Abstract
Background
Two-stage hepatectomy has been proposed for patients with bilateral colorectal liver metastases (CLM). The aim of this study was to compare the outcome of patients with CLM treated with preoperative chemotherapy followed by one- or two-stage hepatectomy.
Methods
From a prospective database, 214 consecutive patients who received preoperative systemic chemotherapy (fluoropyrimidine with irinotecan or oxaliplatin) followed by planned one- or two-stage hepatectomy were retrospectively analyzed (1998–2006). In patients undergoing two-stage procedures, minor hepatectomy (wedge or segmental resection[s]) was systematically performed before major (more than three segments), second-stage hepatectomy. Preoperative portal vein embolization (PVE) was performed if indicated.
Results
One- (group I) and two-stage(group II) hepatectomies were performed in 184 and 21 patients, respectively. Median number of metastases in groups I and II were two (range 1–20) and seven (range 2–20). All patients in group II had bilateral disease vs 39% in group I. Major hepatectomy was performed in all patients in group II and 79% in group I. PVE was performed in 18 group I and 12 group II patients without increase in morbidity. For group I, group II first stage, and group II second stage, respectively, morbidity (24%, 24%, 43%), median hospital stay (7 days, 6 days, 6.5 days) and 30 days postoperative mortality (2%, 0%, 0%) were not significantly different (P = NS). Median follow-up was 25 months; median survival has not been reached. One- and 3-year overall and disease-free survival rates from the time of hepatic resection were 95% and 75%, 63% and 39%, respectively in group I; 95% and 86%, 70% and 51%, respectively in group II (P = NS).
Conclusions
Two-stage hepatectomy with preoperative chemotherapy results in comparable morbidity and survival rates as one-stage hepatectomy. This approach enables selection and treatment of patients with multiple, bilateral CLM who will benefit from aggressive surgery with good outcomes.
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Discussion
Timothy M. Pawlik, M.D. (Baltimore, MD): I would like to congratulate Dr. Chun and the group from M.D. Anderson for another outstanding study regarding the evolving strategies of expanding the criteria of resectability for patients with colorectal liver metastasis. And I want to thank them for providing me a copy of the manuscript beforehand. I do have a number of questions.
If we go through the numbers, you start off with more than 900 patients and you end up with 21 or roughly 2% of patients who actually underwent a two-stage hepatectomy. So clearly this is a highly select subgroup of patients. Could you shed some additional light on exactly how to best select patients who might benefit from this aggressive surgical therapy, as a full one-third of the patients who initially were planned on having a two-stage hepatectomy dropped out and only 21 out of the 30 were able to go on to have both stages of the operation.
Related to this, another manner of treating patients with extensive bilobar disease is to combine resection with contralateral hepatic ablation, and in fact, several investigators from your own institution have reported on both the safety and efficacy of combining resection with ablation. Could you help us understand which patients may benefit from resection plus ablation versus those patients who may benefit more from a two-stage hepatectomy? Also in the current study, there was no mention of portal vein ligation, and hypertrophy was induced exclusively with portal vein embolization. Is it your group’s current recommendation not to ligate the portal vein at the time of the first operation, but rather to embolize between surgeries and to rely exclusively on this modality of hypertrophying the future liver remnant?
Also, I was a little suspicious that the majority of patients who underwent a two-stage procedure had a synchronous colorectal primary in place. Did the patients who underwent a staged procedure truly undergo two operations because of purely anatomic liver-related factors, or do you think some patients were staged because of the surgeon’s reluctance to combine a major colon surgery with a major hepatic resection?
I would also like to comment just briefly on your data regarding the morbidity and mortality. You state in one of your conclusions that the overall morbidity of a two-stage operation is comparable to that of a one-stage and note that there was no statistical difference. However, given that there were only 21 patients in the two-stage arm, the study is clearly underpowered and susceptible to a type II statistical error, and we wouldn’t even expect a p value of less than 0.5. But if you look at the cumulative morbidity, it was over 65% for the two-stage operation compared to only 24% for the single-stage. So could you clarify a little bit your comments about the morbidity?
And then finally, could you comment a little bit on the 3-year survival rate of greater than 85%. The data published by Rene Adam in Paris with regards to his two-stage procedure noted a 5-year survival rate of 35%. So can you help us understand this truly almost unbelievable 3-year survival rate of greater than 80% in patients who clearly have a number of poor prognostic factors?
Again, I would like to thank you for an outstanding presentation and a worthwhile contribution to the literature. Thank you.
Yun Shin Chun, M.D. (Houston, TX): Thank you, Dr. Pawlik, for your questions.
The crux of our approach integrates steps to optimize patient selection. Several components are integrated stepwise, namely, systemic chemotherapy (and assessment of response), first-stage resection (and assessment of recovery), and portal vein embolization (and assessment of hypertrophy), all before second-stage major hepatectomy. This approach is designed to select patients with extensive hepatic disease who are likely to benefit from complete resection of bilateral tumors. It is likely that the outcome reported here at early follow-up is good because of the effect of the selection process.
Regarding survival, it is clear from recent studies that survival following hepatic resection is improving, probably because of many factors including better chemotherapy and patient selection.
To answer your question about portal vein ligation, our policy is to embolize all tumor-bearing liver, which has been shown not only to improve the degree of hypertrophy of the liver remnant, but also to avoid the problem of tumor progression in the nonembolized liver. It is well known that portal vein ligation can lead to recanalization from collateral flow and incomplete portal flow diversion.
With regard to morbidity, there is little difference in the morbidity rates for each stage, but naturally, the additive morbidity of the two operations is greater in the two-stage group, although 100% of patients in the two-stage group underwent major resection and many underwent concomitant colon resection, far more than in the one-stage group.
Regarding RFA, we have shown that ablation results in higher local recurrence rates than complete surgical resection, and our preferred approach is to treat patients with bilateral disease with one- or two-stage hepatectomy rather than combining resection with RFA. Further, if all patients with bilateral lesions undergo major resection on one side and RFA on the other side, one would not expect the results we have shown because the effect of careful, stepwise patient selection is lost. Using this approach, we excluded 1/3 of the initial patient pool who might have been treated with resection plus RFA. We have shown that survival with combined resection/ablation is similar to current best chemotherapy and does not enable survival comparable to complete resection.
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Chun, Y.S., Vauthey, JN., Ribero, D. et al. Systemic Chemotherapy and Two-Stage Hepatectomy for Extensive Bilateral Colorectal Liver Metastases: Perioperative Safety and Survival. J Gastrointest Surg 11, 1498–1505 (2007). https://doi.org/10.1007/s11605-007-0272-2
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DOI: https://doi.org/10.1007/s11605-007-0272-2