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Abd-Eldayem AM, Ali MF, Ahmed EA. Nebivolol rescued the liver and kidney from the coadministration of rivaroxaban and cisplatin by targeting inflammation, oxidative stress, and apoptosis in rats. Int Immunopharmacol 2025; 153:114486. [PMID: 40112601 DOI: 10.1016/j.intimp.2025.114486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 03/10/2025] [Accepted: 03/11/2025] [Indexed: 03/22/2025]
Abstract
Cisplatin is among the most frequently utilized drugs for addressing malignant tumors, yet it can lead to organ harm, especially hepatotoxicity and nephrotoxicity. Furthermore, the anticoagulant rivaroxaban could potentially cause injury to the liver and kidneys. This research aimed to examine the protective benefits of nebivolol, known for its pleiotropic and tissue-protective characteristics, against the harmful effects of rivaroxaban and cisplatin on the liver and kidneys. Male rats received cisplatin and/or rivaroxaban, and we evaluated hepatotoxicity and nephrotoxicity by measuring serum concentrations of AST, ALT, LDH, albumin, bilirubin, creatinine, and blood urea. We also measured MDA, GSH, GPx, NO, TNF-α, and IL-6 in kidney and liver homogenates. Histopathological analysis was performed on liver and kidney tissue sections, and immunohistochemical detection of caspase 3 in liver tissue and NF-κB in kidney tissue was conducted. Our findings demonstrated that nebivolol supported the preservation of the liver and kidney structure and function by reducing the biochemical and pathological alterations caused by cisplatin and rivaroxaban. Nebivolol decreased the elevations in MDA, TNF-α, and IL-6 levels while maintaining GSH, GPx, and NO levels in liver and kidney tissues. Moreover, nebivolol lowered the levels of caspase-3 in the liver and NF-κB in the kidneys. In conclusion, our study indicates that nebivolol protects the liver and kidneys from the detrimental effects of cisplatin and rivaroxaban.
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Affiliation(s)
- Ahmed M Abd-Eldayem
- Department of Medical Pharmacology, Faculty of Medicine, Assiut University, 71515 Assiut. Egypt; Pharmacology department, College of Medicine, Fahad Bin Sultan University (FBSU), 15700, Tabuk 71454, Saudi Arabia.
| | - Marwa F Ali
- Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Assiut, Assiut University, Egypt
| | - Esraa A Ahmed
- Department of Medical Pharmacology, Faculty of Medicine, Assiut University, 71515 Assiut. Egypt
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2
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Li TH, Sun X, Li CG, Yin YP, Tao KX. Hypercoagulation after neoadjuvant immunochemotherapy as a new prognostic indicator in patients with locally advanced gastric cancer undergoing surgery. World J Gastrointest Oncol 2025; 17:100927. [PMID: 40092957 PMCID: PMC11866221 DOI: 10.4251/wjgo.v17.i3.100927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/06/2024] [Accepted: 12/25/2024] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Coagulation status is closely related to the progression of malignant tumors. In the era of neoadjuvant immunochemotherapy (NICT), the prognostic utility of coagulation indicators in patients with locally advanced gastric cancer (LAGC) undergoing new treatments remains to be determined. AIM To determine whether hypercoagulation is an effective prognostic indicator in patients with LAGC who underwent radical resection after NICT. METHODS A retrospective analysis of clinical data from 104 patients with LAGC, who underwent radical resection after NICT between 2020 and 2023, was performed. D-dimer and fibrinogen concentrations were measured one week before NICT, and again one week before surgery, to analyze the association between these two indicators and their combined indices [non-hypercoagulation (D-dimer and fibrinogen concentrations within the upper limit of normal) vs hypercoagulation (D-dimer or fibrinogen concentrations above the upper limit of normal)] with prognosis. After radical resection, patients were followed-up periodically. The median follow-up duration was 21 months. RESULTS Data collected after NICT revealed that the three-year overall survival (OS) and disease-free survival (DFS) rates the non-hypercoagulation group were significantly better than those in the hypercoagulation group [94.4% vs 78.0% (P = 0.019) and 87.0% vs 68.0% (P = 0.027), respectively]. Multivariate analysis indicated that hypercoagulation after NICT was an independent factor for poor postoperative OS [hazard ratio (HR) 4.436, P = 0.023] and DFS (HR 2.551, P = 0.039). Pre-NICT data demonstrated no statistically significant difference in three-year OS between the non-hypercoagulation and hypercoagulation groups (88.3% vs 84.1%, respectively; P = 0.443). CONCLUSION Hypercoagulation after NICT is an effective prognostic indicator in patients with LAGC undergoing radical gastrectomy.
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Affiliation(s)
- Tian-Hao Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Xiong Sun
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Cheng-Guo Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Yu-Ping Yin
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Kai-Xiong Tao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
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Sugiyama F, Kanda M, Shimizu D, Umeda S, Inokawa Y, Hattori N, Hayashi M, Tanaka C, Nakayama G, Kodera Y. Absence of Hypercoagulation Status after Neoadjuvant Treatment is Associated with Favorable Prognosis in Patients Undergoing Subtotal Esophagectomy for Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2024; 31:3417-3425. [PMID: 38245650 DOI: 10.1245/s10434-024-14938-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 12/29/2023] [Indexed: 01/22/2024]
Abstract
BACKGROUND Abnormal activation of the coagulation system is associated with malignant tumor progression. Although neoadjuvant treatment (NAT) for resectable esophageal squamous cell carcinoma (ESCC) is the standard of care, the correlation between coagulation status and prognosis of patients undergoing preoperative treatment is insufficiently understood. METHODS Patients (n = 200) who underwent radical subtotal esophagectomy after preoperative treatment for ESCC between January 2012 and December 2021were included in the analysis. Plasma D-dimer and fibrinogen levels and their combined indices (non-hypercoagulation; D-dimer and fibrinogen levels within the upper normal limit, or hypercoagulation; D-dimer or fibrinogen levels above the upper normal limit) were determined before and after NAT and correlated to clinicopathological factors and prognosis. RESULTS The nonhypercoagulation group achieved superior overall survival (OS) than the hypercoagulation group (5-year OS rates = 89% vs. 55%; hazard ratio 3.62, P = 0.0008) when determined according to coagulation status after NAT. Multivariate analysis showed that hypercoagulation after NAT served as an independent factor for poor postoperative OS (hazard ratio 3.20; P = 0.0028). The nonhypercoagulation group achieved significantly better disease-free survival (76% vs. 54%; P = 0.0065) than the hypercoagulation group that experienced a significantly higher rate of hematogenous metastasis as an initial recurrence (P = 0.0337). CONCLUSIONS Hypercoagulation state after NAT served as a valid indicator correlating with postoperative outcomes of patients with ESCC who underwent NAT followed by radical subtotal esophagectomy.
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Affiliation(s)
- Fumitake Sugiyama
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Dai Shimizu
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shinichi Umeda
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshikuni Inokawa
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Norifumi Hattori
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masamichi Hayashi
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Chie Tanaka
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Goro Nakayama
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Zheng VM, Linn YL, Ch’ng JK, Chng SP. Management of Spontaneous Aortic Thrombus Following Cisplatin-Based Chemotherapy in Urothelial Cancer: A Case Report. Vasc Specialist Int 2023; 39:40. [PMID: 38105728 PMCID: PMC10727851 DOI: 10.5758/vsi.230091] [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: 09/19/2023] [Revised: 11/03/2023] [Accepted: 11/12/2023] [Indexed: 12/19/2023] Open
Abstract
Spontaneous aortic thrombosis is exceedingly rare, and optimal treatment remains uncertain. We present an unusual case of a spontaneous aortic thrombus at the renal artery level in a patient undergoing active cisplatin treatment for urothelial carcinoma. Management included catheter-directed thrombolysis followed by thrombectomy. An open cutdown was performed on the left common femoral artery (CFA), with right groin access via a 6-Fr sheath. Clamping of the left superficial and deep femoral arteries, along with balloon occlusion of the right common iliac artery, prevented distal embolization. A Coda balloon introduced via direct left CFA puncture with a 20-Fr sheath was positioned above the aortic thrombus. After inflation, clots were trawled to the sheath, "sandwiching" the clots before removal of the balloon and sheath via the left groin. Post-operatively, the patient recovered well and received continued therapeutic anticoagulation.
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Affiliation(s)
| | - Yun Le Linn
- Department of Vascular Surgery, Singapore General Hospital, Singapore
| | - Jack Kian Ch’ng
- Department of Vascular Surgery, Singapore General Hospital, Singapore
| | - Siew Ping Chng
- Department of Vascular Surgery, Singapore General Hospital, Singapore
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Zhou Q, Quirk JD, Hu Y, Yan H, Gaut JP, Pham CTN, Wickline SA, Pan H. Rapamycin Perfluorocarbon Nanoparticle Mitigates Cisplatin-Induced Acute Kidney Injury. Int J Mol Sci 2023; 24:6086. [PMID: 37047059 PMCID: PMC10093942 DOI: 10.3390/ijms24076086] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/16/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10-20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and no specific mechanism-based prophylactic approach is available to date. Here, we postulated that systemically delivered rapamycin perfluorocarbon nanoparticles (PFC NP) could reach the injured kidneys at sufficient and sustained concentrations to mitigate cisplatin-induced acute kidney injury and preserve renal function. Using fluorescence microscopic imaging and fluorine magnetic resonance imaging/spectroscopy, we illustrated that rapamycin-loaded PFC NP permeated and were retained in injured kidneys. Histologic evaluation and blood urea nitrogen (BUN) confirmed that renal structure and function were preserved 48 h after cisplatin injury. Similarly, weight loss was slowed down. Using western blotting and immunofluorescence staining, mechanistic studies revealed that rapamycin PFC NP significantly enhanced autophagy in the kidney, reduced the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as decreased the expression of the apoptotic protein Bax, all of which contributed to the suppression of apoptosis that was confirmed with TUNEL staining. In summary, the delivery of an approved agent such as rapamycin in a PFC NP format enhances local delivery and offers a novel mechanism-based prophylactic therapy for cisplatin-induced acute kidney injury.
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Affiliation(s)
- Qingyu Zhou
- Taneja College of Pharmacy, University of South Florida, Tampa, FL 33620, USA
| | - James D. Quirk
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Ying Hu
- Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Huimin Yan
- Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Joseph P. Gaut
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Christine T. N. Pham
- Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Samuel A. Wickline
- Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA
| | - Hua Pan
- Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA
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6
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Rashid F, Omar NE, Aaekl H, Al Homsi U, Shablak A. Successful rechallenge with cisplatin following cisplatin induced ischemic cerebrovascular accident in a patient with small cell lung cancer. Clin Case Rep 2022; 10:e6469. [PMID: 36285031 PMCID: PMC9585048 DOI: 10.1002/ccr3.6469] [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: 05/16/2022] [Revised: 09/13/2022] [Accepted: 09/30/2022] [Indexed: 11/11/2022] Open
Abstract
Cisplatin is a widely used platinum-based chemotherapy agent. Its common adverse effects are neuropathy, nephrotoxicity, electrolyte abnormality, and rarely causing thrombotic vascular toxicity. We present a patient known to have small-cell lung cancer who developed ischemic cerebrovascular accident (CVA) after receiving chemotherapy regimen including cisplatin.
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Affiliation(s)
- Farah Rashid
- Department of Internal MedicineHamad General Hospital, Hamad Medical CorporationDohaQatar
| | - Nabil E. Omar
- Pharmacy DepartmentNational Center for Cancer Care and Research, Hamad Medical CorporationDohaQatar
| | - Hassan Aaekl
- Department of Medical OncologyNational Center for Cancer Care and Research, Hamad Medical CorporationDohaQatar
| | - Ussama Al Homsi
- Department of Medical OncologyNational Center for Cancer Care and Research, Hamad Medical CorporationDohaQatar
| | - Alaaeldin Shablak
- Department of Medical OncologyNational Center for Cancer Care and Research, Hamad Medical CorporationDohaQatar
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7
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Sato N, Mishima T, Okubo Y, Okamoto T, Shiraishi S, Tsuchida M. Acute aortic thrombosis in the ascending aorta after cisplatin-based chemotherapy for esophageal cancer: a case report. Surg Case Rep 2022; 8:75. [PMID: 35461358 PMCID: PMC9035195 DOI: 10.1186/s40792-022-01431-8] [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: 12/20/2021] [Accepted: 04/15/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The risk of thrombus development is considered to be increased by malignant tumors and chemotherapy. In addition, thrombosis of the ascending aorta is rare. We report a case of ascending aortic thrombectomy in a patient with esophageal cancer who developed ascending aortic thrombus after starting neoadjuvant chemotherapy, including operative findings and surgical treatment. CASE PRESENTATION A 63-year-old man with esophageal cancer was administered chemotherapy comprising cisplatin plus 5-fluorouracil. A week after completing 1 cycle of chemotherapy, computed tomography angiography showed acute aortic thrombosis at the ascending aorta. The risk of embolization appeared high because the thrombosis was floating, so we performed emergency ascending aortic thrombectomy. The postoperative course was good and uncomplicated. A month after this surgery, the patient underwent surgery for esophageal cancer. As of 1 year after the cancer surgery, neither cancer nor thrombosis has recurred. CONCLUSION We describe a case of acute aortic thrombosis in the ascending aorta after cisplatin-based chemotherapy, that was treated by aortic thrombectomy. The treatment strategy should depend on thrombus location and the condition of the patient, but surgical treatment should be considered where possible to achieve better prognosis.
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Affiliation(s)
- Noriaki Sato
- Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757, Asahimachi-dori, Niigata, Japan.
| | - Takehito Mishima
- Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757, Asahimachi-dori, Niigata, Japan
| | - Yuka Okubo
- Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757, Asahimachi-dori, Niigata, Japan
| | - Takeshi Okamoto
- Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757, Asahimachi-dori, Niigata, Japan
| | - Shuichi Shiraishi
- Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757, Asahimachi-dori, Niigata, Japan
| | - Masanori Tsuchida
- Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757, Asahimachi-dori, Niigata, Japan
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Cervantes CE, Kant S, Atta MG. The Link Between Conventional and Novel Anti-Cancer Therapeutics with Thrombotic Microangiopathy. Drug Metab Lett 2021; 14:97-105. [PMID: 34279209 DOI: 10.2174/1872312814666210716141633] [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: 01/06/2021] [Revised: 04/28/2021] [Accepted: 05/09/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Kidney disease associated with cancer and anti-cancer therapies has been increasingly recognized in the field of onco-nephrology. In particular, drug-induced nephrotoxicity has important implications since most chemotherapeutic agents have a nephrotoxic potential. Also, standard creatinine clearance methods used for the measurement of kidney function have been questioned in cancer patients due to factors like low muscle mass and poor nutritional status. Overestimations of the glomerular filtration rate, not only can increase the nephrotoxic potential of different agents, but also further limit the use of first-line therapies. OBJECTIVE This review covers specifically the drug-induced thrombotic microangiopathy and its two pathophysiologic mechanisms which include immune or idiosyncratic reactions, and non-immune or dose-dependent ones. CONCLUSION As novel cancer therapies are developed, it is paramount to pursue a better understanding of conventional and novel chemotherapeutic agents and their role in kidney disease.
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Affiliation(s)
- Carmen E Cervantes
- Department of Medicine, Division of Nephrology, Johns Hopkins University, Baltimore, Maryland MD 21218, United States
| | - Sam Kant
- Department of Medicine, Division of Nephrology, Johns Hopkins University, Baltimore, Maryland MD 21218, United States
| | - Mohamed G Atta
- Department of Medicine, Division of Nephrology, Johns Hopkins University, Baltimore, Maryland MD 21218, United States
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9
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Life after Cell Death-Survival and Survivorship Following Chemotherapy. Cancers (Basel) 2021; 13:cancers13122942. [PMID: 34208331 PMCID: PMC8231100 DOI: 10.3390/cancers13122942] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/06/2021] [Accepted: 06/09/2021] [Indexed: 12/21/2022] Open
Abstract
Simple Summary Treatment of aggressive cancers often relies on chemotherapy. This treatment has improved survival rates, but while effective at killing cancer cells, inevitably it also kills or alters the function of others. While many of the known effects are transient and resolve after treatment, as survival rates increase, so does our understanding of the long-term health costs that accompany cancer survivors. Here we provide an overview of common long-term morbidities known to be caused by conventional chemotherapy, including the risk of relapse, but more importantly, the cost of quality of life experienced, especially by those who have cancer in early life. We aim to highlight the importance of the development of targeted therapies to replace the use of conventional chemotherapy, but also that of treating the patients along with the disease to enable not only longer but also healthier life after cancer. Abstract To prevent cancer cells replacing and outnumbering their functional somatic counterparts, the most effective solution is their removal. Classical treatments rely on surgical excision, chemical or physical damage to the cancer cells by conventional interventions such as chemo- and radiotherapy, to eliminate or reduce tumour burden. Cancer treatment has in the last two decades seen the advent of increasingly sophisticated therapeutic regimens aimed at selectively targeting cancer cells whilst sparing the remaining cells from severe loss of viability or function. These include small molecule inhibitors, monoclonal antibodies and a myriad of compounds that affect metabolism, angiogenesis or immunotherapy. Our increased knowledge of specific cancer types, stratified diagnoses, genetic and molecular profiling, and more refined treatment practices have improved overall survival in a significant number of patients. Increased survival, however, has also increased the incidence of associated challenges of chemotherapy-induced morbidity, with some pathologies developing several years after termination of treatment. Long-term care of cancer survivors must therefore become a focus in itself, such that along with prolonging life expectancy, treatments allow for improved quality of life.
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10
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Retinal toxicities of systemic anticancer drugs. Surv Ophthalmol 2021; 67:97-148. [PMID: 34048859 DOI: 10.1016/j.survophthal.2021.05.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 05/08/2021] [Accepted: 05/10/2021] [Indexed: 01/07/2023]
Abstract
Newer anticancer drugs have revolutionized cancer treatment in the last decade, but conventional chemotherapy still occupies a central position in many cancers, with combination therapy and newer methods of delivery increasing their efficacy while minimizing toxicities. We discuss the retinal toxicities of anticancer drugs with an emphasis on the mechanism of toxicity. Uveitis is seen with the use of v-raf murine sarcoma viral oncogene homolog B editing anticancer inhibitors as well as immunotherapy. Most of the cases are mild with only anterior uveitis, but severe cases of posterior uveitis, panuveitis, and Vogt-Koyanagi-Harada-like disease may also occur. In the retina, a transient neurosensory detachment is observed in almost all patients on mitogen-activated protein kinase kinase (MEK) inhibitors. Microvasculopathy is often seen with interferon α, but vascular occlusion is a more serious toxicity caused by interferon α and MEK inhibitors. Crystalline retinopathy with or without macular edema may occur with tamoxifen; however, even asymptomatic patients may develop cavitatory spaces seen on optical coherence tomography. A unique macular edema with angiographic silence is characteristic of taxanes. Delayed dark adaptation has been observed with fenretinide. Interestingly, this drug is finding potential application in Stargardt disease and age-related macular degeneration.
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11
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Abstract
A 59-year-old woman with small-cell lung carcinoma achieved tumor disappearance after cisplatin-based chemotherapy (CBC) and radiation treatment but subsequently experienced right hemiparesis and aphasia. Brain magnetic resonance imaging revealed a left middle cerebral artery territory acute infarction and left internal carotid artery occlusion. Ultrasonography revealed a mobile thrombus in the left common and internal carotid arteries, and contrast computed tomography revealed a mural thrombus in the ascending aorta. Based on these findings, embolic stroke due to aortic mural thrombus following CBC was diagnosed. Aortic mural thrombus is a rare complication of CBC but carries a risk of embolic stroke.
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Affiliation(s)
- Yukiko Ochiai
- Department of Neurology and Stroke Medicine, Tokyo Metropolitan Tama Medical Center, Japan
| | - Marie Tsunogae
- Department of Neurology and Stroke Medicine, Tokyo Metropolitan Tama Medical Center, Japan
| | - Masayuki Ueda
- Department of Neurology and Stroke Medicine, Tokyo Metropolitan Tama Medical Center, Japan
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12
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The incidence of myocardial infarction and stroke in head and neck cancer patients. Sci Rep 2021; 11:4174. [PMID: 33603026 PMCID: PMC7892553 DOI: 10.1038/s41598-021-83665-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 01/12/2021] [Indexed: 11/30/2022] Open
Abstract
Various treatment modalities are used for head and neck cancer (HNC). This study analyzed the incidence and risks of myocardial infarction (MI) and stroke by cancer site and treatment modality in 22,737 patients newly diagnosed with HNC registered in the Korean National Health Insurance Service database in 2007–2013. An additional 68,211 patients without HNC, stroke, or MI were identified as the control group. The risks for MI (hazard ratio [HR] = 1.38, 95% confidence interval [CI] 1.24–1.53), stroke (HR = 1.48, 95% CI 1.37–1.60), and mortality (HR = 5.30, 95% CI 5.14–5.47) were significantly higher in the HNC group. Analysis by cancer site showed the risk of MI and mortality was highest in hypopharynx cancer, while the risk of stroke was highest in nasopharynx and paranasal sinus cancer. Analysis by treatment modality showed the highest risks for MI (HR = 1.88, 95% CI 1.31–2.69) and mortality (HR = 2.95, 95% CI 2.75–3.17) in HNC patients receiving chemotherapy (CT) alone, while HNC patients receiving CT with surgery had the highest risk for stroke (HR = 1.81, 95% CI 1.14–2.88). Careful attention to MI and stroke risks in HNC patients is suggested, especially those who received both CT and radiotherapy.
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13
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Grover SP, Hisada YM, Kasthuri RS, Reeves BN, Mackman N. Cancer Therapy-Associated Thrombosis. Arterioscler Thromb Vasc Biol 2021; 41:1291-1305. [PMID: 33567864 DOI: 10.1161/atvbaha.120.314378] [Citation(s) in RCA: 90] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
[Figure: see text].
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Affiliation(s)
- Steven P Grover
- UNC Blood Research Center, Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill
| | - Yohei M Hisada
- UNC Blood Research Center, Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill
| | - Raj S Kasthuri
- UNC Blood Research Center, Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill
| | - Brandi N Reeves
- UNC Blood Research Center, Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill
| | - Nigel Mackman
- UNC Blood Research Center, Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill
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14
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Murkamilov I, Sabirov I, Fomin V, Kudaibergenova I, Yusupov F, Schastlivenko A, Murkamilova Z. Cerebrovascular complications in patients with malignant neoplasms. Zh Nevrol Psikhiatr Im S S Korsakova 2021; 121:128-133. [DOI: 10.17116/jnevro2021121121128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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15
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Rosner MH, Jhaveri KD, McMahon BA, Perazella MA. Onconephrology: The intersections between the kidney and cancer. CA Cancer J Clin 2021; 71:47-77. [PMID: 32853404 DOI: 10.3322/caac.21636] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 07/17/2020] [Accepted: 07/21/2020] [Indexed: 12/12/2022] Open
Abstract
Onconephrology is a new subspecialty of nephrology that recognizes the important intersections of kidney disease with cancer. This intersection takes many forms and includes drug-induced nephrotoxicity, electrolyte disorders, paraneoplastic glomerulonephritis, and the interactions of chronic kidney disease with cancer. Data clearly demonstrate that, when patients with cancer develop acute or chronic kidney disease, outcomes are inferior, and the promise of curative therapeutic regimens is lessened. This highlights the imperative for collaborative care between oncologists and nephrologists in recognizing and treating kidney disease in patients with cancer. In response to this need, specific training programs in onconephrology as well as dedicated onconephrology clinics have appeared. This comprehensive review covers many of the critical topics in onconephrology, with a focus on acute kidney injury, chronic kidney disease, drug-induced nephrotoxicity, kidney disease in stem cell transplantation, and electrolyte disorders in patients with cancer.
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Affiliation(s)
- Mitchell H Rosner
- Division of Nephrology, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Kenar D Jhaveri
- Division of Kidney Disease and Hypertension, Zucker School of Medicine at Hofstra University, Great Neck, New York
| | - Blaithin A McMahon
- Division of Nephrology. Medical, University of South Carolina, Charleston, South Carolina
| | - Mark A Perazella
- Division of Nephrology, Yale University School of Medicine, New Haven, Connecticut
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16
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Khadka S, Byanju R, Poon S. Chemotherapy-Induced Central Retinal Artery Occlusion in Gestational Trophoblastic Neoplasia: Case Report. Int Med Case Rep J 2020; 13:431-435. [PMID: 32982483 PMCID: PMC7501951 DOI: 10.2147/imcrj.s266456] [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: 06/17/2020] [Accepted: 08/11/2020] [Indexed: 11/23/2022] Open
Abstract
The use of anticancer chemotherapy (ACC) has resulted in longer patient survival but has also increased drug-related adverse effects. A 22-year-old female receiving cisplatin-based intravenous chemotherapy for high risk variant of gestational trophoblastic neoplasia (GTN) presented with complaints of sudden painless loss of vision in her right eye for a duration of 4 hours. Ocular findings were suggestive of central retinal artery occlusion (CRAO). After exclusion of other potential aetiological risk factors, the patient was diagnosed with CRAO associated with cisplatin. Cancer patients are prone to thromboembolic events (TEE) not only due to primary disease but also due to underlying comorbidities and treatment modalities. The high incidence of TEE in patients under cisplatin therapy mandates a high degree of suspicion among the treating physicians. This rare possibility of irreversible visual toxicity should also be considered among the patients under cisplatin chemotherapy.
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Affiliation(s)
- Simanta Khadka
- Department of Vitreo-Retina, Bharatpur Eye Hospital, Bharatpur, Chitwan, Nepal
| | - Raghunandan Byanju
- Department of Vitreo-Retina, Bharatpur Eye Hospital, Bharatpur, Chitwan, Nepal
| | - Suchan Poon
- Department of Vitreo-Retina, Bharatpur Eye Hospital, Bharatpur, Chitwan, Nepal
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17
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Li X, Partovi S, Gadani S, Martin C, Beck A, Vedantham S. Gastrointestinal Malignancies and Venous Thromboembolic Disease: Clinical Significance and Endovascular Interventions. ACTA ACUST UNITED AC 2020; 4:260-266. [PMID: 34296054 DOI: 10.1055/s-0040-1716739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Gastrointestinal malignancy encompasses a wide range of disease processes. Its incidence and mortality rate rank among the highest of all cancers. Venous thromboembolic disease is a common complication of gastrointestinal malignancy. Anticoagulation remains the first-line therapy. However, for patients who cannot tolerate or have failed anticoagulation, inferior vena cava (IVC) filter placement may be an option. Furthermore, to improve symptom resolution and reduce the severity of postthrombotic syndrome, catheter-directed thrombolysis (CDT) may be an option. Recent randomized trials including the ATTRACT (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis) trial have shed new light on the efficacy and safety of CDT and related methods. Overall, the decision to proceed with IVC filter placement or CDT must be individualized.
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Affiliation(s)
- Xin Li
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic Main Campus, Cleveland, Ohio
| | - Sasan Partovi
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic Main Campus, Cleveland, Ohio
| | - Sameer Gadani
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic Main Campus, Cleveland, Ohio
| | - Charles Martin
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic Main Campus, Cleveland, Ohio
| | - Avi Beck
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic Main Campus, Cleveland, Ohio
| | - Suresh Vedantham
- Section of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri
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18
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Shioyama W, Oka T, Yasui T, Fujita M. Single-drug approach with rivaroxaban: A case of successful anticoagulation against cancer-associated thrombosis. J Cardiol Cases 2019; 20:39-41. [PMID: 31440308 PMCID: PMC6698256 DOI: 10.1016/j.jccase.2019.03.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Revised: 02/14/2019] [Accepted: 03/13/2019] [Indexed: 11/16/2022] Open
Abstract
We report a patient with pulmonary embolism and deep vein thrombosis induced by cancer chemotherapy who received successful anticoagulation using a single-drug approach with rivaroxaban. Cancer-associated thrombosis (CAT) is a leading cause of non-cancer death in patients with cancer, which is induced by cancer itself and/or chemotherapy agents including cisplatin and gemcitabine. By contrast, hemorrhagic state is another feature of advanced cancer. In these opposite conditions of cancer patients, CAT have to be controlled by appropriate anticoagulation. This case shows potential for single-drug approach with rivaroxaban and direct oral anticoagulants being effective and safety strategy against CAT. <Learning objective: Single-drug approach of direct oral anticoagulants (DOACs) against CAT induced by cisplatin and gemcitabine showed satisfactory anticoagulation without heparin and warfarin. CAT has been important issue in oncology field, and single-drug approach of DOACs could be an effective and safety strategy for anticoagulation against CAT.>
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Affiliation(s)
- Wataru Shioyama
- Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, Japan
| | - Toru Oka
- Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, Japan
| | - Taku Yasui
- Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, Japan
| | - Masashi Fujita
- Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, Japan
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19
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Abstract
Introduction Cancer is an important risk factor for venous and arterial thromboembolic events. Treatment with chemotherapy was associated with a 6.5-fold increase in the risk of thromboembolic events. Here, we present a patient with cilioretinal artery emboli during cisplatin-based therapy. Case report A 54-year-old male patient with a diagnosis of metastatic small cell carcinoma was under cisplatin-based regimen. He presented with visual disturbance. Retinal fluorescein angiography showed multiple plaques located in cilioretinal artery and cilioretinal artery occlusion. After excluding other potential etiological factors, patient was diagnosed with cilioretinal artery occlusion associated with cisplatin. Discussion In oncology practice, patients are prone to thromboembolic events due to primary disease, underlying comorbidities and treatment modalities. In addition to numerous toxicities, cisplatin is an important risk factor for thromboembolic events. Clinicians caring patients with a diagnosis of cancer should be aware of this rare complication of cisplatin-based therapies.
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Affiliation(s)
- Ali Alkan
- Medical Oncology, Osmaniye Public Hospital, Osmaniye, Turkey
| | - Serap Talaz
- Ophthalmology, Osmaniye Public Hospital, Osmaniye, Turkey
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20
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Sato C, Okuda K, Tamiya H, Yamamoto K, Hoshina K, Narumoto O, Urushiyama H, Noguchi S, Amano Y, Watanabe K, Mitani A, Kage H, Tanaka G, Yamauchi Y, Takai D, Nagase T. Acute Arterial Thrombosis during Postoperative Adjuvant Cisplatin-based Chemotherapy for Completely Resected Lung Adenocarcinoma. Intern Med 2018; 57:557-561. [PMID: 29225246 PMCID: PMC5849553 DOI: 10.2169/internalmedicine.8996-17] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A malignant tumor can cause hypercoagulation and it also often coexists with thrombosis. Cisplatin-based chemotherapy can also induce adverse vascular effects, including arterial thrombosis. We herein report a case of acute arterial thrombosis in a patient undergoing postoperative adjuvant cisplatin-based chemotherapy for completely resected lung cancer. The patient complained of acute leg pain after chemotherapy, and computed tomography revealed multiple thrombi from the thoracic to popliteal arteries. Arterial thrombosis during adjuvant chemotherapy is extremely rare; however, careful clinical observation of patients receiving cisplatin-based chemotherapy is important, because arterial thrombosis, even in the absence of the primary malignant tumor, is possible.
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Affiliation(s)
- Chihiro Sato
- General Education Center, The University of Tokyo Hospital, Japan
| | - Kenichi Okuda
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
| | - Hiroyuki Tamiya
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
| | - Kota Yamamoto
- Department of Vascular Surgery, The University of Tokyo Hospital, Japan
| | - Katsuyuki Hoshina
- Department of Vascular Surgery, The University of Tokyo Hospital, Japan
| | - Osamu Narumoto
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
| | - Hirokazu Urushiyama
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
| | - Satoshi Noguchi
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
| | - Yosuke Amano
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
| | - Kosuke Watanabe
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
| | - Akihisa Mitani
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
| | - Hidenori Kage
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
| | - Goh Tanaka
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
| | - Yasuhiro Yamauchi
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
| | - Daiya Takai
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
- Department of Clinical Laboratory, The University of Tokyo Hospital, Japan
| | - Takahide Nagase
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan
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21
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Khosla S, Kennedy L, Abdulaal Y. Cisplatin induced acute mesenteric ischaemia: A case report and review of the literature. Int J Surg Case Rep 2017; 41:347-351. [PMID: 29145109 PMCID: PMC5686456 DOI: 10.1016/j.ijscr.2017.11.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 11/03/2017] [Indexed: 11/15/2022] Open
Abstract
Arterial thrombosis occurs in 2% of patients having Cisplatin-based chemotherapy. There is only one previous report detailing mesenteric ischaemia secondary to cisplatin. The mechanism relating to the development of arterial thrombosis is not understood. Benefit of prophylactic parenteral anticoagulation during cisplatin chemotherapy is unknown. Introduction Cisplatin is a platinum-based chemotherapeutic agent, widely used in cancer therapies for numerous solid tumours. It is becoming more recognised that a potentially life-threatening complication of cisplatin is accelerated arterial and venous thrombosis. Presentation of case We describe a case of a 62 year-old with no risk factors for vascular disease who presented with thromboembolic acute mesenteric ischaemia of the small bowel during treatment with cisplatin for head and neck cancer. Discussion We review the literature on the incidence and pathogenesis of cisplatin induced arterial thrombosis and discuss current treatment options of acute mesenteric ischaemia detailing our management of this case. Conclusion Cisplatin increases the risk of arterial thrombosis and this case report details acute mesenteric ischaemia secondary to its use. We hope to raise clinician awareness of this sequelae which can occur even in patients in the absence of other identifiable risk factors.
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Affiliation(s)
- Shivun Khosla
- Department of General Surgery, Maidstone and Tunbridge Wells NHS Trust, Tonbridge Road, Pembury, Kent, TN2 4QJ, United Kingdom.
| | - Lauren Kennedy
- Department of General Surgery, Maidstone and Tunbridge Wells NHS Trust, Tonbridge Road, Pembury, Kent, TN2 4QJ, United Kingdom.
| | - Yasser Abdulaal
- Department of General Surgery, Maidstone and Tunbridge Wells NHS Trust, Tonbridge Road, Pembury, Kent, TN2 4QJ, United Kingdom.
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22
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Svilaas T, Lefrandt JD, Gietema JA, Kamphuisen PW. Long-term arterial complications of chemotherapy in patients with cancer. Thromb Res 2017; 140 Suppl 1:S109-18. [PMID: 27067963 DOI: 10.1016/s0049-3848(16)30109-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The number of cancer survivors has gradually increased in recent decades. However, the cancer survivors are at risk for conditions related to their initial disease and its treatment, i.e. surgery, systemic treatment or radiotherapy. Cardiovascular complications, such as myocardial infarction, are common side effects of these therapies. Cardiovascular damage can occur during treatment or month to years after the initial treatment, as late effect of the cancer treatment. The pathophysiology of these effects is not yet fully understood, but an important part of the cardiovascular complications are thought to be the result of effects of anticancer agents on the structural and functional properties of the endothelium. Because these conditions can result in a high degree of morbidity and mortality, understanding how to improve the prevention, recognition, and treatment of vascular disease is an important medical priority in the care for cancer survivors. This review will focus on the long-term arterial complications of chemotherapy in cancer survivors. It will summarize the epidemiology and pathophysiology of these complications. Furthermore, important long-term clinical conditions related to these effects will be outlined, including cardiovascular risk management in terms of prevention, evaluation and therapy.
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Affiliation(s)
- Tone Svilaas
- Department of Vascular Medicine, University Medical Center Groningen, The Netherlands
| | - Joop D Lefrandt
- Department of Vascular Medicine, University Medical Center Groningen, The Netherlands
| | - Jourik A Gietema
- Department of Medical Oncology, University Medical Center Groningen, The Netherlands
| | - Pieter W Kamphuisen
- Department of Vascular Medicine, University Medical Center Groningen, The Netherlands.
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23
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Abstract
The incidence of venous thromboembolism (VTE) in patients with primary brain tumors varies be tween 1 and 60%. This variability in incidence is due to study differences in (a) methods of diagnosis of VTE— i.e., diagnosis at autopsy or clinical diagnosis; (b) amount of time from surgery to VTE diagnosis; (c) proportion of patients receiving deep venous thrombosis (DVT) pro phylaxis ; (d) clinical risk factors associated with VTE, such as paresis, prior thrombotic disease, and chemother apy; and (e) tumor location and histology. The etiology of VTE in patients with primary brain tumors is unknown. The preoperative hemostatic abnormalities noted in clin ical studies have been most consistent with compensated disseminated intravascular coagulation (DIC). These ab normalities, however, appear to be of little predictive value for the subsequent development of VTE. Studies involving brain tumor tissue or cell cultures have impli cated factors released by the tumor or surrounding neural tissue that activate the coagulation system or inhibit fi brinolysis. Recommendations for VTE prophylaxis in clude (a) earliest possible ambulation; (b) intermittent pneumatic compression in all nonambulatory patients preoperatively and postoperatively; and (c) s.c. heparin in high-risk patients. The role of low-molecular-weight heparin in VTE prophylaxis has not been established. Patients with malignant brain tumors can be safely anti coagulated with heparin and warfarin if these agents are carefully monitored. Of 197 patients in seven series who received anticoagulants, only 5 (2.5%) had intracranial bleeding. Vena caval filters and thrombectomy are rarely required. Thrombolytic therapy is contraindicated. Key Words: Venous thromboembolism—Deep venous throm bosis—Malignant brain tumors.
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Affiliation(s)
- Steven J. Jubelirer
- Cancer Care Center of South West Virginia, Charleston Area Medical Center, and West Virginia University-Charleston Division, Charleston, West Virginia, U.S.A
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24
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Bartholomew JR, Bell WR. Thrombotic Thrombocytopenic Purpura. J Intensive Care Med 2016. [DOI: 10.1177/088506668600100606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Thrombotic thrombocytopenic purpura (TTP) is classically highlighted by a pentad of features: fever, hemolytic anemia, thrombocytopenia purpura, transient or permanent central nervous system signs, and renal disease. The antemortem diagnosis is reliant upon the multisystem clinical signs and symptoms in conjunction with severe hemolytic anemia and thrombocytopenia. Relapse is common within the first six months after initial presentation. Laboratory findings have been generally nonspecific per se, and antemortem tissue biopsy findings are frequently unrewarding. Recently, however, unusually large multimers of the Factor VIII:Ag molecule (von Willebrand protein) have been identified in the plasma of patients with TTP who have recovered from an acute attack. This observation is very important because it may lead to essential information on the nature of the inciting event in this devastating illness. The differential diagnosis includes several multisystem disease processes such as the hemolytic uremic syndrome, toxemia of pregnancy, systemic lupus erythematosus, subacute bacterial endocarditis, nonbacterial thrombotic endocarditis, immune thrombocytopenic purpura, and the postpartum renal failure syndrome. The hemolytic uremic syndrome, toxemia of pregnancy, and TTP may resemble each other, exhibit many overlapping features, and are probably related. The cause of TTP remains unknown; the overwhelming majority of cases occur in otherwise healthy people without any recognizable underlying illness. Since 1965 45 to 70% of patients survive, a significant improvement in contrast to the early 1900s when the mortality rate was greater than 90%. The most dramatic advance has been observed in therapeutics, namely the utilization of some mode of plasma therapy (either infusion alone or plasmapheresis followed by plasma infusion). Corticosteroids remain very important in the management of patients with TTP. Vincristine may be very helpful, but additional studies are needed. The efficacy of vinca alkaloids, chronic immunosuppressive therapy, and sple. nectomy remains undefined. At present there is very little, if any, evidence that antiplatelet agents, aspirin, and prostacyclin are beneficial to patients with TTP. Prompt diagnosis and vigorous aggressive therapy is critical for successful management of TTP patients.
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Affiliation(s)
- John R. Bartholomew
- Johns Hopkins University Hospital, Department of Medicine, Division of Hematology, 600 N Wolfe St, Baltimore, MD 21205
| | - William R. Bell
- Johns Hopkins University Hospital, Department of Medicine, Division of Hematology, 600 N Wolfe St, Baltimore, MD 21205
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25
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Yeung KK, Coster E, Floris Vos AW, Van der Vijgh RK, Linsen MAM, Wisselink W. Repeated Arterial Thrombosis as a Complication of Carboplatin-Based Chemotherapy. Vascular 2016; 14:51-4. [PMID: 16849025 DOI: 10.2310/6670.2006.00007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
We describe a case of a 57-year-old woman with repeated acute arterial thrombosis of the femoral arteries following intravenous carboplatin-based combination chemotherapy for metastatic ovarian carcinoma. By extensive workup, no other known causes of arterial thrombosis were found. To our knowledge, this is the first case describing arterial thrombosis occurring as a complication of carboplatin therapy.
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Affiliation(s)
- Kakkhee K Yeung
- Department of Vascular Surgery, VU University Medical Center, Amsterdam, the Netherlands
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26
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Karayama M, Inui N, Kusagaya H, Suzuki S, Inoue Y, Enomoto N, Fujisawa T, Nakamura Y, Suda T. Changes in cross-sectional area of pulmonary vessels on chest computed tomography after chemotherapy in patients with advanced non-squamous non-small-cell lung cancer. Cancer Chemother Pharmacol 2016; 77:1011-8. [PMID: 27034279 DOI: 10.1007/s00280-016-3017-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Accepted: 03/23/2016] [Indexed: 01/11/2023]
Abstract
PURPOSE Chemotherapy is associated with a risk of vascular damage. Novel anti-angiogenic agents, which can directly affect tumor angiogenesis, are increasingly being used. However, the effects of these agents on normal vasculature are not well understood. Here, we evaluated the effects of chemotherapy in general, and the anti-angiogenic agent bevacizumab, more specifically, on the pulmonary vasculature in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). For this, we used the cross-sectional area of pulmonary vessels (CSA), which is an easily measurable indicator of small pulmonary vasculature on non-contrast chest computed tomography (CT). METHODS We retrospectively reviewed CT scans of the lungs of 75 chemo-naïve patients with advanced non-squamous NSCLC, for measurement of CSA, before and after first-line platinum-based chemotherapy, using a semi-automatic image-processing program. Measured vessels were classified in two groups: small vessels with CSA <5 mm(2) and large vessels with CSA between 5 and 10 mm(2). The CSAs for each group of vessels were calculated and summed separately, and expressed as a percentage of the total lung area (%CSA<5 and %CSA5-10). RESULTS Chemotherapy was associated with a selective decrease in small-diameter vessels, with a significant decrease in %CSA<5, but not %CSA5-10. When comparing chemotherapy with bevacizumab (n = 38) and without bevacizumab (n = 37), there was no significant difference in the reduction of %CSA<5. CONCLUSIONS Platinum-based chemotherapy might induce small pulmonary vascular damage. Use of bevacizumab does not enhance the reduction in area of pulmonary vessels.
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Affiliation(s)
- Masato Karayama
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan. .,Department of Clinical Oncology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan.
| | - Naoki Inui
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan.,Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Hideki Kusagaya
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Seiichiro Suzuki
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Yusuke Inoue
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Noriyuki Enomoto
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Tomoyuki Fujisawa
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Yutaro Nakamura
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Takafumi Suda
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
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27
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Kim JH, Jeon YS, Cho SG. Successful management of four unusual cases of acute aortic thrombus induced by chemotherapy. Clin Imaging 2016; 40:224-7. [PMID: 26995575 DOI: 10.1016/j.clinimag.2015.10.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2015] [Revised: 10/06/2015] [Accepted: 10/30/2015] [Indexed: 11/30/2022]
Abstract
An acute aortic thrombus is an unusual finding, and this is a source of distal arterial embolism, which has a poor prognosis. Chemotherapeutics have been reported as possible rare causes of acute arterial thrombus. We report four cases of acute aortic thrombus after chemotherapy, which were effectively treated with systemic anticoagulation or endovascular management.
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Affiliation(s)
- Jun Ho Kim
- Department of Radiology, Inha University Hospital, Inha University School of Medicine, Inhang-ro 27, Jung-gu, Incheon, Korea 400-711
| | - Yong Sun Jeon
- Department of Radiology, Inha University Hospital, Inha University School of Medicine, Inhang-ro 27, Jung-gu, Incheon, Korea 400-711.
| | - Soon Gu Cho
- Department of Radiology, Inha University Hospital, Inha University School of Medicine, Inhang-ro 27, Jung-gu, Incheon, Korea 400-711
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28
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Fennell DA, Summers Y, Cadranel J, Benepal T, Christoph DC, Lal R, Das M, Maxwell F, Visseren-Grul C, Ferry D. Cisplatin in the modern era: The backbone of first-line chemotherapy for non-small cell lung cancer. Cancer Treat Rev 2016; 44:42-50. [PMID: 26866673 DOI: 10.1016/j.ctrv.2016.01.003] [Citation(s) in RCA: 287] [Impact Index Per Article: 31.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 01/12/2016] [Accepted: 01/15/2016] [Indexed: 01/25/2023]
Abstract
The treatment of advanced non-small cell lung cancer (NSCLC) may be changing, but the cisplatin-based doublet remains the foundation of treatment for the majority of patients with advanced NSCLC. In this respect, changes in practice to various aspects of cisplatin use, such as administration schedules and the choice of methods and frequency of monitoring for toxicities, have contributed to an incremental improvement in patient management and experience. Chemoresistance, however, limits the clinical utility of this drug in patients with advanced NSCLC. Better understanding of the molecular mechanisms of cisplatin resistance, identification of predictive markers and the development of newer, more effective and less toxic platinum agents is required. In addition to maximising potential benefits from advances in molecular biology and associated therapeutics, modification of existing cisplatin-based treatments can still lead to improvements in patient outcomes and experiences.
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Affiliation(s)
- D A Fennell
- Cancer Research UK Centre, University of Leicester & University Hospitals of Leicester, NHS Trust, Leicester, UK.
| | - Y Summers
- The Christie Hospital NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, UK.
| | - J Cadranel
- Chest Department and Expert Center in Thoracic Oncology, APHP Hôpital Tenon and Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
| | - T Benepal
- St Georges Hospital NHS Trust, Blackshaw Road, Tooting, London SW17 0QT, UK.
| | - D C Christoph
- Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Hufelandstraße 55, D-45147, Essen, Germany.
| | - R Lal
- Guy's and St Thomas' Foundation Trust, Westminster Bridge Road, London SE1 7EH, UK.
| | - M Das
- Eli Lilly and Company, Lilly House, Priestley Road, Basingstoke, Hampshire RG24 9NL, UK.
| | - F Maxwell
- Eli Lilly and Company, Lilly House, Priestley Road, Basingstoke, Hampshire RG24 9NL, UK.
| | - C Visseren-Grul
- Eli Lilly and Company, Grootslag 1-5, 3991 RA Houten, The Netherlands.
| | - D Ferry
- Eli Lilly and Company, Lilly House, Priestley Road, Basingstoke, Hampshire RG24 9NL, UK.
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29
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Moudgil R, Yeh ETH. Mechanisms of Cardiotoxicity of Cancer Chemotherapeutic Agents: Cardiomyopathy and Beyond. Can J Cardiol 2016; 32:863-870.e5. [PMID: 27117975 DOI: 10.1016/j.cjca.2016.01.027] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Revised: 01/26/2016] [Accepted: 01/27/2016] [Indexed: 12/14/2022] Open
Abstract
Tremendous strides have been made in the treatment of various oncological diseases such that patients are surviving longer and are having better quality of life. However, the success has been tainted by the iatrogenic cardiac toxicities. This is especially concerning in the younger population who are facing cardiac disease such as heart failure in their 30s and 40s as the consequence of the anthracycline's side effects (used for childhood leukemia and lymphoma). This resulted in the awareness of cardiotoxic effects of anticancer drugs and emergence of a new discipline: oncocardiology. Since then, numerous anticancer drugs have been correlated to cardiomyopathy. Additionally, other cardiovascular effects have been identified, which includes but is not limited to myocardial infarction, thrombosis, hypertension, arrhythmias, and pulmonary hypertension. In this review we examine some of the anticancer agents that mitigate cardiotoxicity and present current knowledge of molecular mechanism(s). The aim of the review is to ignite awareness of emerging cardiotoxic effects as new generations of anticancer agents are being tested in clinical trials and introduced as part of the therapeutic armamentarium to our oncological patients.
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Affiliation(s)
- Rohit Moudgil
- Department of Cardiology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA
| | - Edward T H Yeh
- Department of Cardiology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA.
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Yamasaki F, Takayasu T, Nosaka R, Kawaguchi H, Sugiyama K, Kobayashi M, Kurisu K. Cavernous angioma after chemotherapy for desmoplastic/nodular medulloblastoma associated with anhidrotic ectodermal dysplasia. Childs Nerv Syst 2016; 32:395-8. [PMID: 26231569 DOI: 10.1007/s00381-015-2848-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Accepted: 07/19/2015] [Indexed: 10/23/2022]
Abstract
PURPOSE While cavernous angioma (CVA) after cranial irradiation has been documented, its development after high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) has not. We present a patient with desmoplastic/nodular medulloblastoma (DNMB) associated with anhidrotic ectodermal dysplasia (AED) who developed CVA 2 years after high-dose chemotherapy and PBSCT. METHODS A 1-year-old boy with ingravescent vomiting was admitted to our institute. He presented with a large head, a depressed nasal bridge, low-set ears, thick lips with peg-shaped teeth, hypohidrosis, sparse hair, thin atrophic skin, scaly dermatitis with frontal bossing, and a bulging anterior fontanel. Neuroradiological examination revealed multiple cerebellar masses with heterogeneous enhancement and speckled calcifications and severe obstructive hydrocephalus. The histological diagnosis of surgical specimens was DNMB, and he underwent postoperative multiple-drug chemotherapy with autologous PBSCT. The outcome was favorable and he did not undergo radiotherapy. RESULTS After 2 years, intracranial hemorrhage was detected at his regular radiological check-up and he again underwent surgery. The histological diagnosis was CVA. CONCLUSIONS To our knowledge, this is the first report of AED-associated DNMB and CVA.
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Affiliation(s)
- Fumiyuki Yamasaki
- Department of Neurosurgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Takeshi Takayasu
- Department of Neurosurgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Ryo Nosaka
- Department of Neurosurgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroshi Kawaguchi
- Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Kazuhiko Sugiyama
- Department of Clinical Oncology and Neuro-oncology Program, Hiroshima University Hospital, Hiroshima, 734-8551, Japan
| | - Masao Kobayashi
- Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Kaoru Kurisu
- Department of Neurosurgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
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Abstract
Treatment of cancer patients with antineoplastic agents is associated with a heightened risk of thrombotic events, both arterial and venous. In this article, we review the specific agents that are implicated and the pathophysiological processes that are known to be associated with this prothrombotic state. We conclude with current recommendations for prophylactic antithrombotic therapy in these clinical situations.
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Affiliation(s)
- Peter Oppelt
- Case Western Reserve University, Cleveland, OH, USA
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Koyama N, Tomoda K, Matsuda M, Fujita Y, Yamamoto Y, Hontsu S, Tasaki M, Yoshikawa M, Kimura H. Acute Bilateral Renal and Splenic Infarctions Occurring during Chemotherapy for Lung Cancer. Intern Med 2016; 55:3635-3639. [PMID: 27980265 PMCID: PMC5283965 DOI: 10.2169/internalmedicine.55.6891] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
We herein report a rare case of acute bilateral renal and splenic infarctions occurring during chemotherapy for lung cancer. A 60-year-old man presented with acute and intensive upper abdominal and back pain during chemotherapy with cisplatin and etoposide for lung cancer. Contrast-enhanced computed tomography (CT) revealed bilateral renal and splenic infarctions. After the administration of unfractionated heparin his pain was relieved with a clearance of the infarctions in the CT findings and a recovery of renal dysfunction. Enhanced coagulation by lung cancer and arterial ischemia by chemotherapy may therefore contribute to the development of these infarctions.
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Affiliation(s)
- Noriko Koyama
- The Second Department of Internal Medicine, Nara Medical University, Japan
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Yaman M, Ebinc S, Beton O, Mete T. Primary percutaneous coronary intervention for coronary thrombosis during cisplatin, etoposide and bleomycin combination therapy under thromboprophylaxis with nadroparin. INTERNATIONAL JOURNAL OF THE CARDIOVASCULAR ACADEMY 2015. [DOI: 10.1016/j.ijcac.2015.07.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
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Izzedine H, Perazella MA. Thrombotic microangiopathy, cancer, and cancer drugs. Am J Kidney Dis 2015; 66:857-68. [PMID: 25943718 DOI: 10.1053/j.ajkd.2015.02.340] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2014] [Accepted: 02/13/2015] [Indexed: 02/07/2023]
Abstract
Thrombotic microangiopathy (TMA) is a complication that can develop directly from certain malignancies, but more often results from anticancer therapy. Currently, the incidence of cancer drug-induced TMA during the last few decades is >15%, primarily due to the introduction of anti-vascular endothelial growth factor (VEGF) agents. It is important for clinicians to understand the potential causes of cancer drug-induced TMA to facilitate successful diagnosis and treatment. In general, cancer drug-induced TMA can be classified into 2 types. Type I cancer drug-induced TMA includes chemotherapy regimens (ie, mitomycin C) that can potentially promote long-term kidney injury, as well as increased morbidity and mortality. Type II cancer drug-induced TMA includes anti-VEGF agents that are not typically associated with cumulative dose-dependent cell damage. In addition, functional recovery of kidney function often occurs after drug interruption, assuming a type I agent was not given prior to or during therapy. There are no randomized controlled trials to provide physician guidance in the management of TMA. However, previously accumulated information and research suggest that endothelial cell damage has an underlying immunologic basis. Based on this, the emerging trend includes the use of immunosuppressive agents if a refractory or relapsing clinical course that does not respond to plasmapheresis and steroids is observed.
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Affiliation(s)
- Hassan Izzedine
- Department of Nephrology, Monceau Park International Clinic, Paris, France.
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Investigation of Proposed Mechanisms of Chemotherapy-Induced Venous Thromboembolism. Clin Appl Thromb Hemost 2015; 21:420-7. [DOI: 10.1177/1076029615575071] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Venous thromboembolism (VTE) during chemotherapy is common, with 7% mortality in metastatic breast cancer (MBC). In a prospective cohort study of patients with breast cancer, we investigated whether vascular endothelial cell activation (VECA), and whether apoptosis, is the cause of chemotherapy-induced VTE. Methods: Serum markers of VECA, E-selectin (E-sel), vascular cell adhesion molecule 1 (VCAM-1) and d-dimer (fibrin degradation and hypercoagulability marker) were measured prechemotherapy and at 1, 4, and 8 days following chemotherapy. Clinical deep vein thrombosis (DVT) or pulmonary embolism and occult DVT detected by duplex ultrasound imaging were recorded as VTE-positive (VTE+). In patients with MBC, hypercoagulable response to chemotherapy was compared between patients with and without cancer progression. Development of VTE and cancer progression was assessed 3 months following starting chemotherapy. Results: Of the 134 patients, 10 (7.5%) developed VTE (6 [17%] of 36 MBC receiving palliation, 0 of 11 receiving neoadjuvant to downsize tumor, and 4 [5%] of 87 early breast cancer receiving adjuvant chemotherapy, P = .06). Levels of E-sel and VCAM-1 decreased in response to chemotherapy ( P < .001) in both VTE+ and patients not developing VTE (VTE−). However, decrease in VECA markers was similar in VTE+ and VTE− patients, implying this is not the cause of VTE. In patients with MBC following chemotherapy, d-dimer (geometric mean) increased by 36% in the 21 patients with MBC responding to chemotherapy but steadily decreased by 11% in the 15 who progressed (day 4, P < .01), implying patients with tumor response (apoptosis) had an early hypercoagulable response. Conclusions: During chemotherapy for breast cancer, VECA is induced; however, this is not the primary mechanism for VTE. Chemotherapy-induced apoptosis may enhance hypercoagulability and initiate VTE.
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Kuan AS, Teng CJ, Wu HH, Su VYF, Chen YT, Chien SH, Yeh CM, Hu LY, Chen TJ, Tzeng CH, Liu CJ. Risk of ischemic stroke in patients with ovarian cancer: a nationwide population-based study. BMC Med 2014; 12:53. [PMID: 24661584 PMCID: PMC4022213 DOI: 10.1186/1741-7015-12-53] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2014] [Accepted: 02/25/2014] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Cancer patients are at risk of thromboembolism. However, studies investigating the relationship between ovarian cancer and ischemic stroke are lacking. The objectives of this study were to assess the association between ovarian cancer and ischemic stroke, and to determine the predictive risk factors. METHODS Ovarian cancer patients aged 20 years and older without antecedent cerebrovascular events and who were followed up for more than 1 year between 1 January 2003 and 31 December 2011 were recruited from the Taiwan National Health Insurance database. Hazard ratios (HRs) of stroke risk for ovarian cancer patients compared with an age- and comorbidity-matched cohort were calculated by Cox proportional regression analysis. The difference in cumulative ischemic stroke incidence between ovarian cancer patients and the matched cohort was analyzed with the Kaplan-Meier method and tested with the log-rank test. RESULTS Each cohort (ovarian cancer and matched cohort) consisted of 8,810 individuals, with a median age of 49 years. After a median follow-up of 2.68 and 3.85 years, respectively, the ischemic stroke incidence was 1.38-fold higher in the ovarian cancer cohort than in the comparison cohort (9.4 versus 6.8 per 1,000 person-years), with an age- and comorbidity-adjusted HR of 1.49 (P <0.001). The ischemic stroke risk imposed by ovarian cancer was more prominent in patients under 50 years old (HR 2.28; P <0.001) compared with patients 50 years and older (HR 1.33; P = 0.005). Significant risk factors predicting stroke development were age 50 years and older (HR 2.21; P <0.001), hypertension (HR 1.84; P <0.001), diabetes mellitus (HR 1.71; P <0.001), and treatment with chemotherapy (HR 1.45; P = 0.017), especially platinum-based regimens. CONCLUSIONS Ovarian cancer patients were at an increased risk of developing ischemic stroke. Age, hypertension, diabetes, and chemotherapy treatment were independent risk factors.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Chia-Jen Liu
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.
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Early-onset Thrombosis of Internal Jugular Vein Associated with Introducer Catheter for Heart Catheterization in Cardiac Surgery. J Vasc Access 2014; 16:57-63. [DOI: 10.5301/jva.5000303] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2014] [Indexed: 11/20/2022] Open
Abstract
Purpose In cardiac surgery, Swan-Ganz catheter (SGC) is often necessary and is inserted before the intervention through an introducer catheter. Catheter-related thrombosis (CRT) is a frequent complication of this procedure and often remains subclinical. The aims of this prospective cohort study were to determinate the incidence of CRT after positioning an SGC through an introducer and to identify factors relating to their occurrence. Methods One-hundred and sixteen cardiac surgery patients underwent ultrasound examination of the thoracic-cervical vessels, before and after introducer catheter removal. Data about drugs infused through the introducer catheter were also collected. Results The incidence of internal jugular vein CRT was 26.7%, corresponding to 70.5 cases per 1,000 catheter days. The incidence of “fibrin sleeve” was 28.4%. All introducer catheter tips lay in the brachiocephalic vein or in the upper third of the superior vena cava. The incidence of CRT was not associated with duration of the placement of the introducer catheter (average 3.9±2 days) or the SGC (average of 2.4±1.7 days). Infusion of total parenteral nutrition and dextran showed a significantly increased risk of thrombosis in both univariate and multivariate analyses. An overly proximal position of the introducer catheter tip was strongly associated with CRT incidence. Conclusions The presence of an introducer catheter for SGC, even for a short time, is associated with a high incidence of early-onset CRT. This incidence is significantly related to the catheter tip being positioned in the brachiocephalic vein and to its use as a central venous access.
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Meattini I, Scotti V, Pescini F, Livi L, Sulprizio S, Palumbo V, Sarti C, Biti G. Ischemic Stroke During Cisplatin-Based Chemotherapy for Testicular Germ Cell Tumor: Case Report and Review of the Literature. J Chemother 2013; 22:134-6. [DOI: 10.1179/joc.2010.22.2.134] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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40
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Gaddh M, Antun A, Yamada K, Gupta P, Tran H, El Rassi F, Kim HS, Khoury HJ. Venous access catheter-related thrombosis in patients with cancer. Leuk Lymphoma 2013; 55:501-8. [PMID: 23772637 DOI: 10.3109/10428194.2013.813503] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Patients with cancer are at high risk for developing venous thromboembolism (VTE), and the presence of a central venous catheter (CVC) further increases this risk. CVC-related VTE has serious implications related to the loss of vascular access, development of pulmonary embolism, recurrent VTE, infections and post-thrombotic syndrome. The pathogenesis of CVC-related VTE is complex and multifactorial, with risk factors associated with the catheter, the vessel selected for insertion and the underlying cancer as well as the anti-cancer therapy. Clinical presentation of CVC-related VTEs is often non-specific, and ultrasonography is the most commonly used radiological diagnostic test. Management of CVC-related VTE in patients with cancer requires a balance between the need for venous access, the risk of VTE recurrence and the risk of bleeding from treatment-induced thrombocytopenia. Effective VTE prophylaxis methods have yet to be defined. Ongoing studies are evaluating the role of newer oral antithrombotic agents and alternative interventional strategies for the prevention and treatment of CVC-related VTE in patients with cancer.
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Affiliation(s)
- Manila Gaddh
- Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University , Atlanta, GA , USA
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Abstract
The development of aortic thrombosis without the presence of atheroscrelosis, dissection, or aneurysms is rare. A cancer-related hypercoagulable state is a well-known risk factor for venous thrombosis, however, atrial thrombosis has rarely been reported in cancer patients. Cisplatin-based chemotherapy is known to cause various side-effects. Detecting aortic thrombosis is important because it is a fatal condition. We herein present the first reported case of endo-aortic thrombosis occurring during cisplatin-based chemotherapy for gastric cancer.
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Rishi A, Ghoshal S. Acute multiple arterial thrombosis after cisplatin in base of tongue carcinoma: case report. Head Neck 2012; 35:E269-71. [PMID: 22915348 DOI: 10.1002/hed.23123] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/12/2012] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Arterial thromboses following cisplatin-based chemotherapy in head and neck cancers are extremely rare and devastating complication. METHODS AND RESULTS A 54-year-old male smoker had an acute history of left lower limb pain and calf claudication 3 days following the first cycle of cisplatin-based chemotherapy given concurrently with radiotherapy for squamous cell carcinoma of the base of tongue. CT angiography showed extensive abdominal aortic thrombus along with involvement of left common iliac, saphenopopliteal, and tibeal arteries as well as moderate stenosis in the proximal segments of left anterior descending and right coronary artery. We suggest that endothelial damage and hypercoaguable state secondary to cisplatin may have induced severe arterial and coronary thrombosis. CONCLUSIONS This is the first reported case of acute multiple arterial thrombosis following cisplatin in head and neck cancer. It is a dreaded complication and has a dismal prognosis if not promptly recognized and treated.
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Affiliation(s)
- Anupam Rishi
- Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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Soultati A, Mountzios G, Avgerinou C, Papaxoinis G, Pectasides D, Dimopoulos MA, Papadimitriou C. Endothelial vascular toxicity from chemotherapeutic agents: Preclinical evidence and clinical implications. Cancer Treat Rev 2012; 38:473-83. [DOI: 10.1016/j.ctrv.2011.09.002] [Citation(s) in RCA: 147] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2011] [Revised: 09/11/2011] [Accepted: 09/12/2011] [Indexed: 01/13/2023]
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Arterial emboli complicating Cisplatin therapy. Case Rep Oncol Med 2012; 2012:276385. [PMID: 22606452 PMCID: PMC3350183 DOI: 10.1155/2012/276385] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2011] [Accepted: 12/25/2011] [Indexed: 11/18/2022] Open
Abstract
We report three cases of arterial emboli in patients with lung cancer treated with cisplatin chemotherapy. All three patients were managed without surgical intervention but subsequent oncological treatment was complicated by the sequelae of arterial emboli. We discuss the issues surrounding these patients and the importance of identifying patients at risk of arterial embolic phenomena with cisplatin treatment.
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Jeon HK, Kim DU, Baek DH, Ha DW, Lee BE, Ryu DY, Cheong JH, Kim GH, Song GA, Jang AL. Venous thromboembolism in patients with cholangiocarcinoma: focus on risk factors and impact on survival. Eur J Gastroenterol Hepatol 2012; 24:444-449. [PMID: 22410715 DOI: 10.1097/meg.0b013e328350f93c] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND A high incidence of venous thromboembolism (VTE) has been observed in patients with cancer. However, few data are available on patients with cholangiocarcinoma. OBJECTIVES The aim of this study was to evaluate the clinical characteristics and risk factors of VTE and to investigate whether VTE would affect the survival of patients with cholangiocarcinoma. METHODS We retrospectively reviewed 273 patients who were diagnosed with cholangiocarcinoma from January 2004 to December 2008. RESULTS We observed 40 cases of VTE, among which 10 patients had VTE at diagnosis. There were 14 cases of pulmonary thromboembolism with or without deep vein thrombosis, 18 cases of portal vein thrombosis, four cases of inferior vena cava thrombosis, and four of hepatic vein thrombosis. We found that progression of stage, C-reactive protein, and chemotherapy were significantly associated with the occurrence of VTE (P=0.022, 0.006, and 0.014, respectively). The median survival in the VTE and non-VTE groups were 13.0 and 25.0 months, respectively (log-rank test, P=0.026). VTE was an unfavorable prognostic factor for cholangiocarcinoma (hazard ratio=1.626, P=0.042). CONCLUSION In our study, advanced stage, C-reactive protein, and treatment with chemotherapeutic agents were related to the occurrence of VTE in patients with cholangiocarcinoma. VTE was an independent unfavorable prognostic factor for survivors of cholangiocarcinoma.
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Affiliation(s)
- Hye Kyung Jeon
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
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Rogers LR. Neurovascular complications of solid tumors and hematological neoplasms. HANDBOOK OF CLINICAL NEUROLOGY 2012; 105:805-23. [PMID: 22230535 DOI: 10.1016/b978-0-444-53502-3.00025-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Park YJ, Yang KS, Jung HS, Nam HC, Jung SH, Kim BG, Kim KY, Kim JH, Kim YO, Yun YS. A Case of Hemolytic Uremic Syndrome in a Lung Cancer Patient Treated with Gemcitabine. Tuberc Respir Dis (Seoul) 2012. [DOI: 10.4046/trd.2012.72.2.207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Affiliation(s)
- Youn Jung Park
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Keun-Suk Yang
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Hong-Soon Jung
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Hee Chul Nam
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Seung Hye Jung
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Boo Gyoung Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Ka Young Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jung-Ho Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Young-Ok Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Yu-Seon Yun
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
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Blann AD, Balakrishnan B, Shantsila E, Ryan P, Lip GYH. Endothelial progenitor cells and circulating endothelial cells in early prostate cancer: a comparison with plasma vascular markers. Prostate 2011; 71:1047-53. [PMID: 21557269 DOI: 10.1002/pros.21319] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2010] [Accepted: 11/10/2010] [Indexed: 11/05/2022]
Abstract
BACKGROUND Separate studies indicate that endothelial perturbation, as demonstrated by abnormal endothelial progenitor cells (EPCs), circulating endothelial cells (CECs), and plasma markers such as von Willebrand factor (vWf) and soluble E selectin (sEsel) are present in cancer. However, there are no reports where these indices are compared. Accordingly, we hypothesized altered EPCs and CECs in prostate cancer that would correlate with vWf, sEsel, and prostate specific antigen (PSA). METHODS We recruited 29 men with biopsy proven prostate cancer, with 25 with benign prostate disease and 27 free of prostate disease. CECs were defined on flow cytometry as being CD34+, CD146+, CD45-, and CD309-, EPCs were similarly defined as being CD34+, CD309+,CD45-, and CD146-. vWf, sEsel, and PSA were measured by immunoassay. RESULTS Despite higher PSA, sE-sel, and vWf in prostate cancer (all P < 0.02), neither EPCs, CECs, nor their ratio, were significantly different. EPCs and CECs correlated significantly with each other in each group (r > 0.48, P < 0.01) but failed to correlate with any plasma marker. CONCLUSION Unlike plasma endothelial markers, CECs and EPCs may play little part in the pathophysiology of early prostate cancer.
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Affiliation(s)
- Andrew D Blann
- Haemostasis, Thrombosis and Vascular Biology Unit, University of Birmingham Centre for Cardiovascular Sciences, Birmingham, UK.
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Khan OA, Blann AD, Payne MJ, Middleton MR, Protheroe AS, Talbot DC, Taylor M, Kirichek O, Han C, Patil M, Harris AL. Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer. Br J Cancer 2011; 104:1822-7. [PMID: 21587257 PMCID: PMC3111194 DOI: 10.1038/bjc.2011.154] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial. METHODS Patients with advanced cancer received oral cyclophosphamide 50 mg o.d., celecoxib 400 mg b.d. and methotrexate 2.5 mg b.d. for two consecutive days each week. Response was determined every 8 weeks; toxicity was evaluated according to CTC version 2.0. Plasma markers of inflammation, coagulation and angiogenesis were measured. RESULTS Sixty-seven of 69 patients were evaluable for response. Twenty-three patients had stable disease (SD) after 8 weeks, but there were no objective responses to therapy. Median time to progression was 57 days. There was a low incidence of toxicities. Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only. There were no changes in other plasma markers. CONCLUSION This metronomic approach has negligible activity in advanced cancer albeit with minimal toxicity. Analysis of plasma markers indicates minimal effects on endothelium in this trial. These data for this particular regimen do not support basic tenets of metronomic chemotherapy, such as the ability to overcome resistant tumours by targeting the endothelium.
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Affiliation(s)
- O A Khan
- University of Oxford Department of Medical Oncology, Churchill Hospital, Oxford OX3 7LJ, UK
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Hahn SJ, Oh JY, Kim JS, Kim DY. A case of acute aortic thrombosis after cisplatin-based chemotherapy. Int J Clin Oncol 2011; 16:732-6. [DOI: 10.1007/s10147-011-0205-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2010] [Accepted: 02/03/2011] [Indexed: 11/28/2022]
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