Top

Published in:

01-08-2013 | Hepatobiliary Tumors

Optimal Future Liver Remnant in Patients Treated with Extensive Preoperative Chemotherapy for Colorectal Liver Metastases

Authors: Junichi Shindoh, MD, PhD, Ching-Wei D. Tzeng, MD, Thomas A. Aloia, MD, Steven A. Curley, MD, Giuseppe Zimmitti, MD, Steven H. Wei, PA-C, Steven Y. Huang, MD, Armeen Mahvash, MD, Sanjay Gupta, MD, Michael J. Wallace, MD, Jean-Nicolas Vauthey, MD

Published in: Annals of Surgical Oncology | Issue 8/2013

Abstract

Background

Patients with colorectal liver metastases (CLM) are increasingly treated with preoperative chemotherapy. Chemotherapy associated liver injury is associated with postoperative hepatic insufficiency (PHI) and mortality. The adequate minimum future liver remnant (FLR) volume in patients treated with extensive chemotherapy remains unknown.

Methods

All patients with standardized FLR > 20 %, who underwent extended right hepatectomy for CLM from 1993-2011, were divided into three cohorts by chemotherapy duration: no chemotherapy (NC, n = 30), short duration (SD, ≤12 weeks, n = 78), long duration (LD, >12 weeks, n = 86). PHI and mortality were compared by using uni-/multivariate analyses. Optimal FLR for LD chemotherapy was determined using a minimum p-value approach.

Results

A total of 194 patients met inclusion criteria. LD chemotherapy was significantly associated with PHI (NC + SD 3.7 vs. LD 16.3%, p = 0.006). Ninety-day mortality rates were 0 % in NC, 1.3 % in SD, and 2.3% in LD patients, respectively (p = 0.95). In patients with FLR > 30 %, PHI occurred in only two patients (both LD, 2/20, 10 %), but all patients with FLR > 30 % survived. The best cutoff of FLR for preventing PHI after chemotherapy >12 weeks was estimated as >30 %. Both LD chemotherapy (odds ratio [OR] 5.4, p = 0.004) and FLR ≤ 30 % (OR 6.3, p = 0.019) were independent predictors of PHI.

Conclusions

Preoperative chemotherapy >12 weeks increases the risk of PHI after extended right hepatectomy. In patients treated with long-duration chemotherapy, FLR > 30 % reduces the rate of PHI and may provide enough functional reserve for clinical rescue if PHI develops.

Brouquet A, Nordlinger B. Neoadjuvant therapy of colorectal liver metastases: lessons learned from clinical trials. J Surg Oncol. 2010;102:932–6.PubMedCrossRef

Kopetz S, Chang GJ, Overman MJ, Eng C, Sargent DJ, Larson DW, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009;27:3677–83.PubMedCrossRef

Poultsides GA, Bao F, Servais EL, Hernandez-Boussard T, Dematteo RP, Allen PJ, et al. Pathologic response to preoperative chemotherapy in colorectal liver metastases: fibrosis, not necrosis, predicts outcome. Ann Surg Oncol. 2012;19:2797–804.

Vauthey JN, Pawlik TM, Ribero D, Wu TT, Zorzi D, Hoff PM, et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol. 2006;24:2065–72.PubMedCrossRef

Pawlik TM, Olino K, Gleisner AL, Torbenson M, Schulick R, Choti MA. Preoperative chemotherapy for colorectal liver metastases: impact on hepatic histology and postoperative outcome. J Gastrointest Surg. 2007;11:860-8.PubMedCrossRef

Jarnagin WR, Gonen M, Fong Y, DeMatteo RP, Ben-Porat L, Little S, et al. Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade. Ann Surg. 2002;236:397–406; discussion 406–7.PubMedCrossRef

de Jong MC, Pulitano C, Ribero D, Strub J, Mentha G, Schulick RD, et al. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009;250:440–8.PubMed

Palavecino M, Kishi Y, Chun YS, Brown DL, Gottumukkala VN, Lichtiger B, et al. Two-surgeon technique of parenchymal transection contributes to reduced transfusion rate in patients undergoing major hepatectomy: analysis of 1,557 consecutive liver resections. Surgery. 2010;147:40–8.PubMedCrossRef

Madoff DC, Hicks ME, Abdalla EK, Morris JS, Vauthey JN. Portal vein embolization with polyvinyl alcohol particles and coils in preparation for major liver resection for hepatobiliary malignancy: safety and effectiveness–study in 26 patients. Radiology. 2003;227:251–60.PubMedCrossRef

10.

Madoff DC, Abdalla EK, Gupta S, Wu TT, Morris JS, Denys A, et al. Transhepatic ipsilateral right portal vein embolization extended to segment IV: improving hypertrophy and resection outcomes with spherical particles and coils. J Vasc Interv Radiol. 2005;16:215–25.PubMedCrossRef

11.

Azoulay D, Castaing D, Smail A, Adam R, Cailliez V, Laurent A, et al. Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization. Ann Surg. 2000;231:480–6.PubMedCrossRef

12.

Brouquet A, Abdalla EK, Kopetz S, Garrett CR, Overman MJ, Eng C, et al. High survival rate after two-stage resection of advanced colorectal liver metastases: response-based selection and complete resection define outcome. J Clin Oncol. 2011;29:1083–90.PubMedCrossRef

13.

Kishi Y, Abdalla EK, Chun YS, Zorzi D, Madoff DC, Wallace MJ, et al. Three hundred and one consecutive extended right hepatectomies: evaluation of outcome based on systematic liver volumetry. Ann Surg. 2009;250:540–8.PubMed

14.

Zorzi D, Chun YS, Madoff DC, Abdalla EK, Vauthey JN. Chemotherapy with bevacizumab does not affect liver regeneration after portal vein embolization in the treatment of colorectal liver metastases. Ann Surg Oncol. 2008;15:2765–72.PubMedCrossRef

15.

Kishi Y, Zorzi D, Contreras CM, Maru DM, Kopetz S, Ribero D, et al. Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases. Ann Surg Oncol. 2010;17:2870–6.PubMedCrossRef

16.

Azoulay D, Castaing D, Krissat J, Smail A, Hargreaves GM, Lemoine A, et al. Percutaneous portal vein embolization increases the feasibility and safety of major liver resection for hepatocellular carcinoma in injured liver. Ann Surg. 2000;232:665–72.PubMedCrossRef

17.

Elias D, Ouellet JF, De Baere T, Lasser P, Roche A. Preoperative selective portal vein embolization before hepatectomy for liver metastases: long-term results and impact on survival. Surgery. 2002;131:294–9.PubMedCrossRef

18.

Zorzi D, Laurent A, Pawlik TM, Lauwers GY, Vauthey JN, Abdalla EK. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg. 2007;94:274–86.PubMedCrossRef

19.

Karoui M, Penna C, Amin-Hashem M, Mitry E, Benoist S, Franc B, et al. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg. 2006;243:1–7.PubMedCrossRef

20.

Narita M, Oussoultzoglou E, Fuchshuber P, Pessaux P, Chenard MP, Rosso E, et al. What is a safe future liver remnant size in patients undergoing major hepatectomy for colorectal liver metastases and treated by intensive preoperative chemotherapy? Ann Surg Oncol. 2012;19:2526–38.PubMedCrossRef

21.

Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371:1007–16.PubMedCrossRef

22.

Vauthey JN, Chaoui A, Do KA, Bilimoria MM, Fenstermacher MJ, Charnsangavej C, et al. Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical associations. Surgery. 2000;127:512–9.PubMedCrossRef

23.

Vauthey JN, Abdalla EK, Doherty DA, Gertsch P, Fenstermacher MJ, Loyer EM, et al. Body surface area and body weight predict total liver volume in Western adults. Liver Transpl. 2002;8:233–40.PubMedCrossRef

24.

Aloia TA, Zorzi D, Abdalla EK, Vauthey JN. Two-surgeon technique for hepatic parenchymal transection of the noncirrhotic liver using saline-linked cautery and ultrasonic dissection. Ann Surg. 2005;242:172–7.PubMedCrossRef

25.

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;240:205–13.PubMedCrossRef

26.

Mullen JT, Ribero D, Reddy SK, Donadon M, Zorzi D, Gautam S, et al. Hepatic insufficiency and mortality in 1,059 noncirrhotic patients undergoing major hepatectomy. J Am Coll Surg. 2007;204:854–62; discussion 862–4.PubMedCrossRef

27.

Chun YS, Laurent A, Maru D, Vauthey JN. Management of chemotherapy-associated hepatotoxicity in colorectal liver metastases. Lancet Oncol 2009;10:278–86.PubMedCrossRef

28.

Cleary JM, Tanabe KT, Lauwers GY, Zhu AX. Hepatic toxicities associated with the use of preoperative systemic therapy in patients with metastatic colorectal adenocarcinoma to the liver. Oncologist. 2009;14:1095–105.PubMedCrossRef

29.

Kemeny N. Presurgical chemotherapy in patients being considered for liver resection. Oncologist. 2007;12:825–39.PubMedCrossRef

30.

Aloia T, Sebagh M, Plasse M, Karam V, Levi F, Giacchetti S, et al. Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. J Clin Oncol. 2006;24:4983–90.PubMedCrossRef

31.

Brouquet A, Overman MJ, Kopetz S, Maru DM, Loyer EM, Andreou A, et al. Is resection of colorectal liver metastases after a second-line chemotherapy regimen justified? Cancer. 2011;117:4484–92.PubMedCrossRef

32.

Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004;15:460–6.PubMedCrossRef

33.

Rubbia-Brandt L, Mentha G, Terris B. Sinusoidal obstruction syndrome is a major feature of hepatic lesions associated with oxaliplatin neoadjuvant chemotherapy for liver colorectal metastases. J Am Coll Surg. 2006;202:199–200.PubMedCrossRef

34.

Ribero D, Abdalla EK, Madoff DC, Donadon M, Loyer EM, Vauthey JN. Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome. Br J Surg. 2007;94:1386–94.PubMedCrossRef

35.

Takamoto T, Hashimoto T, Sano K, Maruyama Y, Inoue K, Ogata S, et al. Recovery of liver function after the cessation of preoperative chemotherapy for colorectal liver metastasis. Ann Surg Oncol. 2010;17:2747–55.PubMedCrossRef

36.

Dinant S, de Graaf W, Verwer BJ, Bennink RJ, van Lienden KP, Gouma DJ, et al. Risk assessment of posthepatectomy liver failure using hepatobiliary scintigraphy and CT volumetry. J Nucl Med. 2007;48:685–92.PubMedCrossRef

Title: Optimal Future Liver Remnant in Patients Treated with Extensive Preoperative Chemotherapy for Colorectal Liver Metastases
Authors: Junichi Shindoh, MD, PhD
Ching-Wei D. Tzeng, MD
Thomas A. Aloia, MD
Steven A. Curley, MD
Giuseppe Zimmitti, MD
Steven H. Wei, PA-C
Steven Y. Huang, MD
Armeen Mahvash, MD
Sanjay Gupta, MD
Michael J. Wallace, MD
Jean-Nicolas Vauthey, MD
Publication date: 01-08-2013
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue 8/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-012-2864-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Optimal Future Liver Remnant in Patients Treated with Extensive Preoperative Chemotherapy for Colorectal Liver Metastases

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 8/2013

Impact of Multifocality and Lymph Node Metastasis on the Prognosis and Management of Microinvasive Breast Cancer

Comparative Evaluation of [99mTc]Tilmanocept for Sentinel Lymph Node Mapping in Breast Cancer Patients: Results of Two Phase 3 Trials

Analysis of Factors that Influence the Accuracy of Magnetic Resonance Imaging for Predicting Response after Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

C4.4A Expression Is Associated with a Poor Prognosis of Esophageal Squamous Cell Carcinoma

Quantitative Shear Wave Elastography as a Prognostic Implication of Papillary Thyroid Carcinoma (PTC): Elasticity Index Can Predict Extrathyroidal Extension (ETE)

MRI Utilization in Newly Diagnosed Breast Cancer: A Survey of Practicing Surgeons