- Email: [email protected]
Hepatic resection for metastatic cancer
Hepatic
Resection
for Metastatic
Cancer
LATHAM FLANAGAN, JR., M.D.* AND JAMES H. FOSTER, M.D.,~ Portland,
From the Department of Surgery, University of Oregon Medical School, and the Portland Veterans Administrat ion Hospital, Portland) Oregon.
R
CLINICAL
Oregon
MATERIAL
We were able to find thirty-two reports concerning seventy-two patients who survived hepatic resection for metastatic cancer [I-42]. Analysis of these reports forms the basis of this review. The authors of these reports were contacted and current follow-up data were obtained when available. Patients are included in this study when definite information was available concerning the type of primar? tumor, the type of resection, and the length of follow-up study outside the hospital. Patients undergoing hepatic resection in continuity with the primary tumor in order to satisfy the en bloc principle are not included. Patients undergoing hepatic resection for functioning carcinoid metastases are also excluded since clinical experience has clearly shown that in this particular syndrome palliation can be expected when the removal of the carcinoid metastases is technically feasible [431. To determine which patients might benefit
ECENT experience with a patient who under-
went major hepatic resection for metastatic cancer at the Portland Veterans Administration Hospital has raised two fundamental questions: Can palliation be achieved by the resection of hepatic metastases? Does the possibility of significantly benefiting the patient outweigh the risk of hepatic resection? We were unable to find a recent survey of clinical experience which might suggest answers to these important questions. This collected review was, therefore, undertaken to provide this information. CASE REPORT
The patient (R. L.), a sixty-eight year old white man, was admitted to the Portland Veterans Administration Hospital in October 1959. A subtotal gastric resection was performed for a large antral adenocarcinoma without evidence of metastasis. Five years later, in October 1964, he was readmitted with a short history of severe pain and early satiety related to a rapidly enlarging right abdominal mass. Laparotomy revealed replacement of the right lobe of the liver by a mass measuring 18 by 15 by 10 cm. (Fig. I.) Since there was no evidence of other metastases, a subtotal right hepatic lobectomy was performed. The resected tumor and a 2 to 3 cm. margin of liver parenchyma weighed 1,330 g-m. and proved to be metastatic adenocarcinoma, histologically similar to the previously resected gastric tumor. The patient’s symptoms were relieved postoperatively. He lived comfortably at home for a few months and then his condition deteriorated rapidly over a two week course and he died five months after hepatic resection, Autopsy revealed a recurrence of tumor in the right upper quadrant at the line of resection and in the retroperitoneal nodes as well as bilateral pulmonary metastases.
FIG. 1. The line of resection of the right lobe of the liver is represented by the dotted line.
* PRESEXTADDRESS:U. S. Naval Hospital, y. FPO, San Francisco, California 96630. t PRESENTADDRESS:Department of Surgery, Hartford Hospital, Hartford, Connecticut 06115 V-01.11.7.April
1967
551
552
Flanagan and Foster
SURVIVAL RELATED TO INTERVAL BETWEEN
Data
None
TABLE I RESECTION OF PRIMARY TUMOR AND RESECTION
Interval between Operations Less than Two Years
25 26 16 8 (46%) 3 (14%)
Number of patients Average survival (mo.) Median survival (mo.) Two year survivalt Five year survivalt
17 33 24 9 (69%) 3 (21%)
RESULTS
The clinical results achieved in the seventytwo patients who survived hepatic resection for metastatic cancer are presented in Table I. The average length of survival for the group
METASTASES
Total No. of Cases
More than Two Years 28 36
72* 31
:: (50%) 6 (29%)
:: (51%) 12 (24%)
* Interval not known in two patients. t Corrected to include only patients followed until end of interval or death (determinate
from hepatic resection for metastatic cancer we have related length of survival to (1) type of primary tumor, (2) type of hepatic resection, (3) number of metastatic deposits, and (4) interval of time between resection of the primary tumor and resection of the hepatic metastases.
OF HEPATIC
survival).
was thirty-one months, with a median survival time of eighteen months after hepatic resection. Twelve patients lived at least five years. (Table II.) Twenty-one of the patients were still alive when their cases were reported but had not yet lived five years. Fifty-one patients were followed up for five years or until death and were used to calculate a corrected five year survival rate of 23.6 per cent. Thirty patients survived at least two years for a corrected two year survival rate of 50.S per cent. The operative mortality for patients under-
TABLE II CLINICAL HISTORY OF PATIENTS SURVIVING FIVE YEARS OR MORE
Author
Zge (yr.) & sex of Patient
Tumor
of
Interval between Operations
Type of Liver Metastasis
Type of Resection
Right lobectomy
Alive with disease at 5.66 yr.
Right wedge Right lobectomy
Living and well at 9.5 yr. Died with disease at 5.5 yr. Dead at 5 yr. Living and well at 7.5 yr.
29, F
Cancer of rectum
6 m”.
Multiple nodule:. one measuring 4 by 4 by 4.5 cm. Solitary nodule
46, M
of
4 yr.
Islet cell tumor
60, F 52, M
M&~“S~~C”tIl~ Cancer of cecum
0 1 yr., 5 mo
Hittner [131
42, M
cancer of colon
0
Mass measuring 20 cm. involving diaphragm and abdominal wall also Solitary nodule
McKirdie
50, M
cancer of colon
4 yr.
Solitary nodule
Left lateral segment
0
“Nut-sized” nodule
solitarv
Right wedge
5 In”.
“Hen’s egg” solitary nodule Solitary black mass of 7 cm. Solitary tumor of 1,500 gm. Solitary nodule
Right wedge
Woodington and Waugh [42]
Peden and Blalock 125 I
[Zl]
75, F
cancer
4 yr.
Pineau, and Chaleil [7] Buff% [5]
?, M
Cancer of sigmoid
67, M
Cancer of sigmoid
Pack [23]
40, F
Melanoma of eye
Straus and Scanlon [36] Miller [ZZ]
62, F
Cancer of kidney
5 yr.
29, F
,Gran1dosa cell car-
10 yr.
cinoma of “vary
13 yr.
Follow-Up Study
Left wedge Right extended lobectomy Right wedge
Right wedge Left lateral segment Right wedge
American
Living and well at 10 Yr. Died of stroke at 12 no evidence yr., of tumor Living and well at 7 Yr. Living and well at 8 Yr. Died at 6 yr. Living ilod well at 15 Yr. Living and wel! at 6 yr.
Jo~~wtal
of Suvgery
Hepatic Resection for Metastatic TABLE SI.R\‘I!‘AL
RELATED
TO INTERVAL
BETWEEN
RESECTION
IN PATIENTS
1)ata
Number of patients Average survival (mo.) Median survival (mo.) Five year survival
Xone
III
OF PRIMARY
WITH
PRIMARY
TUMOR
AND
CARCINOMA
Interval between Operations Less than Two Years 15 37 26
15 29 16
RESECTION
OF HEPATIC
METASTASES
OF COLON
More than Two Years 14 38 18
3 (33%)
2 (IS%)
553
Cancer
2 (20%)
Total
45* 32 18 7 (23%)
* Interval not available for one patient.
were analyzed. The results suggest that there is no improvement in survival with increasing interval. (Table III.) In Table IV survival is related to the type of primary tumor. There is a significant difference in survival between patients with tumors primary in the stomach and those with tumors primary in the colon. There were seven patients who survived five years (23.3 per cent) among those with carcinoma of the colon and none among those with carcinoma of the stomach. Of those seventeen patients whose primary tumors arose outside of the gastrointestinal tract, five survived at least five years after resection of hepatic metastases. Patient survival figures for the various types of hepatic resection are compared in Table v. The nomenclature of the resections is based upon the anatomic rather than the “classic” divisions of the liver. The classic right lobectomy, which includes all tissue to the right of the falciform ligament, is known as a right extended lobectomy. The classic left lobectomy is known as a left lateral segmentectomy. The term “metastasectomy” means excision of the
going hepatic resection for metastatic cancer varies widely in published reports. Brunschwig reported a 29 per cent mortality after twentyfour major lobectomies for cancer metastatic to or with direct extension into the liver [3]. On the other hand, Woodington and Waugh, reporting a similar series from the Mayo Clinic, described only one death with twenty-five resections [42]. The possible effect upon survival of the interval of time between resection of the primary tumor and resection of the hepatic metastases for all seventy-two patients can be derived from the figures in Table I. The figures for synchronous resection of metastases are found in column 2. The metachronous resections of metastases are arbitrarily divided into intervals of less than two years and greater than two years. There is little difference between the median and the two year survival figures, but there does seem to be some improvement in five year survival with increasing interval. To obtain a more homogenous group for analysis, only cases in which there were metastases from a primary tumor of the colon TABLE RELATION
Data
Number of patients Mean survival (mo.) Median survival (mo.) Two year survivalf Five year survival $
Carcinoma of Colon 45 32 :: (53%) 7 (23%)
OF SURVIVAL
IV
TO TYPE
OF PRIMARY
TUMOR
Carcinoma of Stomach
Sarcoma*
9 17 17 3 (43%) 0
5 55 42 4 (166%) 2 (67%)
Other Locations Carcinomat 13 38 12 4 (31%) 3 (23%)
* Included are melanoma of skin in (1) and of eye (2); leiomyosarcoma of stomach (1) and of omentum t Carcinoma of pancreas (4), uterus (3), kidney (2), ovary (2), breast (l), and lung (1). 1 Determinate survival. Vol. 11.3. iipvil
1967
(1)
of
Flanagan
554
and Foster
TABLE v SURVIVAL RELATEDTO TYPE OF HEPATIC RESECTION
Data
Right Lobectomy
Right Extended Lobectomy
Left Lateral Segment Resection
Number of patients Mean survival (mo.) Median survival (mo.) Two year survival* Five year survival*
15 24 20 54% (7) 25% (2)
5 26 12 20% (1) 29%(l)
22 31 18 53% (8) 15%(2)
* Determinate
COMMENTS
The presence of metastatic carcinoma in the liver is considered by many surgeons to be a relative criterion of unresectability and an TABLE VI SURVIVALRELATEDTO NUMBEROF HEPATICMETASTASES
Number of patients Mean survival (mo.) Median survival (mo.) Two year survival* Five year survival* * Determinate
2 26 50%(l)
Metastasectomy
Multiple Segments
21 41 24 55% (16)
6 23 18 33% (2)
39% (7)
survival.
metastasis plus sufficient liver tissue to obtain an adequate margin, and includes both wedge resections and partial lobectomies. The final column, titled “multiple segments,” represents cases in which the tumor was not confined to one lobe and a combination of resections was performed. It is of special interest that the survival figures reflect quite favorably upon the lesser operations of wedge resection or metastasectomy. The question of whether patients with a solitary hepatic metastasis have an improved survival over patients with multiple metastases appears resolved in Table VI. There is marked difference in all of the parameters of survival, including a 39 per cent five year survival rate for the group with a solitary metastasis.
Data
Quadrate Lobectomy
Solitary Metastasis
Multiple Metastasis
All Cases
34
38
72
44
19
31
24
16
18
78% (21)
27% (8)
51% (30)
39% (9)
12% (3)
24% (12)
survival.
absolute criterion of incurability. The figures presented previously herein refute this concept. There is a small but definite group of patients who will apparently be benefited by excision of hepatic metastases. How many patients have technically resectable hepatic metastases? Raven reported 818 patients with cancer of the stomach, colon, or rectum from the Royal Marsden Hospital [44]. One hundred eighty-six (23 per cent) of these patients had hepatic metastases and forty-two (5 per cent) had metastases that were judged resectable on the basis of a solitary metastasis or multiple metastases confined to one lobe. This author concludes that one of every twenty patients operated upon for cancer of the gastrointestinal tract had technically resectable hepatic metastases. What is the natural history of patients found to have metastatic carcinoma in the liver? This is a difficult question to answer on the basis of published reports. Modlin and Walker reported on seventeen patients with cancer of the colon metastatic to the liver [45]. The average patient survived eleven months and none survived five years. Review of the Tumor Clinic files at the Portland Veterans Administration Hospital reveals twenty-six patients who were found to have carcinoma of the colon or rectum metastatic to the liver at laparotomy. The average patient survived six months and none survived five years. The figures for these two groups are used as controls and are compared to the results of this review in Table VII. This comparison may not be valid because the control groups reflect the fate of patients with all degrees of hepatic metastatic disease, not just those with tumors amenable to resection. Also, the group with resection may not American
Journal of Surgery
Hepatic
Resection
for Metastatic TABLE
SURVIVAL
Number of patients Mean survival (mo.) Median survival (mo.) Two year survival* Five year survival*
17 11.2 1:70 0
2A 5 4 (3)
5
4%(l) 0
METASTASES
43 x2 fj 9% (4) 0
YWith Hepatic Primary Carcinema of Colon
Resectiwl
45 32 18 53% (19) 23% (7)
72 31
-- -..
All Caw
.Z% (30) 23 (12)
survival.
be entirely representative of all patients undergoing resection of hepatic metastases because of the natural bias of the medical writer to report successful cases while leaving failures unreported. Nevertheless, the results obtained from the analysis of these seventy-two cases are impressive. Twenty-four per cent of the fifty-one patients who were followed up for five years or until death lived at least five years, as compared to 0 per cent of the controls; 51 per cent of the fifty-nine patients who were followed up for two years or until death lived at least two years, as compared to 9 per cent of the controls. These figures strongly suggest that resection of hepatic metastases is worth-while for the selected patient. Many contributions are responsible for the declining and now acceptable operative risk for major hepatic resection by skillful surgeons. Among these are advances in the understanding of intrahepatic anatomy [46-48], advances in operative technics [20,29,49,50], and advances in the understanding of pre- and postoperative hepatic pathophysiology [SI ]. The mortality for major hepatic surgery for metastatic cancer is difficult to document. The wide variation between published reports may be related not only to the skill of the surgeon and the physiologic reserve of the patient but perhaps also to the type of resection elected. Brunschwig’s 29 per cent mortality with twenty-four major lobectomies included a 50 per cent mortality with eight right extended lobectomies, an operation in which nearly 80 per cent of the liver was resected. The Mayo Clinic’s -l per cent mortality with ten major lobectomies and fifteen partial lobectomies included eight right lobectomies, but it is not certain whether any of these were right exVol. 113, April
VII
HEPATIC
Without Hepatic Resection in Primarv Carcinoma of Colon-Portland Veterans Combined Modlin and Administration Series Walker (451 Hospital
Data
* Determinate
WITH
Cancer
1’167
tended lobectomies. In light of the differences in mortality and approach to resection, it is of considerable interest that there was only one patient who survived five years in Brunschwig’s series, whereas there were seven patients who survived five years in the Mayo Clinic series. It is an unexpected finding that the results obtained by simple “metastasectomy” with a narrow margin of uninvolved liver were as good, if not better, than the results obtained by major hepatic lobectomy. This finding suggests that intralobar redissemination of metastatic cancer may be a late phenomenon and that the grossly identifiable tumor at laparotomy may be the only tumor present. In this regard Pack studied one hundred patients with cancer of the gastrointestinal tract who died in the postoperative period after resection of the primary tumor [52]. The livers of these patients had been judged by the surgeon at laparotomy to be free of metastasis. Only five patients had hidden metastases at autopsy and only two of these were macroscopic. We were surprised to find that the interval between resection of the primary tumor and resection of the hepatic metastases had little correlation with subsequent length of survival. Brunschwig found the same lack of correlation in his own series [3]. In patients whose hepatic metastases are not demonstrable until two or more years after resection of the primary tumor, it would seem that a favorable host-tumor biologic relationship has existed. In the past, these patients have been considered tnore favorable candidates for further surgical palliation. The findings of this study suggest that this favorable host-tumor relationship no longer exists when the metastases become
Flanagan
556
clinically evident, and that all patients with hepatic metastases should be approached similarly without regard to the time of discovery of the metastases. One of the more impressive findings of this review is the difference in length of survival between patients with a solitary hepatic metastasis and those with multiple metastases. The reason for this is not clear. No conclusion can be drawn about the relation between prognosis and the type of primary tumor. In general it would appear that the prognosis for the patient with hepatic metastases is proportional to the prognosis for the primary tumor. The findings of this review suggest a course of action for the surgeon when faced with the infrequent but not rare situation of a patient with resectable hepatic metastases. Assuming control of the primary tumor, adequate experience of the surgeon, and adequate physiologic reserve of the patient, hepatic resection is indicated at the time resectable metastases are encountered. This is particularly true when the metastasis is solitary and when the primary tumor arises in the colon or rectum. The extent of the resection should be limited and primarily determined by the size, position, and number of metastases, rather than by lobar anatomy.
3. 4.
5.
6.
7.
8. 9.
10. 11.
12. 13.
14. 15.
16.
SUMMARY
A case is reported of a patient with a symptomatic, large, apparently solitary metastasis to the right lobe of the liver from a gastric carcinoma. A major hepatic resection was accomplished successfully in the hope of significant palliation. A review and analysis of the available literature on hepatic resection for cancer metastatic to the liver is presented. The evidence strongly suggests than an aggressive approach should be taken in the surgical treatment of patients with cancer metastatic to the liver. A limited resection should be carried out when the hepatic metastases are technically resectable if the primary tumor is controlled and if no other metastases are evident. Significant palliation and an occasional cure may be achieved by this approach. REFERENCES 1. BASSETT, J. Personal communication. 2. BORDEN, L. and MURPHY, A. J. Right
and Foster
17.
18. 19. 20.
21. 22.
23.
24. 25.
hepatic
lobectomy: report of a case complicated by hemologous serum hepatitis. Gastroenterology, 28: 288, 1955. BRUNSCHWIG,A. Hepatic lobectomy for metastatic cancer. Cancer, 16: 277, 1963. BRUZELILJS,S. Partial hepatectomy and nephrectomy for late metastases from carcinoma of the cervix, uteri: report of one case. Acta chir. scandinav., 126: 379, 1963. BUFFIN, R. P. Cancer du colon gauche avec metastase hepatique unique, etc. Rev. mkd.-chir. mal. joie, 37: 241, 1962. CATTELL, R. B. Successful removal of liver metastases from a carcinoma of the rectum. Lahey Gin. Bull., 2: 7, 1940. CHAMPEAU, M., PINEAU, P., and CHALEIL, B. A propos des depistages et du traitement des metastases hepatique des cancers digestifs. Arch. mal. a$$. digest., 50: 530, 1961. CULLEN, T. S. Large carcinomatous tumor of the liver. J.A.M.A., 44: 1239, 1905. FINEBERG, C., GOLDBURGH, W. P., and TEMPLETON, J. Y., III. Right hepatic lobectomy for primary carcinoma of the liver. Ann. Surg., 14: 881, 1956. GALVIN, C. Solitary liver metastases. J. Irish M. A ., 55: 132, 1964. GUYNN, V. L., REYNOLDS, J. T., and OVERSTREET, R. J. Right hepatic lobectomy. S. C/in. North America, 43: 63, 1963. GUYNN, V. L. Personal communication. HITTNER, V. J. Excision of metastatic carcinoma of the liver with a seven year survival. Wisconsin M. J., 61: 605, 1962. HITTNER, V. J. Personal communication. HONJO, I. and ARAKEI, C. Total resection of right lobe of liver. J. Internat. Coil. Surgeons, 23: 23, 1955. LLOYD-DAVIES, 0. V. Carcinoma of the rectum with a single secondary in the liver. Synchronous combined excision and left hepatectomy. Proc. Roy. Sot. Med., 40: 875, 1947. LLOYD-DAVIES, 0. V. and ANGELLI, C. Right hepatic lobectomy: operative technique, some anatomical points and an account of a case. Brit. J. Surg., 45: 114, 1957. LONGMIRE, W. A., JR. Hepatic surgery: trauma, tumor and cysts. Ann. Surg., 61: 1, 1965. LONGMIRE, W. A. Personal communication. LORTAT-JACOB, J. L. and ROBERT, H. G. Hepatectomies, droites. XVI Congres de la Societe Internationale de Chirurgie, Copenhagen, p. 1060. Brussels, 1955. Imprimerie Medicale et Scientifique. MCKIRDIE, M. Personal communication. MGLLER, W. Resection of liver on account of metastatic carcinoma; case. Acta. chir. scandinav., 78: 103, 1936. PACK, G. T. and BRASFIELD, R. D. Metastatic carcinoma of the liver: clinical problem and its management. Am. J. Surg., 90: 704, 1955. PACK, G. T. and MILLER, T. R. Middle hepatic lobectomy for carcinoma. Cancer, 14: 1295, 1961. PEDEN, J. C., and BLALOCK, W. N. Right hepatic lobectomy for metastatic carcinoma of the large bowel. Five year survival. Cancer, 16: 1133, 1963.
Hepatic Resection for Metastatic Cancer J. C. Personal communication. 27. PETTINAR~, V. and DAGRADI, A. Le Resezioni Epatiche. Rome, 1962. 28. QI.ATTLEBAUM, J. K. Hepatic lotectomy for benign :ind malignant lesions. S. Cl&. North America, 42:. X7, 1962. 29. I
26. PEUEN,
Vol. 113, April
1967
41. Wssrox, P. A. and HARLAND, W. A. Bilobronchial fistula following right hepatic lobectomy for metastatic leiomyosarcoma of the stomach. Rrit. J. Surg., 50: 331, 1962. 42. WOODINGTOS, G. F. and WAUGH, J. M. Results of resection of metastatic tumors of the liver. ;lm. J. Surg., 105: 24, 1963. 43. CHANDLER, J. J. and FOSTER, J. H. Malignant carcinoitl syndrome treated by resection of hepatic metastases. /lm. J &rg., 109: 221, 1965. 44. RAVEN, R. W. Hepatectomy. XVI CongreS de la Soci&i. Internationale de Chirurgie, Copenhagen, p. 1099. Brussels, 1955. Imprimerie Meditale et Scientifique. 45. MODLIN, J. and WALKER, H. S. J. Palliative resection in cancer of the colon and rectum. Cancer, 2: 767, 1949. 46. GOLDSMITH, h’. A. and WOODBURNE, R. T. The surgical anatomy pertaining to liver resection. Surf. Gynec. b Obst., 105: 310, 1957. 47. HEALEY, J. E., JR. Clinical anatomic aspects of radical hepatic surgery. J. Internat. Coil. Surgeon, 22: 542, 1954. 48. WAYSON, E. E. and FOSTER, J. H. Surgical anatomy of theliver. S. Cl&. North Amerita, 44: 1253,1964. 49. BRUNSCHWIG, A. Hepatic lobectomy. In: Atlas of Technics of Surgery, vol. 1, p. 462. Edited by J. L. Madden. New York, 1964. Appleton-Century-crofts, Inc. 50. PACK, G. T. and ISLAMI, A. H. Operative treatment of hepatic tumors. CL&. Sympas., 16: 35, 1964. 51. PACK, G. T. Surgical management of primary and metastatic carcinoma of the liver. Northwest Med., 57: 551) 195x. 52. PACK, G. T. aud ARIEL, I. M. Cancer. Boston, 1960. Little, Brown & Co.
Resection
for Metastatic
Cancer
LATHAM FLANAGAN, JR., M.D.* AND JAMES H. FOSTER, M.D.,~ Portland,
From the Department of Surgery, University of Oregon Medical School, and the Portland Veterans Administrat ion Hospital, Portland) Oregon.
R
CLINICAL
Oregon
MATERIAL
We were able to find thirty-two reports concerning seventy-two patients who survived hepatic resection for metastatic cancer [I-42]. Analysis of these reports forms the basis of this review. The authors of these reports were contacted and current follow-up data were obtained when available. Patients are included in this study when definite information was available concerning the type of primar? tumor, the type of resection, and the length of follow-up study outside the hospital. Patients undergoing hepatic resection in continuity with the primary tumor in order to satisfy the en bloc principle are not included. Patients undergoing hepatic resection for functioning carcinoid metastases are also excluded since clinical experience has clearly shown that in this particular syndrome palliation can be expected when the removal of the carcinoid metastases is technically feasible [431. To determine which patients might benefit
ECENT experience with a patient who under-
went major hepatic resection for metastatic cancer at the Portland Veterans Administration Hospital has raised two fundamental questions: Can palliation be achieved by the resection of hepatic metastases? Does the possibility of significantly benefiting the patient outweigh the risk of hepatic resection? We were unable to find a recent survey of clinical experience which might suggest answers to these important questions. This collected review was, therefore, undertaken to provide this information. CASE REPORT
The patient (R. L.), a sixty-eight year old white man, was admitted to the Portland Veterans Administration Hospital in October 1959. A subtotal gastric resection was performed for a large antral adenocarcinoma without evidence of metastasis. Five years later, in October 1964, he was readmitted with a short history of severe pain and early satiety related to a rapidly enlarging right abdominal mass. Laparotomy revealed replacement of the right lobe of the liver by a mass measuring 18 by 15 by 10 cm. (Fig. I.) Since there was no evidence of other metastases, a subtotal right hepatic lobectomy was performed. The resected tumor and a 2 to 3 cm. margin of liver parenchyma weighed 1,330 g-m. and proved to be metastatic adenocarcinoma, histologically similar to the previously resected gastric tumor. The patient’s symptoms were relieved postoperatively. He lived comfortably at home for a few months and then his condition deteriorated rapidly over a two week course and he died five months after hepatic resection, Autopsy revealed a recurrence of tumor in the right upper quadrant at the line of resection and in the retroperitoneal nodes as well as bilateral pulmonary metastases.
FIG. 1. The line of resection of the right lobe of the liver is represented by the dotted line.
* PRESEXTADDRESS:U. S. Naval Hospital, y. FPO, San Francisco, California 96630. t PRESENTADDRESS:Department of Surgery, Hartford Hospital, Hartford, Connecticut 06115 V-01.11.7.April
1967
551
552
Flanagan and Foster
SURVIVAL RELATED TO INTERVAL BETWEEN
Data
None
TABLE I RESECTION OF PRIMARY TUMOR AND RESECTION
Interval between Operations Less than Two Years
25 26 16 8 (46%) 3 (14%)
Number of patients Average survival (mo.) Median survival (mo.) Two year survivalt Five year survivalt
17 33 24 9 (69%) 3 (21%)
RESULTS
The clinical results achieved in the seventytwo patients who survived hepatic resection for metastatic cancer are presented in Table I. The average length of survival for the group
METASTASES
Total No. of Cases
More than Two Years 28 36
72* 31
:: (50%) 6 (29%)
:: (51%) 12 (24%)
* Interval not known in two patients. t Corrected to include only patients followed until end of interval or death (determinate
from hepatic resection for metastatic cancer we have related length of survival to (1) type of primary tumor, (2) type of hepatic resection, (3) number of metastatic deposits, and (4) interval of time between resection of the primary tumor and resection of the hepatic metastases.
OF HEPATIC
survival).
was thirty-one months, with a median survival time of eighteen months after hepatic resection. Twelve patients lived at least five years. (Table II.) Twenty-one of the patients were still alive when their cases were reported but had not yet lived five years. Fifty-one patients were followed up for five years or until death and were used to calculate a corrected five year survival rate of 23.6 per cent. Thirty patients survived at least two years for a corrected two year survival rate of 50.S per cent. The operative mortality for patients under-
TABLE II CLINICAL HISTORY OF PATIENTS SURVIVING FIVE YEARS OR MORE
Author
Zge (yr.) & sex of Patient
Tumor
of
Interval between Operations
Type of Liver Metastasis
Type of Resection
Right lobectomy
Alive with disease at 5.66 yr.
Right wedge Right lobectomy
Living and well at 9.5 yr. Died with disease at 5.5 yr. Dead at 5 yr. Living and well at 7.5 yr.
29, F
Cancer of rectum
6 m”.
Multiple nodule:. one measuring 4 by 4 by 4.5 cm. Solitary nodule
46, M
of
4 yr.
Islet cell tumor
60, F 52, M
M&~“S~~C”tIl~ Cancer of cecum
0 1 yr., 5 mo
Hittner [131
42, M
cancer of colon
0
Mass measuring 20 cm. involving diaphragm and abdominal wall also Solitary nodule
McKirdie
50, M
cancer of colon
4 yr.
Solitary nodule
Left lateral segment
0
“Nut-sized” nodule
solitarv
Right wedge
5 In”.
“Hen’s egg” solitary nodule Solitary black mass of 7 cm. Solitary tumor of 1,500 gm. Solitary nodule
Right wedge
Woodington and Waugh [42]
Peden and Blalock 125 I
[Zl]
75, F
cancer
4 yr.
Pineau, and Chaleil [7] Buff% [5]
?, M
Cancer of sigmoid
67, M
Cancer of sigmoid
Pack [23]
40, F
Melanoma of eye
Straus and Scanlon [36] Miller [ZZ]
62, F
Cancer of kidney
5 yr.
29, F
,Gran1dosa cell car-
10 yr.
cinoma of “vary
13 yr.
Follow-Up Study
Left wedge Right extended lobectomy Right wedge
Right wedge Left lateral segment Right wedge
American
Living and well at 10 Yr. Died of stroke at 12 no evidence yr., of tumor Living and well at 7 Yr. Living and well at 8 Yr. Died at 6 yr. Living ilod well at 15 Yr. Living and wel! at 6 yr.
Jo~~wtal
of Suvgery
Hepatic Resection for Metastatic TABLE SI.R\‘I!‘AL
RELATED
TO INTERVAL
BETWEEN
RESECTION
IN PATIENTS
1)ata
Number of patients Average survival (mo.) Median survival (mo.) Five year survival
Xone
III
OF PRIMARY
WITH
PRIMARY
TUMOR
AND
CARCINOMA
Interval between Operations Less than Two Years 15 37 26
15 29 16
RESECTION
OF HEPATIC
METASTASES
OF COLON
More than Two Years 14 38 18
3 (33%)
2 (IS%)
553
Cancer
2 (20%)
Total
45* 32 18 7 (23%)
* Interval not available for one patient.
were analyzed. The results suggest that there is no improvement in survival with increasing interval. (Table III.) In Table IV survival is related to the type of primary tumor. There is a significant difference in survival between patients with tumors primary in the stomach and those with tumors primary in the colon. There were seven patients who survived five years (23.3 per cent) among those with carcinoma of the colon and none among those with carcinoma of the stomach. Of those seventeen patients whose primary tumors arose outside of the gastrointestinal tract, five survived at least five years after resection of hepatic metastases. Patient survival figures for the various types of hepatic resection are compared in Table v. The nomenclature of the resections is based upon the anatomic rather than the “classic” divisions of the liver. The classic right lobectomy, which includes all tissue to the right of the falciform ligament, is known as a right extended lobectomy. The classic left lobectomy is known as a left lateral segmentectomy. The term “metastasectomy” means excision of the
going hepatic resection for metastatic cancer varies widely in published reports. Brunschwig reported a 29 per cent mortality after twentyfour major lobectomies for cancer metastatic to or with direct extension into the liver [3]. On the other hand, Woodington and Waugh, reporting a similar series from the Mayo Clinic, described only one death with twenty-five resections [42]. The possible effect upon survival of the interval of time between resection of the primary tumor and resection of the hepatic metastases for all seventy-two patients can be derived from the figures in Table I. The figures for synchronous resection of metastases are found in column 2. The metachronous resections of metastases are arbitrarily divided into intervals of less than two years and greater than two years. There is little difference between the median and the two year survival figures, but there does seem to be some improvement in five year survival with increasing interval. To obtain a more homogenous group for analysis, only cases in which there were metastases from a primary tumor of the colon TABLE RELATION
Data
Number of patients Mean survival (mo.) Median survival (mo.) Two year survivalf Five year survival $
Carcinoma of Colon 45 32 :: (53%) 7 (23%)
OF SURVIVAL
IV
TO TYPE
OF PRIMARY
TUMOR
Carcinoma of Stomach
Sarcoma*
9 17 17 3 (43%) 0
5 55 42 4 (166%) 2 (67%)
Other Locations Carcinomat 13 38 12 4 (31%) 3 (23%)
* Included are melanoma of skin in (1) and of eye (2); leiomyosarcoma of stomach (1) and of omentum t Carcinoma of pancreas (4), uterus (3), kidney (2), ovary (2), breast (l), and lung (1). 1 Determinate survival. Vol. 11.3. iipvil
1967
(1)
of
Flanagan
554
and Foster
TABLE v SURVIVAL RELATEDTO TYPE OF HEPATIC RESECTION
Data
Right Lobectomy
Right Extended Lobectomy
Left Lateral Segment Resection
Number of patients Mean survival (mo.) Median survival (mo.) Two year survival* Five year survival*
15 24 20 54% (7) 25% (2)
5 26 12 20% (1) 29%(l)
22 31 18 53% (8) 15%(2)
* Determinate
COMMENTS
The presence of metastatic carcinoma in the liver is considered by many surgeons to be a relative criterion of unresectability and an TABLE VI SURVIVALRELATEDTO NUMBEROF HEPATICMETASTASES
Number of patients Mean survival (mo.) Median survival (mo.) Two year survival* Five year survival* * Determinate
2 26 50%(l)
Metastasectomy
Multiple Segments
21 41 24 55% (16)
6 23 18 33% (2)
39% (7)
survival.
metastasis plus sufficient liver tissue to obtain an adequate margin, and includes both wedge resections and partial lobectomies. The final column, titled “multiple segments,” represents cases in which the tumor was not confined to one lobe and a combination of resections was performed. It is of special interest that the survival figures reflect quite favorably upon the lesser operations of wedge resection or metastasectomy. The question of whether patients with a solitary hepatic metastasis have an improved survival over patients with multiple metastases appears resolved in Table VI. There is marked difference in all of the parameters of survival, including a 39 per cent five year survival rate for the group with a solitary metastasis.
Data
Quadrate Lobectomy
Solitary Metastasis
Multiple Metastasis
All Cases
34
38
72
44
19
31
24
16
18
78% (21)
27% (8)
51% (30)
39% (9)
12% (3)
24% (12)
survival.
absolute criterion of incurability. The figures presented previously herein refute this concept. There is a small but definite group of patients who will apparently be benefited by excision of hepatic metastases. How many patients have technically resectable hepatic metastases? Raven reported 818 patients with cancer of the stomach, colon, or rectum from the Royal Marsden Hospital [44]. One hundred eighty-six (23 per cent) of these patients had hepatic metastases and forty-two (5 per cent) had metastases that were judged resectable on the basis of a solitary metastasis or multiple metastases confined to one lobe. This author concludes that one of every twenty patients operated upon for cancer of the gastrointestinal tract had technically resectable hepatic metastases. What is the natural history of patients found to have metastatic carcinoma in the liver? This is a difficult question to answer on the basis of published reports. Modlin and Walker reported on seventeen patients with cancer of the colon metastatic to the liver [45]. The average patient survived eleven months and none survived five years. Review of the Tumor Clinic files at the Portland Veterans Administration Hospital reveals twenty-six patients who were found to have carcinoma of the colon or rectum metastatic to the liver at laparotomy. The average patient survived six months and none survived five years. The figures for these two groups are used as controls and are compared to the results of this review in Table VII. This comparison may not be valid because the control groups reflect the fate of patients with all degrees of hepatic metastatic disease, not just those with tumors amenable to resection. Also, the group with resection may not American
Journal of Surgery
Hepatic
Resection
for Metastatic TABLE
SURVIVAL
Number of patients Mean survival (mo.) Median survival (mo.) Two year survival* Five year survival*
17 11.2 1:70 0
2A 5 4 (3)
5
4%(l) 0
METASTASES
43 x2 fj 9% (4) 0
YWith Hepatic Primary Carcinema of Colon
Resectiwl
45 32 18 53% (19) 23% (7)
72 31
-- -..
All Caw
.Z% (30) 23 (12)
survival.
be entirely representative of all patients undergoing resection of hepatic metastases because of the natural bias of the medical writer to report successful cases while leaving failures unreported. Nevertheless, the results obtained from the analysis of these seventy-two cases are impressive. Twenty-four per cent of the fifty-one patients who were followed up for five years or until death lived at least five years, as compared to 0 per cent of the controls; 51 per cent of the fifty-nine patients who were followed up for two years or until death lived at least two years, as compared to 9 per cent of the controls. These figures strongly suggest that resection of hepatic metastases is worth-while for the selected patient. Many contributions are responsible for the declining and now acceptable operative risk for major hepatic resection by skillful surgeons. Among these are advances in the understanding of intrahepatic anatomy [46-48], advances in operative technics [20,29,49,50], and advances in the understanding of pre- and postoperative hepatic pathophysiology [SI ]. The mortality for major hepatic surgery for metastatic cancer is difficult to document. The wide variation between published reports may be related not only to the skill of the surgeon and the physiologic reserve of the patient but perhaps also to the type of resection elected. Brunschwig’s 29 per cent mortality with twenty-four major lobectomies included a 50 per cent mortality with eight right extended lobectomies, an operation in which nearly 80 per cent of the liver was resected. The Mayo Clinic’s -l per cent mortality with ten major lobectomies and fifteen partial lobectomies included eight right lobectomies, but it is not certain whether any of these were right exVol. 113, April
VII
HEPATIC
Without Hepatic Resection in Primarv Carcinoma of Colon-Portland Veterans Combined Modlin and Administration Series Walker (451 Hospital
Data
* Determinate
WITH
Cancer
1’167
tended lobectomies. In light of the differences in mortality and approach to resection, it is of considerable interest that there was only one patient who survived five years in Brunschwig’s series, whereas there were seven patients who survived five years in the Mayo Clinic series. It is an unexpected finding that the results obtained by simple “metastasectomy” with a narrow margin of uninvolved liver were as good, if not better, than the results obtained by major hepatic lobectomy. This finding suggests that intralobar redissemination of metastatic cancer may be a late phenomenon and that the grossly identifiable tumor at laparotomy may be the only tumor present. In this regard Pack studied one hundred patients with cancer of the gastrointestinal tract who died in the postoperative period after resection of the primary tumor [52]. The livers of these patients had been judged by the surgeon at laparotomy to be free of metastasis. Only five patients had hidden metastases at autopsy and only two of these were macroscopic. We were surprised to find that the interval between resection of the primary tumor and resection of the hepatic metastases had little correlation with subsequent length of survival. Brunschwig found the same lack of correlation in his own series [3]. In patients whose hepatic metastases are not demonstrable until two or more years after resection of the primary tumor, it would seem that a favorable host-tumor biologic relationship has existed. In the past, these patients have been considered tnore favorable candidates for further surgical palliation. The findings of this study suggest that this favorable host-tumor relationship no longer exists when the metastases become
Flanagan
556
clinically evident, and that all patients with hepatic metastases should be approached similarly without regard to the time of discovery of the metastases. One of the more impressive findings of this review is the difference in length of survival between patients with a solitary hepatic metastasis and those with multiple metastases. The reason for this is not clear. No conclusion can be drawn about the relation between prognosis and the type of primary tumor. In general it would appear that the prognosis for the patient with hepatic metastases is proportional to the prognosis for the primary tumor. The findings of this review suggest a course of action for the surgeon when faced with the infrequent but not rare situation of a patient with resectable hepatic metastases. Assuming control of the primary tumor, adequate experience of the surgeon, and adequate physiologic reserve of the patient, hepatic resection is indicated at the time resectable metastases are encountered. This is particularly true when the metastasis is solitary and when the primary tumor arises in the colon or rectum. The extent of the resection should be limited and primarily determined by the size, position, and number of metastases, rather than by lobar anatomy.
3. 4.
5.
6.
7.
8. 9.
10. 11.
12. 13.
14. 15.
16.
SUMMARY
A case is reported of a patient with a symptomatic, large, apparently solitary metastasis to the right lobe of the liver from a gastric carcinoma. A major hepatic resection was accomplished successfully in the hope of significant palliation. A review and analysis of the available literature on hepatic resection for cancer metastatic to the liver is presented. The evidence strongly suggests than an aggressive approach should be taken in the surgical treatment of patients with cancer metastatic to the liver. A limited resection should be carried out when the hepatic metastases are technically resectable if the primary tumor is controlled and if no other metastases are evident. Significant palliation and an occasional cure may be achieved by this approach. REFERENCES 1. BASSETT, J. Personal communication. 2. BORDEN, L. and MURPHY, A. J. Right
and Foster
17.
18. 19. 20.
21. 22.
23.
24. 25.
hepatic
lobectomy: report of a case complicated by hemologous serum hepatitis. Gastroenterology, 28: 288, 1955. BRUNSCHWIG,A. Hepatic lobectomy for metastatic cancer. Cancer, 16: 277, 1963. BRUZELILJS,S. Partial hepatectomy and nephrectomy for late metastases from carcinoma of the cervix, uteri: report of one case. Acta chir. scandinav., 126: 379, 1963. BUFFIN, R. P. Cancer du colon gauche avec metastase hepatique unique, etc. Rev. mkd.-chir. mal. joie, 37: 241, 1962. CATTELL, R. B. Successful removal of liver metastases from a carcinoma of the rectum. Lahey Gin. Bull., 2: 7, 1940. CHAMPEAU, M., PINEAU, P., and CHALEIL, B. A propos des depistages et du traitement des metastases hepatique des cancers digestifs. Arch. mal. a$$. digest., 50: 530, 1961. CULLEN, T. S. Large carcinomatous tumor of the liver. J.A.M.A., 44: 1239, 1905. FINEBERG, C., GOLDBURGH, W. P., and TEMPLETON, J. Y., III. Right hepatic lobectomy for primary carcinoma of the liver. Ann. Surg., 14: 881, 1956. GALVIN, C. Solitary liver metastases. J. Irish M. A ., 55: 132, 1964. GUYNN, V. L., REYNOLDS, J. T., and OVERSTREET, R. J. Right hepatic lobectomy. S. C/in. North America, 43: 63, 1963. GUYNN, V. L. Personal communication. HITTNER, V. J. Excision of metastatic carcinoma of the liver with a seven year survival. Wisconsin M. J., 61: 605, 1962. HITTNER, V. J. Personal communication. HONJO, I. and ARAKEI, C. Total resection of right lobe of liver. J. Internat. Coil. Surgeons, 23: 23, 1955. LLOYD-DAVIES, 0. V. Carcinoma of the rectum with a single secondary in the liver. Synchronous combined excision and left hepatectomy. Proc. Roy. Sot. Med., 40: 875, 1947. LLOYD-DAVIES, 0. V. and ANGELLI, C. Right hepatic lobectomy: operative technique, some anatomical points and an account of a case. Brit. J. Surg., 45: 114, 1957. LONGMIRE, W. A., JR. Hepatic surgery: trauma, tumor and cysts. Ann. Surg., 61: 1, 1965. LONGMIRE, W. A. Personal communication. LORTAT-JACOB, J. L. and ROBERT, H. G. Hepatectomies, droites. XVI Congres de la Societe Internationale de Chirurgie, Copenhagen, p. 1060. Brussels, 1955. Imprimerie Medicale et Scientifique. MCKIRDIE, M. Personal communication. MGLLER, W. Resection of liver on account of metastatic carcinoma; case. Acta. chir. scandinav., 78: 103, 1936. PACK, G. T. and BRASFIELD, R. D. Metastatic carcinoma of the liver: clinical problem and its management. Am. J. Surg., 90: 704, 1955. PACK, G. T. and MILLER, T. R. Middle hepatic lobectomy for carcinoma. Cancer, 14: 1295, 1961. PEDEN, J. C., and BLALOCK, W. N. Right hepatic lobectomy for metastatic carcinoma of the large bowel. Five year survival. Cancer, 16: 1133, 1963.
Hepatic Resection for Metastatic Cancer J. C. Personal communication. 27. PETTINAR~, V. and DAGRADI, A. Le Resezioni Epatiche. Rome, 1962. 28. QI.ATTLEBAUM, J. K. Hepatic lotectomy for benign :ind malignant lesions. S. Cl&. North America, 42:. X7, 1962. 29. I
26. PEUEN,
Vol. 113, April
1967
41. Wssrox, P. A. and HARLAND, W. A. Bilobronchial fistula following right hepatic lobectomy for metastatic leiomyosarcoma of the stomach. Rrit. J. Surg., 50: 331, 1962. 42. WOODINGTOS, G. F. and WAUGH, J. M. Results of resection of metastatic tumors of the liver. ;lm. J. Surg., 105: 24, 1963. 43. CHANDLER, J. J. and FOSTER, J. H. Malignant carcinoitl syndrome treated by resection of hepatic metastases. /lm. J &rg., 109: 221, 1965. 44. RAVEN, R. W. Hepatectomy. XVI CongreS de la Soci&i. Internationale de Chirurgie, Copenhagen, p. 1099. Brussels, 1955. Imprimerie Meditale et Scientifique. 45. MODLIN, J. and WALKER, H. S. J. Palliative resection in cancer of the colon and rectum. Cancer, 2: 767, 1949. 46. GOLDSMITH, h’. A. and WOODBURNE, R. T. The surgical anatomy pertaining to liver resection. Surf. Gynec. b Obst., 105: 310, 1957. 47. HEALEY, J. E., JR. Clinical anatomic aspects of radical hepatic surgery. J. Internat. Coil. Surgeon, 22: 542, 1954. 48. WAYSON, E. E. and FOSTER, J. H. Surgical anatomy of theliver. S. Cl&. North Amerita, 44: 1253,1964. 49. BRUNSCHWIG, A. Hepatic lobectomy. In: Atlas of Technics of Surgery, vol. 1, p. 462. Edited by J. L. Madden. New York, 1964. Appleton-Century-crofts, Inc. 50. PACK, G. T. and ISLAMI, A. H. Operative treatment of hepatic tumors. CL&. Sympas., 16: 35, 1964. 51. PACK, G. T. Surgical management of primary and metastatic carcinoma of the liver. Northwest Med., 57: 551) 195x. 52. PACK, G. T. aud ARIEL, I. M. Cancer. Boston, 1960. Little, Brown & Co.