Existence Of Lymph Node Metastasis Research Articles

Premature mortality for patients after completely resected early adenocarcinoma of the esophagus or stomach.

To establish the life expectancy burden of esophago-gastric cancer by analyzing years of life lost (YLL) for a Western patient population after treatment of early esophageal (EAC) or early gastric (GAC) adenocarcinoma. For patients with early EAC or GAC, the short-term prognosis after surgical resection is very good. Little data is available regarding long-term prognosis when compared to the general population. Two hundred and fourteen patients with pT1 EAC (n = 112) or GAC (n = 102) were included in the study. Patients with EAC underwent transthoracic en-bloc esophagectomy; those with GAC had total or subtotal gastrectomy with D2-lymphadenectomy. Surviving patients had a median follow-up of approximately 14 years. YLL was calculated using average life expectancy data from Germany. Patients with EAC were younger (median age 61 years) than those with GAC (66 years) (p = 0.031). The male:female ratio was 10:1 for EAC and 3:2 for GAC (p < 0.001). Multivariate survival analysis showed the age of the patients ≥60 years and the existence of lymph node metastasis was associated with poor prognosis. The median YLL for all patients who died over follow-up was 8.0 years. For patients under 60 years, it was approximately 20 years, and for older patients, approximately 5 years (p < 0.001) without difference in tumor stage between these age cohorts. YLL did not differ for GAC vs. EAC. After surgical resection, the prognostic burden as measured by YLL is relevant for all patients with early esophageal and gastric adenocarcinomas and especially for younger patients. Reasons for YLL need further studies.

Case series of ovarian neuroendocrine carcinoma: overview of clinicopathological features

BackgroundOvarian neuroendocrine carcinoma (O-NEC) is a relatively uncommon neoplasm, and the current knowledge regarding its diagnosis and management is limited. In this series, our objective was to provide an overview of the clinicopathological characteristics of the disease by analyzing clinical case data to establish a theoretical foundation for the diagnosis and management of O-NEC.Case presentationWe included three patients in the present case series, all of whom were diagnosed with primary O-NEC based on pathomorphological observation and immunohistochemistry. Patient 1 was a 62-year-old patient diagnosed with small cell carcinoma (SCC) of the pulmonary type. Post-surgery, the patient was diagnosed with stage II SCC of the ovary and underwent standardized chemotherapy; however, imaging examinations conducted at the 16-month follow-up revealed the existence of lymph node metastasis. Unfortunately, she passed away 21 months after the surgery. The other two patients were diagnosed with carcinoid tumors, one at age 39 and the other at age 71. Post-surgery, patient 2 was diagnosed with a carcinoid in the left ovary, whereas patient 3 was diagnosed with a carcinoid in her right ovary based on clinical evaluation. Neither of the cases received adjuvant therapy following surgery; however, they have both survived for 9 and 10 years, respectively, as of date.ConclusionPrimary O-NECs are rare and of diverse histological types, each of which has its own unique biological features and prognosis. SCC is a neoplasm characterized by high malignancy and a poor prognosis, whereas carcinoid tumors are of lesser malignancy and have a more favorable prognosis.

A Novel Predictive Model of Pathological Lymph Node Metastasis Constructed with Preoperative Independent Predictors in Patients with Renal Cell Carcinoma.

Introduction: Renal cell carcinoma (RCC) is one of the most common urinary tumors. The risk of metastasis for patients with RCC is about 1/3, among which 30−40% have lymph node metastasis, and the existence of lymph node metastasis will greatly reduce the survival rate of patients. However, the necessity of lymph node dissection is still controversial at present. Therefore, a new predictive model is urgently needed to judge the risk of lymph node metastasis and guide clinical decision making before operation. Method: We retrospectively collected the data of 189 patients who underwent retroperitoneal lymph node dissection or enlarged lymph node resection due to suspected lymph node metastasis or enlarged lymph nodes found during an operation in Tongji Hospital from January 2016 to October 2021. Univariate and multivariate logistic regression and least absolute shrinkage and selection operator (lasso) regression analyses were used to identify preoperative predictors of pathological lymph node positivity. A nomogram was established to predict the probability of lymph node metastasis in patients with RCC before surgery according to the above independent predictors, and its efficacy was evaluated with a calibration curve and a DCA analysis. Result: Among the 189 patients, 54 (28.60%) were pN1 patients, and 135 (71.40%) were pN0 patients. Three independent impact factors were, finally, identified, which were the following: age (OR = 0.3769, 95% CI = 0.1864−0.7622, p < 0.01), lymph node size according to pre-operative imaging (10−20 mm: OR = 15.0040, 95% CI = 1.5666−143.7000, p < 0.05; >20 mm: OR = 4.4013, 95% CI = 1.4892−7.3134, p < 0.01) and clinical T stage (cT1−2 vs. cT3−4) (OR = 3.1641, 95% CI = 1.0336−9.6860, p < 0.05). The calibration curve and DCA (Decision Curve Analysis) showed the nomogram of this predictive model had good fitting. Conclusions: Low age, large lymph node size in pre-operative imaging and high clinical T stage can be used as independent predictive factors of pathological lymph node metastasis in patients with RCC. Our predictive nomogram using these factors exhibited excellent discrimination and calibration.

Indocyanine green-guided sentinel lymph node mapping during laparoscopic surgery with vaginal cuff closure but no uterine manipulator for cervical cancer.

Lymph node metastasis is a critical prognostic factor in cervical cancer. Considering the potential complications of lymphadenectomy and desirability of avoiding systemic lymphadenectomy, accurate intraoperative prediction of the existence of lymph node metastasis is important in patients undergoing surgery for cervical cancer. We evaluated the feasibility and value of indocyanine green (ICG) use for sentinel lymph node (SLN) mapping during laparoscopic surgery performed for cervical cancer. This single-center cohort study included 77 patients undergoing a new laparoscopic radical surgery method with pelvic lymphadenectomy for early-stage cervical cancer. The surgery, performed without using a uterine manipulator, included creation of a vaginal cuff. Bilateral ICG-guided SLN mapping and rapid histopathological examination were performed, and results were analyzed in relation to final histopathologic diagnoses. The SLN pelvic side-specific detection rate was 93.5%, sensitivity (SLN-positive cases/SLN-detected pelvic lymph node-positive cases) was 100%, intraoperative negative predictive value (NPV) was 97.8%, and final pathological NPV was 100%. The detection rate was significantly lower for tumors ≥ 2cm in diameter than for tumors < 2cm in diameter. Micrometastases were missed by intraoperative examination in 3 cases. The high NPV suggests the feasibility and usefulness of ICG-based SLN mapping plus rapid intraoperative examination for identification of metastatic SLNs. Use of ICG-based mapping for intraoperative identification of SLNs in patients undergoing this new laparoscopic surgery method for early-stage cervical cancer was particularly effective for tumors < 2cm in diameter. However, incorporating a search for micrometastases into rapid intraoperative histopathologic examination may be necessary.

Case series of gastrointestinal stromal tumors with lymph nodes metastasis: unusual presentations

Gastrointestinal stromal tumor (GIST) is a rare cancer of the gastrointestinal tract, it occurred about 0.1-3.0% of all gastrointestinal neoplasms. Accounted about 10% of small-bowel tumors, and 10-15% of all sarcomas. Liver is a common hematogenous spread in GIST. However, metastasis to lymph nodes is consider extremely rare and routine lymph node dissection for GIST tumor was not recommended. Hence, we reported a case series of GIST that metastasize to lymph node along our experience in our center, hospital Taiping, Malaysia from 2010 until 2020. Hereby we report total of 3 out of 18 GIST cases that we encountered confirmed through histopathology the existence of lymph node metastasis.

MicroRNA-34c-5p Inhibition of NUF2 Suppresses Lung Adenocarcinoma Cell Viability and Invasion

Background. Lung cancer continues to be a burden worldwide with an estimated 2.09 million new cases of lung cancer and 1.76 million deaths in 2018. MicroRNAs (miRs) are key regulators of gene expression and show their oncogenic or antioncogenic role in human cancers including lung cancer. In this study, we test the hypothesis that miR-34c-5p functions as a candidate antioncomiR in lung adenocarcinoma by targeting NUF2. Methods. The expression pattern of miR-34c-5p and NUF2 was evaluated in 202 biopsy specimens from patients with lung adenocarcinoma and 176 biopsy specimens from patients with benign lung diseases. Interaction between miR-34c-5p and NUF2 was verified by the luciferase-based assay. Cell viability and invasion assays were carried out in cultured A549 cells treated with miR-34c-5p mimic, inhibitor, and siRNA against NUF2. Results. NUF2 was highly expressed in lung adenocarcinoma samples and related to the differentiation degree, TNM stage, and presence of lymph node metastasis (LNM). Patients with NUF2 overexpression had reduced overall survival (OS) and disease-free survival (DFS) compared to patients with underexpression. Cox multivariate analysis revealed that high expression of NUF2, advanced TNM stage, well/moderate differentiation, and existence of LNM were unfavorable prognostic factors. siRNA-mediated knockdown of NUF2 inhibits A549 cell viability and invasion. miR-34c-5p was expressed at a poor level in lung adenocarcinoma samples and related to the differentiation degree, TNM stage, and presence of LNM. miR-34c-5p underexpression contributes to reduced OS and DFS, which was demonstrated as an unfavorable prognostic factor by Cox multivariate analysis. siRNA-mediated knockdown of NUF2 could ablate miR-34c-5p inhibition-mediated effects on A549 cells. Conclusion. Our results prove the hypothesis that miR-34c-5p could suppress lung adenocarcinoma progression by binding to the NUF2 gene. The study is a significant step towards extending our understanding of the mode of miRNA regulation in lung adenocarcinoma.

Diagnostic, Therapeutic Predictive, and Prognostic Value of Neutrophil Extracellular Traps in Patients With Gastric Adenocarcinoma.

Neutrophils are a significant population of infiltrated immune cells in the tumor microenvironment. Neutrophil extracellular traps (NETs) are implicated in the biological behavior of many malignant tumors. NETs can be degraded into soluble nucleosomes, leading to the release of fragments containing DNA and granule proteins into the peripheral blood (PB). Using human gastric cancer (GC) biopsies and PB samples, we investigated the specific value of NETs in GC from a clinical perspective. In summary, the formation of NETs was discovered in the tissue microenvironment and PB of GC patients. The amounts of NETs and neutrophil accumulation decreased from tumor tissue to paratumor tissue. In addition, the level of NETs in the PB gradually declined through the following patient populations: advanced disease patients, preoperative patients, postoperative patients, benign disease patients, and healthy controls. The levels of NETs in the plasma and serum were significantly correlated. As a serum biomarker, NETs had a better diagnostic value than carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in GC. The neutrophil count and neutrophil to lymphocyte ratio (NLR) were significantly associated with the level of NETs in the PB. The existence of lymph node metastasis indicated a high level of NETs in the serum. Moreover, the level of NETs in the PB was inversely correlated with short-term efficacy in GC patients who had received advanced first-line treatment. The higher baseline level of NETs in the PB of patients with negative HER2 status was correlated with worse progression-free survival (PFS). And the level of NETs in the PB was a unfavorable independent prognostic factor for PFS in patients with advanced GC who had received first-line treatment. Thus, NETs have novel diagnostic, therapeutic predictive, and prognostic value in GC patients.

Redox Status and Antioxidative Cofactor Metals Influence Clinical and Pathological Characteristics of Papillary Thyroid Carcinoma and Colloid Goiter.

Papillary thyroid carcinoma (PTC) is the endocrine neoplasm that occurs the most often worldwide, and its molecular pathophysiology is still not well characterized. Redox status is recognized as an important factor of carcinogenesis, but its influence on the PTC's clinical course needs to be better elucidated. The aim of this research was to determine the tissue redox status of 65 PTC and 45 colloid goiter (CG) patients together with antioxidative cofactor metal profiling. The malondialdehyde (MDA) concentration was used to access the prooxidation level, while antioxidant mechanisms were estimated by assaying the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). The antioxidative cofactor metals included quantification of Se, Cu, Zn, and Mn concentration. PTC tissues had normal prooxidation levels and increased GPx and GR activity. The activity of SOD has been significantly reduced in multicentric PTC dissemination and increased in smokers. SOD activity was directly dependent on MDA levels in CG tissues. CG patients with retrosternal goiter had reduced MDA concentration and SOD activity. Numerous correlations between redox parameters in PTC tissues reveal good co-activation of antioxidative mechanisms and cooperative response on prooxidation. PTC tissues had decreased Se levels and increased concentration of Cu and Mn in comparison to other tissues. MDA concentration and SOD activity were significant predictors of PTC's multicentric dissemination and for the existence of lymph node metastases, respectively. Particularly, the concentration of Cu predicted the retrosternal localization in CG patients. Significant findings presented in this study provide a possibility for development of novel prognostic molecular biomarkers of PTC and CG.

Rectal cancer: can T2WI histogram of the primary tumor help predict the existence of lymph node metastasis?

To explore if there is a correlation between T2WI histogram features of the primary tumor and the existence of regional lymph node (LN) metastasis in rectal cancer. Eighty-eight patients with pathologically proven rectal adenocarcinoma, who received direct surgical resection and underwent preoperative rectal MRIs, were enrolled retrospectively. Based on pathological analysis of surgical specimen, patients were classified into negative LN (LN-) and positive LN (LN+) groups. The degree of differentiation and pathological T stage were recorded. Clinical T stage, tumor location, and maximum diameter of tumor were evaluated of each patient. Whole-tumor texture analysis was independently performed by two radiologists on axial T2WI, including skewness, kurtosis, energy, and entropy. The interobserver agreement was overall good for texture analysis between two radiologists, with intraclass correlation coefficients (ICCs) ranging from 0.626 to 0.826. The LN- group had a significantly higher skewness (p < 0.001), kurtosis (p < 0.001), and energy (p = 0.004) than the LN+ group, and a lower entropy (p = 0.028). These four parameters showed moderate to good diagnostic power in predicting LN metastasis with respective AUC of 0.750, 0.733, 0.669, and 0.648. In addition, they were both correlated with LN metastasis (rs = - 0.413, - 0.385, - 0.28, and 0.245, respectively). The multivariate analysis showed that lower skewness was an independent risk factor of LN metastasis (odds ratio, OR = 9.832; 95%CI, 1.171-56.295; p = 0.01). Signal intensity histogram parameters of primary tumor on T2WI were associated with regional LN status in rectal cancer, which may help improve the prediction of nodal stage. • Histogram parameters of tumor on T2WI may help to reduce uncertainty when assessing LN status in rectal cancer. • Histogram parameters of tumor on T2WI showed a significant difference between different regional LN status groups in rectal cancer. • Skewness was an independent risk factor of regional LN metastasis in rectal 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.

Preoperative Plasma Fibrinogen is Associated with Lymph Node Metastasis and Predicts Prognosis in Resectable Esophageal Cancer.

Although it is well known that patients with malignant tumors have abnormal blood coagulation, its clinical significance has not been studied. We investigated the clinicopathological and prognostic impact of plasma fibrinogen, which is the major factor of the coagulation system, in patients with esophageal cancer. From February 1995 to December 2006, 100 patients with esophageal cancer who had their plasma fibrinogen measured were enrolled. The associations between plasma fibrinogen, clinicopathological factors, and prognosis were analyzed. A concentration of 2.0-4.0g/L was defined as normofibrinogenemia, and a concentration higher than 4.0g/L was described as hyperfibrinogenemia. Patients with large, advanced tumors, and lymph node metastasis had significantly higher plasma fibrinogen than those with small, early tumors, and no lymph node metastasis (p<0.001, p=0.002, and p=0.03, respectively). Plasma fibrinogen was associated with not only the existence of lymph node metastasis but also the extension of lymph node metastasis and lymphatic recurrence. Patients with hyperfibrinogenemia had a significantly poor prognosis as compared to those with normofibrinogenemia, regardless of pathological staging. Plasma fibrinogen was an independent risk factor for overall survival and relapse-free survival as well as tumor depth and lymph node metastasis (p=0.004 and p=0.031, respectively). Preoperative plasma fibrinogen is a possible biomarker for the prediction of tumor progression, recurrence pattern, and prognosis for esophageal cancer. Preoperative plasma fibrinogen is also associated with lymph node metastasis and may be helpful in adjusting neo-adjuvant therapy.

C-Met in chromophobe renal cell carcinoma.

c-Met plays a role as a prognostic marker in clear cell renal cell carcinoma. In addition, recently the tyrosine kinase inhibitor cabozantinib targeting c-Met was approved for the treatment of advanced renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known about c-Met expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of c-Met expression on chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for c-Met expression by immunohistochemistry. Expression data were associated with clinicopathological parameters including patient survival. Eighty-one chRCC patients were eligible for analysis. Twenty-four (29.6%) patients showed a high c-Met expression (c-Methigh, staining intensity higher than median). Our results showed an association between c-Methigh expression and the existence of lymph node metastasis (p=0.007). No further significant clinicopathological associations with c-Met were identified, also regarding c-Met expression and overall survival. In conclusion, to our knowledge this is the first study evaluating the prognostic impact of c-Met in a considerably large cohort of chRCC. High c-Met expression is associated with the occurrence of lymph node metastasis. This indicates that c-Met might be implicated into metastatic progression in chRCC.

Clinical study on locally advanced rectal cancer patients with pathological complete response after neoadjuvant chemoradiotherapy

To explore the efficacy prediction of the locally advanced rectal cancer patients, especially those with pathological complete response(pCR), receiving neoadjuvant chemoradiotherapy in order to execute precise preoperative neoadjuvant chemoradiotherapy. From January 2000 to January 2011, 125 patients diagnosed as locally advanced rectal cancer receiving preoperative neoadjuvant chemoradiotherapy in our department with complete data were enrolled in this study, including 85 males and 40 females with mean age of 54(15 to 77) years old. All the patients received radiotherapy with 46 Gy(23 times) and administered XELOX regimen (oxaliplatin 100 mg/m(2) plus capecitabine 2 000 mg/m(2)) for 2 courses simultaneously, and underwent radical operation 6 to 8 weeks after chemoradiotherapy. The data of these patients were analyzed retrospectively. Pathological remission was divided into 4 grades. Patients achieving grade 4 were defined as pCR, and those achieving above grade 2 were defined as better response. Logistic regression analysis was used to identify significant predictors of pCR. Among 125 patients, 16(12.8%) achieved pCR status, and 90(72.0%) had better response to the neoadjuvant chemoradiotherapy. Logistic regression analysis showed that age(OR:1.060, P=0.037) and preoperative positive lymph nodes detected by endorectal ultrasonography (OR:0.059, P=0.006) were independent predictors of pCR after neoadjuvant chemoradiotherapy. Preoperative existence of lymph node metastasis around bowel indicates the poor response to neoadjuvant chemoradiotherapy. Age is associated with pCR in patients receiving neoadjuvant chemoradiotherapy.

The Relationship between Telomerase Activity and Clinicopathological Parameters in Colorectal Cancer: A Meta-Analysis.

Recently, accumulated research has found that the expression of telomerase activity (TA) was associated with colorectal cancer (CRC) advancement, whereas the TA prognostic effect in CRC patients is still controversial. To investigate relationships between TA and CRC clinicopathological parameters. Meta-analysis study. We searched published studies in databases, such as EMBASE, the Cochrane Library, PubMed, and Ovid databases (last search updated to October 2014) by meeting specified search criteria. The quality of the included studies was usually evaluated and a meta-analysis was implemented by Stata 12.0 software. We used an odds ratio (OR) with a 95% confidence interval (CI) to evaluate relationship strengths between TA and CRC clinicopathological parameters. In total, 11 studies (715 patients) were included to assess the relation between TA and metastasis-related parameters in CRC patients. The results indicate that a senior TA expression was connected with the existence of lymph node metastasis (180 patients; OR=2.85, 95% CI=1.40-5.81, p=0.004), and tumor site (522 patients; OR=2.93, 95% CI=1.29-6.67, p=0.010). However, a senior TA expression was not connected with tumor size (137 patients; OR=1.57, 95% CI=0.71-3.47, p=0.267), histological differentiation (570 patients; OR=1.28, 95% CI=0.78-2.09, p=0.332), depth of invasion (57 patients; OR=3.76, 95% CI=0.61-23.04, p=0.152), distant metastasis (123 patients; OR=1.76, 95% CI=0.54-5.74, p=0.346), and clinical stage of the cancer (543 patients; OR=1.59, 95% CI=0.74-3.38, p=0.232). This meta-analysis suggests that a positive TA was correlated with lymph node metastasis progression and tumor site of the CRC but did not correlate with other important clinicopathological parameters. TA can play a useful part in the prognosis and treatment of CRC patients, but further studies are required to confirm this.

Risk of Limited Lymph Node Dissection in Patients with Clinically Early Gastric Cancer: Indications of Extended Lymph Node Dissection for Early Gastric Cancer

Laparoscopic gastrectomy is usually indicated in T1 N0-1 early gastric cancer (EGC). Limited lymph node dissection, such as D1+, is applied in these cases. However, preoperative staging is not always correct, and the risk of undertreatment thus exists. Patients with clinically early gastric cancer (cEGC) who underwent gastrectomy with lymph node dissection of D2 and over were selected from 4,021 patients with gastric cancer. The station numbers of all metastatic lymph nodes (MLNs) were identified, and MLNs were classified into groups 1 and 2 (including lymph nodes of second tier and over) on the basis of the system of the Japanese Gastric Cancer Association, irrespective of the number of MLNs. Clinicopathological data were compared according to the existence of lymph node metastasis and the classification of MLNs. Of 1,308 patients with cEGC who fulfilled the inclusion criteria, 1,184 (90.5%) were diagnosed pathologically with EGC. Among 126 patients with cEGC who were diagnosed with lymph node metastasis, 93 patients had only group 1 MLNs and 33 patients had group 2 MLNs. Tumor location in the proximal third of the stomach (odds ratio 5.450) and ulceration (odds ratio 11.928) were significant factors for group 2 metastasis. Extended lymph node dissection is recommended in cEGC with ulceration or disease located in the proximal third of the stomach.

Abstract 404: Effect of miR-122 and its target gene cationic amino acid transporter 1 on colorectal liver metastasis.

Abstract Background: Control of liver metastasis has been an important issue in the treatment of colorectal cancers. Although microRNA (miRNA) has been shown to be involved in the development of many cancers including colorectal cancers, only few studies have investigated the roles of miRNAs in the process of colorectal liver metastasis. In this study, we compared miRNA expression between primary colorectal cancers and their corresponding liver metastasis to identify miRNAs involved in colorectal liver metastasis and to detect novel molecular markers for prediction of the postoperative prognosis of colorectal cancer patients. Methods: Cancer cells were isolated from formalin-fixed paraffin-embedded (FFPE) tissues of primary colorectal cancers and their corresponding metastatic liver tumors in 6 patients using laser capture microdissection methods. miRNA expression was analyzed using TaqMan miRNA array. Protein levels of cationic amino acid transporter 1 (CAT1), a negative target gene of miR-122, in 132 primary colorectal cancers and 22 colorectal liver metastases were analyzed by immunohistochemical staining. Relationship between clinicopathological factors and CAT1 expression levels in 132 primary colorectal cancers were evaluated. Results: miR-122 was the most highly expressed in liver metastasis compared with primary tumor. Immunohistochemical analysis revealed that the expression levels of CAT1 were lower in liver metastases than primary tumors (P &amp;lt;0.001). Expression levels of CAT1 in 132 primary tumors were negatively correlated with the existence of synchronous liver metastasis (P=0.0333) and tumor stage (P &amp;lt;0.0001). In the analysis of 121 colon cancer patients without synchronous liver metastasis, patients with CAT1-low colon cancer had significantly shorter liver metastasis-free survival (P=0.0258) but not overall survival or disease-free survival. Univariate analysis, for clarifying the risk factors of metachronous colorectal liver metastasis after primary resection, revealed that the 5-year liver metastasis-free survival rate was negatively correlated with the existence of lymph node metastasis and positively correlated with expression levels of CAT1 protein in the primary tumors. Conclusions: Overexpression of miR-122 and concomitant suppression of CAT1 in the primary tumor appear to play important roles in the development of colorectal liver metastasis. CAT1 expression in the primary colorectal cancer has a potential to be a novel biomarker with which to predict the risk of postoperative liver metastasis of the patients with colorectal cancer. Citation Format: Ichirota Iino, Hirotoshi Kikuchi, Shinichiro Miyazaki, Yoshihiro Hiramatsu, Manabu Ohta, Kinji Kamiya, Takanori Sakaguchi, Mitsutoshi Setou, Hiroyuki Konno. Effect of miR-122 and its target gene cationic amino acid transporter 1 on colorectal liver metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 404. doi:10.1158/1538-7445.AM2013-404 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

Large Intervening Non-Coding RNA HOTAIR is Associated with Hepatocellular Carcinoma Progression

Increasing evidence suggests that large intervening non-coding RNAs (lincRNAs) regulate key pathways in cancer invasion and metastasis. In this observational retrospective study, the expression of the oncogenic lincRNA HOX transcript antisense RNA (HOTAIR) gene was measured in 63 patients with hepatocellular carcinoma (HCC) following hepatic resection. The HOTAIR gene was significantly overexpressed in HCC tissues compared with adjacent non-tumour tissues. Patients with high HOTAIR gene expression in their tumours had an increased risk of recurrence after hepatectomy. There was also a significant correlation between HOTAIR expression and lymph node metastasis. In vitro assays in the HCC cell line Bel7402 demonstrated that knockdown of HOTAIR lincRNA reduced cell proliferation and was associated with reductions in levels of matrix metalloproteinase-9 and vascular endothelial growth factor protein, which are important for cell motility and metastasis. In conclusion, HOTAIR lincRNA might be a potential biomarker for the existence of lymph node metastasis in HCC.

Multivisceral and standard resections in colorectal cancer

The current study was designed to identify prognostic factors for long-term survival in patients with advanced colorectal cancer in a consecutive cohort. A total of 123 patients were operated because of T4 colorectal cancer between 1 January 2002 and 31 December 2008 in the Clinic of Surgery, UK-SH Campus Luebeck. A total of 78 patients underwent a multivisceral resection. The postoperative morbidity was elevated in the patient group with multivisceral resections (34.6% vs. 26.7%). Nevertheless, we detected no significant differences concerning 30days mortality (7.7% vs. 8.9%; p = 0.815). The main prognostic factor that reached significance in the multivariate analysis was the possibility to obtain a R0 resection (p < 0.0001) resulting in a 5-year survival rate of 55% for patients with curative resection. There were no statistically significant differences in 5-year survival between multivisceral and non-multivisceral resections (p = 0.608). Also we were not able to detect any significant differences for cancer of colonic or rectal origin (p = 0.839), for laparoscopic vs. open procedures (p = 0.610), and for emergency vs. planned operations (p = 0.674). Moreover, the existence of lymph node metastases was not a predictive factor concerning survival as there was no difference between patients with and without lymph node metastases (p = 0.658). Multivisceral resections are associated with the same 5-year survival as standard resections. Therefore, the aim to perform a R0 resection should always be the main goal in surgery for colorectal cancer. In planned operations, a laparoscopic approach is justified in selected patients.

Metallothionein expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patient survival

Metallothionein (MT) has been implicated in several aspects of cancer pathobiology, such as differentiation, proliferation, apoptosis and invasion. The aim of the present study was to evaluate the clinical significance of MT expression in mobile tongue squamous cell carcinoma (SCC). MT protein expression was assessed immunohistochemically on 49 mobile tongue SCC specimens, and was analysed in relation to clinicopathological characteristics, and overall and disease-free patient survival. All of the examined mobile tongue SCC cases showed MT positivity in tumour cells; however, neither MT overexpression nor staining intensity was significantly associated with clinicopathological parameters. MT cellular distribution was significantly associated with histopathological grade of differentiation and depth of invasion (P = 0.0188 and P = 0.0484, respectively). MT staining intensity was identified as a significant predictor of overall patient survival at both univariate (P = 0.0377) and multivariate (P = 0.0472) levels. Twenty-seven (55.10%) of the examined SCC cases showed MT positivity in squamous tongue epithelium adjacent to the tumour, the MT positivity being correlated with depth of invasion (P = 0.0281), vascular invasion (P = 0.0194), and the existence of lymph node metastases (P = 0.0194). MT may be implicated in the development and progression of mobile tongue SCC and could be considered as a useful clinical marker for patient management and prognosis.

Clinical Value of Assaying Tumor Supplied Group of Factor/Tumor Specific Growth Factor in Patients With Solitary Pulmonary Nodule

ObjectiveThis pilot study was designed to evaluate the clinical value of assaying tumor supplied group of factor/tumor specific growth factor (TSGF) in solitary pulmonary nodule (SPN). Patients and MethodsThe study was conducted from March 2007 to September 2010 and included 33 patients with SPN and 28 healthy volunteers. TSGF was assayed in preoperative serum, intraoperative pleural lavage fluid (IPLF), and postoperative serum. ResultsAt operation, 20 patients were diagnosed with malignancy and 13 patients were diagnosed with nonmalignancy and placed in group A and group B, respectively. In group A, pathologic staging demonstrated 8 patients (group A1) with stage T1N0M0, 7 patients (group A2) with stage T1N1M0 and 53 patients (group A) with stage T1N2M0 disease. In group B, 8 patients were diagnosed with tuberculoma (group B1) and 5 patients were diagnosed with inflammatory pseudotumor (group B2). Before operation, levels of TSGF in peripheral blood were significantly higher in group A compared with group B and the control group (98.8 ± 29.9 vs. 62.1 ± 24.9 and 50.1 ± 17.9, Student-Newman-Keuls test; P < .05). The percentage of patients with positive serum TSGF results was significantly higher in group A than in group B or the control group (90.0% vs. 30.8% and 17.9%, χ2 test; P < .05). With respect to the diagnostic value of serum TSGF in malignant SPN, we found sensitivity to be 90%, specificity to be 69.2%, positive forecast rate to be 74.5%, negative forecast rate to be 87.4%, and accurate diagnosed rate to be 79.5%. The TSGF level in IPLF in group A was significantly higher than that in group B (132.2 ± 51.9 vs. 84.6 ± 12.6, Student t test, P < .05). Additionally, TSGF in group A2 and group A3 was significantly higher compared with group A1 (162.2 ± 52.3 and 176.4 ± 17.8 vs. 100.2 ± 35.8, Student-Newman-Keuls test; P < .05). Postoperative serum TSGF in the patients diagnosed with lung cancer decreased significantly after operation. TSGF returned to a normal threshold level (71 U/mL) in the sixth month postoperatively. In addition, there was no appreciable change in the patients in group B. ConclusionSerum TSGF is conducive to discriminating between benign and malignant features of SPN. Additionally, investigation of IPLF TSGF can potentially offer a new approach to predict the existence of lymph node metastases.