Risk Factors For Lymph Node Metastasis Research Articles

Establishment of Decision Rules and Risk Assessment Model for Preoperative Prediction of Lymph Node Metastasis in Gastric Cancer.

Background: Preoperative accurate prediction of lymph node status is especially important for the formulation of treatment plans for patients with gastric cancer (GC). The purpose of this study was to establish decision rules and a risk assessment model for lymph node metastasis (LNM) in GC using preoperative indicators.Methods: The clinical data of 554 patients who underwent gastrectomy with D2 lymphadenectomy were collected. A 1:1 propensity score matching (PSM) system was used, and the clinical data of the matched 466 patients were further analyzed. The important risk factors for LNM were extracted by the random forest algorithm, and decision rules and nomogram models for LNM were constructed with a classification tree and the “rms” package of R software, respectively.Results: Tumor size (OR: 2.058; P = 0.000), computed tomography (CT) findings (OR: 1.969; P = 0.001), grade (OR: 0.479; P = 0.000), hemoglobin (Hb) (OR: 1.211; P = 0.005), CEA (OR: 1.111; P = 0.017), and CA19-9 (OR: 1.040; P = 0.033) were independent risk factors for LNM in GC. Tumor size did rank first in the ranking of important factors for LNM in GC and was the first-level segmentation of the two initial branches of the classification tree. The accuracy, sensitivity, specificity, and positive predictive value of the decision rules in diagnosing preoperative LNM in GC were 75.6, 85.7, 73.9, 73.5, and 79.3%, respectively. The accuracy, sensitivity, and specificity of the risk assessment model in predicting preoperative LNM in GC were 79.3, 80.3, and 79.4%, respectively.Conclusion: Tumor size was the most important factor for evaluating LNM in GC. This decision rules and nomogram model constructed to take into account tumor size, CT findings, grade, hemoglobin, CEA, and CA19-9 effectively predicted the incidence of LNM in preoperative GC.

Establishment and evaluation of a risk-scoring system for lymph node metastasis in early-stage endometrial carcinoma: Achieving preoperative risk stratification.

To establish a risk-scoring system for lymph node metastasis (LNM) of early-stage endometrial carcinoma (EC), and to stratify the preoperative risk of LNM. We retrospectively analyzed the clinical data of 507 patients diagnosed with the early-stage EC (i.e., confined to the uterine corpus). We determined the risk factors for LNM by logistic regression analysis; then constructed a simple logistic scoring system, and an additive scoring system based on the regression coefficient (β), and odds ratio, of each variable, respectively. The overall rate of LNM was 9.1% (46/507). Multivariate analysis showed that preoperative serum cancer antigen 125 (CA125) ≥35 U/mL, histopathology of grade 3 and/or type II, depth of myometrial invasion ≥1/2 and positive immunostaining for Ki-67 ≥50%, were independent risk factors for LNM (P < 0.05). The simple logistic and additive scoring systems exhibited good predictive ability (area under the curve [AUC] >0.8). Based on the additive scoring system, the risk of LNM in patients with early-stage EC was classified into three groups: a low-risk group (total score: <5), an intermediate-risk group (total score: 5-10) and a high-risk group (total score: >10). The incidence of LNM differed significantly across these three groups (P < 0.05). The risk-scoring system constructed in this study can effectively predict the risk of LNM in patients with early-stage EC, achieve preoperative risk stratification and provide a reference guideline for the use of lymphadenectomy.

Risk Factors for Lymph Node Metastasis and Survival Outcomes in Colorectal Neuroendocrine Tumors.

ObjectiveThe aim of our study was to analyze the factors affecting lymph node metastasis (LNM) and the prognosis of colorectal neuroendocrine tumors (NETs).Patients and MethodsA retrospective analysis was conducted to collect the clinical data of 135 patients with colorectal NETs from January 2000 to December 2018, including clinical manifestations, pathological results, treatment methods, etc. Follow-up was regularly performed to observe the recurrence and metastasis of tumors and to identify the clinical and pathological features of colorectal NETs, risk factors for LNM and survival outcomes.ResultsAmong 135 patients, there were 57 (42.2) patients with LNM, and the independent risk factors for LNM in the multivariable analyses were tumor diameter ≥2 cm (P= 0.040) and tumor grade G3 (P=0.001). Patients were followed up for 1 to 190 months, and of the 133 patients who were successfully followed up, the 5-year OS was 71.7%, and the 5-year PFS was 69.0%. The multivariate analysis for survival outcomes showed that age ≥65 years (P=0.002/<0.001) and lymph node metastasis (P=0.018/0.025) were independent risk factors affecting 5-year PFS and OS in colorectal neuroendocrine tumors. Tumors in the colon (P=0.022), moderately positive (++) CgA (P=0.010) and strongly positive (+++) CgA (P=0.007) were independent risk factors for poor 5-year PFS in patients with colorectal NETs.ConclusionRectal NETs have a better prognosis than colonic neuroendocrine tumors. Tumor diameter and tumor grade are independent risk factors for LNM in colorectal neuroendocrine tumors. Age, tumor location, lymph node status and a positive level of the neuroendocrine marker CgA are independent risk factors that affect the prognosis of colorectal NETs.

Systematic Review and Metaanalysis of Lymph Node Metastases of Resected Pancreatic Neuroendocrine Tumors.

The optimal surgical strategy for pancreatic neuroendocrine tumors (PNETs) is unknown. However, current guidelines recommend a watch-and-wait strategy for small nonfunctional PNETs (NF-PNETs). The aim of this study is to investigate the risk stratification and prognostic significance of lymph node metastasis (LNM) of PNETs to guide decision-making for lymphadenectomy. The MEDLINE and Web of Science databases were systematically searched for studies reporting either risk factors of LNM in resected PNETs or survival of patients with LNM. The weighted average incidence of LNM was calculated according to tumor characteristics. Random-effects metaanalyses were performed, and pooled hazard ratios (HR) and their 95% confidence intervals (CI) were calculated to determine the impact of LNM on overall survival (OS). In subgroup analyses, NF-PNETs were assessed. From a total of 5883 articles, 98 retrospective studies with 13,374 patients undergoing resection for PNET were included. In all PNETs, the weighted median rates of LNM were 11.5% for small (≤ 2cm) PNETs and 15.8% for G1 PNETs. In NF-PNETs, the rates were 11.2% for small PNETs and 10.3% for G1 PNETs. LNM of all PNETs (HR 3.87, 95% CI 3.00-4.99, P < 0.001) and NF-PNETs (HR 4.98, 95% CI 2.81-8.83, P < 0.001) was associated with worse OS. LNM is potentially prevalent even in small and well-differentiated PNETs and is associated with worse prognosis. A watch-and-wait strategy for small NF-PNETs should be reappraised, and oncologic resection with lymphadenectomy can be considered. Prospective and controlled studies are needed in the future.

Clinicopathologic Characteristics and Risk Factors of Lymph Node Metastasis in Patients with Early Gastric Cancer in the Wannan Region.

BackgroundTo date, there has been no agreement on the risk factors of lymph node metastasis (LNM) for early gastric cancer (EGC). The objective of this article was to investigate the risk factors of LNM in EGC in the Wannan region of Anhui Province and then to develop a regional practice guideline to manage EGC cases in this population.Material/MethodsThis retrospective analysis was performed from July 1, 2014 to June 30, 2017, at First Affiliated Hospital of Wannan Medical College. We explored the independent risk factors of LNM by using univariate analysis and multivariate analysis.ResultsIn total, 381 patients were selected for analysis. The LNM rate of EGC was 13.65% (52 out of 381 patients). Submucosal invasion, ulcer presence, undifferentiated tumor, vascular tumor thrombus, and neural invasion were significantly associated with LNM in EGC patients. Multivariate analysis suggested that depth of invasion (odds ratio [OR], 3.50; 95% confidence interval [CI], 1.45–8.42; P=0.005), vascular tumor thrombus (OR, 6.33; 95%CI, 2.31–17.31; P=0.001), and neural invasion (OR, 10.95; 95%CI, 3.29–36.41; P=0.001) were independent predictors of LNM in EGC patientsConclusionsIn the Wannan region of Anhui Province in China, depth of invasion, vascular tumor thrombus, and neural invasion were independent predictive risk factors for LNM in EGC patients. EGC patients with these risk factors for LNM are more likely to have LNM, and radical surgical procedure was more likely to be considered. With respective to EGC with submucosal invasion, the flat type pattern had a lower risk of LNM.

Angiopoietin-1 is associated with a decreased risk of lymph node metastasis in early stage cervical cancer.

Lymph node metastasis (LNM) is an important determinant of prognosis in patients with cervical cancer. Members of the angiopoietin family have been demonstrated to regulate tumor-associated angiogenesis and lymphangiogenesis. This study aimed to investigate the expression levels of angiopoietin-1 (ANG1) and angiopoietin-2 (ANG2) in clinically early stage of cervical cancer along with their correlations with LNM. In total, 124 human cervical cancer cases classified into stage IA-IIB in accordance with the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging criteria were included. ANG1 and ANG2 expression levels in the tumor sections were assessed by immunohistochemistry (IHC). Univariate and multivariate logistic regression models, including age at diagnosis, FIGO stage, tumor size, pathological type, histological grading, depth of stromal invasion, lymph-vascular space invasion (LVSI) and the expression status of ANG1 and ANG2, were used to evaluate the odds ratios (ORs) for LNM. ANG1 and ANG2 were positively expressed in 75 (60.5%) and 89 (71.8%) cervical cancers respectively, with predominant staining in the cytoplasm. ANG1 expression was significantly decreased in tumors with LNM, while no correlation was observed between ANG2 expression and LNM. More importantly, the multivariate logistic regression analysis demonstrated that high ANG1 expression was an independent protective factor of LNM (OR 0.107, 95% confidential interval [CI] 0.020~0.567), while LVSI was an independent risk factor of LNM (OR 34.313, 95% CI 5.914~199.092). ANG1 is associated with a significantly decreased risk of LNM in early stage cervical cancer. The predictive value and role of ANG1 in LNM needs to be further investigated in future studies.

A novel risk-scoring system for predicting lymph node metastasis of rectal neuroendocrine tumors.

AimAlthough rectal neuroendocrine tumors (NETs) are considered to be rare low‐grade malignancies when lymph node metastasis (LNM) is present, their degree of malignancy is comparable to that of colorectal cancer (CRC). However, it remains unclear as to which patients require radical lymph node dissection. The aim of this study was to elucidate the risk factors for LNM and develop a risk‐scoring system for LNM to help determine appropriate therapeutic approaches.MethodsIn this study, we examined 103 patients with rectal NETs who underwent local resection (n = 55) or radical resection with LN dissection (n = 48). We evaluated each pathological feature, including the depth of submucosal invasion (SM depth) and tumor budding grade.ResultsAccording to our univariate analyses and previous reports, the significant five risk factors for LNM were weighted with point values: 2 points for tumor size ≥ 15 mm and muscularis invasion, and 1 point each for SM depth ≥ 2000 µm, positive lymphovascular invasion, budding grade 3, and vertical margin. The area under the receiver operating curve for the scoring system was 0.899 (95% CI: 0.843‐0.955). When a score of 2 was used as the cut‐off value, the sensitivity and specificity for the prediction of LNM were 100% and 72.1%, respectively.ConclusionsThe risk‐scoring system for LNM of rectal NETs showed high diagnostic performance. Using this risk‐scoring system, it is possible to predict the risk of LNM and thereby potentially avoid unnecessary surgery. Further prospective external validation studies should be performed. The study was registered in the Japanese Clinical Trials Registry as UMIN000036658.

Tu1488 PREVALENCE AND RISK FACTORS FOR LYMPH NODE METASTASIS AFTER NONCURATIVE ENDOSCOPIC RESECTION FOR EARLY ASTRIC CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS

Additional surgery for patients who do not meet the curability criteria after endoscopic resection (ER) for early gastric cancer (EGC) may be excessive due to the relatively low rate of lymph node metastasis (LNM) in such patients. However, the prevalence and risk factors for LNM after noncurative ER have not been consistent across studies. Hence, we aimed to identify the prevalence and risk factors of LNM in patients with noncurative ER for EGC. We performed a systematic review of electronic databases through August 10, 2018 to identify cohort studies with patients who underwent additional surgery after noncurative ER for EGC. This is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. Missing data were collected from corresponding authors of the included studies. The primary outcome was a pooled prevalence rate of LNM at additional surgery in patients diagnosed as noncurative ER for EGC. The secondary outcome was to reveal pathological risk factors for LNM, including tumor size, deep submucosal invasion, differentiation, lymphatic invasion, vascular invasion, lymphovascular invasion, ulceration (scar), and positive vertical margin. The prevalence of LNM in such patients was extracted for all studies. Odds ratios were combined using random effects meta-analyses to assess the risk of LNM, when possible. We identified 24 studies comprising 3,877 patients with 311 having LNM (pooled prevalence, 8.1%, 95% confidence interval, 7.3%–9.0%). Summary results concerning the prevalence of LNM after noncurative ER for EGC in the subgroup analyses are present in Table 1. The risk of LNM was significantly increased in lymphatic invasion (odds ratio [95% confidence interval] =4.22 [2.88–6.19]), lymphovascular invasion (4.17 [2.90–5.99]), vascular invasion (2.38 [1.65–3.44]), positive vertical margin (2.16 [1.59–2.93]), deep submucosal invasion (2.14 [1.48–3.09]), and tumor size >30 mm (1.77 [1.31–2.40]) (Table 2). In contrast, there was no significant association between undifferentiated-type or ulceration (scar) and LNM. There was no heterogeneity across the studies in each analysis (I2 =0% in all analysis). Funnel plot asymmetry was not present among the studies reporting the prevalence and risk of LNM other than vascular invasion (Egger’s test, P =0.003). When studies were restricted to the studies that evaluated the adjusted odds ratio, the risk of vascular invasion for LNM did not reach statistical significance. In this meta-analysis including the largest cases to date, several pathological factors, most notably lymphatic invasion and lymphovascular invasion, were associated with LNM in patients with noncurative ER for EGC. Lymphatic and vascular invasion should be assessed separately instead of lymphovascular invasion. (PROSPERO CRD42018109996)View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Predictors of nodal metastasis in sinonasal squamous cell carcinoma: A national cancer database analysis

ObjectiveWe present the largest population based study of sinonasal squamous cell carcinoma (SCC) to identify risk factors for presentation with nodal metastasis.MethodsThe National Cancer Database (NCDB) was used for this study. Location codes corresponding to the nasal cavity and paranasal sinuses and histology codes representing SCC malignancy were queried. Logistic regression analysis was performed to identify factors associated with presentation with nodal metastasis.Results6448 cases met inclusion criteria. Nodal metastasis at presentation was seen in 13.2% of patients, with the sinus subsite (19.3%) being a significant risk factor for nodal metastasis at presentation when compared to the nasal cavity (7.9%). Logistic regression analysis showed black, uninsured and Medicaid patients were more likely than white and privately insured patients, respectively, to present with nodal metastasis.ConclusionsIn sinonasal SCC, the sinus subsite has a significantly increased risk of nodal metastasis compared to the nasal cavity. Black race, uninsured and Medicaid patients are more likely to have nodal metastasis at presentation.

Sa1240 PREDICTORS FOR LYMPH NODE METASTASIS OF T1B ESOPHAGEAL CANCER AND SURVIVAL FOLLOWING ENDOSCOPIC THERAPY WITH/WITHOUT ADJUVANT THERAPY AND SURGERY: AN ANALYSIS OF SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS (SEER) DATABASE

Endoscopic therapy (ET) has become a treatment of choice for high grade dysplasia and intramucosal (T1a) esophageal cancer (EC). For T1b EC (tumor invading submucosa), esophagectomy remains the mainstay treatment because previous studies, using single-centered data, reported higher risk of lymph node metastasis (LNM). The use of ET in low risk T1b EC and ET followed by adjuvant chemotherapy ± radiation (CRT) for patients who decline or are unfit for surgery have been reported. However, outcomes data have been limited to a few small studies from tertiary centers. 1) to determine the prevalence and risk factors of LNM of T1b EC using a large national cancer database and 2) evaluate the survival outcomes of T1bN0M0 EC after ET alone, ET+CRT compared to radical surgery. We used the SEER 18 database to identify patients with T1b histologically confirmed EC diagnosed between 1998-2016. Prevalence of LNM at initial diagnosis and its risk factors were analyzed. Cancer-specific survival (CSS) and overall survival (OS) were calculated using Kaplan-Meier’s (KM) estimate. The multivariate analysis was performed with the Cox-regression method after controlling for other relevant covariates. A total of 1374 patients with T1b EC were identified (mean age: 65; 82% men; 89% white; 77% adenocarcinoma[AC]; 22% squamous cell cancer[SCC]) (Table 1).Overall, 283 patients(20.6%) had LNM at the time of diagnosis with prevalence of 20% in AC and 22.8% in SCC(p=0.279). In multivariate analysis, age≦65, diagnosis in 2010-2016(vs older years), tumor size ≧ 2 cm, and poorly differentiation were associated with LNM. Survival of patients with T1b with LNM was significantly lower than those with LNM(-) [3-yr OS: 63.7% and 47.8%, p<0.001; 3-yr CSS: 72.1% and 54.1%, p<0.001]. Subgroup of patients with T1bN0M0 EC who received ET only(n=96), ET+CRT(n=22) and surgery(n=788) were further analyzed. The median follow-up time was 39 months(IQR 14-89). 3-yr OS and CSS were: 65%/81% in ET, 30%/88% in ET+CRT and 73%/79% in surgery. KM curves are shown in Figure 1. In a multivariate proportional hazards model; adjusted for age, gender, race, histologic type, year of diagnosis, site of cancer, SEER region, ET alone and surgery resulted in statistically equivalent in overall mortality[Hazard ratio(HR) 0.93, 95%CI 0.68-1.43, p=0.93] and esophageal cancer mortality[HR 1.47, 95%CI 0.86-2.51, p=0.16]. ET+CRT, as compared to ET alone, was associated with increased overall mortality[HR 2.17, 95%CI 1.03-4.57, p=0.04], with no significant difference in esophageal cancer survival. In this population-based study, the prevalence of LNM in T1b EC is 20%. In patients with T1bN0M0, overall and cancer specific survival of those treated with ET appears to be similar to those treated with surgery. Addition of CRT following ET negatively impacts survival outcomes.Figure 1Kaplan–Meier graphs showing the survival in patients with T1bN0M0 esophageal cancer treated with endoscopic treatment +/- chemoradiation or surgeryView Large Image Figure ViewerDownload Hi-res image Download (PPT)

Tu1491 THE RISK FOR LYMPH NODE METASTASIS IN EPSTEIN-BARR VIRUS-ASSOCIATED GASTRIC CARCINOMA WITH SUBMUCOSAL INVASION IS QUITE LOW: A RETROSPECTIVE MULTICENTER STUDY

Epstein-Barr Virus (EBV)-associated gastric cancer (EBVGC) accounts for approximately 10% of gastric cancers. EBVGC is classified into one of the four molecular subtypes proposed by The Cancer Genome Atlas Research Network (Nature, 2014), and there have been reports which imply the relatively low risk of lymph node metastasis (LNM) in EBVGC with submucosal invasion (pT1b-EBVGC). However, a large cohort study is still lacking. The present study aims to investigate the risk of LNM in pT1b-EBVGC through a multicenter study. This is a retrospective multicenter study. 5 institutes, which have pathologists specializing in the diagnosis of EBVGC, participated in this study. We reviewed medical records and extracted all pT1b-EBVGC cases diagnosed between 2001 and 2016. Lesion characteristics, patients background factors and clinical outcomes were obtained. The diagnostic criteria for EBVGC were as follows: 1) gastric adenocarcinoma with lymphoid stroma; and 2) a positive result of in-situ hybridization for EBV encoded small RNA (EBER-ISH). For surgery cases, LNM was investigated based on the histopathological evaluation of resected LNs. For endoscopic resection (ER) cases, no LNM was defined as the case where computed tomography scan did not identify any LNM during follow-up ≥ 3 years. A total of 190 pT1b-EBVGC cases were enrolled. The number of ER and surgery cases were 30 and 160, respectively. Additional surgery was performed in 25 of 30 ER cases. LNM was identified in 9 cases (4.7%), which were all surgery cases. Table 1 shows the association between LNM and various factors according to univariate analysis. Multivariate logistic regression analysis revealed that lymphatic invasion (Ly) and deep submucosal invasion (≥ 2000 μm) are the significant risk factors for LNM (Table 2); neither lesion size nor venous invasion (V) was significantly correlated to LNM. The present study revealed that the risk for LNM in pT1b-EBVGC without Ly was 1.8% (3/163, 95%CI; 0.6-5.3%). Moreover, as for pT1b-EBVGC without Ly and submucosal invasion depth < 2000 μm, the rate of LNM was 0% (0/101, 95%CI; 0-2.9%). The present study demonstrated the relatively low risk for LNM in pT1b-EBVGC, considering that the LNM risk of all pT1b-GC is approximately 20%. This result implies that pT1b-EBVGC is a good candidate for ER or local resection.Table 2The association between LNM and clinical factors (multivariate analysis)View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Risk factors and predictors of lymph nodes metastasis and distant metastasis in newly diagnosed T1 colorectal cancer.

BackgroundLymph nodes metastasis (LNM) and distant metastasis (DM) are important prognostic factors in colorectal cancer (CRC) and determine the following treatment approaches. We aimed to find clinicopathological factors associated with LNM and DM, and analyze the prognosis of CRC patients with T1 stage.MethodsA total of 17 516 eligible patients with T1 CRC were retrospectively enrolled in the study based on the Surveillance, Epidemiology, and End Results (SEER) database during 2004‐2016. Logistic regression analysis was performed to identify risk factors for LNM and DM. Unadjusted and adjusted Cox proportional hazard models were used to identify prognostic factors for overall survival. We performed the cumulative incidence function (CIF) to further determine the prognostic role of LNM and DM in colorectal cancer‐specific death (CCSD). LNM, DM, and OS nomogram were constructed based on these models and evaluated by the C‐index and calibration plots for discrimination and accuracy, respectively. The clinical utility of the nomograms was measured by decision curve analyses (DCAs) and subgroups with different risk scores.ResultsTumor grade, mucinous adenocarcinoma, and age accounted for the first three largest proportion among the LNM nomogram scores (all, P < .001), whereas N stage, carcinoembryonic antigen (CEA), and tumor size occupied the largest percentage in DM nomogram (all, P < .001). OS nomogram was formulated to visually to predict 3‐, 5‐, and 10‐ year overall survivals for patients with T1 CRC. The calibration curves showed an effectively predictive accuracy of prediction nomograms, of which the C‐index were 0.666, 0.874, and 0.760 for good discrimination, respectively. DCAs and risk subgroups revealed the clinical effectiveness of these nomograms.ConclusionsNovel population‐based nomograms for T1 CRC patients could objectively and accurately predict the risk of LNM and DM, as well as OS for different stages. These predictive tools may help clinicians to make individual clinical decisions, before clinical management.

Identification of risk factors associated with pelvic lymph node metastasis in patients with stage IB1 cervical cancer.

e18005 Background: Evaluation the distribution of nodal metastases in the stage IB1 cervical cancer and the risk factors associated with pelvic lymph node metastasis (LNM) at each anatomic location. Methods: 728 patients with stage IB1 cervical cancer who underwent radical hysterectomies and systemic pelvic lymphadenectomies from January 2008 to December 2017 were retrospectively studied. All removed pelvic lymph nodes were pathologically examined, and the risk factors for LNM at the obturator, internal iliac, external iliac, and common iliac regions were evaluated by univariate and multivariate logistic regression analyses. Results: 20,134 lymph nodes were analysed with the average number of 27.80 (± SD 9.43) lymph nodes per patient. Nodal metastases were present in 266 (14.6%) patients. The obturator was the most common site for nodal metastasis (42.5%) followed by the internal iliac nodes (20.3%) and the external iliac nodes (19.9%), while the common iliac (9.8%) and parametrial (7.5%) nodes were the least likely to be involved. Tumor size more than 2 cm, histologically proven lymphovascular space involvement (LVSI) and parametrial invasion correlated independently significantly with the higher risk of the lymphatic metastasis. Obesity (BMI≥25) was independently significantly negatively correlated with the risk of lymphatic metastases. All the positive common iliac nodes were found in patients with tumors greater than 2 cm. The multivariate analysis showed that tumor size greater than 3 cm was associated with a 16.6-fold increase in the risk for common iliac LNM. Interestingly, tumor size was not an independent risk factor for pelvic LNM in the lower regions, i.e., the obturator, internal iliac and external iliac areas, where LVSI was the most significant predictor for LNM. In addition, parametrial invasion was related to external and internal iliac LNM; deep stromal invasion and age less than 50 years were associated with obturator LNM. Conclusions: The incidence of lymph node metastasis in patients with stage IB1 cervical cancer is low but prognostically relevant. The data offer the opportunity for tailored individual treatment in selected patients with small tumors and obesity.

Risk of lymph node metastasis and prognostic outcome in early gastric cancer patients with mixed histologic type

BackgroundWhether early gastric cancer with mixed histologic type should be considered for endoscopic submucosal dissection (ESD) remains controversial. The objective of this study was to evaluate the risk of lymph node metastasis (LNM) and prognostic significance for early gastric cancer with mixed histologic type. MethodsWe retrospectively reviewed clinicopathologic and survival data of 302 patients who underwent surgical resection for early gastric cancer. Based on the histologic components, all patients were classified as pure differentiated type, pure undifferentiated type and mixed histologic type. The prognostic differences between different types were compared and predictive factors for LNM were evaluated. ResultsHistopathologically, the proportion of mixed histologic type was 12.3% in early gastric cancer. In terms of LNM, mixed histologic type had a more frequent incidence than pure differentiated type (32.4% vs 11.1%, P < 0.01). However, there was no significant difference between mixed type and pure undifferentiated type for LNM (32.4% vs 21.1%, P = 0.139). Multivariate analysis revealed that tumor size >2 cm (odds ratio [OR]: 2.153, 95% confidence interval [CI]: 1.113-4.164, P < 0.05), submucosal invasion (OR: 3.881, 95%CI: 1.832-8.222, P < 0.001), lymphovascular invasion (OR: 8.797, 95% CI: 2.643-29.277, P < 0.001), undifferentiated type (OR: 3.146, 95% CI: 1.352-7.320, P < 0.01), and mixed histologic type (OR: 3.635, 95% CI: 1.272-10.390, P < 0.05) were independent risk factors for LNM in early gastric cancer patients. However, mixed histologic type did not affect the survival outcome of these patients (hazard ratio: 0.629, 95% CI: 0.074-5.311, P > 0.05). ConclusionMixed histologic type was an independent risk factor for lymph node metastasis in early gastric cancer patients. The decisions regarding endoscopic submucosal dissection for mixed histologic type should be carefully considered.

Prediction of lymph node metastasis in superficial esophageal squamous cell carcinoma in Asia: a systematic review and meta-analysis.

A less invasive endoscopic therapy has been used as a routine treatment for superficial esophageal squamous cell carcinoma (SESCC). However, lymph node metastasis (LNM) in SESCC limits the effectiveness of this medical procedure. This meta-analysis aimed to screen the risk factors for LNM in SESCC in Asia to provide evidence for clinicians in selecting treatment. We searched the main reference databases for research involving patients who received esophagectomy (open or minimally invasive) with lymph node dissection for SESCC. Meta-analysis was performed using RevMan 5.3 software. Twenty studies including 3983 patients were obtained in this analysis. The meta-analysis showed that tumor size, macroscopic type of tumor, degree of differentiation, depth of tumor invasion, and lymphovascular involvement are risk factors of LNM in SESCC, whereas age, sex, and tumor location showed no association with LNM. Five variables were screened as predictive factors for LNM in SESCC. The incidence of LNM in SESCC is not rare, and the physicians must be careful when making clinical decisions.

Clinical significance of lymphatic invasion in the esophageal region in patients with adenocarcinoma of the esophagogastric junction.

The lymphatic flow around the esophagogastric junction is complicated. Therefore, it is unclear whether lymphatic invasion in the esophageal region (eLI) and in the gastric region (gLI) in patients with adenocarcinoma of the esophagogastric junction (AEG) equally affect the incidence of lymph node metastases (LNM), and consequently, survival. We retrospectively reviewed clinicopathological data of 175 patients with AEG between January 2008 and July 2017. Risk factors for LNM and impacts of eLI or gLI on survival outcomes were investigated. eLI was identified in 34% of the patients (59/175). By multivariate analysis, eLI was associated with an increased risk of both mediastinal LNM (odds ratio [OR] = 2.98, 95% confidence interval [CI]: 1.26-7.05) and abdominal LNM (OR = 5.44, 95% CI: 1.95-15.20). The 5-year overall survival for patients with eLI (53%) was significantly worse than for patients without eLI (76%) (hazard ratio = 2.45, 95% CI: 1.37-10.01). gLI was not selected in either of these analyses. Positive eLI was strongly associated with mediastinal and abdominal LNM and worse survival in patients with AEG compared with gLI. In the histopathological examination, it seems to make sense to assess eLI and gLI separately.

Synchronous nodal metastatic risk in screening detected and endoscopically removed pT1 colorectal cancers

BackgroundThe population screening campaigns have resulted in increasing the prevalence of endoscopically resected colorectal cancers (CRCs) invading the submucosa (pT1). Synchronous nodal involvement occurs in less than 15 % of these tumors. Histologic criteria currently used for selecting patients needing resection are imprecise and most patients could have been simply followed-up. Tumor infiltrating lymphocytes (TILs) and mismatch repair (MMR) status impact on CRC prognosis. To identify patients requiring completion surgery, the value of histologic variables, TILs and MMR status as risk factors of nodal metastasis was investigated in screening detected and endoscopically removed pT1 CRCs. MethodsIn 102 endoscopically resected pT1 CRCs, the cancer phenotype, CD3+ and CD8+ TILs, and MMR status were assessed. Univariate and multivariate analyses were used to evaluate the correlation with nodal metastasis. ResultsPositive resection margin, evidence of vascular invasion and tumor budding, wide area of submucosal invasion, and high number of CD3+ TILs were associated with nodal metastasis in univariate analyses. Vascular invasion was statistically independent in multivariate analysis. Evidence of neoplastic cells in the vessels and/or at the excision border featured 5 out of 5 metastatic tumors and 13 out of 97 non-metastatic ones. ConclusionsCompletion surgery should be recommended only in pT1 CRC with vascular invasion or with tumor cells reaching the margin. In all other cases, the treatment choice should result from a multidisciplinary discussion on the patient-centered evaluation of the risk-benefit ratio.

Clinicopathologic Features of Submucosal Papillary Gastric Cancer Differ from Those of Other Differentiated-Type Histologies.

Background/AimsPapillary gastric cancer (GC) is classified as differentiated adenocarcinoma, together with well-differentiated (WD) and moderately differentiated (MD) adenocarcinoma. This study evaluated the risk of lymph node metastasis (LNM) in submucosal (SM) invasive papillary GC compared with other differentiated early GC types.MethodsThis retrospective study involved three tertiary hospitals and enrolled 1,798 lesions with differentiated SM invasive GC treated with curative gastrectomy between March 2001 and December 2012. All pathology slides were reviewed, and clinicopathologic findings associated with LNM, including tumor size, location, gross type, ulceration, depth and width of SM invasion, and lymphovascular invasion (LVI), were analyzed.ResultsThe proportion of SM papillary GC was 2.8% (n=51). SM papillary GC was associated with larger tumor size and deeper and wider SM invasion than other differentiated GC types. LNM was significantly higher in the papillary type than in the MD and WD types. LNM was found in 27.5% of SM papillary GC patients (WD 9.0%, MD 21.2%). LVI was the only significant risk factor for LNM in SM papillary GC. The depth or width of SM invasion was not associated with LNM in papillary GC. Lower third location or elevated gross appearance was significantly associated with LVI.ConclusionsSM papillary GC had the highest LNM rate, with features different from those of other differentiated SM invasive GCs. The treatment strategy for SM papillary GC should be carefully approached, especially for lesions located in the lower third or of the elevated gross type.

Prevalence and risk factors for lymph node metastasis after noncurative endoscopic resection for early gastric cancer: a systematic review and meta-analysis.

Additional surgery for all patients with noncurative resection after endoscopic resection (ER) for early gastric cancer (EGC) may be excessive due to the relatively low rate of lymph node metastasis (LNM) in such patients. However, the prevalence and risk factors for LNM after noncurative ER have not been consistent across studies. We performed a systematic review of electronic databases through August 10, 2018 to identify cohort studies with patients who underwent additional surgery after noncurative ER for EGC. The prevalence of LNM in such patients was extracted for all studies. Odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of LNM, when possible. We identified 24 studies comprising 3877 patients with 311 having LNM (pooled prevalence, 8.1%). The risk of LNM was significantly increased in lymphatic invasion (OR [95% confidence interval] = 4.22 [2.88-6.19]), lymphovascular invasion (LVI) (4.17 [2.90-5.99]), vascular invasion (2.38 [1.65-3.44]), positive vertical margin (2.16 [1.59-2.93]), submucosal invasion depth of ≥ 500μm (2.14 [1.48-3.09]), and tumor size > 30mm (1.77 [1.31-2.40]). In contrast, there was no significant association between undifferentiated-type or ulceration (scar) and LNM. When studies were restricted to those that evaluated the adjusted OR, the risk of vascular invasion for LNM did not reach statistical significance. Several pathological factors, most notably lymphatic invasion and LVI, were associated with LNM in patients with noncurative resection after ER for EGC. Lymphatic and vascular invasion should be assessed separately instead of LVI (PROSPERO CRD42018109996).

Preoperative imaging evaluation of the absolute indication criteria for endoscopic submucosal dissection in early gastric cancer patients.

IntroductionGastric cancer (GC) is a common malignant tumor with a high mortality rate.AimTo determine the accuracy of preoperative imaging information obtained from the combined use of general gastroscopy (GS), endoscopic ultrasonography (EUS), and multi-detector computed tomography (MDCT) regarding absolute indication of endoscopic submucosal dissection (ESD) in early gastric cancer (EGC).Material and methodsThe relationship between clinical features of 794 EGC patients and lymph node metastasis (LNM) was analyzed. Multivariate logistic regression analysis was used to investigate the risk factors for LNM. Additionally, the accuracy of diagnosis of imaging techniques for ESD indications was determined by receiver operating characteristic (ROC) analysis.ResultsData showed that tumor size > 2 cm (p = 0.0071), T1b stage (p < 0.0001), undifferentiated histology (p < 0.0001), and vascular invasion (p = 0.0007) were independent risk factors for LNM in patients with EGC. Indications for ESD have a specificity of 100% for the diagnosis of patients with LNM. Additionally, the diagnostic efficacy of the use of GS, EUS, and MDCT in identifying node positive status, T1a disease, tumor size ≤ 2 cm, and ulceration was found to be moderate with area under the curve (AUC) of receiver operating characteristic curve (ROC) of 0.71, 0.64, 0.72, and 0.68, respectively. Furthermore, the use of imaging techniques for overall indication criteria for ESD had a moderate utility value with an AUC of 0.71.ConclusionsOur data suggested that, based on the combined use of GS, EUS, and MDCT, a high specificity of patient selection for ESD treatment can be achieved.