Skip to main content
Log in

New approaches to diagnostics and treatment of cholangiocellular cancer based on photonics methods

  • Research Article
  • Published:
Frontiers of Optoelectronics Aims and scope Submit manuscript

Abstract

Cholangiocellular cancer (CCC) is an oncological disease of the bile ducts characterized by a high mortality rate. To date, the use of standard methods for the diagnosis and treatment of CCC has not been able to reduce mortality from this disease. This work presents the results of fluorescence diagnostics (FD), which consists in using a modified optical fiber and photodynamic therapy (PDT) using a therapeutic laser instead of a low-intensity laser. This technique was tested on 43 patients in a clinical setting. The results obtained indicate a direct correlation between spectroscopic and video FD methods. Furthermore, a direct correlation was found between the photobleaching of a chlorin e6-based photosensitizer, with the commercial names of Photolon Radachlorin and Photoran and stricture regression. Our findings demonstrate the possibility of using a therapeutic laser with a wavelength of 660 nm for both diagnosis and treatment of bile ducts cancer, which results in a significant reduction of the operation time without decreasing its effectiveness.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Isayama H, Tsujino T, Nakai Y, Sasaki T, Nakagawa K, Yamashita H, Aoki T, Koike K. Clinical benefit of radiation therapy and metallic stenting for unresectable hilar cholangiocarcinoma. World Journal of Gastroenterology, 2012, 18(19): 2364–2370

    Article  Google Scholar 

  2. Fan B, Malato Y, Calvisi D F, Naqvi S, Razumilava N, Ribback S, Gores G J, Dombrowski F, Evert M, Chen X, Willenbring H. Cholangiocarcinomas can originate from hepatocytes in mice. Journal of Clinical Investigation, 2012, 122(8): 2911–2915

    Article  Google Scholar 

  3. Kulezneva Y V, Bruslik S V, Musaev G H, Israilov R E, Kirillova M S. Percutaneous modalities of biliary decompression: development and disputable items development and disputable items. Annals of Surgical Hepatology, 2011, 16(3): 35–43

    Google Scholar 

  4. Lee T Y, Cheon Y K, Shim C S. Current status of photodynamic therapy for bile duct cancer. Clinical Endoscopy, 2013, 46(1): 38–44

    Article  Google Scholar 

  5. Quyn A J, Ziyaie D, Polignano F M, Tait I S. Photodynamic therapy is associated with an improvement in survival in patients with irresectable hilar cholangiocarcinoma. HPB: The Official Journal of the International Hepato Pancreato Biliary Association, 2009, 11(7): 570–577

    Article  Google Scholar 

  6. Shevchenko Y L, Karpov O E, Vetshev P S, Maadi A S, Alekseev K I, Osipov A S, Vasiliev I V, Tyurbeev B T. Application of self-expanding nitinol stents in obstructive tumor genesis of icterus. Bulletin of the Pirogov National Medical and Surgical Center, 2014, 9(2): 30–34

    Google Scholar 

  7. Bakhru M, Tekola B, Kahaleh M. Endoscopic palliation for pancreatic cancer. Cancers (Basel), 2011, 3(2): 1947–1956

    Article  Google Scholar 

  8. Tan Y, Zhu J Y, Qiu B A, Xia N X, Wang J H. Percutaneous biliary stenting combined with radiotherapy as a treatment for unresectable hilar cholangiocarcinoma. Oncology Letters, 2015, 10(4): 2537–2542

    Article  Google Scholar 

  9. Boulay B R, Birg A. Malignant biliary obstruction: From palliation to treatment. World Journal of Gastrointestinal Oncology, 2016, 8 (6): 498–508

    Article  Google Scholar 

  10. Khan S A, Thomas H C, Davidson B R, Taylor-Robinson S D. Cholangiocarcinoma. Lancet, 2005, 366(9493): 1303–1314

    Article  Google Scholar 

  11. Kose F, Oguzkurt L, Besen A, Sumbul T, Sezer A, Karadeniz C, Disel U, Mertsoylu H, Ozyilkan O. Effectiveness of percutaneous metal stent placement in cholangiocarcinoma patients with midterm follow-up: Single center experience. European Journal of Radiology, 2012, 81(8): 1724–1727

    Article  Google Scholar 

  12. Tariq N U, McNamara M G, Valle J W. Biliary tract cancers: current knowledge, clinical candidates and future challenges. Cancer Management and Research, 2019, 11: 2623–2642

    Article  Google Scholar 

  13. Kipp B R, Stadheim L M, Halling S A, Pochron N L, Harmsen S, Nagorney D M, Sebo T J, Therneau T M, Gores G J, de Groen P C, Baron T H, Levy M J, Halling K C, Roberts L R. A comparison of routine cytology and fluorescence in situ hybridization for the detection of malignant bile duct strictures. American Journal of Gastroenterology, 2004, 99(9): 1675–1681

    Article  Google Scholar 

  14. Loschenov V B, Konov V I, Prokhorov A M. Photodynamic therapy and fluorescence diagnostics. Laser Physics, 2000, 10(6): 1188–1207

    Google Scholar 

  15. Scalfi-Happ C, Zhu Z, Graefe S, Wiehe A, Ryabova A, Loschenov V, Wittig R, Steiner R W. Chlorin nanoparticles for tissue diagnostics and photodynamic therapy. Photodiagnosis and Photodynamic Therapy, 2018, 22: 106–114

    Article  Google Scholar 

  16. van Straten D, Mashayekhi V, de Bruijn H S, Oliveira S, Robinson D J. Oncologic photodynamic therapy: basic principles, current clinical status and future directions. Cancers (Basel), 2017, 9(12): 19

    Article  Google Scholar 

  17. Moan J. On the diffusion length of singlet oxygen in cells and tissues. Journal of Photochemistry and Photobiology. B, Biology, 1990, 6(3): 343–344

    Google Scholar 

  18. Baskaran R, Lee J, Yang S G. Clinical development of photodynamic agents and therapeutic applications. Biomaterials Research, 2018, 22(1): 25

    Article  Google Scholar 

  19. Allison R R, Moghissi K. Photodynamic therapy (PDT): PDT mechanisms. Clinical Endoscopy, 2013, 46(1): 24–29

    Article  Google Scholar 

  20. Shiryaev A A, Musaev G K, Loshenov M V, Borodkin A V, Levkin V V, Okhotnikova N L, Volkov V V, Makarov V I, Loshenov V B. Fluorescence diagnosis and photodynamic therapy in combined treatment of cholangiocarcinoma. Biomedical Photonics, 2017, 5 (4): 15–24

    Article  Google Scholar 

  21. Farrakhova D, Shiryaev A, Yakovlev D, Efendiev K, Maklygina Y, Borodkin A, Loschenov M, Bezdetnaya L, Ryabova A, Amirkhanova L, Samoylova S, Rusakov M, Zavodnov V, Levkin V, Reshetov I, Loschenov V. Trials of a fluorescent endoscopic video system for diagnosis and treatment of the head and neck cancer. Journal of Clinical Medicine, 2019, 8(12): 2229

    Article  Google Scholar 

  22. Loshchenov M, Zelenkov P, Potapov A, Goryajnov S, Borodkin A. Endoscopic fluorescence visualization of 5-ALA photosensitized central nervous system tumors in the neural tissue transparency spectral range. Photonics & Lasers in Medicine, 2014, 3(2): 159–170

    Article  Google Scholar 

Download references

Acknowledgements

This work was funded by RFBR according to the research project (Nos. 17-00-00162 and 17-00-00159).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dmitry V. Yakovlev.

Ethics declarations

Ethics Approval The trial was conducted in accordance with the Declaration of Helsinki. This study was reviewed and approved by the Integrated Research Ethics Council of First Sechenov State Medical University, Ministry of Health of the Russian Federation (Sechenov University) (approval number 127, 12.09.2018). All registered patients completed an informed consent form.

Additional information

Dmitry V. Yakovlev, graduated student of N.I. Pirogov Russian National Research Medical University in Moscow, Russia (2019). Nowadays, Dmitry is a researcher at Laser Biospectroscopy Laboratory of Prokhorov General Physics Institute of Russian Academy of Sciences. He develops new approaches and equipment for diagnosis of cholangiocellular cancer via spectroscopy methods. The investigation will assist to oncologists in tumor margin detection during less invasive operations with complete removal in hepatobiliary area. In addition, Dmitry is a Ph.D. student at Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, where he develops hybrid nanostructures for fluorescence diagnostics and photodynamic therapy using two-photon excitation.

Dina S. Farrakhova proved master’s thesis at Institute of Laser and Plasma Technology at National Research Nuclear University MEPhI (NRNU MEPhI) in Moscow, Russia (2018). The research is in a fluorescence diagnostic and photodynamic therapy for cancer treatment via spectroscopy and video-fluorescence methods. Nowadays, Dina is a junior researcher at Laser Biospectroscopy Laboratory of Prokhorov General Physics Institute of Russian Academy of Sciences. She develops new approaches and equipment for diagnosis of head and neck cancer via spectroscopy methods. The investigation will assist to oncologists in tumor margin detection during less invasive operations with complete removal in head and neck area. In addition, Dina researches distribution of promising photosensitizers on multicellular tumor spheroid models for enhancing of cancer cell destruction during photodynamic therapy.

Artem A. Shiryaev, Ph.D. (2010), surgeon, oncologist, interventional radiologist of Institute of Cluster Oncology named after L.L. Levshin under Sechenov University, Moscow, Russia. He engages in development of methods for laser-fluorescent diagnostics, and photodynamic therapy (PDT) in oncology, methods of intraoperative video-fluorescence diagnostics and PDT. He takes part as Investigator or Principal Investigator in the research projects that are being implemented with financial support from Russian Foundation for Basic Research (RFBR). Artem has presented in various professional conferences and has more than 40 published works including publications in peer-eviewed journals, such as Photodiagnosis and Photodynamic Therapy, Journal of Clinical Medicine,European Journal of Surgical Oncology, Laser Physics, Optical Engineering, and Biomedical Photonics. He is also the author or co-author of more than 2 patents.

Kanamat T. Efendiev received his Master’s degree in 2019 from National Research Nuclear University MEPhI, Russia. His pre-graduate practice and laboratory research took place at Department of Laser Micro-, Nano-, and Biotechnology, Institute of Engineering Physics for Biomedicine. He was engaged in the development of devices and methods for infrared imaging. Now Kanamat is a postgraduate student of National Research Nuclear University MEPhI at department No. 87 “Laser Micro-, Nano- and Biotechnologies”. He is developing methods for fluorescence imaging of highly pigmented tumors.

Maxim V. Loshchenov is a senior scientist at Prokhorov General Physics Institute of Russian Academy of Sciences, associate professor at National Research Nuclear University MEPhI, Russia. He received the degree of “Candidate of Physical and Mathematical Sciences”, equal to the international Ph.D. degree, in 2006 with the topic of Ph.D. Thesis: “Minimally invasive diagnostics of glucose concentration and light distribution in biological tissues”. During 2006–2010, he accomplished two postdoc terms in University of Toronto, Canada. From 2010 till present, he is working as senior researcher in Laser Biospectroscopy Laboratory (Center for Nature Science Investigations, General Physics Institute of the Russian Academy of Sciences, Moscow, Russia) on research and development of new devices and methods, for fluorescent diagnostics of cancer. Novel video-fluorescent computer-assisted systems for diagnostics are in the field of his scientific interests.

Liana M. Amirkhanova studied at Sechenov First Moscow State Medical Univesity, 2012–2018, Specialty “General Medicine”. She graduated from the residency in oncology in 2018–2020. She currently works as an oncologist.

Dmitry O. Kornev graduated from the medical faculty of Ulyanovsk State University, Russia with a degree in Medicine with a higher degree in 2019. He is currently studying in the residency of Sechenov University, Moscow, with a degree in Oncology, and has a degree in General Medicine.

Vladimir V. Levkin, Ph.D. (1986), surgeon, oncologist, professor of Department and Clinic of Faculty Surgery No. 1 named after academician N.N. Burdenko of I.M. Sechenov First Moscow Medical University (Sechenov University), Russia. He engages in development of methods for laser-fluorescent diagnostics, and photodynamic therapy (PDT) in oncology, methods of preoperative and intraoperative spectro-video-fluorescence diagnostics and PDT. His Ph.D. (1995) and doctoral dissertations (2013) were devoted to these research areas, as well as to improve the functional and long-term results of surgical treatment, primarily for stomach cancer. In addition to medical and scientific activities, he is actively engaged in teaching, instilling interest and love for students in scientific work. Vladimir has presented in various professional conferences and has more than 60 published works including publications in peer-reviewed journals, such as Photodiagnosis and Photodynamic Therapy, Journal of Clinical Medicine, Laser Physics, Optical Engineering, and Biomedical Photonics.

Igor V. Reshetov, Full Member RAS, Professor, Doctor of Medical Sciences, Director of Institute of Cluster Oncology named after L.L. Levshin under Sechenov University, Head of Department of Oncology, Radiotherapy and Plastic Surgery, Institute of Clinical Medicine named after N.V. Sklifosovsky under Sechenov University, Head of Department of Oncology with the course on Reconstructive Plastic Surgery at Federal Medical-Biological Agency, Russia. He graduated from the 2-nd Moscow State Medical Institute named after N.N. Pirogov in 1987. He gained a Doctor of Science Degree in Oncology in 1998. He was elected the Full Member of Russian Academy of Sciences in 2016. He is a laureate of a number of Russian and international awards, including two Russian Federation Government Prize in Science and Technology, the award for the best report by the European Society of Surgical Oncology, and the N.N. Blokhin Prize in Oncology by Russian Academy of Medical Sciences. He was awarded by the Gold Medal of the British Invention Show (2013), the Diploma of the Ministry of Health of the Russian Federation, the Medal of Ivan Kalita Order by the Moscow Region Government, the Lapel badge “Excellent Worker of Public Health”, etc.

Victor B. Loschenov is professor and head of laboratory at Prokhorov General Physics Institute of Russian Academy of Sciences, professor at National Research Nuclear University (NRNU) MEPhI, Russia. His research interests are focused on fundamentals and practical applications of photodynamic therapy and fluorescent diagnostics of cancer, medical devices, phototheranostics, different modalities of optical spectroscopy. He received the Ph.D. degree in 1981 from N.S. Kurnakov Institute of General and Inorganic Chemistry, Academy of Sciences of the USSR on specialty “Quantum radio physics”. In 2006, he received the degree of doctor of science in Laser Physics from Prokhorov General Physics Institute of Russian Academy of Sciences with subject: “Methods and apparatus for spectral-fluorescence diagnosis and photodynamic therapy”. Since 2007, he has a title of professor in Laser physics. His professional experience includes the position of head of Laser Biospectroscopy Laboratory at GPI RAS (Moscow, Russia) (from 1989 till present) and professor and head of department in NRNU MEPhI, Russia.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yakovlev, D.V., Farrakhova, D.S., Shiryaev, A.A. et al. New approaches to diagnostics and treatment of cholangiocellular cancer based on photonics methods. Front. Optoelectron. 13, 352–359 (2020). https://doi.org/10.1007/s12200-020-1093-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12200-020-1093-0

Keywords

Navigation