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Benefits and safety of hepatic resection for colorectal metastases
Benefits and Safety of Hepatic Resection for Colorectal Metastases Kurt E. Harmon, MD, John A. Ryan, Jr., MD, Thomas R. Biehl, MD, Faye T. Lee, RN, Seattle, Washington
BACKGROUND: Metastatic colorectal carcinoma to the liver is a potentially curable disease. The purpose of this study was to determine the safety and efficacy of hepatic resection for metastatic colorectal carcinoma. METHODS: One hundred twenty-one consecutive hepatic resections in 110 patients with metastatic colorectal cancer between January 1978 and September 1998 performed by a single surgeon were reviewed. RESULTS: The actuarial 5-year survival for all patients in the series was 46%. Of the patients operated on before 1993, the actual 5-year survival was 43% and actual disease-free 5-year survival was 28%. The actual 10-year survival was 27%, and of all patients operated on in the last 20 years, 48% are alive today. When comparing initial regional lymph node status, the 5-year survival was 54% for the patients with negative lymph nodes and 40% for patients with positive nodes. Only 18% of patients required a perioperative blood transfusion, and the median length of stay was 7 days. There were complications in 34% of cases, and the operative mortality was 4%. CONCLUSIONS: Hepatic resection for metastatic colon cancer is safe, and significant longevity and cure can be obtained after resection. Am J Surg. 1999;177:402– 404. © 1999 by Excerpta Medica, Inc.
T
he liver is the most common site of metastasis from colorectal cancer. Left untreated, the 5-year survival rate for these patients is 1%.1,2 Adjuvant systemic or regional chemotherapy, radiotherapy, and arterial embolization have shown variable response, but rare long-term survival. Hepatic resection remains the only potentially curative therapy. We evaluated a 20-year experience with hepatic resection by a single surgeon for colorectal metastases in order to determine its safety and efficacy as well as the patient selection criteria.
From the Virginia Mason Medical Center, Seattle, Washington. Requests for reprints should be addressed to John A. Ryan, Jr, MD, Department of Surgery [C6-GSUR], Virginia Mason Medical Center, 1100 Ninth Avenue, PO Box 900, Seattle, Washington 98111. Presented at the 85th Annual Meeting of the North Pacific Surgical Association, Tacoma, Washington, November 13–14, 1998.
402
© 1999 by Excerpta Medica, Inc. All rights reserved.
METHODS Retrospective review was performed of 121 consecutive hepatic resections on 110 patients for metastatic colorectal adenocarcinoma between January 1978 and September 1998. All procedures were performed by a single surgeon (JAR) at Virginia Mason Medical Center. Data were collected via hospital records, computer data base, and patient interviews. Criteria for operative resection were (1) metastatic cancer confined to the liver, (2) anatomic distribution of metastatic cancer such that liver function could be maintained after resection, and (3) patient fitness to withstand the operation. Over 20 years our technique has evolved. Since 1989 all patients had vascular isolation performed by hepatic vein, hepatic artery and portal vein ligation, and intermittent Pringle maneuver or hepatic compression (Storm-Longmire) clamp prior to parenchymal division.3,4 A noncontiguous resection was defined as two separate resections performed at the same procedure (ie, right hepatic lobectomy with wedge resection of left lateral segment). All deaths within 30 days of surgery or during the same hospitalization were considered surgical mortality. Carcinoembryonic antigen (CEA) values were the last recorded level prior to hepatic resection. Transfusions were recorded for the intraoperative and immediate perioperative period. The 5-year survival is determined as time from the patient’s first curative hepatic resection. Both actual and actuarial (Kaplan-Meier) surivivals are described. Multiple chemotherapeutic protocols were employed at various times during the review period. No conclusions were made based on use of chemotherapy. Survival data are recorded as of October 1, 1998 for 107 of 110 patients. All surviving patients were contacted by phone or in person between October 1 and October 18, 1998 (FL). Survival data are complete for all patients operated on prior to 1993. Three patients, after 1993, were lost to follow-up, and thus survival data are recorded up to the last known contact. Statistical Analysis Data were analyzed using the EGRET and BDMP software programs. Survival analysis and Kaplan-Meier curves were confirmed by the Breslow test. Univariate analysis was confirmed by the chi-square test.
RESULTS Demographics One hundred ten patients underwent 121 hepatic resections with the intent for cure. The average age was 63 (range 41 to 90) with a 3:2 male:female ratio. The metastatic lesions were synchronous in 38% of patients (42 of 110) and metachronous in 62% (68 of 110). Of the original 0002-9610/99/$–see front matter PII S0002-9610(99)00070-7
HEPATIC RESECTION FOR COLORECTAL METASTASES/HARMON ET AL
Figure. Actuarial 5-year survival of patients after liver resection.
colorectal cancers 57% (63 of 110) of the patients had regionally positive lymph nodes, while 43% (47 of 110) had negative nodes. Perioperative Data The procedures were 27% trisegmentectomies or extended lobectomies (32 of 121 patients), 28% right hepatic lobectomies (34 of 121), 8% left hepatic lobectomies (10 of 121), 7% left lateral segmentectomies (8 of 121), and 30% partial lobectomies or wedge resections (37 of 121). The average number of metastatic lesions was 2 (range 1 to 12. The average size of the metastatic lesion was 5 cm (range 0.5 cm to 17cm). The median blood loss was 425 cc, and perioperative blood transfusions were used in 18% of patients (22 of 121). The median length of stay was 7 days (range 4 to 34 days). Complications developed in 34% of all procedures (41 of 121). The most common complications were bile leak (7 patients) and atrial fibrillation (7 patients), none of which led to death. There were 5 perioperative deaths in 121 procedures for a mortality of 4%. In the last 10 years the perioperative mortality was 2% (2 of 93). Deaths were due to intraoperative bleeding, hepatic vein thrombosis, adult respiratory distress syndrome, bleeding duodenal ulcer, and disseminated intravascular coagulation with adrenal hemorrhage secondary to deep venous thrombosis. Long-term Survival The Kaplan-Meier survival curve in the Figure illustrates the long-term survival after liver resection. The actual 5-year survival was 43% (26 of 60) for all patients operated on 5 or more years ago, and the actuarial 5-year survival for all patients was 46% by Kaplan-Meier curve. The actual disease-free 5-year survival was 28% (17 of 60), and the
median survival was 42 months. The actual 10-year survival was 27% (6 of 22) for all patients operated on before 1988. Furthermore, 48% (53 of 110) of all patients operated on in the last 20 years are alive today, including 5 of 10 patients (50%) who had more than one major hepatic resection for recurrent disease. Six of the 7 patients with multiple liver procedures with 5-year follow-up lived more than 5 years (86%). Univariate Predictors of 5-year Outcome Table I summarizes the outcome trends for many common predictors of outcome after liver resection. There was a statistically improved survival with lesions less than 5 cm and those found at the time of colorectal excision. Although the other variables did not reach statistical significance, a trend toward worse outcome was found in patients with positive colorectal lymph nodes, older age, elevated CEA, and noncontiguous resections. No individual variable had an actuarial 5-year survival less than 20%.
COMMENTS Metastatic colorectal cancer confined to the liver is potentially curable. Many large reviews have shown that surgical resection is curative approximately one third of the time. The current study supports both the efficacy of resection and its perioperative safety. The actuarial 5-year survival rate for all patients was 46 % (Table II) with a perioperative morbidity and mortality that is acceptable. Also, since the nonoperative management of metastatic colon cancer has a 5-year survival of 1%,1 hepatic resection is not only the best option but also one that is safe and well tolerated. Several predictors of improved 5-year survival in colorectal metastasis have been suggested. They include young
THE AMERICAN JOURNAL OF SURGERY® VOLUME 177 MAY 1999
403
HEPATIC RESECTION FOR COLORECTAL METASTASES/HARMON ET AL
TABLE II
TABLE I Predictors of 5-year Survival Variable Overall Gender Male Female Age ,75 years $75 years Tumor node status Node negative Node positive Preresection CEA level ,30 ng/mL .30 ng/mL Liver metastasis diagnosis Synchronous Metachronous Size of metastasis ,5 cm .5 cm Number liver metastasis 1 2–4 .4 Type of resection Contiguous Noncontiguous Transfusion No Yes
Number of Patients
5-Year Survival
110
46%
Actuarial 5-year Survival after Hepatic Resection P Value 0.51
65 45
47% 45%
94 16
52% 20%
47 63
54% 40%
0.11
0.11
Foster5 Adson6 Hughes7 Iwatsuki/ Starzl8 Fong9 Current series
Year
Number of Resections
5-Year Survival
Multiinstitutional Mayo Clinic Multiinstitutional
1978 1984 1988
170 141 859
20% 25% 33%
Pittsburg/Colorado MSKCC
1988 1997
90 456
36% 38%
Virginia Mason
1998
121
46%
Institution
MSKCC 5 Memorial Sloan-Kettering Cancer Center.
0.076 64 42
56% 38%
42 68
56% 40%
58 51
55% 38%
51 50 8
38% 57% 46%
88 22
49% 43%
89 21
46% 47%
0.004
0.007
0.65
0.43
0.08
CEA 5 carcinoembryonic antigen.
age, negative colorectal nodes, single hepatic lesions, small lesion size, lesions isolated to a single liver lobe, low CEA levels, and absence of transfusions.3,4,9 The present study found evidence supporting these variables. Liver lesions less than 5 cm and synchronous lesions independently conferred a statistically greater survival. Preoperative age less than 75, negative colorectal nodes, and CEA ,30 ng/mL all demonstrated trends toward increased survival, but were not statistically significant (Table I). Most importantly however, no independent factor was shown to be exclusionary when considering a patient for resection. The classic poor prognostic indicators of age greater than 75, lesions greater than 5 cm, lesion number greater than 4, noncontiguous resections, and CEA above 30 all independently demonstrated actuarial 5-year survival still greater than 20%. In addition, patients undergoing hepatic resection had minimal short-term morbidity. The length of hospitalization was on average only 7 days, over 80% did not receive blood products, and only a single patient had a long-term complication (stroke). Ten patients had isolated recurrence of their hepatic disease after resection in an anatomically resectable location. They therefore remained operative candidates and went on to second resection. One
404
Author
patient, with three separate resections, is alive without recurrence 11 years after his last procedure. With 150,000 new cases of colorectal cancer each year and approximately 10,000 with metastases confined to the liver, a large subset of patients are dying of potentially curable disease. Even those with less favorable preoperative indicators have a far superior outcome to nonoperative treatment alone and should not be excluded from surgical consideration. With proper surgical technique and sound perioperative care the morbidity and mortality is acceptably low. This and previous papers demonstrate that surgical resection of metastatic disease to the liver is not only safe but is also curative in many and provides significant long-term survival. We recommend that any patient with metastatic disease confined to the liver, an anatomic distribution of tumors to preserve hepatic function after resection, and fitness to withstand the procedure should be considered for resection.
REFERENCES 1. Wagner JS, Adson MA, van Heerden JA, et al. The natural history of hepatic metastases from colorectal cancer: a comparison with resective treatment. Ann Surg. 1994;199:502–508. 2. 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. 3. Ryan JA, Faulkner DJ. Liver resection without blood transfusion. Am J Surg. 1989;208:679 – 688. 4. Ryan JA, Woods MS. Benefits and safety of hepatic resection for metastases from colorectal carcinoma. Virginia Mason Clin Bull. 1994;48:13–24. 5. Foster JH. Survival after lifer resection for secondary tumors. Am J Surg. 1978;135:389 –394. 6. Adson MA, van Heerden JA, Adson MH, et al. Resection of hepatic metastases from colorectal cancer. Arch Surg. 1984;119: 647– 651. 7. Hughes KS, Simon R, Songhorabodi S, et al. Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence. Surgery. 1986;100:278 –284. 8. Iwatsuki S, Starzl TE. Personal experience with 411 hepatic resection. Ann Surg. 1988;208:421– 434. 9. Fong Y, Cohen AM, Fortner JG, et al. Liver resection for colorectal metastases. J Clin Oncol. 1997;15:938 –946.
THE AMERICAN JOURNAL OF SURGERY® VOLUME 177 MAY 1999
BACKGROUND: Metastatic colorectal carcinoma to the liver is a potentially curable disease. The purpose of this study was to determine the safety and efficacy of hepatic resection for metastatic colorectal carcinoma. METHODS: One hundred twenty-one consecutive hepatic resections in 110 patients with metastatic colorectal cancer between January 1978 and September 1998 performed by a single surgeon were reviewed. RESULTS: The actuarial 5-year survival for all patients in the series was 46%. Of the patients operated on before 1993, the actual 5-year survival was 43% and actual disease-free 5-year survival was 28%. The actual 10-year survival was 27%, and of all patients operated on in the last 20 years, 48% are alive today. When comparing initial regional lymph node status, the 5-year survival was 54% for the patients with negative lymph nodes and 40% for patients with positive nodes. Only 18% of patients required a perioperative blood transfusion, and the median length of stay was 7 days. There were complications in 34% of cases, and the operative mortality was 4%. CONCLUSIONS: Hepatic resection for metastatic colon cancer is safe, and significant longevity and cure can be obtained after resection. Am J Surg. 1999;177:402– 404. © 1999 by Excerpta Medica, Inc.
T
he liver is the most common site of metastasis from colorectal cancer. Left untreated, the 5-year survival rate for these patients is 1%.1,2 Adjuvant systemic or regional chemotherapy, radiotherapy, and arterial embolization have shown variable response, but rare long-term survival. Hepatic resection remains the only potentially curative therapy. We evaluated a 20-year experience with hepatic resection by a single surgeon for colorectal metastases in order to determine its safety and efficacy as well as the patient selection criteria.
From the Virginia Mason Medical Center, Seattle, Washington. Requests for reprints should be addressed to John A. Ryan, Jr, MD, Department of Surgery [C6-GSUR], Virginia Mason Medical Center, 1100 Ninth Avenue, PO Box 900, Seattle, Washington 98111. Presented at the 85th Annual Meeting of the North Pacific Surgical Association, Tacoma, Washington, November 13–14, 1998.
402
© 1999 by Excerpta Medica, Inc. All rights reserved.
METHODS Retrospective review was performed of 121 consecutive hepatic resections on 110 patients for metastatic colorectal adenocarcinoma between January 1978 and September 1998. All procedures were performed by a single surgeon (JAR) at Virginia Mason Medical Center. Data were collected via hospital records, computer data base, and patient interviews. Criteria for operative resection were (1) metastatic cancer confined to the liver, (2) anatomic distribution of metastatic cancer such that liver function could be maintained after resection, and (3) patient fitness to withstand the operation. Over 20 years our technique has evolved. Since 1989 all patients had vascular isolation performed by hepatic vein, hepatic artery and portal vein ligation, and intermittent Pringle maneuver or hepatic compression (Storm-Longmire) clamp prior to parenchymal division.3,4 A noncontiguous resection was defined as two separate resections performed at the same procedure (ie, right hepatic lobectomy with wedge resection of left lateral segment). All deaths within 30 days of surgery or during the same hospitalization were considered surgical mortality. Carcinoembryonic antigen (CEA) values were the last recorded level prior to hepatic resection. Transfusions were recorded for the intraoperative and immediate perioperative period. The 5-year survival is determined as time from the patient’s first curative hepatic resection. Both actual and actuarial (Kaplan-Meier) surivivals are described. Multiple chemotherapeutic protocols were employed at various times during the review period. No conclusions were made based on use of chemotherapy. Survival data are recorded as of October 1, 1998 for 107 of 110 patients. All surviving patients were contacted by phone or in person between October 1 and October 18, 1998 (FL). Survival data are complete for all patients operated on prior to 1993. Three patients, after 1993, were lost to follow-up, and thus survival data are recorded up to the last known contact. Statistical Analysis Data were analyzed using the EGRET and BDMP software programs. Survival analysis and Kaplan-Meier curves were confirmed by the Breslow test. Univariate analysis was confirmed by the chi-square test.
RESULTS Demographics One hundred ten patients underwent 121 hepatic resections with the intent for cure. The average age was 63 (range 41 to 90) with a 3:2 male:female ratio. The metastatic lesions were synchronous in 38% of patients (42 of 110) and metachronous in 62% (68 of 110). Of the original 0002-9610/99/$–see front matter PII S0002-9610(99)00070-7
HEPATIC RESECTION FOR COLORECTAL METASTASES/HARMON ET AL
Figure. Actuarial 5-year survival of patients after liver resection.
colorectal cancers 57% (63 of 110) of the patients had regionally positive lymph nodes, while 43% (47 of 110) had negative nodes. Perioperative Data The procedures were 27% trisegmentectomies or extended lobectomies (32 of 121 patients), 28% right hepatic lobectomies (34 of 121), 8% left hepatic lobectomies (10 of 121), 7% left lateral segmentectomies (8 of 121), and 30% partial lobectomies or wedge resections (37 of 121). The average number of metastatic lesions was 2 (range 1 to 12. The average size of the metastatic lesion was 5 cm (range 0.5 cm to 17cm). The median blood loss was 425 cc, and perioperative blood transfusions were used in 18% of patients (22 of 121). The median length of stay was 7 days (range 4 to 34 days). Complications developed in 34% of all procedures (41 of 121). The most common complications were bile leak (7 patients) and atrial fibrillation (7 patients), none of which led to death. There were 5 perioperative deaths in 121 procedures for a mortality of 4%. In the last 10 years the perioperative mortality was 2% (2 of 93). Deaths were due to intraoperative bleeding, hepatic vein thrombosis, adult respiratory distress syndrome, bleeding duodenal ulcer, and disseminated intravascular coagulation with adrenal hemorrhage secondary to deep venous thrombosis. Long-term Survival The Kaplan-Meier survival curve in the Figure illustrates the long-term survival after liver resection. The actual 5-year survival was 43% (26 of 60) for all patients operated on 5 or more years ago, and the actuarial 5-year survival for all patients was 46% by Kaplan-Meier curve. The actual disease-free 5-year survival was 28% (17 of 60), and the
median survival was 42 months. The actual 10-year survival was 27% (6 of 22) for all patients operated on before 1988. Furthermore, 48% (53 of 110) of all patients operated on in the last 20 years are alive today, including 5 of 10 patients (50%) who had more than one major hepatic resection for recurrent disease. Six of the 7 patients with multiple liver procedures with 5-year follow-up lived more than 5 years (86%). Univariate Predictors of 5-year Outcome Table I summarizes the outcome trends for many common predictors of outcome after liver resection. There was a statistically improved survival with lesions less than 5 cm and those found at the time of colorectal excision. Although the other variables did not reach statistical significance, a trend toward worse outcome was found in patients with positive colorectal lymph nodes, older age, elevated CEA, and noncontiguous resections. No individual variable had an actuarial 5-year survival less than 20%.
COMMENTS Metastatic colorectal cancer confined to the liver is potentially curable. Many large reviews have shown that surgical resection is curative approximately one third of the time. The current study supports both the efficacy of resection and its perioperative safety. The actuarial 5-year survival rate for all patients was 46 % (Table II) with a perioperative morbidity and mortality that is acceptable. Also, since the nonoperative management of metastatic colon cancer has a 5-year survival of 1%,1 hepatic resection is not only the best option but also one that is safe and well tolerated. Several predictors of improved 5-year survival in colorectal metastasis have been suggested. They include young
THE AMERICAN JOURNAL OF SURGERY® VOLUME 177 MAY 1999
403
HEPATIC RESECTION FOR COLORECTAL METASTASES/HARMON ET AL
TABLE II
TABLE I Predictors of 5-year Survival Variable Overall Gender Male Female Age ,75 years $75 years Tumor node status Node negative Node positive Preresection CEA level ,30 ng/mL .30 ng/mL Liver metastasis diagnosis Synchronous Metachronous Size of metastasis ,5 cm .5 cm Number liver metastasis 1 2–4 .4 Type of resection Contiguous Noncontiguous Transfusion No Yes
Number of Patients
5-Year Survival
110
46%
Actuarial 5-year Survival after Hepatic Resection P Value 0.51
65 45
47% 45%
94 16
52% 20%
47 63
54% 40%
0.11
0.11
Foster5 Adson6 Hughes7 Iwatsuki/ Starzl8 Fong9 Current series
Year
Number of Resections
5-Year Survival
Multiinstitutional Mayo Clinic Multiinstitutional
1978 1984 1988
170 141 859
20% 25% 33%
Pittsburg/Colorado MSKCC
1988 1997
90 456
36% 38%
Virginia Mason
1998
121
46%
Institution
MSKCC 5 Memorial Sloan-Kettering Cancer Center.
0.076 64 42
56% 38%
42 68
56% 40%
58 51
55% 38%
51 50 8
38% 57% 46%
88 22
49% 43%
89 21
46% 47%
0.004
0.007
0.65
0.43
0.08
CEA 5 carcinoembryonic antigen.
age, negative colorectal nodes, single hepatic lesions, small lesion size, lesions isolated to a single liver lobe, low CEA levels, and absence of transfusions.3,4,9 The present study found evidence supporting these variables. Liver lesions less than 5 cm and synchronous lesions independently conferred a statistically greater survival. Preoperative age less than 75, negative colorectal nodes, and CEA ,30 ng/mL all demonstrated trends toward increased survival, but were not statistically significant (Table I). Most importantly however, no independent factor was shown to be exclusionary when considering a patient for resection. The classic poor prognostic indicators of age greater than 75, lesions greater than 5 cm, lesion number greater than 4, noncontiguous resections, and CEA above 30 all independently demonstrated actuarial 5-year survival still greater than 20%. In addition, patients undergoing hepatic resection had minimal short-term morbidity. The length of hospitalization was on average only 7 days, over 80% did not receive blood products, and only a single patient had a long-term complication (stroke). Ten patients had isolated recurrence of their hepatic disease after resection in an anatomically resectable location. They therefore remained operative candidates and went on to second resection. One
404
Author
patient, with three separate resections, is alive without recurrence 11 years after his last procedure. With 150,000 new cases of colorectal cancer each year and approximately 10,000 with metastases confined to the liver, a large subset of patients are dying of potentially curable disease. Even those with less favorable preoperative indicators have a far superior outcome to nonoperative treatment alone and should not be excluded from surgical consideration. With proper surgical technique and sound perioperative care the morbidity and mortality is acceptably low. This and previous papers demonstrate that surgical resection of metastatic disease to the liver is not only safe but is also curative in many and provides significant long-term survival. We recommend that any patient with metastatic disease confined to the liver, an anatomic distribution of tumors to preserve hepatic function after resection, and fitness to withstand the procedure should be considered for resection.
REFERENCES 1. Wagner JS, Adson MA, van Heerden JA, et al. The natural history of hepatic metastases from colorectal cancer: a comparison with resective treatment. Ann Surg. 1994;199:502–508. 2. 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. 3. Ryan JA, Faulkner DJ. Liver resection without blood transfusion. Am J Surg. 1989;208:679 – 688. 4. Ryan JA, Woods MS. Benefits and safety of hepatic resection for metastases from colorectal carcinoma. Virginia Mason Clin Bull. 1994;48:13–24. 5. Foster JH. Survival after lifer resection for secondary tumors. Am J Surg. 1978;135:389 –394. 6. Adson MA, van Heerden JA, Adson MH, et al. Resection of hepatic metastases from colorectal cancer. Arch Surg. 1984;119: 647– 651. 7. Hughes KS, Simon R, Songhorabodi S, et al. Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence. Surgery. 1986;100:278 –284. 8. Iwatsuki S, Starzl TE. Personal experience with 411 hepatic resection. Ann Surg. 1988;208:421– 434. 9. Fong Y, Cohen AM, Fortner JG, et al. Liver resection for colorectal metastases. J Clin Oncol. 1997;15:938 –946.
THE AMERICAN JOURNAL OF SURGERY® VOLUME 177 MAY 1999