Download PDF
Endoscopy 2020; 52(09): 727-735
DOI: 10.1055/a-1157-8611
Original article

Endoscopic treatment of gastroesophageal variceal bleeding after oxaliplatin-based chemotherapy in patients with colorectal cancer

Xiaoquan Huang‡   *
1   Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
2   Center of Evidence-Based Medicine, Fudan University, Shanghai, P.R. China
,
Feng Li‡   *
1   Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
,
Lifen Wang
3   Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, P.R. China
,
Mei Xiao
4   Department of Gastroenterology, Anhui Provincial Hospital, Hefei, Anhui, P.R. China
,
Liyuan Ni
1   Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
,
Siyu Jiang
1   Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
,
Yuan Ji
5   Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
,
Chunqing Zhang
3   Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, P.R. China
,
Wei Zhang
6   Department of Biostatistics, School of Public Health, Fudan University, Shanghai, P.R. China
,
Jian Wang
1   Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
,
Shiyao Chen
1   Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
2   Center of Evidence-Based Medicine, Fudan University, Shanghai, P.R. China
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Referred to by:

Author commentary on Xiaoquan Huang et al.Endoscopy 2020; 52(09): v33-v33
DOI: 10.1055/a-1155-0121

Abstract

Background Oxaliplatin, used as first-choice treatment for colorectal cancer (CRC), induces sinusoidal endothelial injury and portal hypertension. This study investigated the characteristics of oxaliplatin-induced portal hypertension and evaluated the efficacy of endoscopic management of gastroesophageal variceal bleeding.

Methods We performed a retrospective, multicenter, case-control study between January 2010 and December 2018. Patients who received oxaliplatin-based chemotherapy after CRC surgery and presented with portal hypertension and gastroesophageal varices were compared with consecutive patients with hepatitis B-related cirrhotic portal hypertension receiving endoscopic treatment for variceal bleeding.

Results 39 patients with oxaliplatin-induced portal hypertension were identified, 35 of whom had a history of variceal bleeding. The median period between start of oxaliplatin-based chemotherapy and the occurrence of varices was 50.4 months (n = 39). A total of 26 patients with oxaliplatin-related portal hypertension and 230 patients with hepatitis B-related portal hypertension underwent endoscopic treatment. Kaplan-Meier analysis revealed that the 1-year rebleeding rate was significantly higher in the oxaliplatin group than in the hepatitis B group (43.3 % vs. 19.0 %, P = 0.001). Multivariable Cox regression analysis showed that oxaliplatin-based chemotherapy was an independent factor for 3-year rebleeding (hazard ratio [HR] 2.46, 95 % confidence interval [CI] 1.24–4.87; P = 0.01) and 3-year overall mortality (HR 9.43, 95 %CI 2.32–38.31; P = 0.002).

Conclusions Oxaliplatin-related portal hypertension was characterized by massive ascites, splenomegaly, gastric varices, concomitant arterioportal fistula, and relatively normal liver function. Endoscopic treatment to prevent variceal rebleeding in these patients was unsatisfactory compared with endoscopic treatment for hepatitis B-related portal hypertension.

* These authors contributed equally to this work.


Appendix Table 1s



Publication History

Received: 02 October 2019

Accepted: 10 March 2020

Article published online:
07 May 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Andre T, Boni C, Navarro M. et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 2009; 27: 3109-3116
    CrossrefPubMedGoogle Scholar
  • 2 Andre T, de Gramont A, Vernerey D. et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol 2015; 33: 4176-4187
    CrossrefPubMedGoogle Scholar
  • 3 Andre T, Boni C, Mounedji-Boudiaf L. et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004; 350: 2343-2351
    CrossrefPubMedGoogle Scholar
  • 4 Aloia T, Sebagh M, Plasse M. et al. Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. J Clin Oncol 2006; 24: 4983-4990
    CrossrefPubMedGoogle Scholar
  • 5 Overman MJ, Maru DM, Charnsangavej C. et al. Oxaliplatin-mediated increase in spleen size as a biomarker for the development of hepatic sinusoidal injury. J Clin Oncol 2010; 28: 2549-2555
    CrossrefPubMedGoogle Scholar
  • 6 Rubbia-Brandt L, Audard V, Sartoretti P. et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 2004; 15: 460-466
    CrossrefPubMedGoogle Scholar
  • 7 Iwai T, Yamada T, Koizumi M. et al. Oxaliplatin-induced increase in splenic volume; irreversible change after adjuvant FOLFOX. J Surg Oncol 2017; 116: 947-953
    CrossrefPubMedGoogle Scholar
  • 8 Slade JH, Alattar ML, Fogelman DR. et al. Portal hypertension associated with oxaliplatin administration: clinical manifestations of hepatic sinusoidal injury. Clin Colorectal Cancer 2009; 8: 225-230
    CrossrefPubMedGoogle Scholar
  • 9 Gioia S, Di Martino M, Minozzi M. et al. Incidence of portal hypertension in patients exposed to oxaliplatin. Dig Liver Dis 2019; 51: 1348-1350
    CrossrefPubMedGoogle Scholar
  • 10 de Franchis R. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63: 743-752
    CrossrefPubMedGoogle Scholar
  • 11 Garcia-Tsao G, Abraldes JG, Berzigotti A. et al. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology 2017; 65: 310-335
    CrossrefPubMedGoogle Scholar
  • 12 Huang X, Ma L, Zeng X. et al. Endoscopic approaches to the treatment of variceal hemorrhage in hemodialysis-dependent patients. Gastroenterol Res Pract 2016; 2016: 9732039
    CrossrefPubMedGoogle Scholar
  • 13 Huang X, Zhang W, Chen S. et al. Therapeutic evaluation of arterio-portal fistula-related gastroesophageal variceal bleeding. Oncotarget 2017; 8: 66584-66592
    CrossrefPubMedGoogle Scholar
  • 14 Lawal TO, Farris AB, El-Rayes BF. et al. Oxaliplatin-induced hepatoportal sclerosis, portal hypertension, and variceal bleeding successfully treated with transjugular intrahepatic portosystemic shunt. Clin Colorectal Cancer 2012; 11: 224-227
    CrossrefPubMedGoogle Scholar
  • 15 Ward J, Guthrie JA, Sheridan MB. et al. Sinusoidal obstructive syndrome diagnosed with superparamagnetic iron oxide-enhanced magnetic resonance imaging in patients with chemotherapy-treated colorectal liver metastases. J Clin Oncol 2008; 26: 4304-4310
    CrossrefPubMedGoogle Scholar
  • 16 Nakano H, Oussoultzoglou E, Rosso E. et al. Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy. Ann Surg 2008; 247: 118-124
    CrossrefPubMedGoogle Scholar
  • 17 Angitapalli R, Litwin AM, Kumar PR. et al. Adjuvant FOLFOX chemotherapy and splenomegaly in patients with stages II-III colorectal cancer. Oncology 2009; 76: 363-368
    CrossrefPubMedGoogle Scholar
  • 18 Hubert C, Sempoux C, Horsmans Y. et al. Nodular regenerative hyperplasia: a deleterious consequence of chemotherapy for colorectal liver metastases?. Liver Int 2007; 27: 938-943
    CrossrefPubMedGoogle Scholar
  • 19 Bissonnette J, Genereux A, Cote J. et al. Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. J Gastroenterol Hepatol 2012; 27: 1336-1340
    CrossrefPubMedGoogle Scholar
  • 20 Robinson SM, Mann J, Vasilaki A. et al. Pathogenesis of FOLFOX induced sinusoidal obstruction syndrome in a murine chemotherapy model. J Hepatol 2013; 59: 318-326
    CrossrefPubMedGoogle Scholar