Journal of Surgical Oncology 51:122-125 (1992)
Hepatic Resection Following Systemic Chemotherapy for Metastatic Colorectal Carcinoma WYATT C. FOWLER, MD, BURTON L. EISENBERG, MD, FAG, AND JOHN P. HOFFMAN, MU, From the Department of Surgical Oncology, Fox Chase Cancer Center and Schooi of Medicrne, Temple University, Philadelphia, Pennsylvania
FACS
Increasingly effective systemic chemotherapy has improved responses in patients with previously unresectable colorectal hepatic metastases. In the future, response to chemotherapy may define a new population of patients that may benefit from hepatic resection. A retrospective review to determine the safety and effectiveness of potentially curative hepatic resection of metastatic colorectal carcinoma after systemic chemotherapy identified 1 1 such patients with resections between July 1987 and October 1991. Five patients had unresectable disease confined to the liver, two had hepatic and limited extrahepatic metastases, two had hepatic recurrences after previous hepatic metastasectomy, and two had initially resectable liver metastases. These patients were resected after a mean of 8 months of systemic chemotherapy. Complications, usually minor, occurred in five patients (45%). There were no deaths. Three patients are disease free at 15, 18, and 31 months (mean 21) after hepatic resection. Eight patients have recurred with a median time to recurrence of 8 months. Five patients have subsequently died of recurrent disease. This study suggests that hepatic resection following systemic chemotherapy can be performed safely and may benefit selected patients. 0 1992 WiIey-Liss, Inc. KEYWORDS:chemotherapy, downstaging, liver
INTRODUCTION Approximately 50% of the estimated 140,000 patients diagnosed annually in the United States with colorectal carcinoma will develop hepatic metastases during the course of their disease [ 11. Resection of isolated hepatic metastases has been employed with increased frequency, and its therapeutic efficacy has been established. Unfortunately, only 5-1 0% of patients will have metastases amenable to surgical resection [2]. Observation or palliative chemotherapy are the only options available to greater than 90% of patients with colorectal hepatic metastases. Recent series employing pharmacological modulation of fluorouracil (5-FU) have demonstrated partial clinical responses in approximately 45% of patients [3-81. Increasingly at our institution, patients with metastases restricted to the liver who were initially judged unresectable because of the size, number, or location of the meta0 1992 Wiley-Liss, Inc.
static deposits were achieving partial responses to systemic chemotherapy regimes. Some of these patients were downstaged to the point where surgical resection became an option. Because the literature has a void of data analyzing this situation, this retrospective review was undertaken to examine our results following major hepatic resection for a group of patients who had surgery following systemic chemotherapy for treatment of their colorectal liver metastases.
MATERIALS AND METHODS A retrospective chart review of 6 1 consecutive hepatic resections performed at our institution between July 1987 and October 199 1 was initiated to identify all patients 1992. Accepted for publicationJune Address reprint rcquests to Burton L Eisenberg, MD, FACS, Department of Surgical Oncology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 191 I 1.
Liver Resection After Systemic Chemotherapy
who underwent hepatic resection for metastatic colorectal cancer after receiving systemic chemotherapy for these lesions. Patients with hepatic resections following remote adjuvant chemotherapy for the primary lesion were not included. The following prognostic factors were evaluated: site, stage, and treatment of the primary lesion, the disease free interval, the site, number, and extent of recurrence, the preoperative CEA, the nature, duration, and response to chemotherapy.
RESULTS This review identified 11 patients, five male and six female, from 37 to 74 years of age (median 68 years), who underwent resection of hepatic colorectal metastases after receiving systemic chemotherapy for these lesions. All were colon primaries, and disease at the primary site was controlled. The study group was not homogenous, but could be separated into four groups. Group I included five patients with hepatic metastases initially judged unresectable because of the number, size, or location of the lesions. Three of the five patients originally presented with stage D disease and were deemed unresectable at the time of colectomy because of multiple bilobar metastases in two, and a large central lesion involving both lobes in the other. The other two developed multiple hepatic lesions found on CT scans 7 and 12 months after colectomy. AII of these patients were treated with modulated 5-FU for 4 to 27 (median 7) months. Partial response to chemotherapy downstaged hepatic deposits such that curative resection was considered technically possible. Single hepatic deposits remained, and all patients were then referred to surgery after the above response was achieved, but the CEA or lesion size began to increase. From one to five (median 2) metastases were resected. Intraoperative ultrasound and careful palpation revealed small lesions not present on preoperative imaging studies in two patients. Several lesions were aggregates of nonviable “ghost cells” with empty outlines resembling viable metastatic cells. One patient is disease free at 15 months, three are alive with recurrent disease at 4, 9, and 16 months, and one has died of disease at 18 months postoperatively. Group 2 consisted of two patients with intrahepatic and limited extrahepatic metastatic deposits involving the abdominal wall in one, and celiac lymph nodes and spleen in the other. Two and 3 months of modulated 5-FU stabilized disease but with significant toxicity. Hepatic and extrahepatic metastases were resected to consolidate therapy. The second patient remains disease free at 18 months, and the other died of disease at 20 months postoperatively. Group 3 included two patients with isolated hepatic recurrences after previous hepatic resections of colorectal metastases. Local progression was noted in both patients
123
TABLE I. Extent of Hepatic Resections Single wedge resection Multiple wedge resections Right posterior segmentectomy Anatomic lobectomy Extended lobectomy Anatomic lobectomy + contralateral wedge resection
3 2 2 2 I I
TABLE 11. Postooerative Comdications Complication
Number
Perihepatic abscess Wound infection Pneumonia Postoperative hemorrhage Pseudomembranous colitis Congestive heart failure Pleural effusion
after 6 and 11 months of modulated 5-FU, but no other lesions developed and both patients subsequently had resections. These patients recurred at 8 and 14 months, and have died of disease at 22 and 36 months, respectively, after reresection. Group 4 consisted of two patients with potentially resectable isolated hepatic metastases treated initially with 5-FU because of patient or physician preference. One patient demonstrated progressive disease after 2 months and underwent resection, but had a recurrence 8 months after resection and died of disease 14 months postoperatively. The other patient had a marginal response, then stable disease during 11 months of 5-FU. A rising CEA prompted surgical evaluation, and a solitary metastasis was resected. This patient remains free of disease at 31 months postoperatively . Single agent 5-FU was used in two patients. Pharmacological modulation of 5-FU with Leucovorin or N-(phosphonacet1y)-L-aspartate (PALA) was employed in the other nine patients. Resections were done with curative intent, and one to five lesions (median 2) per patient measuring I to 17 cm (median 4.8) in greatest diameter were removed with the procedures noted in Table I. All gross disease was resected but microscopically involved margins were found in four patients. Bilobar disease was resected in three patients. Extrahepatic disease was resected in two patients. There were no perioperative deaths in this series of 1 I patients, and complications occurred in five patients (45%), and are noted in Table 11. The median estimated blood loss was 4,700 cc. The median ICU stay was 4 days, and the median hospital stay was 13 days. The mean follow-up for the series is 18.5 months. Three patients are disease free from 15 to 31 months
124
Fowler et al.
TABLE 111. Pattern of Failure Following Hepatic Resection Site of recurrence
Number
Liver only Liver + peritoneal cavity Liver + lung Omentum + brain
postoperatively. Eight patients have developed recurrent disease (Table LII), with a mean and median time to recurrence of 9.1 and 8 months, respectively. Five patients have died of recurrent disease with a mean and median time of 22 and 20 months, respectively. The number of patients in the series is not large enough for meaningful statistical analysis of prognostic variables. At present, none of the variables studied-including the stage of the primary lesion, disease free interval, response to chemotherapy, number and size of hepatic metastases, preoperative CEA level, presence of extrahepatic disease, and involved margins of resectionaiffer significantly between the patients that remain disease free and those who have had recurrent disease.
DISCUSSION Enthusiasm for resection of isolated hepatic colorectal carcinoma metastases has slowly grown [9]. The safety and effectiveness of this treatment method in selected patients has been documented in several series [9-231. Most series report a 5 % perioperative mortality or less and a 5 year survival rate between 25% [ 10,111 and 39% [9], with 21% [lO,l I ] to 29% [9] of patients free of disease. Many authors have looked at the pattern of recurrence, and have tried to determine prognostic factors associated with a poor outcome. There is general agreement that the ideal candidate has a solitary metastasis, involving less than 25% of the hepatic parenchyma, with no extrahepatic disease. Guidelines for resection have been generated by these data, but as Adson [ 181 noted, these indicators are relative, and should only be used to assist in determining the appropriateness of resection. Although the literature is replete with documentation of the efficacy of hepatic resection for metastatic disease, there is little known about the efficacy and safety of hepatic metastasectomy to consolidate systemic chemotherapy. Both Wadler [5]and Attiyeh [20] described one patient each who underwent resection of residual hepatic deposits after systemic chemotherapy, with enduring disease free status. Hughes indicates that some of the patients in their multi-institutional review underwent chemotherapy before hepatic resection, but this is not further clarified [ 1 I]. Chemotherapy prior to hepatic resection is not reported in other recent series. To our knowledge, no prior reports have addressed the rationale of resecting
residual hepatic disease after an attempt at reducing tumor burden with systemic chemotherapy. We made an attempt to identify all patients who underwent resection of hepatic metastasis after systemic chemotherapy so that information concerning the safety of resection in this situation could be ascertained. The number of patients in our series is small, partly due to the fact that in general we tend to observe the “accepted” guidelines for resection of colorectal hepatic metastases. In select circumstances resection was extended to include all gross disease in order to consolidate the response to chemotherapy. There was no mortality within 30 days of resection in this group. Morbidity was similar to other series [ 121 and was clearly related to the extent of the procedure. Relatively short follow-up at this time limits our ability to comment on long-term survival, although our median survival of 20 months compares favorably to other series of hepatic resections. At present three patients with colorectal metastases are disease free greater than 1 year from the time of resection. Hopefully, more definitive statements can be made as these patients are followed. Increasingly effective chemotherapy has resulted in higher clinical response rates, with a moderate improvement in the duration of response, but has had little impact on the long-term survival of patients with unresectable isolated colorectal hepatic metastases [3-81. It is predictable that patients with “resectable” residual hepatic metastases after partial response to systemic chemotherapy may be seen with increased frequency in the future. The question remains whether these patients should undergo resection, or should be considered “unresectable” once they are labeled as such. Similarly there is a question of whether “downstaging” of hepatic metastases promotes surgical re-evaluation as it might in treatment planning for locally advanced primary lesions. It appears that these patients can undergo resection without undue mortality. The long-term effectiveness of such procedures is yet to be determined. However, it must be weighed against the effectiveness of alternative forms of therapy. The long-term survival of patients with unresected hepatic metastases is uniformly poor even after partial response to chemotherapy, and it is in this context that these patients should be considered for aggressive surgical management. Perhaps systemic response to chemotherapy may indeed select out a favorable group of patients who may benefit in terms of longterm survival after resection.
REFERENCES I . American Cancer Society: Cancer Statistics 1986. CA 36( I):% 25, 1986. 2. August DA, Ottow RT, Sugarbaker PH: Clinical perspective of human colorectal cancer metastasis. Cancer Metastasis Rev 3:303-324, 1984. 3. O’Dwyer PJ, Paul AR, Walczak J , Weiner LM, Litwin S, Comis
Liver Resection After Systemic Chemotherapy
4.
5.
6.
7. 8.
9.
10.
11.
RL: Phase I1 study of biochemical modulation of fluorouracil by low-dose PALA in patients with colorectal cancer. J Clin Oncol 8:1497-1503, 1990. Hines JD, Zakem MH, Adelstein DJ, Rustum YM: Treatment of advanced-stage colorectal adenocarcinoma with fluorouracil and high-dose leucovorin calcium: A pilot study. J Clin Oncol 6:142146. 1988. Wadler S, Schwartz EL, Goldman M, Lyver A , Rader M, Zimmerman M, Itri L, Weinberg V , Wiernik PH: Fluorouracil and recombinant alfa-2a-interferon: An active regimen against advanced colorectal carcinoma, J Clin Oncol7: 1769-1775, 1989. Poon MA, O’Connell MJ, Moertel CG, Wieand HS, Cullinan SA, Everson LK, Krook JE, Mailliard JA, Laurie JA, Tschetter LK, Wiesenfeld M: Chemical modulation of fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. J Clin Oncol 7: 1407-1417, 1989. Erlichman C , Fine S, Wong A , Elhakim T: A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma, J Clin Oncol 6:469-475, 1988. Petrelli N, Herrera L, Rustum Y, Burke P, Creaven P, Stulc J , Emrich LJ, Mittelman A: A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and high-dose leucovorin and methotrexate in previously untreated patients with advanced colorectal carcinoma. J Clin Oncol 5:1559-1565, 1987. Scheele J , Stangl R, Altendorf-Hofmann A: Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. BrJ Surg 77:1241-1246, 1990. Hughes KS, Simon R , Songhorabodi S , Adson MA, et al.: Resection of the liver for colorectal carcinoma metastases: A multiinstitutional study of patterns of recurrence. Surgery I OO:278284, 1986. Hughes KS, Simon R, Songhorabodi S, Adson MA, et al.: Resection of the liver for colorectal carcinoma metastases: A multiinstitutional study of indications for resection. Surgery 103:278288, 1988.
125
12. Vetto JF, Hughes KS, Rosenstein R , Sugarbaker PH: Morbidity and mortality of hepatic resection for metastatic colorectal carcinoma. Dis Colon Rectum 33:408413, 1990. 13. Hughes KS, Rosenstein RB, Songhorabodi S, Adson MA, et al.: Resection of the liver for colorectal carcinoma metastases. A multi-institutional study of long-term survivors. Dis Colon Rectum31:14, 1988. 4. 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. Treatement by hepatic resection. Ann Surg 199:30&316, 1984. 5. Steele G, Jr., Osteen RT, Wilson RE, Brooks DC, Mayer RJ, Zaincheck N, Ravikurnar TS: Patterns of failure after surgical cure of large liver tumors. A change in the proximate cause of death and a need for effective systemic adjuvant therapy. Am J Surg 147:554-559, 1984. 6. Fortner JG: Recurrence of colorectal cancer after hepatic resection. Am J Surg 155:378-382, 1988. 7. Bozzetti F, Bignami P, Morabito A. Doci R, Gennari L: Patterns of failure following surgical resection of colorectal cancer liver metastases. Rationale for a multimodal approach. Ann Surg 2051264-270, 1987. 18. Adson MA: Resection of liver metastases-When is it worthwhile? World J Surg 1 1 5 1 1-520. 1987. 19. Petrelli NJ, Nambisan RN, Herrera L, Mittelman A: Hepatic resection for isolated metastasis from colorectal carcinoma. Am J Surg 149:205-209, 1985. 20. Attiyeh FF, Wichern WA, Jr: Hepatic resection for primary and metastatic tumors. Am J Surg 156:368-373, 1988. 2 I . lwatsuki S , Starzl TE: Personal experience with 41 I hepatic resections. Ann Surg 208:421424, 1988. 22. Saenz NC, Cady B, McDermott WV, Jr, Steele GD, Jr: Experience with colorectal carcinoma metastatic to the liver. Surg Clin North Am 69:361-370, 1989. 23. Butler J , Attiyeh FF, Daly JM: Hepatic resection for metastases of the colon and rectum. Surg Gynecol Obstet 162:IOY-1 13, 1986.
Hepatic Resection Following Systemic Chemotherapy for Metastatic Colorectal Carcinoma WYATT C. FOWLER, MD, BURTON L. EISENBERG, MD, FAG, AND JOHN P. HOFFMAN, MU, From the Department of Surgical Oncology, Fox Chase Cancer Center and Schooi of Medicrne, Temple University, Philadelphia, Pennsylvania
FACS
Increasingly effective systemic chemotherapy has improved responses in patients with previously unresectable colorectal hepatic metastases. In the future, response to chemotherapy may define a new population of patients that may benefit from hepatic resection. A retrospective review to determine the safety and effectiveness of potentially curative hepatic resection of metastatic colorectal carcinoma after systemic chemotherapy identified 1 1 such patients with resections between July 1987 and October 1991. Five patients had unresectable disease confined to the liver, two had hepatic and limited extrahepatic metastases, two had hepatic recurrences after previous hepatic metastasectomy, and two had initially resectable liver metastases. These patients were resected after a mean of 8 months of systemic chemotherapy. Complications, usually minor, occurred in five patients (45%). There were no deaths. Three patients are disease free at 15, 18, and 31 months (mean 21) after hepatic resection. Eight patients have recurred with a median time to recurrence of 8 months. Five patients have subsequently died of recurrent disease. This study suggests that hepatic resection following systemic chemotherapy can be performed safely and may benefit selected patients. 0 1992 WiIey-Liss, Inc. KEYWORDS:chemotherapy, downstaging, liver
INTRODUCTION Approximately 50% of the estimated 140,000 patients diagnosed annually in the United States with colorectal carcinoma will develop hepatic metastases during the course of their disease [ 11. Resection of isolated hepatic metastases has been employed with increased frequency, and its therapeutic efficacy has been established. Unfortunately, only 5-1 0% of patients will have metastases amenable to surgical resection [2]. Observation or palliative chemotherapy are the only options available to greater than 90% of patients with colorectal hepatic metastases. Recent series employing pharmacological modulation of fluorouracil (5-FU) have demonstrated partial clinical responses in approximately 45% of patients [3-81. Increasingly at our institution, patients with metastases restricted to the liver who were initially judged unresectable because of the size, number, or location of the meta0 1992 Wiley-Liss, Inc.
static deposits were achieving partial responses to systemic chemotherapy regimes. Some of these patients were downstaged to the point where surgical resection became an option. Because the literature has a void of data analyzing this situation, this retrospective review was undertaken to examine our results following major hepatic resection for a group of patients who had surgery following systemic chemotherapy for treatment of their colorectal liver metastases.
MATERIALS AND METHODS A retrospective chart review of 6 1 consecutive hepatic resections performed at our institution between July 1987 and October 199 1 was initiated to identify all patients 1992. Accepted for publicationJune Address reprint rcquests to Burton L Eisenberg, MD, FACS, Department of Surgical Oncology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 191 I 1.
Liver Resection After Systemic Chemotherapy
who underwent hepatic resection for metastatic colorectal cancer after receiving systemic chemotherapy for these lesions. Patients with hepatic resections following remote adjuvant chemotherapy for the primary lesion were not included. The following prognostic factors were evaluated: site, stage, and treatment of the primary lesion, the disease free interval, the site, number, and extent of recurrence, the preoperative CEA, the nature, duration, and response to chemotherapy.
RESULTS This review identified 11 patients, five male and six female, from 37 to 74 years of age (median 68 years), who underwent resection of hepatic colorectal metastases after receiving systemic chemotherapy for these lesions. All were colon primaries, and disease at the primary site was controlled. The study group was not homogenous, but could be separated into four groups. Group I included five patients with hepatic metastases initially judged unresectable because of the number, size, or location of the lesions. Three of the five patients originally presented with stage D disease and were deemed unresectable at the time of colectomy because of multiple bilobar metastases in two, and a large central lesion involving both lobes in the other. The other two developed multiple hepatic lesions found on CT scans 7 and 12 months after colectomy. AII of these patients were treated with modulated 5-FU for 4 to 27 (median 7) months. Partial response to chemotherapy downstaged hepatic deposits such that curative resection was considered technically possible. Single hepatic deposits remained, and all patients were then referred to surgery after the above response was achieved, but the CEA or lesion size began to increase. From one to five (median 2) metastases were resected. Intraoperative ultrasound and careful palpation revealed small lesions not present on preoperative imaging studies in two patients. Several lesions were aggregates of nonviable “ghost cells” with empty outlines resembling viable metastatic cells. One patient is disease free at 15 months, three are alive with recurrent disease at 4, 9, and 16 months, and one has died of disease at 18 months postoperatively. Group 2 consisted of two patients with intrahepatic and limited extrahepatic metastatic deposits involving the abdominal wall in one, and celiac lymph nodes and spleen in the other. Two and 3 months of modulated 5-FU stabilized disease but with significant toxicity. Hepatic and extrahepatic metastases were resected to consolidate therapy. The second patient remains disease free at 18 months, and the other died of disease at 20 months postoperatively. Group 3 included two patients with isolated hepatic recurrences after previous hepatic resections of colorectal metastases. Local progression was noted in both patients
123
TABLE I. Extent of Hepatic Resections Single wedge resection Multiple wedge resections Right posterior segmentectomy Anatomic lobectomy Extended lobectomy Anatomic lobectomy + contralateral wedge resection
3 2 2 2 I I
TABLE 11. Postooerative Comdications Complication
Number
Perihepatic abscess Wound infection Pneumonia Postoperative hemorrhage Pseudomembranous colitis Congestive heart failure Pleural effusion
after 6 and 11 months of modulated 5-FU, but no other lesions developed and both patients subsequently had resections. These patients recurred at 8 and 14 months, and have died of disease at 22 and 36 months, respectively, after reresection. Group 4 consisted of two patients with potentially resectable isolated hepatic metastases treated initially with 5-FU because of patient or physician preference. One patient demonstrated progressive disease after 2 months and underwent resection, but had a recurrence 8 months after resection and died of disease 14 months postoperatively. The other patient had a marginal response, then stable disease during 11 months of 5-FU. A rising CEA prompted surgical evaluation, and a solitary metastasis was resected. This patient remains free of disease at 31 months postoperatively . Single agent 5-FU was used in two patients. Pharmacological modulation of 5-FU with Leucovorin or N-(phosphonacet1y)-L-aspartate (PALA) was employed in the other nine patients. Resections were done with curative intent, and one to five lesions (median 2) per patient measuring I to 17 cm (median 4.8) in greatest diameter were removed with the procedures noted in Table I. All gross disease was resected but microscopically involved margins were found in four patients. Bilobar disease was resected in three patients. Extrahepatic disease was resected in two patients. There were no perioperative deaths in this series of 1 I patients, and complications occurred in five patients (45%), and are noted in Table 11. The median estimated blood loss was 4,700 cc. The median ICU stay was 4 days, and the median hospital stay was 13 days. The mean follow-up for the series is 18.5 months. Three patients are disease free from 15 to 31 months
124
Fowler et al.
TABLE 111. Pattern of Failure Following Hepatic Resection Site of recurrence
Number
Liver only Liver + peritoneal cavity Liver + lung Omentum + brain
postoperatively. Eight patients have developed recurrent disease (Table LII), with a mean and median time to recurrence of 9.1 and 8 months, respectively. Five patients have died of recurrent disease with a mean and median time of 22 and 20 months, respectively. The number of patients in the series is not large enough for meaningful statistical analysis of prognostic variables. At present, none of the variables studied-including the stage of the primary lesion, disease free interval, response to chemotherapy, number and size of hepatic metastases, preoperative CEA level, presence of extrahepatic disease, and involved margins of resectionaiffer significantly between the patients that remain disease free and those who have had recurrent disease.
DISCUSSION Enthusiasm for resection of isolated hepatic colorectal carcinoma metastases has slowly grown [9]. The safety and effectiveness of this treatment method in selected patients has been documented in several series [9-231. Most series report a 5 % perioperative mortality or less and a 5 year survival rate between 25% [ 10,111 and 39% [9], with 21% [lO,l I ] to 29% [9] of patients free of disease. Many authors have looked at the pattern of recurrence, and have tried to determine prognostic factors associated with a poor outcome. There is general agreement that the ideal candidate has a solitary metastasis, involving less than 25% of the hepatic parenchyma, with no extrahepatic disease. Guidelines for resection have been generated by these data, but as Adson [ 181 noted, these indicators are relative, and should only be used to assist in determining the appropriateness of resection. Although the literature is replete with documentation of the efficacy of hepatic resection for metastatic disease, there is little known about the efficacy and safety of hepatic metastasectomy to consolidate systemic chemotherapy. Both Wadler [5]and Attiyeh [20] described one patient each who underwent resection of residual hepatic deposits after systemic chemotherapy, with enduring disease free status. Hughes indicates that some of the patients in their multi-institutional review underwent chemotherapy before hepatic resection, but this is not further clarified [ 1 I]. Chemotherapy prior to hepatic resection is not reported in other recent series. To our knowledge, no prior reports have addressed the rationale of resecting
residual hepatic disease after an attempt at reducing tumor burden with systemic chemotherapy. We made an attempt to identify all patients who underwent resection of hepatic metastasis after systemic chemotherapy so that information concerning the safety of resection in this situation could be ascertained. The number of patients in our series is small, partly due to the fact that in general we tend to observe the “accepted” guidelines for resection of colorectal hepatic metastases. In select circumstances resection was extended to include all gross disease in order to consolidate the response to chemotherapy. There was no mortality within 30 days of resection in this group. Morbidity was similar to other series [ 121 and was clearly related to the extent of the procedure. Relatively short follow-up at this time limits our ability to comment on long-term survival, although our median survival of 20 months compares favorably to other series of hepatic resections. At present three patients with colorectal metastases are disease free greater than 1 year from the time of resection. Hopefully, more definitive statements can be made as these patients are followed. Increasingly effective chemotherapy has resulted in higher clinical response rates, with a moderate improvement in the duration of response, but has had little impact on the long-term survival of patients with unresectable isolated colorectal hepatic metastases [3-81. It is predictable that patients with “resectable” residual hepatic metastases after partial response to systemic chemotherapy may be seen with increased frequency in the future. The question remains whether these patients should undergo resection, or should be considered “unresectable” once they are labeled as such. Similarly there is a question of whether “downstaging” of hepatic metastases promotes surgical re-evaluation as it might in treatment planning for locally advanced primary lesions. It appears that these patients can undergo resection without undue mortality. The long-term effectiveness of such procedures is yet to be determined. However, it must be weighed against the effectiveness of alternative forms of therapy. The long-term survival of patients with unresected hepatic metastases is uniformly poor even after partial response to chemotherapy, and it is in this context that these patients should be considered for aggressive surgical management. Perhaps systemic response to chemotherapy may indeed select out a favorable group of patients who may benefit in terms of longterm survival after resection.
REFERENCES I . American Cancer Society: Cancer Statistics 1986. CA 36( I):% 25, 1986. 2. August DA, Ottow RT, Sugarbaker PH: Clinical perspective of human colorectal cancer metastasis. Cancer Metastasis Rev 3:303-324, 1984. 3. O’Dwyer PJ, Paul AR, Walczak J , Weiner LM, Litwin S, Comis
Liver Resection After Systemic Chemotherapy
4.
5.
6.
7. 8.
9.
10.
11.
RL: Phase I1 study of biochemical modulation of fluorouracil by low-dose PALA in patients with colorectal cancer. J Clin Oncol 8:1497-1503, 1990. Hines JD, Zakem MH, Adelstein DJ, Rustum YM: Treatment of advanced-stage colorectal adenocarcinoma with fluorouracil and high-dose leucovorin calcium: A pilot study. J Clin Oncol 6:142146. 1988. Wadler S, Schwartz EL, Goldman M, Lyver A , Rader M, Zimmerman M, Itri L, Weinberg V , Wiernik PH: Fluorouracil and recombinant alfa-2a-interferon: An active regimen against advanced colorectal carcinoma, J Clin Oncol7: 1769-1775, 1989. Poon MA, O’Connell MJ, Moertel CG, Wieand HS, Cullinan SA, Everson LK, Krook JE, Mailliard JA, Laurie JA, Tschetter LK, Wiesenfeld M: Chemical modulation of fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. J Clin Oncol 7: 1407-1417, 1989. Erlichman C , Fine S, Wong A , Elhakim T: A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma, J Clin Oncol 6:469-475, 1988. Petrelli N, Herrera L, Rustum Y, Burke P, Creaven P, Stulc J , Emrich LJ, Mittelman A: A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and high-dose leucovorin and methotrexate in previously untreated patients with advanced colorectal carcinoma. J Clin Oncol 5:1559-1565, 1987. Scheele J , Stangl R, Altendorf-Hofmann A: Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. BrJ Surg 77:1241-1246, 1990. Hughes KS, Simon R , Songhorabodi S , Adson MA, et al.: Resection of the liver for colorectal carcinoma metastases: A multiinstitutional study of patterns of recurrence. Surgery I OO:278284, 1986. Hughes KS, Simon R, Songhorabodi S, Adson MA, et al.: Resection of the liver for colorectal carcinoma metastases: A multiinstitutional study of indications for resection. Surgery 103:278288, 1988.
125
12. Vetto JF, Hughes KS, Rosenstein R , Sugarbaker PH: Morbidity and mortality of hepatic resection for metastatic colorectal carcinoma. Dis Colon Rectum 33:408413, 1990. 13. Hughes KS, Rosenstein RB, Songhorabodi S, Adson MA, et al.: Resection of the liver for colorectal carcinoma metastases. A multi-institutional study of long-term survivors. Dis Colon Rectum31:14, 1988. 4. 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. Treatement by hepatic resection. Ann Surg 199:30&316, 1984. 5. Steele G, Jr., Osteen RT, Wilson RE, Brooks DC, Mayer RJ, Zaincheck N, Ravikurnar TS: Patterns of failure after surgical cure of large liver tumors. A change in the proximate cause of death and a need for effective systemic adjuvant therapy. Am J Surg 147:554-559, 1984. 6. Fortner JG: Recurrence of colorectal cancer after hepatic resection. Am J Surg 155:378-382, 1988. 7. Bozzetti F, Bignami P, Morabito A. Doci R, Gennari L: Patterns of failure following surgical resection of colorectal cancer liver metastases. Rationale for a multimodal approach. Ann Surg 2051264-270, 1987. 18. Adson MA: Resection of liver metastases-When is it worthwhile? World J Surg 1 1 5 1 1-520. 1987. 19. Petrelli NJ, Nambisan RN, Herrera L, Mittelman A: Hepatic resection for isolated metastasis from colorectal carcinoma. Am J Surg 149:205-209, 1985. 20. Attiyeh FF, Wichern WA, Jr: Hepatic resection for primary and metastatic tumors. Am J Surg 156:368-373, 1988. 2 I . lwatsuki S , Starzl TE: Personal experience with 41 I hepatic resections. Ann Surg 208:421424, 1988. 22. Saenz NC, Cady B, McDermott WV, Jr, Steele GD, Jr: Experience with colorectal carcinoma metastatic to the liver. Surg Clin North Am 69:361-370, 1989. 23. Butler J , Attiyeh FF, Daly JM: Hepatic resection for metastases of the colon and rectum. Surg Gynecol Obstet 162:IOY-1 13, 1986.
