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Simultaneous liver and colorectal resections are safe for synchronous colorectal liver metastasis
Simultaneous Liver and Colorectal Resections Are Safe for Synchronous Colorectal Liver Metastasis Robert Martin, MD, Philip Paty, MD, Yuman Fong, MD, FACS, Andrew Grace, MD, Alfred Cohen, MD, FACS, Ronald DeMatteo, MD, FACS, William Jarnagin, MD, FACS, Leslie Blumgart, MD, FACS The optimal surgical strategy for the treatment of synchronous resectable colorectal liver metastasis has not been defined. The aims of this study were to review our experience with synchronous colorectal metastasis and to define the safety of simultaneous versus staged resection of the colon and liver. STUDY DESIGN: From September 1984 through November 2001, 240 patients were treated surgically for primary adenocarcinoma of the large bowel and synchronous hepatic metastasis. Clinicopathologic, operative, and perioperative data were reviewed to evaluate selection criteria, operative methods, and perioperative outcomes. RESULTS: One hundred thirty-four patients underwent simultaneous resection of a colorectal primary and hepatic metastasis in a single operation (Group I), and 106 patients underwent staged operations (Group II). Simultaneous resections tend to be performed for right colon primaries (p ⬍ 0.001), smaller (p ⬍ 0.01) and fewer (p ⬍ 0.001) liver metastases, and less extensive liver resection (p ⬍ 0.001). Complications were less common in the simultaneous resection group, with 65 patients (49%) sustaining 142 complications, compared with 71 patients (67%) sustaining 197 complications for both hospitalizations in the staged resection group (p ⬍ 0.003). Patients having simultaneous resection required fewer days in the hospital (median 10 days versus 18 days, p ⫽ 0.001). Perioperative mortality was similar (simultaneous, n ⫽ 3; staged, n ⫽ 3). CONCLUSIONS: Simultaneous colon and liver resection is safe and efficient in the treatment of patients with colorectal cancer and synchronous liver metastasis. By avoiding a second laparotomy, the overall complication rate is reduced, with no change in operative mortality. Given its reduced morbidity, shorter treatment time, and similar cancer outcomes, simultaneous resection should be considered a safe option in patients with resectable synchronous colorectal metastasis. ( J Am Coll Surg 2003;197:233–242. © 2003 by the American College of Surgeons) BACKGROUND:
Colorectal cancer remains the second leading cause of cancer-related death in the United States, with 63,000 deaths annually.1 Liver metastases will develop in more than one-third of patients, and among these the liver will be the only site of metastasis in 20%.2 Surgical resection of liver metastases remains the only therapy with poten-
tial for cure.3 Five-year survival rates of 25% to 35% have been reported in the literature.4-6 Synchronous liver metastasis, commonly defined as liver metastasis occurring within 12 months of the colon primary, represents 13% to 25% of newly diagnosed colorectal liver metastases.7,8 The optimal timing for surgical resection of synchronous metastasis has not been well defined. Most series reporting on the surgical management of synchronous colorectal metastasis have recommended a staged approach with initial resection of the primary lesion followed by hepatic resection 2 to 3 months later9-13 (Table 1). Recently, the paradigm for the surgical management of synchronous colorectal metastasis has begun to change, with authors reporting good results for simultaneous resection of colon and liver tu-
No competing interests declared.
Presented at the American College of Surgeons 88th Annual Clinical Congress, San Francisco, CA, October 2002. Received October 23, 2002; Accepted November 26, 2002. From the Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (Martin, Paty, Fong, Grace, DeMatteo, Jarnagin, Blumgart), and the Lucille Markey Cancer Center, University of Kentucky, Lexington, KY (Cohen). Correspondence address: Philip B Paty, MD, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.
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Table 1. Published Results of Simultaneous Versus Staged Resection for Synchronous Colorectal Hepatic Metastasis First author
Year
n
Vogt27
1991
36
Scheele2
1991
98
Jenkins12
1997
46
Elias15 Jaeck11
1995 1996
53 41
Nordlinger10
1996
1,008
Bolton23
2000
165
Fujita13
2000
97
Lyass14
2001
112
Type of resection
Morbidity (%)
Mortality (%)
19 simul 17 staged 60 simul 38 staged 22 simul 24 staged 53 simul 20 simul 21 staged 115 simul 893 other 50 simul 115 other 83 simul 14 staged 26 simul 86 staged
5.2 17.6 nr
0
nr
nr
19 20 10 nr
0 0
nr 58 27 35
2
7 2 12 4 0 0 2.3
nr, Not recorded; other, staged and metachronous resections; simul, simultaneous resections.
mors.14,15 But, there has not been a large enough series to permit detailed evaluation of the safety and morbidity of simultaneous resection compared with staged resection. The primary goal of this study was to determine if simultaneous resection is similar to staged resection with regard to morbidity and mortality. METHODS Using prospective surgical databases at Memorial SloanKettering Cancer Center, 240 patients were identified from the Colorectal Surgical Service and the Hepatobiliary Surgical Service who underwent resection of a primary colorectal cancer and a synchronous hepatic metastasis between September 1984 and November 2001. Synchronous hepatic metastases were defined as those identified at the time of diagnosis of the primary colon cancer. All colon and hepatic resections were performed at Memorial Sloan-Kettering Cancer Center. The type of liver resection performed was defined by the Couinaud classification.16 The technique for anesthetic management during hepatectomy has been previously reported.17 In principle, we use a low central venous pressure (less than 5 mmHg), while maintaining a urine output of 25 mL/hr and a systolic blood pressure greater than 90 mmHg during parenchymal transection. After the specimen is removed, crystalloid is administered intravenously to
achieve euvolemia. Packed red blood cells and autologous blood are given to maintain a hemoglobin greater than 10 g/dL in patients with evidence of either coronary or cerebrovascular disease. Intraoperative blood products are not administered until blood loss exceeds 25% of the total blood volume. Outflow control of the hepatic veins before parenchymal division was nearly always obtained in lobectomy or extended resections. The liver parenchyma was divided using Kelly clamps to crush liver tissue and expose bile ducts and blood vessels, which were clipped, tied, or stapled. Intermittent inflow vascular occlusion (the Pringle maneuver)18 was used and applied for 5- to 10minute intervals, released briefly, and reapplied as necessary. Pringle time was recorded as the total cumulative Pringle time applied during parenchymal transection. Postoperative complications and length of hospital stay were available from institutional databases using a standard classification scale of complications (Table 2). For patients sustaining more than one complication, comparison of in-hospital and 30-day postoperative complication were evaluated by assigning the complication with the highest severity level for each patient. Complications were defined by published criteria.19 Earlier cardiac history was defined as history of angina, previous coronary artery disease defined by cardiac catheterization, previous myocardial infarction, cardiac valve
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Table 2. Complication Criteria Criteria
0 1
No complication Oral antibiotics, bowel rest, basic monitoring, supportive care IV antibiotics, TPN, Drainage not required, prolonged tube feedings, transfusions, arrhythmia treated with intravenous medication, chest tube insertion Interventional radiology drainage, operative drainage, intensive care unit admission, intubation, pacemaker placement, bronchoscopy, esophagogastroduodenoscopy Chronic disability, organ resection, enteral diversion (colostomy or ileostomy) Death from complication
3
4 5
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Table 3. Patient Demographics
Complication
2
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TPN, total parenteral nutrition.
dysfunction requiring medication, or a history of congestive heart failure or tachyarrhythmia. Previous pulmonary disease history was defined as history of abnormal pulmonary function tests, asthma requiring daily meter-dosed inhalers, or tobacco use greater than 25 pack years. All patients were reviewed and classified using a preoperative Clinical Risk Score (CRS) prognostic scoring system defined for colorectal metastasis.3 This five-point preoperative clinical score evaluates patients by five factors: 1) disease-free interval less than 12 months, 2) CEA greater than 200, 3) lymph node positive primary, 4) more than 1 hepatic lesion, and 5) hepatic lesion greater than 5 cm in size. Chi-square, Student’s t-test, and Mann-Whitney’s U test for nominal, continuous, and ordinal variables were used to evaluate the association of independent variables to surgical complications. Proportional hazards analysis was performed on all variables found significant by univariate analysis. Relative risk with 95% confidence intervals was calculated as a measure of association. Differences of p ⬍ 0.05 were considered significant. Statistical analysis was performed using JMP software (JMP, SAS Institute Inc, Cary, NC). RESULTS A total of 240 patients were treated for synchronous colorectal hepatic metastasis. There was an even distribution of women (46%) and men (54%), with a median age of 63 years (range 23 to 85 years). The primary colorectal adenocarcinoma was located within the anal canal in 16 patients (7%), within the sigmoid or rectum in 95 patients (40%), within the distal transverse colon
Demographics
Gender Female Male Age, (y), median (range) Cardiac history Yes No Pulmonary history Yes No Prior abdominal surgery Yes No
Staged (n ⴝ 106)
Simultaneous (n ⴝ 134)
45 (42%) 61 (58%) 61 (23–82)
65 (49%) 69 (51%) 64 (27–85)
p Value
NS NS
10 (10%) 96 (90%)
20 (15%) 114 (85%)
NS
20 (18%) 86 (82%)
22 (16%) 134 (84%)
NS
22 (20%) 84 (80%)
34 (25%) 100 (75%)
NS
or descending colon in 61 patients (25%), and within the right colon in 68 patients (28%). The majority of patients presented with rectal bleeding or anemia. A small minority presented with obstruction (n ⫽ 18, 7.5%) or perforation (n ⫽ 6, 2.5%). A total of 134 patients underwent simultaneous resection of a colorectal primary and hepatic metastasis (Group I). These patients were compared with 106 patients who underwent staged resection (Group II). There was a similar distribution of gender, age, and comorbid cardiac and pulmonary disease in both groups of patients (Table 3). The extent of hepatic disease was different, with Group I found to have significantly fewer numbers of hepatic metastases (p ⫽ 0.001) and smaller metastases (p ⫽ 0.009) when compared with Group II (Table 4). Overall, patients subjected to a staged resection are a higher risk group in terms of longterm prognosis as defined by the Clinical Risk Score (Table 4). Right hemicolectomy was more common in Group I, and there were a greater number of left hemicolectomies and rectal resections in Group II (Table 4). Simultaneous resection was associated with a significantly greater number of hepatic wedge resections (Table 4), which accounted for the greatest difference in surgical procedures between the two groups. Conversely, a greater proportion of major hepatic resections (lobe or more) were performed as staged resections. The tendency to perform major liver resections as simultaneous procedures appeared to be influenced in part by the location of the primary colon cancer. There was a greater tendency to perform a simultaneous major hepatic resection in patients who required a right colectomy. Con-
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Table 4. Extent of Disease and Resection Performed in Patients with Resectable Synchronous Hepatic Metastasis Staged (n ⴝ 106) Variables
No. of liver lesions 1 ⬎1 Size of lesions (cm) ⱕ5 ⬎5 CEA (median, range) Primary resection Right colectomy Left colectomy LAR APR Liver resection Wedge Segmental ⱖLobe CRS 1 2 3 4 5
n
Simultaneous (n ⴝ 134) %
n
81 53
%
p Value
(60%) (40%)
0.001
(77%) (23%)
0.009
42 64
(40%) (60%)
65 41 21 (0.7–2,327)
(61%) (39%)
15 31 49 11
(14%) (29%) (46%) (10%)
53 30 46 5
(40%) (22%) (33%) (4%)
9 21 76
(8%) (20%) (72%)
49 40 45
(37%) (30%) (34%)
13 34 35 22 2
(12%) (32%) (33%) (21%) (2%)
29 52 41 7 5
(21%) (39%) (31%) (5%) (4%)
103 31 9.9 (1–6,870)
NS
0.001
0.001 0.003
APR, abdominoperineal resection; CRS, Clinical Risk Score; LAR, low anterior resection.
versely, among patients requiring left colectomy or rectal resection, major hepatic resections were more often performed as staged procedures. Overall operative duration for Group I was a median of 235 minutes (range 105 to 645 minutes). Total operative time for Group II was significantly longer, with a median of 411 minutes (range 195 to 793 minutes) (Table 5). Median operative blood loss for the simultaneous group was 550 mL (range 100 to 4,000 mL), compared with the staged group, which had a median blood loss of 400 mL (range 50 to 3,000 mL) for the colectomy and 700 mL (range 70 to 4,300 mL) for the hepatectomy (total ⫽ 1,100 mL, range 250 to 4,950 mL; p ⬍ 0.001). In the 134 patients who underwent a simultaneous resection, 42 patients (31%) received blood transfusion during their hospitalization. In the 106 patients who underwent a staged resection, 41 patients (38%) received a blood transfusion during one of their hospitalizations. The length of hospital stay was also significantly shorter for the simultaneous resection patients than for the combined hospitalizations of the staged colorectal and hepatic resection patients (Table
5). Even when patients with major liver resections (lobectomy or more) were considered, operative time, blood loss, and length of stay were significantly longer for the staged resections. Complications after all surgical procedures occurred in 136 of 240 patients (56%). In Group I, 65 patients (49%) sustained 142 complications. In Group II, 71 different patients (67%) sustained 197 complications for both hospitalizations. When types of complications were evaluated, the difference in the overall complication rate between the simultaneous and the staged group primarily occurred from the need for a second laparotomy in the staged group (Table 5). When specific laparotomy complications were evaluated, there was a twofold increase in Group II (Table 5). When the hepatectomy complications (hepatic fluid and abscess) and colonic complications (pelvic abscess and anastamotic leak) were evaluated, there was no difference in procedure-specific complications. The overall complication rate for simultaneous resection (48%) was significantly less than for staged resections (68%, p ⫽ 0.003). This was true even when the analysis was restricted to the
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Table 5. Outcomes and Complications after Staged or Simultaneous Resection Staged (n ⴝ 106) Complications
Laparotomy Wound infection Ileus Pulmonary Cardiac Pelvic abscess Hepatic fluid/abscess Hepatic failure Operative time, median, min (range) Total blood loss, median, mL (range) Length of stay, median, d (range) Severity of all complications (n ⫽ 136) Colon Grades 1 & 2 Grades 3 & 4 Grade 5 Total Liver Grades 1 & 2 Grades 3 & 4 Grade 5 Total Total Grades 1 & 2 Grades 3 & 4 Grade 5 Total Combined Grades 1 & 2 Grades 3 & 4 Grade 5 Total Most severe complication for each patient Grades 1 & 2 Grades 3 & 4 Grade 5
Simultaneous (n ⴝ 134)
n
%
n
24 26 19 14 3 11 2 411 (195–793) 1,100 (250–4,950) 18 (7–58) 197
23 26 18 13
17 16 9 5 4 13 2 235 (105–645) 550 (100–4,000) 10 (0–49) 142
55 16 0 71
28 8 0 36
84 39 3 126
43 20 2 64
139 55 3 197
71 28 2 100
71 41 27 3
134 patients who underwent major liver resection (lobectomy or more), with the overall complications of simultaneous resections (27 of 45, 60%) being significantly less than for stage resections (53 of 76, 70%, p ⫽ 0.03) (Table 6). When the complications were graded by severity, the relative distribution of mild (Grades 1 and 2), moderate (Grades 3 and 4), and perioperative mortality (Grade 5) was found to be no different between the groups (Table 5). There was a similar predominance of mild complica-
58 38 4
142 97 42 3 142 65 36 25 3
%
13 12 7 4
p Value
0.06 0.02 0.01 0.01 NS NS NS 0.001 0.001 0.001
0.001
68 30 2 100 0.006 55 38 4
tions (Grades 1 and 2) in Group I (68%) and in Group II (71%). An equal proportion of complications were severe (Grades 3 and 4) in Group I (30%) and Group II (28%). There was no significant difference in operative mortality rates (Group I ⫽ 3 [2%] versus Group II ⫽ 2 [2%]). When only the most severe complication was considered for each patient, the relative proportion of mild (Grades 1 and 2) and severe (Grades 3 and 4) complications was not found to be different in Groups I and II (Table 5).
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Table 6. Outcomes and Complications after Staged or Simultaneous Resection Involving Major Liver Resections (Lobectomy or More) Variables
Staged (n ⴝ 76)
Simultaneous (n ⴝ 45)
p Value
Operative time, min (range) Total blood loss, mL (range) Length of stay, d (range) Total no. of complications Total patients with complications Total patients with Grade 3 or 4 complications Mortality
423 (195–793) 1100 (250–4,950) 18 (7–58) 149 53 (70%) 19 (25%) 3 (4%)
290 (203–445) 800 (100–4,000) 12 (0–31) 65 27 (60%) 12 (27%) 2 (4%)
0.001 0.004 0.001 0.03 NS NS
Operative time, blood loss, and length of stay are median values.
The patient population was then analyzed for factors predictive of any complication after surgical resection. Univariate analysis did not demonstrate a significant difference in complications with age, gender, preoperative cardiac history, albumin at the time of colectomy or hepatectomy, hemoglobin at the time of colectomy or hepatectomy, blood loss at the time of colectomy, duration of colectomy, type of colectomy or Pringle time (Table 7). Factors found to be significant on both univariate and logistic regression were preoperative pulmonary history, past abdominal surgery, resection of a lobe or more, and timing of surgery (Table 7). Because this study was not a prospective randomized trial, the timing of surgical resection was biased in both groups. So separate analysis of predictors of any complications and severe complications was evaluated in both the simultaneous and staged groups. In the simultaneous group, univariate analysis identified preoperative pulmonary history (p ⫽ 0.03), a lobe or more resected (p ⫽ 0.01), estimated blood loss of more than 1,000 mL (p ⫽ 0.05), and operative duration of greater than 5.5 hours (p ⫽ 0.003) to be significant for overall complications and severe complications, but logistic regression did not identify these factors to be significant. In the staged group, univariate analysis did not identify any factors when patients underwent a colectomy because the overall complication rate was small. During hepatectomy preoperative pulmonary dysfunction (p ⫽ 0.04) and past abdominal surgery (p ⫽ 0.04) were found to be significant factors, with estimated blood loss greater than 1,000 mL (p ⫽ 0.06) approaching significance. These factors were not found to be significant on logistic regression. DISCUSSION Synchronous colorectal metastases are found in 20% to 30% of patients at the time of initial diagnosis of colo-
rectal cancer.20 Among these stage IV patients, resectable colorectal metastases are seen in 10% to 25%.7,21,22 Surgical management of this large group of patients is controversial and widely debated. Some authors have reported higher complication and mortality rates for patients with simultaneous resection of the colon and liver. Nordlinger and colleagues10 reported an operative mortality of 7% for simultaneous resections, compared with 2% (p ⬍ 0.01) for staged resections. Bolton and Fuhrman23 reported a 12% operative mortality for simultaneous resections and a 24% mortality for simultaneous resections involving major liver resections.23 A staged operative approach was therefore recommended, with the liver resection performed 2 to 3 months after the resection of the primary.24,25 The main reasons cited in favor of a staged operation are theoretical improvements in perioperative outcomes. Some small and moderate-sized studies have reported safety of simultaneous resection of hepatic metastases and primary colorectal cancers. Schlag and associates9 reported 25 patients with synchronous colorectal metastasis treated with a simultaneous resection with a 0% mortality and 34% morbidity (Table 1). The majority of the liver resections in this report were wedge (44%) or segment (17%) resections, with only 27% undergoing hepatic lobectomy. This distribution of liver resections is similar to that in our study population (Table 7). Jatzko and coworkers26 reported 22 patients, with a mortality of 4.5% and a morbidity of 23%, and Vogt and colleagues27 reported 19 patients, with a mortality of 0% and morbidity of 5% (Table 1). Elias and associates’15 report of 53 patients,15 and Fujita and coauthors’13 report of 83 patients have all demonstrated mortality rates of 0% and morbidity of 19% to 33% (Table 1). Our study confirms that simultaneous resection can be performed safely. In fact, the overall complication rate
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Table 7. Evaluation of Factors Predictive of All Complications after Surgical Procedures
Factor
Gender Male (n ⫽ 110) Female (n ⫽ 130) Cardiac history Yes (n ⫽ 30) No (n ⫽ 210) Pulmonary history Yes (n ⫽ 42) No (n ⫽ 198) Past abdominal surgery Yes (n ⫽ 54) No (n ⫽ 186) Type of colectomy Right (n ⫽ 68) Left (n ⫽ 61) Low anterior resection (n ⫽ 95) Abdominoperineal resection (n ⫽ 16) Extent hepatic resection ⬍Lobe (n ⫽ 119) ⱖLobe (n ⫽ 121) Timing of resection Simultaneous Staged Type of liver resection Wedge (n ⫽ 58) Segmentectomy (n ⫽ 48) Right hepatectomy (n ⫽ 55) Left lateral (n ⫽ 23) Left hepatectomy (n ⫽ 1) Extended right hepatectomy (n ⫽ 41) Extended left hepatectomy (n ⫽ 14)
Complication (%)
Univariate
Multivariate, p value, relative risk (95% confidence interval)
75 61
0.7
NS
46 58
0.2
NS
80 52
0.0004
0.002 1.94 (1.31–3.05)
70 53
0.02
p ⫽ 0.02 1.47 (1.05–2.09)
51 54 58 75
0.3
NS
47 66
0.003
0.07 1.31 (0.97–1.76)
47 68
0.03
0.02 1.44 (1.07–1.95)
31 62 63 56 100 63 92
0.001
NS
was found to be higher in the staged resection group (Table 5), and on multivariate analysis, staged resection proved to be an independent predictor of overall complications (Table 6). The increase in complications seen in the staged resection group was explained by the need for two laparotomics and a resulting increase of complications associated with laparotomy (Table 5). Procedure-specific complications related to resection of the colon, or resection of the liver did not differ in either group (Table 6). So, in centers where hepatectomy is performed frequently, simultaneous resection is an acceptable treatment strategy in suitable patients with resectable synchronous hepatic metastases. Because of the retrospective nature of this study, the
selection factors that led surgeons to perform simultaneous resection of the colon and liver cannot be completely defined. It is apparent that a simultaneous resection was more often associated with right colonic primaries and when only a single metastatic lesion was found in the liver. Conversely, a staged resection was more often associated with rectal primaries or multiple liver lesions. But subset analysis of patients according to location of primary tumor (colon versus rectum) and according to extent of hepatic resection (wedge or segment versus lobe or greater) did not reveal a particular group of patients who are placed at unacceptably high risk by the performance of simultaneous colon and liver resection. This indicates that the judgment of the oper-
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ating surgeons appeared to be the most important factor in patient selection. When simultaneous resections were chosen, such resections were well tolerated regardless of the location of the primary or the extent of liver resection. So, at present, we cannot define complete contraindications to performing simultaneous resection. We believe the final decision to perform a simultaneous or staged liver resection should be based on the experience and comfort level of the surgical team. The time necessary to perform both operations can also be a selection criterion, because an extraordinarily long operation would likely result in a more complicated perioperative course. In our series, no simultaneous operation lasted more than 8 hours, and 95% were completed within 7 hours, 86% within 6 hours, and 75% within 5 hours. In general, our institution will use a simultaneous resection if one of the resections will be straightforward, and the total operative time is likely to be less than 6 hours. Two difficult operations in general will not be performed simultaneously. A number of technical considerations should be discussed. Some clinicians have been worried about using the Pringle maneuver because of fear that portal venous occlusion will lead to intestinal mucosal edema and anastamotic breakdown. In the current study, the Pringle maneuver was used in the intermittent fashion with no evidence of increased anastamotic complications. Another reason that some have been reluctant to perform a simultaneous resection is the concern that the incision might preclude either an adequate liver or an adequate colorectal resection from an oncologic standpoint. In practice, a right subcostal incision can be used for any major liver resection and provide more than adequate exposure for a radical right or transverse colectomy. A generous midline incision from xiphoid to pubis will provide adequate exposure for left, sigmoid, or rectal resections while providing good exposure for most major liver resections. If in addition to this midline incision, a right transverse extension is taken, adequate exposure is possible, even in those few individuals who are markedly obese with very high-riding livers, where the midline incision alone provides insufficient exposure. Most importantly, the decision to proceed with a simultaneous hepatectomy at the time of colon resection should not influence the extent of either the colorectal or the hepatic resection. We have previously demonstrated a significantly higher rate of positive surgical margins for nonanatomic wedge resections compared with anatomic
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hepatectomies.28 So if the operating surgeon is not prepared to perform the anatomic hepatic resection required to achieve negative margins in a patient with a synchronous metastasis, then the liver resection should be deferred. So simultaneous resection of the primary colon tumor and hepatic metastasis is safe and efficient in treating patients with synchronous colorectal metastasis. The overall complication rate is lower for simultaneous resection than with staged resection, perioperative mortality rate is the same, and length of hospital stay is significantly less. Because it avoids a second laparotomy and reduces complications, simultaneous resection of the colon primary tumor and liver metastasis should be considered the preferred treatment for suitable patients with resectable synchronous colorectal metastasis. Because effective adjuvant therapies exist for colorectal cancer, a simultaneous resection also provides for prompt completion of surgical therapy and earlier initiation of adjuvant therapy in this group of patients with high risk of additional microscopic disease who are most likely to benefit from such adjuvant therapy. Author Contributions
Study conception and design: Paty, Fong, Blumgart Acquisition of data: Martin, Paty, Fong, Grace Analysis and interpretation of data: Martin, Paty, Fong Drafting of manuscript: Martin, Paty, Fong, Blumgart Critical revision: Fong, Cohen, DeMatteo, Jarnagin, Blumgart Statistical expertise: Martin Supervision: Paty, Fong, Blumgart REFERENCES 1. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1996. CA Cancer J Clin 1996;46:5–27. 2. Scheele J, Stangl R, Altendorf-Hofmann A, Gall FP. Indicators of prognosis after hepatic resection for colorectal secondaries. Surgery 1991;110:13–29. 3. Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 1999;230: 309–318. 4. Fong Y, Cohen AM, Fortner JG, et al. Liver resection for colorectal metastases. J Clin Oncol 1997;15:938–946. 5. Tuttle TM, Curley SA, Roh MS. Repeat hepatic resection as effective treatment of recurrent colorectal liver metastases. Ann Surg Oncol 1997;4:125–130. 6. Nadig DE, Wade TP, Fairchild RB, et al. Major hepatic resection. Indications and results in a national hospital system from 1988 to 1992. Arch Surg 1997;132:115–119.
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nous liver metastases from colorectal cancer. World J Surg 1991; 15:62–67. 28. DeMatteo RP, Palese C, Jarnagin WR, et al. Anatomic segmental hepatic resection is superior to wedge resection as an oncologic operation for colorectal liver metastases. J Gastrointest Surg 2000;4:178–184.
Invited Commentary Susan Galandiuk, MD, FACS Louisville, KY I agree with everything that Dr Martin has said. There are many factors that determine whether or not a simultaneous hepatic resection is performed. These include time in the operating room schedule, the skill of the surgeon, and the possible need for another surgeon. Dr Martin, in how many of your patients was the presence of liver metastasis discovered preoperatively on CT scan versus intraoperatively? Should all colorectal cancer patients have CT scans preoperatively, or only those patients with an elevated preoperative serum carcinoembryonic antigen level? In the group of patients with simultaneous liver resection, there were more wedge resections performed (37%) than resections (8%), compared with the patients with staged resections. Were the hepatic resections in the simultaneous resection group more frequently performed by colon and rectal surgeons, and those in the staged group more frequently performed by hepatobiliary surgeons? Also, why do you believe that tumor location affected the frequency of simultaneous hepatic resection? Dr Martin has shown us that simultaneous hepatic resection is safe, associated with a lower morbidity, and also saves the patient a second procedure. I urge the readers to take this to heart.
Reply Philip Paty, MD, FACS New York, NY We thank Dr Galandiuk for her comments. In this series, liver metastases were identified on preoperative CT scan in nearly all cases. We do advocate obtaining a preoperative CT scan of the abdomen and pelvis for all
Colorectal cancer remains the second leading cause of cancer-related death in the United States, with 63,000 deaths annually.1 Liver metastases will develop in more than one-third of patients, and among these the liver will be the only site of metastasis in 20%.2 Surgical resection of liver metastases remains the only therapy with poten-
tial for cure.3 Five-year survival rates of 25% to 35% have been reported in the literature.4-6 Synchronous liver metastasis, commonly defined as liver metastasis occurring within 12 months of the colon primary, represents 13% to 25% of newly diagnosed colorectal liver metastases.7,8 The optimal timing for surgical resection of synchronous metastasis has not been well defined. Most series reporting on the surgical management of synchronous colorectal metastasis have recommended a staged approach with initial resection of the primary lesion followed by hepatic resection 2 to 3 months later9-13 (Table 1). Recently, the paradigm for the surgical management of synchronous colorectal metastasis has begun to change, with authors reporting good results for simultaneous resection of colon and liver tu-
No competing interests declared.
Presented at the American College of Surgeons 88th Annual Clinical Congress, San Francisco, CA, October 2002. Received October 23, 2002; Accepted November 26, 2002. From the Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (Martin, Paty, Fong, Grace, DeMatteo, Jarnagin, Blumgart), and the Lucille Markey Cancer Center, University of Kentucky, Lexington, KY (Cohen). Correspondence address: Philip B Paty, MD, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.
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Table 1. Published Results of Simultaneous Versus Staged Resection for Synchronous Colorectal Hepatic Metastasis First author
Year
n
Vogt27
1991
36
Scheele2
1991
98
Jenkins12
1997
46
Elias15 Jaeck11
1995 1996
53 41
Nordlinger10
1996
1,008
Bolton23
2000
165
Fujita13
2000
97
Lyass14
2001
112
Type of resection
Morbidity (%)
Mortality (%)
19 simul 17 staged 60 simul 38 staged 22 simul 24 staged 53 simul 20 simul 21 staged 115 simul 893 other 50 simul 115 other 83 simul 14 staged 26 simul 86 staged
5.2 17.6 nr
0
nr
nr
19 20 10 nr
0 0
nr 58 27 35
2
7 2 12 4 0 0 2.3
nr, Not recorded; other, staged and metachronous resections; simul, simultaneous resections.
mors.14,15 But, there has not been a large enough series to permit detailed evaluation of the safety and morbidity of simultaneous resection compared with staged resection. The primary goal of this study was to determine if simultaneous resection is similar to staged resection with regard to morbidity and mortality. METHODS Using prospective surgical databases at Memorial SloanKettering Cancer Center, 240 patients were identified from the Colorectal Surgical Service and the Hepatobiliary Surgical Service who underwent resection of a primary colorectal cancer and a synchronous hepatic metastasis between September 1984 and November 2001. Synchronous hepatic metastases were defined as those identified at the time of diagnosis of the primary colon cancer. All colon and hepatic resections were performed at Memorial Sloan-Kettering Cancer Center. The type of liver resection performed was defined by the Couinaud classification.16 The technique for anesthetic management during hepatectomy has been previously reported.17 In principle, we use a low central venous pressure (less than 5 mmHg), while maintaining a urine output of 25 mL/hr and a systolic blood pressure greater than 90 mmHg during parenchymal transection. After the specimen is removed, crystalloid is administered intravenously to
achieve euvolemia. Packed red blood cells and autologous blood are given to maintain a hemoglobin greater than 10 g/dL in patients with evidence of either coronary or cerebrovascular disease. Intraoperative blood products are not administered until blood loss exceeds 25% of the total blood volume. Outflow control of the hepatic veins before parenchymal division was nearly always obtained in lobectomy or extended resections. The liver parenchyma was divided using Kelly clamps to crush liver tissue and expose bile ducts and blood vessels, which were clipped, tied, or stapled. Intermittent inflow vascular occlusion (the Pringle maneuver)18 was used and applied for 5- to 10minute intervals, released briefly, and reapplied as necessary. Pringle time was recorded as the total cumulative Pringle time applied during parenchymal transection. Postoperative complications and length of hospital stay were available from institutional databases using a standard classification scale of complications (Table 2). For patients sustaining more than one complication, comparison of in-hospital and 30-day postoperative complication were evaluated by assigning the complication with the highest severity level for each patient. Complications were defined by published criteria.19 Earlier cardiac history was defined as history of angina, previous coronary artery disease defined by cardiac catheterization, previous myocardial infarction, cardiac valve
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Table 2. Complication Criteria Criteria
0 1
No complication Oral antibiotics, bowel rest, basic monitoring, supportive care IV antibiotics, TPN, Drainage not required, prolonged tube feedings, transfusions, arrhythmia treated with intravenous medication, chest tube insertion Interventional radiology drainage, operative drainage, intensive care unit admission, intubation, pacemaker placement, bronchoscopy, esophagogastroduodenoscopy Chronic disability, organ resection, enteral diversion (colostomy or ileostomy) Death from complication
3
4 5
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Table 3. Patient Demographics
Complication
2
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TPN, total parenteral nutrition.
dysfunction requiring medication, or a history of congestive heart failure or tachyarrhythmia. Previous pulmonary disease history was defined as history of abnormal pulmonary function tests, asthma requiring daily meter-dosed inhalers, or tobacco use greater than 25 pack years. All patients were reviewed and classified using a preoperative Clinical Risk Score (CRS) prognostic scoring system defined for colorectal metastasis.3 This five-point preoperative clinical score evaluates patients by five factors: 1) disease-free interval less than 12 months, 2) CEA greater than 200, 3) lymph node positive primary, 4) more than 1 hepatic lesion, and 5) hepatic lesion greater than 5 cm in size. Chi-square, Student’s t-test, and Mann-Whitney’s U test for nominal, continuous, and ordinal variables were used to evaluate the association of independent variables to surgical complications. Proportional hazards analysis was performed on all variables found significant by univariate analysis. Relative risk with 95% confidence intervals was calculated as a measure of association. Differences of p ⬍ 0.05 were considered significant. Statistical analysis was performed using JMP software (JMP, SAS Institute Inc, Cary, NC). RESULTS A total of 240 patients were treated for synchronous colorectal hepatic metastasis. There was an even distribution of women (46%) and men (54%), with a median age of 63 years (range 23 to 85 years). The primary colorectal adenocarcinoma was located within the anal canal in 16 patients (7%), within the sigmoid or rectum in 95 patients (40%), within the distal transverse colon
Demographics
Gender Female Male Age, (y), median (range) Cardiac history Yes No Pulmonary history Yes No Prior abdominal surgery Yes No
Staged (n ⴝ 106)
Simultaneous (n ⴝ 134)
45 (42%) 61 (58%) 61 (23–82)
65 (49%) 69 (51%) 64 (27–85)
p Value
NS NS
10 (10%) 96 (90%)
20 (15%) 114 (85%)
NS
20 (18%) 86 (82%)
22 (16%) 134 (84%)
NS
22 (20%) 84 (80%)
34 (25%) 100 (75%)
NS
or descending colon in 61 patients (25%), and within the right colon in 68 patients (28%). The majority of patients presented with rectal bleeding or anemia. A small minority presented with obstruction (n ⫽ 18, 7.5%) or perforation (n ⫽ 6, 2.5%). A total of 134 patients underwent simultaneous resection of a colorectal primary and hepatic metastasis (Group I). These patients were compared with 106 patients who underwent staged resection (Group II). There was a similar distribution of gender, age, and comorbid cardiac and pulmonary disease in both groups of patients (Table 3). The extent of hepatic disease was different, with Group I found to have significantly fewer numbers of hepatic metastases (p ⫽ 0.001) and smaller metastases (p ⫽ 0.009) when compared with Group II (Table 4). Overall, patients subjected to a staged resection are a higher risk group in terms of longterm prognosis as defined by the Clinical Risk Score (Table 4). Right hemicolectomy was more common in Group I, and there were a greater number of left hemicolectomies and rectal resections in Group II (Table 4). Simultaneous resection was associated with a significantly greater number of hepatic wedge resections (Table 4), which accounted for the greatest difference in surgical procedures between the two groups. Conversely, a greater proportion of major hepatic resections (lobe or more) were performed as staged resections. The tendency to perform major liver resections as simultaneous procedures appeared to be influenced in part by the location of the primary colon cancer. There was a greater tendency to perform a simultaneous major hepatic resection in patients who required a right colectomy. Con-
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Table 4. Extent of Disease and Resection Performed in Patients with Resectable Synchronous Hepatic Metastasis Staged (n ⴝ 106) Variables
No. of liver lesions 1 ⬎1 Size of lesions (cm) ⱕ5 ⬎5 CEA (median, range) Primary resection Right colectomy Left colectomy LAR APR Liver resection Wedge Segmental ⱖLobe CRS 1 2 3 4 5
n
Simultaneous (n ⴝ 134) %
n
81 53
%
p Value
(60%) (40%)
0.001
(77%) (23%)
0.009
42 64
(40%) (60%)
65 41 21 (0.7–2,327)
(61%) (39%)
15 31 49 11
(14%) (29%) (46%) (10%)
53 30 46 5
(40%) (22%) (33%) (4%)
9 21 76
(8%) (20%) (72%)
49 40 45
(37%) (30%) (34%)
13 34 35 22 2
(12%) (32%) (33%) (21%) (2%)
29 52 41 7 5
(21%) (39%) (31%) (5%) (4%)
103 31 9.9 (1–6,870)
NS
0.001
0.001 0.003
APR, abdominoperineal resection; CRS, Clinical Risk Score; LAR, low anterior resection.
versely, among patients requiring left colectomy or rectal resection, major hepatic resections were more often performed as staged procedures. Overall operative duration for Group I was a median of 235 minutes (range 105 to 645 minutes). Total operative time for Group II was significantly longer, with a median of 411 minutes (range 195 to 793 minutes) (Table 5). Median operative blood loss for the simultaneous group was 550 mL (range 100 to 4,000 mL), compared with the staged group, which had a median blood loss of 400 mL (range 50 to 3,000 mL) for the colectomy and 700 mL (range 70 to 4,300 mL) for the hepatectomy (total ⫽ 1,100 mL, range 250 to 4,950 mL; p ⬍ 0.001). In the 134 patients who underwent a simultaneous resection, 42 patients (31%) received blood transfusion during their hospitalization. In the 106 patients who underwent a staged resection, 41 patients (38%) received a blood transfusion during one of their hospitalizations. The length of hospital stay was also significantly shorter for the simultaneous resection patients than for the combined hospitalizations of the staged colorectal and hepatic resection patients (Table
5). Even when patients with major liver resections (lobectomy or more) were considered, operative time, blood loss, and length of stay were significantly longer for the staged resections. Complications after all surgical procedures occurred in 136 of 240 patients (56%). In Group I, 65 patients (49%) sustained 142 complications. In Group II, 71 different patients (67%) sustained 197 complications for both hospitalizations. When types of complications were evaluated, the difference in the overall complication rate between the simultaneous and the staged group primarily occurred from the need for a second laparotomy in the staged group (Table 5). When specific laparotomy complications were evaluated, there was a twofold increase in Group II (Table 5). When the hepatectomy complications (hepatic fluid and abscess) and colonic complications (pelvic abscess and anastamotic leak) were evaluated, there was no difference in procedure-specific complications. The overall complication rate for simultaneous resection (48%) was significantly less than for staged resections (68%, p ⫽ 0.003). This was true even when the analysis was restricted to the
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Table 5. Outcomes and Complications after Staged or Simultaneous Resection Staged (n ⴝ 106) Complications
Laparotomy Wound infection Ileus Pulmonary Cardiac Pelvic abscess Hepatic fluid/abscess Hepatic failure Operative time, median, min (range) Total blood loss, median, mL (range) Length of stay, median, d (range) Severity of all complications (n ⫽ 136) Colon Grades 1 & 2 Grades 3 & 4 Grade 5 Total Liver Grades 1 & 2 Grades 3 & 4 Grade 5 Total Total Grades 1 & 2 Grades 3 & 4 Grade 5 Total Combined Grades 1 & 2 Grades 3 & 4 Grade 5 Total Most severe complication for each patient Grades 1 & 2 Grades 3 & 4 Grade 5
Simultaneous (n ⴝ 134)
n
%
n
24 26 19 14 3 11 2 411 (195–793) 1,100 (250–4,950) 18 (7–58) 197
23 26 18 13
17 16 9 5 4 13 2 235 (105–645) 550 (100–4,000) 10 (0–49) 142
55 16 0 71
28 8 0 36
84 39 3 126
43 20 2 64
139 55 3 197
71 28 2 100
71 41 27 3
134 patients who underwent major liver resection (lobectomy or more), with the overall complications of simultaneous resections (27 of 45, 60%) being significantly less than for stage resections (53 of 76, 70%, p ⫽ 0.03) (Table 6). When the complications were graded by severity, the relative distribution of mild (Grades 1 and 2), moderate (Grades 3 and 4), and perioperative mortality (Grade 5) was found to be no different between the groups (Table 5). There was a similar predominance of mild complica-
58 38 4
142 97 42 3 142 65 36 25 3
%
13 12 7 4
p Value
0.06 0.02 0.01 0.01 NS NS NS 0.001 0.001 0.001
0.001
68 30 2 100 0.006 55 38 4
tions (Grades 1 and 2) in Group I (68%) and in Group II (71%). An equal proportion of complications were severe (Grades 3 and 4) in Group I (30%) and Group II (28%). There was no significant difference in operative mortality rates (Group I ⫽ 3 [2%] versus Group II ⫽ 2 [2%]). When only the most severe complication was considered for each patient, the relative proportion of mild (Grades 1 and 2) and severe (Grades 3 and 4) complications was not found to be different in Groups I and II (Table 5).
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Table 6. Outcomes and Complications after Staged or Simultaneous Resection Involving Major Liver Resections (Lobectomy or More) Variables
Staged (n ⴝ 76)
Simultaneous (n ⴝ 45)
p Value
Operative time, min (range) Total blood loss, mL (range) Length of stay, d (range) Total no. of complications Total patients with complications Total patients with Grade 3 or 4 complications Mortality
423 (195–793) 1100 (250–4,950) 18 (7–58) 149 53 (70%) 19 (25%) 3 (4%)
290 (203–445) 800 (100–4,000) 12 (0–31) 65 27 (60%) 12 (27%) 2 (4%)
0.001 0.004 0.001 0.03 NS NS
Operative time, blood loss, and length of stay are median values.
The patient population was then analyzed for factors predictive of any complication after surgical resection. Univariate analysis did not demonstrate a significant difference in complications with age, gender, preoperative cardiac history, albumin at the time of colectomy or hepatectomy, hemoglobin at the time of colectomy or hepatectomy, blood loss at the time of colectomy, duration of colectomy, type of colectomy or Pringle time (Table 7). Factors found to be significant on both univariate and logistic regression were preoperative pulmonary history, past abdominal surgery, resection of a lobe or more, and timing of surgery (Table 7). Because this study was not a prospective randomized trial, the timing of surgical resection was biased in both groups. So separate analysis of predictors of any complications and severe complications was evaluated in both the simultaneous and staged groups. In the simultaneous group, univariate analysis identified preoperative pulmonary history (p ⫽ 0.03), a lobe or more resected (p ⫽ 0.01), estimated blood loss of more than 1,000 mL (p ⫽ 0.05), and operative duration of greater than 5.5 hours (p ⫽ 0.003) to be significant for overall complications and severe complications, but logistic regression did not identify these factors to be significant. In the staged group, univariate analysis did not identify any factors when patients underwent a colectomy because the overall complication rate was small. During hepatectomy preoperative pulmonary dysfunction (p ⫽ 0.04) and past abdominal surgery (p ⫽ 0.04) were found to be significant factors, with estimated blood loss greater than 1,000 mL (p ⫽ 0.06) approaching significance. These factors were not found to be significant on logistic regression. DISCUSSION Synchronous colorectal metastases are found in 20% to 30% of patients at the time of initial diagnosis of colo-
rectal cancer.20 Among these stage IV patients, resectable colorectal metastases are seen in 10% to 25%.7,21,22 Surgical management of this large group of patients is controversial and widely debated. Some authors have reported higher complication and mortality rates for patients with simultaneous resection of the colon and liver. Nordlinger and colleagues10 reported an operative mortality of 7% for simultaneous resections, compared with 2% (p ⬍ 0.01) for staged resections. Bolton and Fuhrman23 reported a 12% operative mortality for simultaneous resections and a 24% mortality for simultaneous resections involving major liver resections.23 A staged operative approach was therefore recommended, with the liver resection performed 2 to 3 months after the resection of the primary.24,25 The main reasons cited in favor of a staged operation are theoretical improvements in perioperative outcomes. Some small and moderate-sized studies have reported safety of simultaneous resection of hepatic metastases and primary colorectal cancers. Schlag and associates9 reported 25 patients with synchronous colorectal metastasis treated with a simultaneous resection with a 0% mortality and 34% morbidity (Table 1). The majority of the liver resections in this report were wedge (44%) or segment (17%) resections, with only 27% undergoing hepatic lobectomy. This distribution of liver resections is similar to that in our study population (Table 7). Jatzko and coworkers26 reported 22 patients, with a mortality of 4.5% and a morbidity of 23%, and Vogt and colleagues27 reported 19 patients, with a mortality of 0% and morbidity of 5% (Table 1). Elias and associates’15 report of 53 patients,15 and Fujita and coauthors’13 report of 83 patients have all demonstrated mortality rates of 0% and morbidity of 19% to 33% (Table 1). Our study confirms that simultaneous resection can be performed safely. In fact, the overall complication rate
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Table 7. Evaluation of Factors Predictive of All Complications after Surgical Procedures
Factor
Gender Male (n ⫽ 110) Female (n ⫽ 130) Cardiac history Yes (n ⫽ 30) No (n ⫽ 210) Pulmonary history Yes (n ⫽ 42) No (n ⫽ 198) Past abdominal surgery Yes (n ⫽ 54) No (n ⫽ 186) Type of colectomy Right (n ⫽ 68) Left (n ⫽ 61) Low anterior resection (n ⫽ 95) Abdominoperineal resection (n ⫽ 16) Extent hepatic resection ⬍Lobe (n ⫽ 119) ⱖLobe (n ⫽ 121) Timing of resection Simultaneous Staged Type of liver resection Wedge (n ⫽ 58) Segmentectomy (n ⫽ 48) Right hepatectomy (n ⫽ 55) Left lateral (n ⫽ 23) Left hepatectomy (n ⫽ 1) Extended right hepatectomy (n ⫽ 41) Extended left hepatectomy (n ⫽ 14)
Complication (%)
Univariate
Multivariate, p value, relative risk (95% confidence interval)
75 61
0.7
NS
46 58
0.2
NS
80 52
0.0004
0.002 1.94 (1.31–3.05)
70 53
0.02
p ⫽ 0.02 1.47 (1.05–2.09)
51 54 58 75
0.3
NS
47 66
0.003
0.07 1.31 (0.97–1.76)
47 68
0.03
0.02 1.44 (1.07–1.95)
31 62 63 56 100 63 92
0.001
NS
was found to be higher in the staged resection group (Table 5), and on multivariate analysis, staged resection proved to be an independent predictor of overall complications (Table 6). The increase in complications seen in the staged resection group was explained by the need for two laparotomics and a resulting increase of complications associated with laparotomy (Table 5). Procedure-specific complications related to resection of the colon, or resection of the liver did not differ in either group (Table 6). So, in centers where hepatectomy is performed frequently, simultaneous resection is an acceptable treatment strategy in suitable patients with resectable synchronous hepatic metastases. Because of the retrospective nature of this study, the
selection factors that led surgeons to perform simultaneous resection of the colon and liver cannot be completely defined. It is apparent that a simultaneous resection was more often associated with right colonic primaries and when only a single metastatic lesion was found in the liver. Conversely, a staged resection was more often associated with rectal primaries or multiple liver lesions. But subset analysis of patients according to location of primary tumor (colon versus rectum) and according to extent of hepatic resection (wedge or segment versus lobe or greater) did not reveal a particular group of patients who are placed at unacceptably high risk by the performance of simultaneous colon and liver resection. This indicates that the judgment of the oper-
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ating surgeons appeared to be the most important factor in patient selection. When simultaneous resections were chosen, such resections were well tolerated regardless of the location of the primary or the extent of liver resection. So, at present, we cannot define complete contraindications to performing simultaneous resection. We believe the final decision to perform a simultaneous or staged liver resection should be based on the experience and comfort level of the surgical team. The time necessary to perform both operations can also be a selection criterion, because an extraordinarily long operation would likely result in a more complicated perioperative course. In our series, no simultaneous operation lasted more than 8 hours, and 95% were completed within 7 hours, 86% within 6 hours, and 75% within 5 hours. In general, our institution will use a simultaneous resection if one of the resections will be straightforward, and the total operative time is likely to be less than 6 hours. Two difficult operations in general will not be performed simultaneously. A number of technical considerations should be discussed. Some clinicians have been worried about using the Pringle maneuver because of fear that portal venous occlusion will lead to intestinal mucosal edema and anastamotic breakdown. In the current study, the Pringle maneuver was used in the intermittent fashion with no evidence of increased anastamotic complications. Another reason that some have been reluctant to perform a simultaneous resection is the concern that the incision might preclude either an adequate liver or an adequate colorectal resection from an oncologic standpoint. In practice, a right subcostal incision can be used for any major liver resection and provide more than adequate exposure for a radical right or transverse colectomy. A generous midline incision from xiphoid to pubis will provide adequate exposure for left, sigmoid, or rectal resections while providing good exposure for most major liver resections. If in addition to this midline incision, a right transverse extension is taken, adequate exposure is possible, even in those few individuals who are markedly obese with very high-riding livers, where the midline incision alone provides insufficient exposure. Most importantly, the decision to proceed with a simultaneous hepatectomy at the time of colon resection should not influence the extent of either the colorectal or the hepatic resection. We have previously demonstrated a significantly higher rate of positive surgical margins for nonanatomic wedge resections compared with anatomic
J Am Coll Surg
hepatectomies.28 So if the operating surgeon is not prepared to perform the anatomic hepatic resection required to achieve negative margins in a patient with a synchronous metastasis, then the liver resection should be deferred. So simultaneous resection of the primary colon tumor and hepatic metastasis is safe and efficient in treating patients with synchronous colorectal metastasis. The overall complication rate is lower for simultaneous resection than with staged resection, perioperative mortality rate is the same, and length of hospital stay is significantly less. Because it avoids a second laparotomy and reduces complications, simultaneous resection of the colon primary tumor and liver metastasis should be considered the preferred treatment for suitable patients with resectable synchronous colorectal metastasis. Because effective adjuvant therapies exist for colorectal cancer, a simultaneous resection also provides for prompt completion of surgical therapy and earlier initiation of adjuvant therapy in this group of patients with high risk of additional microscopic disease who are most likely to benefit from such adjuvant therapy. Author Contributions
Study conception and design: Paty, Fong, Blumgart Acquisition of data: Martin, Paty, Fong, Grace Analysis and interpretation of data: Martin, Paty, Fong Drafting of manuscript: Martin, Paty, Fong, Blumgart Critical revision: Fong, Cohen, DeMatteo, Jarnagin, Blumgart Statistical expertise: Martin Supervision: Paty, Fong, Blumgart REFERENCES 1. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1996. CA Cancer J Clin 1996;46:5–27. 2. Scheele J, Stangl R, Altendorf-Hofmann A, Gall FP. Indicators of prognosis after hepatic resection for colorectal secondaries. Surgery 1991;110:13–29. 3. Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 1999;230: 309–318. 4. Fong Y, Cohen AM, Fortner JG, et al. Liver resection for colorectal metastases. J Clin Oncol 1997;15:938–946. 5. Tuttle TM, Curley SA, Roh MS. Repeat hepatic resection as effective treatment of recurrent colorectal liver metastases. Ann Surg Oncol 1997;4:125–130. 6. Nadig DE, Wade TP, Fairchild RB, et al. Major hepatic resection. Indications and results in a national hospital system from 1988 to 1992. Arch Surg 1997;132:115–119.
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7. Cady B, Monson DO, Swinton NW. Survival of patients after colonic resection for carcinoma with simultaneous liver metastases. Surg Gynecol Obstet 1970;131:697–700. 8. Blumgart LH, Allison DJ. Resection and embolization in the management of secondary hepatic tumors. World J Surg 1982; 6:32–45. 9. Schlag P, Hohenberger P, Herfarth C. Resection of liver metastases in colorectal cancer-competitive analysis of treatment results in synchronous versus metachronous metastases. Eur J Surg Oncol 1990;16:360–365. 10. Nordlinger B, Guiguet M, Vaillant JC, et al. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Francaise de Chirurgie. Cancer 1996;77:1254– 1262. 11. Jaeck D, Bachellier P, Weber JC. Surgical treatment of synchronous hepatic metastases of colorectal cancers. Simultaneous or delayed resection? Ann Chir 1996;50:507–512. 12. Jenkins LT, Millikan KW, Bines SD, et al. Hepatic resection for metastatic colorectal cancer. Am Surg 1997;63:605–610. 13. Fujita S, Akasu T, Moriya Y. Resection of synchronous liver metastases from colorectal cancer. Jpn J Clin Oncol 2000;30:7– 11. 14. Lyass S, Zamir G, Matot I, et al. Combined colon and hepatic resection for synchronous colorectal liver metastases. J Surg Oncol 2001;78:17–21. 15. Elias D, Detroz B, Lasser P, et al. Is simultaneous hepatectomy and intestinal anastomosis safe? Am J Surg 1995;169:254–260. 16. Couinaud C. Le foie: Etudes anatomiques et Chirurgicales. Paris: Masson & Cie; 1957. 17. Melendez JA, Arslan V, Fischer ME, et al. Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction. J Am Coll Surg 1998;187:620– 625. 18. Pringle JH. Notes on the arrest of hepatic hemorrhage due to trauma. Ann Surg 1908;48:541. 19. Martin RC, Jarnagin WR, Fong Y, et al. The use of fresh frozen plasma after major hepatic resection for colorectal metastasis: Is there a standard for transfusion? J Am Coll Surg 2003;196:402– 409. 20. Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of indications for resection. Registry of Hepatic Metastases. Surgery 1988;103:278–288. 21. Michelassi F, Block GE, Vannucci L, et al. A 5- to 21-year follow-up and analysis of 250 patients with rectal adenocarcinoma. Ann Surg 1988;208:379–389. 22. Pescatori M, Mattana C, Maria G, et al. Outcome of colorectal cancer. Br J Surg 1987;74:370–372. 23. Bolton J, Fuhrman GM. Survival after resection of multiple bilobar hepatic metastases from colorectal carcinoma. Ann Surg 2000;231:743–751. 24. Bismuth H, Castaing D, Traynor O. Surgery for synchronous hepatic metastases of colorectal cancer. Scand J Gastroenterol Suppl 1988;149:144–149. 25. Belghiti J. Synchronous and resectable hepatic metastases of colorectal cancer: should there be a minimum delay before hepatic resection? Ann Chir 1990;44:427–429. 26. Jatzko G, Wette V, Muller M, et al. Simultaneous resection of colorectal carcinoma and synchronous liver metastases in a district hospital. Int J Colorectal Dis 1991;6:111–114. 27. Vogt P, Raab R, Ringe B, Pichlmayr R. Resection of synchro-
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nous liver metastases from colorectal cancer. World J Surg 1991; 15:62–67. 28. DeMatteo RP, Palese C, Jarnagin WR, et al. Anatomic segmental hepatic resection is superior to wedge resection as an oncologic operation for colorectal liver metastases. J Gastrointest Surg 2000;4:178–184.
Invited Commentary Susan Galandiuk, MD, FACS Louisville, KY I agree with everything that Dr Martin has said. There are many factors that determine whether or not a simultaneous hepatic resection is performed. These include time in the operating room schedule, the skill of the surgeon, and the possible need for another surgeon. Dr Martin, in how many of your patients was the presence of liver metastasis discovered preoperatively on CT scan versus intraoperatively? Should all colorectal cancer patients have CT scans preoperatively, or only those patients with an elevated preoperative serum carcinoembryonic antigen level? In the group of patients with simultaneous liver resection, there were more wedge resections performed (37%) than resections (8%), compared with the patients with staged resections. Were the hepatic resections in the simultaneous resection group more frequently performed by colon and rectal surgeons, and those in the staged group more frequently performed by hepatobiliary surgeons? Also, why do you believe that tumor location affected the frequency of simultaneous hepatic resection? Dr Martin has shown us that simultaneous hepatic resection is safe, associated with a lower morbidity, and also saves the patient a second procedure. I urge the readers to take this to heart.
Reply Philip Paty, MD, FACS New York, NY We thank Dr Galandiuk for her comments. In this series, liver metastases were identified on preoperative CT scan in nearly all cases. We do advocate obtaining a preoperative CT scan of the abdomen and pelvis for all