Radyoterapi Sonrası Gastrointestinal Sistem Cerrahisi
Özet
Radyoterapi, özefagus, mide, pankreas, rektum ve anüs kanserlerinin tedavisinde nüksleri azaltmak ve sağ kalım oranlarını artırmak adına kritik bir role sahiptir. Ancak eksternal radyasyon maruziyeti, hedef tümöral dokunun etrafındaki normal dokularda da belirgin organ hasarına yol açmaktadır. Akut mukozal hasar ve inflamasyon erken dönemde semptomlara neden olurken, radyoterapiden yaklaşık 90 gün sonra ortaya çıkan gecikmiş etkiler geri dönüşsüz kronik transmural fibrozis ve vasküler skleroz ile ilişkilidir. Bu histopatolojik değişiklikler, özellikle özefajektomi ve rektum rezeksiyonu gibi cerrahi diseksiyonları teknik olarak ciddi ölçüde zorlaştırmaktadır. Özefagus kanserlerinde neoadjuvan tedavi sonrası operasyon için genellikle 2-8 haftalık bir interval süresi önerilmekle birlikte, bu sürenin uzaması fibrozisi şiddetlendirerek postoperatif komplikasyon ve mortalite risklerini artırabilir. Rektum kanserinde ise kısa dönem radyoterapi veya uzun dönem kemoradyoterapi uygulamaları sfinkter koruma ve sağ kalım oranlarını optimize etse de perineal bölgedeki yara iyileşmesini olumsuz etkilemektedir. Sonuç olarak, radyoterapinin sağladığı onkolojik kazanımlar ile dokularda yarattığı fibrotik zorluklar titizlikle analiz edilerek doğru endikasyonlar belirlenmelidir.
Radiotherapy plays a pivotal role in the multimodal management of gastrointestinal cancers, significantly improving survival rates and minimizing local recurrence. However, external beam radiation inevitably impacts the normal anatomical structures surrounding the target tumor tissue. While acute mucosal injury and inflammation manifest as early symptoms, delayed effects appearing after 90 days lead to irreversible chronic transmural fibrosis and vascular sclerosis. These radiation-induced tissue alterations technically complicate subsequent surgical interventions, particularly esophagectomy and rectal resections. In esophageal malignancies, a surgical interval of 2-8 weeks post-neoadjuvant therapy is generally recommended, as prolonged delays can exacerbate fibrosis and elevate postoperative pulmonary complications and early mortality. For rectal cancer, utilizing either short-course radiotherapy or long-course chemoradiotherapy successfully optimizes sphincter preservation and disease-free survival, though it concurrently impairs perineal wound healing. Ultimately, maximizing patient outcomes requires a meticulous pre-treatment evaluation to balance the clear oncological benefits against the distinct surgical challenges posed by tissue fibrosis.
Referanslar
Khan, F.M., J.P. Gibbons, and P.W. Sperduto, Khan's Treatment Planning in Radiation Oncology. 2016: Wolters Kluwer.
Ikushima, H., Radiation therapy: state of the art and the future. J Med Invest. 2010. 57(1-2): 1-11.
Meyer, J., et al., Advanced radiation therapy technologies in the treatment of rectal and anal cancer: intensity-modulated photon therapy and proton therapy. Clin Colorectal Cancer. 2007. 6(5): 348-56.
Andreyev, J., Gastrointestinal complications of pelvic radiotherapy: are they of any importance? Gut. 2005. 54(8): 1051-4.
Podolsky, D.K., et al., Yamada's Textbook of Gastroenterology, 2 Volume Set. 2015: Wiley.
Shadad, A.K., et al., Gastrointestinal radiation injury: prevention and treatment. World J Gastroenterol. 2013. 19(2): 199-208.
Takemura, N., et al., Eosinophil depletion suppresses radiation-induced small intestinal fibrosis. Sci Transl Med. 2018. 10(429).
Haydont, V. and M.C. Vozenin-Brotons, Maintenance of radiation-induced intestinal fibrosis: cellular and molecular features. World J Gastroenterol. 2007. 13(19): 2675-83.
Hauer-Jensen, M., J.W. Denham, and H.J. Andreyev, Radiation enteropathy--pathogenesis, treatment and prevention. Nat Rev Gastroenterol Hepatol. 2014. 11(8): 470-9.
Lefevre, J.H., et al., Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6). J Clin Oncol. 2016. 34(31): 3773-3780.
Ruol, A., et al., Interval between neoadjuvant chemoradiotherapy and surgery for squamous cell carcinoma of the thoracic esophagus: does delayed surgery have an impact on outcome? Ann Surg. 2010. 252(5): 788-96.
Rice, T.W., et al., Worldwide esophageal cancer collaboration. Dis Esophagus. 2009. 22(1): 1-8.
Wong, R. and R. Malthaner, Combined chemotherapy and radiotherapy (without surgery) compared with radiotherapy alone in localized carcinoma of the esophagus. Cochrane Database Syst Rev. 2006(1): Cd002092.
van Hagen, P., et al., Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012. 366(22): 2074-84.
Tepper, J., et al., Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008. 26(7): 1086-92.
Shapiro, J., et al., Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015. 16(9): 1090-1098.
Courrech Staal, E.F., et al., Systematic review of the benefits and risks of neoadjuvant chemoradiation for oesophageal cancer. Br J Surg. 2010. 97(10): 1482-96.
Tsang, J.S., et al., Appropriate timing for surgery after neoadjuvant chemoradiation for esophageal cancer. Dis Esophagus. 2017. 30(9):1-8.
Chiu, C.H., et al., Interval between neoadjuvant chemoradiotherapy and surgery for esophageal squamous cell carcinoma: does delayed surgery impact outcome? Ann Surg Oncol. 2013. 20(13): 4245-51.
Kim, J.Y., et al., Does the timing of esophagectomy after chemoradiation affect outcome? Ann Thorac Surg. 2012. 93(1): 207-12.
Furukawa, T., et al., Impact of Interval Between Neoadjuvant Chemoradiation and Surgery Upon Morbidity and Survival of Patients with Squamous Cell Carcinoma of Thoracic Esophagus. Anticancer Res. 2018. 38(9):5239-5245.
Qin, Q., et al., Does timing of esophagectomy following neoadjuvant chemoradiation affect outcomes? A meta-analysis. Int J Surg. 2018. 59: 11-18.
Lin, F.C., A.E. Durkin, and M.K. Ferguson, Induction therapy does not increase surgical morbidity after esophagectomy for cancer. Ann Thorac Surg. 2004. 78(5): 1783-9.
Law, S., et al., Predictive factors for postoperative pulmonary complications and mortality after esophagectomy for cancer. Ann Surg. 2004. 240(5): 791-800.
Wang, S.L., et al., Investigation of clinical and dosimetric factors associated with postoperative pulmonary complications in esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery. Int J Radiat Oncol Biol Phys. 2006. 64(3): 692-9.
Rüdiger Siewert, J., et al., Adenocarcinoma of the esophagogastric junction: results of surgical therapy based on anatomical/topographic classification in 1,002 consecutive patients. Ann Surg. 2000. 232(3): 353-61.
Nishi, M., et al., Cardia cancer-proposal of cancer in the esophagogastric junction. Geka Shinryo (Surgical Diagnosis and Treatment). 1973. 15: 1328-1338.
Kurokawa, Y. and Y. Doki, Surgical and Multimodality Treatments of Cancers at the Esophagogastric Junction: The Eastern Perspective, in Textbook of Complex General Surgical Oncology, S.Y. Morita, et al., Editors. 2018, McGraw-Hill Education: New York, NY.
Stahl, M., et al., Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009. 27(6): 851-6.
Kukar, M. and S.N. Hochwald, Special Operative and Multimodal Therapy Considerations in EGJ Cancer Care: Western Viewpoints, in Textbook of Complex General Surgical Oncology, S.Y. Morita, et al., Editors. 2018, McGraw-Hill Education: New York, NY.
Siewert, J.R., H.J. Stein, and M. Feith, Adenocarcinoma of the esophago-gastric junction. Scand J Surg. 2006. 95(4): 260-9.
Nilsson, K., et al., Surgical Morbidity and Mortality From the Multicenter Randomized Controlled NeoRes II Trial: Standard Versus Prolonged Time to Surgery After Neoadjuvant Chemoradiotherapy for Esophageal Cancer. Ann Surg. 2020. 272(5): 684-689.
Klevebro, F., et al., Association between time interval from neoadjuvant chemoradiotherapy to surgery and complete histological tumor response in esophageal and gastroesophageal junction cancer: a national cohort study. Dis Esophagus. 2020. 33(5).
Sauer, R., et al., Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004. 351(17): 1731-40.
Huang, M.Y., et al., Comparison of efficacy and safety of preoperative Chemoradiotherapy in locally advanced upper and middle/lower rectal cancer. Radiat Oncol. 2018. 13(1): 53.
Musio, D., et al., Neoadjuvant-intensified treatment for rectal cancer: time to change? World J Gastroenterol. 2013. 19(20): 3052-61.
Sebag-Montefiore, D., et al., Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009. 373(9666): 811-20.
Petrelli, F., et al., Total Neoadjuvant Therapy in Rectal Cancer: A Systematic Review and Meta-analysis of Treatment Outcomes. Ann Surg. 2020. 271(3): 440-448.
Kong, J.C., et al., Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Metaanalysis of Oncological and Operative Outcomes. Ann Surg Oncol. 2021. 28(12): 7476-7486.
Ye, C., et al., A nomogram predicting the difficulty of laparoscopic surgery for rectal cancer. Surg Today. 2021. 51(11): 1835-1842.
Li, Q., et al., Factors Influencing Difficulty of Laparoscopic Abdominoperineal Resection for Ultra-Low Rectal Cancer. Surg Laparosc Endosc Percutan Tech. 2017. 27(2): 104-109.
Kanyılmaz, G., M. Aktan, and B.B. Yavuz, Lokal İleri Evre Rektum Kanserinde Pre-Operatif Radyoterapinin Yeri. Selcuk Med J. 2020. 36(1): 70-78.
Kılıç, D. and F. Demircioğlu, Rektum Kanseri Neoadjuvant Tedavisinde Uzun ve Kısa Süreli Radyoterapi Rejimlerinin Karşılaştırılması. Kolon Rektum Hastalıkları Dergisi. 2013. 24: 1-13.
Bujko, K., et al., Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006. 93(10): 1215-23.
Ngan, S.Y., et al., Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012. 30(31): 3827-33.
Wang, J., et al., Comparing neoadjuvant long-course chemoradiotherapy with short-course radiotherapy in rectal cancer. BMC Gastroenterol. 2021. 21(1): 277.
Ciseł, B., et al., Long-course preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study. Ann Oncol. 2019. 30(8):1298-1303.
Erlandsson, J., et al., Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Lancet Oncol. 2017. 18(3): 336-346.
Wu, H., et al., Short-course radiotherapy with immediate or delayed surgery in rectal cancer: A meta-analysis. Int J Surg. 2018. 56: 195-202.
Preoperative short-term radiation therapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Rectal Cancer Study Group. Cancer. 1990. 66(1): 49-55.
Randomized study on preoperative radiotherapy in rectal carcinoma. Stockholm Colorectal Cancer Study Group. Ann Surg Oncol. 1996. 3(5): 423-30.
