Morbidity and Mortality of Hepatic Resection for Metastatic Colorectal Carcinoma JOHN T . VETTO, M.D.,* KEVIN S. HUGHES, M . D . , t REBECCA ROSENSTEIN, PH.D., + PAUL H. SUGARBAKER, M.D.w
Vetto JT, Hughes KS, Rosenstein R, Sugarbaker PH. Morbidity and mortality of hepatic resection for metastatic colorectal carcinoma. Dis Colon Rectum 1990;33:408-413. Hepatic resection is the only curative therapy currently available for colorectal cancer metastases to the liver. However, concern over high morbidity and mortality of the procedure has limited referral of patients for resection. The authors report on 58 patients undergoing hepatic resection for colorectal metastases at the National Cancer Institute between the years 1976 and 1985. Thirty-two patients underwent a major hepatic resection, and 26 patients underwent one or more wedge resections. Mean anesthesia time was 448 minutes, mean estimated blood loss was 3663 ml, and mean hospital stay was 17.5days. Operative mortality was 3 percent, and morbidity was 62 percent. Using a grading scale for complications, 24 percent of patients had inconsequential complications, 16 percent had moderate complications, and 19 percent had severe complications. Complications were clearly related to extent of procedure. Factors that correlated best with morbidity were high blood loss and trisegmentectomy. The authors conclude that while hepatic resection can carry a high morbidity, much of this morbidity is minor and operative mortality is low. Recent improvements in anesthesia, improved resection technique, and a better understanding of hepatic anatomy have made possible correspondingly lower morbidity and mortality rates. Careful selection of patients can make hepatic resection a safe procedure. [Keywords: Liver neoplasms; Liver resection; Hepatic metastases; Morbidity]
HEPATIC RESECTION is the o n l y c u r r e n t l y available therapy for colorectal metastases that c a n result i n cure. I n fact, hepatic resection is u n i q u e l y suited for colorectal Address reprint requests to Dr. Hughes: Department of Surgery, Lahey Clinic Medical Center, 41 Mall Road, Burlington, Massachusetts 01805. 408
From the UCLA Medical Center, Los Angeles, California,* Lahe~ Clinic Medical Center, Burlington, Massachusetts, t Department of Statistics, Brown University, Providence, Rhode Island, + and the Washington Hospital Cancer Center, Washington, District oJ Columbiaw
c a r c i n o m a therapy, as the v e n o u s d r a i n a g e of the c o l o n is such that the liver m a y be the o n l y site of spl:ead. 1 A r e c e n t l y r e p o r t e d registry of h e p a t i c metastases c o m p i l e d f r o m 24 i n s t i t u t i o n s reported a 5-year actuarial survival of 33 percent a n d a 5-year actuarial disease-free survival of 21 percent after hepatic resection for metastatic c a r c i n o m a . 2 Nonetheless, the lack of c o n s e n s u s r e g a r d i n g i n d i c a t i o n s for hepatic resection, preoperative assessm e n t , operative techniques, a n d p r o g n o s i s have rendered hepatic resection a procedure used less often t h a n is indicated. 3 As m o s t reports of the m o r b i d i t y a n d m o r t a l i t y of this procedure i n c l u d e p a t i e n t s w i t h a worse (e.g., p r i m a r y liver c a r c i n o m a ) or better (e.g., h e p a t i c a d e n o m a ) p r o g n o s i s t h a n p a t i e n t s w i t h colorectal c a r c i n o m a metastases,l,~, 4-8 a n accurate description of the m o r b i d i t y a n d m o r t a l i t y associated w i t h hepatic resection for colorectal metastases is lacking. Therefore, we u n d e r t o o k a retrospective study of these events i n patients resected for colorectal metastases at the N a t i o n a l Cancer Institute.
Volume 33
Number5
409
HEPATIC RESECTION FOR METASTATIC COLORECTAL CARCINOMA
O u r purpose was to accurately describe the morbidity and mortality of resection and the factors that determine it. Materials and Methods T h e records of all patients u n d e r g o i n g hepatic resection for colorectal metastases at the National Cancer Institute, Surgery Branch, in the 10-year period from 1976 to 1985, were reviewed. T h e procedure performed, length of anesthesia, estimated operative blood loss, occurrence of postoperative complications, and the length of stay were noted. For the purposes of this study, a subjective grading scale of complication severity was used. Patients w h o had an uncomplicated postoperative course were given a grade of 0. Grade "1" indicated a "mild" or "inconsequential" c o m p l i c a t i o n that did not effect the hospital course. :(These events m i g h t not be considered complications in other series.) Grade "2" indicated a "moderate" complication that required an invasive procedure or lengthened hospital stay. Grade "3" indicated a "severe" or life-threatening complication that necessitated reoperation or significantly prolonged hospital stay. Grade "4" or postoperative mortality was defined as death within 30 days after the procedure. A tabulation of complications rated by grade is presented in T a b l e 1; all complications, no matter h o w minor, are included. In patients with more than one complication, grade was determined by the most morbid complication (Table 2). Anesthesia time, estimated blood loss, type of procedure, t i m i n g of the p r o c e d u r e (synchronous vs. metachronous), and type of incision used were analyzed with respect to complication and death rates. Statistics were determined by the chi-square test and significance was considered as P < 0.05. Results
Fifty-eight patients underwent hepatic resection for isolated colorectal metastases. T h i r t y - t w o patients u n d e r w e n t a n a t o m i c resection, i n c l u d i n g 19 r i g h t lobectomies, 6 left lobectomies, 5 trisegmentectomies, and 2 left lateral segmentectomies. Twenty-six patients underwent wedge resection including 15 multiple and l l solitary resections. Mean anesthesia time was 452 minutes (range, 270 to 750 minutes). T h e mean estimated blood loss was 3599 ml (range, 700 to 16,000 ml), and mean hospital stay was 17.5 days (range, 8 to 52 days). There were two postoperative deaths (3.1 percent). T h e first occurred in a patient with cirrhosis who underwent a lateral segmentectomy. T h e second occurred after simultaneous trisegmentectomy, bile duct reconstruction, and sigmoid colon resection. T h e r e were a total of 47 complications in 36 patients for an overall patient-related morbidity of 62 percent (36/58). A m o n g survivors, there were 44 complications
TABLE1. Overall Complications Number Mild Pleural effusion (without thoracentesis) Urinary retention Jaundice (asymptomatic) Post-thoracotomy pain Ileus TOTAL Moderated Biliary fistula Pleural effusion (requiting thoracentesis) Arrhythmias requiring treatment Atelectasis (requiring bronchoscopy) Brachial plexopathy Deep venous thrombosis Pelvic hematoma Transfusion reaction Upper respiratory infection Wour;d infection TOTAL Severe Subphrenic abscess Biliary obstruction (requiring reoperation) Hepatic failure/ascites Myocardial infarction Renal insufficiency Small-bowel obstruction (requiring reoperation) Upper gastrointestinal bleeding Wound dehiscence
10 3 1 1 1 16 5 4 3 1 1 1 1 1 1 1 19 5 1 1 1 1 1 1 1
12
TOTAL
in 34 patients for a survivor-related morbidity of 61 percent (34/56). All complications are tabulated in Table 1. Using the most morbid complication to assign grade, a s u m m a r y of related morbidity and mortality is shown in Table 2. As noted in this table, 38 percent of all patients had no complications, and another 24 percent had only " m i l d " or "inconsequential" complications. Thirty-five percent of patients survived with "moderate" or "severe" complications requiring longer hospital stay or some type of intervention. Using our grading scale, data were analyzed to determine the relationship between the severity of complications (including death) and several factors, including procedures performed, length of anesthesia, estimated operative blood loss, timing of procedure
TABLE2. Patient-Related Morbidity and Mortality Grade
n
Percent
0 (no complications) 1 (mild) 2 (moderate) 3 (severe) 4 (death) TOTAL
22 14 9 11 2 58
38 24 16 19 3 100
410
VETTO, ET AL.
TABLE 3. Relationship Between Severity of Complications and Clinical Parameters Parameters Estimated blood loss (Mean -4- SD) Procedure
Grade
Wedge Major Trisegmentectomy Synchronous Metachronous
Timing of procedure Type of incision (All Patients) Thoracoabdominal (All Patients) Abdominal (Anatomic Thoracoabdominat resection only) (Anatomic Abdominal resection only)
0-1
2-4
n o t r e a c h statistical s i g n i f i c a n c e ( P ~ 0.2). O p e r a t i v e b l o o d loss a p p e a r e d to c o r r e l a t e w i t h m o r b i d i t y a n d m o r t a l i t y , b u t this d i d n o t r e a c h statistical s i g n i f i c a n c e (P > 0.1). T h e use of a t h o r o c o a b d o m i n a l i n c i s i o n d i d n o t r e a c h statistical s i g n i f i c a n c e w h e n all p a t i e n t s w e r e c o n s i d e r e d (P = 0.15).
P*
3315 4258 (-- 2656) (+ 3594) 18 18 8 14 ~ 2 3 3 1 [ 21 33 !
14 11 11
22 | 11 f 5
9
4 f
Dis. Col. ~ Rect. May 1990
> 0.1
0.32
Discussion Hepatic metastases constitute a major problem in the t r e a t m e n t of c o l o n cancer; 10 to 25 p e r c e n t of p a t i e n t s w i l l h a v e s y n c h r o n o u s h e p a t i c m e t a s t a s e s at i n i t i a l e x p l o r a t i o n , 9-11 a n d 65 p e r c e n t of p a t i e n t s w h o r e c u r h a v e h e p a t i c m e t a s t a s e s at a u t o p s y . 9 A l t h o u g h t h e r e are a n e s t i m a t e d five to six t h o u s a n d c a n d i d a t e s for this p r o c e d u r e a n n u a l l y , 12 referral h a s b e e n less t h a n o p t i m a l b e c a u s e of p e r c e i v e d p r o h i b i t i v e m o r b i d i t y a n d m o r t a l i t y . P r e v i o u s l y r e p o r t e d m o r t a l i t y rates of 4 to 20 p e r c e n t h a v e b e e n l a r g e l y a t t r i b u t e d to b l e e d i n g , l i v e r f a i l u r e , a n d i n f e c t i o n . 13 Several studies h a v e d o c u m e n t e d i m p r o v e d s u r v i v a l w i t h h e p a t i c r e s e c t i o n for c o l o r e c t a l metastases, q u o t i n g 5-year s u r v i v a l rates f r o m 25 to 42 p e r c e n t w h e n l e s i o n s a r e resectable.2,3,~4,15 S t u d i e s t h a t d i r e c t l y a d d r e s s morbidity and mortality of hepatic resection for c o l o r e c t a l m e t a s t a s e s are l a c k i n g , h o w e v e r . T h e r e f o r e , o u r p u r p o s e i n u n d e r t a k i n g this s t u d y w a s to a c c u r a t e l y d e s c r i b e t h e m o r b i d i t y a n d m o r t a l i t y of r e s e c t i o n a n d the factors t h a t d e t e r m i n e it i n a p u r e p o p u l a t i o n o f p a t i e n t s resected for c o l o r e c t a l metastases. Morbidity data for patients undergoing hepatic
> O.2
0.15
t
O.5
r e l a t i v e to c o l o n r e s e c t i o n , a n d t y p e of i n c i s i o n used. For simplicity, patients without complications or with o n l y m i l d c o m p l i c a t i o n s w e r e c o n s i d e r e d as a s i n g l e g r o u p (grades 0-1), a n d p a t i e n t s w i t h m o r e s e r i o u s c o m p l i c a t i o n s o r d e a t h w e r e c o n s i d e r e d as a s e c o n d g r o u p (grades 2-4). T h e results of these a n a l y s e s are s h o w n i n T a b l e 3. There was no significant relationship between the severity of c o m p l i c a t i o n s a n d the l e n g t h of a n e s t h e s i a o r t i m i n g of p r o c e d u r e . T h e p e r f o r m a n c e of t r i s e g m e n t e c t o m y w a s s u g g e s t i v e of m o r e c o m p l i c a t i o n s b u t d i d
TABLE 4. Number (Percent) of Reported Postoperative Complications of Hepatic Resection ]or all Indications
Number of patients Pulmonary Pleural effusion Pneumonia Costochondritis Empyema Gastrointestinal Subphrenic abscess Infection Bile leak Hepatic failure Bleeding Prolonged subcostal drainage Duodenal leak Bowel obstruction Wound Infection Ventral hernia Cardiac failure Arrhythmias Deep venous thrombosis Brachial plexopathy
Ryan et al. 19826
Thompson et al. 1983~
Former et al. 198412
Pommier et al. 19877
Stimpson et al. 19878
52 (12) --
138
65
50
58
-52 (38) 3 (2) .
6 (9) 3 (5) --
3 (6) 2 (4) --
-6 (10) --
5 (8) ----
-----
---
-1 (2)
6 (10) -4 (7) 4 (7) 1 --1 (2)
1 (2)
1 (2)
--
--
1 (2) 1 (2)
---
----. --. NS (29) . -. ---
.
.
. .
-23 (17) 15 (11) 11 (8) . 9 (6) -. 10 (7) . 9 (6) . ---
.
.
.
.
.
. .
5 (9) 2 (3) 1 (2) 3 (5) 1 (2) --
Volume 33 Number ,5
HEPATIC
RESECTION
FOR METASTATIC
COLORECTAE
CARCINOMA
4 ] l
TABLE 5. N u m b e r (Percent) ol C o m m o n l y Reported Postoperative Complications Jrom Hepatic Resection Jor Colorectal Metastases
Number of patients Pleural effusion S u b p h r e n i c abscess C a t h e t e r sepsis Wound infection Hematoma Gastrointestinal bleeding
Vetto, 1989
H a n k s et al. 19805
N i m s , 19841
N o r d l i n g e r et al. 1987 xs
58 14 (24) 5 (9) -1 (2) l (2) 1 (2)
11 1 (9) --12 (18) 1 (9) --
9 -3 (33) -----
80 3 (4) 2 (3) 3 (4) --1 (1)
resection for a variety of indications are available from a number of studies and are summarized in Table 4. These "mixed" studies are clearly not applicable to a pure p o p u l a t i o n of patients resected for colorectal carcinoma. According to Stimpson, 8 three factors that help to determine outcome after hepatic resection are severity of the primary disease, age, and presence of disease in other organ systems. Patients undergoing resection for benign disease will have a better prognosis because they are young, have no other organs involved, and their disease carries a good prognosis overall. Patients with primary liver tumors carry the least favorable prognosis of all these groups because of the overall poor prognosis of their tumor, their advanced age, the frequent presence of disease elsewhere, and the c o m m o n association with cirrhosis (which can increase operative mortality to 21 to 60 percent because of increased bleeding and poor postoperative regeneration of tissue), t6-18 These different prognostic groups for hepatic resection have been p r e v i o u s l y n o t e d by T h o m p s o n et al. ~ Clearly, patients resected [or colorectal metastases are different from those resected for other indications, and their morbidity and mortality should be considered
separately. In general, these patients are older (with mean ages of 55 to 61 years),l~ noncirrhotic, have malignant disease with its overall poor prognosis, but are usually disease-free in other organ systems (a recognized criterion for hepatic resection), z Morbidity data for this distinct g r o u p are a v a i l a b l e f r o m some studies a n d are summarized in Table 5. In our series, we report a mean anesthesia time of 452 minutes; this is slightly longer than has been reported in other series1, s and is probably due, in part, to a policy o[ intraoperative line placement at our institution. Mean operative blood loss of 3599 ml was more than that reported by Andrus and Kaminski, ~9 and similar to reports by Stimpson et al. 8 and Pommier et al. 7 Our largest blood losses occurred in our earlier patients, before we adopted the use of newer blood saving techniques such as the ultrasonic dissector (which can decrease both blood loss and operative time),t~,~9,20 and improved anatomic resection techniques. Our mean hospital stay of 17.5 days was similar to that of Nordlinger et al. 15 in their series of patients resected for colorectal metastases. Our 30-day postoperative mortality of 3.1 percent is similar to the generally low mortality reported by
TABLE 6. Reported Mortality o/ Hepatic Resection
n
All I n d i c a t i o n s Mortality
Percent
n
W i l s o n a n d A d s o n , 197614 A t t i y e h , et al. 19789 F o r m e r et al., 19784 W a n e b o et al., 19781~ H a n k s et al., 19805 A d s o n a n d v a n H e e r d e n , 198021
--108 -32 --
--10 -4 --
--(9*) -(12.5 +) --
60 25 25]" 29 11]" 34]-
2 1 2
(2) (4) NS (7) (9) (6)
R y a n et al., 19825 F o r m e r et al., 198412 T h o m p s o n et al., 19833 N i m s , 19841 A n d r u s a n d K a m i n s k i , 198619 N o r d l i n g e r et al., 198715 P o m m i e r et al., 19877 S t i m p s o n et al., 19878
52 -138 10 13 -50 58
4 -15 0 1 -0 2
(8) -(11) (0) (8) -(0) (3)
12]58 22 9 -80 25 23 +
NS 4 0 0 -4 0 1
NS (7) (0) (0) -(0) (0) (4)
Series
N = * = ]- = ++ =
n u m b e r of p a t i e n t s ; N S = n o t stated. four percent for standard resection. excluding wedge resections. f o u r p e r c e n t s i n c e 1970.
Colorectal Metasasis Mortality 1 1
Percent
412
Dis. Col. & Rect.
VETTO, ET AL.
previous series of hepatic resection for colorectal metastases (Table 6).~,3-1~ Combining the data from these 11 series with our own data, the operative mortality is 4 percent (18/446). This same operative mortality of 4 percent has also been reported in "mixed" series of hepatic resection for all indications.22, 23 One of our two operative deaths occurred in a patient with cirrhosis; as previously noted, the presence of cirrhosis increases the risk of death from hepatic resection. 3 Newer techniques such as anatomic resection 24 and routine use of the Pringle maneuver z5 may improve the outcome of this procedure in cirrhotics. Our overall patient-related complication rate of 62 percent is higher than that reported by other series but represents a painstaking report of all complications, no matter how minor (Table 1). Viewed in a more favorable way, 38 percent of our patients (including 25 percent of patients undergoing major anatomic resection) had a completely uncomplicated postoperative course, and another 24 percent had only inconsequential events that required neither extended hospital stay nor a therapeutic procedure (Table 2). Our combined rate of moderate and severe complications was 35 percent, which is similar to previously reported series of both "mixed" indicationsS-6,8,19 and colorectal metastases patients, ~ which tend to report only these more serious complications. Clearly, pleural effusionsS,ts,21 (often asymptomatic), s u b p h r e n i c a b s c e s s , i , 7 and w o u n d problems are the most c o m m o n l y reported complications in patients resected for colorectal metastases (Table 5). We analyzed several factors to d e t e r m i n e their relationship to the occurrence of deaths and complications. We found a suggestive correlation between these events and operative blood loss and the performance of trisegmentectomy (Table 3). In general, we agree with Wilson and Adson t4 that the occurrence of complications after hepatic resection is related to extent of resection. Correspondingly, extraordinarily low complication rates reported by these authors (10 percent) may be related to the fact that the majority of their patients (65 percent) were treated by wedge resection. This correlation between extent of resection and complications has also been noted in several other studies of colorectal metastases resection. Nordlinger e t al. 15 noted that all complications in their series occurred in patients undergoing right lobectomy or trisegmentectomy. We have found that anatomic vs. wedge resection does not show a significant difference in major morbidity or mortality when trisegmentectomy is excluded. T h e procedure used should be dictated by the adequacy of the margin of resection, not the extent of resection. T h e correlation between operative blood loss and subsequent morbidity has been previously noted in "mixed" seriesf, 7 and is also believed to be related to
May 1990
extent of resection. Worrisome, however, is the recent report that the n u m b e r of operative blood transfusions is correlated with an increase in disease recurrence independent of size of tumor or anesthesia time36 If this is the case, previously mentioned techniques to decrease operative blood loss may improve long-term and shortterm results. T h e best incision to use for hepatic resection of colorectal metastases remains controversial. 6 In our series, the use of a thoracoabdominal incision was not related to more morbid events than an abdominal incision alone. In addition, if we considered only major hepatic resections, this difference remained insignificant (Table 3). Thus, we agree with Ryan et al. 6 that the extension of the abdominal incision into the chest s h o u l d be d o n e w h e n the a b d o m i n a l i n c i s i o n a l o n e is inadequate. We do not universally condemn thoracotomy, as has been done in other studies.4, 8 Stimpson et al., 8 in a study of patients resected for "mixed" indications, found that postoperative complications were significantly correlated with male gender and with preoperative systemic disease, such as diabetes and chronic obstructive p u l m o n a r y disease, We did not find a correlation with gender in our colorectal metastasis data, but we agree that consideration of preoperative systemic disease should be part of the selection process for hepatic resection. In summary, we have shown that hepatic resection of colorectal metastases can be performed with a 35 percent rate of moderate or severe complications and low (3 percent) 30-day operative mortality. Careful selection of patients, improvements in anesthesia and resection techniques, and a better understanding of hepatic anatomy may further improve the safety and efficacy of this procedure in the future. References 1. Nims JA. Resection of the liver for metastatic cancer. Surg Gynecol Obstet 1984;158:46-8. 2. Hughes KS, Simon R, Songhorabodi S, et al. Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of indications for resection. Surgery 1988;103:278-88. 3. Thompson HH, Thompkins RK, Longmire WP. Major hepatic resection: a 25-year experience. Ann Surg 1983;197:375-88. 4. Former JG, Kim DK, MacClean BJ, et al. Major hepatic resection for neoplasia: personal experience in 108 patients. Ann Surg 1978;193:363-71. 5. Hanks JB, Meyers WC, Filston HC, et al. Surgical resection for benign and malignant liver disease. Ann Surg 1980;191:58492. 6. Ryan WH, Hummel BW, McClellan RN. Reduction in the morbidity and mortality of major resection. Am J Surg 1982; 144:740-3. 7. Pommier RF, Woltering EA, Campbell JR, et al. Hepatic resection for primary and secondary neoplasms of the liver. Am J Surg 1987;153:428-33. 8. Stimpson RE, Pelligrini CA, Way LW. Factors affecting the morbidity of elective liver resection. Am J Surg 1987;153:18996.
Volume33 Number5
ABDOMINOPERINEAL RESECTION FOR CROHN'S DISEASE
9. Attiyeh FF, Wanebo HJ, Stearns MW. Hepatic resection for metastasis from colorectal cancer. Dis Colon Rectum 1978;21:160-2. 10. Wanebo H J, Semoglon C, Attiyeh F, et al. Surgical management of patients with primary operable colorectal cancer and synchronous liver metastases. Am J Surg 1978;135:81-5. 11. Bengmark S, Hafstrom L. The natural course for liver cancer. In: Progress in clinical cancer. New York: Grune and Stratton, 1978;8:195-200. 12. Former JG, Silva JS, Golbey RB, et al. Multiple analysis of a personal series of 247 consecutive patients with liver metastases from colorectal cancer. I. Treatment by hepatic resection. Ann Surg 1984;199:306-16. 13. JoffeSN. Techniques of liver resection. SurgRounds 1988;May:1723. 14. Wilson SM, Adson MA. Surgical treatment of hepatic metastases from colorectal cancers. Arch Surg 1976;11:330-4. 15. Nordlinger B, Quilichini MA, Parc R, et al. Hepatic resection for colorectal liver metastases: influence on survival of preoperative factors and surgery for recurrences in 80 patients. Ann Surg 1987;205:256-63. 16. Ong GB, Chan PK. Primary carcinoma of the liver. Surg Gynecol Obstet 1976;143:31-8. 17. Stone HH, Long WD, Smith RB Ill, et al. Physiological considerations in major hepatic resection. Am J Surg
4 ]3
1969; 117:78-84. 18. Inouye AA, Whelan T J Jr. Primary liver cancer: a review of 205 cases in Hawaii. Am J Surg 1979;138:53-61. 19. Andrus CH, Kaminski DL. Segmental hepatic resection utilizing the ultrasonic dissector. Arch Surg 1986;121:515-21. 20. Ottow RT, Barbieri SA, Sugarbaker PH. Liver transection: a controlled study of four different techniques in pigs. Surgery 1985;97:596-201. 21. Adson MA, van Heerden JA. Major hepatic resections for metastatic colorectal cancer. Ann Surg 1980;191:576-83. 22. Woodington GF, Waugh JM. Results of resection of metastatic tumors of the liver. Am J Surg 1963;105:24-9. 23. Iwatsuki S, Shaw BW, Starzl TE. Experience with 150 liver resections. Ann Surg 1983;197:247-53. 24. Franco D, Bonnet P, Smadja C, et al. Surgical resection of segment VIII (anterosuperior subsequent of the right lobe) in patients with liver cirrhosis and hepatocellular carcinoma. Surgery 1985;98:949-54. 25. Nagasue N, Yukaya H, Ogawa Y. Segmental and subsegmental resection of the cirrhotic liver under hepatic inflow and outflow occlusion. Br J Surg 1985;72:565-8. 26. Stephenson KR, Steinberg SM, Hughes KS, et al. Preoperative blood transfusions are associated with decreased time to recurrence and decreased survival after resection of colorectal liver metastases. Ann Surg (in press).
Vetto JT, Hughes KS, Rosenstein R, Sugarbaker PH. Morbidity and mortality of hepatic resection for metastatic colorectal carcinoma. Dis Colon Rectum 1990;33:408-413. Hepatic resection is the only curative therapy currently available for colorectal cancer metastases to the liver. However, concern over high morbidity and mortality of the procedure has limited referral of patients for resection. The authors report on 58 patients undergoing hepatic resection for colorectal metastases at the National Cancer Institute between the years 1976 and 1985. Thirty-two patients underwent a major hepatic resection, and 26 patients underwent one or more wedge resections. Mean anesthesia time was 448 minutes, mean estimated blood loss was 3663 ml, and mean hospital stay was 17.5days. Operative mortality was 3 percent, and morbidity was 62 percent. Using a grading scale for complications, 24 percent of patients had inconsequential complications, 16 percent had moderate complications, and 19 percent had severe complications. Complications were clearly related to extent of procedure. Factors that correlated best with morbidity were high blood loss and trisegmentectomy. The authors conclude that while hepatic resection can carry a high morbidity, much of this morbidity is minor and operative mortality is low. Recent improvements in anesthesia, improved resection technique, and a better understanding of hepatic anatomy have made possible correspondingly lower morbidity and mortality rates. Careful selection of patients can make hepatic resection a safe procedure. [Keywords: Liver neoplasms; Liver resection; Hepatic metastases; Morbidity]
HEPATIC RESECTION is the o n l y c u r r e n t l y available therapy for colorectal metastases that c a n result i n cure. I n fact, hepatic resection is u n i q u e l y suited for colorectal Address reprint requests to Dr. Hughes: Department of Surgery, Lahey Clinic Medical Center, 41 Mall Road, Burlington, Massachusetts 01805. 408
From the UCLA Medical Center, Los Angeles, California,* Lahe~ Clinic Medical Center, Burlington, Massachusetts, t Department of Statistics, Brown University, Providence, Rhode Island, + and the Washington Hospital Cancer Center, Washington, District oJ Columbiaw
c a r c i n o m a therapy, as the v e n o u s d r a i n a g e of the c o l o n is such that the liver m a y be the o n l y site of spl:ead. 1 A r e c e n t l y r e p o r t e d registry of h e p a t i c metastases c o m p i l e d f r o m 24 i n s t i t u t i o n s reported a 5-year actuarial survival of 33 percent a n d a 5-year actuarial disease-free survival of 21 percent after hepatic resection for metastatic c a r c i n o m a . 2 Nonetheless, the lack of c o n s e n s u s r e g a r d i n g i n d i c a t i o n s for hepatic resection, preoperative assessm e n t , operative techniques, a n d p r o g n o s i s have rendered hepatic resection a procedure used less often t h a n is indicated. 3 As m o s t reports of the m o r b i d i t y a n d m o r t a l i t y of this procedure i n c l u d e p a t i e n t s w i t h a worse (e.g., p r i m a r y liver c a r c i n o m a ) or better (e.g., h e p a t i c a d e n o m a ) p r o g n o s i s t h a n p a t i e n t s w i t h colorectal c a r c i n o m a metastases,l,~, 4-8 a n accurate description of the m o r b i d i t y a n d m o r t a l i t y associated w i t h hepatic resection for colorectal metastases is lacking. Therefore, we u n d e r t o o k a retrospective study of these events i n patients resected for colorectal metastases at the N a t i o n a l Cancer Institute.
Volume 33
Number5
409
HEPATIC RESECTION FOR METASTATIC COLORECTAL CARCINOMA
O u r purpose was to accurately describe the morbidity and mortality of resection and the factors that determine it. Materials and Methods T h e records of all patients u n d e r g o i n g hepatic resection for colorectal metastases at the National Cancer Institute, Surgery Branch, in the 10-year period from 1976 to 1985, were reviewed. T h e procedure performed, length of anesthesia, estimated operative blood loss, occurrence of postoperative complications, and the length of stay were noted. For the purposes of this study, a subjective grading scale of complication severity was used. Patients w h o had an uncomplicated postoperative course were given a grade of 0. Grade "1" indicated a "mild" or "inconsequential" c o m p l i c a t i o n that did not effect the hospital course. :(These events m i g h t not be considered complications in other series.) Grade "2" indicated a "moderate" complication that required an invasive procedure or lengthened hospital stay. Grade "3" indicated a "severe" or life-threatening complication that necessitated reoperation or significantly prolonged hospital stay. Grade "4" or postoperative mortality was defined as death within 30 days after the procedure. A tabulation of complications rated by grade is presented in T a b l e 1; all complications, no matter h o w minor, are included. In patients with more than one complication, grade was determined by the most morbid complication (Table 2). Anesthesia time, estimated blood loss, type of procedure, t i m i n g of the p r o c e d u r e (synchronous vs. metachronous), and type of incision used were analyzed with respect to complication and death rates. Statistics were determined by the chi-square test and significance was considered as P < 0.05. Results
Fifty-eight patients underwent hepatic resection for isolated colorectal metastases. T h i r t y - t w o patients u n d e r w e n t a n a t o m i c resection, i n c l u d i n g 19 r i g h t lobectomies, 6 left lobectomies, 5 trisegmentectomies, and 2 left lateral segmentectomies. Twenty-six patients underwent wedge resection including 15 multiple and l l solitary resections. Mean anesthesia time was 452 minutes (range, 270 to 750 minutes). T h e mean estimated blood loss was 3599 ml (range, 700 to 16,000 ml), and mean hospital stay was 17.5 days (range, 8 to 52 days). There were two postoperative deaths (3.1 percent). T h e first occurred in a patient with cirrhosis who underwent a lateral segmentectomy. T h e second occurred after simultaneous trisegmentectomy, bile duct reconstruction, and sigmoid colon resection. T h e r e were a total of 47 complications in 36 patients for an overall patient-related morbidity of 62 percent (36/58). A m o n g survivors, there were 44 complications
TABLE1. Overall Complications Number Mild Pleural effusion (without thoracentesis) Urinary retention Jaundice (asymptomatic) Post-thoracotomy pain Ileus TOTAL Moderated Biliary fistula Pleural effusion (requiting thoracentesis) Arrhythmias requiring treatment Atelectasis (requiring bronchoscopy) Brachial plexopathy Deep venous thrombosis Pelvic hematoma Transfusion reaction Upper respiratory infection Wour;d infection TOTAL Severe Subphrenic abscess Biliary obstruction (requiring reoperation) Hepatic failure/ascites Myocardial infarction Renal insufficiency Small-bowel obstruction (requiring reoperation) Upper gastrointestinal bleeding Wound dehiscence
10 3 1 1 1 16 5 4 3 1 1 1 1 1 1 1 19 5 1 1 1 1 1 1 1
12
TOTAL
in 34 patients for a survivor-related morbidity of 61 percent (34/56). All complications are tabulated in Table 1. Using the most morbid complication to assign grade, a s u m m a r y of related morbidity and mortality is shown in Table 2. As noted in this table, 38 percent of all patients had no complications, and another 24 percent had only " m i l d " or "inconsequential" complications. Thirty-five percent of patients survived with "moderate" or "severe" complications requiring longer hospital stay or some type of intervention. Using our grading scale, data were analyzed to determine the relationship between the severity of complications (including death) and several factors, including procedures performed, length of anesthesia, estimated operative blood loss, timing of procedure
TABLE2. Patient-Related Morbidity and Mortality Grade
n
Percent
0 (no complications) 1 (mild) 2 (moderate) 3 (severe) 4 (death) TOTAL
22 14 9 11 2 58
38 24 16 19 3 100
410
VETTO, ET AL.
TABLE 3. Relationship Between Severity of Complications and Clinical Parameters Parameters Estimated blood loss (Mean -4- SD) Procedure
Grade
Wedge Major Trisegmentectomy Synchronous Metachronous
Timing of procedure Type of incision (All Patients) Thoracoabdominal (All Patients) Abdominal (Anatomic Thoracoabdominat resection only) (Anatomic Abdominal resection only)
0-1
2-4
n o t r e a c h statistical s i g n i f i c a n c e ( P ~ 0.2). O p e r a t i v e b l o o d loss a p p e a r e d to c o r r e l a t e w i t h m o r b i d i t y a n d m o r t a l i t y , b u t this d i d n o t r e a c h statistical s i g n i f i c a n c e (P > 0.1). T h e use of a t h o r o c o a b d o m i n a l i n c i s i o n d i d n o t r e a c h statistical s i g n i f i c a n c e w h e n all p a t i e n t s w e r e c o n s i d e r e d (P = 0.15).
P*
3315 4258 (-- 2656) (+ 3594) 18 18 8 14 ~ 2 3 3 1 [ 21 33 !
14 11 11
22 | 11 f 5
9
4 f
Dis. Col. ~ Rect. May 1990
> 0.1
0.32
Discussion Hepatic metastases constitute a major problem in the t r e a t m e n t of c o l o n cancer; 10 to 25 p e r c e n t of p a t i e n t s w i l l h a v e s y n c h r o n o u s h e p a t i c m e t a s t a s e s at i n i t i a l e x p l o r a t i o n , 9-11 a n d 65 p e r c e n t of p a t i e n t s w h o r e c u r h a v e h e p a t i c m e t a s t a s e s at a u t o p s y . 9 A l t h o u g h t h e r e are a n e s t i m a t e d five to six t h o u s a n d c a n d i d a t e s for this p r o c e d u r e a n n u a l l y , 12 referral h a s b e e n less t h a n o p t i m a l b e c a u s e of p e r c e i v e d p r o h i b i t i v e m o r b i d i t y a n d m o r t a l i t y . P r e v i o u s l y r e p o r t e d m o r t a l i t y rates of 4 to 20 p e r c e n t h a v e b e e n l a r g e l y a t t r i b u t e d to b l e e d i n g , l i v e r f a i l u r e , a n d i n f e c t i o n . 13 Several studies h a v e d o c u m e n t e d i m p r o v e d s u r v i v a l w i t h h e p a t i c r e s e c t i o n for c o l o r e c t a l metastases, q u o t i n g 5-year s u r v i v a l rates f r o m 25 to 42 p e r c e n t w h e n l e s i o n s a r e resectable.2,3,~4,15 S t u d i e s t h a t d i r e c t l y a d d r e s s morbidity and mortality of hepatic resection for c o l o r e c t a l m e t a s t a s e s are l a c k i n g , h o w e v e r . T h e r e f o r e , o u r p u r p o s e i n u n d e r t a k i n g this s t u d y w a s to a c c u r a t e l y d e s c r i b e t h e m o r b i d i t y a n d m o r t a l i t y of r e s e c t i o n a n d the factors t h a t d e t e r m i n e it i n a p u r e p o p u l a t i o n o f p a t i e n t s resected for c o l o r e c t a l metastases. Morbidity data for patients undergoing hepatic
> O.2
0.15
t
O.5
r e l a t i v e to c o l o n r e s e c t i o n , a n d t y p e of i n c i s i o n used. For simplicity, patients without complications or with o n l y m i l d c o m p l i c a t i o n s w e r e c o n s i d e r e d as a s i n g l e g r o u p (grades 0-1), a n d p a t i e n t s w i t h m o r e s e r i o u s c o m p l i c a t i o n s o r d e a t h w e r e c o n s i d e r e d as a s e c o n d g r o u p (grades 2-4). T h e results of these a n a l y s e s are s h o w n i n T a b l e 3. There was no significant relationship between the severity of c o m p l i c a t i o n s a n d the l e n g t h of a n e s t h e s i a o r t i m i n g of p r o c e d u r e . T h e p e r f o r m a n c e of t r i s e g m e n t e c t o m y w a s s u g g e s t i v e of m o r e c o m p l i c a t i o n s b u t d i d
TABLE 4. Number (Percent) of Reported Postoperative Complications of Hepatic Resection ]or all Indications
Number of patients Pulmonary Pleural effusion Pneumonia Costochondritis Empyema Gastrointestinal Subphrenic abscess Infection Bile leak Hepatic failure Bleeding Prolonged subcostal drainage Duodenal leak Bowel obstruction Wound Infection Ventral hernia Cardiac failure Arrhythmias Deep venous thrombosis Brachial plexopathy
Ryan et al. 19826
Thompson et al. 1983~
Former et al. 198412
Pommier et al. 19877
Stimpson et al. 19878
52 (12) --
138
65
50
58
-52 (38) 3 (2) .
6 (9) 3 (5) --
3 (6) 2 (4) --
-6 (10) --
5 (8) ----
-----
---
-1 (2)
6 (10) -4 (7) 4 (7) 1 --1 (2)
1 (2)
1 (2)
--
--
1 (2) 1 (2)
---
----. --. NS (29) . -. ---
.
.
. .
-23 (17) 15 (11) 11 (8) . 9 (6) -. 10 (7) . 9 (6) . ---
.
.
.
.
.
. .
5 (9) 2 (3) 1 (2) 3 (5) 1 (2) --
Volume 33 Number ,5
HEPATIC
RESECTION
FOR METASTATIC
COLORECTAE
CARCINOMA
4 ] l
TABLE 5. N u m b e r (Percent) ol C o m m o n l y Reported Postoperative Complications Jrom Hepatic Resection Jor Colorectal Metastases
Number of patients Pleural effusion S u b p h r e n i c abscess C a t h e t e r sepsis Wound infection Hematoma Gastrointestinal bleeding
Vetto, 1989
H a n k s et al. 19805
N i m s , 19841
N o r d l i n g e r et al. 1987 xs
58 14 (24) 5 (9) -1 (2) l (2) 1 (2)
11 1 (9) --12 (18) 1 (9) --
9 -3 (33) -----
80 3 (4) 2 (3) 3 (4) --1 (1)
resection for a variety of indications are available from a number of studies and are summarized in Table 4. These "mixed" studies are clearly not applicable to a pure p o p u l a t i o n of patients resected for colorectal carcinoma. According to Stimpson, 8 three factors that help to determine outcome after hepatic resection are severity of the primary disease, age, and presence of disease in other organ systems. Patients undergoing resection for benign disease will have a better prognosis because they are young, have no other organs involved, and their disease carries a good prognosis overall. Patients with primary liver tumors carry the least favorable prognosis of all these groups because of the overall poor prognosis of their tumor, their advanced age, the frequent presence of disease elsewhere, and the c o m m o n association with cirrhosis (which can increase operative mortality to 21 to 60 percent because of increased bleeding and poor postoperative regeneration of tissue), t6-18 These different prognostic groups for hepatic resection have been p r e v i o u s l y n o t e d by T h o m p s o n et al. ~ Clearly, patients resected [or colorectal metastases are different from those resected for other indications, and their morbidity and mortality should be considered
separately. In general, these patients are older (with mean ages of 55 to 61 years),l~ noncirrhotic, have malignant disease with its overall poor prognosis, but are usually disease-free in other organ systems (a recognized criterion for hepatic resection), z Morbidity data for this distinct g r o u p are a v a i l a b l e f r o m some studies a n d are summarized in Table 5. In our series, we report a mean anesthesia time of 452 minutes; this is slightly longer than has been reported in other series1, s and is probably due, in part, to a policy o[ intraoperative line placement at our institution. Mean operative blood loss of 3599 ml was more than that reported by Andrus and Kaminski, ~9 and similar to reports by Stimpson et al. 8 and Pommier et al. 7 Our largest blood losses occurred in our earlier patients, before we adopted the use of newer blood saving techniques such as the ultrasonic dissector (which can decrease both blood loss and operative time),t~,~9,20 and improved anatomic resection techniques. Our mean hospital stay of 17.5 days was similar to that of Nordlinger et al. 15 in their series of patients resected for colorectal metastases. Our 30-day postoperative mortality of 3.1 percent is similar to the generally low mortality reported by
TABLE 6. Reported Mortality o/ Hepatic Resection
n
All I n d i c a t i o n s Mortality
Percent
n
W i l s o n a n d A d s o n , 197614 A t t i y e h , et al. 19789 F o r m e r et al., 19784 W a n e b o et al., 19781~ H a n k s et al., 19805 A d s o n a n d v a n H e e r d e n , 198021
--108 -32 --
--10 -4 --
--(9*) -(12.5 +) --
60 25 25]" 29 11]" 34]-
2 1 2
(2) (4) NS (7) (9) (6)
R y a n et al., 19825 F o r m e r et al., 198412 T h o m p s o n et al., 19833 N i m s , 19841 A n d r u s a n d K a m i n s k i , 198619 N o r d l i n g e r et al., 198715 P o m m i e r et al., 19877 S t i m p s o n et al., 19878
52 -138 10 13 -50 58
4 -15 0 1 -0 2
(8) -(11) (0) (8) -(0) (3)
12]58 22 9 -80 25 23 +
NS 4 0 0 -4 0 1
NS (7) (0) (0) -(0) (0) (4)
Series
N = * = ]- = ++ =
n u m b e r of p a t i e n t s ; N S = n o t stated. four percent for standard resection. excluding wedge resections. f o u r p e r c e n t s i n c e 1970.
Colorectal Metasasis Mortality 1 1
Percent
412
Dis. Col. & Rect.
VETTO, ET AL.
previous series of hepatic resection for colorectal metastases (Table 6).~,3-1~ Combining the data from these 11 series with our own data, the operative mortality is 4 percent (18/446). This same operative mortality of 4 percent has also been reported in "mixed" series of hepatic resection for all indications.22, 23 One of our two operative deaths occurred in a patient with cirrhosis; as previously noted, the presence of cirrhosis increases the risk of death from hepatic resection. 3 Newer techniques such as anatomic resection 24 and routine use of the Pringle maneuver z5 may improve the outcome of this procedure in cirrhotics. Our overall patient-related complication rate of 62 percent is higher than that reported by other series but represents a painstaking report of all complications, no matter how minor (Table 1). Viewed in a more favorable way, 38 percent of our patients (including 25 percent of patients undergoing major anatomic resection) had a completely uncomplicated postoperative course, and another 24 percent had only inconsequential events that required neither extended hospital stay nor a therapeutic procedure (Table 2). Our combined rate of moderate and severe complications was 35 percent, which is similar to previously reported series of both "mixed" indicationsS-6,8,19 and colorectal metastases patients, ~ which tend to report only these more serious complications. Clearly, pleural effusionsS,ts,21 (often asymptomatic), s u b p h r e n i c a b s c e s s , i , 7 and w o u n d problems are the most c o m m o n l y reported complications in patients resected for colorectal metastases (Table 5). We analyzed several factors to d e t e r m i n e their relationship to the occurrence of deaths and complications. We found a suggestive correlation between these events and operative blood loss and the performance of trisegmentectomy (Table 3). In general, we agree with Wilson and Adson t4 that the occurrence of complications after hepatic resection is related to extent of resection. Correspondingly, extraordinarily low complication rates reported by these authors (10 percent) may be related to the fact that the majority of their patients (65 percent) were treated by wedge resection. This correlation between extent of resection and complications has also been noted in several other studies of colorectal metastases resection. Nordlinger e t al. 15 noted that all complications in their series occurred in patients undergoing right lobectomy or trisegmentectomy. We have found that anatomic vs. wedge resection does not show a significant difference in major morbidity or mortality when trisegmentectomy is excluded. T h e procedure used should be dictated by the adequacy of the margin of resection, not the extent of resection. T h e correlation between operative blood loss and subsequent morbidity has been previously noted in "mixed" seriesf, 7 and is also believed to be related to
May 1990
extent of resection. Worrisome, however, is the recent report that the n u m b e r of operative blood transfusions is correlated with an increase in disease recurrence independent of size of tumor or anesthesia time36 If this is the case, previously mentioned techniques to decrease operative blood loss may improve long-term and shortterm results. T h e best incision to use for hepatic resection of colorectal metastases remains controversial. 6 In our series, the use of a thoracoabdominal incision was not related to more morbid events than an abdominal incision alone. In addition, if we considered only major hepatic resections, this difference remained insignificant (Table 3). Thus, we agree with Ryan et al. 6 that the extension of the abdominal incision into the chest s h o u l d be d o n e w h e n the a b d o m i n a l i n c i s i o n a l o n e is inadequate. We do not universally condemn thoracotomy, as has been done in other studies.4, 8 Stimpson et al., 8 in a study of patients resected for "mixed" indications, found that postoperative complications were significantly correlated with male gender and with preoperative systemic disease, such as diabetes and chronic obstructive p u l m o n a r y disease, We did not find a correlation with gender in our colorectal metastasis data, but we agree that consideration of preoperative systemic disease should be part of the selection process for hepatic resection. In summary, we have shown that hepatic resection of colorectal metastases can be performed with a 35 percent rate of moderate or severe complications and low (3 percent) 30-day operative mortality. Careful selection of patients, improvements in anesthesia and resection techniques, and a better understanding of hepatic anatomy may further improve the safety and efficacy of this procedure in the future. References 1. Nims JA. Resection of the liver for metastatic cancer. Surg Gynecol Obstet 1984;158:46-8. 2. Hughes KS, Simon R, Songhorabodi S, et al. Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of indications for resection. Surgery 1988;103:278-88. 3. Thompson HH, Thompkins RK, Longmire WP. Major hepatic resection: a 25-year experience. Ann Surg 1983;197:375-88. 4. Former JG, Kim DK, MacClean BJ, et al. Major hepatic resection for neoplasia: personal experience in 108 patients. Ann Surg 1978;193:363-71. 5. Hanks JB, Meyers WC, Filston HC, et al. Surgical resection for benign and malignant liver disease. Ann Surg 1980;191:58492. 6. Ryan WH, Hummel BW, McClellan RN. Reduction in the morbidity and mortality of major resection. Am J Surg 1982; 144:740-3. 7. Pommier RF, Woltering EA, Campbell JR, et al. Hepatic resection for primary and secondary neoplasms of the liver. Am J Surg 1987;153:428-33. 8. Stimpson RE, Pelligrini CA, Way LW. Factors affecting the morbidity of elective liver resection. Am J Surg 1987;153:18996.
Volume33 Number5
ABDOMINOPERINEAL RESECTION FOR CROHN'S DISEASE
9. Attiyeh FF, Wanebo HJ, Stearns MW. Hepatic resection for metastasis from colorectal cancer. Dis Colon Rectum 1978;21:160-2. 10. Wanebo H J, Semoglon C, Attiyeh F, et al. Surgical management of patients with primary operable colorectal cancer and synchronous liver metastases. Am J Surg 1978;135:81-5. 11. Bengmark S, Hafstrom L. The natural course for liver cancer. In: Progress in clinical cancer. New York: Grune and Stratton, 1978;8:195-200. 12. Former JG, Silva JS, Golbey RB, et al. Multiple analysis of a personal series of 247 consecutive patients with liver metastases from colorectal cancer. I. Treatment by hepatic resection. Ann Surg 1984;199:306-16. 13. JoffeSN. Techniques of liver resection. SurgRounds 1988;May:1723. 14. Wilson SM, Adson MA. Surgical treatment of hepatic metastases from colorectal cancers. Arch Surg 1976;11:330-4. 15. Nordlinger B, Quilichini MA, Parc R, et al. Hepatic resection for colorectal liver metastases: influence on survival of preoperative factors and surgery for recurrences in 80 patients. Ann Surg 1987;205:256-63. 16. Ong GB, Chan PK. Primary carcinoma of the liver. Surg Gynecol Obstet 1976;143:31-8. 17. Stone HH, Long WD, Smith RB Ill, et al. Physiological considerations in major hepatic resection. Am J Surg
4 ]3
1969; 117:78-84. 18. Inouye AA, Whelan T J Jr. Primary liver cancer: a review of 205 cases in Hawaii. Am J Surg 1979;138:53-61. 19. Andrus CH, Kaminski DL. Segmental hepatic resection utilizing the ultrasonic dissector. Arch Surg 1986;121:515-21. 20. Ottow RT, Barbieri SA, Sugarbaker PH. Liver transection: a controlled study of four different techniques in pigs. Surgery 1985;97:596-201. 21. Adson MA, van Heerden JA. Major hepatic resections for metastatic colorectal cancer. Ann Surg 1980;191:576-83. 22. Woodington GF, Waugh JM. Results of resection of metastatic tumors of the liver. Am J Surg 1963;105:24-9. 23. Iwatsuki S, Shaw BW, Starzl TE. Experience with 150 liver resections. Ann Surg 1983;197:247-53. 24. Franco D, Bonnet P, Smadja C, et al. Surgical resection of segment VIII (anterosuperior subsequent of the right lobe) in patients with liver cirrhosis and hepatocellular carcinoma. Surgery 1985;98:949-54. 25. Nagasue N, Yukaya H, Ogawa Y. Segmental and subsegmental resection of the cirrhotic liver under hepatic inflow and outflow occlusion. Br J Surg 1985;72:565-8. 26. Stephenson KR, Steinberg SM, Hughes KS, et al. Preoperative blood transfusions are associated with decreased time to recurrence and decreased survival after resection of colorectal liver metastases. Ann Surg (in press).
