INTRAOPERATIVE FLUORESCENCE DIAGNOSIS OF PERITONEAL DISSEMINATION IN PATIENTS WITH GASTRIC CANCER

The study of diagnostic efficiency of intraoperative fluorescence diagnosis (IOFD) of peritoneal dissemination in patients with gastric cancer comparing with standard laparoscopy was performed in P.A. Hertsen MCRI (the branch of NMRRC). The study included 114 patients with verified diagnosis of gastric cancer stage III–IV. For IOFD the domestic medication alasens (the active agent – 5-aminolevulinic acid) was used orally at dose of 30 mg/kg body weight 3 h prior to the study procedure. As the result of fluorescence diagnosis 10 (6.9%) patients had peritoneal tumor dissemination verified morphologically and undetected by standard laporoscopy. The sensitivity of peritoneal revision for standard laparoscopy in patients with gastric cancer stage III–IV was 60.8%, the specificity – 75.8%, the overall accuracy – 69.1%. The sensitivity for IOFD in patients with gastric cancer stage III–IV was 91.1%, the specificity – 93.9%, the overall accuracy – 92.7%. Thus, fluorescence study allowed improving the specificity, the sensitivity and the overall accuracy of diagnostic test. In the trial IOFD had the maximal diagnostic value in patients with visually undetectable microdissemination in «whight» light and with solitary visible peritoneal foci (the average number of additionally detected metastatic lesions in one patient – 1.22 and 1.4, respectively). Moreover, in the case of fluorescence diagnosis the number of detected microfoci of peritoneal dissemination was showed to increase with enlargement of area of tumor invasion to gastric serosa (at average of 2.29 additionally detected lesions in one patient with serosal invasion more than 2 cm²). The obtained results confirm the perspective of use of fluorescence diagnosis for detection of peritoneal dissemination, determination of true tumor extent, staging of the tumor and also for adjustment of following treatment tactics for this group of patients.

1. Moghimi-Dehkordi B., Safaee A., Ghiasi S., Zali M.R. Survival in gastric cancer patients: univariate and multivariate analysis, East Afr. J. Public Health. Apr., 2009, Vol. 6, No. 1, pp. 41-4.

2. Lepage C., Sant M., Verdecchia A., Forman D., Esteve J., Faivre J. Operative mortality after gastric cancer resection and long-term survival differences across Europe, Br. J. Surg., 2010, Vol. 97(2), pp. 235-9.

3. Davydov M.I., Ter-Ovanesov M.D., Abdikhakimov A.N., Marchuk V.A. Gastric cancer: preoperative examination and essential aspects of staging, Prakticheskaya onkologiya, 2001, No. 3, pp. 18-24. (In Russian).

4. Harmon R.L., Sugarbaker P.H. Prognostic indicators in peritoneal carcinomatosis from gastrointestinal cancer, International Seminars in Surgical Oncology, 2005, Vol. 2, 3.

5. Tong D., Russell A.H., Dawson L.E. Adenocarcinoma of the caecum: natural history and clinical patterns of reccurrence following radical surgery, Int. J. Radiol. Oncol. Biol. Phys., 1983, Vol. 9, pp. 357-360.

6. Mansfield P. Snap-shot MRI, Les Prix Nobel. The Nobel Prizes 2003, Nobel Foundation, 2004, pp. 266-283.

7. Sadeghi B., Arvieiix C., Glehen O., Beaujard A.C., Rivoive M., Baulieux J. Peritoneal carcinomatosis from non-gynecologic malignancies results of the EVOCAPE 1 multicentric prospective study, Cancer, 2000, Vol. 88, pp. 358-363.

8. Berthed D., Sugarbaker T.A., Chang D., Sugarbaker P.H. Qantitative methodologies for selection of patients with recurrent abdominopelvic sarcoma for treatment. (In) 8th World Congress of the international Gastro-Surgical Club, Bologna, Monduzzi Editore Publ., 1998, pp. 899-903.

9. Sugarbacker P.H., Yonemura Y. Clinical pathway for the management of respectable gastric cancer with peritoneal seedings: best palliation with a ray of hope for cure, Oncology, 2000, Vol. 58, pp. 96-107.

10. Sugarbaker P.H. Peritoneal surface oncology: review of a personal experience with colorectal and appendiceal malignancy, Tech. Coloproctol., 2005, Vol. 9(2), pp. 95-103.

11. Chissov V.I., Vashakmadze L.A., Butenko A.V., Pikin O.V., Lozhkin M.V. Possibilities of surgical treatment of resectable gastric cancer stage IV, Rossiiskii onkologicheskii zhurnal, 2003, No. 6, pp. 4-7. (In Russian).

12. Sugarbaker P.H. Peritonectomy procedures, Ann. Surg., 1995, Vol. 221, pp. 29-42.

13. Sugarbaker P.H. Management of peritoneal carcinomatosis, AMA, 1989, Vol. 16, pp. 57-60.

14. Yonemura Y., Fujimura T., Fushida S. Hyperthermohemotherapy combined with cytoreductive surgery for the treatment of gastric cancer with peritoneal dissemination, World J. Surg., 1991, Vol. 15, pp. 530-536.

15. Yonemura Y., Fudjimura T., Fushida S., Fujita H., Bando E., Nishimura G. A new surgical approach (peritonectomy) for the treatment of peritoneal dissemination, Hepatogastroenterology, 1999, Vol. 46(25), pp. 601-609.

16. Hendren S.K., Hahn S.M., Spitz F.R., Bauer T.W., Rubin S.C., Zhu T., Glatstein E., Fraker D.L. Phase II Trial of Debulking Surgery and Photodynamic Therapy for Disseminated Intraperitoneal Tumors, Annals of Surgical Oncology, 2001, Vol. 8(1), pp. 65-71.

17. Verwaal V.J., Van Ruth S., De Bree E., Van Slooten G.W., Van Tinteren H., Boot H., Zoetmulder F.A.N. Randomized Trial of Cytoreduction and HyperthermicIntraperitoneal Chemotherapy Versus Systemic Chemotherapyand Palliative Surgery in Patients With Peritoneal Carcinomatosis of Colorectal Cancer, J Clin Oncol by American Society of Clinical Oncology, 2003, Vol. 21, pp. 3737-3743.

18. Glehen O., Mithieux F., Osinsky D., Beaujard A.C., Freyer G., Guertsch Ph., Francois Y., Peyrat P., Panteix G., Vignal J., Gilly F.N. Surgery Combined With Peritonectomy Procedures and Intraperitoneal Chemohyperthermia in Abdominal Cancer With Peritoneal Carcinomatosis: A Phase II Study, J Clin Oncol by American Society of Clinical Oncology, 2003, Vol. 21, pp. 799-806.

19. Vashakmadze L.A., Filonenko Е.V., Butenko А.V., Suleymanov E.A., Kirillov N.V., Khomyakov V.M. Long-term outcomes for surgical treatment in patients with locally advanced and disseminated gastric cancer combined with intraoperative photodynamic therapy, Biomedical Photonics, 2013, Vol.2, No.1, pp. 3-10. (In Russian).

20. Filonenko E.V., Serova L.G. Photodynamic therapy in clinical practice, Biomedical Photonics, 2016, Vol. 5, No. 2, pp. 26-37. (In Russian).

21. Canis M., Botchorishvili R., Berreni N., Manhes H., Wattiez A., Mage G., Pouly J.L., Bruhat M.A. 5-aminolevulinic acid-induced (ALA) fluorescence for the laparoscopic diagnosis of peritoneal metastasis. AST An experimental study, Surg Endosc, 2001, Vol. 15(10), pp. 1184-1186.

22. Gahlen J., Prosst R.L., Pietschmann M., Haase T., Rheinwald M., Skopp G., Stern J, Herfarth C. Laparoscopic fluorescence diagnosis for intraabdominal fluorescence targeting of peritoneal carcinosis experimental studies, Ann Surg, 2002, Vol. 235(2), pp. 252-260.

23. Poddubnyi B.K., Gubin A.N., Sholokhov V.N., Vakurova E.S., Cherkes L.V., Vakulovskaya E.G., Blyumenberg A.G. Modern techniques of laparoscopic diagnosis of peritoneal tumor diseases, Sovremennaya onkologiya, 2005, Vol. 7, No. 3, pp. 130-133. (In Russian).

24. Vakulovskaya E.G., Gubin A.N., Poddubnyi B.K., Vakurova E.S. First experience of use of fluorescence laparoscopy with the medication “Alasens” in patients with ovarian cancer, Rossiiskii bioterapevticheskii zhurnal, 2005, Vol. 1, No. 4, p. 32. (In Russian).

25. Löning M.C., Diddens H.C., Holl-Ulrich K., Löning U., Küpker W., Diedrich K., Hüttmann G. Fluorescence staining of human ovarian cancer tissue following application of 5-aminolevulinic acid: fluorescence microscopy studies, Lasers Surg Med, 2006, Vol. 38(5), pp. 549-54.

26. Collinet P., Sabban F., Cosson M., Farine M.O., Villet R., Vinatier D., Mordon S. Laparoscopic photodynamic diagnosis of ovarian cancer peritoneal micro metastasis: an experimental study, Photochem Photobiol, 2007, Vol. 83(3), pp. 647-51.

27. Filonenko E.V. Fluorescence diagnostics and photodynamic therapy: justification of applications and opportunities in oncology, Biomedical Photonics, 2014, Vol. 3, No.1, pp. 3-7. (In Russian).

28. Pak D.D., Filonenko E.V., Frank G.A., Barsamyan G.S., Efremov G.D. Intraoperative fluorescence diagnosis of regional lymph node metastasis from breast cancer // Rossiyskiy onkologicheskiy zhurnal, 2011, Vol. 2, pp. 7-9. (In Russian).

29. Lukin V.A., Filonenko E.V., Vashakmadze L.A., Suleymanov E.A. Flu-orescense laparoscopy in patients with gastric cancer. Biomedical Photonics, 2013, Vol. 2, No.4, pp. 7-12. (In Russian).