%,74.07%,85.00%,and 77.27%,respectively.CD34-marked MVD expression increased with increasing T and N stages.Specificity and sensitivity of three-phase dynamic contrast-enhanced CT in T staging were 86.79%and 88.68%;for N staging,89.06%and 92.86%;for CD34 in T staging,64.15%and 88.68%;and for CD34 in N staging,84.38%and 78.57%,respectively.Specificity and sensitivity of joint diagnosis in T staging were 55.68%and 98.72%,and N staging were 75.15%and 98.47%,respectively,with the area under the curve for diagnosis improving accordingly.According to multivariate analysis,a longer tumor diameter,higher pathological T stage,lower differ-entiation degree,and higher expression of CD34-marked MVD were independent risk factors for lymph node metastasis in patients with GC.CONCLUSION With high accuracy in preoperatively determining the invasion depth and lymph node metastasis of GC,CD34 expression and three-phase dynamic contrast-enhanced CT can provide a reliable basis for surgical resection.展开更多
Gastric carcinoma (GC) progression is mainly caused by local aggression and lymph node metastasis. However, some patients with early T-stage disease have lymph node metastasis, whereas some patients with late T-stage ...Gastric carcinoma (GC) progression is mainly caused by local aggression and lymph node metastasis. However, some patients with early T-stage disease have lymph node metastasis, whereas some patients with late T-stage disease do not have lymph node metastasis, which indicates that invasion and metastasis are not always sequential in some GC patients. In the present study, the data of 101 GC cases were acquired from TCGA and divided into T-late-N-negative and T-early-N-positive groups according to pathological stages. A total of 338 genes were identified as differential genes between the T-late-N-negative and T-early-N-positive groups. GSEA showed that epithelial cell signaling in the Helicobacter pylori (HP ) infection pathway was enriched in the T-early-N-positive group. MB staining indicated that the HP infection rate was 63% (39/62) in N-positive patients compared to 42% (16/38) in N-negative patients. To investigate the potential mechanism, we focused on the gene chemokine (C-X-C motif) receptor 2 (CXCR2), which was not only clustered in the gene set of epithelial cells signaling in the HP infection pathway but also significantly upregulated in T-early-N-positive GC by the analysis of the different genes based on the TCGA dataset. A meta-analysis showed that CXCR2 expression was positively correlated with N-stage but not with T-stage in GC. This study indicated that invasion and metastasis could be independent processes driven by different molecular mechanisms in some GC patients. HP infection was a potential factor that promoted lymph node metastasis by upregulating CXCR2 expression.展开更多
基金supported by a grant from the National Key Research and Development Program of China(No.2023YFC2507406).
文摘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.
文摘Objective: To study the correlation of Slug gene expression with lymph node metastasis and invasion molecule expression in oral squamous cell carcinoma tissue. Methods: Oral squamous cell carcinoma tissue surgical removed in Affiliated Stomatological Hospital of Nanjing Medical University between March 2015 and April 2017 was selected and divided into the oral squamous cell carcinoma tissue with neck lymph node metastasis and the oral squamous cell carcinoma tissues without lymph node metastasis according to the condition of lymph node metastasis. The expression of Slug, epithelial-mesenchymal transition molecules and invasion molecules in the oral squamous cell carcinoma tissue were detected. Results:Slug, N-cadherin, Vimentin, CD147, OPN, GRP78, SDF-1 and CXCR4 protein expression in oral squamous cell carcinoma tissue with neck lymph node metastasis were significantly higher than those in oral squamous cell carcinoma tissue without lymph node metastasis while E-cadherin, P120ctn and ZO-1 protein expression were significantly lower than those in oral squamous cell carcinoma tissue without lymph node metastasis;N-cadherin, Vimentin, CD147, OPN, GRP78, SDF-1 and CXCR4 protein expression in oral squamous cell carcinoma tissue with high Slug expression were significantly higher than those in oral squamous cell carcinoma tissue with low Slug expression while E-cadherin, P120ctn and ZO-1 protein expression were significantly lower than those in oral squamous cell carcinoma tissue with low Slug expression. Conclusion: The highly expressed Slug in oral squamous cell carcinoma tissue can promote the epithelial-mesenchymal transition and invasion of the cells to participate in the lymph node metastasis of tumor cells.
基金Supported by Medical Science and Technology Development Foundation of Nanjing Department of Health,No.201402032
文摘AIM To investigate the relationship between histological mixed-type of early gastric cancer(EGC) in the mucosa and submucosa and lymph node metastasis(LNM).METHODS This study included 298 patients who underwent gastrectomy for EGC between 2005 and 2012. Enrolled lesions were divided into groups of pure differentiated(pure D), pure undifferentiated(pure U), and mixed-type according to the proportion of the differentiated and undifferentiated components observed under a microscope. We reviewed the clinicopathological features, including age, sex, location, size, gross type, lymphovascular invasion, ulceration, and LNM, among the three groups. furthermore, we evaluated the predictors of LNM in the mucosa-confined EGC.RESULTS Of the 298 patients, 165(55.4%) had mucosa-confined EGC and 133(44.6%) had submucosa-invasive EGC. Only 13(7.9%) cases of mucosa-confined EGC and 30(22.6%) cases of submucosa-invasive EGC were observed to have LNM. The submucosal invasion(OR = 4.58, 95%CI: 1.23-16.97, P = 0.023), pure U type(OR = 4.97, 95%CI: 1.21-20.39, P = 0.026), and mixedtype(OR = 5.84, 95%CI: 1.05-32.61, P = 0.044) were independent risk factors for LNM in EGC. The rate of LNM in mucosa-confined EGC was higher in the mixedtype group(P = 0.012) and pure U group(P = 0.010) than in the pure D group, but no significant difference was found between the mixed-type group and pure U group(P = 0.739). Similarly, the rate of LNM in the submucosa-invasive EGC was higher in the mixedtype(P = 0.012) and pure U group(P = 0.009) than in the pure D group but was not significantly different between the mixed-type and pure U group(P = 0.375). Multivariate logistic analysis showed that only female sex(OR = 5.83, 95%CI: 1.64-20.70, P = 0.028) and presence of lymphovascular invasion(OR = 13.18, 95%CI: 1.39-125.30, P = 0.020) were independent risk factors for LNM in mucosa-confined EGC, while histological type was not an independent risk factor for LNM in mucosa-confined EGC(P = 0.106).CONCLUSION for mucosal EGC, histological mixed-type is not an independent risk factor for LNM and could be managed in the same way as the undifferentiated type.
文摘AIM:To explore the feasibility of pertorming minimally invasive surgery(MIS)on subsets of submucosal gastric cancers that are unlikely to have regional lymph node metastasis. METHODS:A total of 105 patients underwent radical gastrectomy with lymph node dissection for submucosal gastric cancer at our hospital from January 1995 to December 1995.Besides investigating many clinicopathological features such as tumor size,gross appearance,and differentiation, we measured the depth of invasion into submucosa minutely and analyzed the clinicopathologic features of these patients regarding lymph node metastasis. RESULTS:The rate of lymph node metastasis in cases where the depth of invasion was<500 μm,500-2 000 μm,or >2 000 μm was 9%(2/23),19%(7136),and 33%(15/46), respectively(P<0.05).In univariate analysis,no significant correlation was found between lymph node metastasis and clinicopathological characteristics such as age,sex,tumor location,gross appearance,tumor differentiation,Lauren's classification,and lymphatic invasion.In multivariate analysis, tumor size(>4 cm vs≤2 cm,odds ratio=4.80, P=0.04)and depth of invasion(>2 000 μm vs ≤500 μm, odds ratio=6.81,P=0.02)were significantly correlated with lymph node metastasis.Combining the depth and size in cases where the depth of invasion was less than 500 μm, we found that lymph node metastasis occurred where the tumor size was greater than 4 cm.In cases where the tumor size was less than 2 cm,lymph node metastasis was found only where the depth of tumor invasion was more than 2 000 μm. CONCLUSION:MIS can be applied to submucosal gastric cancer that is less than 2 cm in size and 500 μm in depth.
基金This work was supported by the National Natural Science Foundation of China (No.30470667) the Project was sponsored by SRF for ROCS, SEM (No. 2003-2005), and Tianjin Medical University Foundation for Introduction of the Talented Man (No.2003- 2005).
文摘OBJECTIVE To investigate the relationship between lymphatic vessel density and lymph node metastasis of invasive micropapillary carcinoma (IMPC) of the breast. METHODS The immunohistochemical study for vascular endothelial growth factor-c (VEGF-C), VEGF Receptor-3 (VEGFR-3) and lymphatic vessel density of 51 cases of IMPC were performed, and lymph node metastases were examined by microscopic analysis of these cases. RESULTS In IMPC, VEGF-C was expressed in the cytoplasm and/or on the membrane of the tumor cells, and the expression of VEGF-C showed a positive correlation with lymph node metastasis (P<0.01). Lymphatic vessel density was determined by the number of micro-lymphatic vessels with VEGFR-3 positive staining. Lymphatic vessel density was positively correlated with VEGF-C expression (P<0.01) and lymph node metastasis (P<0.01). The percentage of IMPC in the tumor was not associated with the incidence of lymph node metastasis. The metastatic foci in lymph nodes were either pure or predominant micropapillary carcinoma. CONCLUSION The results suggested that VEGF-C overexpression stimulated tumor lymphangiogenesis, and the increased lymphatic vessel density may be the key factor that influenced lymph node metastasis of IMPC.
基金supported by the Science and Technology Development Planning of Shandong Provincethe China Postdoctoral Science Fund (Grant No.2012GGE27088 andNo.2011M500531)
文摘Objective: This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion (LVI) labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma (ESCC). Methods: Immunohistochemical assay was used to detect the expression of D2-40 and LVI in 107 ESCC patients. Then, the correlation between the clinicopathologic feature and the overall survival time of the patients was analyzed. Results: The lymph node metastasis rates were 70% and 21% in the LVI-positive and LVI-negative groups, respectively. The nodal metastasis rate was higher in the LVI-positive group than in the LVI-negative group. Multivariate regression analysis showed that LVI was related to nodal metastasis (P〈0.001). The median survival time of the patients was 26 and 43 months in the LVI-positive and LVI-negative groups, respectively. Mthough univariate regression analysis showed significant difference between the two groups (P=0.014), multivariate regression analysis revealed that LVI was not an independent prognostic factor for overall survival in the ESCC patients (P=0.062). Lymphatic node metastasis (P=0.031), clinical stage (P=0.019), and residual tumor (P=0.026) were the independent prognostic factors. Conclusion: LVI labeled by D2-40 monoclonal antibody is a risk factor predictive of lymph node metastasis in ESCC patients.
基金Supported by Gazi UniversityScientific Research Projects DivisionNo.01/2007-62
文摘AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan (Trp) and kynurenine (Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologically and were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies.RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups (both P > 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp (r = 0.450, P < 0.01). Urinary biopterin was significantly higher in cancer cases (P < 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients (P < 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group (44.56% ± 6.11%) than negative colorectal cancer patients (24.04% ± 6.90%), (P < 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis (P < 0.01 and P < 0.05, respectively). A significant difference between the accuracy of diagnosis by using either total indoleamine-2,3-dioxygenase immunostaining score or of lymph node metastasis was found during the evaluation of cancer patients.CONCLUSION: Indoleamine-2,3-dioxygenase expression may predict the presence of unrecognized LI and lymph node metastasis and may be included in the histopathological evaluation of colorectal carcinoma cases.
文摘Purpose: Submucosal invasive colorectal carcinoma (SICC) exhibits lymph node metastasis in about 10% of patients. Therefore, endoscopic resection is insufficient for cases of SICC at risk of lymph node metastasis, and surgical resection accompanied with lymph node dissection is necessary. However, because additional intestinal resection is unnecessary for cases without lymph node metastasis, more rigid criteria are required in order to decrease the incidence of unnecessary further intestinal resection. We retrospectively identified predictive factors for lymph node metastasis in submucosal invasive colorectal carcinoma. Methods: One hundred and two patients who underwent intestinal resection as the first treatment or additional intestinal resection after endoscopic resection at our department between 1999 and 2012 were enrolled in the present study. Clinicopathological factors were analyzed to determine predictive factors related to lymph node metastasis. Results: The multivariate analysis revealing only depth of submucosal invasion (≤2700 μm) was found to be a significant, independent predictive factor of lymph node metastasis (P = 0.04, Odds ratio: 4.18, 95% CI: 1.06 - 16.40). Conclusion: It is considered that the refinement of the criteria in the present study will be very useful, especially in the patients for whom careful judgment is required when considering additional intestinal resection.
文摘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.
文摘AIM To evaluate a novel grading system to predict lymph node metastasis(LNM) in patients with submucosal invasive colorectal carcinoma(SICRC).METHODS We analyzed the associations between LNM and various clinicopathological features in 252 patients with SICRC who had undergone radical surgery at the Seoul Saint Mary's hospital between 2000 and 2015.RESULTS LNM was observed in 31 patients(12.3%). The depth and width of the submucosal invasion, lymphatic invasion, tumor budding, and the presence of poorly differentiated clusters(PDCs) were significantly associated with the incidence of LNM. Using multivariate analysis, the receiver operating characteristic curvewas calculated and the area under curve(AUC) was used to compare the ability of the different parameters to identify the risk of LNM. The most powerful clinicopathological parameter for predicting LNM was lymphatic invasion(difference AUC = 0.204), followed by the presence or absence of tumor budding(difference AUC = 0.190), presence of PDCs(difference AUC = 0.172) and tumor budding graded by the Ueno method(difference AUC = 0.128). CONCLUSION Our results indicate that the tumor budding and the depth multiplied by the width measurements of submucosal invasion can provide important information for patients with SICRC.
文摘AIM To assess clinical outcomes for submucosal (T1b) oesophageal adenocarcinoma (OAC) patients managed with either surgery or endoscopic eradication therapy.METHODS Patients found to have T1b OAC following endoscopic resection between January 2008 to February 2016 at University College London Hospital were retrospectively analysed. Patients were split into low-risk and high-risk groups according to established histopathological criteria and were then further categorised according to whether they underwent surgical resection or conservative management. Study outcomes include the presence of lymphnode metastases, disease-specific mortality and overall survival. RESULTS A total of 60 patients were included; 22 patients were surgically managed (1 low-risk and 21 high-risk patients) whilst 38 patients were treated conservatively (12 low-risk and 26 high-risk). Overall, lymph node metastases (LNM) were detected in 10 patients (17%); six of these patients had undergone conservative management and LNM were detected at a median of 4 mo after endoscopic mucosal resection (EMR). All LNM occurred in patients with highrisk lesions and this represented 21% of the total high-risk lesions. Importantly, there was no statistically significant difference in tumor-related deaths between those treated surgically or conservatively (P = 0.636) and disease-specific survival time was also comparable between the two treatment strategies (P = 0.376).CONCLUSION T1b tumours without histopathological high-risk markers of LNM can be treated endoscopically with good outcomes. In selected patients, endoscopic therapy may be appropriate for high-risk lesions.
基金Supported by Grants from Coordenao de Aperfeioamentode Pessoal de Nível Superior
文摘AIM: To evaluate and compare detection of lymphatic and blood vessel invasion (LVI and BVI) by hematox-ylin-eosin (HE) and immunohistochemistry (IHC) in gastric cancer specimens, and to correlate with lymph node status. METHODS: IHC using D2-40 (a lymphatic endothelial marker) and CD34 (a pan-endothelial marker) was performed to study LVI and BVI in surgical specimens froma consecutive series of 95 primary gastric cancer cases. The results of the IHC study were compared with the detection by HE using McNemar test and kappa index. The morphologic features of the tumors and the presence of LVI and BVI were related to the presence of lymph node metastasis. A χ2 test was performed to obtain associations between LVI and BVI and other prognostic factors for gastric cancer. RESULTS: The detection rate of LVI was considerably higher than that of BVI. The IHC study identified eight false-positive cases and 13 false-negative cases for LVI, and 24 false-positive cases and 10 false-negative cases for BVI. The average Kappa value determined was moderate for LVI (k=0.50) and low for BVI (k=0.20). Both LVI and BVI were statistically associated with the presence of lymph node metastasis (HE: P=0.001, P=0.013, and IHC: P=0.001, P=0.019). The mor-phologic features associated with LVI were location of the tumor in the distal third of the stomach (P=0.039), Borrmann's macroscopic type (P=0.001), organ inva-sion (P=0.03) and the depth of tumor invasion (P=0.001). The presence of BVI was related only to the depth of tumor invasion (P=0.003). CONCLUSION: The immunohistochemical identification of lymphatic and blood vessels is useful for increasing the accuracy of the diagnosis of vessel invasion and for predicting lymph node metastasis.
文摘Objective: T-stage and N-stage have been proven to be the most important factors influencing survival in gastric cancer patients, and have been accepted for use in the Japanese Classification of Gastric Carcinoma(JCGC) and the Union International Cancer Control(UICC-TNM) staging systems. The purpose of this study was to compare the prognostic values of the different N classification systems in gastric cancer patients without serosal invasion.Methods: We retrospectively compared the clinicopathological results of 1,115 patients with primary gastric cancer who underwent curative gastric resection.Results: Serosal invasion was identified in 212 of 1,115 patients(19.0%), and it was associated with lymph node metastasis according to the JCGC^13th(P〈0.001) and TNM^7th(P〈0.001) systems. The 5-year survival rate for the serosal invasion-negative patients(78.2%) was significantly higher than that for the serosal invasion-positive patients(31.1%)(P〈0.001). Multivariate Cox regression survival analysis showed that depth of invasion(P=0.013), 13 th JCGC PN stage(P〈0.001), and 7th TNM PN stage(P〈0.001) were independent prognostic factors for serosal invasion-negative gastric cancer patients.Conclusions: The prognosis of gastric cancer patients with serosal invasion is very poor. Both the 13 th JCGC and 7th TNM N-staging systems were able to accurately estimate the prognosis of gastric cancer patients, but the 7th TNM system was simpler and easier to use.
文摘BACKGROUND Accurate preoperative staging of gastric cancer(GC),a common malignant tumor worldwide,is critical for appropriate treatment plans and prognosis.Dynamic three-phase enhanced computed tomography(CT)scanning for preoperative staging of GC has limitations in evaluating tumor angiogenesis.CD34,a marker on vascular endothelial cell surfaces,is promising in evaluating tumor angiogenesis.We explored the value of their combination for preoperative staging of GC to improve the efficacy and prognosis of patients with GC.Medical records of 106 patients with GC treated at the First People's Hospital of Lianyungang between February 2021 and January 2023 were retrospectively studied.All patients underwent three-phase dynamic contrast-enhanced CT scanning before surgery,and CD34 was detected in gastroscopic biopsy specimens.Using surgical and pathological results as the gold standard,the diagnostic results of three-phase dynamic contrast-enhanced CT scanning at different T and N stages were analyzed,and the expression of CD34-marked microvessel density(MVD)at different T and N stages was determined.The specificity and sensitivity of three-phase dynamic contrast-enhanced CT and CD34 in T and N staging were calculated;those of the combined diagnosis of the two were evaluated in parallel.Independent factors affecting lymph node metastasis were analyzed using multiple logistic regression.RESULTS The accuracy of three-phase dynamic contrast-enhanced CT scanning in diagnosing stages T1,T2,T3 and T4 were 68.00%,75.00%,79.41%,and 73.68%,respectively,and for diagnosing stages N0,N1,N2,and N3 were 75.68%,74.07%,85.00%,and 77.27%,respectively.CD34-marked MVD expression increased with increasing T and N stages.Specificity and sensitivity of three-phase dynamic contrast-enhanced CT in T staging were 86.79%and 88.68%;for N staging,89.06%and 92.86%;for CD34 in T staging,64.15%and 88.68%;and for CD34 in N staging,84.38%and 78.57%,respectively.Specificity and sensitivity of joint diagnosis in T staging were 55.68%and 98.72%,and N staging were 75.15%and 98.47%,respectively,with the area under the curve for diagnosis improving accordingly.According to multivariate analysis,a longer tumor diameter,higher pathological T stage,lower differ-entiation degree,and higher expression of CD34-marked MVD were independent risk factors for lymph node metastasis in patients with GC.CONCLUSION With high accuracy in preoperatively determining the invasion depth and lymph node metastasis of GC,CD34 expression and three-phase dynamic contrast-enhanced CT can provide a reliable basis for surgical resection.
基金supported by the National Natural Science Foundation of China(No.81974385).
文摘Gastric carcinoma (GC) progression is mainly caused by local aggression and lymph node metastasis. However, some patients with early T-stage disease have lymph node metastasis, whereas some patients with late T-stage disease do not have lymph node metastasis, which indicates that invasion and metastasis are not always sequential in some GC patients. In the present study, the data of 101 GC cases were acquired from TCGA and divided into T-late-N-negative and T-early-N-positive groups according to pathological stages. A total of 338 genes were identified as differential genes between the T-late-N-negative and T-early-N-positive groups. GSEA showed that epithelial cell signaling in the Helicobacter pylori (HP ) infection pathway was enriched in the T-early-N-positive group. MB staining indicated that the HP infection rate was 63% (39/62) in N-positive patients compared to 42% (16/38) in N-negative patients. To investigate the potential mechanism, we focused on the gene chemokine (C-X-C motif) receptor 2 (CXCR2), which was not only clustered in the gene set of epithelial cells signaling in the HP infection pathway but also significantly upregulated in T-early-N-positive GC by the analysis of the different genes based on the TCGA dataset. A meta-analysis showed that CXCR2 expression was positively correlated with N-stage but not with T-stage in GC. This study indicated that invasion and metastasis could be independent processes driven by different molecular mechanisms in some GC patients. HP infection was a potential factor that promoted lymph node metastasis by upregulating CXCR2 expression.