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Xu YH, Lu P, Gao MC, Wang R, Li YY, Guo RQ, Zhang WS, Song JX. Nomogram based on multimodal magnetic resonance combined with B7-H3mRNA for preoperative lymph node prediction in esophagus cancer. World J Clin Oncol 2024; 15:419-433. [PMID: 38576593 PMCID: PMC10989267 DOI: 10.5306/wjco.v15.i3.419] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 01/15/2024] [Accepted: 02/06/2024] [Indexed: 03/22/2024] Open
Abstract
BACKGROUND Accurate preoperative prediction of lymph node metastasis (LNM) in esophageal cancer (EC) patients is of crucial clinical significance for treatment planning and prognosis. AIM To develop a clinical radiomics nomogram that can predict the preoperative lymph node (LN) status in EC patients. METHODS A total of 32 EC patients confirmed by clinical pathology (who underwent surgical treatment) were included. Real-time fluorescent quantitative reverse transcription-polymerase chain reaction was used to detect the expression of B7-H3 mRNA in EC tissue obtained during preoperative gastroscopy, and its correlation with LNM was analyzed. Radiomics features were extracted from multi-modal magnetic resonance imaging of EC using Pyradiomics in Python. Feature extraction, data dimensionality reduction, and feature selection were performed using XGBoost model and leave-one-out cross-validation. Multivariable logistic regression analysis was used to establish the prediction model, which included radiomics features, LN status from computed tomography (CT) reports, and B7-H3 mRNA expression, represented by a radiomics nomogram. Receiver operating characteristic area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the predictive performance and clinical application value of the model. RESULTS The relative expression of B7-H3 mRNA in EC patients with LNM was higher than in those without metastasis, and the difference was statistically significant (P < 0.05). The AUC value in the receiver operating characteristic (ROC) curve was 0.718 (95%CI: 0.528-0.907), with a sensitivity of 0.733 and specificity of 0.706, indicating good diagnostic performance. The individualized clinical prediction nomogram included radiomics features, LN status from CT reports, and B7-H3 mRNA expression. The ROC curve demonstrated good diagnostic value, with an AUC value of 0.765 (95%CI: 0.598-0.931), sensitivity of 0.800, and specificity of 0.706. DCA indicated the practical value of the radiomics nomogram in clinical practice. CONCLUSION This study developed a radiomics nomogram that includes radiomics features, LN status from CT reports, and B7-H3 mRNA expression, enabling convenient preoperative individualized prediction of LNM in EC patients.
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Affiliation(s)
- Yan-Han Xu
- School of Clinical Sciences, Graduate School of Nantong University, Yancheng 226019, Jiangsu Province, China
- Department of Thoracic Surgery, Yancheng Third People's Hospital, The Affiliated Hospital 6 of Nantong University, Yancheng 224000, Jiangsu Province, China
| | - Peng Lu
- Department of Imaging, Yancheng Third People's Hospital, The Affiliated Hospital 6 of Nantong University, Yancheng 224000, Jiangsu Province, China
| | - Ming-Cheng Gao
- School of Clinical Sciences, Graduate School of Nantong University, Yancheng 226019, Jiangsu Province, China
- Department of Thoracic Surgery, Yancheng Third People's Hospital, The Affiliated Hospital 6 of Nantong University, Yancheng 224000, Jiangsu Province, China
| | - Rui Wang
- School of Clinical Sciences, Graduate School of Nantong University, Yancheng 226019, Jiangsu Province, China
- Department of Thoracic Surgery, Yancheng Third People's Hospital, The Affiliated Hospital 6 of Nantong University, Yancheng 224000, Jiangsu Province, China
| | - Yang-Yang Li
- School of Clinical Sciences, Graduate School of Nantong University, Yancheng 226019, Jiangsu Province, China
- Department of Thoracic Surgery, Yancheng Third People's Hospital, The Affiliated Hospital 6 of Nantong University, Yancheng 224000, Jiangsu Province, China
| | - Rong-Qi Guo
- School of Clinical Sciences, Graduate School of Nantong University, Yancheng 226019, Jiangsu Province, China
- Department of Thoracic Surgery, Yancheng Third People's Hospital, The Affiliated Hospital 6 of Nantong University, Yancheng 224000, Jiangsu Province, China
| | - Wei-Song Zhang
- School of Clinical Sciences, Graduate School of Nantong University, Yancheng 226019, Jiangsu Province, China
- Department of Thoracic Surgery, Yancheng Third People's Hospital, The Affiliated Hospital 6 of Nantong University, Yancheng 224000, Jiangsu Province, China
| | - Jian-Xiang Song
- Department of Thoracic Surgery, Yancheng Third People's Hospital, The Affiliated Hospital 6 of Nantong University, Yancheng 224000, Jiangsu Province, China
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Ibrahim-Shaikh S, Shaikh N, Daboul N, Alshaikhnassir E, Hafez M, Freiser ME. Metastatic Esophageal Adenocarcinoma Presenting as Neck Dermal Metastasis. Case Rep Dermatol Med 2024; 2024:7951391. [PMID: 38264294 PMCID: PMC10805548 DOI: 10.1155/2024/7951391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/18/2023] [Accepted: 11/15/2023] [Indexed: 01/25/2024] Open
Abstract
Dermal metastasis is a rare manifestation of visceral disease, and esophageal adenocarcinomas represent around only 1% of primaries that present with cutaneous metastasis. In this case, we discuss a patient who presented with a painless submental mass and extensive right neck cutaneous induration and erythema. Core needle biopsy demonstrated poorly differentiated adenocarcinoma. Blood testing also demonstrated elevated carbohydrate antigen 19-9, carcinoembryonic antigen, and alkaline phosphatase. PET/CT followed by esophagoscopy led to the diagnosis of esophageal signet-cell adenocarcinoma primary with isolated dermal metastasis. The patient was started on palliative radiotherapy and passed away two months later from a suspected thoracic fistula and hydropneumothorax.
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Affiliation(s)
| | - Noah Shaikh
- Department of Otolaryngology-Head and Neck Surgery, West Virginia University, Morgantown, West Virginia, USA
| | - Nour Daboul
- Department of Hematology/Oncology, West Virginia University, Morgantown, West Virginia, USA
| | - Esra Alshaikhnassir
- Department of Pathology, West Virginia University, Morgantown, West Virginia, USA
| | - Maria Hafez
- Department of Hematology/Oncology, West Virginia University, Morgantown, West Virginia, USA
| | - Monika E. Freiser
- Department of Otolaryngology-Head and Neck Surgery, West Virginia University, Morgantown, West Virginia, USA
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Zhang X, Qi K, Huang W, Liu J, Lin G, Li J. Left versus right approach for middle and lower esophageal squamous cell carcinoma: A propensity score-matched study. Front Oncol 2022; 12:858660. [PMID: 36582805 PMCID: PMC9792602 DOI: 10.3389/fonc.2022.858660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 11/17/2022] [Indexed: 12/15/2022] Open
Abstract
Background Despite superior short-term outcomes, there is considerable debate about the oncological efficacy of the left approach esophagectomy for middle and lower squamous esophageal carcinoma (ESCC). A propensity score-matched retrospective study was conducted to evaluate the left approach's short- and long-term effects. Methods We recorded data from patients with ESCC who underwent curative resection via the left or right approach between January 2010 and December 2015. Propensity score matching (PSM) was performed, and maximally selected rank statistics (MSRS) were utilized to determine the appropriate number of lymph nodes to resect during esophagectomy. Results One hundred and forty-eight ESCC patients underwent esophagectomy via the right approach, and 108 underwent the left approach esophagectomy. After PSM, the left approach esophagectomy showed statistically significant superiority in operative time and time to oral intake, and there was a trend toward a shorter length of hospital stay. Fewer cervical, upper thoracic, and recurrent laryngeal nerve lymph nodes were harvested via the left approach than the right approach; the total number of lymph nodes harvested via the left and right approaches was similar. Similar long-term survival outcomes were achieved. MSRS suggested that at least 25 lymph nodes are needed to be resected during esophagectomy to improve survival in N0 patients. Conclusions The left approach esophagectomy might facilitate postoperative recovery in patients with middle and lower ESCC. With adequate lymphadenectomy, the left approach esophagectomy might achieve similar long-term outcomes for middle and lower ESCC patients.
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Peng G, Zhan Y, Wu Y, Zeng C, Wang S, Guo L, Liu W, Luo L, Wang R, Huang K, Huang B, Chen J, Chen C. Radiomics models based on CT at different phases predicting lymph node metastasis of esophageal squamous cell carcinoma (GASTO-1089). Front Oncol 2022; 12:988859. [PMID: 36387160 PMCID: PMC9643555 DOI: 10.3389/fonc.2022.988859] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 10/07/2022] [Indexed: 02/05/2023] Open
Abstract
PURPOSE To investigate the value of radiomics models based on CT at different phases (non-contrast-enhanced and contrast-enhanced images) in predicting lymph node (LN) metastasis in esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS Two hundred and seventy-four eligible patients with ESCC were divided into a training set (n =193) and a validation set (n =81). The least absolute shrinkage and selection operator algorithm (LASSO) was used to select radiomics features. The predictive models were constructed with radiomics features and clinical factors through multivariate logistic regression analysis. The predictive performance and clinical application value of the models were evaluated by area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA). The Delong Test was used to evaluate the differences in AUC among models. RESULTS Sixteen and eighteen features were respectively selected from non-contrast-enhanced CT (NECT) and contrast-enhanced CT (CECT) images. The model established using only clinical factors (Model 1) has an AUC value of 0.655 (95%CI 0.552-0.759) with a sensitivity of 0.585, a specificity of 0.725 and an accuracy of 0.654. The models contained clinical factors with radiomics features of NECT or/and CECT (Model 2,3,4) have significantly improved prediction performance. The values of AUC of Model 2,3,4 were 0.766, 0.811 and 0.809, respectively. It also achieved a great AUC of 0.800 in the model built with only radiomics features derived from NECT and CECT (Model 5). DCA suggested the potential clinical benefit of model prediction of LN metastasis of ESCC. A comparison of the receiver operating characteristic (ROC) curves using the Delong test indicated that Models 2, 3, 4, and 5 were superior to Model 1(P< 0.05), and no difference was found among Model 2, 3, 4 and Model 5(P > 0.05). CONCLUSION Radiomics models based on CT at different phases could accurately predict the lymph node metastasis in patients with ESCC, and their predictive efficiency was better than the clinical model based on tumor size criteria. NECT-based radiomics model could be a reasonable option for ESCC patients due to its lower price and availability for renal failure or allergic patients.
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Affiliation(s)
- Guobo Peng
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
- Department of Radiation Oncology, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, China
| | - Yizhou Zhan
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Yanxuan Wu
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Chengbing Zeng
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Siyan Wang
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
- Shantou University Medical College, Shantou, China
| | - Longjia Guo
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Weitong Liu
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
- Department of Radiation Oncology, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, China
| | - Limei Luo
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
- Shantou University Medical College, Shantou, China
| | - Ruoheng Wang
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
- Shantou University Medical College, Shantou, China
| | - Kang Huang
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
- Shantou University Medical College, Shantou, China
| | - Baotian Huang
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Jianzhou Chen
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Chuangzhen Chen
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
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Tumor microenvironment characterization in esophageal cancer identifies prognostic relevant immune cell subtypes and gene signatures. Aging (Albany NY) 2021; 13:26118-26136. [PMID: 34954689 PMCID: PMC8751614 DOI: 10.18632/aging.203800] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 12/08/2021] [Indexed: 12/12/2022]
Abstract
Esophageal cancer (ESCA) is a common malignancy in the digestive system with a high mortality rate and poor prognosis. Tumor microenvironment (TME) plays an important role in the tumorigenesis, progression and therapy resistance of ESCA, whereas its role in predicting clinical outcomes has not been fully elucidated. In this study, we comprehensively estimated the TME infiltration patterns of 164 ESCA patients using Gene Set Variation Analysis (GSVA) and identified 4 key immune cells (natural killer T cell, immature B cell, natural killer cell, and type 1 T helper cell) associated with the prognosis of ESCA patients. Besides, two TME groups were defined based on the TME patterns with different clinical outcomes. According to the expression gene set between two TME groups, we built a model to calculate TMEscore based on the single-sample gene-set enrichment analysis (ssGSEA) algorithm. TMEscore systematically correlated the TME groups with genomic characteristics and clinicopathologic features. In conclusion, our data provide a novel TMEscore which can be regarded as a reliable index for predicting the clinical outcomes of ESCA.
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Liesenfeld LF, Schmidt T, Zhang-Hagenlocher C, Sauer P, Diener MK, Müller-Stich BP, Hackert T, Büchler MW, Schaible A. Self-expanding Metal Stents for Anastomotic Leaks After Upper Gastrointestinal Cancer Surgery. J Surg Res 2021; 267:516-526. [PMID: 34256194 DOI: 10.1016/j.jss.2021.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 04/25/2021] [Accepted: 06/08/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Anastomotic leakage (AL) is a common and severe complication after upper gastrointestinal (UGI) surgery. Although evidence is scarce, endoscopic deployed self-expanding metal stents (SEMS) are well-established for the management of AL in UGI surgery. The present study aimed to evaluate the feasibility, effectiveness, and safety of SEMS in terms of success, mortality, and morbidity in patients with AL after UGI cancer surgery. MATERIALS AND METHODS Patients with AL after primary UGI cancer surgery were retrospectively analyzed with regard to demographics, disease, surgical and endoscopic procedures, and complications. Stent treatment success was divided into technical, primary (within 72 hours of stent deployment), sustained (after 72 hours of stent deployment), and sealing success. RESULTS In a total of 63 patients, 74 stents were used and 11 were deployed in endoscopic reinterventions. Stent deployment was successful in all patients. Primary and sustained success rates were 68.3% (n = 43) and 65.1% (n = 41), respectively. Of the primarily successfully treated patients, 87.8% remained successfully treated. If primary treatment was unsuccessful, it remained unsuccessful in 66.6% of the patients (P = 0.002). Final sealing of the leakage was observed in 65.1% of patients (n = 41). Longer stent shafts and wider stent end widths were correlated with successful stent treatment (P < 0.05). CONCLUSION SEMS are a safe and sufficient tool in the treatment of AL after UGI cancer surgery. Treatment success is improved with longer stent shafts and wider stent end widths. Switching to alternative treatments is strongly suggested if signs of persistent leakage are present beyond 72 hours after stent placement, as this is highly indicative of sustained stent failure.
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Affiliation(s)
- Lukas F Liesenfeld
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
| | - Thomas Schmidt
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | | | - Peter Sauer
- Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany
| | - Markus K Diener
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Beat P Müller-Stich
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Anja Schaible
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
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Wang F, Zhang L, Xu Y, Xie Y, Li S. Comprehensive Analysis and Identification of Key Driver Genes for Distinguishing Between Esophageal Adenocarcinoma and Squamous Cell Carcinoma. Front Cell Dev Biol 2021; 9:676156. [PMID: 34124063 PMCID: PMC8194272 DOI: 10.3389/fcell.2021.676156] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 04/09/2021] [Indexed: 01/01/2023] Open
Abstract
Background: Esophageal cancer (EC) is one of the deadliest cancers in the world. However, the mechanism that drives the evolution of EC is still unclear. On this basis, we identified the key genes and molecular pathways that may be related to the progression of esophageal adenocarcinoma and squamous cell carcinoma to find potential markers or therapeutic targets. Methods: GSE26886 were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) among normal samples, EA, and squamous cell carcinoma were determined using R software. Then, potential functions of DEGs were determined using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The STRING software was used to identify the most important modules in the protein-protein interaction (PPI) network. The expression levels of hub genes were confirmed using UALCAN database. Kaplan-Meier plotters were used to confirm the correlation between hub genes and outcomes in EC. Results: In this study, we identified 1,098 genes induced in esophageal adenocarcinoma (EA) and esophageal squamous cell carcinoma (ESCC), and 669 genes were reduced in EA and ESCC, suggesting that these genes may play an important role in the occurrence and development of EC tumors. Bioinformatics analysis showed that these genes were involved in cell cycle regulation and p53 and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. In addition, we identified 147 induced genes and 130 reduced genes differentially expressed in EA and ESCC. The expression of ESCC in the EA group was different from that in the control group. By PPI network analysis, we identified 10 hub genes, including GNAQ, RGS5, MAPK1, ATP1B1, HADHA, HSDL2, SLC25A20, ACOX1, SCP2, and NLN. TCGA validation showed that these genes were present in the dysfunctional samples between EC and normal samples and between EA and ESCC. Kaplan-Meier analysis showed that MAPK1, ACOX1, SCP2, and NLN were associated with overall survival in patients with ESCC and EA. Conclusions: In this study, we identified a series of DEGs between EC and normal samples and between EA and ESCC samples. We also identified 10 key genes involved in the EC process. We believe that this study may provide a new biomarker for the prognosis of EA and ESCC.
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Affiliation(s)
- Feng Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lan Zhang
- Department of Pathology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Yue Xu
- Department of Pathology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Yilin Xie
- Department of Pathology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Shenglei Li
- Department of Pathology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
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Macedo-Silva C, Miranda-Gonçalves V, Lameirinhas A, Lencart J, Pereira A, Lobo J, Guimarães R, Martins AT, Henrique R, Bravo I, Jerónimo C. JmjC-KDMs KDM3A and KDM6B modulate radioresistance under hypoxic conditions in esophageal squamous cell carcinoma. Cell Death Dis 2020; 11:1068. [PMID: 33318475 PMCID: PMC7736883 DOI: 10.1038/s41419-020-03279-y] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 10/30/2020] [Accepted: 11/03/2020] [Indexed: 12/24/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC), the most frequent esophageal cancer (EC) subtype, entails dismal prognosis. Hypoxia, a common feature of advanced ESCC, is involved in resistance to radiotherapy (RT). RT response in hypoxia might be modulated through epigenetic mechanisms, constituting novel targets to improve patient outcome. Post-translational methylation in histone can be partially modulated by histone lysine demethylases (KDMs), which specifically removes methyl groups in certain lysine residues. KDMs deregulation was associated with tumor aggressiveness and therapy failure. Thus, we sought to unveil the role of Jumonji C domain histone lysine demethylases (JmjC-KDMs) in ESCC radioresistance acquisition. The effectiveness of RT upon ESCC cells under hypoxic conditions was assessed by colony formation assay. KDM3A/KDM6B expression, and respective H3K9me2 and H3K27me3 target marks, were evaluated by RT-qPCR, Western blot, and immunofluorescence. Effect of JmjC-KDM inhibitor IOX1, as well as KDM3A knockdown, in in vitro functional cell behavior and RT response was assessed in ESCC under hypoxic conditions. In vivo effect of combined IOX1 and ionizing radiation treatment was evaluated in ESCC cells using CAM assay. KDM3A, KDM6B, HIF-1α, and CAIX immunoexpression was assessed in primary ESCC and normal esophagus. Herein, we found that hypoxia promoted ESCC radioresistance through increased KDM3A/KDM6B expression, enhancing cell survival and migration and decreasing DNA damage and apoptosis, in vitro. Exposure to IOX1 reverted these features, increasing ESCC radiosensitivity and decreasing ESCC microtumors size, in vivo. KDM3A was upregulated in ESCC tissues compared to the normal esophagus, associating and colocalizing with hypoxic markers (HIF-1α and CAIX). Therefore, KDM3A upregulation in ESCC cell lines and primary tumors associated with hypoxia, playing a critical role in EC aggressiveness and radioresistance. KDM3A targeting, concomitant with conventional RT, constitutes a promising strategy to improve ESCC patients' survival.
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Affiliation(s)
- Catarina Macedo-Silva
- Cancer Biology & Epigenetics Group - Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Porto, Portugal
| | - Vera Miranda-Gonçalves
- Cancer Biology & Epigenetics Group - Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Porto, Portugal
| | - Ana Lameirinhas
- Cancer Biology & Epigenetics Group - Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Porto, Portugal
| | - Joana Lencart
- Medical Physics, Radiobiology and Radiation Protection Group - Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Porto, Portugal
- Departments of Medical Physics, Portuguese Oncology Institute of Porto, Porto, Portugal
| | - Alexandre Pereira
- Medical Physics, Radiobiology and Radiation Protection Group - Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Porto, Portugal
- Departments of Medical Physics, Portuguese Oncology Institute of Porto, Porto, Portugal
| | - João Lobo
- Cancer Biology & Epigenetics Group - Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Porto, Portugal
- Departments of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal
- Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar - University of Porto (ICBAS-UP), Porto, Portugal
| | - Rita Guimarães
- Departments of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal
| | - Ana Teresa Martins
- Departments of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal
| | - Rui Henrique
- Cancer Biology & Epigenetics Group - Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Porto, Portugal
- Departments of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal
- Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar - University of Porto (ICBAS-UP), Porto, Portugal
| | - Isabel Bravo
- Medical Physics, Radiobiology and Radiation Protection Group - Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Porto, Portugal
| | - Carmen Jerónimo
- Cancer Biology & Epigenetics Group - Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Porto, Portugal.
- Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar - University of Porto (ICBAS-UP), Porto, Portugal.
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Liesenfeld LF, Sauer P, Diener MK, Hinz U, Schmidt T, Müller-Stich BP, Hackert T, Büchler MW, Schaible A. Prognostic value of inflammatory markers for detecting anastomotic leakage after esophageal resection. BMC Surg 2020; 20:324. [PMID: 33298038 PMCID: PMC7726907 DOI: 10.1186/s12893-020-00995-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 12/01/2020] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Early diagnosis of anastomotic leakage (AL) after esophageal resection is crucial for the successful management of this complication. Inflammatory serological markers are indicators of complications during the postoperative course. The aim of the present study was to evaluate the prognostic value of routine inflammatory markers to predict anastomotic leakage after transthoracic esophageal resection. METHODS Data from all consecutive patients undergoing transthoracic esophageal resection between January 2010 and December 2016 were analyzed from a prospective database. Besides clinicodemographic parameters, C-reactive protein, white blood cell count and albumin were analyzed and the Noble/Underwood (NUn) score was calculated to evaluate their predictive value for postoperative anastomotic leakage. Diagnostic accuracy was measured by sensitivity, specificity, and negative and positive predictive values using area under the receiver operator characteristics curve. RESULTS Overall, 233 patients with transthoracic esophageal resection were analyzed, 30-day mortality in this group was 3.4%. 57 patients (24.5%) suffered from AL, 176 patients were in the AL negative group. We found significant differences in WBCC, CRP and NUn scores between patients with and without AL, but the analyzed markers did not show an independent relevant prognostic value. For CRP levels below 155 mg/dl from POD3 to POD 7 the negative predictive value for absence of AI was > 80%. Highest diagnostic accuracy was detected for CRP levels on 4th POD with a cut-off value of 145 mg/l reaching negative predictive value of 87%. CONCLUSIONS In contrast to their prognostic value in other surgical procedures, CRP, WBCC and NUn score cannot be recommended as independent markers for the prediction of anastomotic leakage after transthoracic esophageal resection. CRP is an accurate negative predictive marker and discrimination of AL and no-AL may be helpful for postoperative clinical management. Trial registration The study was approved by the local ethical committee (S635-2013).
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Affiliation(s)
- Lukas F Liesenfeld
- Department of Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany.
| | - Peter Sauer
- Department of Gastroenterology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - Markus K Diener
- Department of Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Ulf Hinz
- Department of Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Thomas Schmidt
- Department of Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Beat P Müller-Stich
- Department of Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Thilo Hackert
- Department of Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Markus W Büchler
- Department of Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Anja Schaible
- Department of Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
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Scholer AJ, Uppal A, Chang SC, Ghosh D, Garland-Kledzik M, Santamaria-Barria J, Khader A, Dehal A, Fischer T, Goldfarb M. Inaccurate pretreatment staging can impact survival in early stage esophageal adenocarcinoma. J Surg Oncol 2020; 122:914-922. [PMID: 32632944 DOI: 10.1002/jso.26101] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 06/15/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Given the survival advantage of neoadjuvant treatment for locally advanced esophageal cancer, accurate clinical staging is necessary. The aim of this study was to assess the clinical (c) and pathologic (p) staging concordance rates for presumably early stage esophageal adenocarcinoma patients that had upfront esophagectomy (UFE) and evaluate if survival (OS) was negatively affected by inaccurate preoperative staging and subsequent treatment selection. METHODS An NCDB retrospective review of nonmetastatic esophageal adenocarcinoma patients that had UFE. The rates of concordance between c and p staging system and OS were calculated. RESULTS Of 2775 patients, most patients presented with cN0 (82.8%) and cT1 tumors (53.6%). The overall concordance between c and p staging was 78.8% for T-classification (moderate agreement; weighted κ = 0.729; P < .001) and 78.8% for N-classification (weak agreement; weighted κ = 0.448; P < .001). Patients that were upstaged due to a lack of concordance between T-classification had decreased 5- and 10-year OS (30% and 16%, P < .001) and those upstaged due to discordant N-classification had decreased 5- and 10-year OS (28% and 23%, P < .001)." CONCLUSIONS Preoperative staging of esophageal adenocarcinoma has moderate reliability and accuracy for predicting pT and pN classification. Up to 25% of patients have discordant clinical and pathological staging, which impacts OS.
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Affiliation(s)
- Anthony J Scholer
- Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California
| | - Abhineet Uppal
- Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California
| | - Shu-Ching Chang
- Medical Data Research Center, Providence Health and Services Oregon and Southwest Washington, Portland, Oregon
| | - Debopriya Ghosh
- Rutgers Institute of Data Science, Learning, and Applications, Rutgers University, Newark, New Jersey
| | - Mary Garland-Kledzik
- Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California
| | | | - Adam Khader
- Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California
| | - Ahmed Dehal
- Department of Surgery, Kaiser Permanente Southern California, Pasadena, California
| | - Trevan Fischer
- Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California
| | - Melanie Goldfarb
- Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California
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11
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Kassardjian A, Wang HL. SMAD4-Expressing Pancreatic Ductal Adenocarcinomas Have Better Response to Neoadjuvant Therapy and Significantly Lower Lymph Node Metastasis Rates. Pancreas 2020; 49:1153-1160. [PMID: 32897998 DOI: 10.1097/mpa.0000000000001636] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE For many patients whose pancreatic ductal adenocarcinoma (PDAC) is locally advanced, neoadjuvant therapy has been proposed as a way to decrease tumor burden. Pancreatic ductal adenocarcinoma is generally thought to be resistant to chemotherapy and radiation, however, response to neoadjuvant therapy in PDAC has been described in a subset of patients. The SMAD4 status is considered to be an important molecular feature which distinguishes two subsets of PDAC, SMAD4-positive and -negative tumors. The objective of this study was to evaluate the neoadjuvant treatment response rate as well as compare the different clinicopathologic variables between SMAD4-positive and -negative tumors. METHODS We analyzed the data of patients who underwent surgical resection for PDAC from 2009-2019. Our cohort from a single institution included 233 patients. RESULTS Of the 233 cases, 143 (61.4%) were SMAD4-negative and 90 (38.6%) were SMAD4-positive. Overall, SMAD4-positive tumors with neoadjuvant therapy had better treatment response and better tumor regression scores. In addition, SMAD4-positive tumors had a significantly lower lymph node metastasis rate in both the neoadjuvant and nonneoadjuvant setting. CONCLUSIONS Further characterization of the role of SMAD4 within the context of neoadjuvant therapy will lead to improved personalized therapeutic strategies.
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Affiliation(s)
- Ari Kassardjian
- From the Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA
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12
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Lv Y, Song M, Tian X, Yv X, Liang N, Zhang J. Impact of radiotherapy on circulating lymphocyte subsets in patients with esophageal cancer. Medicine (Baltimore) 2020; 99:e20993. [PMID: 32898991 PMCID: PMC7478455 DOI: 10.1097/md.0000000000020993] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Radiotherapy (RT) can affect the immune function of patients with cancer. The purpose of this study was to investigate the effect of RT on lymphocyte and its subsets in patients with esophageal cancer (EC).All patients received RT with a mean dose of 5369 cGy (gray). Blood parameters were measured in 31 patients on 3 occasions (before, at the end of radiotherapy, and at 3 months follow-up). The whole blood count and lymphocyte subsets were measured and correlated with short time efficiency and radiation dose parameters.White blood count (WBC) and lymphocyte count (ALC) were greatly decreased at the end of radiotherapy, and the percentages of CD3+, CD3+CD8+ T cells were significantly increased, on the other hand, a decrease in the CD4/CD8 ratio was observed. The percentages of CD3-CD16/56+NK cells and CD19+ B cell were decreased at the end of RT compared with prior RT. The percentages of CD3+ T cells before RT and the WBC and ALC count after RT can be used as prognostic indicators for survival. The PTV dose can cause significant changes in lymphocytes count after RT. CD3+T cells after RT were significantly correlated with mean heart dose and heart V50.Our study identified that RT causes changes in lymphocyte subsets, and these changes may indicate differences in immune function between individuals. Radiotherapy plan should be designed to minimize normal tissue dose to reduce the impact on WBC and lymphocytes.
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Affiliation(s)
- Yajuan Lv
- Shandong Provincial Qianfoshan Hospital, Shandong University
| | - Meijuan Song
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Xiufang Tian
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Xinshuang Yv
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Ning Liang
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Jiandong Zhang
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
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13
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Yang Y, Tian Z, Zhao X, Li Y, Duan S. A novel antitumor dithiocarbamate compound inhibits the EGFR/AKT signaling pathway and induces apoptosis in esophageal cancer cells. Oncol Lett 2020; 20:877-883. [PMID: 32566015 PMCID: PMC7285826 DOI: 10.3892/ol.2020.11638] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 04/16/2020] [Indexed: 01/03/2023] Open
Abstract
Dithiocarbamate has been reported to possess a potent antitumor efficacy against several types of cancer, such as ovarian cancer, breast cancer and hepatocellular carcinoma; however, only a few studies have investigated its inhibitory effect on esophageal cancer. Dipyridylhydrazone dithiocarbamate (DpdtC) is a novel dithiocarbamate derivative that was recently designed, synthesized and evaluated in our previous study. In the present study, the cell growth inhibition and apoptosis induced by DpdtC were measured using the CCK-8 and Annexin V-FITC/propidium iodide staining assays, respectively. Epidermal growth factor receptor (EGFR) signaling pathway and apoptosis related protein levels were examined by western blotting. In vivo effect of DpdtC was evaluated in nude mice bearing KYSE-450 ×enograft tumors. The aims of the present study were to further evaluate the antitumor effects of DpdtC on esophageal cancer cells (KYSE-150 and KYSE-450 cells), and to investigate its potential mechanism of action in vitro and in vivo. It was found that DpdtC significantly inhibited KYSE-150 and KYSE-450 cell proliferation by regulating the EGFR/AKT signaling pathway and inducing apoptosis. In addition, this effect was further identified in vivo; DpdtC inhibited the growth of the KYSE-450 esophageal cancer xenografts by regulating the EGFR/AKT signaling pathway. Furthermore, DpdtC did not affect the body weight in mice. Collectively, the present results suggested that DpdtC may be a promising antitumor drug candidate for the treatment of esophageal cancer.
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Affiliation(s)
- Yun Yang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China.,Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
| | - Ziyin Tian
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
| | - Xinghua Zhao
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
| | - Ya Li
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Shuyan Duan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
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14
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Wang M, Wang L, He X, Zhang J, Zhu Z, Zhang M, Li X. lncRNA CCAT2 promotes radiotherapy resistance for human esophageal carcinoma cells via the miR‑145/p70S6K1 and p53 pathway. Int J Oncol 2019; 56:327-336. [PMID: 31789385 DOI: 10.3892/ijo.2019.4929] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 09/09/2019] [Indexed: 11/06/2022] Open
Abstract
The long non‑coding RNA colon cancer‑associated transcript 2 (CCAT2) is abnormally expressed in various types of malignant tumor tissues and considered to be an oncogene, including for esophageal cancer (EC). Radiotherapy is an important and widely used cancer treatment. However, some patients with EC do not respond to radiotherapy. This study was designed to investigate effects of CCAT2 expression on radiotherapy dynamics for EC cells and to explore underlying molecular mechanisms. Reverse transcription‑quantitative PCR was used to measure CCAT2 expression in EC tissues, normal esophageal mucosa, EC cells and normal human esophageal epithelial cells. TUNEL assays were used to assess the effect of CCAT2 on X‑ray‑induced apoptosis of EC cells. Protein expression was detected by western blot. CCAT2 was highly expressed in EC tissues and EC cells, and was negatively associated with radiotherapy efficacy in patients with EC. In vitro, knockdown of CCAT2 enhanced radiosensitivity of EC cells and promoted apoptosis by increasing Bax/Bcl2 and active‑caspase 3/caspase 3 following X‑ray treatment. In addition, CCAT2 negatively regulated miR‑145 and P70 ribosomal protein S6 kinase 1 (p70S6K1) expression, and inhibited phosphorylation of Akt, ERK and p70S6K1 in EC cells. After X‑ray treatment, CCAT2 negatively regulated protein levels of p53, P21 and c‑Myc. These results showed that CCAT2 promoted the radiotherapy resistance of EC cells via negative regulation of the miR‑145/p70S6K1 and the p53 signaling pathways and associated elements may be potential targets for improving the sensitivity of EC radiotherapy.
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Affiliation(s)
- Ming Wang
- Department of Radiation Therapy, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
| | - Liang Wang
- Department of Digestive Endoscopy, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
| | - Xiang He
- Department of CT Diagnosis, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
| | - Jinhua Zhang
- Department of Pediatrics, Mengcun County Hospital, Cangzhou, Hebei 061400, P.R. China
| | - Zhongcheng Zhu
- Department of Radiation Therapy, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
| | - Mingyun Zhang
- Department of Radiation Therapy, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
| | - Xingde Li
- Department of Digestive Endoscopy, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
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15
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The Critical Role of Hypoxic Microenvironment and Epigenetic Deregulation in Esophageal Cancer Radioresistance. Genes (Basel) 2019; 10:genes10110927. [PMID: 31739546 PMCID: PMC6896142 DOI: 10.3390/genes10110927] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 11/01/2019] [Accepted: 11/12/2019] [Indexed: 12/24/2022] Open
Abstract
Esophageal cancer (EC) is the seventh most common cancer worldwide and the sixth leading cause of death, according to Globocan 2018. Despite efforts made for therapeutic advances, EC remains highly lethal, portending a five-year overall survival of just 15-20%. Hence, the discovery of new molecular targets that might improve therapeutic efficacy is urgently needed. Due to high proliferative rates and also the limited oxygen and nutrient diffusion in tumors, the development of hypoxic regions and consequent activation of hypoxia-inducible factors (HIFs) are a common characteristic of solid tumors, including EC. Accordingly, HIF-1α, involved in cell cycle deregulation, apoptosis, angiogenesis induction and proliferation in cancer, constitutes a predictive marker of resistance to radiotherapy (RT). Deregulation of epigenetic mechanisms, including aberrant DNA methylation and histone modifications, have emerged as critical factors in cancer development and progression. Recently, interactions between epigenetic enzymes and HIF-1α transcription factors have been reported. Thus, further insight into hypoxia-induced epigenetic alterations in EC may allow the identification of novel therapeutic targets and predictive biomarkers, impacting on patient survival and quality of life.
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16
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Yang Y, Tian Z, Ding Y, Li X, Zhang Z, Yang L, Zhao F, Ren F, Guo R. EGFR-Targeted Immunotoxin Exerts Antitumor Effects on Esophageal Cancers by Increasing ROS Accumulation and Inducing Apoptosis via Inhibition of the Nrf2-Keap1 Pathway. J Immunol Res 2018; 2018:1090287. [PMID: 30596104 PMCID: PMC6286775 DOI: 10.1155/2018/1090287] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2018] [Revised: 09/20/2018] [Accepted: 10/30/2018] [Indexed: 12/11/2022] Open
Abstract
Previously, we developed a novel EGFR-targeted antibody (denoted as Pan), which has superior antitumor activity against EGFR-overexpressed tumors. However, it shows marginal effect on the growth of esophageal cancers. Therefore, the variable region of Pan was fused to a fragment of Pseudomonas exotoxin A (PE38) to create the immunotoxin, denoted as Ptoxin (PT). Results indicated that PT shows more effective antitumor activity as compared with Pan both on EGFR-overexpressed KYSE-450 and KYSE-150 esophageal cancer cells, especially on KYSE-450 cells. Moreover, treatment of PT induces regression of KYSE-450 tumor xenografts in nude mice. Furthermore, we investigated the potential mechanism involved in the enhanced antitumor effects of PT. Data showed that PT was more potent in reducing the phosphorylation of EGFR and ERK1/2. More importantly, we for the first time found that PT was more effective than Pan in inducing ROS accumulation by suppression of the Nrf2-Keap1 antioxidant pathway, and then induced apoptosis in KYSE-450 esophageal cancer cells, which may partly explain the more sensitive response of KYSE-450 to PT treatment. To conclude, our study provides a promising therapeutic approach for immunotoxin-based esophageal cancer treatment.
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Affiliation(s)
- Yun Yang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
- State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China
| | - Ziyin Tian
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Yanke Ding
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Xiaojing Li
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Ziheng Zhang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Liu Yang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Fangyu Zhao
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Feng Ren
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Rui Guo
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
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17
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Bunting D, Berrisford R, Wheatley T, Humphreys L, Ariyarathenam A, Sanders G. Prospective cohort study of neoadjuvant therapy toxicity in the treatment of oesophageal adenocarcinoma. Int J Surg 2018; 52:126-130. [PMID: 29455047 DOI: 10.1016/j.ijsu.2018.02.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Revised: 01/24/2018] [Accepted: 02/12/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Early studies investigating the benefits of neoadjuvant therapy in oesophageal cancer showed conflicting results, taking many years before a survival advantage was demonstrated in randomised trials. Gains are modest, limited by progressive disease and toxicity. This study aimed to investigate the relationship between neoadjuvant therapy-associated toxicity and clinical outcomes including survival in patients with potentially curable oesophageal adenocarcinoma. MATERIALS AND METHODS A cohort of 286 patients undergoing neoadjuvant therapy followed by surgical resection at a single institution was identified from a prospective database. Adverse events from neoadjuvant therapy were recorded and graded. Patients were divided into two groups according to whether they suffered toxicity or not. Clinical outcomes including whether patients completed the neoadjuvant course, whether they proceeded to resection and overall survival, were compared between the groups. RESULTS Neoadjuvant therapy-related toxicity was identified in 67/286 patients. 46 patients suffered severe, life-threatening or fatal adverse events. In patients with toxicity, 47% did not complete the chemotherapy course compared to 17% without toxicity, RR 2.7 (95%CI 1.7-4.4), (P < 0.001). In patients suffering toxicity, 17.9% failed to proceed to resection compared with 7.8% in those without toxicity, RR 2.3 (95%CI 1.2-4.6) P = 0.02. Median overall survival was shorter in patients suffering toxicity (20.7 months) compared to those without toxicity (37.8 months), P = 0.008. When patients failing to proceed to resection were excluded, median overall survival was shorter in patients suffering toxicity (26.2 months) compared with those without toxicity (47.8), P = 0.039. CONCLUSION Neoadjuvant therapy-related toxicity is common and can have serious consequences including failure to complete chemotherapy cycles, a higher risk of not proceeding to surgical resection and poorer overall survival. Efforts should be made to reduce toxicity and research should aim to identify responders and factors predictive of toxicity.
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Affiliation(s)
- David Bunting
- Peninsula Oesophago-gastric Surgery Unit, Derriford Hospital, Plymouth, Devon, PL3 5AN, UK.
| | - Richard Berrisford
- Peninsula Oesophago-gastric Surgery Unit, Derriford Hospital, Plymouth, Devon, PL3 5AN, UK
| | - Tim Wheatley
- Peninsula Oesophago-gastric Surgery Unit, Derriford Hospital, Plymouth, Devon, PL3 5AN, UK
| | - Lee Humphreys
- Peninsula Oesophago-gastric Surgery Unit, Derriford Hospital, Plymouth, Devon, PL3 5AN, UK
| | - Arun Ariyarathenam
- Peninsula Oesophago-gastric Surgery Unit, Derriford Hospital, Plymouth, Devon, PL3 5AN, UK
| | - Grant Sanders
- Peninsula Oesophago-gastric Surgery Unit, Derriford Hospital, Plymouth, Devon, PL3 5AN, UK
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18
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Luu C, Amaral M, Klapman J, Harris C, Almhanna K, Hoffe S, Frakes J, Pimiento JM, Fontaine JP. Endoscopic ultrasound staging for early esophageal cancer: Are we denying patients neoadjuvant chemo-radiation? World J Gastroenterol 2017; 23:8193-8199. [PMID: 29290655 PMCID: PMC5739925 DOI: 10.3748/wjg.v23.i46.8193] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 07/04/2017] [Accepted: 08/02/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the accuracy of endoscopic ultrasound (EUS) in early esophageal cancer (EC) performed in a high-volume tertiary cancer center.
METHODS A retrospective review of patients undergoing esophagectomy was performed and patients with cT1N0 and cT2N0 esophageal cancer by EUS were evaluated. Patient demographics, tumor characteristics, and treatment were reviewed. EUS staging was compared to surgical pathology to determine accuracy of EUS. Descriptive statistics was used to describe the cohort. Student’s t test and Fisher’s exact test or χ2 test was used to compare variables. Logistic regression analysis was used to determine if clinical variables such as tumor location and tumor histology were associated with EUS accuracy.
RESULTS Between 2000 and 2015, 139 patients with clinical stageIorIIA esophageal cancer undergoing esophagectomy were identified. There were 25 (18%) female and 114 (82%) male patients. The tumor location included the middle third of the esophagus in 11 (8%) and lower third and gastroesophageal junction in 128 (92%) patients. Ninety-three percent of patients had adenocarcinoma. Preoperative EUS matched the final surgical pathology in 73/139 patients for a concordance rate of 53%. Twenty-nine patients (21%) were under-staged by EUS; of those, 19 (14%) had unrecognized nodal disease. Positron emission tomography (PET) was used in addition to EUS for clinical staging in 62/139 patients. Occult nodal disease was only found in 4 of 62 patients (6%) in whom both EUS and PET were negative for nodal involvement.
CONCLUSION EUS is less accurate in early EC and endoscopic mucosal resection might be useful in certain settings. The addition of PET to EUS improves staging accuracy.
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Affiliation(s)
- Carrie Luu
- Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Marisa Amaral
- Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Jason Klapman
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Cynthia Harris
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Khaldoun Almhanna
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Sarah Hoffe
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Jessica Frakes
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Jose M Pimiento
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Jacques P Fontaine
- Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
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19
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Włodarczyk J, Kużdżał J. Composite metrics in response assessment-new hope in oesophageal cancer? J Thorac Dis 2017; 9:2786-2787. [PMID: 29221240 DOI: 10.21037/jtd.2017.08.28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Janusz Włodarczyk
- Department of Thoracic Surgery, Jagiellonian University Collegium Medicum, John Paul II Hospital, Cracow, Poland
| | - Jarosław Kużdżał
- Department of Thoracic Surgery, Jagiellonian University Collegium Medicum, John Paul II Hospital, Cracow, Poland
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20
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Liu Y, Xie D, Li C, Lin C, Zhao J. Effects of neoadjuvant chemotherapy combined with radiotherapy in patients with advanced esophageal carcinoma. Oncol Lett 2017; 14:2803-2807. [PMID: 28927038 PMCID: PMC5588106 DOI: 10.3892/ol.2017.6515] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Accepted: 01/09/2017] [Indexed: 11/25/2022] Open
Abstract
We analyzed the improvement of survival time and the effects of neoadjuvant chemotherapy combined with radiotherapy on treating patients with advanced esophageal carcinoma. Retrospectively, 43 patients were selected with esophageal carcinoma who were administered neoadjuvant chemotherapy combined with radiotherapy. According to gender, and tumor staging, the nearest neighbor matching was carried out. Eighty-six patients (1:2) who received neoadjuvant chemotherapy and 129 patients (1:3) who underwent surgery only were taken and compared for clinical outcomes. It was found that in the combination group, the median survival time was prolonged and the 1-year survival rate improved. The diameter of tumors was significantly reduced, and the surgical resection, margin negative and total effective rates improved. In addition, the recurrence rate significantly decreased, whereas quality of life scores significantly increased (p<0.05). The comparison of overall incidence of complications was not statistically significant (p>0.05). Tumor staging, location, and diameter after neoadjuvant therapy, as well as therapeutic regimen, treatment cycle, margin negative rate and effective rate were independent risk factors for significantly influencing survival outcomes and time (p<0.05). In conclusion, neoadjuvant chemotherapy combined with radiotherapy can be utilized to treat advanced esophageal carcinoma improve survival time and promote prognosis.
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Affiliation(s)
- Yu Liu
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, Jiangsu 215006, P.R. China.,Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Deyao Xie
- Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Chang Li
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, Jiangsu 215006, P.R. China
| | - Chaoxi Lin
- Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Jun Zhao
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, Jiangsu 215006, P.R. China
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21
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Findlay JM, Bradley KM, Wang LM, Franklin JM, Teoh EJ, Gleeson FV, Maynard ND, Gillies RS, Middleton MR. Metabolic nodal response as a prognostic marker after neoadjuvant therapy for oesophageal cancer. Br J Surg 2017; 104:408-417. [PMID: 28093719 DOI: 10.1002/bjs.10435] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 07/01/2016] [Accepted: 10/26/2016] [Indexed: 02/01/2023]
Abstract
BACKGROUND The ability to predict recurrence and survival after neoadjuvant chemotherapy (NAC) and surgery for oesophageal cancer remains elusive. This study evaluated the role of [18 F]fluorodeoxyglucose (FDG) PET-CT in assessing tumour and nodal response as a prognostic marker. METHODS This was a single-centre UK cohort study. From 2006 to 2014, patients with oesophageal cancer staged with PET-CT before NAC, and restaged by CT or PET-CT before resection, were included. Pathological tumour response was evaluated using Mandard regression grades. Metabolic tumour and nodal responses (mTR and mNR respectively) were quantified using absolute and threshold reductions. RESULTS Among 294 included patients, mTR and mNR independently predicted prognosis before surgery. After surgery, mNR (but not mTR), pathological tumour response, resection margin status and pathological node category predicted prognosis. Patients with FDG-avid nodal disease after NAC were at high risk of recurrence/death at 1 and 2 years (43 and 71 per cent respectively; P = 0·030 and P = 0·025 versus patients without avid nodes), and had a worse prognosis than patients with non-avid nodal metastases: hazard ratio 4·19 (95 per cent c.i. 1·87 to 9·40) and 2·11 (1·12 to 3·97) respectively versus patients without nodal metastases. Considering mTR and mNR response separately improved prognostication. CONCLUSION mNR is a novel prognostic factor, independent of conventional N status. Primary and nodal tumours may respond discordantly and patients with FDG-avid nodes after NAC have a poor prognosis.
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Affiliation(s)
- J M Findlay
- Oxford OesophagoGastric Centre, Oxford, UK
- National Institute for Health Research, Oxford Biomedical Research Centre, Oxford, UK
| | - K M Bradley
- Department of Nuclear Medicine, Churchill Hospital, Oxford, UK
| | - L M Wang
- National Institute for Health Research, Oxford Biomedical Research Centre, Oxford, UK
- Department of Pathology, John Radcliffe Hospital, Oxford, UK
| | - J M Franklin
- Department of Nuclear Medicine, Churchill Hospital, Oxford, UK
| | - E J Teoh
- Department of Nuclear Medicine, Churchill Hospital, Oxford, UK
| | - F V Gleeson
- Department of Nuclear Medicine, Churchill Hospital, Oxford, UK
| | | | | | - M R Middleton
- National Institute for Health Research, Oxford Biomedical Research Centre, Oxford, UK
- Department of Oncology, University of Oxford, Oxford, UK
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DaVee T, Ajani JA, Lee JH. Is endoscopic ultrasound examination necessary in the management of esophageal cancer? World J Gastroenterol 2017; 23:751-762. [PMID: 28223720 PMCID: PMC5296192 DOI: 10.3748/wjg.v23.i5.751] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 11/23/2016] [Accepted: 12/21/2016] [Indexed: 02/06/2023] Open
Abstract
Despite substantial efforts at early diagnosis, accurate staging and advanced treatments, esophageal cancer (EC) continues to be an ominous disease worldwide. Risk factors for esophageal carcinomas include obesity, gastroesophageal reflux disease, hard-alcohol use and tobacco smoking. Five-year survival rates have improved from 5% to 20% since the 1970s, the result of advances in diagnostic staging and treatment. As the most sensitive test for locoregional staging of EC, endoscopic ultrasound (EUS) influences the development of an optimal oncologic treatment plan for a significant minority of patients with early cancers, which appropriately balances the risks and benefits of surgery, chemotherapy and radiation. EUS is costly, and may not be available at all centers. Thus, the yield of EUS needs to be thoughtfully considered for each patient. Localized intramucosal cancers occasionally require endoscopic resection (ER) for histologic staging or treatment; EUS evaluation may detect suspicious lymph nodes prior to exposing the patient to the risks of ER. Although positron emission tomography (PET) has been increasingly utilized in staging EC, it may be unnecessary for clinical staging of early, localized EC and carries the risk of false-positive metastasis (over staging). In EC patients with evidence of advanced disease, EUS or PET may be used to define the radiotherapy field. Multimodality staging with EUS, cross-sectional imaging and histopathologic analysis of ER, remains the standard-of-care in the evaluation of early esophageal cancers. Herein, published data regarding use of EUS for intramucosal, local, regional and metastatic esophageal cancers are reviewed. An algorithm to illustrate the current use of EUS at The University of Texas MD Anderson Cancer Center is presented.
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Findlay JM, Bradley KM, Wang LM, Franklin JM, Teoh EJ, Gleeson FV, Maynard ND, Gillies RS, Middleton MR. Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemotherapy: The Implications of Metabolic Nodal Response for Personalized Therapy. J Nucl Med 2017; 58:266-275. [PMID: 27635027 DOI: 10.2967/jnumed.116.176313] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 07/13/2016] [Indexed: 12/12/2022] Open
Abstract
Only a minority of esophageal cancers demonstrates a pathologic tumor response (pTR) to neoadjuvant chemotherapy (NAC). 18F-FDG PET/CT is often used for restaging after NAC and to assess response. Increasingly, it is used during therapy to identify unresponsive tumors and predict pTR, using avidity of the primary tumor alone. However, definitions of such metabolic tumor response (mTR) vary. We aimed to comprehensively reevaluate metabolic response assessment using accepted parameters, as well as novel concepts of metabolic nodal stage (mN) and metabolic nodal response (mNR). METHODS This was a single-center retrospective U.K. cohort study. All patients with esophageal cancer staged before NAC with PET/CT and after with CT or PET/CT and undergoing resection from 2006 to 2014 were identified. pTR was defined as Mandard tumor regression grade 1-3; imaging parameters included metrics of tumor avidity (SUVmax/mean/peak), composites of avidity and volume (including metabolic tumor volume), nodal SUVmax, and our new concepts of mN stage and mNR. RESULTS Eighty-two (27.2%) of 301 patients demonstrated pTR. No pre-NAC PET parameters predicted pTR. In 220 patients restaged by PET/CT, the optimal tumor ΔSUVmax threshold was a 77.8% reduction. This was as sensitive as the current PERCIST 30% reduction, but more specific with a higher negative predictive value (P < 0.001). ΔSUVmax and Δlength independently predicted pTR, and composite avidity/spatial metrics outperformed avidity alone. Although both mTR and mNR were associated with pTR, in 82 patients with 18F-FDG-avid nodes before NAC we observed mNR in 10 (12.2%) not demonstrating mTR. CONCLUSION Current definitions of metabolic response are suboptimal and too simplistic. Composite avidity/volume measures improve prediction. mNR may further improve response assessment, by specifically assessing metastatic tumor subpopulations, likely responsible for disease relapse, and should be urgently assessed when considering aborting therapy on the basis of mTR alone.
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Affiliation(s)
- John M Findlay
- Oxford OesophagoGastric Centre, Churchill Hospital, Oxford, United Kingdom
- NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom
| | - Kevin M Bradley
- Department of Nuclear Medicine, Churchill Hospital, Oxford, United Kingdom
| | - Lai Mun Wang
- NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom
- Department of Pathology, John Radcliffe Hospital, Oxford, United Kingdom; and
| | - James M Franklin
- Department of Nuclear Medicine, Churchill Hospital, Oxford, United Kingdom
| | - Eugene J Teoh
- Department of Nuclear Medicine, Churchill Hospital, Oxford, United Kingdom
| | - Fergus V Gleeson
- Department of Nuclear Medicine, Churchill Hospital, Oxford, United Kingdom
| | - Nicholas D Maynard
- Oxford OesophagoGastric Centre, Churchill Hospital, Oxford, United Kingdom
| | - Richard S Gillies
- Oxford OesophagoGastric Centre, Churchill Hospital, Oxford, United Kingdom
| | - Mark R Middleton
- NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom
- Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, United Kingdom
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Sukharamwala P, Hennessey D, Wood T, Singh S, Ryan C, Rosemurgy A. Molecular profiles in foregut oncology. Cancer Genet 2016; 209:537-553. [PMID: 27887938 DOI: 10.1016/j.cancergen.2016.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 09/30/2015] [Accepted: 09/19/2016] [Indexed: 02/07/2023]
Abstract
Oncology is and will continue to evolve resulting from a better understanding of the biology and intrinsic genetic profile of each cancer. Tumor biomarkers and targeted therapies are the new face of precision medicine, so it is essential for all physicians caring for cancer patients to understand and assist patients in understanding the role and importance of such markers and strategies to target them. This review was initiated in an attempt to identify, characterize, and discuss literature supporting clinically relevant molecular markers and interventions. The efficacy of targeting specific markers will be examined with data from clinical trials focusing on treatments for esophageal, gastric, liver, gallbladder, biliary tract, and pancreatic cancers.
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Affiliation(s)
| | - Daniel Hennessey
- Florida Hospital Tampa, 3000 Medical Park Drive Suite 310, Tampa, FL 33613, USA
| | - Thomas Wood
- Florida Hospital Tampa, 3000 Medical Park Drive Suite 310, Tampa, FL 33613, USA
| | - Shelly Singh
- Florida Hospital Tampa, 3000 Medical Park Drive Suite 310, Tampa, FL 33613, USA
| | - Carrie Ryan
- Florida Hospital Tampa, 3000 Medical Park Drive Suite 310, Tampa, FL 33613, USA
| | - Alexander Rosemurgy
- Florida Hospital Tampa, 3000 Medical Park Drive Suite 310, Tampa, FL 33613, USA.
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Findlay JM, Gillies RS, Franklin JM, Teoh EJ, Jones GE, di Carlo S, Gleeson FV, Maynard ND, Bradley KM, Middleton MR. Restaging oesophageal cancer after neoadjuvant therapy with (18)F-FDG PET-CT: identifying interval metastases and predicting incurable disease at surgery. Eur Radiol 2016; 26:3519-33. [PMID: 26883329 DOI: 10.1007/s00330-016-4227-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2015] [Revised: 01/08/2016] [Accepted: 01/15/2016] [Indexed: 01/17/2023]
Abstract
OBJECTIVES It is unknown whether restaging oesophageal cancer after neoadjuvant therapy with positron emission tomography-computed tomography (PET-CT) is more sensitive than contrast-enhanced CT for disease progression. We aimed to determine this and stratify risk. METHODS This was a retrospective study of patients staged before neoadjuvant chemotherapy (NAC) by (18)F-FDG PET-CT and restaged with CT or PET-CT in a single centre (2006-2014). RESULTS Three hundred and eighty-three patients were restaged (103 CT, 280 PET-CT). Incurable disease was detected by CT in 3 (2.91 %) and PET-CT in 17 (6.07 %). Despite restaging unsuspected incurable disease was encountered at surgery in 34/336 patients (10.1 %). PET-CT was more sensitive than CT (p = 0.005, McNemar's test). A new classification of FDG-avid nodal stage (mN) before NAC (plus tumour FDG-avid length) predicted subsequent progression, independent of conventional nodal stage. The presence of FDG-avid nodes after NAC and an impassable tumour stratified risk of incurable disease at surgery into high (75.0 %; both risk factors), medium (22.4 %; either), and low risk (3.87 %; neither) groups (p < 0.001). Decision theory supported restaging PET-CT. CONCLUSIONS PET-CT is more sensitive than CT for detecting interval progression; however, it is insufficient in at least higher risk patients. mN stage and response (mNR) plus primary tumour characteristics can stratify this risk simply. KEY POINTS • Restaging (18) F-FDG-PET-CT after neoadjuvant chemotherapy identifies metastases in 6 % of patients • Restaging (18) F-FDG-PET-CT is more sensitive than CT for detecting interval progression • Despite this, at surgery 10 % of patients had unsuspected incurable disease • New concepts (FDG-avid nodal stage and response) plus tumour impassability stratify risk • Higher risk (if not all) patients may benefit from additional restaging modalities.
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Affiliation(s)
- John M Findlay
- Oxford OesophagoGastric Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
- NIHR Oxford Biomedical Research Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK.
| | - Richard S Gillies
- Oxford OesophagoGastric Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK
| | - James M Franklin
- Department of Nuclear Medicine, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK
| | - Eugene J Teoh
- Department of Nuclear Medicine, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK
| | - Greg E Jones
- Oxford OesophagoGastric Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK
- Royal Berkshire Hospital, Craven Road, Reading, RG1 5AN, UK
| | - Sara di Carlo
- Oxford OesophagoGastric Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK
- Queen's Medical Centre, Derby Road, Nottingham, NG7 2UH, UK
| | - Fergus V Gleeson
- Department of Nuclear Medicine, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK
| | - Nicholas D Maynard
- Oxford OesophagoGastric Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK
| | - Kevin M Bradley
- Department of Nuclear Medicine, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK
| | - Mark R Middleton
- NIHR Oxford Biomedical Research Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK
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Esophageal stent fixation with endoscopic suturing device improves clinical outcomes and reduces complications in patients with locally advanced esophageal cancer prior to neoadjuvant therapy: a large multicenter experience. Surg Endosc 2016; 31:1414-1419. [PMID: 27495331 DOI: 10.1007/s00464-016-5131-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2016] [Accepted: 07/13/2016] [Indexed: 01/15/2023]
Abstract
BACKGROUND Endoscopic placement of fully covered self-expanding metal stents (FCSEMS) to treat malignant dysphagia in patients with esophageal cancer significantly improves dysphagia; however, these stents have a high migration rate. AIM To determine whether FCSEMS fixation using an endoscopic suturing device treated malignant dysphagia and prevented stent migration in patients with locally advanced esophageal cancer receiving neoadjuvant therapy when compared to patients with FCSEMS placement alone. METHOD A review of patients with locally advanced esophageal cancer who underwent FCSEMS placement at 3 centers was performed. Patients were divided into two groups: Group A (n = 26) was composed of patients who underwent FCSEMS placement with suture placement, and Group B (n = 67) was composed of patients with FCSEMS placement alone. RESULTS There were no significant differences between Groups A and B in demographics, and tumor characteristics. The technical success rate for stent placement was 100 %. There was no difference between Groups A and B in the median stent diameter and stent lengths. Mean dysphagia score obtained at 1 week after stent placement had improved significantly from baseline (2.4 and 1, respectively, p < 0.001). Patients had a median follow-up of 4 months. Immediate adverse events were mild chest discomfort in 4 patients in Group A and 2 patients in Group B (p = 0.05), and significant acid reflux in 3 patient in Group A compared to 2 patients in Group B (p = 0.1). The stent migration rate was significantly lower in Group A compared to compared to Group B (7.7 vs 26.9 %, respectively, p = 0.004). There was a delayed perforation in 1 patient and 1 death due to aspiration pneumonia in Group B. CONCLUSION Fixation of esophageal FCSEMSs by using an endoscopic suturing device in patients receiving neoadjuvant therapy was shown to be feasible, safe, and relatively effective at preventing stent migration compared to those who had stent placed alone.
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27
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Fiore M, Trodella L, Valeri S, Borzomati D, Floreno B, Ippolito E, Trecca P, Trodella LE, D'Angelillo RM, Ramella S, Coppola R. Prospective study of cetuximab and gemcitabine in combination with radiation therapy: feasibility and efficacy in locally advanced pancreatic head cancer. Radiat Oncol 2015; 10:255. [PMID: 26670587 PMCID: PMC4681028 DOI: 10.1186/s13014-015-0564-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 12/08/2015] [Indexed: 01/03/2023] Open
Abstract
Background Radio-chemotherapy is one of the steps of multidisciplinary management in locally advanced pancreatic cancer. The Epidermal Growth Factor Receptor (EGFR) plays an important role in the disease pathway. The purpose of this prospective study is to evaluate the feasibility and the efficacy of radiotherapy in combination with gemcitabine and EGFR targeting therapy for patients with locally advanced disease. Materials and methods From November 2008 through January 2012, 34 patients were included in this study. In all cases an accurate pre-treatment staging including CT scan, Endoscopic Ultra-Sonography (EUS), 18F - fluorodeoxyglucose (18F-FDG) PET-CT and laparoscopy with peritoneal washing was performed. External beam radiation was delivered with a total dose of 50.4 Gy (1.8 Gy per fraction). Patients were treated using 3D- conformal radiotherapy, and the clinical target volume was the primary tumor and involved lymph nodes. Gemcitabine 300 mg/m2 and Cetuximab were given weekly during radiation therapy. Results Ten patients (29.4 %) were excluded from the protocol because of the evidence of metastatic disease at the pre-treatment staging. Three patients refused radiochemotherapy. Twenty-one patients completed the therapy protocol. During the combined therapy grade 3–4 toxicities observed were only haematological (leukopenia 47,6 %, trombocytopenia 4.8 %, elevated gamma-GT 23.8 %, elevated alkaline phosphatase 4,8 %). Non-haematological toxicity grade 3–4 was never reported. Post-treatment workup showed partial response in five patients (24 %), stable disease in 11 patients (52 %) and disease progression in 5 patients (24 %). Two-year Local Control was 49 % (median, 18.6 months), 2-year Metastases Free Survival was 24 % (median, 10.8 months). One and two-year Overall Survival were 66 % and 28 % respectively, with a median survival time of 15.3 months. Conclusions The combination of cetuximab and gemcitabine with concurrent radiation therapy provides a feasible and well tolerated treatment for locally advanced pancreatic cancer. Patients’ selection is crucial in order to treat patients appropriately.
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Affiliation(s)
- Michele Fiore
- Radiotherapy Unit, Campus Bio-Medico University, Via A. del Portillo, 21, 00128, Rome, Italy.
| | - Lucio Trodella
- Radiotherapy Unit, Campus Bio-Medico University, Via A. del Portillo, 21, 00128, Rome, Italy.
| | - Sergio Valeri
- Department of General Surgery, Campus Bio-Medico University, Rome, Italy.
| | - Domenico Borzomati
- Department of General Surgery, Campus Bio-Medico University, Rome, Italy.
| | - Barnaba Floreno
- Radiotherapy Unit, Campus Bio-Medico University, Via A. del Portillo, 21, 00128, Rome, Italy.
| | - Edy Ippolito
- Radiotherapy Unit, Campus Bio-Medico University, Via A. del Portillo, 21, 00128, Rome, Italy.
| | - Pasquale Trecca
- Radiotherapy Unit, Campus Bio-Medico University, Via A. del Portillo, 21, 00128, Rome, Italy.
| | - Luca Eolo Trodella
- Radiotherapy Unit, Campus Bio-Medico University, Via A. del Portillo, 21, 00128, Rome, Italy.
| | | | - Sara Ramella
- Radiotherapy Unit, Campus Bio-Medico University, Via A. del Portillo, 21, 00128, Rome, Italy.
| | - Roberto Coppola
- Department of General Surgery, Campus Bio-Medico University, Rome, Italy.
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Cao W, Peters JH, Nieman D, Sharma M, Watson T, Yu J. Macrophage subtype predicts lymph node metastasis in oesophageal adenocarcinoma and promotes cancer cell invasion in vitro. Br J Cancer 2015; 113:738-46. [PMID: 26263481 PMCID: PMC4559839 DOI: 10.1038/bjc.2015.292] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Revised: 07/02/2015] [Accepted: 07/21/2015] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Currently, there is a lack of ideal biomarkers for predicting nodal status in preoperative stage of oesophageal adenocarcinoma (EAC) to aid optimising therapeutic options. We studied the potential of applying subtype macrophages to predict lymph node metastasis and prognosis in EAC. MATERIAL AND METHODS Fifty-three EAC resection specimens were immunostained with CD68, CD40 (M1), and CD163 (M2). Lymphatic vessel density (LVD) was estimated with the staining of D2-40. Subsequently, we tested if M2d macrophage could promote EAC cell migration and invasion. RESULTS In EAC without neoadjuvant treatment, an increase in M2-like macrophage was associated with poor patient survival, independent of the locations of macrophages in tumour. The M2/M1 ratio that represented the balance between M2- and M1-like macrophages was significantly higher in nodal-positive EACs than that in nodal-negative EACs, and inversely correlated with patient overall survival. The M2/M1 ratio was not related to LVD. EAC cell polarised THP1 cell into M2d-like macrophage, which promoted EAC cell migration and invasion. Neoadjuvant therapy appeared to diminish the correlation between the M2/M1 ratio and survival. CONCLUSIONS The ratio of M2/M1 macrophage may serve as a sensitive marker to predict lymph node metastasis and poor prognosis in EAC without neoadjuvant therapy. M2d macrophage may have important roles in EAC metastasis.
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Affiliation(s)
- Wenqing Cao
- Department of Pathology, NYU School of Medicine, 560 First Avenue, New York, NY, USA
| | - Jeffrey H Peters
- Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA
| | - Dylan Nieman
- Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA
| | - Meenal Sharma
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Centre, 601 Elmwood Avenue, Box 626, Rochester, NY, USA
| | - Thomas Watson
- Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA
| | - JiangZhou Yu
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Centre, 601 Elmwood Avenue, Box 626, Rochester, NY, USA
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Lin G, Sun XJ, Han QB, Wang Z, Xu YP, Gu JL, Wu W, Zhang GU, Hu JL, Sun WY, Mao WM. Epidermal growth factor receptor protein overexpression and gene amplification are associated with aggressive biological behaviors of esophageal squamous cell carcinoma. Oncol Lett 2015; 10:901-906. [PMID: 26622592 DOI: 10.3892/ol.2015.3277] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Accepted: 04/28/2015] [Indexed: 12/23/2022] Open
Abstract
Alterations of the epidermal growth factor receptor (EGFR), including overexpression or gene mutations, contribute to the malignant transformation of human epithelial cells. The aim of this study was to assess EGFR overexpression or gene amplification in esophageal squamous cell carcinoma (ESCC) tissue samples and investigate their correlations with biological behaviors. Tissue specimens from 56 patients with surgically resected ESCC were obtained for immunohistochemical analysis of EGFR expression and fluorescence in situ hybridization analysis of EGFR amplification. The data were statistically analyzed to determine the associations with patient clinicopathological and survival data. EGFR was overexpressed in 30 of the 56 (53.6%) ESCC samples and was associated with poor tumor differentiation (P=0.047). EGFR amplification was detected in 13 cases (23.2%) and was associated with advanced pathological stage (P=0.042) and tumor lymph node metastasis (P=0.002). The univariate analysis identified no association between EGFR overexpression and the overall survival (OS) of the patients. By contrast, EGFR amplification predicted ESCC prognosis (P=0.031), while the multivariate analysis revealed a marginal statistical significance for the association between EGFR amplification and OS (P=0.056). EGFR overexpression and increased EGFR copy number were common events in ESCC and contributed to malignant biological behaviors, including tumor dedifferentiation and lymph node metastasis. EGFR amplification may therefore be useful in predicting OS in patients with ESCC.
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Affiliation(s)
- Gang Lin
- First Clinical Medical School, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China ; Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Xiao-Jiang Sun
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Qian-Bo Han
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Zhun Wang
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Ya-Ping Xu
- First Clinical Medical School, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China ; Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Jia-Lei Gu
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Wei Wu
- Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - G U Zhang
- Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Jin-Lin Hu
- Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Wen-Yong Sun
- Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Wei-Min Mao
- Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
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Vaiphei K, Sinha SK, Kochhar R. Comparative analysis of Oct4 in different histological subtypes of esophageal squamous cell carcinomas in different clinical conditions. Asian Pac J Cancer Prev 2015; 15:3519-24. [PMID: 24870750 DOI: 10.7314/apjcp.2014.15.8.3519] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. It has been hypothesized that Oct4 positive radioresistant stem cells may be responsible for tumor recurrence. Hence, we evaluated Oct4 expression in ESCC in pre-treatment, post neo-adjuvant residual and post-surgical recurrent tumours. MATERIALS AND METHODS Endoscopic mucosal biopsies were used to study Oct4 expression and the observations were correlated with histological tumor grades, patient data and clinical background. RESULTS All patients presented with dysphagia with male predominance and a wide age range. Majority of the patients had intake of mixed diet, history of alcohol and tobacco intake was documented in less than half of the patients. Oct 4 expression was significantly higher in poorly differentiated (PDSCC) and basaloid (BSCC) subtypes than the other better differentiated tumor morphology. Oct4 was also expressed by adjoining esophageal mucosa showing low grade dysplasia and basal cell hyperplasia (BCH). Biopsies in PDSCC and BSCC groups were more likely to show a positive band for Oct4 by polymerase chain reaction (PCR). Dysplasia and BCH mucosa also showed Oct4 positivity by PCR. All mucosal biopsies with normal morphology were negative for Oct4. Number of tissue samples showing Oct4 positivity by PCR was higher than that by the conventional immunohistochemistry (p>0.05). Oct4 expression pattern correlated only with tumor grading, not with other parameters including the clinical background or patient data. CONCLUSIONS Our observations highlighted a possible role of Oct4 in identifying putative cancer stem cells in ESCC pathobiology and response to treatment. The implications are either in vivo existence of Oct4 positive putative cancer stem cells in ESCC or acquisition of cancer stem cell properties by tumor cells as a response to treatment given, resulting ultimately an uncontrolled cell proliferation and treatment failure.
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Talvas J, Garrait G, Goncalves-Mendes N, Rouanet J, Vergnaud-Gauduchon J, Kwiatkowski F, Bachmann P, Bouteloup C, Bienvenu J, Vasson MP. Immunonutrition stimulates immune functions and antioxidant defense capacities of leukocytes in radiochemotherapy-treated head & neck and esophageal cancer patients: A double-blind randomized clinical trial. Clin Nutr 2014; 34:810-7. [PMID: 25575640 DOI: 10.1016/j.clnu.2014.12.002] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 11/13/2014] [Accepted: 12/03/2014] [Indexed: 12/31/2022]
Abstract
BACKGROUND Immunonutrition has been reported to improve the immune status of perioperative cancer patients, thereby reducing complications and length of hospital stay. AIM This study aimed to assess whether immunonutrition enriched in arginine, EPA & DHA and nucleotides could impact the immune cells responses in head & neck and esophageal cancer patients treated by radiochemotherapy (RCT). METHODS A double-blind clinical trial was carried out in 28 patients randomized into two groups, receiving either an immunomodulating enteral nutrition formula (IEN, n = 13, Impact(®), Nestlé) or an isoenergetic isonitrogenous standard enteral nutrition formula (SEN, n = 15) throughout RCT (5-7 weeks). After isolation from whole blood, immune cells metabolism and functions were assessed at the beginning (Db) and at the end (De) of RCT. RESULTS Immunonutrition maintained CD4(+)/CD8(+) T-lymphocyte counts ratio and CD3 membrane expression between Db and De. Polymorphonuclear cells CD62L and CD15 densities and ROS production were increased in IEN patients. Peripheral blood mononuclear cells (PBMC) production of pro-inflammatory prostaglandin-E2 was stable in IEN patients and lower than in SEN patients at De. Genes coding for immune receptors, antioxidant enzymes and NADPH oxidase subunits were overexpressed in the PBMC of IEN vs SEN patients at De. CONCLUSION Immunonutrition can enhance immune cell responses through the modulation of their phenotypes and functions. By modulating the gene expression of immune cells, immunonutrition could make it easier for the organism to adapt to the systemic inflammation and oxidative stress induced by RCT. CLINICAL TRIAL REGISTRATION This clinical trial has been registered on ClinicalTrial.gov website: NCT00333099.
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Affiliation(s)
- J Talvas
- Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000 Clermont-Ferrand, France; INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France
| | - G Garrait
- Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000 Clermont-Ferrand, France; INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France
| | - N Goncalves-Mendes
- Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000 Clermont-Ferrand, France; INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France
| | - J Rouanet
- Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000 Clermont-Ferrand, France; INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France
| | - J Vergnaud-Gauduchon
- Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000 Clermont-Ferrand, France; INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France
| | - F Kwiatkowski
- Centre Jean Perrin, Service de Statistiques, F-63000 Clermont-Ferrand, France
| | - P Bachmann
- Centre Léon Bérard, Unité de Nutrition Clinique, F-69000 Lyon, France
| | - C Bouteloup
- Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000 Clermont-Ferrand, France; INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France; CHU Clermont-Ferrand, Service de Médecine Digestive et Hépatobiliaire, F-63003 Clermont-Ferrand, France
| | - J Bienvenu
- CH Lyon Sud, Laboratoire d'Immunologie, F-69000 Lyon, France
| | - M-P Vasson
- Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000 Clermont-Ferrand, France; INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, CHU Clermont-Ferrand, Unité de Nutrition, CLARA, F-63000 Clermont-Ferrand, France.
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Findlay JM, Middleton MR, Tomlinson I. A systematic review and meta-analysis of somatic and germline DNA sequence biomarkers of esophageal cancer survival, therapy response and stage. Ann Oncol 2014; 26:624-644. [PMID: 25214541 PMCID: PMC4374384 DOI: 10.1093/annonc/mdu449] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Recent advances in next generation sequencing reinforce the potential for DNA sequence markers to guide esophageal cancer management. We report the first systematic review and meta-analysis, identifying 94 markers of outcome and 41 of stage. Overall, evidence was poor. Meta-analyses demonstrated outcome associations for 6 tumor and 9 germline variants: priorities for prospective evaluation. Introduction There is an urgent need for biomarkers to help predict prognosis and guide management of esophageal cancer. This review identifies, evaluates and meta-analyses the evidence for reported somatic and germline DNA sequence biomarkers of outcome and stage. Methods A systematic review was carried out of the PubMed, EMBASE and Cochrane databases (20 August 2014), in conjunction with the ASCO Level of Evidence scale for biomarker research. Meta-analyses were carried out for all reported markers associated with outcome measures by more than one study. Results Four thousand and four articles were identified, 762 retrieved and 182 studies included. There were 65 reported markers of survival or recurrence 12 (18.5%) were excluded due to multiple comparisons. Following meta-analysis, significant associations were seen for six tumor variants (mutant TP53 and PIK3CA, copy number gain of ERBB2/HER2, CCND1 and FGF3, and chromosomal instability/ploidy) and seven germline polymorphisms: ERCC1 rs3212986, ERCC2 rs1799793, TP53 rs1042522, MDM2 rs2279744, TYMS rs34743033, ABCB1 rs1045642 and MTHFR rs1801133. Twelve germline markers of treatment complications were reported; 10 were excluded. Two tumor and 15 germline markers (11 excluded) of chemo (radio)therapy response were reported. Following meta-analysis, associations were demonstrated for mutant TP53, ERCC1 rs11615 and XRCC1 rs25487. There were 41 tumor/germline reported markers of stage; 27 (65.9%) were excluded. Conclusions Numerous DNA markers of outcome and stage have been reported, yet few are backed by high-quality evidence. Despite this, a small number of variants appear reliable. These merit evaluation in prospective trials, within the context of high-throughput sequencing and gene expression.
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Affiliation(s)
- J M Findlay
- Molecular and Population Genetics, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford; Oxford OesophagoGastric Centre
| | - M R Middleton
- NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK
| | - I Tomlinson
- Molecular and Population Genetics, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford; NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK.
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Hardacker TJ, Ceppa D, Okereke I, Rieger KM, Jalal SI, LeBlanc JK, DeWitt JM, Kesler KA, Birdas TJ. Treatment of clinical T2N0M0 esophageal cancer. Ann Surg Oncol 2014; 21:3739-43. [PMID: 25047477 DOI: 10.1245/s10434-014-3929-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND Management of clinical T2N0M0 (cT2N0M0) esophageal cancer remains controversial. We reviewed our institutional experience over 21 years (1990-2011) to determine clinical staging accuracy, optimal treatment approaches, and factors predictive of survival in this patient population. METHODS Patients with cT2N0M0 esophageal cancer determined by endoscopic ultrasound (EUS) were identified through a prospectively collected database. Demographics, perioperative data, and outcomes were examined. Cox regression model and Kaplan-Meier plots were used for statistical survival analysis. RESULTS A total of 731 patients underwent esophagectomy, of whom 68 cT2N0M0 patients (9 %) were identified. Fifty-seven patients (84 %) had adenocarcinoma. Thirty-three patients (48.5 %) were treated with neoadjuvant chemoradiation followed by surgery, and 35 underwent surgical resection alone. All resections except one included a transthoracic approach with two-field lymph node dissection. Thirty-day operative mortality was 2.9 %. Only 3 patients (8.5 %) who underwent surgery alone had T2N0M0 disease identified by pathology: the disease of 15 (42.8 %) was found to be overstaged and 17 (48.5 %) understaged after surgery. Understaging was more common in poorly differentiated tumors (p = 0.03). Nine patients (27.2 %) had complete pathologic response after chemoradiotherapy. Absence of lymph node metastases (pN0) was significantly more frequent in the neoadjuvant group (29 of 33 vs. 21 of 35, p = 0.01). Median follow-up was 44.2 months. Overall 5-year survival was 50.8 %. On multivariate analysis, adenocarcinoma (p = 0.001) and pN0 after resection (p = 0.01) were significant predictors of survival. CONCLUSIONS EUS was inaccurate in staging cT2N0M0 esophageal cancer in this study. Poorly differentiated tumors were more frequently understaged. Adenocarcinoma and absence of lymph node metastases (pN0) were independently predictive of long-term survival. pN0 status was significantly more common in patients undergoing neoadjuvant therapy, but long-term survival was not affected by neoadjuvant therapy. A strategy of neoadjuvant therapy followed by resection may be optimal in this group, especially in patients with disease likely to be understaged.
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Affiliation(s)
- Thomas J Hardacker
- Section of Thoracic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA,
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Wang L, Feng J, Chen X, Guo W, Du Y, Wang Y, Zang W, Zhang S, Zhao G. Myricetin enhance chemosensitivity of 5-fluorouracil on esophageal carcinoma in vitro and in vivo. Cancer Cell Int 2014; 14:71. [PMID: 25788859 PMCID: PMC4364039 DOI: 10.1186/s12935-014-0071-2] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2014] [Accepted: 07/10/2014] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Flavonoids are structurally heterogeneous, polyphenolic compounds present in high concentrations in fruits, vegetables, and other plant-derived foods. Currently, there is growing interest in the therapeutic applications of bioflavonoids for the treatment and prevention of diseases in humans. Myricetin is a naturally occurring flavonoid that is commonly found in tea, berries, fruits, vegetables, and medicinal herbs. Previous studies have shown that myricetin has antioxidant, anti-inflammatory and potent anticancer effects. It was interesting to investigate whether myricetin has the cooperative inhibitory effect combined with 5-fluorouracil on esophageal cancer cells. METHODS EC9706 cells were treated with 5-fluorouracil combination with or without myricetin. Colony formation assays, CCK-8 assay and flow cytometry were used to evaluate the chemosensitization activity of myricetin combine with 5-fluorouracil on the cell growth and viability, cell proliferation and apoptosis in vitro. Western blot was engaged to detect changes of Survivin, Cyclin D, Bcl-2, Caspase-3 and P53 protein expression level, which were associated with cells proliferation and apoptosis. Nude mouse tumor xenograft model was built to assessed chemosensitization effect of myricetin combine with 5-fluorouracil in vivo. RESULTS Compared with the 5-fluorouracil group without myricetin treatment, the groups treated with 5-fluorouracil combine with myricetin showed significantly suppressed cell survival fraction and proliferation, increased the cell apoptosis. Decreased Survivin, Cyclin D, Bcl-2, and increased Caspase-3, P53 expression level were aslo confirmed by western blot in 5-fluorouracil combine with myricetin groups in vitro. And in vivo assay, growth speed of tumor xenografts was significantly decreased in the mice treated with 5-fluorouracil + myricetin combiantion group. CONCLUSIONS The study demonstrated both in vitro and in vivo evidence that combination of myricetin with 5-fluorouracil chemotherapy can enhance tumor chemosensitivity of esophageal cancer EC9706 cells, and myricetin could be a potential chemosensitizer for esophageal cancer therapy.
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Affiliation(s)
- Lei Wang
- Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No.1, Jianshe Road, Zhengzhou 450052, China
| | - Jianfang Feng
- Medical College of Henan University of Science and Technology, Luoyang 471003, China
| | - Xiaonan Chen
- College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
| | - Wei Guo
- Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China
| | - Yuwen Du
- College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
| | - Yuanyuan Wang
- College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
| | - Wenqiao Zang
- College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
| | - Shijie Zhang
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, No.1, Jianshe Road, Zhengzhou 450052, China
| | - Guoqiang Zhao
- College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
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Guo XF, Zhu XF, Yang WC, Zhang SH, Zhen YS. An EGFR/HER2-Bispecific and enediyne-energized fusion protein shows high efficacy against esophageal cancer. PLoS One 2014; 9:e92986. [PMID: 24664246 PMCID: PMC3963964 DOI: 10.1371/journal.pone.0092986] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Accepted: 02/27/2014] [Indexed: 01/27/2023] Open
Abstract
Esophageal cancer is one of the most common cancers, and the 5-year survival rate is less than 10% due to lack of effective therapeutic agents. This study was to evaluate antitumor activity of Ec-LDP-Hr-AE, a recently developed bispecific enediyne-energized fusion protein targeting both epidermal growth factor receptor (EGFR) and epidermal growth factor receptor 2 (HER2), on esophageal cancer. The fusion protein Ec-LDP-Hr-AE consists of two oligopeptide ligands and an enediyne antibiotic lidamycin (LDM) for receptor binding and cell killing, respectively. The current study demonstrated that Ec-LDP-Hr had high affinity to bind to esophageal squamous cell carcinoma (ESCC) cells, and enediyne-energized fusion protein Ec-LDP-Hr-AE showed potent cytotoxicity to ESCC cells with differential expression of EGFR and HER2. Ec-LDP-Hr-AE could cause significant G2-M arrest in EC9706 and KYSE150 cells, and it also induced apoptosis in ESCC cells in a dosage-dependent manner. Western blot assays showed that Ec-LDP-Hr-AE promoted caspase-3 and caspase-7 activities as well as PARP cleavage. Moreover, Ec-LDP-Hr-AE inhibited cell proliferation via decreasing phosphorylation of EGFR and HER2, and further exerted inhibition of the activation of their downstream signaling molecules. In vivo, at a tolerated dose, Ec-LDP-Hr-AE inhibited tumor growth by 88% when it was administered to nude mice bearing human ESCC cell KYSE150 xenografts. These results indicated that Ec-LDP-Hr-AE exhibited potent anti-caner efficacy on ESCC, suggesting it could be a promising candidate for targeted therapy of esophageal cancer.
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Affiliation(s)
- Xiao-Fang Guo
- Department of Microbiology, Xinxiang Medical University, Xinxiang, China
| | - Xiao-Fei Zhu
- School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China
| | - Wan-Cai Yang
- Department of Pathology, Xinxiang Medical University, Xinxiang, China
- Department of Pathology, University of Illinois at Chicago, Chicago, United States of America
| | - Sheng-Hua Zhang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Perking Union Medical College, Beijing, China
| | - Yong-Su Zhen
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Perking Union Medical College, Beijing, China
- * E-mail:
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Yamamoto M, Weber JM, Karl RC, Meredith KL. Minimally invasive surgery for esophageal cancer: review of the literature and institutional experience. Cancer Control 2013; 20:130-7. [PMID: 23571703 DOI: 10.1177/107327481302000206] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Esophageal cancer represents a major public health problem in the world. Several minimally invasive esophagectomy (MIE) techniques have been described and represent a safe alternative for the surgical management of esophageal cancer in selected centers with high volume and surgeons experienced in minimally invasive procedures. METHODS The authors reviewed the most recent and largest studies published in the medical literature that reported the outcomes for MIE techniques. RESULTS In larger series, MIE has proven to be equivalent in postoperative morbidity and mortality to the open esophagectomy. However, MIE has been associated with less blood loss, reduced postoperative pain, decreased time in the intensive care unit, and shortened length of hospital stay compared with the conventional open approaches. Despite limited data, no significant difference in survival stage for stage has been observed between open esophagectomy and MIE. CONCLUSIONS The myriad of MIE techniques complicates the debate for defining the optimal surgical approach for the treatment of esophageal cancer. Randomized controlled trials comparing MIE with conventional open esophagectomy are needed to clarify the ideal procedure with the lowest postoperative morbidity, best quality of life after surgery, and long-term survival.
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Affiliation(s)
- Maki Yamamoto
- Gastrointestinal Tumor Program, H Lee Moffitt Cancer Center, Tampa, FL 33612, USA
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Gogineni A, Caunt M, Crow A, Lee CV, Fuh G, van Bruggen N, Ye W, Weimer RM. Inhibition of VEGF-C modulates distal lymphatic remodeling and secondary metastasis. PLoS One 2013; 8:e68755. [PMID: 23874750 PMCID: PMC3712991 DOI: 10.1371/journal.pone.0068755] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2012] [Accepted: 06/04/2013] [Indexed: 12/26/2022] Open
Abstract
Tumor-associated lymphatics are postulated to provide a transit route for disseminating metastatic cells. This notion is supported by preclinical findings that inhibition of pro-lymphangiogenic signaling during tumor development reduces cell spread to sentinel lymph nodes (SLNs). However, it is unclear how lymphatics downstream of SLNs contribute to metastatic spread into distal organs, or if modulating distal lymph transport impacts disease progression. Utilizing murine models of metastasis, longitudinal in vivo imaging of lymph transport, and function blocking antibodies against two VEGF family members, we provide evidence that distal lymphatics undergo disease course-dependent up-regulation of lymph transport coincidental with structural remodeling. Inhibition of VEGF-C activity with antibodies against VEGF-C or NRP2 prevented these disease-associated changes. Furthermore, utilizing a novel model of adjuvant treatment, we demonstrate that antagonism of VEGF-C or NRP2 decreases post SLN metastasis. These data support a potential therapeutic strategy for inhibiting distant metastatic dissemination via targeting tumor-associated lymphatic remodeling.
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Affiliation(s)
- Alvin Gogineni
- Department of Biomedical Imaging, Genentech Inc., South San Francisco, California, United States of America
| | - Maresa Caunt
- Department of Molecular Biology, Genentech Inc., South San Francisco, California, United States of America
| | - Ailey Crow
- Department of Molecular Biology, Genentech Inc., South San Francisco, California, United States of America
| | - Chingwei V. Lee
- Department of Antibody Engineering, Genentech Inc., South San Francisco, California, United States of America
| | - Germaine Fuh
- Department of Antibody Engineering, Genentech Inc., South San Francisco, California, United States of America
| | - Nicholas van Bruggen
- Department of Biomedical Imaging, Genentech Inc., South San Francisco, California, United States of America
| | - Weilan Ye
- Department of Molecular Biology, Genentech Inc., South San Francisco, California, United States of America
| | - Robby M. Weimer
- Department of Biomedical Imaging, Genentech Inc., South San Francisco, California, United States of America
- * E-mail:
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Experience with oesophageal cancer: a ten-year single centre study reflecting daily practice. ISRN GASTROENTEROLOGY 2013; 2013:205417. [PMID: 23710364 PMCID: PMC3655664 DOI: 10.1155/2013/205417] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Accepted: 03/27/2013] [Indexed: 01/09/2023]
Abstract
Introduction. Studied patients with oesophageal cancer do not represent normal daily presentation. Aim. A retrospective study was done in all consecutive patients in order to describe presentation, treatment, and survival. Patients. All patients in a ten-year period were included. Patients were grouped in three groups. Group 1: no metastases and potentially curable, dead, or alive at time of evaluation. Group 2: patients presenting with metastases and treated with palliative chemotherapy, and group 3: patients with or without metastases but untreatable because of low Karnofsky index or important comorbidity rendering treatment not feasible. Results. One hundred thirty one evaluable patients were included. There was no difference in histological type of the tumour. Patients in group 3 were significantly older. Survival was not different between groups 2 and 3. Survival in group 1 was significantly longer (P < 0.0001) compared with groups 2 and 3. Patients in group 1 received treatment with chemoradiation and surgery. Patients in groups 2 and 3 were more often treated with palliative chemotherapy and endoscopic stenting. Conclusion. The overall survival of oesophageal cancer in normal daily life is poor. Supportive care seems to be the best treatment option in patients with metastases or low Karnofsky index. Palliative chemotherapy does not add to overall survival.
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Allan BJ, Pedroso F, Gennis ER, Livingstone AS, Montero A, Lally B, Ardalan B, Koniaris LG, Solomon NL, Franceschi D. Influence of Treatment Modality in Outcomes for Different Stages of Resectable Esophageal Adenocarcinomas. Ann Surg Oncol 2013; 20:1660-7. [DOI: 10.1245/s10434-012-2766-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2012] [Indexed: 11/18/2022]
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Multimodality management of esophageal cancer. Indian J Surg Oncol 2013; 4:96-104. [PMID: 24426708 DOI: 10.1007/s13193-013-0216-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Accepted: 01/07/2013] [Indexed: 12/21/2022] Open
Abstract
Esophageal cancer is a highly lethal and aggressive disease and a major public health problem worldwide. The incidence of esophageal cancer in the western hemisphere has increased by 400 % in the past few decades (Posner et al. 2011). Surgery is the mainstay of definitive management of esophageal cancer; however, the results of surgery alone have been dismal, with survival rates of approximately 15 to 20 % at 5 years (Hingorani et al., Clin Oncol 23:696-705, 2011). The last three decades have seen growing interest in various adjuvant and neoadjuvant treatment strategies, with an aim to improve disease control and overall survival. However, due to conflicting and often contradictory results, there was controversy on the ideal treatment paradigm. Recent evidence suggests an improvement in overall survival with neoadjuvant therapy, both chemotherapy and chemoradiotherapy, over surgery. In this review we address various issues concerning multimodality management of locally advanced esophageal cancers: Does neoadjuvant therapy offer a definite benefit over surgery alone? If so, which neoadjuvant strategy? Does the survival benefit outweigh the increased treatment related toxicity/morbidity? Finally, is neoadjuvant treatment the standard of care for locally advanced resectable esophageal cancer?
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Yang H, Fu JH. Progress in surgery-based multimodality therapy for resectable esophageal cancer. Shijie Huaren Xiaohua Zazhi 2012; 20:3471-3475. [DOI: 10.11569/wcjd.v20.i35.3471] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The incidence of esophageal cancer is rather high in China. For patients with resectable esophageal cancer, surgery is the standard treatment. However, the overall survival of patients with locally advanced esophageal cancer remains low, which necessitates the development of multimodality therapies for this malignancy. Among currently available multimodality treatments, preoperative chemoradiotherapy followed by surgery is the most promising strategy in terms of improving the prognosis of advanced esophageal cancer. Postoperative chemotherapy or radiotherapy is also feasible for selected patients. The aim of this article is to provide a complete review of the current status of esophageal cancer treatment with the addition of chemotherapy and radiotherapy to the surgical management of resectable disease.
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Villaflor VM, Allaix ME, Minsky B, Herbella FA, Patti MG. Multidisciplinary approach for patients with esophageal cancer. World J Gastroenterol 2012; 18:6737-46. [PMID: 23239911 PMCID: PMC3520162 DOI: 10.3748/wjg.v18.i46.6737] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2012] [Revised: 11/19/2012] [Accepted: 11/24/2012] [Indexed: 02/06/2023] Open
Abstract
Patients with esophageal cancer have a poor prognosis because they often have no symptoms until their disease is advanced. There are no screening recommendations for patients unless they have Barrett's esophagitis or a significant family history of this disease. Often, esophageal cancer is not diagnosed until patients present with dysphagia, odynophagia, anemia or weight loss. When symptoms occur, the stage is often stage III or greater. Treatment of patients with very early stage disease is fairly straight forward using only local treatment with surgical resection or endoscopic mucosal resection. The treatment of patients who have locally advanced esophageal cancer is more complex and controversial. Despite multiple trials, treatment recommendations are still unclear due to conflicting data. Sadly, much of our data is difficult to interpret due to many of the trials done have included very heterogeneous groups of patients both histologically as well as anatomically. Additionally, studies have been underpowered or stopped early due to poor accrual. In the United States, concurrent chemoradiotherapy prior to surgical resection has been accepted by many as standard of care in the locally advanced patient. Patients who have metastatic disease are treated palliatively. The aim of this article is to describe the multidisciplinary approach used by an established team at a single high volume center for esophageal cancer, and to review the literature which guides our treatment recommendations.
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Jia Y, Yang Y, Brock MV, Cao B, Zhan Q, Li Y, Yu Y, Herman JG, Guo M. Methylation of TFPI-2 is an early event of esophageal carcinogenesis. Epigenomics 2012; 4:135-46. [PMID: 22449186 DOI: 10.2217/epi.12.11] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
AIMS To explore the epigenetic changes and the function of TFPI-2 in esophageal cancer. MATERIALS & METHODS Nine esophageal cancer cell lines, nine normal esophageal mucosa, 60 esophageal dysplasia and 106 advanced esophageal cancer samples were included in this study. TFPI-2 methylation was examined by methylation-specific PCR. TFPI-2 expression was evaluated by immunohistochemistry in tissue samples. The effect of TFPI-2 on proliferation, apoptosis, invasion and migration was analyzed by colony formation assay, western blot assay, transwell assay and flow cytometric analysis. RESULTS TFPI-2 expression was regulated by promoter region hypermethylation in human esophageal cancer cell lines, and TFPI-2 expression is inversely correlated with methylation in primary cancer. Methylation was found in 28.2, 33.3 and 33.3% of grade 1, 2 and 3 esophageal dysplasia, and 67% of primary esophageal cancer, but no methylation was found in normal mucosa. Methylation is significantly related to tumor differentiation. Inhibition of invasion, migration, colony formation and proliferation, and induction of apoptosis occurred with the restoration of TFPI-2 expression in the KYSE70 cell line. CONCLUSION TFPI-2 is frequently methylated in esophageal cancer with a progression tendency. TFPI-2 is a potential tumor suppressor in esophageal cancer.
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Affiliation(s)
- Yan Jia
- Department of Gastroenterology & Hepatology, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853, China
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Siddiqui AA, Sarkar A, Beltz S, Lewis J, Loren D, Kowalski T, Fang J, Hilden K, Adler DG. Placement of fully covered self-expandable metal stents in patients with locally advanced esophageal cancer before neoadjuvant therapy. Gastrointest Endosc 2012; 76:44-51. [PMID: 22726465 DOI: 10.1016/j.gie.2012.02.036] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Accepted: 02/20/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND Most patients with locally advanced esophageal cancer requiring neoadjuvant therapy have significant dysphagia. OBJECTIVE To report our experience in using a fully covered self-expandable metal stent (FCSEMS) to treat malignant dysphagia and for maintenance of nutritional support during neoadjuvant therapy. DESIGN Retrospective study. SETTING Two tertiary-care referral centers. PATIENTS This study involved 55 patients with locally advanced esophageal cancer (50 adenocarcinoma, 5 squamous cell carcinoma). Forty-three patients were men, and the mean age was 65.8 years. INTERVENTION EUS followed by FCSEMS placement. MAIN OUTCOME MEASUREMENTS Procedural success, dysphagia scores, patient weights, stent migration, and stent-related complications. RESULTS All stents were successfully placed. Tumors were located in the middle esophagus (n = 10) and distal esophagus (n = 45). The mean dysphagia score obtained at 1 week after stent placement had improved significantly from baseline (2.4 and 1, respectively; P < .001). Patients maintained their weights at 1 month follow-up when compared with baseline (153 and 149 pounds, respectively; P = .58). Immediate complications included chest discomfort in 13 patients; 2 patients required stent removal because of intractable pain. One patient had stent removal because of significant acid reflux. Stent migration occurred at some point in 17 of 55 patients (31%). There was a delayed perforation in 1 patient. Because of disease progression or the discovery of metastasis after neoadjuvant therapy, only 8 of 55 patients underwent curative surgery. LIMITATIONS Retrospective study. CONCLUSION Placement of FCSEMSs in patients with locally advanced esophageal cancer significantly improves dysphagia and allows for oral nutrition during neoadjuvant therapy. FCSEMSs appear to be effective for palliating dysphagia. Migration was not associated with injury or harm to the patient and usually represented a positive response to neoadjuvant therapy. Few patients undergoing stenting in this situation ultimately undergo surgery because of disease progression or poor operative candidacy.
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Affiliation(s)
- Ali A Siddiqui
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA
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Abstract
Esophageal cancer is the eighth most common cancer and causes the sixth highest cancer-related mortality worldwide. The 5-year survival of patients suffering from esophageal cancer in either advanced stage or metastasis is less than 20%. MicroRNAs are small, well conserved, non-coding RNA molecules that either repress translation or promote mRNA degradation based on the degree of complementary between miRNAs and mRNAs. Based on biogenesis and function of microRNAs, specific microRNA profiles, either from cancerous tissues or serum, were able to serve as diagnostic and prognostic biomarkers of esophageal cancer and predicted the effectiveness of surgery and chemoradiotherapy. MicroRNAs could also influence the biological behaviors of esophageal cancer cells, such as cellular proliferation, apoptosis, invasion and metastasis. MicroRNAs were also associated with multi-drug resistance of esophageal cancer. Further studies on the roles of microRNAs in esophageal cancer would provide a strategy to prevent and treat esophageal cancer, and reverse multi-drug resistance of esophageal cancer.
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Affiliation(s)
- Yu Fang
- Department of Cardiovascular and Thoracic Surgery, 2nd Xiangya Hospital, Central South University, Changsha, China
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Herskovic A, Russell W, Liptay M, Fidler MJ, Al-Sarraf M. Esophageal carcinoma advances in treatment results for locally advanced disease: review. Ann Oncol 2012; 23:1095-1103. [PMID: 22003242 DOI: 10.1093/annonc/mdr433] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The treatment results of patients with locally advanced esophageal carcinomas have evolved since the publication of the first trial of concurrent mitomycin C and 5-fluorouracil with radiotherapy (RT) in 1983. Subsequent studies refined and improved on the concurrent chemotherapy (chemo) with administration of cisplatin and 5-fluorouracil infusion (PF). Chemo (PF) before surgery improved overall survival (OS) in those patients in most of the randomized trials and in meta-analyses. Two courses of PF concurrent with irradiation followed by additional two courses of PF were superior to RT alone without surgery for both groups. Concurrent chemoradiotherapy followed by surgery was found to have statistically improved OS as compared with surgery only in randomized trials and meta-analyses. In most of these studies, it was found that those patients with pathologic complete response to the initial treatment(s) did better than those who had no improvement at all. Current treatment outcome for these diseases is disappointing; newer strategies including induction chemo with the optimal combination, proper dosage of each drug, and proper number of courses before concurrent chemoradiotherapy; improvement in RT; and immunotherapy with or without subsequent surgery are exciting and definitely need to be investigated in prospective randomized trial(s).
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Affiliation(s)
| | | | | | - M J Fidler
- Department of Section of Medical Oncology, Rush University Medical Center, Chicago
| | - M Al-Sarraf
- Department of Medicine, Wm Beaumont Hospital, Royal Oak, USA
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Tsuchikawa T, MD MM, Yamamura Y, Shichinohe T, Hirano S, Kondo S. The Immunological Impact of Neoadjuvant Chemotherapy on the Tumor Microenvironment of Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2012; 19:1713-1719. [DOI: 10.1245/s10434-011-1906-x] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Assifi MM, Lu X, Eibl G, Reber HA, Li G, Hines OJ. Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. Surgery 2011; 150:466-73. [PMID: 21878232 DOI: 10.1016/j.surg.2011.07.006] [Citation(s) in RCA: 150] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2011] [Accepted: 07/06/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND Neoadjuvant treatment has proven beneficial for many gastrointestinal (GI) malignancies, but no phase III trials have been completed examining this approach in pancreatic cancer. This meta-analysis examines the best available phase II trials using neoadjuvant treatment for resectable and borderline/unresectable pancreatic adenocarcinoma. METHODS Phase II trials were identified using a MEDLINE search, and the Cochrane Central Register of Controlled Trials from 1960 to July 2010. Patients were divided into 2 groups: Patients with initially resectable tumors (group A), and patients with borderline/unresectable tumors (group B). Primary outcome measures were rate of resection and survival. Pooled proportions and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. RESULTS A total of 14 phase II clinical trials including 536 patients were analyzed. After treatment, resectability was 65.8% (95% CI, 55.4-75.6%) compared with 31.6% in group B (95% CI, 14.0-52.5%). A partial response was observed in patients with borderline/unresectable tumors; 31.8 (95% CI, 24.2-39.8%) in group B and 9.5% (95% CI, 2.9-19.4%) in group A (P = .003). Progressive disease was seen in 17.0% (95% CI, 11.9-22.7) of patients in group A versus 21.8% (95% CI, 10.1-36.5%) in group B (P = .006). Median survival in resected patients was 23 months for group A and 22 months for group B. CONCLUSION Neoadjuvant treatment seems to have some activity in patients with borderline/unresectable pancreatic adenocarcinoma. Nearly one third of tumors initially deemed marginal for operative intervention were able to be ultimately resected after treatment. Until more effective targeted chemotherapeutics are developed, the only group of patients with pancreatic cancer that may benefit from neoadjuvant treatment are those with locally advanced disease.
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Affiliation(s)
- M Mura Assifi
- Department of Surgery, UCLA School of Public Health, Los Angeles, CA, USA
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Hsu PK, Wang BY, Huang CS, Wu YC, Hsu WH. Prognostic factors for post-recurrence survival in esophageal squamous cell carcinoma patients with recurrence after resection. J Gastrointest Surg 2011; 15:558-65. [PMID: 21327531 DOI: 10.1007/s11605-011-1458-1] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2010] [Accepted: 01/31/2011] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The survival of recurrent esophageal cancer is poor. But reports regarding prognostic factors for post-recurrence survival are limited. We analyzed the recurrence pattern and the prognostic factors for post-recurrence survival in esophageal squamous cell carcinoma with recurrence after resection. METHODS Two hundred sixty-eight patients were included. Tumor recurrence occurred in 115 (42.9%) patients. Recurrence pattern was classified as locoregional, distant, and combined recurrence. The post-recurrence survival was defined as the interval between initial recurrence and either death or the last follow-up. RESULTS Mediastinum lymphadenopathy was the most common site for locoregional recurrence, whereas lung, liver, and bone were the most common sites for distant recurrence. The overall 1- and 2-year post-recurrence survival rates were 32.6% and 12.6% with a median survival after recurrence of 6.0 months. The independent prognostic factors included liver recurrence (HR = 2.255, 95%CI = 1.073-4.741, p = 0.032), time to recurrence ≤10 months (HR = 2.657, 95%CI = 1.438-4.911, p = 0.002), and no treatment for recurrences (HR = 2.745, 95%CI = 1.635-4.608, p < 0.001). CONCLUSIONS We identify liver recurrence, early recurrence, and no treatment for recurrence as risk factors for dismal post-recurrence survival.
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Affiliation(s)
- Po-Kuei Hsu
- Department of Surgery, Chutung Veterans Hospital, Hsinchu County, Taiwan
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Zhang XM, Guo MZ. The value of epigenetic markers in esophageal cancer. ACTA ACUST UNITED AC 2010; 4:378-84. [PMID: 21107750 DOI: 10.1007/s11684-010-0230-3] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2010] [Accepted: 10/10/2010] [Indexed: 12/12/2022]
Abstract
Developing esophageal cancer is a multi-step process that begins with the accumulation of genetic and epigenetic alterations, and leads to the activation of oncogenes and the inactivation or loss of tumor suppressor genes (TSG). In addition to genetic alteration, epigenetic modifications, and in particular DNA methylation, are recognized as a common molecular alteration in human tumors. In esophageal cancer, aberrant methylation of promoter regions occurs not only in advanced cancer, but also in premalignant lesions. DNA methylation is related to survival time and sensitivity of chemoradiotherapy. This review is mainly focused on epigenetic changes in esophageal cancer and the value of early detection for patient prognosis, treatment choices, and potential targeting therapy.
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Affiliation(s)
- Xiao-Mei Zhang
- Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, 100853, China
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