Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases.
Journal: 1999/October - Annals of Surgery
ISSN: 0003-4932
PUBMED: 10493478
Abstract:
OBJECTIVE
There is a need for clearly defined and widely applicable clinical criteria for the selection of patients who may benefit from hepatic resection for metastatic colorectal cancer. Such criteria would also be useful for stratification of patients in clinical trials for this disease.
METHODS
Clinical, pathologic, and outcome data for 1001 consecutive patients undergoing liver resection for metastatic colorectal cancer between July 1985 and October 1998 were examined. These resections included 237 trisegmentectomies, 394 lobectomies, and 370 resections encompassing less than a lobe. The surgical mortality rate was 2.8%.
RESULTS
The 5-year survival rate was 37%, and the 10-year survival rate was 22%. Seven factors were found to be significant and independent predictors of poor long-term outcome by multivariate analysis: positive margin (p = 0.004), extrahepatic disease (p = 0.003), node-positive primary (p = 0.02), disease-free interval from primary to metastases <12 months (p = 0.03), number of hepatic tumors >1 (p = 0.0004), largest hepatic tumor >5 cm (p = 0.01), and carcinoembryonic antigen level >200 ng/ml (p = 0.01). When the last five of these criteria were used in a preoperative scoring system, assigning one point for each criterion, the total score was highly predictive of outcome (p < 0.0001). No patient with a score of 5 was a long-term survivor.
CONCLUSIONS
Resection of hepatic colorectal metastases may produce long-term survival and cure. Long-term outcome can be predicted from five criteria that are readily available for all patients considered for resection. Patients with up to two criteria can have a favorable outcome. Patients with three, four, or five criteria should be considered for experimental adjuvant trials. Studies of preoperative staging techniques or of adjuvant therapies should consider using such a score for stratification of patients.
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Discussion board
Ann Surg 230(3): 309

Clinical Score for Predicting Recurrence After Hepatic Resection for Metastatic Colorectal Cancer

From the *Hepatobiliary Service and the †Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York City, New York

Abstract

Objective

There is a need for clearly defined and widely applicable clinical criteria for the selection of patients who may benefit from hepatic resection for metastatic colorectal cancer. Such criteria would also be useful for stratification of patients in clinical trials for this disease.

Methods

Clinical, pathologic, and outcome data for 1001 consecutive patients undergoing liver resection for metastatic colorectal cancer between July 1985 and October 1998 were examined. These resections included 237 trisegmentectomies, 394 lobectomies, and 370 resections encompassing less than a lobe. The surgical mortality rate was 2.8%.

Results

The 5-year survival rate was 37%, and the 10-year survival rate was 22%. Seven factors were found to be significant and independent predictors of poor long-term outcome by multivariate analysis: positive margin (p = 0.004), extrahepatic disease (p = 0.003), node-positive primary (p = 0.02), disease-free interval from primary to metastases <12 months (p = 0.03), number of hepatic tumors >1 (p = 0.0004), largest hepatic tumor >5 cm (p = 0.01), and carcinoembryonic antigen level >200 ng/ml (p = 0.01). When the last five of these criteria were used in a preoperative scoring system, assigning one point for each criterion, the total score was highly predictive of outcome (p < 0.0001). No patient with a score of 5 was a long-term survivor.

Conclusion

Resection of hepatic colorectal metastases may produce long-term survival and cure. Long-term outcome can be predicted from five criteria that are readily available for all patients considered for resection. Patients with up to two criteria can have a favorable outcome. Patients with three, four, or five criteria should be considered for experimental adjuvant trials. Studies of preoperative staging techniques or of adjuvant therapies should consider using such a score for stratification of patients.

Abstract

Secondary procedures were liver procedures or arterial infusion pump placements performed in addition to and at the same time as the primary procedures.

Each risk factor is one point: node-positive primary, disease-free interval <12 months, >1 tumor, Size >5 cm, CEA >200 ng/ml.

Discussion

Dr. Henry A. Pitt (Milwaukee, Wisconsin): I would like to thank Drs. Blumgart and Fong and their colleagues for the opportunity to review their manuscript and to discuss this excellent paper.

As you just heard, their experience is extensive. Their short- and long-term results are excellent, and their analysis is very complete. Their data are very important because their analysis includes a large number of patients from a single institution managed by a small number of surgeons. With this power, they confirmed that all of the factors suggested in other analyses are predictors of outcome in their patients. With this information, they have proposed a clinical risk score that should be useful in the design of future studies. Analysis of this and other studies suggests that extrahepatic disease, positive margins, and the number of liver lesions are the best predictors of outcome.

Among these three factors, the one that can be assessed most accurately preoperatively is the number of liver lesions. Thus, in this and most other similar analyses in the literature, the vast majority of patients who have been explored for surgical therapy have had four or fewer lesions on preoperative studies. However, with the introduction of new techniques such as cryotherapy and radiofrequency ablation, the value of the number of lesions as a predictor of outcome must be questioned.

To address this issue, a more aggressive surgical approach to colorectal liver metastases was undertaken by Dr. Edward Quebbeman at the Medical College of Wisconsin in 1993. With the addition of cryoablation to the surgical armamentarium, 28% of 106 patients undergoing a potentially curative procedure had more than four metastases.

This slide demonstrates the survival by the number of tumors treated. As you can see, the median and 3-year survival was actually slightly greater in the patients with five to eight lesions compared to those with one to four, although this difference was not statistically significant. With this approach, the presence of extrahepatic disease and the ability to perform a curative procedure were predictors of outcome in a multivariate analysis, but the number of lesions was not predictive of outcome.

On the basis of these data, which were presented at the Central Surgical Association last month, we recommended that patients with up to eight liver lesions should be explored, with the goal to resect and/or ablate all of the liver lesions. Therefore, my two questions are whether you have used ablative procedures in any of your patients and whether you believe that the number of metastases should be used as a criterion for exploration now that we have the availability of ablative procedures.

Presenter Dr. Leslie H. Blumgart (New York, New York): Thank you, Dr. Pitt. Of course we have used ablative procedures. But the patients are not included in this series of resection. The purpose of the study was to examine exactly what you are suggesting, that is, to assess these factors in such a manner that we could define a reasonable scoring system to allow stratification of patients for study with such modalities as cryosurgery and other ablative procedures.

Dr. Robert M. Beazley (Boston, Massachusetts): To my knowledge, the first reported resection for colorectal metastasis to the liver occurred in 1941 by Richard Catell at the Lahey Clinic, and since that time, a considerable body of literature has developed in this area. Dr. Fong’s paper is a notable addition in that it is the largest single-institution experience, one accumulated during a relatively short period of time by a small number of surgeons. Their conclusions are straightforward and clinically quite useful. It is especially helpful from a clinical standpoint that their proposed clinical risk score can be applied in making preoperative decisions and thus permit appropriate focusing of our resources.

For example, patients presenting with liver metastasis 4 to 6 months after a primary resection currently present a bit of a dilemma. I have always suggested some chemotherapy and a watch-and-wait attitude before surgery. The clinical risk score provides us with selection guidance, suggesting that a low-score patient is an immediate resection candidate, while those patients who might be three, four, or five are not, and perhaps watch-and-wait is the best course for them.

I have a few questions for the authors. First, in that you have done a large number of extended liver resections with an extremely acceptable mortality, is there any special testing that you do preoperatively to predict liver reserve in those patients you anticipate extended resection? Should age be a consideration in major extended resection, particularly in the elderly where you may be anticipating a trisegmentectomy? Would you suggest that we not resect or delay resection in those who have scores in the 4 and 5 range? In your study, this constituted a small group of patients, and I would like to know how you feel about that. Lastly, comment on your criteria for reresection of patients, the patient who is successfully resected and comes back a year or two later with another metastasis. How do you decide about that?

I think the authors are to be congratulated on their skill and perseverance in performing these demanding procedures. We are in debt to you for providing us with your data, which I predict will prove to be clinically quite useful.

Dr. Blumgart: Thank you very much, Dr. Beazley. I will take the points you mentioned one at a time and then I would like to take up one other comment you made.

First, in relation to liver reserve: We have not taken any particular refined measurements of liver functional capacity (these patients were not cirrhotic) but relied on the fact that we can see a good functional piece of liver on, for instance, a CT scan with good vascularization and good outflow. If we can resect these patients and maintain a good portal inflow and a good hepatic venous outflow, we have had no particular concerns even with very extensive resection.

In relation to age, we presented at this Society some years ago a paper relating age to mortality and outcome in pancreaticoduodenectomy and in liver resection, and showed no difference in outcome between patients older than or younger than 70 years.

The question of a delay in the timing of resection for patients with score of 4 or 5: I wonder if I could answer that by just relating it to the other comment you made in relation to patients who have a recurrence within the first year or have a synchronous metastasis. These are small metastases less than 3 cm in size, maybe one or two metastases present. You are quite right, these patients present a dilemma for us as well as for you.

It is of some interest that we took the proposed score and we looked at patients with tumors 3 cm or less in size and applied the score to the outcome. Those patients with a score of 0 to 2 had a 5-year survival of 47%, whereas patients with a score of 3 to 5 had only a survival of 24%.

This is a very significant difference and does suggest that the proposed scoring system may be of some value in selecting patients with such small lesions either for immediate resection or for study, for instance, in neoadjuvant regimes. I think that your question is relevant and important and it is one which the use of this scoring system may help answer.

You asked about the reresection. Yes, we have published in that area as well. But so have many others. Reresection has been shown to be safe, with no greater operative mortality than primary resection, and also to yield good results. I think you were asking how did we select such patients. I think the answer is, with some difficulty, but always looking to the feasibility of resection based on the anatomical distribution of the recurrence.

Dr. John Terblanche (Cape Town, South Africa): It is a great privilege to be able to congratulate the authors on their seminal paper, which I think will alter our practice. Two questions for Dr. Blumgart.

The first is: In the abstract you have proposed six criteria, while in the presentation and the paper you use five criteria. I understand the reason for the change. Is there a subset of the patients who have either a score of 6 or of 5 where it is not worthwhile treating them? It would be important to identify those patients who we are currently treating, but who should be considered to be inoperable. They could then be considered for alcohol injection or other palliative treatment.

The second question is: In several published papers, other criteria have been presented as important. Why the difference? Is it because you have been able to assess a very large number of patients?

Dr. Blumgart: Thank you, Dr. Terblanche. Yes, the abstract is different from the presentation. This is because when we looked at the bilaterality of tumors, it was not, in fact, of significance. It is impossible to separate, as Dr. Fong said in the presentation, number and size of tumors from bilaterality, so we dropped bilaterality and concentrated on the five score points mentioned.

If I have the second question right, I think you are asking how this score differs from that of others. It doesn’t really. It simply takes a limited number of factors which are easily available preoperatively. It omits things which we cannot know preoperatively and allows anybody in any institution to use the system and to participate in the staging of patients in, for example, multicenter studies.

It is important that I emphasize that a score of 5 would not cause us to refuse resection to any one patient. The results are often good in spite of adverse factors. However, the score does give a good prognostic index. Its major value, however, will be in allowing stratification of patients in prospective studies of adjuvant or alternative treatment modalities.

Dr. Shunzaburo Iwatsuki (Pittsburgh, Pennsylvania): We also have a fair-sized database of hepatic metastasis in Pittsburgh and recently completed our study. Our prognostic scoring system will be published in the August issue of the Journal of the American College of Surgeons.

Our study revealed 12 risk factors to be significant by univariate analysis, and only four factors to be independently significant by a stepwise Cox regression model with likelihood ratio test, as shown in the slide. The two factors, CEA level and positive node at colon surgery, were not independent factors, and therefore both were eliminated from the scoring system.

High CEA level is known to have a close relationship with tumor load, such as size and number of tumor. Positive node at colon surgery, or stage of primary tumor has a close relationship to tumor-free interval (time to hepatic recurrence).

The inclusion of those two confounding factors in scoring system surely makes the grading less accurate by counting the same kind of risk factors repeatedly.

My questions are: One, did you use a stepwise Cox regression model or nonstepwise Cox regression model? Two, did you statistically confirm that all of your six risk factors in the grading system were independent to each other? Finally, I have a great concern in your statistical methods.

Dr. Blumgart: Thank you very much, Dr. Iwatsuki, for telling me what we should have done! At least I think I understand what you are telling me I should have done.

In point of fact, we did do a multivariate analysis and the data have been presented. I am not sure why it differs from the data that you say you are about to publish. I know that your publication—I think the author was Dr. Gayowski—in 1994 in fact mentioned many of the same factors we have discussed. Maybe the difference in opinion relates to the number of patients in the studies. It may be that with the large number of patients we have, we are seeing a different result to those which you would wish us to report.

Dr. Harold J. Wanebo (Providence, Rhode Island): Dr. Blumgart, I would like to congratulate you, Dr. Fong, and your coauthors for an outstanding series and for coming up with a clinical scoring system that has some statistical validity.

I have two questions. The first is regarding intraoperative selection factors that would preclude resection. What factors are you currently utilizing for patients on the operating table to exclude a resection and what do you subsequently do with that patient?

The second question refers back again to the problem of liver reserve. On a practical basis, what is the bottom line regarding the amount of liver that can be left behind in a patient without cirrhosis within the middle-aged group? Is 20% acceptable? Give us a bottom line.

Dr. Blumgart: Thank you, Dr. Wanebo. I will start with the last question first. As you know, I visited with you not long ago and we debated this point. I think it is all right if you want to do refined tests of hepatic functional reserve. We just don’t find them useful. If you look at our results, even with very extensive resection, I think our attitude is substantiated. It is quite different in the cirrhotic liver and you can make an argument for your approach there. However, I don’t really feel that the time, effort, and money spent doing these tests in the patient with a noncirrhotic liver justifies the effort. The results speak for themselves. We have a 2.8% mortality in 1000 cases. I don’t think more than three or four of these people died of liver failure. So I don’t think that refined liver functional assessment is very important.

I think the other question you raise is more interesting: What do we do at operation? Well, we resected 79% of all tumors in patients that we took to the operating room. In fact, in the recent year or so, we have been doing laparoscopy prior to laparotomy in these patients. Doing that, you pick up some patients who would not go on to open operation. Using this approach, the resectability rate is now in excess of 90%. This means that we have relatively few patients in which we have the problem you raise.

Dr. Wanebo: Finally, I guess the real question is a philosophical one regarding the management of nonresectable patients. Many of us believe in the use of hepatic artery infusion in patients who are not candidates for resection. This, of course, means that one has to plan for placing a hepatic artery catheter and pump up front. The question is whether the patient would benefit from placement of a hepatic artery catheter so the operation is not wasted. We are aware of the controversy regarding its contribution to improved survival, but believe there is confirmed benefit of controlling disease in the liver.

Dr. Blumgart: It really is a question of how you design clinical trials in relation to the use of infusaid therapy or other approaches. You say you “believe in it.” Yes, we probably are beginning to believe in it, too.

As you know, there has been a prospective randomized trial of infusaid pump chemotherapy running at Memorial Sloan-Kettering Cancer Center. That trial has recently closed. Initial results suggest that infusaid pump chemotherapy may improve survival, particularly in patients with more than two tumors. I think for those few patients that you cannot resect, it is appropriate to have some form of alternative therapy available. This is, in fact, what you are suggesting. However, I would again emphasize that a scoring system such as we propose is important in stratifying patients for prospective studies of adjuvant or alternative therapy.

Dr. Henri Bismuth (Villejuif, France): This is an important paper, and I congratulate Dr. Fong and Leslie Blumgart for it. My question concerns the group of patients who have more than three predictors of mortality. I am upset by the possibility that some physicians, or even surgeons, might take this score as an argument against liver resection. Indeed, what this paper shows is that, in this group of patients, the 5-year survival is around 20%, less than the 54% in Group 1, but certainly better than the 0% which would be expected in similar patients without resection. This is a very important point. My policy is to try to resect when it is technically possible in terms of anatomy and function of the remaining liver, and to use some kind of neoadjuvant treatment, especially chemotherapy. We must try to give the patient the chance, even small, of a cure. I am sure, Leslie, that you will agree with this.

Dr. Blumgart: Thank you very much, Professor Bismuth. As always, you make a very important point, and it is a pleasure to be able to agree with you. I don’t know what to do with these patients either. But you are absolutely right; the current results of chemotherapy leave much to be desired.

I think your approach, which you have published and championed recently, of trying to convert some patients who appear to be irresectable to resectability is an aggressive chemotherapeutic regime which you have shown can work. I think it is an appropriate approach which others should attempt to duplicate. We have recently operated on a few patients in whom we have had multiple small tumors in the right lobe and a very small hemiliver on the other side (i.e., a small left lobe). This has been of some concern coming back to the point that Dr. Wanebo raised in relation to liver function. We have used unilateral portal vein embolization to induce atrophy on the affected side and hypertrophy in the proposed remnant. This approach, first championed by Makuuchi in Japan, can be of value in this situation.

So I am sure you are right. As we get better at hepatic resection, we could use a scoring system like this to pick the cases more likely to have a poor outcome.

Footnotes

Correspondence: Yuman Fong, MD, Hepatobiliary Surgery Service, Dept. of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.

Presented at the 119th Annual Meeting of the American Surgical Association, April 15–17, 1999, Hyatt Regency Hotel, San Diego, California.

Supported in part by NIH grants RO1CA76416, RO1CA72632, and RO1CA61524 (YF).

Accepted for publication April 1999.

Footnotes

References

  • 1. Scheele J, Stang R, Altendorf-Hofmann A, Paul M. Resection of colorectal liver metastases. World J Surg 1995; 19: 59–71. [[PubMed]
  • 2. Gayowski TJ, Iwatsuki S, Madariaga JR, et al. Experience in hepatic resection for metastatic colorectal cancer: analysis of clinical and pathological risk factors. Surgery 1994; 116: 703–711.
  • 3. Rosen CB, Nagorney DM, Taswell HF, et al. Perioperative blood transfusion and determinants of survival after liver resection for metastatic colorectal carcinoma. Ann Surg 1992; 216: 492–505.
  • 4. Nordlinger B, Parc R, Delva E, Quilichini M, Hannoun L, Huguet C. Hepatic resection for colorectal liver metastases. Ann Surg 1987; 205: 256–263.
  • 5. Hughes KS, Simons R, Songhorabodi S, et al. Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of indications for resection. Surgery 1988; 103: 278–288.
  • 6. Fong Y, Cohen AM, Fortner JG, et al. Liver resection for colorectal metastases. J Clin Oncol 1997; 15: 938–946. [[PubMed]
  • 7. Jaffe BM, Donegan WL, Watson F, et al. Factors influencing survival in patients with untreated hepatic metastases. Surg Gynecol Obstet 1968; 127: 1–11. [[PubMed]
  • 8. Bengmark S, Hafstrom L. The natural history of primary and secondary malignant tumors of the liver: I. The prognosis for patients with hepatic metastases from colonic and rectal carcinoma by laparotomy. Cancer 1969; 23: 198–202. [[PubMed]
  • 9. Chang AE, Schneider PD, Sugarbaker PH, Simpson C, Culnane M, Steinberg SMA prospective randomized trial of regional vs. systemic continuous 5-FU chemotherapy in the treatment of colorectal metastases. Ann Surg 1987; 206: 685–693.
  • 10. Cunningham D, Pyrhonen S, James RD, et alRandomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer [see comments]. Lancet 1998; 352: 1413–1418. [[PubMed]
  • 11. Geller AI. A system, using neural cell lines, to characterize HSV-1 vectors containing genes which affect neuronal physiology, or neuronal promoters. J Neurosci Meth 1991; 36: 91–103. [[PubMed]
  • 12. Nordlinger B, Guiguet M, Vaillant JC, et al. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Française de Chirurgie Cancer 1996; 77: 1254–1262. [[PubMed]
  • 13. Goldsmith NA, Woodburne RT. The surgical anatomy pertaining to liver resection. Surg Gynecol Obstet 1957; 105: 310–318. [[PubMed]
  • 14. Couinaud C. Bases anatomiques des hepatectomies gauche et droite reglées. J Chirurgie 1954; 70: 933–966. [[PubMed]
  • 15. Starzl TE, Bell RH, Beart RW, Putnam CW. Hepatic trisegmentectomy and other liver resections. Surg Gynecol Obstet 1975; 141: 429–438.
  • 16. Matthews DE, Farewell VT. Understanding medical statistics. New York: Karger; 1990.
  • 17. Cox DR. Regression models and life tables (with discussion). J R Stat Soc B 1972; 187–220.
  • 18. Polk W, Fong Y, Karpeh M, Blumgart LH. A technique for the use of cryosurgery to assist hepatic resection. J Am Coll Surg 1995; 180: 171–176. [[PubMed]
  • 19. Lorenz M, Muller HH, Schramm H, et alRandomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer. Ann Surg 1998; 228: 756–762.
  • 20. Kemeny N, Huang Y, Cohen AM, et alRandomized study of hepatic arterial infusion and systemic chemotherapy versus systemic chemotherapy alone as adjuvant treatment following resection of hepatic metastases from colorectal cancer [abstract]. Proceedings of the American Society of Clinical Oncology, Atlanta, GA, May 1999.
  • 21. Kemeny N, Fong Y. Treatment of liver metastases. In: Holland JF, Frei E, Bast RC, Kufe DW, Morton DL, Weichselbaum RR, eds. Cancer medicine. Baltimore: Williams &amp; Wilkins; 1997: 1939–1954.
  • 22. Fleming ID, Cooper JS, Henson DE, et al. Manual for staging of cancer. 5th ed. Philadelphia: Lippincott-Raven; 1997.
  • 23. Silen W. Hepatic resection for metastases from colorectal carcinoma is of dubious value. Arch Surg 1989; 124: 1021–1024. [[PubMed]
  • 24. Gilbert HA, Kagan AR. Metastases: incidence, detection, and evaluation without histologic confirmation. In: Weiss L, ed. Fundamental aspects of metastasis. Amsterdam: North Holland Publishing Co.; 1976: 385–405.
  • 25. Foster JH. Survival after liver resection for secondary tumors. Am J Surg 1978; 135: 389–394. [[PubMed]
  • 26. Adson MA, Van Heerden JA, Adson MH, Wagner JS, Ilstrup DM. Resection of hepatic metastases from colorectal cancer. Arch Surg 1984; 119: 647–651. [[PubMed]
  • 27. Fortner JG, Silva JS, Golbey RB, Cox EB, Maclean BJ. Multivariate analysis of a personal series of 247 consecutive patients with liver metastases from colorectal cancer. I. Treatment by hepatic resection. Ann Surg 1984; 199: 306–316.
  • 28. Butler J, Attiyeh FF, Daly JM. Hepatic resection for metastases of the colon and rectum. Surg Gynecol Obstet 1986; 162: 109–113. [[PubMed]
  • 29. Pagana TJ. A new technique for hepatic infusional chemotherapy. Sem Surg Oncol 1986; 2: 99–102. [[PubMed]
  • 30. Cobourn CS, Makowka L, Langer B, Taylor B, Falk R. Examination of patient selection and outcome for hepatic resection for metastatic disease. Surg Gynecol Obstet 1987; 165: 239–246. [[PubMed]
  • 31. Schlag P, Hohenberger P, Herfarth CResection of liver metastases in colorectal cancer: competitive analysis of treatment results in synchronous versus metachronous metastases. Eur J Surg Oncol 1990; 16: 360–365. [[PubMed]
  • 32. Doci R, Gennari L, Bignami P, Montalto F, Morabito A, Bozetti F. One hundred patients with hepatic metastases from colorectal cancer treated by resection: analysis of prognostic determinants. Br J Surg 1991; 78: 797–801. [[PubMed]
  • 33. Younes RN, Rogatko A, Brennan MF. The influence of intraoperative hypotension and perioperative blood transfusion on disease-free survival in patients with complete resection of colorectal liver metastases. Ann Surg 1991; 214: 107–113.
  • 34. Scheele J, Stangl R, Altendorf-Hofmann A, Gall FP. Indicators of prognosis after hepatic resection for colorectal secondaries. Surgery 1991; 110: 13–29. [[PubMed]
  • 35. Cady B, Stone MD, McDermott WV Jr, et al. Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases. Arch Surg 1992; 127: 561–569. [[PubMed]
  • 36. Cady B, Stone MD. The role of surgical resection of liver metastases in colorectal carcinoma. Semin Oncol 1991; 18: 399–406. [[PubMed]
  • 37. Belluco C, Guillem JG, Kemeny N, et al. p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of survival in patients with advanced hepatic metastases. J Clin Oncol 1996; 14: 2696–2701. [[PubMed]
  • 38. Lai DT, Fulham M, Stephen MS, et al. The role of whole-body positron emission tomography with [18F]fluorodeoxyglucose in identifying operable colorectal cancer metastases to the liver. Arch Surg 1996; 131: 703–707. [[PubMed]
  • 39. Rivoire M, Yoshida K, Divgi C, Welt S, Cohen A, Sigurdson ER. Radioimmunodetection of hepatic metastases with gamma-detecting probe. Cancer Res 1990; 50: 877s–879s. [[PubMed]
  • 40. August DA, Sugarbaker PH, Schneider PD. Lymphatic dissemination of hepatic metastases: implications for the follow-up and treatment of patients with colorectal cancer. Cancer 1985; 55: 1490–1494. [[PubMed]
  • 41. Morris DL, Ross WB. Australian experience of cryoablation of liver tumors. Surg Oncol Clin North Am 1996; 5: 391–397. [[PubMed]
  • 42. McGahan JP, Browning JP, Brock JM, et al. Hepatic ablation using radiofrequency electrocautery. Invest Radiol 1990; 25: 267–270. [[PubMed]
  • 43. Kooby DA, Carew JF, Halterman MW, et al. Oncolytic viral therapy for human colorectal cancer and liver metastases using a multimutated herpes simplex virus type-1 (G207). FASEB J 1999 (in press). [[PubMed]
  • 44. Macapinlac HA, Kemeny N, Daghighian F, et al. Pilot clinical trial of 5-[125I]-Iodo-2′-deoxyuridine in the treatment of colorectal cancer metastatic to the liver. J Nucl Med 1996; 37: 25S–32S. [[PubMed]
  • 45. Karpoff HM, D’Angelica M, Blair S, Brownlee MD, Federoff H, Fong Y. Prevention of hepatic tumor metastases in rats with herpes viral vaccines and gamma-interferon. J Clin Invest 1997; 99: 799–804.
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