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Showing papers on "Surgical oncology published in 2012"


Journal ArticleDOI
TL;DR: In this paper, the authors reported long-term results with a median follow-up of 134 months, where they found a difference of 10% in 5-year overall survival as the primary end point.
Abstract: Purpose Preoperative chemoradiotherapy (CRT) has been established as standard treatment for locally advanced rectal cancer after first results of the CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society] trial, published in 2004, showed an improved local control rate. However, after a median follow-up of 46 months, no survival benefit could be shown. Here, we report long-term results with a median follow-up of 134 months. Patients and Methods A total of 823 patients with stage II to III rectal cancer were randomly assigned to preoperative CRT with fluorouracil (FU), total mesorectal excision surgery, and adjuvant FU chemotherapy, or the same schedule of CRT used postoperatively. The study was designed to have 80% power to detect a difference of 10% in 5-year overall survival as the primary end point. Secondary end points included the cumulative incidence of local and distant relapses and disease-free survival...

1,611 citations


Journal ArticleDOI
TL;DR: The presence of one or more circulating tumour cells predicted early recurrence and decreased overall survival in chemonaive patients with non-metastatic breast cancer and results suggest that assessment of circulating tumours might provide important prognostic information in these patients.
Abstract: Summary Background The identification of circulating tumour cells correlate with poor prognosis in metastatic breast cancer, but there are few data describing the importance of circulating tumour cells in patients with non-metastatic disease. Our aim was to establish if circulating tumour cells predicted worse outcome in patients with non-metastatic breast cancer. Methods We prospectively collected data on circulating tumour cells at the time of definitive surgery from chemonaive patients with stage 1–3 breast cancer from February, 2005, to December, 2010. We deemed eligible all patients with operable breast cancer presenting at The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients were ineligible if they had bilateral breast cancer or any other malignancy within 5 years of the diagnosis of the present cancer. We measured circulating tumour cells with the CellSearch System (Veridex, Raritan, NJ). We correlated findings of circulating tumour cells with standard tumour characteristics, including tumour size and grade; oestrogen and progesterone receptor and human epidural growth factor receptor 2 (HER2) status; and axillary lymph node status with χ 2 or Fisher exact tests. We assessed outcomes at a median follow-up of 35 months. Log-rank test and Cox regression analysis was applied to establish the association of circulating tumour cells with progression-free and overall survival. Findings No patients reported adverse events or complications from blood collections. We identified one or more circulating tumour cells in 73 (24%) of 302 patients. Detection of one or more circulating tumour cells predicted both decreased progression-free survival (log-rank p=0·005; hazard ratio [HR] 4·62, 95% CI 1·79–11·9) and overall survival (log-rank p=0·01; HR 4·04, 1·28–12·8). Interpretation The presence of one or more circulating tumour cells predicted early recurrence and decreased overall survival in chemonaive patients with non-metastatic breast cancer. These results suggest that assessment of circulating tumour cells might provide important prognostic information in these patients. Funding Society of Surgical Oncology, Morgan Welch Inflammatory Breast Cancer Program, The University of Texas MD Anderson Cancer Center, and the State of Texas Rare and Aggressive Breast Cancer Research Program.

456 citations


Journal ArticleDOI
TL;DR: The evidence review demonstrated that SLN biopsy is an acceptable method for lymph node staging of most patients with newly diagnosed melanoma, and completion lymph node dissection (CLND) is recommended for all patients with a positive SLNBiopsy and achieves good regional disease control.
Abstract: Purpose The American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO) sought to provide an evidence-based guideline on the use of lymphatic mapping and sentinel lymph node (SLN) biopsy in staging patients with newly diagnosed melanoma.

305 citations


Journal ArticleDOI
TL;DR: High tumor grade and tumor size ≥5 cm predict adverse DSS for MPNST in the context of a multidisciplinary treatment regimen, and local recurrence and survival outcomes at 5 and 10 years were better than previously reported for MPnST.
Abstract: Background Malignant peripheral nerve sheath tumors (MPNST) are a rare form of soft tissue sarcoma with few studies reporting on patient outcomes and prognostic variables.

263 citations


Journal ArticleDOI
TL;DR: A review examines the most widely postulated mechanisms for the impact of anesthesia on neuroendocrine and immune function, and proposes that an upregulation of HIFs in tumor cells by these anesthetics may contribute to a tumor's recurrence by stimulating cytoprotective or protumorigenic behavior in residual cells.
Abstract: Surgery is of paramount importance in the management of solid tumors as definitive resection can be totally curative. Nonetheless, metastatic recurrence after surgery remains a major cause of morbidity and mortality. Interest in the impact of the perioperative period on cancer recurrence is now growing rapidly, with recent research suggesting that some anesthetics or anesthetic techniques may influence the pathophysiology of postoperative metastatic spread. Our review examines the most widely postulated mechanisms for this, including the impact of anesthesia on neuroendocrine and immune function. We also consider evidence for a direct impact on tumor cell signaling pathways based on findings from organ protection research. These studies have demonstrated that certain volatile anaesthetics confer cytoprotective properties to exposed cells and lead to significant upregulation of Hypoxia Inducible Factor-1α (HIF-1α). This ubiquitous transcription factor exerts many effects in cancer: its activity has been linked with more aggressive phenotypes and poorer clinical prognosis. It is proposed that such an upregulation of HIFs in tumor cells by these anesthetics may contribute to a tumor's recurrence by stimulating cytoprotective or protumorigenic behavior in residual cells. Conversely, other anesthetic agents appear to downregulate HIFs or cause negligible effect and thus may prove more suitable for use in cancer surgery. As anesthetic drugs are given at a point of potentially high vulnerability in terms of dissemination and establishment of metastases, there is an urgent need to determine the most appropriate anesthetic strategy for surgical oncology so that the optimal techniques are used to maximize long-term survival.

252 citations


Journal ArticleDOI
TL;DR: The evidence review demonstrated that SLN biopsy is an acceptable method for lymph node staging of most patients with newly diagnosed melanoma and is recommended for patients with intermediate-thickness melanomas of any anatomic site.
Abstract: The American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO) sought to provide an evidence-based guideline on the use of lymphatic mapping and sentinel lymph node (SLN) biopsy in staging patients with newly diagnosed melanoma. A comprehensive systematic review of the literature published from January 1990 through August 2011 was completed using MEDLINE and EMBASE. Abstracts from ASCO and SSO annual meetings were included in the evidence review. An Expert Panel was convened to review the evidence and develop guideline recommendations. Seventy-three studies met full eligibility criteria. The evidence review demonstrated that SLN biopsy is an acceptable method for lymph node staging of most patients with newly diagnosed melanoma. SLN biopsy is recommended for patients with intermediate-thickness melanomas (Breslow thickness, 1–4 mm) of any anatomic site; use of SLN biopsy in this population provides accurate staging. Although there are few studies focusing on patients with thick melanomas (T4; Breslow thickness, >4 mm), SLN biopsy may be recommended for staging purposes and to facilitate regional disease control. There is insufficient evidence to support routine SLN biopsy for patients with thin melanomas (T1; Breslow thickness, <1 mm), although it may be considered in selected patients with high-risk features when staging benefits outweigh risks of the procedure. Completion lymph node dissection (CLND) is recommended for all patients with a positive SLN biopsy and achieves good regional disease control. Whether CLND after a positive SLN biopsy improves survival is the subject of the ongoing Multicenter Selective Lymphadenectomy Trial II. Copyright © 2012 American Society of Clinical Oncology and Society of Surgical Oncology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the American Society of Clinical Oncology and Society of Surgical Oncology.

173 citations


Journal ArticleDOI
TL;DR: The CD44+/CD24− phenotype in ovarian cancer cells demonstrate cancer stem cell-like properties of enhanced differentiation, invasion, and resistance to chemotherapy that correlates to clinical endpoints with increased risk of recurrence and shorter progression-free survival in patients with ovarian cancer.
Abstract: Cancer cells with the surface marker profile CD44+/CD24− have previously been described to possess cancer stem cell-like properties. This manuscript evaluates those properties in ovarian cancer cell lines. The proportion of CD44+/CD24− cells corresponded to the clinical aggressiveness of each ovarian cancer cell line histologic subtype. CD44+/CD24− cells demonstrated enhanced progressive differentiation as well as showing a 60-fold increase in Matrigel invasion in both SKOV3 and OV90 cell lines (p 25 % CD44+/CD24− were significantly more likely to recur (83 vs. 14 %, p = 0.003) and had shorter median progression-free survival (6 vs. 18 months, p = 0.01). In conclusion, the CD44+/CD24− phenotype in ovarian cancer cells demonstrate cancer stem cell-like properties of enhanced differentiation, invasion, and resistance to chemotherapy. This CD44+/CD24− phenotype correlates to clinical endpoints with increased risk of recurrence and shorter progression-free survival in patients with ovarian cancer.

151 citations


Journal ArticleDOI
TL;DR: A number of surgical approaches have demonstrated beneficial effects for select patients with lymphedema, but most of these reports are based on small numbers of patients, use nonstandardized or inconsistent measurement techniques, and lack long-term follow-up.
Abstract: Purpose A systematic review of the literature was performed to examine contemporary peer-reviewed literature (2004–2010) evaluating the surgical treatment of lymphedema.

135 citations


Journal ArticleDOI
TL;DR: A sizable fraction of patients with early-stage pancreatic NETs are diagnosed incidentally during evaluations for other conditions or unrelated symptoms, and incidental detection of tumors was the strongest prognostic factor for progression.
Abstract: Pancreatic neuroendocrine tumors (NETs) are increasingly discovered incidentally during radiologic or endoscopic examinations. The frequency of incidental detection is unknown. It is also unclear whether patients with incidentally discovered, early-stage, asymptomatic tumors should be treated similarly to patients who present with tumor-related symptoms. Patients with nonmetastatic pancreatic NETs treated at the H. Lee Moffitt Cancer Center between 1999 and 2010 were assigned a stage (I–III) on the basis of the new American Joint Committee on Cancer classification. The frequency of incidentally diagnosed tumors was evaluated and stratified by stage. Progression-free survival was measured by log rank testing to compare patients with incidentally detected versus symptomatic tumors. Multivariate analysis was performed controlling for other prognostic factors including tumor stage, grade, and location, and patient age. Among 143 patients with nonmetastatic pancreatic NETs, 56 patients (40%) had tumors that were discovered incidentally. Most stage I tumors (55%) were incidental. The 5-year progression-free survival rate was 86% for incidentally diagnosed tumors, versus 59% for symptomatic tumors (P = 0.007). On multivariate analysis, incidental detection of tumors was the strongest prognostic factor for progression. A sizable fraction of patients with early-stage pancreatic NETs are diagnosed incidentally during evaluations for other conditions or unrelated symptoms. This study highlights the necessity of developing guidelines for management of patients with incidentally discovered early-stage tumors.

111 citations


Journal ArticleDOI
TL;DR: Sharpening the needlepoint of surgical expertise will not compensate for the major infrastructural deficiencies, but must proceed in tandem with resource development and allow heath planners to realize that pediatric surgical oncology is a cost-effective service that can uplift regional services.

107 citations


Journal ArticleDOI
TL;DR: Despite R0 resection, two-thirds of the patients developed a local recurrence and the prognosis was dismal and median DSS was just over 3 years.
Abstract: Background Secondary angiosarcoma of the breast is a rare but severe long-term complication of breast cancer treated with breast-conserving surgery and radiotherapy. We characterized a population-based cohort of patients with secondary angiosarcomas from two tertiary hospitals to investigate this complication with respect to surgical treatment and outcome.

Journal ArticleDOI
TL;DR: Recurrence remains a problem following resection of desmoid tumors with as many as 50 % of patients experiencing a recurrence within 5 years with the need for more effective adjuvant therapies.
Abstract: Background Desmoid tumors are rare soft-tissue neoplasms with limited data on their management. We sought to determine the rates of recurrence following surgery for desmoid tumors and identify factors predictive of disease-free survival.

Journal ArticleDOI
TL;DR: The 30-day mortality rate highly underestimates the risk of dying in the first year after surgery, with excess 1-year mortality rates varying from 15 to 30%.
Abstract: Background Thirty-day mortality after surgery for colorectal cancer may vastly underestimate 1-year mortality. This study aimed to quantify the excess mortality in the first postoperative year of stage I–III colorectal cancer patients and to identify risk factors for excess mortality.

Journal ArticleDOI
TL;DR: Jumonji Domain Containing 6 (JMJD6) protein was expressed at highest levels in tumors associated with worse outcomes, including ER- and basal-like, Claudin-low, Her2-enriched, and ER+ Luminal B tumors, suggesting that JMJD6 may affect similar pathways in primary breast cancer.
Abstract: We developed an analytic strategy that correlates gene expression and clinical outcomes as a means to identify novel candidate oncogenes operative in breast cancer. This analysis, followed by functional characterization, resulted in the identification of Jumonji Domain Containing 6 (JMJD6) protein as a novel driver of oncogenic properties in breast cancer. Through microarray informatics, Cox proportional hazards regression was used to analyze the correlation between gene expression and distant metastasis-free survival (DMFS) of patients in 14 independent breast cancer cohorts. JMJD6 emerged as a top candidate gene robustly associated with poor patient survival. Immunohistochemistry, siRNA-mediated silencing, and forced overexpression of JMJD6 in cell-based assays elucidated molecular mechanisms of JMJD6 action in breast cancer progression and shed light on the clinical breast cancer subtypes relevant to JMJD6 action. JMJD6 was expressed at highest levels in tumors associated with worse outcomes, including ER- and basal-like, Claudin-low, Her2-enriched, and ER+ Luminal B tumors. High nuclear JMJD6 protein was associated with ER negativity, advanced grade, and poor differentiation in tissue microarrays. Separation of ER+/LN- patients that received endocrine monotherapy indicated that JMJD6 is predictive of poor outcome in treatment-specific subgroups. In breast cancer cell lines, loss of JMJD6 consistently resulted in suppressed proliferation but not apoptosis, whereas forced stable overexpression increased growth. In addition, knockdown of JMJD6 in invasive cell lines, such as MDA-MB231, decreased motility and invasion, whereas overexpression in MCF-7 cells slightly promoted motility but did not confer invasive growth. Microarray analysis showed that the most significant transcriptional changes occurred in cell-proliferation genes and genes of the TGF-β tumor-suppressor pathway. High proliferation was characterized by constitutively high cyclin E protein levels. The inverse relation of JMJD6 expression with TGF-β 2 could be extrapolated to the breast cancer cohorts, suggesting that JMJD6 may affect similar pathways in primary breast cancer. JMJD6 is a novel biomarker of tumor aggressiveness with functional implications in breast cancer growth and migration.

Journal ArticleDOI
TL;DR: It is demonstrated that brain metastases often show very complex genomic-aberration patterns, suggesting a potential role of PTEN and EGFR in brain metastasis formation.
Abstract: With the improvement of therapeutic options for the treatment of breast cancer, the development of brain metastases has become a major limitation to life expectancy in many patients. Therefore, our aim was to identify molecular markers associated with the development of brain metastases in breast cancer. Patterns of chromosomal aberrations in primary breast tumors and brain metastases were compared with array-comparative genetic hybridization (CGH). The most significant region was further characterized in more detail by microsatellite and gene-expression analysis, and finally, the possible target gene was screened for mutations. The array CGH results showed that brain metastases, in general, display similar chromosomal aberrations as do primary tumors, but with a notably higher frequency. Statistically significant differences were found at nine different chromosomal loci, with a gain and amplification of EGFR (7p11.2) and a loss of 10q22.3-qter being among the most significant aberrations in brain metastases (P < 0.01; false discovery rate (fdr) < 0.04). Allelic imbalance (AI) patterns at 10q were further verified in 77 unmatched primary tumors and 21 brain metastases. AI at PTEN loci was found significantly more often in brain metastases (52%) and primary tumors with a brain relapse (59%) compared with primary tumors from patients without relapse (18%; P = 0.003) or relapse other than brain tumors (12%; P = 0.006). Loss of PTEN was especially frequent in HER2-negative brain metastases (64%). Furthermore, PTEN mRNA expression was significantly downregulated in brain metastases compared with primary tumors, and PTEN mutations were frequently found in brain metastases. These results demonstrate that brain metastases often show very complex genomic-aberration patterns, suggesting a potential role of PTEN and EGFR in brain metastasis formation.

Journal ArticleDOI
TL;DR: Patients with CRLM could get long-term survival benefit from different types of therapy, and resection of liver metastases was the optimal strategy.
Abstract: Objective This study was designed to evaluate the long-time outcome of patients with colorectal liver metastasis (CRLM) undergoing different types of therapy and identify prognosis factors.

Journal ArticleDOI
TL;DR: miR-133a expression was lost in breast cancer tissues, loss of which was associated with lymph nodes metastasis, high clinical stages and shorter relapse-free survivals of patients with breast cancer.
Abstract: miRNAs, endogenous oligonucleotide RNAs, play an important role in mammary gland carcinogenesis and tumor progression. Detection of their expression and investigation of their functions could lead to discovery of novel biomarkers for breast cancer. In situ hybridization was used to detect miR-133a expression in formalin-fixed paraffin-embedded breast surgical specimens from 26 benign, 34 pericancerously normal and 90 cancerous tissues. qRT-PCR was performed to assess miR-133a levels in 6 breast cell lines and 10 benign and 18 cancerous fresh breast tissue specimens. Cell viability, migration, and invasion assays were used to determine the role of miR-133a in regulation of breast cancer cell growth, migration, and invasion, respectively. Luciferase assay was performed to assess miR-133a binding to FSCN1 gene. Expression of miR-133a was reduced from normal through benign to cancerous breast tissues. Expression of miR-133a was also low in breast cancer cell lines. The reduced miR-133a expression was associated with lymph nodes metastasis, high clinical stages, and shorter relapse-free survivals of patients with breast cancer. Furthermore, transfection of miR-133a oligonucleotides slightly inhibited growth but significantly decreased migration and invasion capacity of breast cancer cells, compared with negative controls, whereas knockdown of miR-133a expression induced breast cancer cell migration and invasion. In addition, we identified a putative miR-133a binding site in the 3'-untranslated region (UTR) of Fascin1 (FSCN1) gene using an online bioinformatical tool. We found that miR-133a transfection significantly reduced expression of FSCN1 mRNA and protein. The luciferase reporter assay confirmed that FSCN1 was the direct target gene of miR-133a. miR-133a expression was lost in breast cancer tissues, loss of which was associated with lymph nodes metastasis, high clinical stages and shorter relapse-free survivals of patients with breast cancer. Functionally, miR-133a can suppress tumor cell invasion and migration and targeted the expression of FSCN1. Future study will verify whether detection of miR-133a expression can served as a novel biomarker for breast cancer progression and patient prognosis.

Journal ArticleDOI
18 Jun 2012-PLOS ONE
TL;DR: Investigating whether miR levels in breast tumors are predictive of breast cancer local recurrence (LR) found higher expression of miR-9 was significantly associated with breast cancer LR in all cases as well as the subset of estrogen receptor (ER) positive cases (p = 0.02).
Abstract: MicroRNAs (miRs) are small, non-protein coding transcripts involved in many cellular functions Many miRs have emerged as important cancer biomarkers In the present study, we investigated whether miR levels in breast tumors are predictive of breast cancer local recurrence (LR) Sixty-eight women who were diagnosed with breast cancer at the Lombardi Comprehensive Cancer Center were included in this study Breast cancer patients with LR and those without LR were matched on year of surgery, age at diagnosis, and type of surgery Candidate miRs were identified by screening the expression levels of 754 human miRs using miR arrays in 16 breast tumor samples from 8 cases with LR and 8 cases without LR Eight candidate miRs that showed significant differences between tumors with and without LR were further verified in 52 tumor samples using real-time PCR Higher expression of miR-9 was significantly associated with breast cancer LR in all cases as well as the subset of estrogen receptor (ER) positive cases (p = 002) The AUCs (Area Under Curve) of receiver operating characteristic (ROC) curves of miR-9 for all tumors and ER positive tumors are 068 (p = 002) and 069 (p = 002), respectively In ER positive cases, Kaplan-Meier analysis showed that patients with lower miR-9 levels had significantly better 10-year LR-free survival (679% vs 308%, p = 002) Expression levels of miR-9 and another miR candidate, miR-375, were also strongly associated with ER status (p<0001 for both) The potential of miR-9 as a biomarker for LR warrants further investigation with larger sample size

Journal ArticleDOI
TL;DR: Calcifications on preoperative computed tomography correlate with intermediate grade and lymph node metastasis in well-differentiated PNET and supports the routine dissection of regional lymph nodes through formal pancreatectomy rather than enucleation in calcified PNET.
Abstract: Studies to identify preoperative prognostic variables for pancreatic neuroendocrine tumor (PNET) have been inconclusive. Specifically, the prevalence and prognostic significance of radiographic calcifications in these tumors remains unclear. From 1998 to 2009, a total of 110 patients with well-differentiated PNET underwent surgical resection at our institution. Synchronous liver metastases present in 31 patients (28%) were addressed surgically with curative intent. Patients with high-grade PNET were excluded. The presence of calcifications in the primary tumor on preoperative computed tomography was recorded and correlated with clinicopathologic variables and overall survival. Calcifications were present in 16% of patients and were more common in gastrinomas and glucagonomas (50%), but never encountered in insulinomas. Calcified tumors were larger (median size 4.5 vs. 2.3 cm, P = 0.04) and more commonly associated with lymph node metastasis (75 vs. 35%, P = 0.01), synchronous liver metastasis (62 vs. 21%, P < 0.01), and intermediate tumor grade (80 vs. 31%, P < 0.01). On multivariate analysis of factors available preoperatively, calcifications (P = 0.01) and size (P < 0.01) remained independent predictors of lymph node metastasis. Overall survival after resection was significantly worse in the presence of synchronous liver metastasis (5-year, 64 vs. 86%, P = 0.04), but not in the presence of radiographic calcifications. Calcifications on preoperative computed tomography correlate with intermediate grade and lymph node metastasis in well-differentiated PNET. This information is available preoperatively and supports the routine dissection of regional lymph nodes through formal pancreatectomy rather than enucleation in calcified PNET.

Journal ArticleDOI
TL;DR: MMP-9 is superior to MMP-2 for the prediction of tumor recurrence and survival in HCC patients after surgical resection and the prognostic value of M MP-9 overexpression was validated in the independent data set.
Abstract: Background The extracellular matrix metalloproteases MMP-9 and MMP-2 are critical for the invasive potential of tumors However, it is not clear which of the two plays the predominant role in tumor invasion and progression In the present study, we compared the clinical efficacy of MMP-9 and MMP-2 overexpression for predicting tumor recurrence and survival after surgical resection in HCC patients

Journal ArticleDOI
TL;DR: This retrospective study suggests that surgical resection in metastatic gastric cancer may improve survival when combined with chemotherapy, especially when metastasis is confined to one site.
Abstract: Purpose The purpose of this study was to examine the value of surgical resection and to find prognostic factors for metastatic gastric cancer.

Journal ArticleDOI
TL;DR: The data suggest that LSM can be a useful predictor of recurrence after curative resection of HCC, and this population was stratified into two groups using the optimal cutoff value, which maximized the sum of sensitivity and specificity from time-dependent receiver operating characteristic curves.
Abstract: Background The purpose of this study was to investigate whether preoperative liver stiffness measurement (LSM) can predict recurrence after curative resection of hepatocellular carcinoma (HCC). LSM using FibroScan® can assess the severity of liver fibrosis, which is significantly associated with recurrence after curative resection of HCC.

Journal ArticleDOI
TL;DR: Loss of Stat5a represents a new independent marker of poor prognosis in node-negative breast cancer and may be a predictor of response to antiestrogen therapy if validated in randomized clinical trials.
Abstract: Signal transducer and activator of transcripton-5a (Stat5a) and its close homologue, Stat5b, mediate key physiological effects of prolactin and growth hormone in mammary glands. In breast cancer, loss of nuclear localized and tyrosine phosphorylated Stat5a/b is associated with poor prognosis and increased risk of antiestrogen therapy failure. Here we quantify for the first time levels of Stat5a and Stat5b over breast cancer progression, and explore their potential association with clinical outcome. Stat5a and Stat5b protein levels were quantified in situ in breast-cancer progression material. Stat5a and Stat5b transcript levels in breast cancer were correlated with clinical outcome in 936 patients. Stat5a protein was further quantified in four archival cohorts totaling 686 patients with clinical outcome data by using multivariate models. Protein levels of Stat5a but not Stat5b were reduced in primary breast cancer and lymph node metastases compared with normal epithelia. Low tumor levels of Stat5a but not Stat5b mRNA were associated with poor prognosis. Experimentally, only limited overlap between Stat5a- and Stat5b-modulated genes was found. In two cohorts of therapy-naive, node-negative breast cancer patients, low nuclear Stat5a protein levels were an independent marker of poor prognosis. Multivariate analysis of two cohorts treated with antiestrogen monotherapy revealed that low nuclear Stat5a levels were associated with a more than fourfold risk of unfavorable outcome. Loss of Stat5a represents a new independent marker of poor prognosis in node-negative breast cancer and may be a predictor of response to antiestrogen therapy if validated in randomized clinical trials.

Journal ArticleDOI
TL;DR: The key issues raised by the recent availability of esophageal SCC treatment with the addition of chemotherapy, radiotherapy, and chemoradiotherapy to the surgical management of resectable disease are discussed and how clinical trials and meta-analysis inform current clinical practice are discussed.
Abstract: Esophageal cancer is the eighth most common cancer worldwide, and especially in some areas of China is the fourth most common cause of death and is of squamous cell carcinoma (SCC) histology in >90% of cases. Surgery alone was the mainstay of therapeutic intervention in the past, but high rates of local and systemic failure have prompted investigation into multidisciplinary management. In this review, we discuss the key issues raised by the recent availability of esophageal SCC treatment with the addition of chemotherapy, radiotherapy, and chemoradiotherapy to the surgical management of resectable disease and discuss how clinical trials and meta-analysis inform current clinical practice. None of the randomized trials that compared neoadjuvant radiotherapy or chemotherapy with surgery alone in esophageal SCC has demonstrated an increase in overall survival in those patients treated with neoadjuvant radiotherapy or chemotherapy. Neoadjuvant chemoradiotherapy has been accepted recently for esophageal cancer because such a regimen offers great opportunity for margin negative resection, improved loco-regional control and increased survival. The majority of the available evidence currently reveals that only selected locally advanced esophageal SCC are more likely to benefit from the adjuvant therapy. The focus of future trials should be on identification of the optimum regimen and should aim to minimize treatment toxicities and effect on quality of life, as well as attempt to identify and select those patients most likely to benefit from specific treatment options.

Journal ArticleDOI
TL;DR: Most patients develop liver-confined recurrence, which is usually amenable to ablative therapies that offer ongoing disease and symptom control, and an initial surgical approach combining simultaneous resection of liver metastases and primary/recurrent tumors can be performed with low mortality.
Abstract: Background Surgical approach is an accepted approach for metastatic neuroendocrine tumors (NET), but the safety and effectiveness of synchronous liver metastases resection with primary and/or locally recurrent NET is unclear.

Journal ArticleDOI
TL;DR: The interim analyses suggest that bursectomy may improve survival and should not be abandoned as a futile procedure until more definitive data can be obtained.
Abstract: Background Bursectomy is regarded as a standard surgical procedure during gastrectomy for serosa-positive gastric cancer in Japan. There is little evidence, however, that bursectomy has clinical benefit. We conducted a randomized controlled trial to demonstrate non-inferiority of treatment with the omission of bursectomy.

Journal ArticleDOI
TL;DR: Coexpression of stemness markers Oct4 and Nanog in HCC indicated the aggressive tumor behaviors and predicted a worse clinical outcome, which may be a useful biomarker to identify patients at high risk of postoperative recurrence.
Abstract: Background Oct4 and Nanog are two major transcription factors related to the stem cell self-renewal and differentiation. The aim of this study was to evaluate the correlation between these two stemness markers with recurrence, metastasis, and prognosis of hepatocellular carcinoma (HCC).

Journal ArticleDOI
TL;DR: IMRT is an advanced technique, its excellent treatment outcomes have been reproduced in many single institution studies, and perhaps IMRT-delivered RT can replace the benefit provided by chemotherapy when added to conventional RT.
Abstract: Introduction Advances in radiation therapy, such as intensity-modulated radiation therapy (IMRT), have allowed high-dose delivery to tumors while sparing normal tissues. However, IMRT requires careful delineation of target volumes to prevent marginal recurrences.

Journal ArticleDOI
TL;DR: Pre-ALP was an independent prognostic factor for the survival of osteosarcoma patients in south China, and correlated with MMP-9 expression and lung metastasis, and can also serve as a prognostic marker for treatment, and merit large-scale validation studies.
Abstract: Osteosarcoma is a malignant tumor with high ability to form invasion and metastasis. Identifying prognostic factor in osteosarcoma is helpful to select those patients for more aggressive management. Our study evaluated serum alkaline phosphatase (ALP) cooperating with matrix metalloproteinase-9 (MMP-9) as an important prognostic predictor for local recurrence and distant metastasis of osteosarcoma. 177 cases were included from the osteosarcoma patients treated at 1st Affiliated Hospital of Sun Yat-sen University (1999-2008). Pre-chemotherapy serum ALP (pre-ALP) were studied and correlated with tumor recurrence, lung metastasis and patient survival. MMP-9 protein in tumor tissues was detected by immunohistochemistry and correlated with pre-ALP level. Pre-ALP were partitioned into normal, high, and very high groups, in each group the incidence of metastases was 12.2%, 21.2% and 34.6%, respectively (p = 0.007). In the three groups the mean disease-free survival (DFS) was 57 ± 3.15, 28 ± 3.57 and 14 ± 3.35 months, respectively (p < 0.001); overall survival (OS) was 92 ± 26.89, 39 ± 8.61 and 17 ± 5.07 months, respectively (p < 0.001). By multivariate analysis, elevated serum pre-ALP were associated with shorter DFS (p = 0.018) and OS (p = 0.031). If elevated ALP levels decreased after clinical treatment, the incidence of lung metastasis rate decreased (p = 0.028); DFS and OS were both prolonged (p < 0.001). Pre-ALP was also positively correlated with MMP-9 expression (p = 0.015) in tumor tissue. Pre-ALP was an independent prognostic factor for the survival of osteosarcoma patients in south China, and correlated with MMP-9 expression and lung metastasis. ALP can also serve as a prognostic marker for treatment, and merit large-scale validation studies.

Journal ArticleDOI
TL;DR: Period 3 expression was analyzed in the normal and cancerous tissues from patients with colon cancer by establishing a long serial analysis of gene expression (SAGE) database as well as by real-time PCR and immunohistochemistry and revealed that PER3 mRNA levels in tumor tissues were lower than in normal tissues.
Abstract: Period 3 (PER3), a circadian regulation protein, influences cell cycle, growth, and differentiation. The aim of the present study was to determine whether PER3 expression is associated with colon cancer incidence and progression. PER3 expression was analyzed in the normal and cancerous tissues from patients with colon cancer by establishing a long serial analysis of gene expression (SAGE) database as well as by real-time PCR and immunohistochemistry. As compared with normal tissue, a 2.8-fold decrease in PER3 mRNA levels in colon cancerous tissue was observed. Real-time PCR analysis revealed that PER3 mRNA levels in tumor tissues were lower than in normal tissues (P < 0.001) in both patients with colon tumor and those with rectal tumor. In addition, PER3 expression was related to multiple clinicopathologic factors, including tumor location, differentiation, and stage. Furthermore, the incidence of death was higher in subjects with PER3-negative tumors (P = 0.025); the estimated overall survival time was 71.5 ± 2.2 months and 58.6 ± 5.0 months in subjects with PER3-positive and PER3-negative tumors, respectively (P = 0.020). PER3 may play a role in colon cancer progression.