Poor Degree Of Differentiation Research Articles

The development and validation of automated machine learning models for predicting lymph node metastasis in Siewert type II T1 adenocarcinoma of the esophagogastric junction.

Lymph node metastasis (LNM) is considered an essential prognosis factor for adenocarcinoma of the esophagogastric junction (AEG), which also affects the treatment strategies of AEG. We aimed to evaluate automated machine learning (AutoML) algorithms for predicting LNM in Siewert type II T1 AEG. A total of 878 patients with Siewert type II T1 AEG were selected from the Surveillance, Epidemiology, and End Results (SEER) database to develop the LNM predictive models. The patients from two hospitals in Suzhou were collected as the test set. We applied five machine learning algorithms to develop the LNM prediction models. The performance of predictive models was assessed using various metrics including accuracy, sensitivity, specificity, the area under the curve (AUC), and receiver operating characteristic (ROC) curve. Patients with LNM exhibited a higher proportion of male individuals, a poor degree of differentiation, and submucosal infiltration, with statistical differences. The deep learning (DL) model demonstrated relatively good accuracy (0.713) and sensitivity (0.868) among the five models. Moreover, the DL model achieved the highest AUC (0.781) and sensitivity (1.000) in the test set. The DL model showed good predictive performance among five AutoML models, indicating the advantage of AutoML in modeling LNM prediction in patients with Siewert type II T1 AEG.

Supplier selection in sustainable supply chains: Using the integrated BWM, fuzzy Shannon entropy, and fuzzy MULTIMOORA methods

With the increasing awareness of environmental protection and social responsibility, sustainable supplier selection (SSS) has been receiving more and more attention. However, traditional methods for selecting sustainable suppliers suffer from three main drawbacks: (i) Few existing studies have considered criteria weightings that have been determined both subjectively and objectively, reasonably and simultaneously. Moreover, among these limited studies, existing methods for combining weightings that have been calculated both subjectively and objectively provide only a poor degree of differentiation. (ii) Although MULTIMOORA method has high potential to solve the complex SSS problem, few researchers have given it much attention. (iii) The current Reference Point Approach within MULTIMOORA is not comprehensive as it only considers the distance between the alternative and the positive ideal point. Together, these drawbacks result in both inefficiency and ineffectiveness in SSS. This paper proposes a novel fuzzy MULTIMOORA-based method for SSS. The proposed method, firstly, obtains weights by both group Best Worst Method (subjective method) and fuzzy Shannon Entropy Method (objective method), respectively. Then the two types of weights are combined by Deviation Maximization method, reasonably and effectively. Finally, the paper introduces an improved fuzzy MULTIMOORA method to rank alternative suppliers, which considers both the minimum distance from the positive ideal point and the maximum distance from the negative ideal point. The practicability and effectiveness of the proposed method is verified in an illustrative application in Company L, a well-known international forklift truck manufacturer in China.

Protein overexpression of toll-like receptor 4 and myeloid differentiation factor 88 in oral squamous cell carcinoma and clinical significance.

Oral squamous cell carcinoma (OSCC) is the most common type of malignancy of the head and neck. In the present study, the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) was evaluated in 55 OSCC tissues and their corresponding adjacent tissues using immunohistochemistry and reverse-transcription quantitative PCR. The results indicated that TLR4 and MyD88 were overexpressed in OSCC. Furthermore, high expression of MyD88 was negatively associated with a poor degree of differentiation, recurrence and metastasis of the tumor and was positively associated with underlying disease, including hypertension, heart disease and diabetes mellitus. Furthermore, high expression of TLR4 was positively associated with a long growth time of the tumor. In conclusion, the present study evaluated the expression levels of TLR4 and MyD88 in OSCC, as well as the association between them and clinicopathological factors, to provide markers for the prognosis and treatment of OSCC. These two genes may serve as biomarkers to optimize OSCC treatment, setting a new direction for stratifying patients and developing precise and personalized treatment regimens; the TLR4/MyD88 pathway may serve as a potential therapeutic target in the future.

Clinical and histopathological evaluation of 50 acantholytic cutaneous squamous cell carcinomas: Analysis outcome in a retrospective case-control study.

Acantholytic cutaneous squamous cell carcinomas (aCSCCs) have been classically considered as a high-risk variant of CSCC. However, more recent studies show that aCSCC does not confer more aggressiveness. This study aims to establish whether the prognosis of the aCSCC is worse than that of the non-acantholytic (naCSCC) or not. Retrospective case-control study with 50 aCSCCs and 50 naCSCCs. For each aCSCC, an naCSCC with similar high-risk features to the aCSCC but with no acantholysis was selected. Prognosis between both groups was compared. The mean age was 86 years (SD 9.61). Sixty-one patients were men. Thirty-nine CSCCs were located in high-risk head and neck areas. Twenty CSCCs exhibited a poor degree of differentiation, and 36 showed an infiltrative growth pattern. The tumor diameter was 18.71 mm (interquartile range, IQR 35), and the tumor thickness was 6.72 mm (IQR 15.50). Twelve CSCCs exhibited perineural infiltration, and eight CSCCs exhibited invasion beyond the subcutaneous fat. Positive margins after excision of the tumor in 22 aCSCCs vs eight naCSCCs (P < 0.02). Nineteen poor-prognosis events were observed (local recurrence, lymph node metastasis, and death from CSCC). However, no differences were observed between both groups when comparing poor-prognosis events. The proportion of unfavorable events is similar in aCSCC and naCSCC. The acantholytic histopathological subtype is not associated with a poorer prognosis than the non-acantholytic CSCC in our cohort.

Prognostic and clinicopathological role of long noncoding RNA NORAD in various cancers: a meta-analysis.

Aim: Long noncoding RNA (lncRNA) noncoding RNA activated by DNA damage (NORAD) is widely investigated in different tumors. Our meta-analysis intends to assess the prognostic and clinicopathological value of NORAD in cancers. Materials & methods: We searched PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure from inception to 1August 2020. Results: The results showed that higher expression of NORAD had a significant association with worse overall survival. Additionally, correlations were detected between elevated level of NORAD and poor differentiation degree, positive lymph node metastasis and large tumor size in cancer patients. Conclusion: LncRNA NORAD can serve as a novel and promising biomarker for prognosis and clinicopathological characteristics in different cancers.

Interaction of CD147 and human epididymis protein 4 promotes invasion and metastasis of ovarian cancer.

Background: Ovarian cancer is one of the most common malignant tumors in female reproductive system. The expression of CD147 and human epididymis protein 4 (HE4) are both upregulated and associated with malignant progression in ovarian cancer. However, the important role of interaction between CD147 and HE4 in the invasion and metastasis of ovarian cancer remains unclear.Methods: The co-expression and co-localization of CD147 and HE4 in cells and tissues of ovarian cancer were detected by co-immunoprecipitation, immunohistochemistry and immunocytochemistry, double-labeling immunofluorescence method. The interaction between CD147 and annexin A2 (ANXA2) was also investigated. Furthermore, we detect the regulatory relationship between CD147 and HE4 by Western blot. Transwell assay and scratch test were conducted to explore the effect of CD147-HE4 interaction on migration and invasion of ovarian cancer.Results: The protein CD147 and HE4 were co-immunoprecipitated and co-located in the cytoplasm and membrane of ovarian cancer tissues and cells. Both of two proteins were highly expressed and positively associated with advanced FIGO stages, poor differentiation degree and poor prognosis of ovarian cancer, and HE4 was confirmed as an independent risk factor for CD147 in ovarian cancer tissues. What's more, AXNA2 was also identified as a CD147 interacting protein in ovarian cancer. It is further confirmed that interaction between CD147 and HE4 can affect the invasion and metastasis of ovarian cancer.Conclusion: This study demonstrated that HE4 and ANXA2 were both CD147 interacting proteins, the expression of CD147 and HE4 can affect each other, and HE4 could promote the invasion and metastasis of ovarian cancer by regulating the expression of CD147, which may provide novel thought for early diagnosis and therapeutic target of ovarian cancer.

TO STUDY OF CHARACTERISTICS OF OBJECTIVE MULTIPLE-CHOICE TEST FOR MEDICAL MODULES

Background: The objective multiple-choice test is an assessment method that has been applied widely in universities. The meticulous judgment of complication and differentiation level of objective test questionnaire can beneficially lead to the growth of high quality multiple-choice questionnaire bank and effective examination. Objectives: To evaluate the difficulty level and differentiate level of the objective multiple-choice tests. Materials and method: The multiple-choice theory test (01 Elemental medical exam with 242 students, 01 Clinical medicine exam with 163 students). The difficulty degree of questions was determined by calculating the percentage of students who gave the answers correctly for the given questions in total. The differentiation level was differentiated by the percentage of students who answered correctly in corresponding groups: excellent, good, average, below average, poor. Results: The elemental medical examination comprises 7 hard questions, 58 medium questions, and 35 simple questions; 10 questions have poor degree of difference, 83 questions have good and very good degree of difference. The clinical medicine examination comprises 9 hard questions, 57 medium questions and, 34 simple questions; 23 questions have poor degree of differentiation, 51 questions have good and very good degree of difference. Conclusions: It is crucial to evaluate the difficulty and differentiation standards of the objective multiple-choice examination which enhance the quality of assessment. Thereby, the faculties need to regularly judge these factors while creating the questionnaire and completely evaluating the tests, and the inappropriate questions will be eliminated. Keywords: difficulty level, differentiation level, Objective multiple-choice test.

CircPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway

BackgroundLaryngeal squamous cell carcinoma (LSCC) is the second most common malignant tumor in head and neck. Autophagy and circular RNAs (circRNAs) play critical roles in cancer progression and chemoresistance. However, the function and mechanism of circRNA in autophagy regulation of LSCC remain unclear.MethodsThe autophagy-suppressive circRNA circPARD3 was identified via RNA sequencing of 107 LSCC tissues and paired adjacent normal mucosal (ANM) tissues and high-content screening. RT-PCR, Sanger sequencing, qPCR and fluorescence in situ hybridization were performed to detect circPARD3 expression and subcellular localization. Biological functions of circPARD3 were assessed by proliferation, migration, invasion, autophagic flux, and chemoresistance assays using in vitro and in vivo models. The mechanism of circPARD3 was investigated by RNA immunoprecipitation, RNA pulldown, luciferase reporter assays, western blotting and immunohistochemical staining.ResultsAutophagy was inhibited in LSCC, and circPARD3 was upregulated in the LSCC tissues (n = 100, p < 0.001). High circPARD3 level was associated with advanced T stages (p < 0.05), N stages (p = 0.001), clinical stages (p < 0.001), poor differentiation degree (p = 0.025), and poor prognosis (p = 0.002) of LSCC patients (n = 100). Functionally, circPARD3 inhibited autophagy and promoted LSCC cell proliferation, migration, invasion and chemoresistance. We further revealed that activation of the PRKCI-Akt-mTOR pathway through sponging miR-145-5p was the main mechanism of circPARD3 inhibited autophagy, promoting LSCC progression and chemoresistance.ConclusionOur study reveals that the novel autophagy-suppressive circPARD3 promotes LSCC progression and chemoresistance through the PRKCI-Akt-mTOR pathway, providing new insights into circRNA-mediated autophagy regulation and potential biomarker and target for LSCC treatment.Graphical abstract

MiR-940 inhibits cell proliferation and promotes apoptosis in esophageal squamous cell carcinoma cells and is associated with post-operative prognosis.

The present study aimed to examine microRNA (miR)-940 expression in esophageal squamous cell carcinoma (ESCC) tissues and cells, analyze its association with the clinicopathological features and prognosis of patients, and explore the potential underlying mechanisms. miR-940 expression in ESCC cell lines and a normal esophageal cell line was detected using reverse transcription-quantitative (RT-q)PCR. Furthermore, 210 resected ESCC tissue and para-carcinoma tissue specimens were collected, and miR-940 expression in those tissues was detected by RT-qPCR. In addition, the association of miR-940 with the clinicopathological features and prognosis of patients was analyzed. In an in vitro experiment, miR-940 mimics were transduced into ESCC cells by the liposome method. An MTT assay was used to detect the effect of miR-940 on the viability of ESCC cells. The influence of miR-940 on the cell cycle and apoptotic rate of ESCC cells was detected by flow cytometry. The present results indicated that the expression levels of miR-940 in human ESCC tissues and cell lines were markedly downregulated, and that low expression of miR-940 in ESCC tissues was significantly associated with a poor degree of differentiation, positive lymph node metastasis and advanced clinical stage. Kaplan-Meier survival analysis suggested that low miR-940 expression was associated with poor prognosis. Cox regression analysis revealed that lymph node metastasis, clinical stage and miR-940 expression were independent risk factors affecting the prognosis of patients. Overexpression of miR-940 in ESCC cells markedly reduced the cell viability, blocked the cell cycle at G0/G1 phase and promoted cell apoptosis. These results suggest that miR-940 is downregulated in ESCC, which is linked to the occurrence and progression of ESCC. Conversely, overexpression of miR-940 reduced the cell viability and promoted apoptosis of ESCC cells. Therefore, miR-940 may be a promising novel prognostic marker and anti-cancer target in ESCC.

Small RNA sequencing revealed aberrant piRNA expression profiles in colorectal cancer.

Piwi‑interacting RNAs (piRNAs), a novel class of non‑coding RNAs, are enriched in germ cells and implicated in spermatogenesis. Emerging evidence demonstrated deregulated expression of piRNAs in numerous tumor types. However, changes in piRNA expression profiles in colorectal cancer (CRC) have not yet been investigated. In the present study, small RNA sequencing was used to evaluate the differences in piRNA expression profiles between CRC and adjacent non‑tumor tissues, as well as to screen for differentially expressed piRNAs. The present results demonstrated that the percentage of unique piRNA reads had no notable difference between the paired CRC and adjacent non‑tumor samples (0.12% vs. 0.13%); however, the counts of total piRNA reads in CRC samples were increased, compared with those in adjacent non‑tumor samples (0.15% vs. 0.07%). Differential expression analysis identified 33 upregulated piRNAs and 2 downregulated piRNAs in CRC samples, among which piR‑18849, piR‑19521 and piR‑17724 were the top three upregulated piRNAs. Reverse transcription‑quantitative polymerase chain reaction further confirmed that the expression levels of piR‑18849, piR‑19521 and piR‑17724 were increased in 80 CRC tissues, compared with paired adjacent non‑tumor tissues. Furthermore, the high expression of piR‑18849 and piR‑19521 was associated with a poor degree of differentiation. The increased expression of piR‑18849 was also associated with high lymph node metastasis. However, no associations were determined between piR‑17724 expression and clinicopathological characteristics of patients. In summary, the present study is the first to provide an overview of the changes in piRNA expression patterns in CRC, shedding new light on the regulatory roles of piRNAs in colorectal carcinogenesis. piR‑18849 and piR‑19521 may be prognostic biomarkers for patients with CRC.

Comparing the eighth and the seventh editions of the American Joint Committee on Cancer staging system and the Brigham and Women's Hospital alternative staging system for cutaneous squamous cell carcinoma: Implications for clinical practice

The new eighth edition of the American Joint Committee on Cancer staging system (AJCC-8) incorporates changes regarding cutaneous squamous cell carcinoma (CSCC). We aimed to compare the AJCC-8 staging system with the previous seventh edition of the AJCC staging system (AJCC-7) and the Brigham and Women's Hospital (BWH) alternative staging system to identify their usefulness and the utility of their risk factors in defining prognostic groups in CSCC. A series of 186 CSCCs of the head and neck were retrospectively collected. All 3 staging systems were compared from the standpoint of their ability to predict poor prognosis. Binary logistic regression models were built to determine which risk factors were most relevant. Poor prognosis was mainly associated with stage T2 of the AJCC-7, with stages T2b/T3 of the BWH system, and with stage T3 of the AJCC-8. The AJCC-8 and the BWH staging systems displayed overlap with each another in predicting poor prognosis, and both were superior to the AJCC-7. The new risk factors incorporated into the AJCC-8 and the poor degree of differentiation were independently associated with poor outcome. Retrospective study and few cases with bone invasion. The AJCC-8 is more distinctive, monotonous, and homogeneous than the AJCC-7 and shows some overlap with the BWH system in stratification of tumors.

FOXM1: A potential indicator to predict lymphatic metastatic recurrence in stage IIA esophageal squamous cell carcinoma.

BackgroundPrevious studies have elucidated that FOXM1 may predict poor prognosis in patients with multiple solid malignant tumors. In this study we explored the differential expression of FOXM1 in stage IIA esophageal squamous cell carcinoma (ESCC) and investigated its prognostic value.MethodsImmunohistochemistry (IHC) and Western blot were used to detect FOXM1 expression in ESCC. Correlations between FOXM1 expression and clinicopathological variables, and five‐year lymphatic metastatic recurrence (LMR) and overall survival (OS) of patients were analyzed.ResultsFOXM1 was aberrantly expressed in ESCC. Statistical analysis revealed a close relationship between FOXM1 expression and tumor size (P = 0.024), depth of invasion (P = 0.048), and degree of differentiation (P = 0.043). The five‐year LMR of patients in the FOXM1 overexpression group was significantly increased compared to the low expression group (P = 0.001). The five‐year OS of patients in the FOXM1 overexpression group was significantly reduced compared to the low expression group (P = 0.007). Log‐rank tests demonstrated that large tumor size (P = 0.044), poor differentiation degree (P = 0.005), deep invasion (P = 0.000), and FOXM1 overexpression (P = 0.007) may indicate poor prognosis in stage IIA ESCC. Cox multivariate regression analysis revealed that all of these variables were independent predictors of unfavorable outcome (P < 0.05).ConclusionFOXM1 could be a predictor of lymphatic metastatic recurrence in stage IIA ESCC after Ivor Lewis esophagectomy.

Downregulated Tim-3 expression is responsible for the incidence and development of colorectal cancer.

The present study aimed to investigate the role of T cell immunoglobulin domain and mucin-3 (Tim-3) in its gene and protein forms in colorectal cancer (CRC), and to verify the significance of Tim-3 expression in patients with CRC. A prospective analysis of 258 patients with CRC and 246 normal controls was conducted between December 2012 and June 2015. Intestinal samples were collected, including of CRC tissues, paracancerous tissues and normal colon mucosa tissues. Peripheral venous blood samples were also collected. Polymerase chain reaction (PCR) amplification, reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis was performed for the detection and evaluation of Tim-3 gene and protein in various tissues. PCR analysis indicated that the T and G alleles of -882C/T and 4259T/G are associated with a significantly increased risk of CRC. Following the confirmation of Tim-3 expression in CRC tissues, RT-qPCR detection and western blot analysis revealed clear downregulation of Tim-3 mRNA and protein expression in the blood and tissue samples obtained from patients with CRC, as compared with in the corresponding control samples. Similar trends of decreased Tim-3 mRNA levels and protein expression were observed in CRC tissues compared with in the paracancerous and the normal colon mucosa tissues. In addition, the mRNA and protein expression levels in the paracancerous tissues were lower than those in the normal colon mucosa tissues. Furthermore, significantly lower Tim-3 mRNA levels were observed in patients with a tumor size >5 cm, a poor differentiation degree, higher tumor-node-metastasis stage (stage III-IV), and lymph node and distant metastasis. Collectively, genetic changes to Tim-3, expressed as polymorphisms in Tim-3, and decreased mRNA/protein expression may be partially responsible for the incidence and development of CRC.

Overexpression of IFITM3 predicts poor prognosis in stage IIA esophageal squamous cell carcinoma after Ivor Lewis esophagectomy.

BackgroundRecent research has shown that IFITM3 plays an important role in the tumorigenesis of many malignancies. We investigated the clinicopathological variables and prognostic value of IFITM3 in stage IIA esophageal squamous cell carcinoma (ESCC) patients.MethodsImmunohistochemistry and Western blot analysis were used to examine IFITM3 expression in tumor specimens. The relationships between IFITM3 expression and clinicopathological variables, as well as the five‐year survival and recurrence status of patients, were analyzed.Results IFITM 3 was aberrantly expressed in tumor tissue. Statistical analysis showed a close correlation of IFITM3 expression with T tumor status (P = 0.004). Additionally, IFITM3 overexpression, advanced T status, poor degree of differentiation, and large tumor size were not only associated with poor survival but were high lymphatic metastatic recurrence predictors in ESCC patients (P < 0.05).ConclusionOur data indicated that IFITM3 overexpression may predict poor prognosis in stage IIA ESCC patients after Ivor Lewis esophagectomy.

Reduced EBP50 expression levels are correlated with unfavorable clinicopathological features of extrahepatic bile duct carcinoma and promote the proliferation and migration of QBC939 cells.

The present study aimed to clarify the association between ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) expression level and the tumor phenotype and clinicopathological features of extrahepatic bile duct carcinoma. Tissue samples from patients with extrahepatic bile duct carcinoma (54 cases) and patients with normal bile duct epithelia from gallbladder of cholecystitis (20 cases) were collected, and immunohistochemical staining was used to detect the expression levels of EBP50 in these tissues. In addition, small interfering (si)RNA-EBP50 was used to knock down the expression of EBP50 in the QBC939 human cholangiocarcinoma (CC) cell line. The effect of EBP50 expression on QBC939 cell proliferation and migration was analyzed using the Cell Counting kit-8 and wound healing assays, respectively. EBP50 expression was significantly downregulated in CC tissue samples (P<0.01), with low EBP50 expression levels positively correlated with a high pathological stage and a poor differentiation degree (P<0.01 and P<0.001, respectively). EBP50 expression in QBC939 cells was knocked down by ≤80% using siRNA-EBP50, and EBP50 knockdown significantly promoted QBC939 cell proliferation, as compared with the vector control cells (P=0.04). EBP50 knockdown also significantly enhanced the wound healing ability of QBC939 cells (P=0.02). These results demonstrated that EBP50 expression levels are significantly correlated with a malignant phenotype in patients with CC, and decreased expression levels of EBP50 may promote CC cell proliferation and migration. These findings provide insight into novel potential diagnostic and therapeutic approaches for patients with CC.

Surgical management of advanced pancreatic neuroendocrine tumors: short-term and long-term results from an international multi-institutional study.

The role of extended resections in the management of advanced pancreatic neuroendocrine tumors (PNETs) is not well defined. Between 1995 and 2012, 134 patients with PNET underwent isolated (isoPNET group: 91 patients) or extended pancreatic resection (synchronous liver metastases and/or adjacent organs) (advPNET group: 43 patients). The associated resections included 27 hepatectomies, 9 vascular resections, 12 colectomies, 10 gastrectomies, 4 nephrectomies, 4 adrenalectomies, and 3 duodenojejunal resections. R0 was achieved in 41 patients (95%) in the advPNET. The rates of T3-T4 (73 vs 16%; p < .0001) and N+ (35 vs 13%; p = .007) were higher in the advPNET group. Mortality (5 vs 2%) and major morbidity (21 vs 19%) rates were similar between the 2 groups. The 5-year overall survival (OS) of the series was 87% in the isoPNET group and 66% in the advPNET group (p = .006). Only patients with both locally advanced disease and liver metastases showed worse survival (p = .0003). The advPNET group developed recurrence earlier [disease-free survival (DFS) at 5 years: 26 vs 81%; p < .001]. In univariate analysis, negative prognostic factors of survival were: poor degree of differentiation (p < .001), liver metastasis (p = .011), NE carcinoma (p < .001), and resection of adjacent organs (p = .013). The multivariate analysis did not highlight any factor that influenced OS. In multivariate analysis independent DFS factors were a poor degree of differentiation (p = .03) and the European Neuroendocrine Tumor Society stage (p = .01). An aggressive surgical approach for locally advanced or metastatic tumors is safe and offers long-term survival.

“Very Early” Intrahepatic Cholangiocarcinoma in Cirrhotic Patients: Should Liver Transplantation Be Reconsidered in These Patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Clinicopathology of recurrent hepatocellular carcinomas after radiofrequency ablation treated with salvage surgery

Radiofrequency ablation (RFA) is an effective standard local therapy for small hepatocellular carcinoma (HCC). However, local recurrence and/or tumor seeding after RFA remain major problems. For better understanding of underlying factors, we clarified clinicopathological features of recurrent HCC treated with RFA. This retrospective study included 21 patients who underwent surgical resection for HCC disease recurrence after RFA. Clinicopathological findings, including patterns of recurrence, immunohistochemical expression of proliferation markers (Ki-67 and p27(Kip1) ) and survival outcome were assessed. The median time interval after RFA until the diagnosis of intrahepatic and/or extrahepatic tumor progression was 12 months (range, 3-84). Radical surgical resection was attempted for intrahepatic local recurrence in 16 patients (18 lesions), for peritoneal dissemination in four, for lymph node metastases in three and for adrenal metastasis in two. In 14 of the 21 (67%) patients, the recurrent HCC were histologically diagnosed as of poorly differentiated type. Their average Ki-67 and p27(Kip1) labeling indices were significantly higher (P = 0.020) and lower (P < 0.001), respectively, compared with values for the 108 HCC surgically resected at the initial treatment. Portal involvement was significantly higher (P = 0.01) in recurrent tumors after RFA (72%) than in HCC surgically resected at the initial treatment (43%). The mortality rate of salvage surgery was 0%, with cumulative survival rates at 1 and 3 years of 58.9% and 35.7%, respectively. The recurrent tumors after RFA have characteristics of poor differentiation degree and abnormalities in cell-cycle regulators and are associated with aggressive vascular invasiveness.

The impact of E-cadherin expression on the prognosis of esophageal cancer: a meta-analysis

E-cadherin is a 120-KD transmembrane calcium-dependent cell adhesion protein that has been demonstrated drownregulated in a large amount of invasive tumors. However, its effect on the prognosis of esophageal cancer (EC) remains controversial. All the relevant English articles that reported survival data or clinicopathological parameters were enrolled in this meta-analysis. A total of 24 studies, including 2691 cases, were included in this study. Twelve studies containing 1669 cases were enrolled to synthesize with hazard ratio (HR) and its 95% confidence interval (CI). The pooled HR for all 12 studies enrolled in this meta-analysis was 1.33 (95% CI 1.16-1.52; z = 3.99, P = 0.00). When the study measured by enzyme-linked immunosorbent assay is excluded, the pooled HR-evaluated E-cadherin to reduce the expression in EC, and in esophageal squamous cell carcinoma was 1.39 (95% CI 1.22-1.58; z = 5.08, P = 0.00) and 1.38 (95% CI 1.21-1.56; z = 4.87, P = 0.00), respectively. The risk of reduced E-cadherin expression on poor differentiation degree was 1.636 (95% CI 1.33-2.02). The pooled odds ratio of reduced E-cadherin expression on deeper tumor invasion, lymph node metastasis, and higher clinical stage were 2.63 (95% CI 1.75-3.94), 1.77 (95% CI 1.06 -2.97), and 3.39 (95% CI 1.85-6.23). Reduced E-cadherin expression detected by immunohistochemistry could be a valid prognostic marker in patients with EC, especially in patients with esophageal squamous cell carcinoma. Reduced E-cadherin expression is significantly associated with poorer differentiation degree.

Neuroendocrine gastroenteropancreatic tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Neuroendocrine gastroenteropancreatic tumours : ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up