Absence Of Lymph Node Metastasis Research Articles

The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma.

BackgroundInflammation plays an important albeit dual role in carcinogenesis. Survival studies have highlighted the prognostic significance of peritumorous inflammation. Currently, the theoretical background allows inflammation, epithelial mesenchymal transition (EMT) and the closely associated stem cell differentiation in colorectal carcinoma (CRC) to be linked. However, there is scarce direct morphological evidence.Purpose and methodsThe aim of our study was to investigate the role of inflammation in cancer growth and invasion by analyzing the association between inflammation and known morphological prognostic features of colorectal cancer, EMT, stemness and mismatch repair (MMR) protein expression. The study was designed as a retrospective morphological and immunohistochemical assessment of 553 consecutive cases of surgically treated primary CRC.ResultsThere were statistically significant associations between high-grade inflammation and lower pT (p = 0.002), absence of lymph node metastases (p < 0.001) and less frequent lymphatic (p = 0.003), venous (p = 0.017), arterial (p = 0.012), perineural (p = 0.001) and intraneural (p = 0.01) invasion. In contrast, Crohn’s like reaction (CLR) by density of lymphoid follicles in the invasive front lacked significant differences in regard to pT, pN, tumor invasion into surrounding structures (blood or lymphatic vessels, nerves), grade or necrosis (all p > 0.05). The expression of E-cadherin, CD44 and MMR proteins yielded no statistically significant associations with peritumorous inflammation by Klintrup-Mäkinen score or the density of lymphoid follicles. Nevertheless, E-cadherin levels were significantly associated with the density of eosinophils (p = 0.007).ConclusionHigh-grade peritumorous inflammation is associated with beneficial morphologic CRC features, including less frequent manifestations of invasion, and is not secondary to tissue damage and necrosis. CLR is not associated with cancer spread by pTN; this finding indirectly suggests an independent role of CLR in carcinogenesis. Further, inflammation by Klintrup-Mäkinen grade and CLR is not dependent on epithelial-mesenchymal transition and stem cell differentiation. Our study highlights the complex associations between inflammation, tumor morphology, EMT, stemness and MMR protein expression in human CRC tissues.

NOX4 overexpression is a poor prognostic factor in patients undergoing curative esophagectomy for esophageal squamous cell carcinoma

BackgroundNox4 has been associated with tumor progression in various types of malignancies. This study aimed to evaluate the importance of the expression of Nox4 in patients undergoing curative esophagectomy for esophageal squamous cell carcinoma. MethodsWe reviewed retrospectively 121 patients with esophageal squamous cell carcinoma who had undergone a curative esophagectomy, including 67 patients with overexpression and 54 patients with low expression of Nox4 as evaluated by immunohistochemical analysis. In addition, 2 esophageal squamous cell carcinoma cell lines, TE11 and KYSE270, were treated with the Nox4 inhibitor GKT-137831 to explore the expression of Nox4, cell proliferative activity, and selected downstream pathways in these esophageal squamous cell carcinoma cell lines by Western blot analysis. ResultsUnivariate analysis showed that T1-2 status, absence of nodal metastasis, and low Nox4 expression were associated with greater disease-free survival (P = .001) and overall survival (P < .001), and Nox4 overexpression was an independent prognostic factor of worse disease-free survival and overall survival (P = .013 and P = .007, respectively). The esophageal squamous cell carcinoma cell lines treated with the Nox4 inhibitor GKT-137831 showed decreased cell proliferation in a dose-dependent manner (P < .01). Western blot analysis demonstrated that expression of AKT, phosphorylated AKT, mammalian target of rapamycin, and phosphorylated mammalian target of rapamycin were less in esophageal squamous cell carcinoma cells treated with the Nox4 inhibitor (P < .01). ConclusionThis study suggests that Nox4 overexpression is a poor prognostic factor for patients with esophageal squamous cell carcinoma undergoing curative esophagectomy.

2991 Preoperative Imaging of Gastric Neuroendocrine Tumors and Lymph Node Metastases

INTRODUCTION: In recent years, detection of gastric neuroendocrine tumor (GNET) lymph node (LN) metastasis has become more apparent with innovative imaging such as endoscopic ultrasound and PET. Currently, the National Comprehensive Cancer Network recommends multiphasic CT or MRI as part of the initial workup for GNETS. We sought to evaluate these recommendations with respect to the detection of LN metastases and compare CT to alternative pre-operative modalities for gastric staging at our institution. METHODS: This is a single center retrospective study evaluating consecutive patients who underwent surgical resection or endoscopic submucosal dissection of biopsy proven GNET from April 1988 to January 2019 at a tertiary referral center. LN metastases were defined by positive nodes following resection. Local invasion was characterized by tumor involvement of any gastric layers beyond the mucosa. Regional metastases included perigastric (gastroduodenal, gastrohepatic, gastroepiploic, pyloric, pancreaticoduodenal), celiac, and peripancreatic LN abnormalities. Distant metastases were defined as involving another solid organ, retroperitoneal or distant LN. Imaging modalities included endoscopic ultrasound, CT, MRI, and PET. RESULTS: Thirty patients were included in the study with each patient's respective GNET imaging in Table 1. Mean age of diagnosis was 63.9 ± 12.3 years old. There were no type 2 NET's identified based on documented history. Twenty patients underwent CT, and 13 of these patients underwent additional imaging or preop staging (EUS, PET, MRI, Octreotide, pre-op surgical biopsy). Of those undergoing CT, 12.5% of patients were identified as having regional or distant metastases; however, when correlating CT findings in patients with LN pathology, no patients were correctly identified as having positive LN's (Table 2). Conversely, patients with regional LN metastases on biopsy had CT's showing no lymphadenopathy or local metastases. CONCLUSION: As in most cancers, successful interventions vary according to presence or absence of LN metastases. Despite a limited number of patients in this study who had true LN metastases resected, CT and alternative modalities appeared comparable in their ability to “rule out” LN metastases for GNET. Of some concern, none of the imaging appeared sensitive for GNET LN metastases. Investigation of imaging modalities more sensitive for GNET LN metastases, such as PET Dotatate, is needed to better inform decisions regarding medical and surgical intervention.

The binary presence or absence of lymph node metastasis or extrathyroidal extension is not associated with survival in papillary thyroid cancers: Implications for staging systems

BackgroundThe characteristics of diagnosed papillary thyroid cancer (PTC) have changed over time with the increasing trend of early diagnosis, and the survival impact of conventional prognostic factors such as lymph node metastasis (LNM) and extrathyroidal extension (ETE) is controversial. We investigated PTC prognostic factors for overall survival (OS) and disease specific survival (DSS), focusing on LNM, ETE, and their implications for PTC staging systems. MethodsWe assessed prognostic factors for OS and DSS in a nationwide sample of Korean PTC patients (N = 5192, median follow-up 121 months) using Cox regression. The binary presence or absence of LNM and ETE, as well as other measures of LNM and ETE, were examined for their survival impact. We also evaluated the relative performance of PTC staging systems before and after revising the staging criteria for LNM and ETE. ResultsThe binary presence of LNM or ETE was not a prognostic factor for OS or DSS, nor were other various measures of LNM. However, the extent of ETE as none, microscopic, or gross independently influenced survival (OS hazard ratio for gross vs. none: 3.28, 95% confidence interval (CI) 1.97–5.46; DSS hazard ratio for gross vs. none: 3.75, 95% CI 1.59–8.81). The performance of PTC staging systems improved when the extent of ETE and/or location of LNM were used as staging components. ConclusionThe extent of ETE and/or location of LNM may be better survival indicators than their binary presence or absence, and we propose staging criteria revisions to pertinent staging systems to better reflect the contemporary PTC population.

Lesion Detection and Interobserver Agreement with Advanced Image Reconstruction for 18F-DCFPyL PET/CT in Patients with Biochemically Recurrent Prostate Cancer.

Biochemically recurrent prostate cancer (BCR) is the main indication to perform prostate-specific membrane antigen PET/CT. However, localizing BCR with prostate-specific membrane antigen PET/CT remains challenging in patients with low prostate-specific antigen (PSA) values. Here, we studied the impact of advanced PET image reconstruction methods on BCR localization and interobserver agreement with 18F-DCFPyL PET/CT scans in patients with BCR and low PSA values. Methods: Twenty-four patients with BCR and a PSA level of less than 2.0 ng/mL were included. PET images were reconstructed with 4-mm voxels and 2-mm voxels, both with and without point-spread function. All scans were interpreted by 4 nuclear medicine physicians. Additionally, PET examinations of 5 patients with primary prostate cancer and confirmed absence of lymph node metastases (after lymph node dissection) were included, to assess the risk of introducing false-positive findings when using advanced reconstruction. Calculation of BCR localization rates (scan positivity) was based on consensus among our readers (≥3 readers regarding a scan positive for BCR), as well as the individual scan interpretations of the readers. Results: In the consensus analysis, BCR localization rates were not higher using advanced reconstruction (62.5%-66.7%) than using 4-mm reconstruction (62.5%). On the basis of individual readings, however, more scans were positive using 2-mm reconstruction (74.0%; 95% confidence interval [CI], 65.0%-82.9%) (P = 0.027) and 2-mm reconstruction with point-spread function (75.0%; 95% CI, 66.2%-83.8%) (P = 0.014) than 4-mm reconstruction (65.6%; 95% CI, 56.0%-75.3%). A higher number of lesions was detected on the 2-mm scans (median, 2 lesions; interquartile range, 1-3) than the 4-mm scans (median, 1; interquartile range, 0-3; P = 0.008). The advanced reconstruction methods did not increase interobserver agreement (80.6%-84.7%), compared with the 4-mm scans (75.7%, P = 0.08-0.25). In the patients with primary prostate cancer, an equal number of false-positive lesions was observed among the different reconstruction methods (overall, n = 13). Conclusion: Applying advanced image reconstruction for 18F-DCFPyL PET/CT scans did not increase BCR localization in patients with BCR and low PSA values (reader consensus). Yet, the increased number of positive individual readings may imply that further development of image reconstruction methods holds potential to improve BCR localization. No improved interobserver agreement was observed with advanced reconstruction compared with standard 4-mm reconstruction.

Clinicopathological features and survival for gallbladder NEN: a population-based study.

PurposeGallbladder neuroendocrine neoplasm (GB-NEN) is a relatively rare neoplasm, accounting for 0.5% of all neuroendocrine neoplasm cases and 2.1% of gallbladder cancers. Because of the limited understanding of GB-NEN, the aim of this study was to explore the clinicopathology and survival of GB-NEN patients selected from the Surveillance, Epidemiology, and End Results (SEER) database.MethodsA total of 248 GB-NEN patients from the SEER database diagnosed between 2004 and 2015 were included. Kaplan–Meier curves were used to examine the survival time. Multivariate Cox proportional hazard models were used to estimate hazard ratios with 95% confidence intervals to analyze the impact of factors on overall survival and cancer-specific survival.ResultsThe majority of the GB-NEN patients were women (67.3%), white (77%), and married (61.7%). Most tumors were <2 cm in size (31.0%), G3 stage (25.8%), and distant SEER stage (41.1%). 62.9% and 64.5% of cases showed an absence of lymph node metastasis and tumor metastasis, respectively. Patients who received gallbladder surgery had significantly better survival outcomes (P < 0.001). However, patients who received both gallbladder surgery and lymph node resection did not have better survival outcome compared with patients who received only gallbladder surgery. Multivariate Cox proportional hazard models indicated that older age, unmarried status, large tumor size (>5 cm), and distant SEER stage were significant independent predictors for decreased overall survival time and cancer-specific survival time (P < 0.05).ConclusionAge, marital status, tumor size, and SEER stage were predictors for the survival of GB-NEN patients. Gallbladder surgery was associated with better survival, but the combination of gallbladder surgery and lymphadenectomy had no effect on survival outcomes.

A simple scoring system to determine axillary lymph node metastasis in carcinoma breast

Background: The aim of this study is to develop a scoring system wherein axillary lymph node metastasis in carcinoma breast can be predicted preoperatively using simple variables.Methods: A prospective study carried out from December 2017-November 2018 at Rajarajeswari Medical College and Hospital. All clinically node negative cases were included. Data from clinical examination, histopathology report and immunohistochemistry (obtained from trucut biopsy preoperatively) is correlated with presence or absence of lymph node metastasis obtained after modified radical mastectomy. And a scoring system is proposed according to the results obtained. Results: Out of 36 cases studied, 12 cases had score &lt;10, 11 cases had score 11-13, 13 cases had score &gt;14, indicating that more than 50% of cases were over treated with axillary lymph node dissection.Conclusions: Lymph node metastasis in carcinoma breast can be predicted clinically using a scoring system. Further a recommendation for or against axillary node dissection can be made according to the respective scores.

Proportion and role of CD45+ erythroid progenitor cells in patients with tongue cancer metastasis

Objective: To investigate the proportion and role of CD45+ erythroid progenitor cells (EPC) in patients with tongue cancer metastasis. Methods: The initial treatment of tongue cancer patients (n=40) from January 2017 to June 2018 in He'nan Provincial People's Hospital was included in this study. According to the presence or absence of lymph node metastasis, they were divided into tumor group (no lymph node metastasis was found in imaging and pathology) and metastasis group (both imaging and pathology confirmed lymph node metastasis). The expression of Ki-67 was detected by immunohistochemistry and the proportion of CD45+CD71+TER119+EPC was detected by flow cytometry. EPC was sorted by flow cytometry, interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) were detected by enzyme-linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) was detected by flow cytometry. Transwell was used for tumor invasion test; methyl thiazolyltetrazolium (MTT) assay was used to detect proliferation level. Results: There were 20 cases in the tumor group and metastasis group. There was no significant difference between the two groups in terms of age, sex, time of onset and size of tumors. Flow cytometry showed that the ratio of CD45+EPC in peripheral blood of tumor group and metastasis group was (1.2±0.2)% and (3.1±0.2)% (t=7.823, P<0.001). Correlation analysis showed that the ratio of CD45+EPC was positively correlated with the proliferation index of Ki-67 cells (r=0.592, P=0.006). The results of flow cytometry showed that the mean fluorescence intensity (MFI) of ROS in EPC was 102.1±22.9 in tumor group and 530.0±67.2 in metastasis group (t=6.025,P<0.001). The results of ELISA showed that the mass concentrations of IL-10 and TGF-β in EPC supernatant of tumor group were (10.8±1.6) and (3.2±0.8) μg/L, respectively. The mass concentrations of IL-10 and TGF-beta in EPC supernatant of metastasis group were (26.9±3.7) and (6.4±0.9) μg/L, respectively (t=3.956, P=0.003; t=2.595, P=0.027). Transwell results showed that the proportion of invasive cells in the CD45+EPC group [(40.3±4.4)%] was higher than that in the control group [(17.5±2.2)%] (t=4.607, P=0.001). MTT proliferation experiment showed that the proliferation rate of the CD45+EPC group [(52.0±3.3)%] was higher than that of the control group [(30.5±1.9)%] (t=5.656, P<0.001). Conclusions: The proportion of CD45+EPC in patients with tongue cancer metastasis is significantly increased. CD45+EPC can promote the proliferation and metastasis of tongue cancer by secreting immunosuppressive molecules and ROS.

Prognostic Value of Programed Cell Death-1 Ligand Expression in Colorectal Cancer and Its Correlation with Cytotoxic Tumor-Infiltrating Lymphocytes

Background: colorectal cancer (CRC) is a major cause of cancer-related death worldwide. In recent years, targeting the programed cell death (PD-1)/ programed cell death-1 ligand (PD-L1) immune checkpoint signaling has been tested as a novel promising treatment strategy in several tumors. Aim of the work: the present study aimed to examine expression of PD-L1 and CD 8+ T cells in CRC and to evaluate the relationship between their expressions and the different clinicopathological features. Material and methods: expression of PD-L1 in tumor cells (TC) as well as in tumor infiltrating immune cells (TIMC) was separately evaluated in 85 cases of CRC by the immunohistochemistry, in addition, CD8+ T cell count was assessed. Results: 12.9 % of cases showed PD-L1 expression in TC while, 28.2% showed PD-L1expression in TIMC. PD-L1 expression in TC was significantly associated with higher tumor grade (P =0.001), lymph node metastasis (LNM) (P =0.006) and lymphovascular invasion (LVI) (P > 0.001). On the other hand, PDL-1 expression in TIMC was significantly associated with low tumor grade (P=0.016), negative LVI (P = 0.004), high tumor infiltrating lymphocytes (TILs) count (P <0.0001), as well as high CD8+ T cells count (P = 0.002). High intra CD8-positive T cells was significantly associated with absence of LNM (P =0.013) and negative LVI (P =0.035). Conclusion: these findings indicated that expression of PD-L1 can be used as a new biomarker to predict the prognosis of colon cancer and may provide a clue for immunotherapy in the adjuvant treatment of CRC patients.

Predicting systemic spread in early colorectal cancer: Can we do better?

Through the implementation of national bowel cancer screening programmes we have seen a three-fold increase in early pT1 colorectal cancers, but how these lesions should be managed is currently unclear. Local excision can be an attractive option, especially for fragile patients with multiple comorbidities, but it is only safe from an oncological point of view in the absence of lymph node metastasis. Patient risk stratification through careful analysis of histopathological features in local excision or polypectomy specimens should be performed according to national guidelines to avoid under- or over-treatment. Currently national guidelines vary in their recommendations as to which factors should be routinely reported and there is no established multivariate risk stratification model to determine which patients should be offered major resectional surgery. Conventional histopathological parameters such as tumour grading or lymphovascular invasion have been shown to be predictive of lymph node metastasis in a number of studies but the inter- and intra-observer variation in reporting is high. Newer parameters including tumour budding and poorly differentiated clusters have been shown to have great potential, but again some improvement in the inter-observer variation is required. With the implementation of digital pathology into clinical practice, quantitative parameters like depth/area of submucosal invasion and proportion of stroma can be routinely assessed. In this review we present the various histopathological risk factors for predicting systemic spread in pT1 colorectal cancer and introduce potential novel quantitative variables and multivariable risk models that could be used to better define the optimal treatment of this increasingly common disease.

Circulating adipokines and metabolic setting in differentiated thyroid cancer.

The associative link relating insulin resistance (IR) and adipokines to the occurrence and phenotype of differentiated thyroid cancer (DTC) is unknown. The aim of this study was to evaluate the relationship between IR and adipokines in DTC patients, as compared with carriers of benign thyroid diseases (BTD) and healthy controls. This observational study enrolled 77 subjects phenotyped as DTC (N = 30), BTD (N = 27) and healthy subjects (N = 20). Each subject underwent preoperative analysis of anthropometric parameters, thyroid function and autoimmunity, insulin resistance (HOMA-IR) and levels of unacylated (UAG) and acylated ghrelin (AG), obestatin, leptin and adiponectin. Multivariate regression models were used to test the predictive role of metabolic correlates on thyroid phenotypes and DTC extension. The three groups showed similar age, gender distribution, smoking habit, BMI and thyroid parameters. Obestatin was significantly higher in DTC group compared to BTD (P < 0.05) and control subjects (P < 0.0001). DTC and BTD groups showed higher levels of UAG (P < 0.01) and AG (P < 0.05). Leptin levels were comparable between groups, whereas adiponectin levels were lower in DTC compared to BTD group (P < 0.0001) and controls (P < 0.01). In parallel, HOMA-IR was higher in DTC than BTD (P < 0.05) and control group (P < 0.01). Stepwise multivariable regression analysis showed that obestatin and UAG were independent predictors of DTC (P = 0.01 for both). In an analysis restricted to the DTC group, obestatin levels were associated with the absence of lymph node metastases (P < 0.05). Our results highlight a potential association between metabolic setting, circulating adipokines and thyroid cancer phenotype.

Prognostic value of tumor deposits for disease free survival in patients with stage III colon cancer: A post hoc analysis of IDEA France phase III trial (PRODIGE-GERCOR).

3519 Background: Tumor deposits (TDs) are isolated tumor foci in the pericolic, perirectal or mesocolic fat without residual lymph node (LN) tissue. TDs seem to impact the prognosis of stage III colon cancer (CC) patients (pts) but are only considered in TNM staging in the absence of LN metastases (LNM). We aimed at evaluating the prognosis value for disease free survival (DFS)of TDs in International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France phase III study (NCT00958737) that compared 3 versus 6 months of adjuvant FOLFOX or CAPOX for stage III CC pts. Methods: All pathological reports of pts included in IDEA France trial were retrospectively analyzed. DFS according to the presence or absence of TDs was evaluated using Kaplan-Meier estimator. Multivariable Cox model analysis was performed to evaluate the association between TDs and DFS. This analysis did not included immunohistochemical biomarkers. Results: Among the 2022 pts included in IDEA France study, 1942 (96%) were analyzed. 80 pts were excluded: no pathological report (n = 68), pts without treatment (n = 12). TDs were found in 184 pts (9.47%), of whom 74 with N1a/b (40%), 55 with N1c (30%) and 55 with N2 LN stage (30%). All characteristics were similar according to the presence of TDs, except for tumor/node (TN) stage (T4 and/or N2 are more frequent in pts with TDs; p = .0046). The 3-year DFS rates were 65.59% [95% confidence interval (95%CI) 58.04-72.12] and 74.71% [95%CI 72.57-76.71] for pts with and without TDs, respectively (p = 0.0079). In multivariable analysis, TDs were associated with higher risk of recurrence or death (hazard ratio (HR) = 1.36, 95%CI 1.05-1.75, p = .0201), as well as T4 and/or N2 (HR = 2.21, 95%CI 1.03-1.59, p &lt; .001), 3 months of adjuvant treatment (HR = 1.29, 95%CI 1.09-1.52, p = .0029), obstruction (HR = 1.28, 95%CI 1.03-1.59, p = .0233) and male (HR = 1.24, 95%CI 1.04-1.46, p = .0151). Adding TDs count to the LNM count, 35 out of 1454 N1a/b/c CC pts (2.4%) were reclassified as N2 and experienced worse 3 years DFS than confirmed N1 CC pts (p = .0151). Conclusions: TD is an independent and valuable prognostic factor for DFSin stage III CC pts and should be considered whatever the LNM status.

Prediction of lymph-node metastasis and lymphatic invasion of superficial pharyngeal cancer on narrow band imaging with magnifying endoscopy

ObjectiveWe studied factors related to lymphatic invasion and lymph-node metastasis in patients with superficial pharyngeal cancer who underwent transoral surgery. MethodsThe study group comprised 67 patients with superficial pharyngeal cancer (92 lesions) in whom squamous cell carcinoma was histopathologically diagnosed. The primary endpoint was clinicopathological findings according to the presence or absence of lymph-node metastasis, lymphatic invasion, or both. The secondary endpoints were (1) endoscopic findings according to the presence or absence of subepithelial invasion and (2) tumor thickness according to the endoscopic findings. ResultsLymph-node metastasis, lymphatic invasion, or both were related to the white light findings of the main macroscopic type (p = 0.006), the NBI magnifying endoscopy findings of the classification of type B vessels (p = 0.005) and avascular area (AVA) (p = 0.003), and the histopathological findings of subepithelial invasion (p = 0.027), solitary nests (p = 0.013), venous invasion (p = 0.003), and tumor thickness (p = 0.028). The white light findings of white coat (p = 0.027), main macroscopic type (p = 0.005), and protruding type (p = 0.027) and the NBI magnifying endoscopy findings of the classification of type B vessels (p = 0.0002) were significantly related to subepithelial invasion. Tumor thickness was significantly related to the white light findings of white coat (p = 0.0002), main macroscopic type (p < 0.0001), protruding type (p < 0.0001), and mixed type (p = 0.017) and the NBI magnifying endoscopy findings of the classification of type B vessels (p < 0.0001) and AVA (p = 0.005). ConclusionDetailed assessment by means of NBI magnifying endoscopy at the time of transoral surgery may contribute to the prediction of lymphatic invasion and lymph-node metastasis in patients with superficial pharyngeal cancer.

Study of expression levels and clinical significance of miR-503 and miR-375 in patients with esophageal squamous cell carcinoma.

This study aims to investigate the expression levels and clinical significance of miR-503 and miR-375 in patients with esophageal squamous cell carcinoma. 40 cases of cancer tissues and adjacent tissues in patients with esophageal squamous cell carcinoma were collected from March 2017 to September 2017 in the Department of Gastroenterology in the First Affiliated Hospital of Henan Polytechnic University. qRT-PCR was used to analyze the expressions of miR-503 and miR-375 in cancer tissues and adjacent normal tissues. The association between their expressions and the gender, age, degree of tumor differentiation, TNM staging, presence or absence of lymph node metastasis, and other clinicopathological characteristics of patients with esophageal squamous cell carcinoma was analyzed. The results showed that the expression level of miR-503 in esophageal squamous cell carcinoma tissues (6.83±2.14) was significantly higher than that in adjacent tissues (2.45±1.13). The expression level of miR-375 in esophageal squamous cell carcinoma tissues (3.75±1.06) was significantly lower than that in adjacent tissues (7.45±1.13). The expression levels of miR-503 and miR-375 in esophageal squamous cell carcinoma were related to the existence of lymph node metastasis, degree of differentiation of esophageal squamous cell carcinoma and TNM staging (p<0.001). There was no correlation between the expressions of miR-503 and miR-375 and the age, gender and tumor size of patients (p>0.05). miR-503 was highly expressed in esophageal squamous cell carcinoma and miR-375 was lowly expressed in esophageal squamous cell carcinoma. miR-503 and miR-375 were closely related to the lymphatic metastasis, degree of differentiation and TNM staging of the tumor.

Cure and survival of sporadic medullary thyroid carcinoma following systematic preoperative calcitonin screening.

The improvement in outcome of sporadic medullary thyroid carcinoma (MTC) during the last decades remains controversial, even if a trend toward a better prognosis has been recently proposed. This study was aimed to determine the time trend cure and survival rates in sporadic MTC according to the use of systematic preoperative calcitonin screening. Retrospective analysis of 178 sporadic MTC patients operated between 1980 and 2017 was performed. The impact of prognostic factors on cure and survival following the introduction of routine preoperative calcitonin screening in 2001 was evaluated according to the year of surgery. Since 2001, a significant decline of node-positive tumors (from 56.1 to 34.7%) and advanced stage at diagnosis (stage III/IV from 56.1 to 34.7%) occurred, with a concomitant significant increase in cure rate (64.5% vs 38.6%; p = 0.0012) and survival (p < 0.05). At univariate analysis, the cure was achieved more frequently in more recently operated patients (64.5% vs 38.6%; p = 0.0012), in disease staging I/II (86.5% vs 13.5%; p < 0.0001), in patients undergoing preoperative calcitonin screening (63.8% vs 23.5%; p < 0.0001) and in the absence of lymph node metastases (86.5% vs 13.5%; p < 0.0001). At multivariate analysis, only preoperative calcitonin screening and stage at diagnosis turned out to be significant independent prognostic factors for cure and survival. The outcome of sporadic MTC improved in the new millennium; diagnosis was achieved earlier, at a less advanced stage. Routine preoperative calcitonin screening may have contributed to improve cure and survival rates.

Correlations of Twist Expression with Pathological and Computed Tomography (CT) Characteristics and Prognosis of Non-Small Cell Lung Cancer (NSCLC).

BackgroundThe aim of this study was to assess the correlations of Twist expression with pathological and computed tomography (CT) characteristics and prognosis of non-small cell lung cancer (NSCLC).Material/MethodsWe enrolled 120 patients with lung cancer who underwent CT examination. The Twist protein expression level was detected in 120 cases of cancer tissues and a control group using immunohistochemical method. The survival curve was plotted using the Kaplan-Meier method and analyzed via log-rank test.ResultsThe Twist expression was associated with tumor stage, differentiation degree, and presence or absence of lymph node metastasis, but had no correlations with sex, age, or histological type. Grade-3 bronchial involvement, pleural indentation, and hilar and mediastinal lymph node enlargement occurred more frequently in the high-expression Twist group compared with the low-expression Twist group. The overall survival rate of patients with Twist overexpression was significantly lower than that of patients with normal Twist expression. The mean survival time was 69.8 months in Twist protein expression-negative patients and 45.8 months in Twist protein expression-positive patients. Finally, the positive expression of Twist protein was significantly correlated with the long-term survival and prognosis of patients.ConclusionsThe Twist gene might be involved in the occurrence and development of NSCLC, which is correlated with patient prognosis.

The expression and clinical significance of miRNA-99a and miRNA-224 in non-small cell lung cancer.

To investigate the expression and clinical significance of miRNA-99a and miRNA-224 in the serum of patients with non-small cell lung cancer (NSCLC). 83 patients with NSCLC, who were diagnosed and treated in our hospital from January 2014 to September 2017, were included in the experiment group. 79 patients, who made health check up, were included in the control group. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) technique was used to test the expressions of miRNA-99a and miRNA-224 in the serum of the patients in the two groups, and the relationship between the expression levels of miRNA-99a and miRNA-224 and the clinicopathological features of the patients with NSCLC was analyzed; the correlation between the expression of miRNA-99a and the expression of miRNA-224 in NSCLC was also analyzed. The expression level of miRNA-99a in the patients with NSCLC was significantly lower than that in the patients in the normal control group; the differences were statistically significant (p<0.001). The expression level of miRNA-224 in the patients with NSCLC was markedly higher than that in the patients in the normal control group; the differences were statistically significant (p<0.001). The expression level of miRNA-99a in the patients with NSCLC was remarkably correlated with pathological stage, the presence or absence of lymph node metastasis and tissue differentiation (p<0.001). The expression level of miRNA-224 in the patients with NSCLC was significantly correlated with pathological stage, the presence or absence of lymph node metastasis and pathological grade (p<0.001). The results of partial correlation analysis showed that the expression levels of miRNA-99a and miRNA-224 were negatively correlated with each other in NSCLC (r=-0.985, p<0.001). MiRNA-99a and miRNA-224 may be involved in the development and progression of NSCLC. MiRNA-99a is associated with NSCLC pathological stage, lymph node metastasis and tissue differentiation, while miRNA-224 is associated with NSCLC pathological stage, lymph node metastasis and pathological grade. MiRNA-99a and miRNA-224 can be used as clinical monitoring indicators for NSCLC.

Travel time to provider is associated with advanced stage at diagnosis among low income head and neck squamous cell carcinoma patients in North Carolina

ObjectiveThere is considerable variation in the travel required for a patient with head and neck squamous cell carcinoma (HNSCC) to receive a diagnosis. The impact of this travel on the late diagnosis of cancer remains unexamined, even though presenting stage is the strongest predictor of mortality. Our aim is to determine whether travel time affects HNSCC stage at diagnosis independently of other risk factors, and whether this association is affected by socioeconomic status. Materials and methodsCases were obtained from the CHANCE database, a population-based case-control study in North Carolina (n = 808). The mean age was 59.6 and 72% were male. Stage at diagnosis was categorized as early (T1-T2) or advanced (T3-T4) T stage and the presence or absence of nodal metastasis. Multivariate logistic regression models were used to estimate odds ratios for stage-at-diagnosis based on travel time, after adjustment for variables including demographics, income, insurance status, alcohol, and tobacco use. ResultsThe adjusted odds ratio (OR) of advanced T-stage at diagnosis was 1.97 for each hour driven (95% CI 1.36–2.87). There was no association with nodal metastases. There was a significant interaction between travel time and income (p = 0.026) with a pattern of higher ORs for increased distance among lower income (<$20,000) patients compared to the ORs for higher income (>$20,000) patients. DiscussionTravel time was an independent contributor to advanced T stage at diagnosis among low income patients. This suggests travel burden may be a barrier to early diagnosis of HNSCC for impoverished patients.

A systemic review and meta-analysis for prognostic values of pretreatment lymphocyte-to-monocyte ratio on gastric cancer

The systemic inflammation plays a crucial role in carcinogenesis and cancer progression. Pretreatment lymphocyte-to-monocyte ratio (LMR) has been suggested to be associated with clinical outcomes in various malignancies. To evaluate the prognostic significance of pretreatment LMR on gastric cancer, we conducted a comprehensive literature search in PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov (Prospero Registration No. CRD42018087263). This meta-analysis included all studies evaluating the prognostic significance of pretreatment LMR on gastric cancer. The main outcome measures included overall survival (OS), progression-free survival (PFS), and the relationship between LMR and clinicopathological features. In total, 11 studies (12 cohorts) enrolling 14,262 patients with gastric cancer were included. The pooled estimates showed that elevated pretreatment LMR was significantly associated with better OS (hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.58–0.83) and better PFS (HR: 0.71, 95% CI: 0.44–0.99). The elevated LMR was also significantly associated with young patients, female, low level of carcinoembryonic antigen (CEA), low level of carbohydrate antigen 19-9 (CA19-9), stage I–II, small tumor size, absence of lymph node metastasis, absence of vascular invasion, and absence of perineural invasion. In conclusion, the elevated pretreatment LMR predicted the better clinical outcomes in patients with gastric cancer.

Evaluation of 18F-FDG PET/CT parameters for reflection of aggressiveness and prediction of prognosis in early-stage cervical cancer.

The aim of this study was to investigate the value of five typical fluorine-18-fluorodeoxyglucose PET/computed tomography (CT) parameters (including SUVmax, SUVmean, SUVpeak, MTV and TLG) in the reflecting aggressiveness and predicting prognosis in patients with early-stage cervical cancer. Our study enrolled 85 primary cervical cancer patients who underwent preoperative fluorine-18-fluorodeoxyglucose PET/CT scans. We investigated the association of five parameters derived from PET/CT with clinicopathological characteristics. Immunohistochemistry was utilized to evaluate the expression of glucose transporter protein-1 (GLUT-1), TP53-induced glycolysis and apoptosis regulator (TIGAR), and vascular endothelial growth factor (VEGF), and the correlation between PET/CT parameters and the expression of GLUT-1, TIGAR, and VEGF was analyzed. In addition, we also investigated the correlation between disease-free survival of cervical cancer patients and PET/CT parameters. The mean peak standardized uptake value (SUV)peak showed significant differences between all three International Federation of Gynecology and Obstetrics stages (P<0.001-0.032). The patients with lymph node metastasis had significantly higher SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) compared with those with the absence of lymph node metastasis (P=0.038, 0.024, and 0.010, respectively). All the five parameters showed an association with tumor size and cervical stromal invasion depth. Immunohistochemistry results indicated that the SUVpeak showed the highest association with the expression of GLUT-1, TIGAR, and VEGF (rs=0.705, P<0.001, rs=-0.466, P<0.001, rs=0.580, P<0.001, respectively) in these five parameters. The survival analysis showed that SUVpeak, MTV, and TLG were correlated with disease-free survival (P=0.042, P<0.001, and P=0.004, respectively). Early-stage cervical cancer with high SUVpeak may reflect more aggressive behavior, and SUVpeak, MTV, and TLG can be used to predict the prognosis of early-stage cervical cancer patients. It may help with the choice of individualized treatment options.