Incidence Of Lymph Node Metastasis Research Articles

Optimal Initial Workup in Patients With Superficial Primary Gastric MALT Lymphoma.

The prognosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is favorable, especially in the absence of lymph node metastasis (LNM). We investigated LNM incidence and location in superficial type gastric MALT lymphoma. We performed a retrospective analysis of 450 patients newly diagnosed with gastric MALT lymphoma with tumor infiltration confined to the mucosa or submucosa as evidenced by endoscopic ultrasonography. LNM incidence and location were evaluated. Of the 450 patients, most patients (434, 96.4%) were initially LNM negative as confirmed by computed tomography (CT) scanning. Sixteen patients (3.6%) were LNM positive. There was no difference in clinical characteristics between the 2 groups except for the extent of lymphoma involvement and endoscopic findings. Among 41 patients undergoing abdominal/pelvic CT (APCT) only, LNM was detected in 1 (2.4%). There were 8 LNM cases among 238 patients undergoing both APCT and chest CT (3.4%). Among 171 patients undergoing APCT, chest CT, and neck CT, 7 cases of LNM were detected (4.1%). The detection rates for each CT were as follows: abdominal CT, 13/450 (2.9%); chest CT, 6/408 (1.5%); and neck CT, 1/171 (0.6%). Among 6 patients with chest CT-positive findings, 3 showed no evidence of LNM on APCT. LNM was an infrequent finding in gastric MALT lymphoma patients with tumor infiltration confined to the mucosa or submucosa. Besides endoscopy and endoscopic ultrasonography, APCT and chest CT are considered as optimal initial workup modalities in patients with assumed primary superficial gastric MALT lymphoma.

Prognostic Significance of Tumor Location in T2 Gallbladder Cancer: A Korea Tumor Registry System Biliary Pancreas (KOTUS-BP) Database Analysis.

Background: T2 gallbladder cancer (GBC) is subdivided into T2a and T2b by the American Joint Committee on Cancer (AJCC) 8th edition. However; there is a lack of evidence for the prognostic significance of tumor location and validation with large-scale studies is needed. The aims of this study were to investigate the clinical features and clinical outcomes of T2 GBC according to tumor location and determine the prognostic significance of tumor location and an appropriate surgical strategy. Methods: Between 2000 and 2014 the Korea Tumor Registry System Biliary Pancreas (KOTUS-BP) database was used to identify and enroll a total 707 patients with pathologically diagnosed T2 GBC who underwent curative resection. Clinicopathological findings and long-term follow-up results were analyzed. Results: The incidence of lymph node metastasis in T2b was significantly higher than that of T2a tumors (37.9% vs. 29.5%, p = 0.032). The 5-year disease-specific survival of T2a was better than that of T2b tumors (74.8% vs. 65.4%, p = 0.019). There was no significant survival difference in T2a between extended cholecystectomy and simple cholecystectomy with lymph node dissection (81.8% vs. 73.7%, p = 0.361). However; there was a better survival trend for T2b tumor after extended cholecystectomy (71.7% vs. 59.3%, p = 0.057). Adjuvant chemotherapy was associated with improved survival for patients with lymph node metastasis in T2a (72.1% vs. 56.9; p = 0.022) and in T2b (68.2 vs. 48.5; p < 0.001). Multivariate analysis revealed that lymph node metastasis was the only significant poor prognostic factor (Hazard ratio 3.222; 95% confidential interval 1.960–4.489; p < 0.001). Conclusions: For T2 GBC; tumor location was not an independent prognostic factor. Lymph node metastasis was a significant poor prognostic factor and adjuvant chemotherapy should be considered for the patients with lymph node metastasis.

S1336 Absolute vs Expanded Criteria Lymph Node Metastasis in Early Gastric Cancer: A Novel U.S. Criterion

INTRODUCTION: Endoscopic resection (ER) for early gastric cancer (EGC) is the principal treatment for lesions fulfilling the absolute and expanded criteria (Exp) developed by the Japanese Gastric Cancer Association. Cohorts showing a minimal risk of lymph node metastasis (LNM) are primarily from eastern Asia. Endoscopic management is adopted in the West, despite the lack of data in Western cohorts. We aims to describe the incidence of LNM by absolute and Exp criteria in the U.S. population using the Surveillance, Epidemiology, End Results (SEER) database, and to define a novel absolute criteria (absence of LNM) for the U.S. METHODS: EGC data was analyzed in the U.S. SEER database. To identify novel absolute criteria in the U.S., we assumed that all the lesions were positive for LVI and ulceration, since SEER does not include this data (a limitation of the database). RESULTS: 161,854 gastric cancers were identified. 2020 EGC met inclusion criteria, 781 T1a and 1239 T1b. No LNM cases were noted in T1a well differentiated lesions < 1cm (0/80). In T1a well differentiated lesions < 2cm, the rate of LNM was 1/125 (0.8%). 277 patients fulfilled absolute criteria (T1a, differentiated < 2cm in size), and 8/277 had LNM (2.9%). The Exp criteria 1-4 findings are summarized in Table 1, with LNM ranging from 7.8% to 16.7%. There were 154 lesions fulfilling Exp criteria 1 (T1a, differentiated, >2cm); LNM occurred in 12/154 (7.8%). There were 353 lesions fulfilling the Exp 2 criteria (T1a, differentiated, < 3cm); LNM occurred in 13/353 (3.7%). There were 197 lesions fulfilling the Exp 3 criteria (T1a, undifferentiated, < 2cm); LNM occurred in 13/197 (6.6%). There were 441 lesions fulfilling the Exp criteria 4 (T1b, differentiated < 3cm); LNM occurred in 74/441 (16.7%). No significant differences were noted between the rates of LNM in the absolute vs Exp criteria 2 or 3 respectively (P = 0.5 , P = 0.053), However, Exp criteria 1 and 4 were associated with a higher incidence of LNM respectively (P = 0.02 , P = 0.001). On multivariate logistic regression, tumor size, T stage, grade, and the number of lymph nodes examined were significant predictors of LNM. CONCLUSION: We propose a new absolute criterion in the U.S. for well differentiated T1a EGC < 1cm regardless of the ulcer status and LVI, with 0% LNM; endoscopic resection should be the standard of care for these lesions. The rate of LNM was 0.8% for T1a well differentiated lesions < 2cm regardless of ulcer status and LVI. The Exp criteria 1 and 4 had an increased risk of LMN.Table 1.: EGC study characteristicsTable 2.: Lymph node metastasis

ASSOCIATION OF THE DEPTH OF TUMOR & LYMPHATIC METASTASIS IN ORAL TONGUE CANCER

Carcinoma of tongue is one of the most notorious cancer of head and neck region. It constitutes about 36.5% of all oral malignancies. Neck node status is the single most important prognostic factor in oral tongue cancers and other head and neck cancers . Another important parameter which has the greatest influence on survival is the tumor thickness especially in carcinoma tongue . In this study, we assessed the association between tumor thickness &amp; lymphatic metastasis in oral tongue cancer. The optimal cut-off point for tumor thickness was 4mm. Total 126 cases were studied of which maximum cases were between 40-49 years of age .Cases were more prevalent in males (69.05%) than females(30.95%) . As the T-stage of cancer progressed , the incidence of nodal metastasis also progressively advanced. It was also observed that as the tumor thickness increased , the proportion of positive lymph node cases also significantly increased. There was significant positive correlation between the tumor thickness measured on MRI and histopathology (r=0.709 , p&lt;0.001)

Ultrasonographic Features, Nodule Size, Capsular Invasion, and Lymph Node Metastasis of Solitary Papillary Carcinoma of Thyroid Isthmus.

Objective: This retrospective study aimed to analyze the ultrasound (US) imaging features of solitary papillary thyroid carcinoma (PTC) located in the isthmus and to assess the risk factors for lymph node metastasis (LNM) and tumor capsular invasion.Methods: We included a total of 135 patients with solitary PTC located in the isthmus. All the cases underwent US, total thyroidectomy, and prophylactic central lymph node dissection. Patients' demographic and thyroid isthmus nodules' US characteristics, as well as risk factors associated with LNM and tumor capsular invasion, were analyzed.Results: It was revealed that the occurrence of LNM was higher in male patients than in female patients (P < 0.001). As risk factors, the size of PTC in the isthmus was found to be associated with LNM and tumor capsular invasion (P = 0.005 and 0.000, respectively). The area under the receiver operating characteristic curve (AUC) of the size of the isthmus PTC was 0.64 [95% confidence interval (CI) = 0.55–0.72], indicating a probability for LNM. The AUC value for tumor capsular invasion was 0.77 (95% CI: 0.68–0.83). When the threshold was set to 1.1 cm, the larger size indicated that there was a probability of occurrence of LNM with sensitivity and specificity of 47.4 and 73.7%, respectively. When the threshold was set to 0.7 cm, the larger size indicated that there was potentially a tumor capsular invasion, with sensitivity and specificity of 80.6 and 56.3%, respectively. Wider-than-tall nodules were found to be significantly different from those in LNM and tumor capsular invasion (P = 0.038 and 0.030, respectively). There were significant differences in tumor capsular invasion in extrathyroidal extension (ETE) compared with smooth or ill-defined and lobulated or irregular nodules (P = 0.017).Conclusions: This study showed that the incidence of LNM in male patients was higher than that in female ones. When a US image shows a thyroid isthmus nodule with a wider-than-tall shape, LNM and tumor capsular invasion were likely to occur. When a US image shows a thyroid isthmus nodule with an ETE, tumor capsular invasion was likely to occur. ETE and wider-than-tall may be indicators of FNA under US guidance, even though the size of thyroid isthmus nodule may be <1 cm.

Long-term outcome after endoscopic resection for early colorectal carcinoma

Objective: To analysis the clinical and follow-up data of the early colorectal carcinoma (ECC) after endoscopic resection, and explore the long-term outcome of patients who underwent the endoscopic resection. Methods: During June 2008 to June 2016, data of endoscopic resection for 550 cases of ECC were collected, including general information and follow-up data. The influence factors of disease-free survival rate of ECC after endoscopic resection were analyzed and the risk factors on long-term outcomes such as submucosa invasion depth, poorly differentiated adenocarcinoma, vascular invasion and positive vertical margin were investigated. Results: The mean follow-up time of 550 patients treated with endoscopy was (60.7±36.8) months. Among them, 433 cases were high-level intra-mucosal neoplasia, 117 cases were submucosa invasion carcinoma (the invasion depth <1 000 μm were 33 cases, ≥1 000 μm were 84 cases), 461 cases were curative resection, while 89 cases were non-curative resection. During the follow-up, 6 patients occurred recurrence or metastasis, including 2 patients with local recurrence (1 patient accompanied by lymph node metastasis) and 4 patients with lymph node metastasis (2 patients accompanied by distant metastasis). The overall 5-years disease-free survival rate was 98.8%, the 5-years disease-free survival rate was 100.0% for patients with curative resection and 93.3% for patients with non-curative resection. A total of 89 cases underwent non-curative resection were accompanied with invasion depth ≥1 000 μm, vascular invasion, poorly differentiated adenocarcinoma and positive vertical margin. Among them, 62 cases were accompanied with 1 risk factor, 23 cases with 2 risk factors and 4 cases with 3 risk factors. The risks of lymph nodes and distant metastasis raised with the increase of risk factors. Conclusions: The incidence of lymph node metastasis in ECC is extremely low. Endoscopic treatment can achieve a good long-term outcome. Close follow-up should be conducted after endoscopic treatment, and additional treatment should be selected reasonably for the early colorectal carcinoma after endoscopic non-curative resection to improve the therapeutic efficacy of endoscopic resection.

Lymph node metastatic patterns and its clinical significance for thoracic superficial esophageal squamous cell carcinoma

Background and objectivesThe optimal therapeutic method for patients with superficial esophageal squamous cell carcinoma (sESCC) remains to be established.MethodsClinical data of all the patients from 2002 to 2014 who underwent curative esophagectomy and three-field lymphadenectomy for thoracic sESCC were collected based on a prospectively-maintained database. The pattern of lymph node metastasis was analyzed based on the depth of tumor invasion, tumor location and surgical fields.ResultsThe involved lymph node region was associated to the tumor location, however, upper mediastinal and perigastric region was the most vulnerable region. The incidence of lymph node metastasis increased with the depth of tumor invasion. No lymph node involvement was found in tumors invading proper mucosa (M2), while the pattern of positive lymph nodes in tumors invading the deepest 1/3 submucosa was similar to that in advanced ESCC. Lymphatic invasion, tumor location and upper mediastinal lymph node involvement were independent predictors for cervical lymph node metastasis. For patients without lymphatic invasion, the positive predictive value of upper mediastinal lymph node metastasis for positive cervical lymph node was low (0 ~ 25%), while the negative predictive value was extremely high, wherever the tumor located (93.8 ~ 100%).ConclusionsTumors invading till proper mucosa was the best indication for endoscopic mucosa resection. Mediastinal-abdominal lymphadenectomy was essential for sESCC invading beyond proper mucosa. For those without lymphatic invasion, cervical lymphadenectomy might be avoided in case of negative upper mediastinal lymph node.

The risk of lymph node metastasis in T1 colorectal cancer: new parameters to assess the degree of submucosal invasion.

In T1 colorectal cancer, the depth is the main factor assessing the degree of submucosal invasion (DSI) to predict the risk of lymph node metastasis (LNM). The width (WSI) and the area of submucosal invasion (ASI) have been suggested as additional parameters to assess the risk of LNM. A review of the literature was undertaken on the correlation between WSI and ASI parameters and the incidence of LNM. A Medline, PubMed, and Cochrane Library search was performed to retrieve all studies reporting correlation between WSI/ASI and risk of LNM in T1 colorectal cancer. Eight studies including 1727 patients were identified. All considered the degree of WSI and its influence on LNM: seven assessed different width cut-off of submucosal invasion, and onestudy the mean width of submucosal invasion in patients having or not involved lymph nodes. The WSI was significantly a prognostic factor for LNM (p < 0.05) in four studies. Both 2 and 3mm seem to be the most discriminatory cut-off values of submucosal width invasion in defining the risk difference of LNM above and below the cut-off (2mm, OR = infinite; 3mm, OR = 6.9). Patients having a cut-off ≤ 5mm of WSI showed a low risk (5.6%) of LNM rendering radical surgery unnecessary. Four studies assessed the risk of LNM according to the involved submucosal area (width × depth). In two of these, the ASI was a significant prognostic factor for LNM (p < 0.05). The WSI and ASI seem to be reliable prognostic factors for LNM in T1 colorectal cancer. There is no agreement on ideal cut-off value.

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

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

IMMUNE CHECKPOINT INHIBITOR EXPRESSION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA AND IMMUNOTHERAPY USE

Objective: Despite the standard treatment of head and neck squamous cell carcinoma (HNSCC) with chemotherapy, radiotherapy, and/or surgery, survival rates are still low. In recent years, a greater understanding of cellular interaction within the tumor microenvironment has allowed for the identification of (1) immune evasion that promotes the development and progression of tumors and (2) the application of immunotherapy. The aim of this study is to summarize the main findings of the research on the expression of immune- checkpoint inhibition molecules in HNSCC cases and possible immunotherapeutic use. Study Design: A narrative review of several relevant known papers (MEDLINE). Results: Studies have shown that 50% to 60% of HNSCC cases expressed high levels of PD-L1 in situ compared to peripheral blood. This high expression is associated with the high incidence of lymph node metastases, poor prognosis, and low survival. Experimental studies of immunotherapy with monoclonal antibodies against immune-checkpoint inhibition molecules showed a significant decrease in tumor growth, few adverse effects, and increased patient survival compared to conventional treatment. Conclusion: Adequate intervention against immune-checkpoint inhibition molecules shows positive treatment potential. However, it is necessary to standardize protocols for identifying these molecules within the tumor microenvironment for the selection of patients who may benefit from this immunotherapy. Objective: Despite the standard treatment of head and neck squamous cell carcinoma (HNSCC) with chemotherapy, radiotherapy, and/or surgery, survival rates are still low. In recent years, a greater understanding of cellular interaction within the tumor microenvironment has allowed for the identification of (1) immune evasion that promotes the development and progression of tumors and (2) the application of immunotherapy. The aim of this study is to summarize the main findings of the research on the expression of immune- checkpoint inhibition molecules in HNSCC cases and possible immunotherapeutic use. Study Design: A narrative review of several relevant known papers (MEDLINE). Results: Studies have shown that 50% to 60% of HNSCC cases expressed high levels of PD-L1 in situ compared to peripheral blood. This high expression is associated with the high incidence of lymph node metastases, poor prognosis, and low survival. Experimental studies of immunotherapy with monoclonal antibodies against immune-checkpoint inhibition molecules showed a significant decrease in tumor growth, few adverse effects, and increased patient survival compared to conventional treatment. Conclusion: Adequate intervention against immune-checkpoint inhibition molecules shows positive treatment potential. However, it is necessary to standardize protocols for identifying these molecules within the tumor microenvironment for the selection of patients who may benefit from this immunotherapy.

Golgi phosphoprotein-3 (GOLPH3) promote metastasis of nasopharyngeal carcinoma through regulating E-cadherin.

The purpose of this study was to investigate GOLPH3 expression in nasopharyngeal carcinoma (NPC) and its influence on the metastatic ability of NPC cells; meanwhile, the underlying mechanism of GOLPH3 promoting the malignant progression of NPC was also explored. In this study, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression of GOLPH3 in 34 pairs of tumor tissue and paracancerous tissue specimens collected from NPC patients, and the interplay between GOLPH3 expression and clinical indicators was analyzed, as well as the prognosis of NPC patients. Meanwhile, GOLPH3 expression in NPC cell lines was further verified by qRT-PCR assay. Furthermore, GOLPH3 knockdown model was constructed in NPC cell lines, including SUNE2 and CNE. Then, cell counting kit-8 (CCK-8), transwell invasion, and cell wound healing assays were applied to analyze the effect of GOLPH3 on the biological function of NPC cells. In addition, an in-depth study of the relationship between GOLPH3 and E-cadherin was conducted. QRT-PCR results indicated that the expression level of GOLPH3 in NPC was remarkably higher than that in adjacent tissues, and the difference was statistically significant. Compared with patients with low expression of GOLPH3, those with high expression of GOLPH3 had a higher incidence of lymph node metastasis. Compared with sh-NC group, the proliferation and invasive ability of NPC cells decreased remarkably after knockdown of GOLPH3. Subsequently, E-cadherin expression was found to be remarkably reduced and negatively correlated with GOLPH3 in NPC cell lines and tissues. Finally, the recovery experiment demonstrated that GOLPH3 might have a mutual regulatory relation with E-cadherin, both of which jointly affect the malignant progression of NPC. GOLPH3 expression is remarkably associated with lymph node metastasis and poor prognosis of NPC patients; in addition, it may promote the proliferation and metastatic ability of NPC cells by regulating E-cadherin.

Predictive Factors of Lymph Node Metastasis in Patients With Papillary Microcarcinoma of the Thyroid: Retrospective Analysis on 293 Cases.

Introduction: Papillary thyroid microcarcinoma (PTMC) is defined as a tumor with a larger diameter ≤ 1 cm and is considered having an indolent course and an excellent prognosis. Nevertheless, the incidence of lymph node metastasis in PTMC is not negligible, reaching up to 65% in some series. The aim of this study was to assess the incidence of lymph node metastasis in patients with PTMC and to evaluate predictive factors for lymph node metastasis.Methods: We included in this retrospective observational study patients who underwent thyroidectomy with pathological diagnosis of PTMC at our department from January 2003 to June 2019.Results: Two hundred ninety-three patients were included in the study. The incidence of lymph node metastasis was 13.7%. Multivariate analysis revealed as independent risk factors for lymph node metastasis age <45 years, nodule size ≥6 mm, tall cell variant of PTC, extrathyroidal extension, and angioinvasion. Conversely, autoimmune thyroiditis was found as a protective factor for lymph node metastasis. A subgroup of patients, with nodule size ≤ 5 mm, presented non-aggressive features.Conclusion: The incidence of lymph node metastasis in PTMC is considerable; the size of the tumor appears to be the most significant predictive factor for lymph node metastasis. The traditional cut-off value used for definition of microcarcinoma could be reconsidered to identify patients with an indolent course of the tumor, where active surveillance could be the appropriate treatment, and on the other hand, patients with potentially aggressive tumors requiring an adequate surgical intervention.Clinical Trial Registration: The trial was registered at ClinicalTrials.gov (ID: NCT04274829).

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

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

Clinical relevance of high–intermediate risk endometrial cancer according to European risk classification

ObjectiveRisk models in endometrial cancer define prognosis and indicate adjuvant therapy. One of the currently used classifications was designed in 2016 in collaboration with the European Society of Medical Oncology...

Diffusion-Weighted MRI Predicts Lymph Node Metastasis and Tumor Aggressiveness in Resectable Pancreatic Neuroendocrine Tumors.

The aim of this study was to identify whether diffusion-weighted magnetic resonance imaging (DW-MRI) can predict the malignant behavior of preoperative well-differentiated pancreatic neuroendocrine tumors (PanNETs). Forty patients with PanNETs who underwent pancreatectomy were enrolled in this study. The apparent diffusion coefficient (ADC) values were measured. Clinicopathological factors were compared in patients with high ADC and low ADC values and in patients with and without lymph node metastasis (LNM). The low ADC group was significantly associated with higher Ki-67 index, higher mitotic count, larger tumor size, higher rate of LNM, and venous invasion. In patients with low ADC values, the incidence of LNMs was 33.3%. In patients with high ADC values, there were no patients with LNM being 0%. A significant negative correlation was found between the mean ADC values and the Ki-67 index and between the mean ADC values and the mitotic count. In multivariate analysis, neural invasion and mean ADC values ≤ 1458 were independent predictors of LNM. ADC values obtained using DW-MRI in the preoperative assessment of patients with PanNETs might be a useful predictor of malignant potential, especially LNM.

Incidence of lymph node metastasis at each station in Siewert types Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction: A systematic review and meta-analysis

The optimal extent of lymphadenectomy for adenocarcinoma of the esophagogastric junction (AEG) has been continuously debatable. The study aimed to determine the incidence of lymph node metastasis at each station in Siewert types Ⅱ/Ⅲ AEG. PubMed was searched and publications reporting metastasis at each nodal station were eligible. Meta-analysis was performed using RevMan 5.3. Twenty-one studies involving 4662 patients were included. The incidence of lymph node metastasis was high (≥20%) in stations No. 3, 1, 2 and 7 in decreasing order, and moderate (10–20%) in stations No. 9, 19 and 110. The incidence did not exceed 10% in stations No. 10, 11p, 20, 8a, 4sa, 4 s b and 4d, was less than 5% in stations No. 5, 6, 11d, 12a, and even close to 0 in stations No. 107, 111 and 112. Compared with type Ⅲ tumors, type Ⅱ tumors had significantly lower incidence in some abdominal stations including No. 3, 4sa, 4 s b, 6, 8a and 10, while significantly higher in the lower mediastinal stations. The present analysis established a map of lymph node metastasis in Siewert types Ⅱ/Ⅲ AEG, which may serve as a valuable reference for the extent of lymphadenectomy.

Long noncoding RNA CBR3 antisense RNA 1 promotes the aggressive phenotypes of non‑small‑cell lung cancer by sponging microRNA‑509‑3p and competitively upregulating HDAC9 expression.

Long noncoding RNA CBR3 antisense RNA 1 (CBR3-AS1) plays significant roles in the initiation and progression of osteosarcoma. The aim of the present study was to investigate the involvement of CBR3-AS1 in the development of non-small cell lung cancer (NSCLC). Reverse transcription-quantitative PCR was performed to detect CBR3-AS1 expression in NSCLC tissues and cell lines. The impacts of CBR3-AS1 on cellular proliferation, apoptosis, migration and invasiveness in vitro, and tumor growth in vivo, were investigated using the Cell Counting Kit-8 assay, flow cytometry, Transwell migration and invasion assays, and tumor xenograft model-based analysis, respectively. The results indicated that CBR3-AS1 was markedly upregulated in NSCLC tissues and cell lines. High CBR3-AS1 expression was correlated with larger tumor size, advanced TNM stage, increased incidence of lymph node metastasis and shorter overall survival times in patients with NSCLC. Furthermore, CBR3-AS1-knockdown notably suppressed cellular proliferation, migration and invasiveness in vitro, and also promoted apoptosis and suppressed tumorigenicity in vivo. Mechanistic investigation demonstrated that CBR3-AS1 functions as a competing endogenous RNA for microRNA-509-3p (miR-509-3p) in NSCLC cells. Furthermore, miR-509-3p exerted tumor-suppressive effects in NSCLC, and histone deacetylase 9 (HDAC9) was identified as a direct target of miR-509-3p. HDAC9 expression was suppressed by CBR3-AS1 depletion, which was abolished by miR-509-3p inhibition. Further rescue experiments revealed that increasing the output of the miR-509-3p/HDAC9 axis counteracted the CBR3-AS1 depletion-induced inhibitory effects on NSCLC cells. Collectively, the results of the present study indicate that the CBR3-AS1/miR-509-3p/HDAC9 pathway exerts tumor-promoting actions in NSCLC oncogenesis and progression, suggesting that this pathway is an effective target for the management of NSCLC.

Malic Enzyme 1 Indicates Worse Prognosis in Breast Cancer and Promotes Metastasis by Manipulating Reactive Oxygen Species.

PurposeMalic enzyme 1 (ME1) catalyzes malate to pyruvate and thus promotes glycolysis. Its function in breast cancer remains to be fully clarified. The aim of this work was to investigate the prognostic value of ME1 and its possible mechanism in breast cancer.MethodsWe evaluated ME1 expression in 220 early breast cancer patients with tissue microarray-based immunohistochemistry and explored the relationships between ME1 expression and clinicopathological features. Survival analyses were further performed to determine its prognostic value. The public database was used to confirm tissue microarray results. Further, cell proliferation, migration, invasion ability and reactive oxygen species (ROS) were examined in breast cancer cells.ResultsIn breast cancer tissues, high ME1 expression was significantly associated with larger tumor size, higher incidence of lymph node metastasis and higher incidence of lymph-vascular invasion. High ME1 expression significantly correlated with worse recurrence-free survival (RFS), and was an independent prognostic factor for RFS, which was confirmed by mRNA results in the public database. In vitro, upregulation of ME1 by transfecting MCF-7 cells with virus vector remarkably enhanced viability, motility and epithelial–mesenchymal transition (EMT) and decreased ROS levels, whereas knockdown in MDA-MB-468 cells produced totally opposite effects as expected. When pretreated with oxidizing agent, MCF-7 cells overexpressing ME1 lost its motility, whereas MDA-MB-468 cells with knockdown of ME1 restored its motility when pretreated with antioxidant.ConclusionTo our knowledge, these clinical and experiment works first suggested that ME1 may be a novel biomarker and potential therapeutic target for breast cancer metastasis, and its biological effect is mainly controlled by manipulating ROS.

Tumour radiological appearance evaluated by enhanced CT correlates with tumour progression and survival in curable gallbladder cancer

BackgroundSurgical resection has been proposed for curable gallbladder cancer (GBCA); however, optimal preoperative evaluation and resection planning methods remain unestablished. The aim of this study was to establish the types of CT tumour radiological appearances in GBCA with a focus on its association with clinicopathologic features and its prognostic impact in curable GBCA. MethodsIn all, 118 patients surgically treated for GBCA were identified and CT tumour radiological appearances were reviewed. Models were established and internally validated. Clinicopathologic variables and prognostic impact were analysed for correlation with tumour radiological appearance. ResultsThe classification and distribution of tumour radiological appearance in these patients was Type 1 (n = 14), Type 2 (n = 60), Type 3 (n = 21), Type 4 (n = 18), and undetermined (n = 5). Among the 113 patients, a higher tendency of T stage and incidence of lymph node metastasis was observed from Type 1 to Type 4. Most Type 1 patients were T1 stage, they have no lymph node involvement or recurrence. With a median follow-up of 25 months (range, 1–135 months), a clear prognostic difference was observed among the 4 types after surgical treatment (p < 0.001). Type 1 patients showed 100% 5-year survival rate. Among the 66 T2 tumours, both tumour location and tumour radiological appearance effectively stratified patient prognosis (p < 0.001, p = 0.007). Introducing tumour radiological appearance into tumour location enabled further prognostic stratification of the 35 T2h tumours (p < 0.001). ConclusionsType of CT tumour radiological appearance is a predictor of tumour biology. It may improve preoperative evaluation and resection planning.

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

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