OUR EXPERIENCE OF HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY FOR PATIENTS WITH ADVANCED GASTRIC CANCER

Purpose. Improvement of the results of treatment of patients with locally advanced and metastatic gastric cancer. Material and methods. From the 2010–2014 we performed 30 surgeries using techniques HICT. Among patients there were 17 men and 13 women. The median of age was 50 years. Locally advanced gastric cancer (T4a-T4b) was observed in 22 cases, including 4 patients in the emergency immunocytochemical study with peritoneal lavage detected cancer-free (Cyt +) cells in the abdominal cavity. The group of patients with metastatic gastric cancer accounted for 8 patients. Narrow carcinomatosis (P1) was 4 cases, carcinomatosis (P2-P3) — 4. Adjuvant systemic chemotherapy in the study group was not carried out. In the control group No 1 (n = 51) performed surgery alone, without additional anticancer therapy. In the control group No 2 (n = 66), a combined treatment (surgery + chemotherapy). Results. Follow-up median was 25 months. Overall 1-year survival rate for all three groups was 55%, 39% and 52%, respectively. Median survival in the intervention group versus 21.4 months in the 8 and 12 months, respectively. The most effective HICT is shown for patients with locally advanced gastric cancer. In the study group, median overall survival was 29 months. The survival rate of 1-, 2-, 3-year-old was equal to 68%, 61% and 42%. In the first control group, 1-year survival of 45%. None of the patients did not survive 2 years. In the second control group, one-year survival rate was 60%, 2-year survival is not. Results of treatment of metastatic gastric cancer proved to be more modest. In the main group the median survival was 10 months, compared with 6 and 7 months of the two control groups. There were no statistically significant differences.
Conclusions. 1. Availability of limited dissemination, free cancer cells in the abdominal cavity, as well as a massive defeat of serous membrane of the stomach can be seen as indications for HICT in gastric cancer.
2. In gastric cancer with carcinomatosis P2-P3 effectiveness of HICT is questionable, even with the full cytoreduction.

1. Jemal A., Siegel R., Xu J., Ward E. Cancer statistics. CA Cancer J. Clin. 2010; 60 (5): 277–300.

2. Ferlay J., Shin H. R., Bray F., Forman D., Mathers C., Parkin D. M. Estimates of worldwide burden of cancer in 2008. Int J Cancer. 2010; 15;127 (12): 893–917.

3. López-Basave H. N., Morales-Vásquez F., Ruiz-Molina J. M., Namendys-Silva S. A., Vela-Sarmiento I., Ruan J. M., Rosciano A. E., Calderillo-Ruiz G., Díaz-Romero C., Herrera-Gómez A., Meneses-García A. A. Gastric cancer in young people under 30 years of age: worse prognosis, or delay in diagnosis? Cancer Manag Res. 2013; 4;5: 1–6.

4. Kaprin A. D., Starinskiy V. V., Petrova G. V., 2015. (ed). Sostoyanie onkologicheskoy pomoshchi naseleniyu Rossii v 2013. Moscow, 2013. (Russian).

5. Kaibara N., Sumi K., Yonekawa M., Ohta M., Makino M., Kimura O., Nishidoi H., Koga S. Does extensive dissection of lymph nodes improve the results of surgical treatment of gastric cancer? Am. J. Surg. 1990; 159 (2):18–21.

6. Onkologiya: natsional’noe rukovodstvo. Chissov V. I., Davydov M. I. (ed). Moscow: “GEOTAR-Media” Publ., 2008. (Russian). 7. Oh D. Y., Bang Y. J. Adjuvant and neoadjuvant therapy for gastric cancer. Curr Treat Options Oncol. 2013; 14 (3): 311–320.

7. Taketa T., Sudo K., Wadhawa R., Blum M. M., Ajani J. A. Adjuvant therapy in gastric cancer: what is the optimal approach? Curr Oncol Rep. 2013; 15 (2): 146–151.

8. Gordon M. A., Gundacker H. M., Benedetti J., Macdonald J. S., Baranda J. C., Levin W. J., Blanke C. D., Elatre W., Weng P., Zhou J. Y., Lenz H. J., Press M. F. Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Ann Oncol. 2013; 24 (7): 1754–1761.

9. Chu D. Z., Lang N. P., Thompson C., Osteen P. K., Westbrook K. C. Peritoneal carcinomatosis in nongynecologic malignancy. A prospective study of prognostic factors. Cancer. 1989; 63 (2): 364–367.

10. Eltabbakh G. H., Werness B. A., Piver S., Blumenson L. E. Prognostic factors in extraovarian primary peritoneal carcinoma. Gynecol Oncol. 1998; 71 (2): 230–239.

11. Puhlmann M., Fink U., Siewert J. R. Value of tumor debulking in gastrointestinal tumors. Chirurg. 1999; 70 (12): 1408–1414.

12. Makino M., Kaibara N., Kimura O., Nishidoi H., Koga S. Correlation between subserosal venous invasion by gastric cancer and the occurrence of liver metastasis. Am J Clin Oncol. 1989; 12 (5): 407–410.

13. Bozzetti F., Bonfanti G., Audisio R. A., Doci R., Dossena G., Gennari L., Andreola S. Prognosis of patients after palliative surgical procedures for carcinoma of the stomach. Surg Gynecol Obstet. 1987; 164 (2): 151–154.

14. Santoro E., Garofalo A., Carlini M., Rinaldi G., Santoro E. Early and late results of 100 consecutive total gastrectomies for cancer. Hepatogastroenterology. 1994; 41 (5): 489–496.

15. Sugarbaker P. H. Management of peritoneal surface malignancy using intraperitoneal chemotherapy and cytoreductive surgery. Michig an: Ludann Company, 1998.

16. Sadeghi B., Arvieux C., Glehen O., Beaujard A. C., Rivoire M., Baulieux J., Fontaumard E., Brachet A., Caillot J. L., Faure J. L., Porcheron J., Peix J. L., François Y., Vignal J., Gilly F. N. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer. 2000; 88 (2): 358–363.

17. Jacquet P., Vidal-Jove J., Zhu B. W., Sugarbaker P. Peritoneal carcinomatosis from intraabdominal malignancy: natural history and new prospects for management. Acta Belg Chir. 1994; 94 (4): 191–197.

18. Jacquet P., Stuart O. A., Chang D., Sugarbaker P. H. Effects of intra-abdominal pressure on pharmacokinetics and tissue distribution of doxorubicin after intraperitoneal administration. Anticancer Drugs. 1996; 7 (5): 596–603.

19. Sugarbaker P. H. Review of a personal experience in the management of carcinomatosis and sarcomatosis Jpn J Clin Oncol. 2001; 31 (12): 573–583.

20. Beaujard A. C., Glehen O., Caillot J. L., Francois Y., Bienvenu J., Panteix G., Garbit F., Grandclément E., Vignal J., Gilly F. N. Intraperitoneal chemohyperthermia with mitomycin C for digestive

21. tract cancer patients with peritoneal carcinomatosis. Cancer. 2000; 88 (11): 2512–2519.

22. Ceelen W. P., Flessner M. F. Intraperitoneal therapy for peritoneal tumors: biophysics and clinical evidence. Nat Rev Clin Oncol. 2010; 7 (2): 108–115.

23. Lippmann H. G., Graichen D., Sarembe B., Schmidt D., Löffler I., Schilling W., Preissler J. Clinical examination of the conception ‘86 of “Canсer Multistep-Therapie” (CMT) by M. v. Ardene. Arch Geschwulstforsch. 1976; 46 (7): 568–609.

24. Spratt J. S., Adcock R. A., Muskovin M., Sherrill W., McKeown J. Clinical delivery system for intraperitoneal hyperthermic chemotherapy. Cancer Res. 1980; 40 (2): 256–60.

25. Athanasoulis C. A., Baum S., Rösch J., Waltman A. C., Ring E. J., Smith J. C. Jr, Sugarbaker E., Wood W. Mesenteric arterial infusions of vasopressin for hemorrhage from colonic diverticulosis. Am J Surg. 1975; 129 (2): 212–6.

26. Storm F. K. Clinical hyperthermia and chemotherapy. Radiol Clin North Am. 1989; 27 (3): 621–7.

27. Jacquet P., Stephens A. D., Averbach A. M., Chang D., Ettinghausen S. E., Dalton R.R, Steves M. A., Sugarbaker P. H. Analysis of morbidity and mortality in 60 patients with peritoneal carcino matosis treated by cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy. Cancer. 1996; 77 (12): 2622–2629.

28. Kunisaki C., Shimada H., Nomura M, Matsuda G., Otsuka Y., Akiyama H. Therapeutic strategy for signet ring cell carcinoma of the stomach. Br J Surg. 2004; 91 (10):1319–1324.

29. Kochi M., Fujii M., Kanamori N., Kaiga T., Takahashi T., Kobayashi M., Takayama T. Neoadjuvant chemotherapy with S-1 and CDDP in advanced gastric cancer. J Cancer Res Clin Oncol. 2006; 132 (12): 781–785.

30. Costa W. L., Jr, Coimbra F. J., Ribeiro H. S., Diniz A. L., de Godoy A. L., Begnami M., Silva M. J., Fanelli M. F., Mello C. A. Safety and preliminary results of perioperative chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) for high-risk gastric cancer patients. World J Surg Oncol. 2012; 19 (10): 195.