Value Of Lymph Node Metastasis Research Articles

Radiologists vs. AI-based software: Predicting Lymph Node Metastasis and Prognosis in Lung Adenocarcinoma from CT under Various Image Display Conditions

PurposeTo compare the variability of quantitative values from lung adenocarcinoma CT images independently assessed by two radiologists and AI-based software under different display conditions, and to identify predictors of pathological lymph node metastasis (LNM), disease-free survival (DFS), and overall survival (OS). MethodsPreoperative CT images of 307 patients were displayed under four conditions: lung-1, lung-2, mediastinum-1, and mediastinum-2. Two radiologists (R1, R2) measured total diameter (tD) and the longest solid diameter (sD) under each condition. The AI-based software automatically detected lung nodules, providing tD, sD, total volume (tV), and solid volume (sV). ResultsAll measurements by R1 and R2 with AI-based software were identical. Four out of the eight measurements showed significant variation between R1 and R2. For LNM, multivariate logistic regression identified significant indicators including sD at mediastinum-2 of R1, sD at mediastinum-1 and mediastinum-2 of R2, tV, and the proportion of sV to tV (sV/tV) of AI-based software. For DFS, multivariate Cox regression identified sD at lung-1 of R1, the proportions of sD to tD at lung-2 of R1, sD at lung-2 and mediastinum-1 of R2, tV, and sV/tV of AI-based software as significant. For OS, multivariate Cox regression identified sD at lung-1 and mediastinum-2 of R1, tD at lung-2 of R2, sD at mediastinum-1 of R2, sV, and sV/tV of AI-based software as significant. ConclusionRadiologists’ CT measurements were significant predictors of LNM and prognosis, but variability existed among radiologists and display conditions. AI-based software can provide accurate and reproducible indicators for predicting LNM and prognosis.Micro-abstract: Accurate measurement of lung adenocarcinoma is crucial for determining treatment plan and predicting prognosis. However, inter-observer variability and display conditions can affect these measurements. We compared tumor size measurements between radiologists and commercially available AI-based software using preoperative CT images from 307 cases and evaluated their predictive value for lymph node metastasis, disease-free survival, and overall survival. We concluded that while radiologist measurements showed inter-observer variability, AI-based software provided accurate and reproducible prognostic indicators.

Comparative Diagnostic Value of 18F-FDG–PET–CT and Intraoperative Examination in Cervical Cancer Staging

Background and Objectives: The primary objective of this study is to assess the effectiveness of 18F-FDG–PET–CT in preoperative staging of cervical cancer, focusing on determining surgical operability and exploring the correlation between its quantitative parameters and clinicopathological characteristics. Materials and Methods: This retrospective study included 62 cervical cancer patients treated at the Department of Gynecology, Clinic for Operative Oncology at the Institute of Oncology Vojvodina between January 2016 and January 2020, where preoperative clinical examinations and 18F-FDG–PET–CT were performed to assess the extent of cancer, followed by intraoperative and pathohistological examinations of surgically removed specimens to provide a comprehensive evaluation. Results: The mean tumor size measured by 18F-FDG–PET–CT was slightly greater than that obtained through clinical examination (26.4 mm vs. 26.0 mm), with a strong linear correlation (r = 0.678, p < 0.001) observed between the two measurement methods. The overall prediction accuracy of 18F-FDG–PET–CT for primary tumors is 88.7% (55/62) [sensitivity 86.8%, specificity 100.0%, PPV 100.0%, NPV 56.2%] and for intraoperative examination is 88.7% (55/62) [sensitivity 98.1%, specificity 33.3%, PPV 89.7%, NPV 75.0%]. The agreement with histopathological examination was good for 18F-FDG–PET–CT and moderate for intraoperative examination for primary tumors. Regarding lymph nodes, the overall prediction accuracy of 18F-FDG–PET–CT is 82.2% (51/62) [sensitivity 53.8%, specificity 89.8%, PPV 58.3%, NPV 88.8%] and for intraoperative examination 66.1% (41/62) [sensitivity 76.9%, specificity 63.3%, PPV 35.7%, NPV 91.2%]. The agreement with histopathological examination was moderate for 18F-FDG–PET–CT and poor for intraoperative examination for lymph node metastasis, highlighting that the overall accuracy of 18F-FDG–PET–CT (82.1%) was significantly higher than that of intraoperative examination (66.1%) (p = 0.002). Conclusions: In conclusion, 18F-FDG–PET–CT provides high accuracy in detecting primary tumors and superior predictive value for lymph node metastases compared to intraoperative examination, highlighting the importance of incorporating this imaging modality into the preoperative evaluation process to enhance diagnostic precision and inform treatment decisions.

Refining Risk Criteria May Substantially Reduce Unnecessary Additional Surgeries after Local Resection of T1 Colorectal Cancer.

The low positive predictive value for lymph node metastases (LNM) of common practice risk criteria (CPRC) in T1 colorectal carcinoma (CRC) leads to manyunnecessary additional surgeries following local resection. This study aimed to identify criteria that may improve on the CPRC. Logistic regression analysis was performed to determine the association of diverse variables with LNM or 'poor outcome' (LNM and/or distant metastases and/or recurrence) in a single center T1 CRC cohort. The diagnostic capacity of the set of variables obtained was compared with that of the CPRC. The study comprised 161 cases. Poorly differentiated clusters (PDC) and tumor budding grade > 1 (TB > 1) were the only independent variables associated with LNM. The area under the curve (AUC) for these criteria was 0.808 (CI 95% 0.717-0.880) compared to 0.582 (CI 95% 0.479-0.680) for CPRC. TB > 1 and lymphovascular invasion (LVI) were independently associated with 'poor outcome', with an AUC of 0.801 (CI 95% 0.731-0.859), while the AUC for CPRC was 0.691 (CI 95% 0.603-0.752). TB > 1, combined either with PDC or LVI, would reduce false positives between 41.5% and 45% without significantly increasing false negatives. Indicating additional surgery in T1 CRC only when either TB > 1, PDC, or LVI are present could reduce unnecessary surgeries significantly.

Tumor-to-stroma cd8+ t cells ratio combined with cancer-associated fibroblasts: an innovative approach to predicting lymph node metastases of cervical cancer

PurposePrecise identification of lymph node metastases is vital for the management of cervical cancer. However, the existing diagnostic methods for lymph node metastases have certain drawbacks. In this study, we aim to explore the expression of cancer-associated fibroblasts (CAFs) and tumor-to-stroma CD8+ T cells ratio (CD8+ T cells T:S ratio) and its association with lymph node metastases of cervical cancer.MethodsHundred and ten cervical cancer tissues and 39 biopsy tissues from patients were investigated immunocytochemically for the expression of CAFs and CD8+ T cells. The statistical correlation analysis was carried out using the SPSS system.ResultsA strong and statistically significant negative correlation (r= − 0.690; P < 0.001) was observed between CAF density and CD8+ T cells T:S ratio. Not only were CAFs density and CD8+ T cells T:S ratio correlated with lymph node metastases respectively (P < 0.001), but the combination of them also significantly correlated with lymph node metastases (P < 0.001). Then, we constructed the combined diagnosis model (Logit (P) = − 4.446 + 0.300 × CAFs + 0.752 × CD8+ T cells T:S Ratio) of cervical cancer lymph node metastases. ROC curves analysis showed that the ROC curves areas for CAFs, CD8+ T cells T:S ratio, and a combination of both are 0.879, 0.747, and 0.951. Then, the prediction model was verified by biopsy specimens and consistent results were obtained.ConclusionsThe combination of CAF density and CD8+ T cells T:S ratio has a significant predictive value for lymph node metastases in patients with cervical cancer.

Expression of CXCL8 and its relationship with prognosis in patients with non-small cell lung cancer.

To determine the expression of chemokine 8 (CXCL8) in non-small cell lung cancer (NSCLC) patients and analyze its correlation with tumor characteristics and patient prognosis. We conducted a retrospective analysis of 149 NSCLC patients treated between January 2016 and April 2018, measuring serum CXCL8 expression upon admission or prior to treatment. The clinical characteristics, including lymph node metastasis and staging, based on CXCL8 expression levels, were analyzed. Receiver Operating Characteristic (ROC) curves was drawn to assess its predictive value for lymph node metastasis and staging in NSCLC patients. Furthermore, the Kaplan-Meier curve was plotted to assess the impact of CXCL8 on 5-year survival in NSCLC Patients. NSCLC patients exhibited significantly higher serum CXCL8 levels than those with benign tumors (P<0.001), with the high CXCL8 expression group showing a higher incidence of lymph node metastasis or stage III NSCLC (P<0.01). CXCL8 was identified as an independent predictor of lymph node metastasis (AUC=0.730) and higher TNM stage (AUC=0.708), as well as a validated biomarker for predicting five-year survival in NSCLC patients. This study highlights the strong association between CXCL8 expression in NSCLC and patient prognosis, particularly regarding lymph node metastasis and clinical staging, suggesting the need for further research to explore CXCL8's specific role in the tumor microenvironment and its impact on different NSCLC subtypes.

The ability of magnetic resonance imaging to predict lymph node metastases and the risk of recurrence in rectal cancer.

This study aimed to examine the diagnostic accuracy and prognostic value of magnetic resonance imaging (MRI) detected lymph nodes in rectal cancer. We evaluated 806 rectal cancer patients consecutively operated on between 2015 and 2018 at Helsinki University Hospital. In total, 485 patients met the inclusion criteria of presenting with stage I-III disease and were intended for curative treatment at the time of diagnosis. The effect of MRI-detected clinical lymph node status (cN) on cumulative overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) was calculated using the Kaplan-Meier analysis. Negative predictive value (NPV) of MRI-lymphnode negativity was 74.8%. Positive predictive value of lymph node metastasis was only 48.6%. In the Kaplan-Meier survival analysis, OS (p = 0.989), DSS (p = 0.911), and DFS (p = 0.109) did not significantly differ according to MRI nodal status. However, cumulative disease-free survival significantly (p < 0.001) differed according to the histopathological lymph node metastasis status (pN). MRI detected lymph node positivity appears insufficiently precise and cannot predict disease recurrence or survival. Therefore, it should not serve as an independent risk factor when considering neoadjuvant treatment options for rectal cancer patients.

Tumor-infiltrating T cells as a risk factor for lymph node metastasis in patients with submucosal colorectal cancer

Approximately 10% of patients with colorectal cancer with submucosal invasion have lymph node metastasis. Pathological risk factors for lymph node metastasis have varying sensitivities and specificities. To predict the risk of lymph node metastasis, the identification of new risk factors is vital. Tumor-infiltrating T cells have been reported to improve the prognosis of many solid tumors. Therefore, the purpose of this study was to examine the relationship between lymph node metastasis and tumor-infiltrating T cells in patients with colorectal cancer with submucosal invasion. We examined CD8+ tumor-infiltrating T cells level as a risk factor for lymph node metastasis in patients with colorectal cancer with submucosal invasion. Using immunohistochemical staining, we identified CD8 + T cells in surgically resected specimens from 98 patients with SM-CRC. We showed that low CD8+ tumor-infiltrating T cells levels are positively correlated with lymph node metastasis. Furthermore, by combining the number of CD8+ tumor-infiltrating T cell and the number of CD103+ tumor-infiltrating T cells, the results showed a high positive predictive value for lymph node metastasis in cases with low numbers of both types of tumor-infiltrating T cells and a high negative predictive value in cases with high numbers of both types of tumor-infiltrating T cells.

Silva cumulative score and its relationship with prognosis in Endocervical adenocarcinoma

BackgroundThe Silva system has been demonstrated to have a good predictive value of lymph node metastasis (LNM) in endocervical adenocarcinoma (EAC). Tumours were classified based on the highest identified pattern of invasion in this system, this may not exactly reflect the true situation when it presents with a “mixed pattern” in some cases. Recent study has shown that patients with lymphovascular invasion (LVI) have worse prognosis in EAC. Here we design a Silva cumulative score (SCS) system which also combined the LVI status to explore its prognostic role in EAC patients.MethodsA total of 120 patients with EAC were included in this study. Clinicopathological characteristics were retrospectively retrieved from the medical records and follow-up data were obtained. The clinicopathological information included age at diagnosis, depth of invasion (DOI), LNM, LVI, Silva classification, and SCS. SCS is a classification system based on the sum score of different Silva pattern which is founded on morphological phenomena. The relationships between the pathological characteristics and prognoses were analyzed.ResultsAccording to the Silva system, 11 (9.2%), 22 (18.3%) and 87 (72.5%) patients had patterns A, B, and C, respectively. Patients with pattern C had the highest incidence of LVI and LNM (p < 0.05). Although the Kaplan-Meier curves demonstrated that survival decreased with increasing Silva classification for A-C cancers, there was no statistically significant difference [disease-free survival (DFS): p = 0.181; overall survival (OS): p = 0.205]. There were 45 cases presented as mixed-type of Silva patterns. According to the SCS, 23 cases (19.2%) were rated as grade I, 31 cases (25.8%) as grade II and 66 (55.0%) cases as grade III. Patients with SCS grade III had the highest incidence of LVI and LNM (p < 0.05). Kaplan–Meier analysis revealed that patients with higher SCS had significantly shorter DFS and OS than those with lower SCS (p < 0.05). High SCS was an independent predictor of poorer OS and DFS (p < 0.05) in patients with EAC.ConclusionsThe application of the Silva system could effectively predict the LNM of patients and may be helpful in selecting an appropriate surgical procedure. The SCS system we designed showed a good predictive value for DFS and OS in EAC.

Improved stratification of stage-specific survival for cervical uterine cancer by integrating FDG-PET/CT and MRI for lymph node staging in 2018 FIGO classification

ObjectiveStaging carcinoma of the uterine cervix (CCU) by FIGO-2018 suggests stage migration of FIGO-2009 stage I-III patients with lymph node metastasis into FIGO-2018 stage IIIC. We aimed to investigate the prognostic value of lymph node metastases identified by imaging. MethodsWe enrolled all patients with biopsy-verified CCU from 2007 to 2016 at Odense University Hospital, Denmark. FDG-PET/CT and MRI were performed before clinical examination in general anesthesia. Disease-specific mortality was compared between women with lymph node-positive and lymph node-negative imaging. ResultsIn total, 488 patients underwent clinical staging according to FIGO-2009. Lymph node-positive imaging was identified in 146 (30%) patients: 0/36 (0%) in stage IA, 22/195 (11%) in IBI, 14/30 (47%) in IB2, 70/164 (43%) in II and 40/63 (63%) in III. The 5-year cumulative incidence of death due to CCU lymph node-negative vs. lymph node-positive patients was 0.8% vs. 7.1% (p = 0.034) in stage IBI, 0% vs. 34.5% (p = 0.003) in stage IB2, 15.1% vs. 41.4% (p < 0.0001) in stage II, and 33.3% vs. 46.6% (p = 0.28) in stage III by FIGO-2009. ConclusionsOne of three women with FIGO-2009 stage I-III CCU had suspected lymph node metastasis on imaging and is upstaged to stage IIIC according to FIGO-2018. The cancer-specific mortality by CCU was significantly lower in the lymph node-negative women stages IBI-II, thus supporting stage migration due to suspected lymph node metastasis. However, the exact prognostic value within stage IIIC is challenged, and future revision of FIGO stages may include new sub-stages.

Eyelid sebaceous gland carcinoma, validation of AJCC 8th edition T staging- a retrospective study from North India.

This study compares the 8th edition staging of AJCC for prognosis of eyelid Sebaceous Gland Carcinoma (SGC) patients with respect to the 7th edition. A retrospective study was undertaken over a period of 100 months. Ninety-nine histopathologically proven cases of eyelid SGC available for follow-up were recruited. Patients were staged by both the 7th and 8th editions of AJCC and followed up at six monthly intervals after surgery. Of the 99 eyelid SGC patients recruited, recurrence and orbital invasion developed in 22%, lymph node metastasis in 21% and 4% had distant metastasis and also died. High-risk features include tumour size>20 mm, orbital invasion, exenteration and staging by both the 7th and 8th editions of AJCC. Cox regression analysis revealed that staging by AJCC 8th edition was associated with greater risk for local recurrence (HR 3.01,95% CI-1.65-5.51%, p < 0.01) lymph node metastasis (HR 8.26, 95% CI 3.96-17.19%, p < 0.01) and disease-free survival (HR 4.61, 95% CI 2.81-7.54). The Kaplan-Meir survival curves of eyelid SGC patients by the 8th edition AJCC staging were also significantly associated with lymph node metastasis (p < 0.01), tumour-related deaths (p < 0.01) and reduced disease-free survival (p=0.07). The higher Harrell's values by the 8th edition signify better predictive value for lymph node metastasis and DFS (disease-free survival). The lower AIC values indicate a better monotonicity of gradients for lymph node metastasis, recurrence and DFS. Staging by the 8th AJCC edition is, therefore, recommended for eyelid SGC as it gives a better perspective about disease outcome. The orbital extension was the single most important predictor of lymph node metastasis, recurrence and death.

Value of lymphadenectomy in patients with surgically resected pancreatic neuroendocrine tumors

BackgroundAlthough some factors that predict the prognosis in pancreatic neuroendocrine tumor (pNET) have been confirmed, the predictive value of lymph node metastasis (LNM) in the prognosis of pNETs remains conflicting and it is not clear whether regional lymphadenectomy should be performed in all grades of tumors.MethodsWe included pNET patients undergoing surgery in Shanghai pancreatic cancer institute (SHPCI). The risk factors for survival were investigated by the Kaplan–Meier method and Cox regression model. We evaluated the predictors of LNM using Logistic regression.ResultsFor 206 patients in the SHPCI series, LNM was an independent prognostic factor for entire cohort suggested by multivariate Cox regression analysis. LNM (P = 0.002) predicted poorer overall survival (OS) in grade 2/3 cohort, but there is no significant association between LNM and OS in grade 1 cohort. Grade (P < 0.001) and size (P = 0.049) predicted LNM in entire cohort. Grade (P = 0.002) predicted LNM while regardless of size in grade 2/3 cohort.ConclusionsBased on our own retrospective data obtained from a single center series, LNM seems to be associated with poorer outcome for patients with grade 2/3 and/or grade 1 > 4 cm tumors. On the other way, LNM was seems to be not associated with prognosis in patients with grade 1 tumors less than 4 cm. Moreover, tumor grade and tumor size seem to act as independent predictors of LNM. Thus, regional lymphadenectomy should be performed in grade 2/3 patients but was not mandatory in grade 1 tumors < 4 cm. It is reasonable to perform functional sparing surgery for grade 1 patients or propose a clinical-radiological monitoring.

Ultrasound Measurement of Tumor-Free Distance from the Serosal Surface as the Alternative to Measuring the Depth of Myometrial Invasion in Predicting Lymph Node Metastases in Endometrial Cancer.

Background: Ultrasonography’s usefulness in endometrial cancer (EC) diagnosis consists in its roles in staging and prediction of metastasis. Ultrasound-measured tumor-free distance from the tumor to the uterine serosa (uTFD) is a promising marker for these diagnostic and prognostic variables. The aim of the study was to determine the usefulness of this biomarker in locoregional staging, and thus in the prediction of lymph node metastasis (LNM). Methods: We conducted a single-institutional, prospective study on 116 consecutive patients with EC who underwent 2D transvaginal ultrasound examination. The uTFD marker was compared with the depth of ultrasound-measured myometrial invasion (uMI). Univariable and multivariable logit models were evaluated to assess the predictive power of the uTFD and uMI in regard to LNM. The reference standard was a final histopathology result. Survival was assessed by the Kaplan–Meier method. Results: LNM was found in 17% of the patients (20/116). In the univariable analysis, uMI and uTFD were significant predictors of LNM. The accuracy was 70.7%, and the NPV was 92.68% (OR 4.746, 95% CI 1.710–13.174) for uMI (p = 0.002), and they were 63.8% and 89.02% (OR 0.842, 95% CI 0.736–0.963), respectively, for uTFD (p = 0.01). The cutoff value for uTFD in the prediction of LNM was 5.2 mm. The association between absence of LNM and biomarker values of uMI < 1/2 and uTFD ≥ 5.2 mm was greater than that between the presence of metastases and uMI > 1/2 and uTFD values <5.2 mm. In the multivariable analysis, the accuracy of the uMI–uTFD model was 74%, and its NPV was 90.24% (p = non-significant). Neither uMI nor uTFD were surrogates for overall and recurrence-free survivals in endometrial cancer. Conclusions: Both uMI and uTFD, either alone or in combination, were valuable tools for gaining additional preoperative information on expected lymph node status. Negative lymph nodes status was better described by ultrasound biomarkers than a positive status. It was easier to use the uTFD rather than the uMI measurement as a biomarker of EC invasion, and the former still maintained a similar predictive value for lymph node metastases to the latter at diagnosis.

The prognostic value of lymph node metastasis and the eighth edition of AJCC for patients with anaplastic thyroid cancer.

ObjectiveThe eighth edition of the American Joint Committee on Cancer (AJCC‐v8) for anaplastic thyroid cancer (ATC) made a revision in staging for patients with lymph node metastasis (LNM) based on the seventh edition of AJCC (AJCC‐v7). Our study aimed to evaluate the predictive ability of AJCC‐v8 for survival in patients with ATC by exploring the association between lymph node stage and prognosis of ATC patients.MethodsRetrospective study of ATC in Surveillance, Epidemiology and End Results (SEER) database. The association between LNM and survival of ATC was estimated by the Kaplan‐Meier method and Cox regression model. The predictive performances of the AJCC‐v8 and AJCC‐v7 were estimated through C‐index, Akaike information criterion (AIC) and Bayesian information criterion (BIC).ResultsA total of 313 patients with ATC were included in our analysis. Notably, LNM was identified as an independent risk factor for ATC mortality (adjusted HR, 1.47, 95% CI, 1.10–1.96; p = .009), while the risk of mortality in N1a group was comparable to that in N1b group according to univariate (HR, 1.30, 95% CI, 0.92–1.82; p = .133) and multivariate (adjusted HR 0.87, 95% CI, 0.60–1.27; p = .467) cox analyses. Applying the AJCC‐v8, the survival of migration population staged T1‐3aN1M0 was significantly worse than that of T1‐3aN0M0 patients (IVA stage), while was not different from that of T3b‐T4bN0/N1M0 patients (IVB stage). With a higher C‐index (0.60 vs. 0.59), lower AIC (2728 vs. 2732) and BIC (2732 vs. 2735), AJCC‐v8 was demonstrably a more favourable prediction model than AJCC‐v7.ConclusionsThis study demonstrated that LNM was independently associated with poor prognosis of ATC, and AJCC‐v8 with the modified staging of patients with LNM showed better survival predictive performance in ATC patients than AJCC‐v7.

The value of morphological characteristics of cervical adenocarcinoma biopsy tissue in predicting tumor invasion pattern and prognosis

Objective: To evaluate the pathologic findings from biopsy samples to predict the status of nodal metastasis for patients with usual cervical adenocarcinoma. Methods: The 32-pair samples of cervical adenocarcinoma specimens (32 cervical biopsies and 32 hysterectomies with staging) from 2013 to 2019 were selected for retrospective study in Shanghai first Maternal and infant Health Care Hospital Affiliated to Tongji University. The correlation between histopathologic features including necrotic tumor debris (NTD), nuclear grade, mitotic count and pattern-based classification system and the status of lymph node metastasis was evaluated. Results: Tumor invasive patterns of cervical adenocarcinoma, as described previously, could be discerned in hysterectomy/staging specimens, but not in cervical biopsies. Because the biopsy tissues were small, only 14(14/32, 43.8%) cases could be classified according to pattern of invasion, and the concordance rate with resected specimens was 37.5%. NTD (9/19) and grade 3 nuclei (11/19) were positively correlated with invasive pattern C and nodal metastases (P<0.05). Moreover, when NTD and (or) nuclear grade were evaluated at the same time, the sensitivity for type C infiltration was higher. Conclusions: Evaluation of NTD and nuclear grade in biopsies for cervical adenocarcinoma provides good predictive value for lymph node metastasis. It is helpful for patient stratification and management andto avoid unnecessary staging procedures. However, multicenter studies and prospective clinical trials are necessary to confirm the findings before clinical application can be considered.

Risk Factors of Lymph Node Metastasis in Patients with Pancreatic Neuroendocrine Tumors (PNETs).

Background The prognostic value of lymph node metastasis in patients with PNETs is controversial. Understanding the effect of lymph node metastasis on prognosis in pancreatic neuroendocrine tumors is helpful for surgery and follow-up. The purposes of this study are to identify predictors of lymph node metastasis among patients with PNETs and determine its prognostic associations. Methods A retrospective analysis of the surveillance, epidemiology, and end results (SEER) database was performed. Patients with PNETs that underwent surgery and pathologic nodal staging were identified. Logistic regression and Cox regression were performed to identify independent predictors and prognostic factors, respectively. Results Of 1956 patients (age: 56.8 ± 13.4 years, 53.3% males), 748 (38.2%) had lymph node metastasis. On multivariable analysis, tumor located in pancreas head, distant metastasis, and poorly differentiated, undifferentiated, and unknown differentiated histology grades were three independent risk factors of lymph node metastasis. In the entire cohort, lymph node metastasis indicated a worse overall survival (HR: 1.48, 95% CI: 1.17-1.88, p < 0.001) and disease-specific survival (HR: 1.87, 95% CI: 1.41-2.48, p < 0.001) on multivariable analysis. Lymph node metastasis was associated with worse overall (HR: 1.45, 95% CI: 1.08-1.93, p = 0.012) and disease-specific survival (HR: 2.13, 95% CI: 1.48-3.05, p < 0.001) in patients without distant metastasis on multivariate analysis. Lymph node metastasis was also independently associated with worse disease-specific survival among patients in well differentiation (HR: 2.16, 95% CI: 1.35-3.46, p = 0.001) and moderately differentiation (HR: 2.67, 95% CI: 1.28-5.56, p = 0.009) groups on multivariate analysis. Conclusions Tumor located in pancreas head, distant metastasis, and poorly differentiated, undifferentiated, and unknown differentiated histology grades were three independent risk factors for lymph node metastasis. Lymph node metastasis was an independent prognostic factor of worse OS and DSS in patients with tumor located in pancreas head. Lymph node metastasis was an independent prognostic factor of worse OS and DSS in patients without distant metastasis. Lymph node metastasis was an independent prognostic factor of worse DSS in well differentiation and moderately differentiation groups.

Diagnostic and Predictive Values of Inflammatory Factors in Pathology and Survival of Patients Undergoing Total Cystectomy.

Background Inflammation and tumorigenesis are related. We conducted this study to evaluate whether inflammatory factors (IFs) have a diagnostic value for pathology and a predictive value for survival and recurrence in bladder cancer patients undergoing total cystectomy. Methods The patients who were diagnosed with bladder cancer and underwent total cystectomy in our center from 2014 to 2020 were enrolled. The values of neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and systemic immune-inflammation index (SII) were calculated by blood routine test results before operation. The AUC of ROC was calculated to judge the diagnostic value of the IFs in pathology and their corresponding cut-off values. For overall survival (OS) and recurrence-free survival (RFS), the above IFs were grouped according to the cut-off value. The differences between different groups were analyzed by the Kaplan-Meier curves, and the predictive value of these IFs was determined by the Cox proportional hazards regression model. Results A total of 79 patients were enrolled. All IFs had no diagnostic value for the pathological grade, tumor T stage, and systemic metastasis. Only NLR (AUC = 0.706, cut‐off value = 3.12, sensitivity = 75.00%, specificity = 70.00%, P = 0.014), dNLR (AUC = 0.700, cut‐off value = 2.49, sensitivity = 66.67%, specificity = 76.67%, P = 0.015), and SII (AUC = 0.704, cut‐off value = 463.56, sensitivity = 100.00%, specificity = 40.00%, P = 0.004) had a diagnostic value for lymph node metastasis. The median follow-up time was 31 months, and there was no significant difference in OS between the two groups for all IFs. For RFS, Kaplan-Meier suggested PLR might be predictive when the cut-off value was 266.70 (P = 0.044), but the subsequent Cox proportional hazards regression analysis showed that all IFs had no predictive value for OS and RFS. Conclusions We found that in patients undergoing total cystectomy preoperative NLR, dNLR and SII had a diagnostic value for lymph node metastasis, while all these five IFs had no predictive value for OS and RFS. However, this conclusion needs to be further verified by large-scale studies in the future.

Analysis of diagnostic and prognostic value of lncRNA MEG3 in cervical cancer.

The present study aimed to explore the diagnostic and prognostic value of lncRNA maternally expressed 3 (MEG3) in cervical cancer. Eighty-four patients with cervical cancer from February 2013 to March 2014 were enrolled in the observation group (OG), and another 58 female subjects who underwent physical examination at Huangshi Central Hospital were enrolled as the control group (CG). The serum MEG3 expression of patients in the two groups was detected by RT-qPCR, and the ability of MEG3 to aid in the diagnosis of cervical cancer, lymph node metastasis and FIGO staging, as well as to predict mortality was evaluated by ROC curve. In addition, the patients in the OG were divided into high- and low-expression groups according to the median value of MEG3. Kaplan Meier was employed to analyze the survival status, and Cox regression to analyze the independent prognostic factors of cervical cancer patients. The results of the present study revealed that the serum MEG3 expression in the OG was significantly lower than that of the CG (P<0.05). The area under the curve (AUC) of MEG3 in diagnosing cervical cancer was 0.844, the AUC in predicting mortality was 0.858, while that in diagnosing lymph node transfer was 0.707, and that in diagnosing FIGO staging was 0.791. The 5-year survival rate of the high-expression group was higher than that of the low-expression group (P=0.020). Multivariate analysis indicated that MEG3 (HR, 0.173; 95 CI%, 0.028-0.919), lymph node metastasis (HR, 2.259; 95 CI%, 1.004-5.025) and FIGO staging (HR, 0.008; 95 CI%, 1.453-6.248) were independent prognostic factors for cervical cancer patients. Collectively, lncRNA MEG3 may be a diagnostic marker and prognostic indicator for cervical cancer, and has a certain diagnostic value for lymph node metastasis and FIGO staging. Lymph node metastasis, FIGO stage III and IV, and low MEG3 levels were revealed to be independent prognostic factors for cervical cancer patients.

Protocol for expanded indications of endoscopic submucosal dissection for early gastric cancer in China: a multicenter, ambispective, observational, open-cohort study

BackgroundThe main treatment methods for early gastric cancer (EGC) include endoscopic submucosal dissection (ESD) and radical gastrectomy. However, appropriate treatment for patients who exceed the absolute indications for ESD remains unestablished. In China, evidence-based medicine for the expanding indications of ESD and accurate diagnostic staging for EGC patients are lacking. Thus, clinical studies involving Chinese patients with EGC are necessary to select appropriate treatment options and promote China’s expanded indications for ESD and diagnostic staging scheme.MethodsThis is a multicenter, ambispective, observational, open-cohort study that is expected to enroll 554 patients with EGC. The study was launched in May 2018 and is scheduled to end in March 2022. All enrolled patients should meet the inclusion criteria. Case report forms and electronic data capture systems are used to obtain clinical data, which includes demographic information, results of perioperative blood- and auxiliary examinations, surgical information, results of postoperative pathology, and the outcomes of postoperative recovery and follow-up. Patients are followed up every 6 months after surgery for a minimum of 5 years. The primary endpoint is the rate of lymph node metastasis (LNM), whereas the secondary endpoints include the following: consistency, sensitivity, and specificity of the results of preoperative examinations and postoperative pathology; cut-off values for LNM; logistic regression model of expanded indications for ESD; and incidence of postoperative complications within the 30-day and 5-year relapse-free survival rates.DiscussionThis study will explore and evaluate expanded indications for ESD that match the characteristics of the Chinese population in patients with EGC and will introduce a related staging procedure and examination scheme that is appropriate for China. Ethical approval was obtained from all participating centers. The findings are expected to be disseminated through publications or presentations and will facilitate clinical decision-making in EGC.Trial registrationThe name of the registry is ChiCTR. It was registered on May 9, 2018, with the registration number (ChiCTR1800016084). The clinical trial was launched in May 2018 and will end in March 2022, with enrollment to be completed by December 2021. Trial status: Ongoing.

Tumor microRNA profile and prognostic value for lymph node metastasis in oral squamous cell carcinoma patients.

Neck lymph node metastasis (LN+) is one of the most significant prognostic factors affecting 1-in-2 patients diagnosed with oral squamous cell carcinoma (OSCC). The different LN outcomes between clinico-pathologically similar primary tumors suggest underlying molecular signatures that could be associated with the risk of nodal disease development. MicroRNAs (miRNAs)are short non-coding molecules that regulate the expression of their target genes to maintain the balance of cellular processes. A plethora of evidence has indicated that aberrantly expressed miRNAs are involved in cancers with either an antitumor or oncogenic role. In this study, we characterized miRNA expression among OSCC fresh-frozen tumors with known outcomes of nodal disease (82 LN+, 76 LN0). We identified 49 differentially expressed miRNAs in tumors of the LN+ group. Using penalized lasso Cox regression, we identified a group of 10 miRNAs of which expression levels were highly associated with nodal-disease free survival. We further reported a 4-miRNA panel (miR-21-5p, miR-107, miR-1247-3p, and miR-181b-3p) with high accuracy in discriminating LN status, suggesting their potential application as prognostic biomarkers for nodal disease.

Tumor infiltrative growth pattern correlates with the immune microenvironment and is an independent factor for lymph node metastasis and prognosis in stage T1 esophageal squamous cell carcinoma.

In this retrospective study, we analyzed the association between the tumor infiltrative growth pattern (INF) and tumor immune environment and its predictive value for lymph node metastasis and overall survival (OS) in stage T1 esophageal squamous cell carcinoma (ESCC). In total, 593 patients with a diagnosis of stage T1 ESCC who underwent esophagectomy and regional lymphadenectomy between 2009 and 2018 were included. The INF type and elements of the tumor immune microenvironment, including tumor infiltrative lymphocytes (TILs) and tertiary lymphoid structures (TLSs), were microscopically evaluated within the tumor invasive margin with hematoxylin and eosin (HE)-stained slices. The infiltrative-type INF (INFc) was associated with low-grade TILs and the absence of TLSs, deep tumor invasion, poorly differentiated phenotype. Multivariate logistic regression identified INFc as one of the independent risk factors for lymph node metastasis. INFc and low-grade TILs were independent inferior predictive factors for OS. A novel histologic risk stratification model was classified as INFa/b and high-grade TILs, INFa/b and low-grade TILs, INFc and high-grade TILs, and INFc and low-grade TILs. The Kaplan-Meier curves showed that INFa/b and high-grade TILs were associated with the best prognosis, and INFc and low-grade TILs were associated with the worst prognosis, and there was significant difference between groups. In conclusion, INFc is an independent risk factor for lymph node metastasis and an independent inferior prognostic factor for stage T1 ESCC. Furthermore, INFc is associated with immunosuppression, and the combination of the INF and TILs is useful for the risk stratification of prognosis.