M.Yu. Reutovich ¹, O.V. Krasko ², A.V. Ivanov ³,

1. State Educational Establishment «Belarusian Medical Academy of Postgraduate Education» Minsk, Belarus;
2. United Institute of Informatics Problems, National Academy of Sciences of Belarus, Minsk, Belarus;
3. N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus

DOI: https://www.doi.org/10.52532/2663-4864-2023-3-69-53-58

UDC: [616.33-006.6-089+616.428-089.87]:616.381-006.6-033.2-036

Year: 2023 issure: 69 number: 3 pages: 53-58

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ABSTRACT

Relevance:Metachronous peritoneal dissemination (MPD) is among the top factors in the structure of gastric cancer (GC) progression, considerably worsening radical surgery outcomes. Since cancer cell dissemination in the peritoneal cavity is often triggered during surgery, assessing its role in MPD development is important.
The study aimed to assess the effect of the extent of radical surgery and lymph node dissection on the MPD development in radically operated gastric cancer patients.
Methods: The results of radical surgery performed on 1080 patients with gastric cancer (рТ1-4N0-3M0) without spreading to the esophagus were assessed (647 males and 433 females) depending on the extent of surgical treatment (proximal/distal subtotal gastric resection (SGR), n=639/gastrectomy (GE), n=334; standard/combined surgery, n=973/107) and the extent of lymph node dissection (LD) – D1 (n=151) or D2 (n=929). Also assessed were survival rates (Kaplan-Meyer multiplier estimation method), cumulative incidence (CI) of competing events –MPD, metastases of other localizations, and mortality cases unrelated to gastric cancer (competing risks analysis).
Results: The analysis showed a statistically significant increase in the cumulative incidence of GC progression after combined operations (55.6±4.9%) as compared with the standard radical treatment (GE – 42.3±2.7%, SRG – 25.6±1.7%, respectively), including an increase in MPD CI in each of applied surgical procedures (after combined operations – 36.8±4.7%, after standard GE – 21.6±2.3% and SRG – 11.1±1.2%, respectively; рGray<0.001). In the presence of lymphohematogenous metastases of other localizations, the relevant figures were 9.4±2.9% after combined operations, 9.3±1.6% after standard GE, and 5.0±0.9% after SRG (рGray=0.022). Lymph node metastases increased MPD CI after LD D1 from 8.3±2.8% (pN0) to 29.1±6.2% (рN1-3) (рGray<0.05), those after LD D2 increased from 9.4±1.3% (pN0) to 27.3±2.1% (рN1-3) (рGray<0.05).
Conclusion: It is advisable to assess the extent of the planned surgical treatment and the condition of local lymph nodes when evaluating the probability of MPD development. The applied lymph dissection procedure did not affect the cumulative incidence of GC progression, including MPD development.
Keywords: gastric cancer, metachronous peritoneal dissemination (MPD), cumulative incidence, surgical treatment.

List of sources used:

1. Agnes A., Biondi A., Laurino A., Strippoli A., Ricci R., Pozzo C., Persiani R., D’Ugo D. A detailed analysis of the recurrence timing and pattern after curative surgery in patients undergoing neoadjuvant therapy or upfront surgery for gastric cancer // J. Surg. Oncol. – 2020. – Vol. 122, № 2. – P. 293-305. https://doi.org/10.1002/jso.25959
2. Aoyama T., Yoshikawa T., Hayashi T., Kuwabara H., Mikayama Y., Ogata T., Cho H., Tsuburaya A. Risk factors for peritoneal recurrence in stage II/III gastric cancer patients who received S-1 adjuvant chemotherapy after D2 gastrectomy // Ann. Surg. Oncol. – 2012. – Vol.19, №5. – P. 1568-1574. https://doi.org/10.1245/s10434-011-2158-5
3. Соломенный С.В., Ганцев К.Ш., Кзыргалин Ш.Р., Минигазимов Р.С. Анатомические предпосылки развития и особенности течения канцероматоза брюшины // Ульян. мед. журн. – 2016. – № 3. – С. 91-99 [Solomennyj S.V., Gancev K.SH., Kzyrgalin SH.R., Minigazimov R.S. Anatomicheskie predposylki razvitiya i osobennosti techeniya kanceromatoza bryushiny // Ul’yan. med. zhurn. – 2016. – № 3. – S. 91-99 (in Russ.)]. https://cyberleninka.ru/article/n/anatomicheskie-predposylki-razvitiya-i-osobennosti-techeniya-kantseromatoza-bryushiny/viewer
4. Revtovich M.YU. Ocenka statusa metilirovaniya gena RECK pri prognozirovanii metahronnoj peritoneal’noj disseminacii u pacientov s rezektabel’nym rakom zheludka // Evrazijskij onkolog. zhurn. – 2021. – T. 9, №1. – S. 40-48 [Revtovich M.Yu. Assessment of the methylation status of the RECK gene in predicting metachronous peritoneal dissemination in patients with resectable gastric cancer // Eurasian Oncol. J. – 2021. – T. 9, No. 1. – P. 40-48 (in Russ.)]. https://www.elibrary.ru/item.asp?id=45599483
5. Takebayashi K., Murata S., Yamamoto H., Ishida M., Yamaguchi T., Kojima M., Shimizu T., Shiomi H., Sonoda H., Naka S., Mekata E., Okabe H., Tani T. Surgery-induced peritoneal cancer cells in patients who have undergone curative gastrectomy for gastric cancer // Ann. Surg. Oncol. – 2014. – Vol. 21. – P. 1991-1997. https://doi.org/10.1245/s10434-014-3525-9
6. Prikaz Ministerstva zdravooxraneniya Respubliki Belarus’. Algoritmy diagnostiki i lecheniya bol’nyx zlokachestvennymi novoobrazovaniyami: utv. 11 marta 2012 goda, № 258 [Order of the Ministry of Health of the Republic of Belarus. Algorithms for diagnosis and treatment of patients with malignant neoplasms: approved. March 11, 2012, No. 258 (in Russ.)].
7. Japanese gastric cancer association. Japanese classification of gastric carcinoma // Gastric Cancer. – 2011. – Vol. 14, № 2. – P. 101-112. https://doi.org/10.1007/s10120-011-0041-5
8. Fine J.P., Gray R.J. A proportional hazards model for the sub­distribution of a competing risk // J. Amer. Stat. Assoc. – 1999. – Vol. 94(446) – Р. 496-509. https://doi.org/10.2307/2670170
9. Kuk D., Varadhan R. Model selection in competing risks regres­sion // Stat. Med. – 2013. – Vol. 32, № 18. – Р. 3077-3088. https://doi.org/10.1002/sim.5762
10. cmprsk: Subdistribution Analysis of Competing Risks. R package version 2.2-7. http://CRAN.R-project.org/package=cmprsk. 18.11.2022
11. Kuznetsova A., Bruun Brockhoff P., Haubo Bojesen Christensen R. lmerTest: tests in linear mixed effects models. R package version 2.0-29. [Electronic resource]. – 2015. http://CRAN.R-project.org/package=lmerTest
12. Deng J., Zhang R., Pan Y., Ding X., Cai M., Liu Y., Liu H., Bao T., Jiao X., Hao X., Liang H. Tumor size as a recommendable variable for accuracy of the prognostic prediction of gastric cancer: a retrospective analysis of 1,521 patients // Annals of Surgical Oncology. – 2015. – Vol. 22, № 2. – P. 565-572. https://doi.org/10.1245/s10434-014-4014-x
13. Chen F.F., Huang D.D., Lu J.X., Zhou C.J., Zhuang C.L., Wang S.L., Shen X., Yu Z., Chen X.L. Feasibility of total gastrectomy with D2 lymphadenectomy for gastric cancer and predictive factors for its short- and long-term outcomes // J. of Gastrointestinal Surgery. – 2016. – Vol. 20, № 3. – P. 521-530. https://doi.org/10.1007/s11605-015-3059-x
14. De Manzoni G., Roviello F., Siquini W. Surgery in the multimodal management of gastric cancer. – Milan: Springer Milano, 2012. – 266 p. https://doi.org/10.1007/978-88-470-2318-5
15. Ilhan E., Alemdar A., Ureyen O., Bas K. The Importance of Extensive Intraoperative Peritoneal Lavage as a Promising Method in Patients with Gastric Cancer Showing Positive Peritoneal Cytology Without Overt Peritoneal Metastasis and Other Therapeutic Approach // J. Invest. Surg. – 2017. – Vol. 30, №5. – P. 318-324. https://doi.org/10.1080/08941939.2016.1247930
16. Kang L.Y., Mok K.T., Liu S.I., Tsai C.C., Wang B.W., Chen I.S., Chen Y.C., Chang B.M., Chou N.H. Intraoperative hyperthermic intraperitoneal chemotherapy as adjuvant chemotherapy for advanced gastric cancer patients with serosal invasion // J. of the Chinese Med. Assoc. – 2013. – Vol. 76, № 8. – P. 425-431. https://doi.org/10.1016/j.jcma.2013.04.004