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

Abstract

Cholangiocellular cancer (CCС) 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 CCС 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.

Graphical abstract

Keywords

cholangiocellular cancer (CCC) / fluorescent diagnostics (FD) / photodynamic therapy (PDT) / chlorin e6 / Photolon / spectroscopic method / video fluorescent method / photobleaching / cancer / bile ducts / tumor / intraoperation diagnostics / photosensitizer (PS)

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

[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

[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

[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

[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

[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

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

[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

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

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

[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

[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

[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

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

[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

[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

[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

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

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

[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

[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

[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

Acknowledgements

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

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.

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