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Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

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Journal of Pharmaceutical Analysis 2024年第2期14卷 196-210页

作者： Mariola Olkowicz Khaled Ramadan Hernando Rosales-Solano Miao Yu Aizhou Wang Marcelo Cypel Janusz Pawliszyn Department of Chemistry University of WaterlooWaterlooONCanada Jagiellonian Centre for Experimental Therapeutics(JCET) Jagiellonian UniversityKrakowPoland Latner Thoracic Surgery Research Laboratories Toronto General Hospital Research InstituteUniversity Health NetworkTorontoONCanada The Jackson Laboratory JAX Genomic MedicineFarmingtonCTUSA Division of Thoracic Surgery Department of SurgeryUniversity Health NetworkUniversity of TorontoToronto Lung Transplant ProgramTorontoONCanada

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

关键词： pulmonary metastases Colorectal cancer Adjuvant chemotherapy In vivo lung chemo-perfusion Solid-phase microextraction(SPME)microprobes Spatial metabolomics

Radiofrequency ablation as treatment for pulmonary metastasis of colorectal cancer

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World Journal of Gastroenterology 2014年第4期20卷 988-996页

作者： Takao Hiraki Hideo Gobara Toshihiro Iguchi Hiroyasu Fujiwara Yusuke Matsui Susumu Kanazawa Department of Radiology Okayama University Medical School

Radiofrequency ablation (RFA) causes focal coagulation necrosis in tissue. Its first clinical application was reported in 2000, and RFA has since been commonly used in both primary and metastatic lung cancer. The procedure is typically performed using computed tomography guidance, and the techniques for introducing the electrode to the tumor are simple and resemble those used in percutaneous lung biopsy. The most common complication is pneumothorax, which occurs in up to 50% of procedures; chest tube placement for pneumothorax is required in up to 25% of procedures. Other severe complications, such as pleural effusion requiring chest tube placement, infection, and nerve injury, are rare. The local efficacy depends on tumor size, and local progression after RFA is not rare, occurring in 10% or more of patients. The local progression rate is particularly high for tumors > 3 cm. Repeat RFA may be used to treat local progression. Short- to mid-term survival after RFA appears promising and is approximately 85%-95% at 1 year and 45%-55% at 3 years. Long-term survival data are sparse. Better survival may be expected for patients with small metastasis, low carcinoembryonic antigen levels, and/or no extrapulmonary metastasis. The notable advantages of RFA are that it is simple and minimally invasive; preserves pulmonary function; can be repeated; and is applicable regardless of previous treatments. Its most substantial limitation is limited local efficacy. Although surgery is still the method of choice for treatment with curative intent, the ultimate application of RFA may be to replace metastasectomy for small metastases. Randomized trials comparing RFA with surgery are needed.

关键词： Radiofrequency ablation pulmonary metastases Colorectal cancer Ablation therapy Lung

Case Report: Bilateral Pneumothoraces due to Targeted Tumor Therapy with Regorafenib in a Young Woman with Metastatic Colorectal Cancer

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Case Reports in Clinical Medicine 2022年第5期11卷 139-145页

作者： Tobias Rachow Tim Sandhaus Thomas Ernst Helmut Schiffl Susanne M. Lang Klinik für Innere Medizin II Universit&auml tsklinikum Jena Jena Germany Klinik für Innere Medizin V Universit&auml tsklinikum Jena Jena Germany Klinik für Herz- und Thoraxchirurgie Universit&auml tsklinikum Jena Jena Germany Medizinische Klinik IV LMU München München Germany

Background: Colorectal cancer is one of the most common cancer types, frequently metastasizing into the lungs. Treatment options have been vastly improved over the last years. With the increasing use of targeted therapies, novel and rare adverse effects can be seen. Case Presentation: A 43-year-old woman presented in our oncology department with chest pain and dyspnea. The patient was diagnosed with colorectal cancer seven years earlier and had received chemoradiation, surgery, and multiple chemotherapies before she was started on regorafenib because of progressive pulmonary metastases. Computed tomography scans demonstrated cavitation of former nodular bilateral pulmonary metastases. After drainage and resolution of the right-sided pneumothorax, the patient returned eleven days later with recurrent symptoms caused by left-sided tension pneumothorax. Video-assisted thoracoscopy and bilateral pleurodeses were performed. Persistent air leaks with severe pain and pulmonary infiltrates led to the death of the patient. Conclusions: This case demonstrates the efficacy of oral antiangiogenetic therapy in advanced metastatic colorectal cancer. Nevertheless, it also depicts an important potential side effect by transforming multiple solid lung metastases into cavitations which led to recurrent pneumothoraces. Special attention should be paid to this phenomenon as treatment of these complications can be challenging.

关键词： Regorafenib Pneumothorax pulmonary metastases Colorectal Cancer

Giant cell tumor of bone in *** analysis of 272 cases in China

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Giant cell tumor of bone in *** analysis of 272 cases in Chi...