Exceeding 30 ELNs is strongly recommended for pT3-4N0 patients with gastric cancer: A multicenter study of survival,recurrence, and prediction model

The argument concerning the exact minimum number of examined lymph nodes (ELNs) has continued for a long time among various regions, and no consensus has been reached for stratified pathological T stages for data to date. Data from 4607 pN0 patients with gastric cancer were analyzed. Kaplan-Meier analysis showed the similar overall survival (OS) outcomes among the 3 groups (ELNs ≤ 15, 16 ≤ ELNs ≤ 29 and ELNs ≥ 30, P = .171). However, the ELNs ≥ 30 group had a better disease-free survival (DFS) outcome compared with the others (all P < .05). An increased ELN group (ELNs ≥ 30) showed an improved OS only for pT3 patients (hazard ratio [HR] = 0.397, 95% confidence interval (CI): 0.182-0.866, P = .020), while an improved DFS for pT3 patients (HR = 0.362, 95%CI: 0.152-0.860, P = .021) and pT4 patients (HR = 0.484, 95%CI: 0.277-0.844, P = .011) in the multivariate analysis. A well discriminated and calibrated nomogram was constructed to predict the probability of the OS and DFS, with the C-index for OS and DFS prediction of 0.782 (95%CI: 0.735 to 0.829) and 0.738 (95%CI: 0.685 to 0.791), respectively. This study provides new and useful insights into the impact of ELN count on reducing stage migration and postoperative recurrence of pN0 patients with gastric cancer in 2000-2017. In conclusion, a larger number of ELNs is suggested for surgeons to prolong the prognosis of pN0 gastric cancer, especially for pT3 patients.     

Determining the optimal number of examined lymph nodes for accurate staging of pancreatic cancer: An analysis using the nodal staging score model

IntroductionThe aim of this study was to determine the optimal number of examined lymph nodes (ELNs) for accurate staging of pancreatic cancer using the nodal staging score model.Materials and methodsClinicopathological data for patients with resected pancreatic cancer were collected from SEER database (development cohort [DC]) and Fudan University Shanghai Cancer Center database (validation cohort [VC]). Multivariable models were constructed to assess how the number of ELNs was associated with stage migration and overall survival (OS). Using the β-binomial distribution, we developed a nodal staging score model from the DC and tested it with the VC.ResultsBoth cohorts exhibited significant proportional increases from node-negative to node-positive disease (DC: odds ratio [OR], 1.047; P < 0.001; VC: OR, 1.035; P < 0.001) and improved OS (DC: hazard ratio [HR], 0.982; P < 0.001; VC: HR, 0.979; P < 0.001) as ELNs increased. Nodal staging scores escalated separately as ELNs increased for different tumor (T) stages, with plateaus at 16, 21, and 23 LNs (cut-offs) for T1, T2, and T3 tumors, respectively. Multivariable analysis indicated that examining more LNs than the corresponding cut-off value was a significant survival predictor (DC: HR, 0.813; P < 0.001; VC: HR, 0.696; P = 0.028).ConclusionThe optimal number of ELNs for adequate staging of pancreatic cancer was related to T stage. We recommend examining at least 16, 21, and 23 LNs for T1, T2, and T3 tumors, respectively, as a nodal staging quality measure for both surgery and pathological analysis.     

Prognostic Significance of Lymph Node Count Removed at Sublobar Resection in Pathologic Stage IA Non–Small-cell Lung Cancer: A Population-Based Analysis

BackgroundWe sought to elucidate the associations between the examined lymph node (ELN) count and survival after sublobar resection (SLR) in pathologic stage IA non–small-cell lung cancer and assess the survival efficacy for patients undergoing SLR with an adequate ELN count compared with lobar resection (LR).Patients and MethodsThe newly released U.S. Surveillance, Epidemiology, and End Results database was queried. The association between the ELN count in SLR and survival was analyzed using Cox regression and propensity score matching analyses. The optimal cutoff for the ELN count in SLR was determined using the Chow test and “segmented” function. Survival differences between SLR with an adequate ELN count and LR were compared using the log-rank test.ResultsA total of 16,630 lobectomies, 3979 wedge resections, and 1119 segmentectomies were included in the present study. The median ELN count was 3 (interquartile range [IQR], 1-7), 1 (IQR, 0-4), and 7 (IQR, 4-12) for segmentectomy, wedge resection, and lobectomy, respectively (P < .001). The optimal cutoff for ELNs was 2.40 (IQR, 2.15-2.65) and 2.59 (IQR, 2.19-3.00) for patients undergoing wedge and segmental resection. SLR patients with ≥ 3 ELNs showed better overall survival and lung cancer-specific survival compared with those with < 3 ELNs. SLR patients with ≥ 3 ELNs had a noninferior prognosis compared with LR patients after matching of potential confounders.ConclusionsIn SLR, an adequate ELN count (≥ 3) could confer an improved prognosis compared with an inadequate ELN count (< 3). SLR patients with an adequate ELN count had noninferior survival outcomes compared with LR patients when the ELNs were well matched.     

The optimal number of examined lymph nodes for accurate staging of intrahepatic cholangiocarcinoma: A multi-institutional analysis using the nodal staging score model

BackgroundThis study aims to develop a nodal staging score (NSS) to determine the optimal number of lymph nodes (LNs) examined in intrahepatic cholangiocarcinoma (iCCA) patients.MethodsClinicopathologic data were collected from the SEER database (development cohort, n = 2782) and seven Chinese tertiary hospitals (validation cohort, n = 363). NSS was constructed based on a binomial distribution to indicate the probability of nodal disease absence. In addition, its prognostic value was examined by survival analysis and multivariable modeling on pN0 patients.ResultsA model fit was performed in node-positive patients and a subgroup analysis was performed according to clinical characteristics. Statistically significant differences were only found in the subgroups when divided by the tumor size of 3 cm. As the number of examined lymph nodes (ELNs) increased, the likelihood of missing a metastatic LN decreased. NSS escalated as ELNs increased in groups with different tumor sizes, with plateaus at 7 and 11 LNs ensuring an NSS of 90.0% for ≤3 cm and >3 cm tumors, respectively. For pN0 patients, multivariate analysis revealed that NSS was an independent prognostic factor for overall survival (OS) and recurrence-free survival (RFS).ConclusionsFor accurate staging of iCCA, the optimal number of ELNs was related to tumor size. We recommend that at least 7 and 11 LNs should be examined for tumor size ≤3 cm and >3 cm, respectively. Therefore, the NSS model could be helpful to make clinical decisions for pN0 iCCA.     

Nomogram for Predicting the Overall Survival of Patients With Breast Cancer With Pathologic Nodal Status N3

BackgroundPatients with breast cancer with pathologic N3 (pN3) lymph node status have been proven to have a poor prognosis. This study aimed to establish a nomogram to predict overall survival (OS) in patients with pN3 breast cancer.Materials and MethodsThe eligible patients from the Surveillance, Epidemiology, and End Results (SEER) database were randomly divided into training and validation cohorts. χ² tests and survival curves were performed to define the consistency between these 2 cohorts. Univariate and multivariate logistic regressions were carried out to identify the independent clinicopathologic factors of patients with pN3 breast cancer. A nomogram was developed and validated internally and externally by a calibration curve and compared with the seventh edition American Joint Committee on Cancer TNM staging classification in discrimination ability.ResultsRace, age at diagnosis, marital status, grade, T stage, N stage, breast cancer subtype, surgery, radiotherapy, and chemotherapy were independent predictive factors of OS in pN3 breast cancer. We developed a nomogram to predict 1-, 3-, and 5-year OS and further validated it in both cohorts, demonstrating better prediction capacity in OS than that of the seventh edition American Joint Committee on Cancer TNM staging classification (area under the curve in the receiver operating characteristic curve, 0.745 and 0.611 in the training cohort and 0.768 and 0.624 in the validation cohort, respectively).ConclusionWe have developed and validated the first nomogram for predicting the survival of pN3 breast cancer. This nomogram accurately and reliably predicted the OS of patients with pN3 breast cancer. However, more prognostic factors need to be further explored to improve the nomogram.     

The number of lymph nodes examined is associated with survival outcomes and nodal upstaging in patients with stage I small cell lung cancer

Objective(s)Lymph node status is vital for patients with small cell lung cancer (SCLC). We sought to evaluate the association between the number of lymph nodes examined (NLNE) and prognosis and nodal upstaging in stage I SCLC patients.MethodsWe queried the Surveillance, Epidemiology and End Results (SEER) database and our department for surgically treated patients with pathologic stage I SCLC to evaluate the correlation between NLNE and overall survival (OS). We further investigated the association between the NLNE and nodal upstaging in clinical stage I SCLC.ResultsA total of 878 patients with pathologic stage I SCLC were enrolled from the SEER database. Univariate and multivariate Cox regression analysis revealed that removing more than 6 lymph nodes was associated with significantly improved OS. We validated the prognostic impact from examining more than 6 nodes in pathologic stage I SCLC patients from our department. Logistic regression analysis found that removing more than 6 nodes increased the odds of nodal upstaging for clinical stage I SCLC.ConclusionsAdequate nodal examination leads to survival benefits and accurate nodal staging. Our analysis indicated that examining more than 6 lymph nodes could confer better OS and predict nodal upstaging for stage I SCLC patients.     

Predictors of nodal metastases in early stage HER2+ breast cancer: Deciding on treatment approach with neoadjuvant chemotherapy vs. upfront surgery

BackgroundThe purpose of this study is to evaluate preoperative predictors of nodal metastases in patients with early-stage, HER2-positive (HER2+) breast cancer.MethodsThe SEER Database was queried to identify women with a first diagnosis of stage I-II (T1-T2) HER2-positive breast cancer treated with upfront surgery in 2018. Multivariable logistic regression was used to identify clinical characteristics independently associated with nodal involvement.ResultsOverall, 3333 women with stage I-II HER2+ breast cancer met inclusion criteria and were included in the study. The median age at diagnosis was 59 years (IQR, 51–69 years). Most patients underwent breast-conserving surgery (60.9%), with a median of 3 (IQR 2–4) axillary lymph nodes removed. On final pathology, 762 (22.9%) of T1-T2 HER2+ patients were node positive; 2.7% pN0[i+], 3.7% pN1mi, 15.1% pN1, and 1.4% pN2. Women less than 40 years and those between 40 and 49 years showed the highest proportion of axillary lymph node metastasis, in 33.7% and 30.7% respectively, and declining with age (p < 0.001). Patients with triple-positive breast cancer had the highest rates of nodal involvement (24.8%), compared to 20.7% ER+/PR-/HER2+ and 19.6% of HER2-enriched patients (p = 0.006). On adjusted analysis, age, biologic subtype, tumour size, and type of surgery remained independent predictors of nodal involvement. On subgroup analysis, women under age 50 with T1c HER2-enriched or triple-positive breast cancer had a 33% and 35% incidence of nodal involvement, which declined with age.ConclusionsThe likelihood of pathologic nodal involvement in early-stage HER2+ breast cancer is contingent on age, ER/PR status, and tumour size.     

Lymph Node Ratio and pN Staging Show Different Superiority As Prognostic Predictors Depending on the Number of Lymph Nodes Dissected in Chinese Patients With Luminal A Breast Cancer

BackgroundThe lymph node ratio (LNR) classification has shown superiority to pN staging (the number of positive lymph nodes) in breast cancers, but it has not been examined according to whether sufficient lymph nodes have been dissected.MethodsAll Chinese patients with luminal A breast cancer with positive lymph nodes seen at Sun Yat-sen University Cancer Center between 1995 and 2009 were enrolled. Disease-free survival (DFS) and overall survival (OS) were the endpoints, and the patients were further classified into 2 groups according to whether ≤ 10 or > 10 lymph nodes were dissected.ResultsFor the whole group, the OS curves of the pN stages overlapped, whereas they were separated in the LNR survival curves. LNR was an independent prognostic factor for OS and DFS, whereas the pN stage was not. In the ≤ 10 lymph nodes dissected group, both OS and DFS curves were clearly separated in the pN staging but overlapped in the LNR classification. In the > 10 lymph nodes dissected group, LNR showed no overlap in the OS curves and was an independent prognostic factor of OS and DFS when compared with pN staging.ConclusionIn Chinese patients with luminal A breast cancer, LNR classification and the pN stage show different superiority as prognostic predictors according to whether > 10 or < 10 lymph nodes are dissected.     

Validation of the American Joint Committee on Cancer 8th edition staging system for the pancreatic ductal adenocarcinoma

Background & aimsThe American Joint Commission on Cancer (AJCC) 8th edition staging system for pancreatic ductal adenocarcinoma (PDA) contains several significant changes. This study aimed to validate the AJCC 8th edition staging system of PDA.MethodsWe analyzed patients with resected PDA between 2001 and 2017 using the Korean Pancreatic Cancer (K-PaC) registry. Overall survival (OS) was estimated using the Kaplan-Meier survival curves and compared via the log-rank test.ResultsIn total, 701 resected PDA patients were identified. During a median follow-up of 24.5 months, the median OS was 21.7 months. Meanwhile, the median OS of each stage according to the AJCC 8th edition was 73.5 months (stage IA), 41.9 months (stage IB), 24.2 months (stage IIA), 18.3 months (stage IIB), and 16.8 months (stage III). However, the new N-category (pN1 vs. pN2) did not subdivide prognosis, although the lymph node ratio (i.e., the ratio of the number of LN involved to the number of examined LN) did. Although pT3 and pN2 belong under stage III, pN2 has a significantly longer median OS than pT3 (16.9 months vs 11.2 months; p < 0.01).ConclusionThe AJCC 8th edition staging system appropriately stratifies the prognosis of PDA patients. However, the cutoff of the N-category is not statistically valid, and the new stage III includes a heterogeneous category (pN2 and pT4). Therefore, we propose that stage III be divided into stage IIIA (Tany N2 M0) and stage IIIB (T4 Nany M0).     

AJCC 8th edition pathologic nodal staging of resected pancreatic adenocarcinoma predicts survival regardless of treatment sequencing

ObjectiveThe primary aim was to compare overall survival (OS) between neoadjuvant therapy (NT) and surgery-first (SF) patients with pancreatic adenocarcinoma (PDAC) by nodal stage using the American Joint Commission on Cancer 8th Edition (AJCC8).BackgroundRates of nodal positivity are consistently lower following NT versus SF sequencing. It's unclear whether post-NT nodal stage (ypNx) has similar survival compared to SF (pNx) using AJCC8.MethodsThis is a single-institution retrospective cohort study with routine consideration of NT. Patients undergoing PDAC resection from 2010 to 2018 were analyzed and OS compared by nodal stage using AJCC8.ResultsOf 450 total patients, 24% were treated with SF and 76% NT. SF patients had potentially resectable disease in 97% of the cases, whereas NT patients had more advanced clinical stages at diagnosis: borderline resectable 34%, locally advanced 5%. NT patients had higher rates of node-negativity (52.4% vs 22.7%) and lower rates of pathologic N2 disease (19.1% vs 43.6%) vs. SF (p < 0.001). For each pathologic nodal stage, SF and NT groups had similar 5-year OS [pN0/ypN0 52.7% vs. 53.6%, p = 0.723], [pN1/ypN1 37.0% vs. 36.7%, p = 0.872], and [pN2/ypN2 16.6% vs. 21.0%, p = 0.508].ConclusionsAJCC8 stratifies outcomes for each post-NT nodal stage similar to SF counterparts. Despite presenting with more advanced clinical stage, NT patients had lower rates of nodal metastases yet comparable OS when stratified by final nodal status. These data provide both hope for patients with obvious radiographic nodal disease at presentation and further support for considering NT sequencing for most patients diagnosed with localized PDAC.     

Impact of Detecting Occult Pathologic Nodal Disease During Resection for Malignant Pleural Mesothelioma

BackgroundLymph node (LN) involvement is a poor prognostic factor for malignant pleural mesothelioma (MPM). However, to our knowledge, postresection outcomes of node-negative (cN0/pN0), occult pathologic nodal disease (cN0/pN+), and clinical node-positive disease (cN+) have not been compared to date.Patients and MethodsThe National Cancer Data Base was queried for newly diagnosed, resected MPM with known clinical/pathologic LN information. Three cohorts were compared: cN0/pN0, cN+, and cN0/pN+. Multivariable logistic regression examined predictors of pathologic nodal upstaging. Kaplan-Meier analysis with propensity matching assessed overall survival (OS); multivariate Cox proportional hazards modeling examined predictors thereof.ResultsOf 1369 patients, 687 (50%) had cN0/pN0, 457 (33%) cN+, and 225 (16%) cN0/pN+ disease. Median follow-up was 29 months. In patients with cN0 disease, factors associated with pathologic nodal upstaging were younger age, greater number of examined LNs, and nonsarcomatoid histology (P < .05 for all). Relative to pN0 cases, occult LN involvement (65% being pN2) was associated with 51% higher hazard of mortality on multivariate analysis (P = .005). Following propensity matching, the OS of cN0/pN+ was similar to cN+ cases (P = .281). On multivariate analysis, the number of involved LNs (continuous variable, P = .013), but not nodal tumor, node, metastasis (TNM) classification or LN ratio (P > .05 for both), was associated with OS.ConclusionDetecting occult nodal disease during resection for cN0 MPM is associated with poorer prognosis, with similar survival as cN+ cases, underscoring the importance of routine preoperative pathologic nodal assessment for potentially resectable MPM. The number of involved LNs (rather than current location-based classification) may provide more robust prognostic stratification for future TNM staging.     

Is Elective Inguinal or External Iliac Irradiation During Neoadjuvant (Chemo)radiotherapy Necessary for Locally Advanced Lower Rectal Cancer With Anal Sphincter Invasion?

PurposeTo investigate the impact of excluding irradiation of inguinal lymph nodes (ILNs) and external iliac lymph nodes (ELNs) during neoadjuvant (chemo)radiotherapy in a locally advanced lower rectal cancer (LALRC) with anal sphincter invasion.Methods and MaterialsA total of 214 LALRC patients with anal sphincter invasion according to pre-treatment magnetic resonance imaging who underwent neoadjuvant (chemo)radiotherapy followed by surgery between September 2010 and May 2019 were enrolled. ILNs and ELNs were clinically negative pre-treatment and were excluded from irradiation. Failure rates and patterns of ILNs and ELNs and survival were analyzed. Nomograms for predicting ILN and ELN failure risk were also constructed.ResultsThe median follow-up was 53.3 months. The 3-year failure rates were 3.7% for ILNs and 3.3% for ELNs. Only 1 patient developed isolated ILN failure, and no patient experienced isolated ELN failure. Multivariate analyses demonstrated that lower edge of tumors invaded or located below the dentate line (odds ratio [OR], 7.513; P = .013), high histological grade (OR, 6.892; P = .017), and perineural invasion (OR, 7.111; P = .023) were significantly related to ILN failure. Both perineural invasion (OR, 8.923; P = .011) and high histological grade (OR, 8.129; P = .011) showed a strong correlation with ELN failure. The concordance index of nomograms for predicting ILN and ELN failure risk were 0.842 and 0.880, respectively. The 3-year local recurrence free survival, disease-free survival, and overall survival were 94.6% (95% confidence interval [CI], 91.3%-97.9%), 77.7% (95% CI, 71.8%-83.6%), and 91.9% (95% CI, 87.8%-96.0%), respectively, for the whole cohort.ConclusionsExcluding ILNs and ELNs from irradiation was associated with an acceptably low failure risk for LALRC invading the anal sphincter. These findings help to refine existing guidelines for clinical target volume delineation of ILNs and ELNs during neoadjuvant (chemo)radiotherapy in rectal cancer.     

A novel lymph node staging system for gastric cancer including modified Union for cancer Control/American Joint Committee on cancer and Japanese Gastric Cancer Association criteria

BackgroundThe TNM system of the International Union for Cancer Control/American Joint Committee on Cancer (UICC/AJCC) and the Japanese Gastric Cancer Association (JGCA) systems are the most used lymph node (LN) staging systems in gastric cancer. This study estimated the influence of anatomic location-based node stations on survival and proposed a new staging method based on both the number and anatomical distribution of metastatic LNs (mLNs).MethodsStage I–III gastric cancer patients with radical gastrectomy were retrospectively evaluated. Overall survival (OS) was estimated in 1786 patients with UICC/AJCC stage N1–N3b disease and compared with estimates obtained using JGCA group 1–3 mLN staging.ResultsThe OS of UICC/AJCC stage N1–N3b patients with group 2 JGCA mLNs was significantly worse than that of patients with only group 1 mLNs. The OS of the patients with group 2 mLNs was similar to that of patients with group 1 mLNs but in the next more advanced UICC/AJCC-N stage. The OS of patients with group 3 mLNs was worse than that of patients with any UICC/AJCC-N stage and was similar to that of N3b patients with group 2 mLNs. A new pathological node (pN) staging classification was developed that advanced the N-staging of patients with group 2 mLNs. It was a better indicator of prognosis than the eighth UICC/AJCC-N and the thirteenth JGCA group staging systems.ConclusionsA simple, accurate pN staging system including both the number and location of mLNs had improved homogeneity, discriminatory ability, and gradient monotonicity.     

Number of negative lymph nodes should be considered for incorporation into staging for breast cancer

This study aimed to investigate the prognostic value of the number of involved lymph nodes (pN), number of removed lymph nodes (RLNs), lymph node ratio (LNR), number of negative lymph nodes (NLNs), and log odds of positive lymph nodes (LODDS) in breast cancer patients. The records of 2,515 breast cancer patients who received a mastectomy or breast-conserving surgery were retrospectively reviewed. The log-rank test was used to compare survival curves, and Cox regression analysis was performed to identify prognostic factors. The median follow-up time was 64.2 months, and the 8-year disease-free survival (DFS) and overall survival (OS) were 74.6% and 82.3%, respectively. Univariate analysis showed that pN stage, LNR, number of RLNs, and number of NLNs were significant prognostic factors for DFS and OS (all, P < 0.05). LODDS was a significant prognostic factor for OS (P = 0.021). Multivariate analysis indicated that pN stage and the number of NLNs were independent prognostic factors for DFS and OS. A higher number of NLNs was associated with higher DFS and OS, and a higher number of involved lymph nodes were associated with poorer DFS and OS. Patients with a NLNs count > 9 had better survival (P < 0.001). Subgroup analysis showed that the NLNs count had a prognostic value in patients with different pT stages and different lymph node status (log-rank P < 0.05). For breast cancer, pN stage and NLNs count have a better prognostic value compared to the RLNs count, LNR, and LODDS. Number of negative lymph nodes should be considered for incorporation into staging for breast cancer.     

Vasculogenic mimicry contributes to lymph node metastasis of laryngeal squamous cell carcinoma

Background

Survival of laryngeal squamous cell carcinoma (LSCC) patients has remained unchanged over recent years due to its uncontrolled recurrence and local lymph node metastasis. Vasculogenic mimicry (VM) is an alternative type of blood supplement related to more aggressive tumor biology and increased tumor-related mortality. This study aimed to investigate the unique role of VM in the progression of LSCC.

Methods

We reviewed clinical pathological data of 203 cases of LSCC both prospectively and retrospectively. VM and endothelium-dependent vessel (EDV) were detected by immunohistochemistry and double staining to compare their different clinical pathological significance in LSCC. Survival analyses were performed to assess their prognostic significance as well.

Results

Both VM and EDV existed in LSCC type of blood supply. VM is related to pTNM stage, lymph node metastasis and pathology grade. In contrust, EDV related to location, pTNM stage, T stage and distant metastasis. Univariate analysis showed VM, pTNM stage, T classification, nodal status, histopathological grade, tumor size, and radiotherapy to be related to overall survival (OS). While, VM, location, tumor size and radiotherapy were found to relate to disease free survival (DFS). Multivariate analysis indicated that VM, but not EDV, was an adverse predictor for both OS and DFS.

Conclusions

VM existed in LSCC. It contributed to the progression of LSCC by promoting lymph node metastasis. It is an independent predictors of a poor prognosis of LSCC.     

Node positivity in T1b gallbladder cancer: A high volume centre experience

IntroductionIdentification of early stage gallbladder cancer (GBC) is difficult with simple cholecystectomy being considered curative for T1a GBC but T1b requires radical cholecystectomy due to chances of lymph node metastasis. However there is no consensus regarding the optimal treatment strategy for T1b disease.MethodologyA retrospective review of a prospectively maintained database of GBC patients operated at our institute from March 2010 to March 2021 was conducted. Only patients with proven gallbladder adenocarcinoma on final histopathology report were included.ResultsA total of 1245 patients of suspected GBC who underwent surgery during this period with 76 patients of T1b stage were analysed. We divided the group into a node positive cohort (n = 16, 9 received neoadjuvant treatment due to uptake in periportal nodes and 7 patients were pN1) and a node negative cohort (n = 60). The median nodal harvest was 8 nodes (2–24 nodes). Considering the radiological and pathological parameters, the rate of lymph node positivity was 21% (16/76). The overall major morbidity was 5.2% and there was no mortality. After a median follow up of 47.5 months, 3-year OS and DFS of the node negative and positive cohort was 96.7%, 91.7% and 75% and 62.5% (p = 0.058). The node positive cohort had 43% recurrences whereas the node negative cohort had 8.3% with all recurrences limited to periportal lymph nodes, distant nodes or liver metastasis.ConclusionNodal positivity for T1b gall bladder cancer ranges around 21% and radical surgery with complete peri –portal lymphadenectomy should be considered as standard of care.     

Prognostic Markers for Invasive Micropapillary Carcinoma of the Breast: A Population-Based Analysis

BackgroundInvasive micropapillary carcinoma (IMPC) is a rare and distinct variant of breast carcinoma with a high propensity for regional lymph node involvement. Because of its lymphotropic nature, IMPC is considered to have an unfavorable prognosis when compared with invasive ductal carcinoma (IDC).Patients and MethodsThis study of 624 patients diagnosed with breast IMPC (2001-2008) listed in the National Cancer Institute's Surveillance, Epidemiology, and End Results (NCI SEER) database was performed to evaluate prognostic factors for disease-specific survival (DSS) and overall survival (OS).ResultsThe 5-year DSS and OS for patients with IMPC were 91.9% and 83.8%, respectively. Of those with known estrogen receptor (ER) status, 84.8% were ER-positive (ER⁺), which was associated with better DSS (hazard ratio [HR], 0.27; P < .0002) and OS (HR 0.45; P < .006). At presentation, 52.9% of the patients with lymph node examinations had nodal involvement and 4.1% had distant metastases. Patients with 4 or more positive lymph nodes had worse DSS (HR 6.43; P = .0013) and OS (HR 3.47; P = .00067) than did patients with node-negative disease, but those with 1 to 3 positive lymph nodes had DSS and OS similar to those of patients with node-negative disease.ConclusionAlthough IMPC has a high propensity for lymph node metastasis, it has a DSS and overall prognosis comparable to those of IDC. Patients with ER-negative (ER?) disease or those with 4 or more positive lymph nodes have the worst prognosis. This is the largest study of IMPC to date, and these findings will help address some of the inconsistencies regarding this rare histologic variant of breast cancer.     

Validity and Necessity of Sub-classification of N3 in the 7thUICC TNM Stage of Gastric Cancer

Background: The 7th TNM staging is the first authoritative standard for evaluation of effectiveness oftreatment of gastric cancer worldwide. However, revision of pN classification within TNM needs to be discussed.In particular, the N3 sub-stage is becoming more conspicuous. Methods: Clinical data of 302 pN3M0 stagegastric cancer patients who received radical gastrectomy in Tianjin Medical University Cancer Institute andHospital from January 2001 to May 2006 were retrospectively analyzed. Results: Location of tumor, depth ofinvasion, extranodal metastasis, gastric resection, combined organs resection, lymph node metastasis, rate oflymph node metastasis, negative lymph nodes count were important prognostic factors of pN3M0 stage gastriccancers. TNM stage was also associated with prognosis. Patients at T2N3M0 stage had a better prognosis thanother sub-classification. T3N3M0 and T4aN3aM0 patients had equal prognosis which followed the T2N3M0.T4aN3bM0 and T4bN3aM0 had lower survival rate than the formers. T4bN3bM0 had worst prognosis. Inmultivariate analysis, TNM stage group and rate of lymph node metastasis were independent prognostic factors.Conclusions: The sub-stage of N3 may be useful for more accurate prediction of prognosis; it should thereforebe applied in the TNM stage system.     

Determining of metastatic lymph node ratio in patients who underwent D2 dissection for gastric cancer

The purpose of this study was to determine outcome of the ratio of metastatic lymph nodes to the total number of dissected lymph nodes (MLR) in patients with gastric cancer. We retrospectively analyzed 111 patients who underwent D₂ lymph node dissection. The prognostic factors including UICC/AJCC TNM classification and MLR were evaluated by univariate and multivariate analysis. The MLR was significantly higher in patients with a larger tumor, lymphatic vessel invasion, blood vessel invasion and perineural invasion, and advanced stage. Moreover, the MLR was significantly associated with the depth of invasion and the number of lymph node metastasis. The univariate analysis revealed for overall survival (OS) that stage of disease, lymphatic vessel invasion, blood vessel invasion, perineural invasion, lymph node metastasis (UICC/AJCC pN stage) and MLR were relevant prognostic indicators. Furthermore, both UICC/AJCC pN stage and MLR were detected as prognostic factor by multivariate analysis, as was perineural invasion. Our results indicated that MLR and UICC/AJCC pN staging system were important prognostic factors for OS of patients with D₂ lymph node dissection in gastric cancer in a multivariate analysis. MLR may be useful for evaluating the status of lymph node metastasis in gastric cancer.     

Comprehensive analysis of prognostic value of lymph node staging classifications in patients with head and neck squamous cell carcinoma after cervical lymph node dissection

PurposeTo determine the optimal threshold of examined lymph node (ELN) number from cervical lymph node dissection for head and neck squamous cell carcinoma (HNSCC). Further to compare the prognostic value of multiple lymph node classification systems and to determine the most suitable scheme to predict survival.MethodsA total of 20991 HNSCC patients were included. Odds ratios (ORs) for negative-to-positive node stage migration and hazard ratios (HRs) for survival were fitted using the LOWESS smoother. Structural breakpoints were determined by the Chow test. The R square, C-index, likelihood ratio, and Akaike information criterion (AIC) were used to compare the prognostic abilities among AJCC N stage, number of positive lymph nodes (pN), positive lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) stages.ResultsA minimal threshold ELN number of fifteen had the discriminatory capacities for both stage migration and survival. LODDS stages had the highest R square value (0.208), C-index (0.736) and likelihood ratio (2467) and the smallest AIC value (65874). LODDS stages also showed prognostic value in estimating patients with AJCC N0 stage. A novel staging system was proposed and showed good prognostic performance when stratified by different primary sites.ConclusionFifteen lymph nodes should be examined for HNSCC patients. LODDS stage allows better prognostic stratification, especially in N0 stage. The proposed staging system may serve as precise evaluation tools to estimate postoperative prognoses.