Originally published as JCO Early Release 10.1200/JCO.2005.08.009 on October 17 2005

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One Surgeon's Unabashedly Biased View on Liver Resection

Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX

All of us who publish the results of our academic endeavors in peer-reviewed journals, or present our findings at local, regional, national or international meetings, are accustomed to signing disclaimers. Scientific and intellectual integrity requires that our studies be performed free of any conflict of interest on the part of the investigators. However, I have never been required, or even requested, to sign a document or to disclose another important point of conflict: my baseline beliefs and biases. Thus, I will state openly and clearly that as a hepatobiliary surgical oncologist, my biases lead me to agree wholeheartedly with the recommendation for aggressive surgical treatment of colorectal liver metastases whenever feasible, as outlined in the article by Khatri et al,¹ entitled "Extending the Frontiers of Surgical Therapy for Hepatic Colorectal Metastases: Is There a Limit?" Having declared my particular and potentially peculiar proclivity to remove or surgically destroy colon cancer liver metastases, I will explain the background for my bias.

Elective liver resection of isolated colorectal cancer metastases provides properly selected patients the best chance for long-term disease-free and overall survival.² Nihilistic opponents to surgical treatment of metastatic disease argue that stage IV cancer is a systemic disease that requires treatment with systemic cytotoxic agents and, furthermore, complain that there has never been a prospective, randomized study comparing resection of liver metastases with systemic chemotherapy. Proponents of an aggressive surgical approach, including myself, counter with the extensive literature documenting the outcome of thousands of patients surgically treated, with 5-year overall survival rates of 33% to 58%.² Conversely, even in the current era of a dizzying array of combinations of active cytotoxic and biologic agents for colorectal cancer, the complete response rate in patients with liver metastases treated with systemic therapy alone is less than 5%, and 5-year survivorship with systemic agents is still anecdotal. In centers where large numbers of liver resections are performed, the ability to perform complex liver operations safely, with perioperative mortality rates of less than 1% and blood transfusion rates of approximately 5%, would make it impossible, if not unethical, to randomly assign properly selected patients to complete surgical resection versus systemic therapy alone.³

Several surgical groups have published results defining prognostic factors associated with a higher risk of developing recurrent disease in patients undergoing resection of colorectal cancer liver metastases. I believe the vast majority of surgeons would agree that the patients with the highest probability of a good long-term outcome after surgical treatment of colorectal cancer liver metastases are those with no radiographic or intraoperative evidence of extrahepatic malignant disease. However, it is important not to become too dogmatic because there are subsets of patients who may benefit from aggressive surgical treatment if they have only nodal disease confined to the porta hepatis, a perianastomotic recurrence, or one or two isolated pulmonary metastases also amenable to surgical resection. Patients with diffuse metastatic disease, including peritoneal carcinomatosis, are unlikely to benefit from surgical treatment of their liver metastases, further emphasizing the importance of proper patient selection. For many years, the number of liver metastases was thought to be a critical prognostic determinant, but recent results have also questioned the validity of this premise.⁴ Frankly, determination of preoperative prognostic scores or calculation of the statistical probability of the development of recurrent disease is a futile activity because there currently are no clinical or molecular determinants that will predict the future course of a given specific patient who has resectable colorectal cancer liver metastases. Every patient deserves the best treatment possible, so thoughtful but aggressive hepatobiliary surgical oncologists will proceed with resection whenever possible, regardless of the number of tumors or the prognostic score.

As readers of the article by Khatri et al¹ will learn, the surgeon embarking on resection of colorectal cancer liver metastases is trained in more than technical proficiency. The surgeon uses preoperative imaging studies to determine the number and extent of metastatic lesions and to plan the volume of liver that will be resected. Importantly, intraoperative ultrasonography performed by the surgeon offers the optimal assessment of the number, size, and proximity of tumors to key vascular and biliary structures. The surgeon is well versed in a number of techniques to reduce blood loss in an organ that receives approximately 1 L/min of blood flow in an adult, and works in close collaboration with the anesthesia team to reduce central venous pressure and limit bleeding from hepatic vein branches encountered during the liver transsection. Given the remarkable regenerative capacity of the liver, it is possible to perform staged hepatic resections wherein the dominant volume of metastases is resected during the first operation, and then any remaining metastases in the regenerated liver remnant are removed 6 to 8 weeks later. Similarly, in patients who develop recurrent liver metastases after resection, proper selection can produce long-term success in a subset of patients who undergo a second or even third resection. Finally, hepatobiliary surgeons have become adept in visualizing the approximate amount of liver that will be resected in a given patient. If the volume of liver resected is too great as determined by volumetric imaging studies and would thus be associated with a high probability of postresection liver failure, portal vein embolization of the tumor-bearing segments of liver to produce compensatory hypertrophy of the segments of liver that will remain can increase the volume of liver and reduce the incidence of postoperative liver failure.⁵

The authors of the article published in this issue of the Journal of Clinical Oncology¹ have addressed surgical issues associated with treatment of colorectal cancer liver metastases. Of interest to surgeons and medical oncologists is the expanding, but inconclusive, volume of literature regarding the role of neoadjuvant therapy for patients with resectable colorectal cancer liver metastases. Neoadjuvant therapy became interesting in colorectal liver metastases after reports of successful downsizing in some patients with previously unresectable metastatic disease to a resectable state, with subsequent 5-year survival rates of 33%.⁶ It appears that combined-modality approaches using multiagent chemotherapy have expanded the population of patients who may benefit from a curative liver resection. The potential toxicities of cytotoxic chemotherapy before liver resection, including the development or worsening of steatosis, impairment of hepatic regeneration associated with antiangiogenesis agents, or the development of blue liver syndrome associated with chemotherapy-induced vascular disease within the liver is still being assessed by surgeons, medical oncologists, pathologists, and diagnostic radiologists.

The availability of active chemotherapeutic regimens and advanced surgical techniques occasionally has combined to produce a decision-making morass in patients who present with stage IV disease that is potentially resectable at both the primary and metastatic site. The timing, quantity, and sequencing of chemotherapy; the timing and order of surgical treatment of the primary and metastatic disease; and the timing of radiation therapy for rectal primary tumors must be planned carefully to optimize the treatment in an individual patient. The authors have also not mentioned data that have been published combining surgical resection with tumor ablation techniques.² Clearly, our own data suggest that resection is superior to ablation or ablation combined with resection. Nonetheless, there are patients who heretofore were considered unresectable who have achieved long-term survival with tumor ablation techniques or resection of large and dominant metastases combined with ablation of smaller tumors. Although it is a declaration of the obvious, I am compelled to declare that state-of-the-art treatment of patients with colorectal cancer liver metastases includes multidisciplinary planning, evaluation, and therapy based on the input from medical oncologists, diagnostic and interventional radiologists, pathologists, and hepatobiliary surgical oncologists. All patients with resectable or possibly resectable colorectal cancer liver metastases should be evaluated for safe surgical treatment by an experienced, well-trained hepatobiliary surgical oncologist.

Author's Disclosures of Potential Conflicts of Interest

The author or immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Authors Employment Leadership Consultant Stock Honoraria Research Funds Testimony Other Steven A. Curley Pfizer(A)

Dollar Amount Codes (A) < $10,000 (B) $10,000-99,999 (C) $100,000 (N/R) Not Required

REFERENCES

1. Khatri V, Petrelli N, Belghiti J: Extending the frontiers of surgical therapy for hepatic colorectal metastases: Is there a limit? J Clin Oncol 23:8490-8499, 2005

2. Abdalla EK, Vauthey JN, Ellis LM, et al: Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 239:818-825, 2004[CrossRef][Medline]

3. Smith DL, Arens JF, Barnett CC, et al: A prospective evaluation of ultrasound-directed transparenchymal vascular control with linear cutting staplers in major hepatic resections. Am J Surg 190:23-29, 2005[Medline]

4. Minagawa M, Makuuchi M, Torzilli G, et al: Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: Long-term results. Ann Surg 231:487-499, 2000[CrossRef][Medline]

5. Abdalla EK, Barnett CC, Doherty D, et al: Extended hepatectomy in patients with hepatobiliary malignancies with and without preoperative portal vein embolization. Arch Surg 137:675-680, 2002[Abstract/Free Full Text]

6. Adam R, Delvart V, Pascal G, et al: Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: A model to predict long-term survival. Ann Surg 240:644-657, 2004[Medline]

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Related Article

• Extending the Frontiers of Surgical Therapy for Hepatic Colorectal Metastases: Is There a Limit?
  Vijay P. Khatri, Nicholas J. Petrelli, and Jacques Belghiti
  JCO 2005 23: 8490-8499 [Abstract] [Full Text]

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