M. Kemal Temel, Cem Terzi, Kursat R. Serin, Muhammed Z. Ücüncü, Önder Karabay, Adnan Hacim

Karaciğer Metastazlı Kolorektal Kanserde Bireyselleştirilmiş Tedavi Sonuçları

Amaç: Karaciğer metastazı (KM), kolorektal kanserde (KRK) en yaygın ölüm nedenidir. Daha iyi sağkalım sonuçları için reküren KM vakalarında bireyselleştirilmiş agresif lokal tedaviler önerilmektedir. Bu çalışmada iyi seçilmiş bir grup metastatik KRK hastasında kaydedilen sonuçları paylaşmak amaçlanmıştır. Gereç ve Yöntemler: Mart 2013—Kasım 2018 döneminde karaciğer metastazlı KRK tanısı almış ve cerrahi tedavi görmüş olan toplam 45 (28 erkek, 17 kadın) hastanın tıbbi kayıtları retrospektif olarak incelenmiştir. Bulgular: Medyan hasta yaşı 61 yıl idi. Otuz iki hastada senkron metastaz teşhis edilmiş olup bunların 21’i eş zamanlı ameliyat edilmişti. Metakron metastaz için medyan süre 18 aydı. Bilober metastaz gelişen 23 hastada medyan metastaz sayısı 4 (1–18) idi. On bir (10 senkron ve 1 metakron metastaz) hastada perioperatif kemoterapi uygulanmadan karaciğer rezeksiyonu yapılmışken diğer 34 hastada perioperatif tedavi uygulanmıştı. Parankima-koruyucu karaciğer cerrahisi (metastazektomi/segmentektomi) 34 hasta ile en çok tercih edilen cerrahi yaklaşım olurken yine onkolojik prensipler doğrultusunda 10 hastada 31 metastaz için cerrahi–ablasyon kombinasyonu uygulanmıştı. Medyan tümör boyutu 35 mm, medyan cerrahi marj genişliği 3 mm idi. Dört hastada cerrahi marj pozitif olup bunlardan sadece 1’inde lokal nüks gelişmişti. Toplam 20 hastada medyan 12 aylık dönemde reküren KM gelişmiş, bu hastalara tekrar cerrahi tedavi uygulanmıştı. Medyan sağkalım süresi 45 hastanın tümü için 32 ay, nüks nedeniyle sekonder cerrahi uygulanan 12 hasta içinse 36 ay idi. Tartışma ve Sonuç: Karaciğer metastazlı KRK’de agresif bireyselleştirilmiş multidisipliner tedaviler uzun vadede daha iyi sağkalım sonuçları sağlayabilmektedir. Senkron veya aşamalı girişimler kabul edilebilir bir morbidite ve mortalite ile uygulanabilir. Reküren metastazlı hastalarda tekrar cerrahi tedavi görebilme şansını artırmak için parankima-koruyucu prosedürler tercih edilmelidir.

Individualized Treatment Outcomes in Colorectal Cancer with Liver Metastasis

Aim: Liver metastasis (LM) is the most common cause of death in colorectal cancer (CRC). In cases ofrecurrent LM, individualized aggressive local treatments are recommended for better survival outcomes.In this study, we aimed to present the health outcomes obtained in a group of highly selected patientswith metastatic CRC.Materials and Methods: We retrospectively reviewed the medical records of a total of 45 (28 males, 17females) patients who were diagnosed with liver-metastatic CRC and underwent surgical treatment between March 2013 and November 2018.Results: The median patient age was 61 years. Thirty-two patients were diagnosed with synchronousmetastases, and 21 of these patients underwent synchronous surgery. The median time for metachronousmetastases was 18 months. Twenty-three patients developed bilobar metastases, with a median numberof 4 (1–18) metastases. Eleven (10 synchronous and 1 metachronous metastasis) patients underwent liverresection without perioperative chemotherapy while the other 34 received perioperative treatment. Parenchymal-sparing liver surgery (metastasectomy/segmentectomy) as performed in 34 patients was themost preferred surgical approach and, again in accordance with the oncological principles, surgery wascombined with ablation procedures to treat 31 metastases in 10 patients. The median tumor size and surgical margin width were 35 mm and 3 mm, respectively. Surgical margin positivity was present in 4 patients,of whom only 1 developed local recurrence. In a median time of 12 months, a total of 20 patients developedrecurrent LM, and 12 of them underwent secondary surgery. The median survival time was 32 months forall 45 patients and 36 months for the 12 patients who underwent secondary surgery due to recurrences.Discussion and Conclusion: In CRC with LM, aggressive individualized multidisciplinary treatments canprovide better survival outcomes in the long term. Synchronous or staged interventions are applicablewith an acceptable morbidity and mortality. In patients with recurrent metastasis, parenchymal-sparingprocedures should be preferred in order to increase the patient’s chance of repeated surgical treatment.

PDF

___

1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimated for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374–403.
2. Brown RE, Bower MR, Martin RC. Hepatic resection for colorectal liver metastases. Surg Clin North Am. 2010;90(4):839–52.
3. Fong Y, Cohen AM, Fortner JG, Enker WE, Turnbull AD, Coit DG, et al. Liver resection for colorectal metastases. J Clin Oncol. 1997;15(3):938–46.
4. Rees M, Tekkis PP, Welsh FK, O’Rourke T, John TG. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg. 2008;247(1):125–35.
5. Alvarez FA, Sanchez Claria R, Oggero S, de Santibañes E. Parenchymal-sparing liver surgery in patients with colorectal carcinoma liver metastases. World J Gastrointest Surg. 2016;8(6):407–23.
6. Moris D, Dimitroulis D, Vernadakis S, Papalampros A, Spartalis E, Petrou A, et al. Parenchymal-sparing hepatectomy as the new doctrine in the treatment of livermetastatic colorectal disease: beyond oncological outcomes. Anticancer Res. 2017;37(1):9–14.
7. Torzilli G, Viganò L, Cimino M, Imai K, Vibert E, Donadon M, et al. Is enhanced one-stage hepatectomy a safe and feasible alternative to the two-stage hepatectomy in the setting of multiple bilobar colorectal liver metastases? A comparative analysis between two pioneering centers. Dig Surg. 2018;35(4):323–32.
8. Gold JS, Are C, Kornprat P, Jarnagin WR, Gönen M, Fong Y, et al. Increased use of parenchymal-sparing surgery for bilateral liver metastases from colorectal cancer is associated with improved mortality without change in oncologic outcome: trends in treatment over time in 440 patients. Ann Surg. 2008;247(1):109–17.
9. Reddy SK, Pawlik TM, Zorzi D, Gleisner AL, Ribero D, Assumpcao L, et al. Simultaneous resections of colorectal cancer and synchronous liver metastases: a multi-institutional analysis. Ann Surg Oncol. 2007;14:3481–91.
10. Hillingsø JG, Wille-Jørgensen P. Staged or simultaneous resection of synchronous liver metastases from colorectal cancer--a systematic review. Colorectal Dis. 2009;11(1):3–10.
11. Gavriilidis P, Sutcliffe RP, Hodson J, Marudanayagam R, Isaac J, Azoulay D, et al. Simultaneous versus delayed hepatectomy for synchronous colorectal liver metastases: a systematic review and meta-analysis. HPB (Oxford). 2018;20:11–9.
12. Torzilli G, Adam R, Viganò L, Imai K, Goransky J, Fontana A, et al. Surgery of colorectal liver metastases: pushing the limits. Liver Cancer. 2016;6(1):80–9.
13. Rentsch M, Schiergens TS. Treatment plan improvement by multidisciplinary case conferences for patients with colorectal cancer and synchronous liver metastases. Hepatobiliary Surg Nutr. 2018;7(2):147–8.
14. Schiergens TS, von Einem J, Thomas MN, Albertsmeier M, Giessen-Jung C, Dörsch M, et al. Multidisciplinary treatment of colorectal liver metastases. Minerva Med. 2017;108(6):527–46.
15. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.
16. Ferrarotto R, Pathak P, Maru D, Agarwal A, Overman M, Hoff PM, et al. Durable complete responses in metastatic colorectal cancer treated with chemotherapy alone. Clin Colorectal Cancer. 2011;10(3):178–82.
17. Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25(29):4575–80.
18. Ekberg H, Tranberg KG, Andersson R, Lundstedt C, Hägerstrand I, Ranstam J, et al. Determinants of survival in liver resection for colorectal secondaries. Br J Surg. 1986;73(9):727–31.
19. Scheele J, Stang R, Altendorf-Hofmann A, Paul M. Resection of colorectal liver metastases. World J Surg. 1995;19(1):59–71.
20. Ercolani G, Grazi GL, Ravaioli M, Cescon M, Gardini A, Varotti G, et al. Liver resection for multiple colorectal metastases: influence of parenchymal involvement and total tumor volume, vs number or location, on longterm survival. Arch Surg. 2002;137(10):1187–92.
21. Malik HZ, Hamady ZZ, Adair R, Finch R, Al-Mukhtar A, Toogood GJ, et al. Prognostic influence of multiple hepatic metastases from colorectal cancer. Eur J Surg Oncol. 2007;33(4):468–73.
22. Carlomagno C, De Stefano A, Rosanova M, De Falco S, Attademo L, Fiore G, et al. Multiple treatment lines and prognosis in metastatic colorectal cancer patients. Cancer Metastasis Rev. 2019;38(1–2):307–13.
23. Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004;240(4):644–57.
24. Pawlik TM, Vauthey JN. Surgical margins during hepatic surgery for colorectal liver metastases: complete resection not millimeters defines outcome. Ann Surg Oncol. 2008;15(3):677–9.
25. Pawlik TM, Scoggins CR, Zorzi D, Abdalla EK, Andres A, Eng C, et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg. 2005;241(5):715–22.
26. De Haas RJ, Wicherts DA, Flores E, Azoulay D, Castaing D, Adam R. R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? Ann Surg. 2008;248(4):626–37.
27. Postriganova N, Kazaryan AM, Røsok BI, Fretland Å, Barkhatov L, Edwin B. Margin status after laparoscopic resection of colorectal liver metastases: does a narrow resection margin have an influence on survival and local recurrence? HPB (Oxford). 2014;16(9):822–9.
28. Temel MK. Sitotoksik kemoterapötiklerin yirminci yüzyıldaki gelişimi [The development of cytotoxic chemotherapeutics in the twentieth century]. Turkish J Oncol. 2015;30(2):96–108.
29. Hugh TJ, Kinsella AR, Poston GJ. Management strategies for colorectal liver metastases--Part II. Surg Oncol. 1997;6(1):31–48.
30. Silberhumer GR, Paty PB, Temple LK, Araujo RL, Denton B, Gonen M, et al. Simultaneous resection for rectal cancer with synchronous liver metastasis is a safe procedure. Am J Surg. 2015;209:935–42.
31. Chen J, Li Q, Wang C, Zhu H, Shi Y, Zhao G. Simultaneous vs staged resection for synchronous colorectal liver metastases: a metaanalysis. Int J Colorectal Dis. 2011;26(2):191–9.
32. Yin Z, Liu C, Chen Y, Bai Y, Shang C, Yin R, et al. Timing of hepatectomy in resectable synchronous colorectal liver metastases (SCRLM): simultaneous or delayed? Hepatology. 2013;57:2346–57.
33. Slesser AA, Simillis C, Goldin R, Brown G, Mudan S, Tekkis PP. A meta-analysis comparing simultaneous versus delayed resections in patients with synchronous colorectal liver metastases. Surg Oncol. 2013;22:36–47.
34. Feng Q, Wei Y, Zhu D, Ye L, Lin Q, Li W, et al. Timing of hepatectomy for resectable synchronous colorectal liver metastases: for whom simultaneous resection is more suitable--a meta-analysis. PLoS One. 2014;9:e104348.
35. Yang C, Rahbari NN, Mees ST, Schaab F, Koch M, Weitz J, et al. Staged resection of bilobar colorectal liver metastases: surgical strategies. Langenbecks Arch Surg. 2015;400(6):633–40.
36. Ikoma N, Raghav K, Chang G. An update on randomized clinical trials in metastatic colorectal carcinoma. Surg Oncol Clin N Am. 2017;26(4):667–87.
37. Waisberg J, Ivankovics IG. Liver-first approach of colorectal cancer with synchronous hepatic metastases: a reverse strategy. World J Hepatol. 2015;7(11):1444–9.
38. Wicherts DA, de Haas RJ, Salloum C, Andreani P, Pascal G, Sotirov D, et al. Repeat hepatectomy for recurrent colorectal metastases. Br J Surg. 2013;100:808–18.
39. Adam R, Bismuth H, Castaing D, Waechter F, Navarro F, Abascal A, et al. Repeat hepatectomy for colorectal liver metastases. Ann Surg. 1997;225(1):51–60.