Metastatic Lymph Node Ratio Research Articles

Lymph node metastases >5 and metastatic lymph node ratio >0.30 of differentiated thyroid cancer predict response to radioactive iodine.

PurposeThe study was designed to elucidate the predictive value of the number of lymph node metastases (LNMs) and lymph node ratio (LNR) for response to therapy restratification system (RTRS).MethodsFrom December 2015 to December 2019, 1228 patients who accepted radioactive iodine (RAI) were collected in the study. After 6–8 months, response to RAI was evaluated as complete response (excellent response) and incomplete response (indeterminate, biochemical, and structural incomplete response). The study developed classification tree to determine the optimum LNMs and LNR that predicted response to RAI. Multivariate logistic regression analyses were further analyzed to find independent factors of response to RAI.ResultThe mean age of patients was 44 ± 12 and 71.09% (873/1228) were females. The best cutoff value of LNMs to affect RAI treatment response determined by classification tree was 5. Further in 388 patients with LNMs >5, the best cutoff value of LNR to affect RAI treatment response determined by classification tree was 0.30. With multivariate analysis, the study found that LNMs (>5), gender, lymph node dissection, and American Thyroid Association (ATA) risk classification were independent predictors of response to RAI for all 1228 patients; and LNR (>0.30), gender, and ATA risk classification for 388 patients with LNMs >5. The sensitivity analysis indicated that whether patients with LNM or not were included, the multivariate logistic regression model was kept stable. On subgroup analysis, no significant interactions were observed between the effect of LNMs/LNR and gender, N stage, ATA risk classification, lymph node dissection, or T stage.ConclusionsWith classification tree, the study found that LNMs and LNR could predict initial response to RAI, and their optimal cutoff values were 5 and 0.30, separately.

Predictive Impact of Metastatic Lymph Node Burden on Distant Metastasis Across Papillary Thyroid Cancer Variants.

Background: While numerous factors determine prognosis in papillary thyroid carcinoma (PTC), distant metastasis (M1) represents one of the most dire. Escalating nodal burden and aggressive histology may contribute to higher metastatic risk, but this relationship is poorly defined and challenging to anticipate. We evaluate the predictive impact of these histological features on predicting distant metastases at initial presentation. Methods: Univariate and multivariable logistic regression models of conventional and aggressive thyroid cancer variants (well-differentiated papillary thyroid carcinoma [WDPTC], diffuse sclerosing variant [DSV], tall cell variant [TCV], poorly differentiated thyroid cancer [PDTC], and anaplastic thyroid carcinoma [ATC]) identified via U.S. cancer registry data were constructed to determine associations between M1 status and quantitative nodal burden. Associations between metastatic lymph node (LN) number and M1 disease were modeled using univariate and multivariable logistic regression with interaction terms, as well as a linear continuous probability model. Results: Overall, M1 prevalence at disease presentation was 3.6% (n = 1717). When stratified by subtype, M1 prevalence varied significantly by histology (WDPTC [1.0%], DSV [2.3%], TCV [4.1%], PDTC [17.4%], ATC [38.4%] [p < 0.001]). For WDPTC, M1 prevalence escalated with metastatic LN number (0 LN+ [0.5%], 1-5 LN+ [2.0%], 6-10 LN+ [3.4%], >10 LN+ [5.5%] [p < 0.001]) and LN ratio (p < 0.001). A statistically significant interaction was observed between histology and increasing nodal burden for M1 risk. On multivariable analysis, each successive metastatic LN conferred increased M1 risk for WDPTC (odds ratio [OR] 1.06 [1.05-1.08], p < 0.001) and TCVs (OR 1.04 [1.02-1.07], p < 0.001). In contrast, other aggressive variants had a higher baseline M1 risk, but this did not vary based on the number of positive LN (DSV, OR 1.02 [0.95-1.10], p = 0.52; PDTC, OR 1.00 [0.98-1.02], p = 0.66; ATC, 1.00 [0.98-1.02], p = 0.97). Conclusions: Progressive nodal burden independently escalates the risk of distant metastasis in WDPTC and TCVs of PTC. Conversely, aggressive variants such as PDTC and ATC have substantial M1 risk at baseline and appear to be minimally affected by metastatic nodal burden. Consideration of these factors after surgery may help tailor clinical decision-making for treatment and surveillance. Further studies are warranted to calibrate the ideal management approach for these higher risk patient groups.

A prediction model incorporating the BRAFV600E protein status for determining the risk of cervical lateral lymph node metastasis in papillary thyroid cancer patients with central lymph node metastasis

Background and objectivesCervical lateral lymph node metastasis (LLNM) is a predictor of poor prognosis for papillary thyroid carcinoma (PTC) patients. However, the risk factors for LLNM remain unclear. The purpose of the study was to examine the risk factors for LLNM and construct a prediction model. MethodsWith Ethics Committee approval, a total of 1198 PTC patients were retrospectively included in our study. Univariate and multivariate analyses were performed to explore the relationship between clinicopathological characteristics and LLNM. A nomogram for predicting LLNM in PTC patients with central lymph node metastasis (CLNM) was constructed and validated. ResultsThe negative BRAFV600E protein expression was significantly correlated with positive LLNM status in PTC patients. In PTC patients with CLNM, the number of metastatic central lymph nodes (LNN) ≥ 3 and the ratio of metastatic central lymph nodes (LNR) ≥ 0.565 were found to be significantly associated with positive LLNM status. The nomogram for predicting LLNM risk in PTC patients with CLNM incorporated four risk factors: tumor size, the BRAFV600E protein expression, LNN and LNR. The prediction model showed excellent discrimination, with a C-index of 0.714. ConclusionsThe negative BRAFV600E protein expression was more likely to lead to LLNM. LNN ≥3 and LNR ≥0.565 were associated with LLNM risk in PTC patients with CLNM. Our nomogram might assist clinicians in developing individual suitable follow-up strategies for PTC patients with CLNM.

Comparison of staging systems in gastric carcinoma.

Gastric carcinoma is one of the most frequent cancers and leading causes of cancer-related death worldwide. Treatment strategies are planned according to the Tumour-Node-Metastasis (TNM) stage of the disease. However, the prognosis varies substantially even within the same stage. Prognostic nomograms were designed to overcome this diversity. In this study, staging systems and prognostic tools are compared in the context of their ability to predict patients' prognosis. Records of 391 patients operated for gastric cancer from January 2006 to September 2013 were analysed retrospectively. TNM staging system, Metastatic lymph node ratio (LNR), Kattan Prognostic Tool and Prognostic Tool of Italian Research Group on Gastric Cancer (GIRCG) were compared with the patients' survival times by their concordance indices and correlation coefficients. A total of 343 patients were included in the study. Concordance indices of the compared staging systems were 0.678 for TNM, 0.601 for GIRCG scale, 0.646 for LNR stage and 0.680 for Kattan scale. Pearson correlation coefficients were 0.404 for TNM staging, 0.314 for GIRCG scale, 0.304 for LNR stage and -0.406 for Kattan scale. Spearman correlation coefficients were 0.383, 0.311, 0.310 and -0.400 respectively. Based on these results, Kattan prognostic scale was found to be the most accurate system for predicting mortality. This was followed by TNM staging system.

P-241 Metastatic lymph node ratio as an addition to the nodal evaluation of TNM staging: A new sight for prevention of stage migrations

TNM staging is a routine grading system for gastric cancer, but the survival of gastric cancer gets better with early diagnoses and a better management with the correlation of oncology and general surgery departments. Making additions to TNM classification is important in terms of clarifying surveillance and preventing stage migrations. The purpose of this study was to evaluate the metastatic lymph node ratios in locally advanced gastric cancer patients who have undergone curative gastrectomy with D2 dissection. From January 2011 to December 2015, 341 patients were diagnosed with gastric adenocarcinoma and 226 patients underwent curative gastrectomy in our hospital. As curative gastrectomies with R0 resection and patients without distant metastasis were included in the study, palliative surgeries, R1-R2 resections, emergent surgeries and surgeries with insufficient lymph node dissection are excluded. From 226 patients, 193 patients whose tumor was not T1 and whose both preoperative and postoperative data were present were included in the study. In particular, lymph node metastasis was not present in 81 patients. The ratio between the number of metastatic lymph nodes and total number of dissected lymph nodes was analysed to evaluate their influences on the disease outcome. Patients were divided into three groups according to the ratio (NR) between metastatic lymph nodes and total nodes dissected. The number of metastatic lymph nodes ranged from 0 to 43 (mean, 6.77±4.82) and the number of dissected total lymph nodes ranged from 15 to 93 (mean 27.13±6.91). There was no significant correlation between numbers of metastatic and dissected lymph nodes (p:0.142). Survival of patients at 5 years regardless of their stage was 54.1%, with a median survival of 23.24±4.18 months. According to regional nodal status (N) of the 8th edition of the AJCC, patients with N0 (n=81), pN1 (n=24), pN2 (n=31) and pN3 (n=67) showed survival rates at 5 years of 81.7%, 75.0%, 45.2% and 40.3%, respectively (p=0.009). Patients were stratified into NR0 (ratio 0%), NR1 (ratio 1-49%) and NR2 (ratio >50%). Their survival rates at 5 years were 81.7%, 53.5% and 36.1%, respectively (p=0.008). Metastatic lymph node ratio is an independent prognostic factor in survival regardless of the number dissected in the surgical process. The metastatic lymph node ratio has a more beneficial effect on disease-free and overall survival than the number of metastatic lymph nodes. If D2 dissection is done, metastatic lymph node ratio should be added to pathological TNM staging for a better foresight and for the prevention of stage migrations.

Predictive value of ipsilateral central lymph node metastasis for contralateral central lymph node metastasis in patients with thyroid cancer: Systematic review and meta-analysis.

Careful consideration of prophylactic central compartment dissection is required to ensure that its benefits outweigh its risks in the thyroid cancer. Sixteen prospective or retrospective studies were included. True positive, true negative, false positive, and false negative were extracted from each study. The diagnostic odds ratio of ipsilateral central lymph node metastasis (iCLNM) for predicting contralateral central lymph node metastasis (cCLNM) was 12.9237 (95% confidence interval [CI], 8.1595-20.4695). The area under the summary receiver operating characteristic curve was 0.854. The sensitivity, specificity, and negative predictive value were 0.8925 [0.8232-0.9368], 0.6884 [0.6311-0.7404], and 0.9802 [0.9631-0.9894], respectively. There were strong correlations between cCLNM and clinicopathologic characteristics. Ipsilateral central lymph node pathology is useful for predicting contralateral central compartment invasion in patients with thyroid cancer. In addition, clinicopathologic characteristics were associated with cCLNM in patients with unilateral thyroid cancer.

Comparison of Two Proposed Changes to the Current Nodal Classification for Non--small Cell Lung Cancer Based on the Number and Ratio of Metastatic Lymph Nodes

The current nodal classification is unsatisfactory in distinguishing the prognostically heterogeneous N1 or N2 non-small cell lung cancer (NSCLC). Is the combination of the current N category and the number of metastatic lymph nodes (N-#number) or the combination of the current N category and the ratio of the number of positive to resected lymph nodes (N-#ratio) better than the current N category alone? We identified 2,162 patients with N1 or N2 NSCLC from the Surveillance, Epidemiology, and End Results database (2004-2016). We classified these patients into three N-#number categories (N-#number-1, N-#number-2a, N-#number-2b) and three N-#ratio categories (N-#ratio-1, N-#ratio-2a, N-#ratio-2b). Lung cancer-specific survival (LCSS) were compared using the Kaplan-Meier method. The prognostic significance of the new nodal classifications was validated across each tumor size category (≤3cm, 3-5cm, 5-7cm, >7cm). Cox proportional hazards regression was used to evaluate the association between each nodal classification and LCSS. The survival curves showed clear differences between each pair of N-#number and N-#ratio categories. A significant tendency toward the deterioration of LCSS from N-#number-1 to N-#number-2b was observed in all tumor size categories. However, the differences between each pair of N-#ratio categories were significant only in tumors from 3 to 7cm. Although all three nodal classifications were independent prognostic indicators, the N-#number classification provided more accurate prognostic stratifications compared with the N-#ratio classification and the current nodal classification. The N-#number classification followed by the N-#ratio classification might be better prognostic determinants than the current nodal classification in prognostically heterogeneous N1 or N2 NSCLC.

A Stepwise Approach Using Metastatic Lymph Node Ratio-Combined Thyroglobulin for Customization of [18F]FDG-PET/CT Indication to Detect Persistent Disease in Patients with Papillary Thyroid Cancer.

We investigated whether an indication for [18F]FDG-PET/CT to detect FDG-avid persistent disease (PD) could be identified precisely using the extent of metastatic lymph nodes (MLNs) and serum thyroglobulin (Tg) in papillary thyroid cancer (PTC) patients. This retrospective study included 429 PTC patients who underwent surgery and radioactive iodine (RAI) therapy. [18F]FDG-PET/CT and serum Tg were evaluated just before RAI therapy. The MLN ratio (LNR) was defined as the ratio of the number of MLNs to the number of removed LNs. To derive the LNR-combined criteria, different Tg cut-off values for identifying the PET/CT-indicated group for PD detection were applied individually to subgroups initially classified based on LNR cut-off values. The cut-off values for serum Tg, the number of MLNs, and LNR for a PET/CT indication were 6.0 ng/mL, 5, and 0.51, respectively. Compared to a single parameter (serum Tg, total number of MLNs, and LNR), the LNR-combined criteria showed significantly superior diagnostic performance in detecting FDG-avid PD (p < 0.001). The diagnostic performance of PET/CT in detecting FDG-avid PD was significantly improved when the PET/CT-indicated group was identified through the LNR-combined criteria in a stepwise manner; this can contribute to a customized PET/CT indication in PTC patients.

Predictive factors for prolonged operative time of robotic thyroidectomy via bilateral axillo-breast approach: Analysis of 359 cases of differentiated thyroid cancer

ObjectiveThis study assessed the results of robotic thyroidectomy for differentiated thyroid cancer in early stage, to identify the predictive factors of operative time and complication rate. MethodsA patient cohort of 359 cases in total was involved in this retrospective study. The data of clinical characteristics and follow-up results were collected. ResultsThe cohort of patients involved was composed of 285 female patients and 74 male ones. The mean age was 34.91 ± 7.93 years old. The mean Body Mass Index (BMI) was 22.43 ± 3.47. The mean tumor size was 0.75 ± 0.56 cm, and the mean gland size was 4.68 ± 0.83 cm. Among all the specimen, the ratio of tumor invasion of gland capsule was 63/296, and the ratio of chronic thyroiditis was 110/249. 75 patients underwent total thyroidectomy + central compartment node dissection (CCND). 284 patients underwent Lobectomy + CCND. The ratio of central lymph node metastasis was 144/215 (40.1%). The mean number of lymph node dissected was 5.26 ± 4.09. The mean operative time was 96.53 ± 25.69 min. 21(5.8%) patients had hoarseness after operation. 22(29.3%) patients had hypocalcemia after total thyroidectomy. The inadvertent parathyroidectomy was found in 66(18.4%) cases. The surgical extent (unilateral/bilateral resection), BMI and gland size were found to have a significantly correlation with the operative time (p < 0.05) after multivariate analysis. ConclusionThe surgical extent, BMI and gland size are found to be independent risk factors of prolonged operative time of robotic thyroidectomy. However, these factors are not associated with a higher complication rate.

Predictive Value of Lymph Node Ratio in Patients with Pancreatic Cancer Treated with Pancreatoduodenectomy

Background: Recently, the predictive value of lymph node ratio (LNR, the ratio of metastatic lymph nodes to total examined lymph nodes) has been evaluated in patients with gastrointestinal malignancies, including pancreatic cancer. However, there is not enough evidence about the prognostic value of this factor. Objectives: We aimed at determining the value of LNR in predicting the survival of patients who have undergone the Whipple procedure. Methods: This cohort study was performed on 96 patients with pancreatic cancer undergoing the Whipple procedure during 2014 - 2019. Demographic, clinical, and pathological data of the patients were extracted from their records and patients' survival status was determined through follow-up. LNR and its effect on survival was calculated using the Cox model. Results: Of the 96 eligible patients, 51 (53.13%) were men. The mean age of the patients was 57.1 ± 14.1 (range: 19 - 82) years. The median total lymph nodes examined was 7 (range: 1 - 27), and no metastatic lymph nodes were found in 57 (59.37%) patients. The median involved lymph nodes and LNR were 2 and 0.17, respectively. Patients with LNR &gt; 0.20 had the lowest 1 and 3-year survival rates. Age (P = 0.04), surgical radial margin (P = 0.001), lymph node status (N0, N1) (P = 0.01), and LNR (P = 0.01) were the most important prognostic factors for survival. Conclusions: LNR is a valuable indicator that can be used in patients with lymph node involvement as a prognostic factor for poor survival after the Whipple procedure. The lowest 1, 3, and 5-year survival rates were seen in patients with LNR &gt; 0.20.

Machine learning-based prediction model using clinico-pathologic factors for papillary thyroid carcinoma recurrence

This study analyzed the prognostic significance of clinico-pathologic factors, including the number of metastatic lymph nodes (LNs) and lymph node ratio (LNR), in patients with papillary thyroid carcinoma (PTC), and attempted to construct a disease recurrence prediction model using machine learning techniques. We retrospectively analyzed clinico-pathologic data from 1040 patients diagnosed with PTC between 2003 and 2009. We analyzed clinico-pathologic factors related to recurrence through logistic regression analysis. Among the factors that we included, only sex and tumor size were significantly correlated with disease recurrence. Parameters such as age, sex, tumor size, tumor multiplicity, ETE, ENE, pT, pN, ipsilateral central LN metastasis, contralateral central LNs metastasis, number of metastatic LNs, and LNR were input for construction of a machine learning prediction model. The performance of five machine learning models related to recurrence prediction was compared based on accuracy. The Decision Tree model showed the best accuracy at 95%, and the lightGBM and stacking model together showed 93% accuracy. Among those factors mentioned above, LNR and contralateral LN metastasis were used as important features in all machine learning prediction models. We confirmed that all machine learning prediction models showed an accuracy of 90% or more for predicting disease recurrence in PTC. LNR and contralateral LN metastasis were used as important features for constructing a robust machine learning prediction model. In the future, we have a plan to perform large-scale multicenter clinical studies to improve the performance of our prediction models and verify their clinical effectiveness.

Prognostic value of the lymph node metastasis in patients with ampulla of Vater cancer after surgical resection

Backgrounds/AimsPatients with Ampulla of Vater cancer have a better prognosis than those with other periampullary cancers. This study aimed to determine the prognostic impact of lymph node metastasis on survival in patients with ampulla of Vater cancer after surgical resection.MethodsFrom 1991 to 2016, we retrospectively reviewed data on 104 patients with ampulla of Vater cancer who had received pancreaticoduodenectomy. Clinicopathologic factors such as lymph node ratio (LNR) and number of metastatic lymph nodes that influence survival were statistically analyzed.Results5-year survival rate after resection was 57.8%. Mean number of retrieved and metastatic lymph nodes was 13 and 0.95, respectively. In patients with lymph node metastasis, the median number of metastatic lymph nodes and was 1, and the mean LNR was 0.18. LNR >0.2 was a significant prognostic factor for overall survival. Patients with 0 or 1 metastatic lymph nodes had better survival than those with ≥2 metastatic lymph nodes. Univariate analysis revealed that histologic differentiation of tumor, lymph node metastasis, and T stage were significant prognostic factors for overall survival. Multivariate analysis revealed that tumor differentiation and number of metastatic lymph nodes were independent prognostic factors for survival.ConclusionsPancreaticoduodenectomy is an appropriate surgical procedure with acceptable long-term survival for ampulla of Vater cancer. Patients with LNR >0.2 and ≥2 positive lymph node metastasis had a poor survival. Tumor differentiation and ≥2 metastatic lymph nodes were independent significant prognostic factors for overall survival. Curative resection with lymph node dissection might control lymph node spread and enhance survival outcomes.

Factors Affecting Central Node Metastasis and Metastatic Lymph Node Ratio in Papillary Thyroid Cancer

Despite the growing evidence that metastatic lymph node ratio (MLNR) is a valuable predictor for the prognosis of papillary thyroid carcinoma, it has not yet been fully determined which factors give the ratio predictive value independent of the number of metastatic lymph nodes (MLNs). Retrospective cohort study. A comprehensive cancer center. Recurrence and clinicopathologic factors were analyzed in 2409 patients with papillary thyroid carcinoma who underwent total thyroidectomy and central node dissection. Cutoff values of MLNs ≥2 and MLNR ≥28.2% increased the recurrence risk (hazard ratio [95% CI], 9.97 [4.73-21.0] and 11.4 [5.53-23.3], respectively). Younger age, male sex, multifocality, tumor size, lymphatic and vascular invasion, and gross extrathyroidal extension positively correlated with MLN and MLNR (all P < .05). Meanwhile, lymphocytic thyroiditis negatively correlated with MLNR in female patients (P < .001), by increasing total lymph node yields as compared with papillary thyroid carcinoma without lymphocytic thyroiditis. In multivariate analysis, younger age, tumor size, and lymphatic invasion remained significant in male and female patients for MLN and MLNR; lymphocytic thyroiditis was also significantly correlated with MLNR in female patients. Our study demonstrates that MLN and MLNR are independently observed prognostic markers for tumor recurrence. However, lymphocytic thyroiditis in female patients seems to have lower MLNR by increasing total lymph node yields. In light of their association, a different cutoff for MLNR needs to be applied according to the presence or absence of underlying lymphocytic thyroiditis in the use of MLNR for predicting the recurrence. 4.

Predictors of thyroglobulin in the lymph nodes recurrence of papillary thyroid carcinoma undergoing total thyroidectomy

BackgroundTo investigate the association between postoperative lymph nodes (LNs) recurrence and distinct serum thyroglobulin (Tg) levels in patients with papillary thyroid carcinoma (PTC).MethodsThis study included PTC patients who underwent total thyroidectomy (TT) with at least central neck dissection and then re-operated due to recurrence of LNs between January 2013 and June 2018. These patients were grouped by negative or positive serum Tg levels according to the American Thyroid Association guidelines.ResultsOf the 60 included patients, 49 underwent radioactive iodine (RAI) treatment. Maximum unstimulated Tg (uTg) ≥ 0.2 ng/mL were associated with larger diameter of recurrent LNs (P = 0.027), and higher rate of metastatic LNs (P < 0.001). Serum-stimulated Tg (off-Tg) ≥ 1 ng/mL (P = 0.047) and unstimulated Tg (on-Tg) ≥ 0.2 ng/Ml (P = 0.013) were associated with larger diameter of recurrent LNs. Number of metastatic LNs ≥ 8 was an independent predictor for postoperative maximum uTg ≥ 0.2 ng/mL (OR = 8.767; 95% CI = 1.392–55.216; P = 0.021). Ratio of metastatic LNs ≥ 25% was an independent predictor for off-Tg ≥ 1 ng/mL (OR = 20.997; 95% CI = 1.649–267.384; P = 0.019).ConclusionPostoperative Tg-positive status was associated with larger size of recurrent LNs. Number of metastatic LNs ≥ 8 and ratio of metastatic LNs ≥ 25% were independent predicators for uTg-positive and off-Tg-positive status, respectively.

Impact of Lymph Node Ratio on Survival Outcome in Esophageal Squamous Cell Carcinoma After Minimally Invasive Esophagectomy.

Esophageal squamous cell cancer (ESCC) is one of the deadliest cancers in the world. Esophagectomy remains the principal treatment, and minimally invasive esophagectomy (MIE) has been performed worldwide. This study aimed to clarify whether the lymph node ratio (LNR), defined as the ratio of metastatic lymph nodes (LNs) to examined, is a prognostic factor for ESCC after MIE. This study included 327 MIEs with the patient in the prone position at two institutions from 2010 to 2015. Cox proportional hazards regression analyses using clinicopathologic characteristics and the LNR were performed for the pN1 patients and the whole cohort. In the multivariate analysis for all stages, independent prognostic factors were depth of tumor invasion (P < 0.0001), LNR (P = 0.014), operative time (P = 0.003), and pneumonia (P = 0.012). In the analysis of the pN1 subgroup, the optimum LNR cutoff level for overall survival (OS) was 9 based on receiver operation characteristic analysis. The LNR was significantly associated with depth of tumor invasion (P = 0.004) and number of metastatic LNs (P < 0.0001). The OS curve for the group with an LNR of 9 or higher was significantly worse than for the group with an LNR lower than 9 (P < 0.001). Multivariate analyses demonstrated that the LNR is a unique independent prognostic factor for the pN1 subgroup (hazard ratio, 6.811; 95% confidence interval, 2.009-23.087; P = 0.002). The LNR is an independent prognostic factor in ESCC after MIE. Especially for patients with pN1 status, the LNR is more useful than the number of metastatic LNs for predicting survival outcome.

The metastatic lymph node ratio is a better prognostic factor than the number of metastatic limph node after curative resection for gastric cancer.

Aim:Evaluate impact of lymph node ratio as prognostic factor in gastric cancer.Methods:We studied 463 patients with gastric cancer who underwent curative gastric surgery with D1 or D2 lymphadenectomy, Data were collected from May 1996 through December 2010 at Department of General Surgery of Parma University Hospital. We divided patients in two groups according to number of nodes removed.Results:The results of the present nonrandomized retrospective single center study confirm the promising role of the LNR as an indipendent prognostic factor. Overall survival between LNR categories are statistically significant different between LNR0 and LNR1.Conclusion:The ratio between the number of metastatic and analyzed lymph nodes in patients with gastric cancer can discriminate patients better than the AJCC/UICC staging system: it seems to be related to a more sensitive in the evaluation of overall survival. (www.actabiomedica.it)

Prognostic impact of para-aortic lymph node involvement in solid pancreatic ductal adenocarcinoma and malignant intraductal papillary mucinous neoplasm

Purpose: Para-aortic lymph nodes (PALN) metastases in solid pancreatic ductal adenocarcinoma (sPDAC) indicates short survival. In malignant intraductal papillary mucinous neoplasms (mIPMN) the role of PALN has not been well explored. The present study investigated the rate of metastatic PALN, N status, and lymph node (LN) ratio as prognostic factors in sPDAC and mIPMN. Method: This consecutive single-center series included patients with sPDAC and mIPMN in the pancreatic head who underwent pancreatoduodenectomy or total pancreatectomy including PALN resection during a ten-year period, 2009-2018. Median overall survival (mOS) and impact of clinicopathological factors including PALN status on survival were evaluated. Results: There were 403 patients, of which 89 had mIPMN and 314 sPDAC. PALN were metastatic in 16% of sPDAC and 17% of mIPMN (p=0.962). N0 status was present in 6% and 16%, respectively (p=0.007). A LN ratio>15% was more common in sPDAC (52%) than in mIPMN (34%) (p=0.004). The mOS was 12.7 months in the presence of PALN metastases and 22.7 months without (p<0.0001)(Figure). Age>70 years, CA19-9>200, sPDAC and N2 status were significant in multivariable analysis but PALN status and LN ratio were not independent prognostic factors. There was no difference in mOS in N2 status regardless the presence of PALN metastases. Conclusion: The frequency of PALN metastases was similar in sPDAC and mIPMN. Although mOS was shorter in PALN positive status it was not an independent risk factor and in N2 disease PALN metastases did not influence survival.

Stage III and Metastatic Lymph Node Ratio Are the only Independent Prognostic Factors in Colorectal Signet-ring Cell Carcinoma Patients.

Signet-ring cell carcinoma (SRCC) is an uncommon histological variant of colorectal cancer (CRC). Knowledge is scarce due to its rarity. Our aim was to better evaluate the clinicopathologic and prognostic features of this little-known malignancy. Thirty-nine consecutive patients with non-metastatic colorectal SRCC undergoing curative resection at University Hospital of Parma between 2000 and 2018 were examined in this retrospective analysis. Mean overall (OS) and disease-free survival (DFS) were 33.6 and 31.5 months, respectively. At univariate analysis, the lymph-related parameters (nodal status, Stage III, metastatic lymph node ratio and lymphovascular invasion) were significantly associated with shorter OS and poorer DFS. At multivariate analysis, Stage III and a metastatic lymph node ratio ≥25% were found to be the only independent prognostic factors significantly correlated with worse OS and DFS. Nodal and lymphatic status should be carefully pondered when planning the most appropriate management of patients with colorectal SRCC.

Deaths of colon neuroendocrine tumors are associated with increasing metastatic lymph nodes and lymph node ratio.

Colon neuroendocrine tumors (NETs) are uncommon. Currently, the impact of the number of metastatic lymph nodes (LNs) and lymph node ratio (LNR) on survival has been well investigated in other colon malignancies, but both remain nebulous for patients with colon NETs. Surgically resected patients with histologically proven nonmetastatic colon NETs were queried from the Surveillance, Epidemiology, and End Results database between 1988 and 2011. Patients with lymph nodes involved were investigated and categorized into four LNs-based classifications (≤4, >4-10, >10-13, and >13) or three LNR-based subgroups (≤0.51, >0.51-0.71, and >0.71) according to the threshold, determined by Harrell's C statistic. Univariate and multivariate survival analyses were performed by log-rank test and Cox stepwise regression analysis, respectively. Eight hundred fifty-one patients met the inclusion criteria. Among them, higher LNR and LNs classification are associated with a worse prognosis. The 10-year NETs-specific survival rate was 78.3% (74.2-82.6%), 61.3% (52.4-71.7%), 40.8% (20.7-80.7%) for patients in the ≤4, >4-10, and 10-13 LNs groups, respectively. When patients were classified with LNR, the observed 10-year NETs-specific survival rate was 79.9% (74.8-85.5%) for ≤0.51, 57.4% (43.8-75.2%) for >0.51-0.71, and 40.0% (31.0-51.5%) for >0.71. In stratified analysis, higher LNs and LNR groups have worse prognosis only in patients with advanced T stage (T3-T4). Regarding stage migration, the LNR-based system did not show superiority to LNs-based classification. Current TNM staging classification could be improved by considering the count of metastatic nodes and LNR instead of a simple record of lymph node status (N1 or N0) for colon NETs.

Villin is a biomarker for reverse polarity in colorectal micropapillary carcinoma.

Colorectal cancer (CRC) is a common malignant tumor of digestive system. CRC with micropapillary pattern (MPP) is an aggressive variant of colorectal adenocarcinoma. The aim of the present study was to clarify the clinicopathological significance and the prognostic role of an immunohistochemical marker, MPP, in CRC. The association between MPP and clinicopathological characteristics and prognosis in 286 cases of CRC (286/453 cases had follow-up information) were analysed. Then, 81 tissues without MPP and 90 tissues with MPP were analysed by immunohistochemistry using antibodies against villin, E-cadherin and epithelial membrane antigen (EMA). Bioinformatics was used to evaluate the expression of these three indicators in CRC. The proportion of micropapillary carcinoma in the overall tumour was ≥5%, and was observed in 90/453 cases (19.8%). The present data showed that CRC with MPP displayed higher rates of vascular and lymphatic invasion, a higher metastatic lymph node ratio and a higher pathological tumour and metastasis stage compared with CRC without MPP. The positive expression rates of EMA, E-cadherin and villin were 50.3, 93.4 and 96.5%, respectively. In 90 CRC cases with MPP, EMA inside-out pattern (I/OP) staining was observed in 26 cases (28.9%), and it was often focal and partial, while 37 cases (41.1%) had E-cadherin focal and partial staining compatible with reverse polarity. Villin I/OP staining was observed in 77 cases (85.6%), and circumferential staining predominated over partial staining. Overall, the data suggested that the presence of MPP is significantly associated with aggressive tumour behaviour and worse overall survival rate in CRC. Visualization and distinction of reverse polarity of colorectal micropapillary carcinomas is improved villin compared with EMA or E-cadherin.