Prognostic Value Of Lymphovascular Invasion Research Articles

Prognostic Value of Lymphovascular Invasion in Patients With Pyriform Sinus Carcinoma Treated With Surgery Plus Adjuvant Chemo-/Radiotherapy.

We aimed to determine the prognostic value of lymphovascular invasion (LVI) in pyriform sinus carcinoma (PSC) after primary surgery with adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Patients who underwent primary surgery at our institution between 2000 and 2018 were included in this study and retrospectively analyzed. The endpoints were locoregional recurrence (LRR), distant metastasis (DM), and disease-specific survival (DSS). We reviewed 117 patients with PSC. LVI was identified in 29 patients (24.8%). The 5-year LRR rate, DM rate, and DSS rate were 29.4%, 31.7%, and 45.9%, respectively. Tumors with LVI were associated with a significantly higher LRR (P = 0.002, HR 3.678, 95% CI 1.646-8.218) and DM (P = 0.003, HR 3.666, 95% CI 1.543-8.709) and a lower DSS (P = 0.001, HR 2.814, 95% CI 1.519-5.213) in multivariate analysis. LVI is a significant predictor of poor prognosis in patients with PSC treated with surgery plus adjuvant RT/CCRT.

Prognostic value of lymphovascular invasion in patients with muscle-invasive bladder cancer

Background. Bladder cancer ranks 9 in prevalence among malignancies and 2 among malignant tumors of the human urogenital tract. Removal of the bladder together with a tumor significantly reduces the quality of patients’ life and contributes to the emergence of postoperative complications that can lead to the patient’s death during the first year after the surgery. Along with radical methods of removing muscleinvasive bladder cancer (MIBC), organ-sparing operations can be performed, which can be an effective alternative to radical cystectomy. Purpose of study was to compare the results of treatment of MIBC with presence of lymphovascular invasion (LVI) in the primary tumor in two groups: after radical cystectomy with ileocystoneoplasty and partial cystectomy (PC) with adjuvant chemotherapy. Materials and methods. Depending on the method of treatment, patients were divided into 2 groups. The 1st group included 46 (42,4%) patients who underwent PC with adjuvant chemotherapy; 2nd group – 63 (57,6%) patients after radical cystectomy with ileocystoneoplasty or ureterocutaneostomy. Patient selection criteria for bladder preservation were generally recommended. Overall survival, cancer-specific and recurrencefree survival rates were evaluated according to the method of Kaplan–Meier. The median age of patients in the 1st group was 55 (48–65 years), in the 2nd – 60 (55–71 years). Results. The obtained data show that during 5-year follow-up period, the oncological results of the treatment of 2 groups have no significant difference, but taking into account significantly better quality of life of patients who underwent organ-preserving treatment, it is possible to claim that the use of bimodal therapy of MIBC in selectively chosen patients is justified. LVI was an independent predictor of both disease recurrence and cancer-specific survival rates. Patients who received complex therapy in presented studies demonstrated satisfactory cancer-specific and overall survival rates. Conclusions. The use of organ-preserving treatment with adjuvant chemotherapy in patients with MIBC and positive LVI allows the oncological results, which are comparable to radical cystectomy, to be achieved. Taking into consideration significant advantages of organ-preserving treatment compared with radical cystectomy with various methods of urine derivation, the proposed treatment strategy is an appropriate alternative to radical cystectomy.

Gene expression associated with lymphovascular invasion and genomic risk in early-stage breast cancer.

559 Background: Lymphovascular invasion (LVI), the passage of carcinoma cells through lymphatic and blood vessels, is an important early step in metastasis; however, LVI is excluded from most breast cancer (BC) clinical risk assessments. Previous studies assessed the prognostic value of LVI to estimate clinical outcomes. To gain understanding of the molecular basis of LVI, we evaluated differentially expressed genes (DEGs) between tumors with LVI versus those without LVI, stratified by the 70-gene signature (MammaPrint/MP) and 80-gene molecular subtyping signature (BluePrint/BP). Methods: The prospective, observational FLEX Study (NCT03053193) includes stage I-III BC patients who receive MP/BP testing and consent to full transcriptome and clinical data collection. Patients with LVI (n=581) and without LVI (n=600, randomly selected), enrolled from 2017 to present, were included. LVI was assessed by local pathology laboratories. Differential gene expression analysis of 44k Agilent microarray data was performed with R limma package. DEGs were compared within all samples, BP Luminal subtype, MP risk groups (Low Risk [LR]/Luminal A and High Risk [HR]/Luminal B), and by lymph node (LN) status. DEGs with FDR<0.05 were considered significant. Results: Of tumors with LVI (LVI+), 66% were MP HR; notably, 51% of tumors without LVI (LVI-) were MP HR. LVI was associated with larger T stage, LN involvement, high grade, negative ER status by IHC, and younger patient age (LVI+ vs. LVI-, p<0.05 for all comparisons). Patient ethnicity, obesity, and tumor type did not differ by LVI status; however, prevalence of type 2 diabetes trended higher in patients with LVI+ HR tumors (21%), compared with LVI- HR (15%, p=0.09) and LVI+ LR (11%, p=0.004). There were significant transcriptomic differences between LVI+ and LVI, with most DEGs evident in the Luminal B subset. DEGs in LVI+, LN-negative (LN-) tumors overlapped substantially with the overall Luminal group analysis. Functional enrichment analysis showed dysregulation of cell cycle, extracellular matrix (ECM) organization, cell adhesion, and cytokine receptor pathways. Gene sets related to insulin growth factor pathways were also enriched in LVI+ tumors. Conclusions: DEGs associated with LVI were primarily found in MP HR Luminal, LN-negative tumors; enrichment analysis suggested dysregulation of ECM organization and cell adhesion pathways, consistent with previous reports. DEGs were not associated with LVI presence in LN+ tumors, suggesting that LVI assessment may be less relevant in LN+ breast cancer. Future studies will assess clinical outcomes, as well as LVI-associated gene expression in BP Basal- and HER2-type tumors. However, the current analysis indicates few DEGs in LVI+ MP LR tumors; thus, the potential prognostic information gained from LVI-associated gene expression is likely already captured by the MP and BP signatures. Clinical trial information: NCT03053193.

Prognostic value of lymphovascular invasion in stage II colorectal cancer patients with an inadequate examination of lymph nodes

BackgroundLymphovascular invasion (LVI) is defined as the presence of cancer cells in lymphatics or blood vessels. This study aimed to evaluate the prognostic value of LVI in stage II colorectal cancer (CRC) patients with inadequate examination of lymph nodes (ELNs) and further combined LVI with the TNM staging system to determine the predictive efficacy for CRC prognosis. Adjuvant chemotherapy (ACT) was then evaluated for stage II CRC patients with LVI positivity (LVI+).MethodsIn order to avoid the effects of different ACT regimens, among 409 stage II patients, we chose 121 patients who received FOLFOX regimen and the 144 patients who did not receive ACT as the object of study. LVI was examined by hematoxylin-eosin (HE) staining. Kaplan-Meier analysis followed by a log-rank test was used to analyze survival rates. Univariate and multivariate analyses were performed using a Cox proportional hazards model. Harrell’s concordance index (C-index) was used to evaluate the accuracy of different systems in predicting prognosis.ResultsThe LVI+ status was significantly associated with pT stage, degree of differentiation, tumor stage, serum CEA and CA19-9 levels, perineural invasion (PNI), tumor budding (TB), and KRAS status. The 5-year overall survival (OS) rate of stage II patients with < 12 ELNs and LVI+ was less than stage IIIA. Multivariate analyses showed that LVI, pT-stage, serum CEA and CA19-9 levels, PNI, TB, and KRAS status were significant prognostic factors for stage II patients with < 12 ELNs. The 8th TNM staging system combined with LVI showed a higher C-index than the 8th TNM staging system alone (C-index, 0.895 vs. 0.833). Among patients with LVI+, the ACT group had a significantly higher 5-year OS and 5-year disease-free survival (DFS) than the surgery alone (SA) group (5-year OS, 66.7% vs. 40.9%, P = 0.004; 5-year DFS, 64.1% vs. 36.3%, P = 0.002).ConclusionsLVI is an independent prognostic risk factor for stage II CRC patients. Combining LVI with the 8th TNM staging system improved the predictive accuracy for CRC prognosis. ACT in stage II CRC patients with LVI+ is beneficial for survival.

MP11-19 LYMPHOVASCULAR INVASION AND PRESENCE OF EMBRYONAL CARCINOMA AS RISK FACTORS FOR OCCULT METASTASES IN CLINICAL STAGE I NONSEMINOMATOUS GERM CELL TUMOR: A SYSTEMATIC REVIEW AND META-ANALYSIS

You have accessJournal of UrologyPenile & Testicular Cancer: Penile & Testicular Cancer I (MP11)1 Apr 2020MP11-19 LYMPHOVASCULAR INVASION AND PRESENCE OF EMBRYONAL CARCINOMA AS RISK FACTORS FOR OCCULT METASTASES IN CLINICAL STAGE I NONSEMINOMATOUS GERM CELL TUMOR: A SYSTEMATIC REVIEW AND META-ANALYSIS Joost Blok*, Ilse Pluim, Gedske Daugaard, Thomas Wagner, Katarzyna Jozwiak, Erica Wilthagen, Leendert Looijenga, Ruud Bosch, Simon Horenblas, and Richard Meijer Joost Blok*Joost Blok* More articles by this author , Ilse PluimIlse Pluim More articles by this author , Gedske DaugaardGedske Daugaard More articles by this author , Thomas WagnerThomas Wagner More articles by this author , Katarzyna JozwiakKatarzyna Jozwiak More articles by this author , Erica WilthagenErica Wilthagen More articles by this author , Leendert LooijengaLeendert Looijenga More articles by this author , Ruud BoschRuud Bosch More articles by this author , Simon HorenblasSimon Horenblas More articles by this author , and Richard MeijerRichard Meijer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000831.019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The presence of lymphovascular invasion (LVI) and embryonal carcinoma (EC) are important factors that aid clinical decision-making in patients with clinical stage I (CS I) nonseminomatous germ cell tumor (NSGCT). Several studies have investigated the association between these predictors and occult metastasis. A systematic review with meta-analysis is necessary to quantify the strength of these predictors more precisely. Our aim was to review the literature on the prognostic value of LVI and EC for occult metastasis in CS I NSGCT. In particular, we aimed to compare the prognostic value of two different methods of EC assessment. METHODS: The Pubmed, Embase (OVID) and SCOPUS databases were searched up to March 2019. Studies reporting on the association between LVI and/or EC and occult metastasis were considered for inclusion. EC was assessed as EC predominance (presence of >50% EC in the primary tumor) or as EC presence (without a percentage cut-off value). The meta-analysis was performed using Cochrane's Review Manager tool. The PRISMA guidelines were followed and risk of bias was evaluated using the Quality in Prognosis Studies tool. RESULTS: We screened 5,287 abstracts and 207 full-text articles. We included 35 studies in the narrative synthesis and 24 studies in one of the meta-analyses. LVI showed the strongest effect. Pooled rates of occult metastasis were 47.5% and 16.9% for LVI positive and LVI negative patients, respectively (OR 4.33; 95% CI 3.55-5.30; p<0.001). Presence of EC showed a significantly higher pooled rate of occult metastasis (33.2%), compared to EC absence (16.2%; OR 2.49; 95% CI; 1.64-3.77; p<0.001). For EC predominance, defined as >50%, the pooled rate of occult metastasis was 40.0%. This was significantly higher than patients without EC predominance (20.0%; OR 2.62; 95% CI 1.93-3.56; p<0.001). The risk of bias was moderate or high for all studies. CONCLUSIONS: LVI is the strongest risk factor for relapse. The prognostic value of EC is high, but there is no common agreement on how to define this risk factor. EC presence and EC>50% have similar ORs for occult metastasis. This suggests that the assessment of EC presence is sufficient for risk stratification. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e142-e143 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joost Blok* More articles by this author Ilse Pluim More articles by this author Gedske Daugaard More articles by this author Thomas Wagner More articles by this author Katarzyna Jozwiak More articles by this author Erica Wilthagen More articles by this author Leendert Looijenga More articles by this author Ruud Bosch More articles by this author Simon Horenblas More articles by this author Richard Meijer More articles by this author Expand All Advertisement PDF downloadLoading ...

Lymphovascular invasion and presence of embryonal carcinoma as risk factors for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour: a systematic review and meta-analysis.

ObjectiveTo systematically review the literature on the prognostic value of lymphovascular invasion (LVI) and embryonal carcinoma (EC) for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour (CS I NSGCT).Materials and methodsThe PubMed, Embase (OVID) and SCOPUS databases were searched up to March 2019. Studies reporting on the association between LVI and/or EC and occult metastatic disease were considered for inclusion. The quality and risk of bias were evaluated by the Quality in Prognosis Studies tool.ResultsWe screened 5287 abstracts and 207 full‐text articles. We included 35 studies in the narrative synthesis and 24 studies in a meta‐analysis. LVI showed the strongest effect. Pooled rates of occult metastasis were 47.5% and 16.9% for LVI‐positive and LVI‐negative patients, respectively (odds ratio [OR] 4.33, 95% confidence interval [CI] 3.55–5.30; P < 0.001). Pooled rates of occult metastasis were 33.2% for EC presence and 16.2% for EC absence (OR 2.49, 95% CI 1.64–3.77; P < 0.001). Pooled rates of occult metastasis were 40.0% for EC >50% and 20.0% for EC <50% (OR 2.62, 95% CI 1.93–3.56; P < 0.001).ConclusionsLVI is the strongest risk factor for relapse. The prognostic value of EC is high, but there is no common agreement on how to define this risk factor. Both EC presence and EC >50% have similar ORs for occult metastasis. This shows that the assessment of EC presence is sufficient for the classification of EC.

Prognostic Value of Lymphovascular Invasion in Patients with Stage III Colorectal Cancer: A Retrospective Study.

BackgroundLymph node metastasis and tumor progression depend on lymphovascular invasion (LVI). This study aimed to investigate the prognostic role of LVI in patients with stage III colorectal cancer (CRC) and to develop a prognostic nomogram.Material/MethodsA retrospective study included 437 patients with stage III CRC. The impact of LVI on overall survival (OS) was analyzed with the Kaplan-Meier method and Cox regression model. A nomogram was constructed, and its predictive accuracy was evaluated using the concordance index (C-index) and the calibration plot.ResultsLVI was found in 19.7% of cases of stage III CRCs and was significantly correlated with high tumor grade (poor differentiation) and advanced tumor stage (all P<0.05). Patients age, a family history of cancer in a first-degree relative, pre-treatment levels of carcinoembryonic antigen (CEA), prognostic nutritional index (PNI), histological tumor grade, tumor-node-metastasis (TNM) stage, and LVI were independent prognostic indicators (all P<0.05). Compared with the LVI(−) group, patients in the LVI(+) group showed a 1.748-fold increased risk of death (P=0.004) and a significantly reduced OS rate (P<0.001). In the prognostic nomogram, the C-index was significantly increased with LVI compared with the TNM stage alone (0.742 vs. 0.593; P<0.001). Calibration plots showed good fitness of the nomogram for prediction of survival. Comparison of the nomograms with and without LVI showed that inclusion of LVI improved the C-index from 0.715 to 0.742.ConclusionsLVI was an indicator of more aggressive biological behavior and poor prognosis in patients with stage III CRC.

Prognostic value of lymphovascular invasion in patients with esophageal squamous cell carcinoma.

Whether lymphovascular invasion (LVI) in esophageal squamous cell carcinoma (ESCC) should be considered an independent prognostic factor for survival is controversial. The aim of this report was to investigate the prognostic value of LVI for patients with ESCC. Between October 2010 and July 2011, 152 ESCC patients were retrospectively reviewed. All of the patients underwent curative resection as their primary treatment. Clinicopathological features and overall survival (OS) rate were investigated. Kaplan-Meier curves were used to calculate the OS rate, and the prognostic factors were identified by Cox regression model. Positive LVI was found in 49 (32.2%) patients. Patients with negative LVI had a significantly better 5-year OS rate than those with positive LVI (52.9% vs. 28.8%; P=0.000). The age, T stage, N stage, tumor differentiation, and LVI were demonstrated to be significant prognostic factors for OS through univariate analyses. LVI was confirmed as an independent prognostic factor for OS through multivariate survival analyses. Subgroup analyses revealed that LVI was associated with a decreased OS in node-negative patients, and no significant difference was observed in node-positive cases. Our study highlighted that LVI is an independent prognostic factor in patients with resectable ESCC. LVI may facilitate the stratification of patients with poor survival.

Prognostic value of lymphovascular invasion in patients with squamous cell carcinoma of the penis following surgery

BackgroundTo evaluate the prognostic value of Lymphovascular Invasion (LVI) in patients with squamous cell carcinoma of the penis (SCCP) following surgery.Patients and methodsThis retrospective study analyzed the data of 891 eligible patients with SCCP who were diagnosed between 2010 and 2014, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were categorized by LVI, age, grade, T stage, lymph nodes status, distant metastasis, regional lymph nodes removed, and surgery. Overall survival (OS) and penile carcinoma-specific survival (PCSS) were evaluated by Kaplan-Meier method and Cox proportional hazards regression model.ResultsThe presence of LVI was significantly associated with increased risk of advanced T stage, high grade, lymph node metastasis, and distant metastasis (P < 0.001 for all). In Kaplan-Meier analyses, patients with the presence of LVI had significantly lower OS and PCSS than those with the absence of LVI (P < 0.001 for both,). The presence of LVI was also significantly associated with poorer OS and worse PCSS in patients with Tx + Ta + T1 stage (P = 0.007, P < 0.001), N0 stage (P < 0.001, P = 0.040), grade 1 (P = 0.001, P < 0.001), grade 2 (P = 0.001, P = 0.014), no distant metastasis (P < 0.001 for both), no regional lymph nodes removed (P < 0.001 for both), Non-radical surgery (P < 0.001 for both) and radical surgery(P = 0.037, P = 0.002). In multivariate analyses, the presence of LVI in patients with SCCP following surgery was found to be a significant independent predictor of decreased OS (hazard ratio 1.403, P = 0.039).ConclusionsThe LVI status might be a crucial prognostic indicator for overall survival in patients with SCCP.

Lymphovascular invasion as an independent prognostic indicator in radically resected thoracic esophageal squamous cell carcinoma.

BackgroundThe prognostic value of lymphovascular invasion (LVI) in esophageal cancer remains controversial. This study investigated the impact of LVI on prognosis in thoracic esophageal squamous cell carcinoma (ESCC).MethodsA total of 1586 patients who underwent radical esophagectomy were selected for the study. Correlations between LVI and clinicopathological features were evaluated by χ2 test. Univariate analysis of the survival curve was conducted using the Kaplan–Meier method. Multivariate analysis was carried out by Cox regression. The Akaike information criterion (AIC) and the concordance index (c‐index) were employed to assess model prognostic accuracy of different pN staging systems.ResultsThe presence of LVI was detected in 406 of 1586 (25.6%) patients. LVI frequency was significantly higher in patients with higher pN classifications (P < 0.001). LVI had independent significant prognostic value in ESCC (P < 0.001). In subgroup analyses, the presence of LVI significantly decreased overall survival in pN0, pN2, and pN3 stage patients. The AIC value of the pN staging system modified by LVI was lower than that of the current pN staging system, while the c‐index of the modified pN staging system was higher than that of the current pN staging system.ConclusionOur results suggest that LVI is an independent prognostic indicator in radically resected thoracic ESCC. LVI could potentially supplement the pN ESCC staging system. ESCC patients with LVI could be staged at more advanced pN classifications.

Lymphovascular invasion have a similar prognostic value as lymph node involvement in patients undergoing radical cystectomy with urothelial carcinoma

To determine the prognostic value of lymphovascular invasion (LVI) in patients with bladder cancer who underwent radical cystectomy. Total of 747 patients underwent radical cystectomy; of these, only 164 did not undergo lymph node dissection (LND). The patients were divided into 4 groups: N0, N1, LVI without LND, and non-LVI without LND. Patients in the N1 and LVI groups had significantly higher T stages and grades, as well 1.5- to 2-fold higher recurrence and mortality rates. Overall survival (OS) was significantly poorer in the N1 group, compared with the N0 and non-LVI groups (p = 0.001 and 0.012), and in the LVI group relative to the N0 and non-LVI groups (p = < 0.001 and <0.001). Recurrence-free survival (RFS) was also significantly poorer in the N1 group relative to the N0 and non-LVI groups (p = < 0.001 and <0.001), and in the LVI group relative to the N0 and non-LVI groups (p = < 0.001 and <0.001). Among patients undergoing radical cystectomy, the clinical results predicted by LVI were similar to those predicted by lymph node involvement. Therefore, the role of adjuvant chemotherapy or immunotherapy may need to be prospectively evaluated in LVI-positive patients regardless of T stage after radical cystectomy.

P2.16-04 Prognostic Value of Lymphovascular Invasion and Its Effect on Patterns of Recurrence in T1-3N0 Non-Small Cell Lung Cancer

P2.16-04 Prognostic Value of Lymphovascular Invasion and Its Effect on Patterns of Recurrence in T1-3N0 Non-Small Cell Lung Cancer

The clinical prognostic value of lymphovascular invasion in bladder cancer following radical cystectomy: a systematic review and Meta-analysis

To systematically evaluate the expression of lymphovascular invasion (LVI) in predicting the clinical prognosis of patients after radical cystectomy. Methods The relevant search strategy, including and excluding criteria for the relevant literature were developed by two independent researchers. The study of tumor prognosis in the patients with LVI following radical cystectomy cancer were searched by computerized PubMed, EMBASE, Web of Science, Cochrane library, China National Knowledge Infrastructure (CNKI) , Wanfang and VIP citation database. The search period was setted from the beginning of establishment of library until May 2017, and the search language was English and Chinese. The methodological quality of the included studies was assessed by the NOS. Besides, the relationship between LVI and the clinical outcome in patients following radical cystectomy was calculated by RevMan 5.3 and Stata 12.0 software. Results A total of 18 related clinical studies were included, published from 2008 to 2017. There were 12 354 patients with bladder cancer, of which 4 272 cases of LVI, with a proportion rate 34.6% .The results showed that the patients with LVI in pathological sections had a lower overall survival rate (HR=1.26, 95%CI 1.16-1.38 , P<0.001), recurrence-free survival (HR=1.27, 95%CI 1.06-1.52, P<0.001), cancer-specific survival rate (HR=1.30, 95%CI 1.18-1.42 , P<0.001) . Egger′s publication bias analysis showed no significant publication bias in terms of overall survival(P=0.636), recurrence-free survival (P=0.077), and cancer-specific survival (P=0.342). Conclusions LVI had a significant poor outcome in patients with radical resection of bladder cancer. It can be used as an independent risk factor to evaluate the postoperative prognosis of those patients, but more randomized controlled studies are still needed to make a further conformity in our completion. Key words: Urothelial carcinoma of the bladder; Lymphovascular invasion; Radical cystectomy; Survival prognosis; Meta-analysis

Prognostic value of lymphovascular invasion in Bismuth-Corlette type IV hilar cholangiocarcinoma.

AIMTo assess the prognostic value of lymphovascular invasion (LVI) in Bismuth-Corlette type IV hilar cholangiocarcinoma (HC) patients.METHODSA retrospective analysis was performed on 142 consecutively recruited type IV HC patients undergoing radical resection with at least 5 years of follow-up. Survival analysis was performed by the Kaplan-Meier method, and the association between the clinicopathologic variables and survival was evaluated by log-rank test. Multivariate analysis was adopted to identify the independent prognostic factors for overall survival (OS) and disease-free survival (DFS). Multiple logistic regression analysis was performed to determine the association between LVI and potential variables.RESULTSLVI was confirmed histopathologically in 29 (20.4%) patients. Multivariate analysis showed that positive resection margin (HR = 6.255, 95%CI: 3.485-11.229, P < 0.001), N1 stage (HR = 2.902, 95%CI: 1.132-7.439, P = 0.027), tumor size > 30 mm (HR = 1.942, 95%CI: 1.176-3.209, P = 0.010) and LVI positivity (HR = 2.799, 95%CI: 1.588-4.935, P < 0.001) were adverse prognostic factors for DFS. The independent risk factors for OS were positive resection margin (HR = 6.776, 95%CI: 3.988-11.479, P < 0.001), N1 stage (HR = 2.827, 95%CI: 1.243-6.429, P = 0.013), tumor size > 30 mm (HR = 1.739, 95%CI: 1.101-2.745, P = 0.018) and LVI positivity (HR = 2.908, 95%CI: 1.712-4.938, P < 0.001). LVI was associated with N1 stage and tumor size > 30 mm. Multiple logistic regression analysis indicated that N1 stage (HR = 3.312, 95%CI: 1.338-8.198, P = 0.026) and tumor size > 30 mm (HR = 3.258, 95%CI: 1.288-8.236, P = 0.013) were associated with LVI.CONCLUSIONLVI is associated with N1 stage and tumor size > 30 mm and adversely influences DFS and OS in type IV HC patients.

Rho-GTPase activating-protein 18: a biomarker associated with good prognosis in invasive breast cancer

Background:The prognostic value of lymphovascular invasion (LVI) in breast cancer (BC) has been demonstrated in several independent studies. However, identification of driver molecules for LVI remains a challenging task. Large-scale transcriptomic profiling of histologically validated LVI can potentially identify genes that regulate LVI.Methods:Integrative bio-informatics analyses of the METABRIC study were performed utilising a subset of strictly defined LVI using histological and immunohistochemical (IHC) criteria. ARHGAP18 was among the top differentially expressed genes between LVI+ and LVI− BC with a 1.8-fold change. The prognostic impact of ARHGAP18 gene expression was assessed in the METABRIC data set (n=1980) and externally validated using the online BC gene expression data sets utilising bc-GenExMiner v4.0 (n=2016). Subsequently, ARHGAP18 protein expression was assessed on a large cohort of invasive BC (n=959) with long-term follow-up using IHC.Results:Pooled analysis of ARHGAP18 mRNA expression showed that overexpression was associated with better outcome (P<0.001, hazard ratio (HR)=0.82, 95% CI 0.75–0.90). ARHGAP18 protein was expressed in the cytoplasm and nuclei of the tumour cells and its expression was positively associated with good prognostic variables. Lack of cytoplasmic expression showed associations with LVI (P=0.006), epithelial-mesenchymal transition and the HER+ subtype (P=0.01). Loss of nuclear expression was associated with higher grade, HER2+ and high Ki67LI (P=0.001). Cytoplasmic and nuclear expression showed a positive association with improved survival independent of other variables (P=0.01, HR=0.74, 95% CI 0.60–87).Conclusions:ARHGAP18 expression at transcriptomic and protein levels is associated with improved patients’ outcomes whose deregulation may play a role in tumour progression and the development of LVI in BC. Further assessment of its potential therapeutic value in BC is warranted.

Prognostic value of lymphovascular invasion of the primary tumor in hypopharyngeal carcinoma after total laryngopharyngectomy.

We aimed to determinate the prognostic value of lymphovascular invasion in the specimens resected during total laryngopharyngectomy for hypopharyngeal carcinoma. Patients who underwent total laryngopharyngectomy at our institution between 2004 and 2014 were included in this study and retrospectively analyzed. We then discriminated for vascular invasion and lymphatic invasion of the primary tumor in all cases. We reviewed 135 records (120 men and 15 women; age range, 36-84 years). Tumors with lymphatic invasion tended to be associated with more metastatic lymph nodes and extracapsular spread (ECS) of metastatic lymph nodes. Tumors with vascular invasion tended to be associated with nonpyriform sinus locations. In a multivariate analysis, nonpyriform sinus locations, >3 metastatic lymph nodes, and vascular invasion remained significant prognostic factors for overall survival (OS); in recursive partitioning analysis, ECS and vascular invasion remained important categorical variables for OS. Vascular invasion is a strong prognostic biomarker for advanced hypopharyngeal carcinoma. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1535-1543, 2017.

Lymphovascular invasion is a high risk factor for stage I/II colorectal cancer: a systematic review and meta-analysis.

The prognostic value of lymphovascular invasion (LVI) in stage I/II colorectal cancer (CRC) does not reach a consensus. To systematically assess prognostic significance of LVI, databases of PubMed, Web of Science, and Embase were searched from inception up to 10 Dec 2016. The pooled hazard ratio (HR) and 95% confidence intervals (CI) were used to determine the prognostic effects. Nineteen relevant studies including 9881 total patients were enrolled. Our results showed that LVI is significantly associated with poor prognosis in overall survival (OS) (HR=2.15, 95 % CI=1.72–2.68, P < 0.01) and disease-free survival (DFS) (HR=1.73, 95% CI=1.50–1.99, P < 0.01), which is similar in stage II patients. Further subgroup analysis revealed that the significance of the association between LVI and worse prognosis in CRC patients is not affected by below factors, including geographic setting, LVI positive rate, treatment, tumor site, and quality of the study. The current meta-analysis suggests that LVI may be a poor prognostic factor for stage I/II CRC patients.

Poor prognostic value of lymphovascular invasion for pT1 urothelial carcinoma with squamous differentiation in bladder cancer.

Lymphovascular invasion (LVI) is the primary and essential step in the systemic dissemination of cancer cells. The aim of our study was to assess the independent prognostic role of LVI for pT1 urothelial carcinoma with squamous differentiation in bladder cancer. We retrospectively analyzed the clinical and pathological information of 206 patients diagnosed pT1 urothelial carcinoma with squamous differentiation. Of the 206 patients, LVI was detected in 57 (27.6%) patients. The 5 year cancer specific survival (CSS) rates were 87.2% in LVI (−) and 52.4% in LVI (+) (p < 0.001). According to univariate analysis, tumor multiplicity, tumor size, recurrence and LVI were the prognostic factors associated with CSS. Additionally, tumor size and LVI significantly influenced the CSS in multivariate analysis. TURBT had shorter median CSS than RC in recurred patients with LVI (+). Our study suggested that LVI is an important predictor for survival of pT1 urothelial carcinoma with squamous differentiation. LVI positive status and tumor size ≥3 cm led to a higher risk of death. RC should be routinely performed in recurred LVI (+) bladder cancer patients of pT1 urothelial carcinoma with squamous differentiation.

Prognostic value of lymphovascular invasion in squamous cell carcinoma of the urinary bladder.

454 Background: The prognostic value of lymphovascular invasion (LVI) has been well studied in urothelial carcinoma of the bladder (UCB) but not in squamous cell carcinoma (SCC). Herein, we evaluate the association of LVI with oncologic outcomes of SCC following radical cystectomy (RC). Methods: We retrospectively evaluated 1280 patients who underwent RC and pelvic lymph node dissection (LND) for invasive bladder cancer between 1997– 2003 at a single institution in Mansoura, Egypt. Only patients with pure SCC pathology were included. Prognostic significance of LVI was evaluated for patients with SCC. Results: Our cohort included 360 patients with SCC. Median patient age and follow-up were 55 years (20 – 87) and 44 months (0 – 108), respectively. LVI was present in 47 (13.1%) and lymph node metastasis (LN+) was present in 66 (18.3%). In Kaplan-Meier analyses, 5-year disease free survival rates for LVI-/LN- and LVI+/LN- patients were 80.2±3% and 38.9±12% (p &lt; 0.001), respectively; 5-year cancer specific survival rates were 88.2±2% and 50.4±13% (p &lt; 0.001), respectively. Moreover, cancer specific mortality was highest in LVI+/LN- patients (HR = 3.657; 95% CI: 1.614 – 8.284; p = 0.002). Multivariate Cox-regression analyses showed that LVI+ status was independently associated with disease recurrence (HR = 2.827; 95% CI: 1.451 – 5.509; p = 0.002 and cancer specific mortality in patients with SCC (HR = 3.657; 95% CI: 1.614 – 8.284; p = 0.002). Conclusions: Lymphovascular invasion is a strong independent predictor of oncological outcomes after RC for SCC of the urinary bladder. The incorporation of LVI status into classic prognostic models for SCC of the bladder may lead to improved identification of high-risk patients.

The prognostic value of lymphovascular invasion in radical prostatectomy: a systematic review and meta-analysis.

To systematically evaluate the prognostic value of lymphovascular invasion (LVI) in radical prostatectomy (RP) by a meta-analysis based on the published literature. To identify relevant studies, PubMed, Cochrane Library, and Web of Science database were searched from 1966 to May 2014. Finally, 25 studies (9503 patients) were included. LVI was found in 12.2% (1156/9503) of the RP specimens. LVI was found to be correlated with higher pathological tumor stages (greater than pT3 stage) (risk ratio [RR] 1.90, 95% confidence interval [CI] 1.73–2.08, P < 0.00001), higher Gleason scores (greater than GS = 7) (RR 1.30, 95% CI 1.23–1.38, P < 0.00001), positive pathological node (pN) status (RR 5.67, 95% CI 3.14–10.24, P < 0.00001), extracapsular extension (RR 1.72, 95% CI 1.46–2.02, P < 0.00001), and seminal vesicle involvement (RR 3.36, 95% CI 2.41–4.70, P < 0.00001). The pooled hazard ratio (HR) was statistically significant for Biochemical Recurrence-Free (BCR-free) probability (HR 2.05, 95% CI 1.64–2.56; Z = 6.30, P < 0.00001). Sensitivity analysis showed that the pooled HR and 95% CI were not significantly altered by the omission of any single study. Begg's Funnel plots showed no significant publication bias (P = 0.112). In conclusion, LVI exhibited a detrimental effect on the BCR-Free probability and clinicopathological features in RP specimens, and may prove to be an independent prognostic factor of BCR.