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Fang Z, Xia T, Pan S, Xu C, Ju S, Shen Z, Zhao J. Esophageal carcinosarcoma comprising undifferentiated pleomorphic sarcoma and squamous cell carcinoma: a case report. J Cardiothorac Surg 2022; 17:210. [PMID: 36028859 PMCID: PMC9419343 DOI: 10.1186/s13019-022-01957-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Accepted: 08/16/2022] [Indexed: 11/29/2022] Open
Abstract
Background Esophageal carcinosarcoma (ECS) is a rare malignant tumor that often presents as an intraluminal polypoid lesion in the esophageal lumen. The pathogenesis of esophageal carcinosarcoma is not clear and its etiology is still being discussed. Case presentation We report the case of a 68-year-old male who had dysphagia for approximately three months. Contrast-enhanced computed tomography showed an irregular enhancing mass in the lower esophagus. Endoscopy showed a gray-white mass with a smooth surface that almost filled the esophageal lumen at a location 28 cm from the incisor tooth. Considering the location of the tumor, we opted for Ivor-Lewis esophagectomy with intrathoracic anastomosis through a 5-port laparoscope and uniport video-assisted thoracic surgery (VATS). Pathological analysis showed that the mass comprised carcinoma in situ and pleomorphic sarcoma, without lymphatic metastasis. The postoperative pathological stage was T1bN0M0, stage I (Japanese Classification of Esophageal Cancer 11th Edition). The latest follow-up of the patient was 14 months after the surgery, and no signs of recurrence or metastasis were found. Conclusion This case demonstrates a rare esophageal malignancy with a peculiar histological composition. Successful VATS esophagectomy with intrathoracic anastomosis was conducted without recurrence or metastasis at the 14-month follow-up.
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Affiliation(s)
- Ziyao Fang
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Pinghai Road, Suzhou, 215000, Jiangsu, China
| | - Tian Xia
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Pinghai Road, Suzhou, 215000, Jiangsu, China
| | - Shu Pan
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Pinghai Road, Suzhou, 215000, Jiangsu, China
| | - Chun Xu
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Pinghai Road, Suzhou, 215000, Jiangsu, China
| | - Sheng Ju
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Pinghai Road, Suzhou, 215000, Jiangsu, China
| | - Ziqing Shen
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Pinghai Road, Suzhou, 215000, Jiangsu, China
| | - Jun Zhao
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Pinghai Road, Suzhou, 215000, Jiangsu, China.
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Imaging findings of granulocyte colony-stimulating factor-producing tumors: a case series and review of the literature. Jpn J Radiol 2021; 39:857-867. [PMID: 34021462 PMCID: PMC8413199 DOI: 10.1007/s11604-021-01130-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 04/28/2021] [Indexed: 11/21/2022]
Abstract
Granulocyte colony-stimulating factor (G-CSF)-producing tumors have an aggressive clinical course. Here, we report five cases of G-CSF-producing tumors and review the literature, focusing on imaging findings related to tumor-produced G-CSF. In addition to our cases, we identified 30 previous reports of G-CSF-producing tumors on which 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT, bone scintigraphy, or evaluation of bone marrow MR findings was performed. White blood cell count, serum C-reactive protein, and serum interleukin-6 were elevated in all cases for which these parameters were measured. G-CSF-producing tumors presented large necrotic masses (mean diameter 83.2 mm, range 17–195 mm) with marked FDG uptake (mean maximum standardized uptake value: 20.09). Diffuse FDG uptake into the bone marrow was shown in 28 of the 31 cases in which FDG-PET/CT was performed. The signal intensity of bone marrow suggested marrow reconversion in all seven MRI-assessable cases. Bone scintigraphy demonstrated no significant uptake, except in two cases with bone metastases. Splenic FDG uptake was increased in 8 of 10 cases in which it was evaluated. These imaging findings may reflect the effects of tumor-produced G-CSF. The presence of G-CSF-producing tumors should be considered in patients with cancer who show these imaging findings and marked inflammatory features of unknown origin.
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Karagiannidis I, Salataj E, Said Abu Egal E, Beswick EJ. G-CSF in tumors: Aggressiveness, tumor microenvironment and immune cell regulation. Cytokine 2021; 142:155479. [PMID: 33677228 DOI: 10.1016/j.cyto.2021.155479] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 02/17/2021] [Accepted: 02/18/2021] [Indexed: 12/14/2022]
Abstract
Granulocyte colony-stimulating factor (G-CSF) is a cytokine most well-known for maturation and mobilization of bone marrow neutrophils. Although it is used therapeutically to treat chemotherapy induced neutropenia, it is also highly expressed in some tumors. Case reports suggest that tumors expressing high levels of G-CSF are aggressive, more difficult to treat, and present with poor prognosis and high mortality rates. Research on this topic suggests that G-CSF has tumor-promoting effects on both tumor cells and the tumor microenvironment. G-CSF has a direct effect on tumor cells to promote tumor stem cell longevity and overall tumor cell proliferation and migration. Additionally, it may promote pro-tumorigenic immune cell phenotypes such as M2 macrophages, myeloid-derived suppressor cells, and regulatory T cells. Overall, the literature suggests a plethora of pro-tumorigenic activity that should be balanced with the therapeutic use. In this review, we present an overview of the multiple complex roles of G-CSF and G-CSFR in tumors and their microenvironment and discuss how clinical advances and strategies may open new therapeutic avenues.
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Affiliation(s)
- Ioannis Karagiannidis
- Division of Gastroenterology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, United States
| | - Eralda Salataj
- Institute of Molecular Biology and Biotechnology-Foundation for Research and Technology Hellas, Heraklion, Crete, Greece
| | - Erika Said Abu Egal
- Division of Gastroenterology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, United States
| | - Ellen J Beswick
- Division of Gastroenterology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, United States.
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Tullio V, Gasperi V, Catani MV, Savini I. The Impact of Whole Grain Intake on Gastrointestinal Tumors: A Focus on Colorectal, Gastric, and Esophageal Cancers. Nutrients 2020; 13:E81. [PMID: 33383776 PMCID: PMC7824588 DOI: 10.3390/nu13010081] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/22/2020] [Accepted: 12/25/2020] [Indexed: 02/08/2023] Open
Abstract
Cereals are one of staple foods in human diet, mainly consumed as refined grains. Nonetheless, epidemiological data indicate that whole grain (WG) intake is inversely related to risk of type 2 diabetes, cardiovascular disease, and several cancer types, as well as to all-cause mortality. Particularly responsive to WG positive action is the gastrointestinal tract, daily exposed to bioactive food components. Herein, we shall provide an up-to-date overview on relationship between WG intake and prevention of gastrointestinal tumors, with a particular focus on colorectal, stomach, and esophagus cancers. Unlike refined counterparts, WG consumption is inversely associated with risk of these gastrointestinal cancers, most consistently with the risk of colorectal tumor. Some WG effects may be mediated by beneficial constituents (such as fiber and polyphenols) that are reduced/lost during milling process. Beside health-promoting action, WGs are still under-consumed in most countries; therefore, World Health Organization and other public/private stakeholders should cooperate to implement WG consumption in the whole population, in order to reach nutritionally effective intakes.
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Okamoto H, Kikuchi H, Naganuma H, Kamei T. Multiple carcinosarcomas of the esophagus with adeno-carcinomatous components: A case report. World J Gastroenterol 2020; 26:2111-2118. [PMID: 32536778 PMCID: PMC7267695 DOI: 10.3748/wjg.v26.i17.2111] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 04/08/2020] [Accepted: 04/27/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Carcinosarcoma (spindle cell carcinoma) of the esophagus is an extremely rare event; the etiology and origins of this neoplasm have not yet been determined. Epithelial-mesenchymal transition (EMT) has been associated with invasion and metastasis, and may be related to the generation of a stem cell population within this tumor.
CASE SUMMARY We present the case of a 61-year-old male with nausea and fever. Upper gastrointestinal endoscopy revealed the presence of type 1 and 0-IIc lesions located 35 cm from the incisors toward the esophago-gastric junction. Thoracoscopic esophagectomy was performed. Macroscopic analysis revealed three polypoid lesions in the abdominal esophagus that accompanied the main lesion in the lower thoracic esophagus and 0-IIc lesions that spread continuously with them. Histologically, the lesions included proliferating spindle cells. Adeno-carcinomatous components were detected in a section near the foot, and squamous cell carcinoma was identified in the mucosa at the base of the tumor. The patient was diagnosed with multiple carcinosarcomas, staged at pT1b (SM3), pN1 (#110, #7), cM0, Stage II (sarcomatous metastasis to the lymph nodes). Spindle cells did not express E-cadherin but were positive for EMT markers, including zinc finger E-box-binding homeobox 1, TWIST, and snail family transcriptional repressor 2. The patient has experienced no recurrence at 5 years and 2 mo after surgery.
CONCLUSION This report suggests that multiple sarcomatous tumors may be generated from primary squamous cell carcinoma via mechanisms related to EMT.
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Affiliation(s)
- Hiroshi Okamoto
- Department of Gastroenterological Surgery, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan
| | - Hiroshi Kikuchi
- Department of Surgery, South Miyagi Medical Center, Miyagi 989-1253, Japan
| | - Hiroshi Naganuma
- Department of Pathology, Sendai City Hospital, Sendai 982-8502, Japan
| | - Takashi Kamei
- Department of Gastroenterological Surgery, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan
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Yoshida Y, Sibusa T, Ishii Y, Akino K, Kikuchi T, Mita H, Adachi Y, Nakamura M, Adachi Y, Kato Y, Endo T. Granulocyte Colony-stimulating Factor- and Interleukin-6-producing Large-cell Carcinoma of the Lung with Sarcomatoid Changes Suggestive of Epithelial-mesenchymal Transition: An Autopsy Case Report. Intern Med 2019; 58:3305-3311. [PMID: 31366794 PMCID: PMC6911748 DOI: 10.2169/internalmedicine.2819-19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
A rare case of lung cancer with the simultaneous production of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) is reported. A 79-year-old man was admitted to our hospital due to cachectic symptoms and an increased inflammatory response. Laboratory tests and imaging studies suggested metastatic lung cancer with high serum levels of G-CSF and IL-6. He died of progressive disease, and an autopsy showed that the lung tumor had positive protein expression of both cytokines and a solid growth of large-cell carcinoma with sarcomatoid changes, possibly resulting from the epithelial-mesenchymal transition mediated by IL-6 and leading to widespread metastases.
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Affiliation(s)
- Yukinari Yoshida
- Department of Internal Medicine and Gastroenterology, Sapporo Shirakabadai Hospital, Japan
| | - Takashi Sibusa
- Department of Respiratory Medicine, Sapporo Shirakabadai Hospital, Japan
| | - Yoshifumi Ishii
- Department of Pathology, Sapporo Shirakabadai Hospital, Japan
| | - Kimishige Akino
- Department of Internal Medicine and Gastroenterology, Sapporo Shirakabadai Hospital, Japan
| | - Takefumi Kikuchi
- Department of Internal Medicine and Gastroenterology, Sapporo Shirakabadai Hospital, Japan
| | - Hiroaki Mita
- Department of Internal Medicine and Gastroenterology, Sapporo Shirakabadai Hospital, Japan
| | - Yasuyo Adachi
- Department of Internal Medicine and Gastroenterology, Sapporo Shirakabadai Hospital, Japan
| | - Masahiro Nakamura
- Department of Internal Medicine and Gastroenterology, Sapporo Shirakabadai Hospital, Japan
| | - Yasushi Adachi
- Department of Internal Medicine and Gastroenterology, Sapporo Shirakabadai Hospital, Japan
| | - Yasuo Kato
- Department of Internal Medicine and Gastroenterology, Sapporo Shirakabadai Hospital, Japan
| | - Takao Endo
- Department of Internal Medicine and Gastroenterology, Sapporo Shirakabadai Hospital, Japan
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Qiu JG, Wang L, Liu WJ, Wang JF, Zhao EJ, Zhou FM, Ji XB, Wang LH, Xia ZK, Wang W, Lin MCM, Liu LZ, Huang YX, Jiang BH. Apigenin Inhibits IL-6 Transcription and Suppresses Esophageal Carcinogenesis. Front Pharmacol 2019; 10:1002. [PMID: 31572184 PMCID: PMC6749068 DOI: 10.3389/fphar.2019.01002] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Accepted: 08/06/2019] [Indexed: 01/05/2023] Open
Abstract
Esophagus cancer is the seventh cause of cancer-related deaths globally. In this study, we analyzed interleukin 6 (IL-6) gene expression in human esophagus cancer patients and showed that IL-6 mRNA levels are significantly higher in tumor tissues and negatively correlated with overall survival, suggesting that IL-6 is a potential therapeutic target for esophagus cancer. We further demonstrated that apigenin, a nature flavone product of green plants, inhibited IL-6 transcription and gene expression in human esophagus cancer Eca-109 and Kyse-30 cells. Apigenin significantly and dose-dependently inhibited cell proliferation and promoted apoptosis while stimulating the cleaved PARP (poly ADP-ribose polymerase) (C-PARP) and caspase-8 expression. It suppressed VEGF (Vascular endothelial growth Factor) expression and tumor-induced angiogenesis. Pretreatment of cells with IL-6 could completely reverse apigenin-induced cellular changes. Finally, using a preclinical nude mice model subcutaneously xenografted with Eca-109 cells, we demonstrated the in vivo antitumor activity and mechanisms of apigenin. Taken together, this study revealed for the first time that apigenin is a new IL-6 transcription inhibitor and that inhibiting IL-6 transcription is one of the mechanisms by which apigenin exhibits its anticancer effects. The potential clinical applications of apigenin in treating esophagus cancer warrant further investigations.
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Affiliation(s)
- Jian-Ge Qiu
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Lin Wang
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Wen-Jing Liu
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Ju-Feng Wang
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Er-Jiang Zhao
- Department of Biostatistics, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Feng-Mei Zhou
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Xiang-Bo Ji
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Li-Hong Wang
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Zhong-Kun Xia
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Wei Wang
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Marie Chia-mi Lin
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Ling-Zhi Liu
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa, IA, United States
| | - Ying-Xue Huang
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
- *Correspondence: Ying-Xue Huang, ; Bing-Hua Jiang,
| | - Bing-Hua Jiang
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa, IA, United States
- *Correspondence: Ying-Xue Huang, ; Bing-Hua Jiang,
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