Author Affiliations: University of Pittsburgh Medical Center Liver Cancer Center, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
Laparoscopic hepatic resection is a growing option in the field of hepatic surgery. Nearly 3000 laparoscopic hepatic resections have been reported in the literature for both benign and malignant tumors with a reported perioperative mortality of 0.3% and morbidity of 10.5%.1,2 Multiple series3- 21 have attested to the feasibility and safety of laparoscopic liver resections; however, to our knowledge, no randomized controlled trial has been reported comparing laparoscopic with open liver resection. Further, the overall benefits of a minimally invasive approach to hepatic resection have not been systematically defined.
We reviewed the published series that directly compared laparoscopic with open hepatic resection in case-cohort matched patients. In addition, we analyzed our experience of minimally invasive hepatic resections at a tertiary medical center in 314 patients over a 9-year period (2001-2010). We matched our experience of laparoscopic hepatic resections to open hepatic resections for colorectal cancer (CRC) metastasis and hepatocellular carcinoma (HCC) for comparison of perioperative, oncological, and survival outcomes. Finally, financial cost comparisons were presented.
A literature search was performed using PubMed for cited English-language publications. Search phrases were “laparoscopic liver resection,” “open liver resection,” “versus,” “compared with,” and “advantages.” All titles and abstracts were screened, selecting those that compared laparoscopic liver resection with open liver resection. A total of 31 publications were identified and carefully reviewed totaling 2473 patients.4,12,14,22- 49
From March 2001 to June 2010, 1294 patients with symptomatic benign liver lesions or primary or secondary liver cancers underwent liver resection by 4 hepatobiliary surgeons at the University of Pittsburgh Medical Center Liver Cancer Center. All patients consented for participation in an institutional review board–approved Hepatic Registry. Of these patients, 314 patients (24.3%) underwent minimally invasive liver resection.
Data were analyzed using Microsoft Excel (Microsoft, Redmond, Washington) and SPSS version 16 (SPSS Inc, Chicago, Illinois). Descriptive statistics were performed to provide characteristics of the sample and distribution of outcomes. Parametric statistics (analysis of variance) were performed to test differences between treatment groups when continuous data were normally distributed and nonparametric statistics (Mann-Whitney U test) were performed for nonnormally distributed continuous data. We used χ2 analyses to test differences between groups of categorical data. Kaplan-Meier statistics (log rank and Breslow) were used to test differences in survival or time to recurrence between treatment groups.
To our knowledge, no prospective randomized controlled trial has been reported comparing laparoscopic vs open liver resection; however, a number of retrospective case-cohort matched studies have compared laparoscopic liver resection with open liver resection (Table 1, arranged by number of patients undergoing laparoscopic liver resection). We analyzed major perioperative variables between the laparoscopic and open hepatic resection in 31 publications.
Most studies do not show any significant differences in operative times between the laparoscopic and open liver resection; however, 5 studies22,32,37,40,48 did show significantly longer operative time with the laparoscopic approach compared with open resection, while 3 studies4,14,28 showed shorter operative time using a laparoscopic approach (Table 1). The difference between the first and second groups may be due to the method of parenchymal transection. Longer operative times are seen when the surgeon uses the Harmonic scalpel, LigaSure (Covidien, Boulder, Colorado), or ultrasonic surgical aspirator, while shorter operative times are observed when the endostaplers are serially deployed for parenchymal transection. No specific method appears to be superior over the other. Surgeon preference and experience dictated the methods used. With increasing experience, 2 studies showed significant improvement in the second half of their laparoscopic group in terms of operative time (90-120 minutes vs 120-240 minutes; P = .004 to .005).26,31
Fifteen studies showed significantly decreased blood loss using laparoscopic compared with open liver resection (Table 1).4,12,14,22,23,25,26,28,30,31,33,35,37,45,49 With increasing experience through the learning curve of laparoscopic liver surgery, blood loss was significantly decreased between the first and second halves of the laparoscopic group (200 mL vs 50 mL; P = .004).26 Blood loss may be improved with laparoscopic liver resection because of improved visualization and magnification, coupled with more meticulous dissection.
Transfusion requirements were not significantly different in most studies; however, 4 studies showed significantly lower blood transfusion requirement with laparoscopic resection, compared with open liver resection (0% vs 17.3%; P = .04) (Table 1).22,27,28,32 The largest series on laparoscopic liver resection showed a blood transfusion rate of 0.7% vs a rate of 8% for open liver resections, although no statistical comparison was presented.4
Minimally invasive surgery, in general, has been touted to improve immediate postoperative outcomes, such as pain control, time to return of bowel function for oral intake, and time to normal activity. Postoperative pain control was better with a laparoscopic approach with fewer days of required narcotic pain medication (1 vs 5 days; P = .001)39 and decreased total amount of pain medication required (Table 2).22,23,34,41,45,47,48
Seven studies showed quicker return to oral intake after laparoscopic liver resection (1-2.4 days) compared with open liver resection (2-4.3 days) (P = .001 to <.01),22,23,34,36,41,42,45 while 3 studies showed no difference (Table 2).39,43,47
Only 1 study evaluated postoperative day to ambulation and showed that patients who underwent laparoscopic liver resection ambulated quicker than their counterparts who underwent open liver resection (2.8 vs 3.8 days; P < .005).42
Average lengths of stay after laparoscopic liver surgery were variable, although almost all the studies consistently showed a significant earlier discharge to home after laparoscopic liver resection (Table 2, arranged by increasing length of stay within each continent). Interestingly, there appears to be a cultural bias with regard to how long patients are kept in the hospital after liver resection (laparoscopic or open). Four studies published in the United States4,14,22,23 presented a length of stay of 1.9 to 4.0 days after laparoscopic liver resection. Studies from Europe12,26- 40 showed an average length of stay of 3.5 to 10 days, while those from Asia41- 49 reported an average of length of stay of 4 to 20 days after laparoscopic liver resection. However, the trend was consistent for each continent, with an approximately 50% decrease in length of stay for laparoscopic vs open hepatic resection.
Most studies showed comparable complication rates between laparoscopic and open liver resections. Seven studies reported significantly lower complication rates after laparoscopic vs open liver resection (6%-13.8% vs 28.9%-47.8%; P = .001-.04).22,25,26,28,30,32,33 No differences in mortality were reported between the groups.
There are concerns that the minimally invasive approach to liver resection may be associated with increased cost because of laparoscopic equipment/instrumentation; however, this may be offset by a shorter length of hospital stay in patients who undergo the laparoscopic approach. Koffron et al4 showed that the operating room costs for minimally invasive liver resection cases were significantly higher than those of open liver resection cases (operating room cost for partial and right hemihepatectomy were 39% and 36% of total hospital costs, respectively, for open cases, compared with 51% and 47% of total hospital costs, respectively, for minimally invasive cases); however, the non–operating room costs were less with the minimally invasive group (non–operating room cost for partial and right hemihepatectomy were 61% and 64% of total hospital costs, respectively, for open cases, compared with 48% and 35% of total hospital costs, respectively, for minimally invasive cases) and this cost was significantly dependent on length of hospital stay (P < .001). Rowe et al25 showed that the cost of stapler/trocar devices was similar between the laparoscopic vs the open groups, while Polignano et al30 showed that costs of disposable instruments and other devices were significantly higher for laparoscopic hepatic resection vs open hepatic resection (P < .001). Tsinberg et al23 and Polignano et al30 showed that the hospital and overall costs were less for the laparoscopic group because of shorter lengths of stay (P ≤ .04). When comparing the clinical and economical impact of laparoscopic vs open left lateral segmentectomies at the University of Pittsburgh, patients undergoing laparoscopic left lateral segmentectomy had a shorter length of stay (3 vs 5 days; P < .001) and a weighted average median cost savings of $1527 to $2939 compared with open left lateral segmentectomy.50
Initial concerns of adequate margins and tumor seeding prevented the widespread application of laparoscopic liver resection for malignant tumors. However, in comparison studies, 1 study found that the laparoscopic resection group had a significantly wider resection margin than the open resection group,28 while 13 studies showed that there were no differences in margin-free resections between laparoscopic vs open liver resection.22- 24,26,27,29,30,32,33,40,41,46,47 In addition, to our knowledge, no incidence of port-site recurrence or tumor seeding has been reported.
There were no significant differences in 3- or 5-year overall survival in 12 studies that compared laparoscopic with open liver resection for either HCC or CRC metastases (Table 3).12,22,24,27,28,40- 42,44- 47 For example, Cai et al41 showed that the 1-, 3-, and 5-year survival rates after resection for HCC were 95.4%, 67.5%, and 56.2%, respectively, after laparoscopic resection vs 100%, 73.8%, and 53.8%, respectively, after open resection. Ito et al22 showed no difference in 3-year overall survival for laparoscopic resection for CRC metastasis compared with well-matched patients undergoing open liver resection.
From March 2001 to June 2010, 1294 patients underwent liver resection at the Liver Cancer Center at the University of Pittsburgh Medical Center. The laparoscopic approach was used in 314 patients (24.3%). Our laparoscopic liver surgery service started in March 2001 with 2 patients with symptomatic benign liver lesions and has grown considerably over the years, averaging more than 40 cases per year for the last 8 years. The median age was 57 years (range, 18-92 years). The majority were female (65.5%). Median body mass index (calculated as weight in kilograms divided by height in meters squared) was 26.5 (range, 17.3-48.7). The majority of liver lesions were solid lesions (75.1%). The remaining lesions were giant hepatic cysts (24.2%). Of the solid lesions, 54.6% were benign lesions and 45.4% were malignant lesions.
There were several variations of the minimally invasive approach that were used at our institute. Liver lesions were resected totally laparoscopically in 177 of 314 patients (56.1%). A hand-assisted approach was used in 117 of 314 patients (37.3%). A laparoscopic-assisted open approach (hybrid) was used in 11 of 314 patients (3.5%). A robotic-assisted minimally invasive approach was used in 2 cases. Seven cases (2.2%) required conversion to open surgery because of poor exposure or failure to progress from large tumor size, additional cancers in the contralateral lobe, or bleeding.
The most common type of laparoscopic liver resection performed in 203 of 314 patients (64.6%) was sectionectomy or nonanatomical wedge resection. For anatomical resections, 59 left lateral sectionectomies (18.8%), 26 left hepatic lobectomies (8.3%), 21 right hepatic lobectomies (6.7%), and 5 right posterior sectionectomies (1.6%) were performed.
Median operative time for all patients was 196 minutes (range, 53-540 minutes). The median operative time for the first 25 patients was significantly longer than the remaining cases (258 minutes vs 169 minutes; P = .001). Median blood loss was 50 mL (range, 0-550 mL). There was no significant difference in blood loss between the first 25 cases and those performed thereafter. Median length of stay was 3 days (range, 1-17 days) with 24% of patients discharged on the first postoperative day. As expected, lengths of stay were longer in patients undergoing synchronous colon resections.
A total of 206 benign liver lesions were resected laparoscopically, of which the majority were symptomatic giant hepatic cysts (37%), followed by focal nodular hyperplasia (19%), hemangioma (15%), adenoma (5.8%), gallbladder mass requiring adjacent liver resection (5.3%), biliary cyst adenoma (4.9%), and bile duct cyst (1.5%). The size of the benign lesions averaged 7.9 cm.
A total of 108 primary and secondary cancers were resected laparoscopically. Of these malignant lesions, the majority were HCC (38%) or CRC metastases (34%). Macronodular cirrhosis was present in 68% of patients with HCC. Other cancers included cholangiocarcinoma, breast cancer, neuroendocrine cancer, esophageal cancer, sarcoma, and lung cancer. The size of the malignant tumors resected averaged 3.2 cm.
We performed a matched comparison of the 24 laparoscopic liver resections for CRC metastases (21 hand-assisted; 3 pure laparoscopic) with 25 open liver resections for CRC metastases during the same period (Table 4). There were no significant differences in sex, age, body mass index, type of resection, concurrent resection (eg, liver wedge, diaphragmatic resection), or concurrent procedure (eg, radiofrequency ablation). There were no significant differences in the size of the largest lesion (P = .63), the percentage of negative margins (P = .75), and the distance of the closest margins (P = .92) between the groups. Operative time and blood loss were significantly less with laparoscopic liver resections (P = .04). Postoperatively, patients who underwent laparoscopic liver resection required significantly less narcotic requirement as indicated by a significantly lower epidural pain catheter placement for postoperative pain control compared with patients who underwent open liver resection (8.3% vs 40%; P = .01). There were no significant differences in bile leaks or total complications; however, the length of stay was significantly shorter by more than 3 days for patients who underwent the laparoscopic resection approach (3.1 days vs 6.3 days; P = .001). From an oncological standpoint, there was no significant difference between the actual disease-free survival at 1, 2, and 3 years (laparoscopic: 92%, 83%, and 79% vs open: 84%, 52%, and 52%; P = .13) and actual overall survival (laparoscopic: 86%, 66%, and 55% vs open: 88% 57%, and 43%; P = .32) (Table 4).
We also performed a matched comparison of the 17 laparoscopic resections for HCC for curative intent (10 hand-assisted; 7 pure laparoscopic) with 20 open liver resections for HCC during the same period (Table 4). There were no significant differences in sex, age, percentage of patients with cirrhosis, type of resection, concurrent resection, or concurrent procedure. The laparoscopic liver resection group for HCC had a statistically significant smaller body mass index compared with the open liver resection group for HCC, but the clinical significance is uncertain. There were no statistical differences between the tumor size and percentage of negative margins between the laparoscopic or open groups; however, open liver resection for HCC was associated with significantly closer negative margins than the laparoscopic group (0.69 cm vs 1.12 cm; P = .04). When comparing laparoscopic and open liver resection for HCC, there were no statistically significant differences in operative time, blood loss, or transfusion rate. As an indication of pain medication requirement, patients who underwent open liver resection for HCC had a significantly higher epidural requirement, while no patients who underwent laparoscopic resection for HCC required an epidural for pain control. No bile leak was reported in either treatment group and the complication rates were not significantly different. The length of stay was significantly shorter for patients who underwent laparoscopic liver resection for HCC compared with patients who underwent open liver resection (4.1 days vs 5.7 days; P = .002). From an oncological standpoint, the actual disease-free survival was significantly better for the laparoscopic liver resection group compared with the open liver resection group at 1, 2, and 3 years (laparoscopic: 88%, 88%, and 82% vs open: 60%, 50%, and 50%; P = .007) (Table 4). This may be associated with the previously mentioned significantly closer margin seen with open liver resection for HCC compared with the laparoscopic group; however, there was no difference in actual overall survival between the 2 groups (laparoscopic: 75%, 67%, and 52% vs open: 66% 66%, and 44%; P = .09).
Financial cost data were available for 21 patients who underwent laparoscopic liver resection for CRC metastases, 25 patients who underwent open liver resection for CRC metastases, 13 patients who underwent laparoscopic liver resection for HCC, and 17 patients who underwent open liver resection for HCC. Cost analyses were performed between the combined laparoscopic group and the open group and between the laparoscopic and open groups among the patients with CRC and HCC. The cost data were referenced to the combined open operating room cost, which was normalized to $1. Patients who underwent laparoscopic surgery had higher operating room costs when compared with those who underwent open resection ($1.30 vs $1.00; P = .001); however, no significant difference was found between surgery types in regard to total hospital costs ($1.87 vs $1.92; P = .33). For patients with CRC metastasis, the operating room costs for the laparoscopic liver resection were significantly higher than the operating room costs for the open liver resection ($1.39 vs $0.98; P = .001); however, the total hospital costs were not significantly different between the 2 groups ($1.89 vs $1.87; P = .60). For patients with HCC, the operating room costs for the laparoscopic liver resection were not significantly higher than the operating room costs for open liver resection cases ($1.14 vs $1.03; P = .68). In addition, the total hospital costs were not significantly different between the 2 groups ($1.85 vs $2.00; P = .39). Hence, the potential higher cost of the laparoscopic case was offset by the shorter length of stay compared with the open cases, similar to what others have reported.
This study represents the first, to our knowledge, comprehensive review of the benefits of laparoscopic liver resection compared with the more traditional open hepatic approach. In addition, our original series of 314 patients undergoing laparoscopic hepatic resection at University of Pittsburgh Medical Center represents 1 of the 3 largest single-center series reported.4,7 The major features of this study entail (1) a review of the literature comparing perioperative benefits of laparoscopic vs open liver resections for benign and malignant lesions, (2) matched outcomes comparisons of laparoscopic and open liver resection for CRC metastases and HCC, and (3) financial cost comparisons of laparoscopic vs open liver resections.
Thirty-one studies were reviewed that compared laparoscopic with open hepatic resection in 2473 patients. The majority of studies showed that patients undergoing laparoscopic liver resection had less intraoperative blood loss, less postoperative pain medication requirement, quicker resumption of oral diet, and shorter length of stay compared with well-matched open hepatic resection patients. Hence, there are major benefits to patients undergoing laparoscopic liver resection compared with open liver surgery. In addition, from a financial standpoint, although the minimally invasive approach to liver resection was associated with higher operating room costs in some studies, the total hospital costs were either offset or improved because of the associated shorter length of hospital stay with the minimally invasive approach.
In our matched comparison of laparoscopic vs open liver resection for CRC metastases and HCC, we found that the laparoscopic approach did not compromise oncological measures, such as margin status, disease-free survival, or overall survival, while it improved short-term perioperative measures. In noncomparative studies, the largest series of laparoscopic resection for CRC metastasis was a recently reported international multi-institutional study in 109 patients.5 The 5-year overall survival was 50%. Three additional recent publications report 5-year overall survival for laparoscopic resection of CRC metastasis at 46% to 64%.27,51,52 These 5-year overall survival results for laparoscopic resection of CRC metastasis are comparable with recent reports of overall survival for open resection of CRC metastasis from major hepatobiliary centers.53- 55 Likewise, in noncomparative studies, the 5-year overall survival rate after laparoscopic liver resection for HCC ranged from 50% to 75% and is comparable with contemporaneous open hepatic resection survival data.1
We recognize the limitations of this study, which represents an analysis of retrospective series of laparoscopic liver resections in highly selected patients. Clearly, there is some variation as to the selection criteria among surgeons. Only 25% of patients undergoing hepatic resection at our institution over the past 9 years were deemed suitable for a minimally invasive approach. Critics would argue that a selection bias exists in choosing which patients are suitable for the laparoscopic approach. We acknowledge that not all patients are eligible for a laparoscopic approach. However, the data from our series as well as the review of 31 other reports clearly indicate the advantages of a minimally invasive liver resection in selected patients. Certainly, a randomized multicenter clinical trial comparing laparoscopic with open resection for HCC or a solitary CRC metastasis would be desirable; however, it is unclear if such a trial will ever be conducted. Patients may not subject themselves to an invasive procedure when a more minimally invasive approach has been shown to be safe in more than 2800 reported cases.1 In addition, a large number of patients would have to be accrued to detect differences in complications that already occur infrequently. Furthermore, many patients are well informed and seek out centers offering a minimally invasive approach. Short of a large randomized controlled clinical trial, case-cohort matched comparisons provide the next best option to compare laparoscopic vs open liver resection, and our data clearly show the advantages of laparoscopic liver resection in patients with benign lesions, HCC, and CRC metastasis.
Minimally invasive hepatic resection for benign and malignant liver lesions is safe and feasible with definite short-term benefits, no economic disadvantage, and no compromise of oncological principles. These results indicate that laparoscopic hepatic resection offers clinical benefits in well-selected patients, and it is likely that this technique will be offered to a growing number of patients in the future as experience increases.
Correspondence: David A. Geller, MD, University of Pittsburgh Medical Center Liver Cancer Center, University of Pittsburgh, Starzl Transplant Institute, 3459 Fifth Ave, UPMC Montefiore, 7 S, Pittsburgh, PA 15213-2582 (email@example.com).
Accepted for Publication: August 26, 2010.
Published Online: November 15, 2010. doi:10.1001/archsurg.2010.248
Author Contributions:Study concept and design: Nguyen, Marsh, Tsung, Gamblin, and Geller. Acquisition of data: Nguyen. Analysis and interpretation of data: Nguyen, Tsung, Steel, and Geller. Drafting of the manuscript: Nguyen, Marsh, Tsung, Steel, Gamblin, and Geller. Critical revision of the manuscript for important intellectual content: Nguyen, Tsung, and Geller. Statistical analysis: Steel. Obtained funding: Tsung and Geller. Administrative, technical, and material support: Nguyen, Marsh, Tsung, Gamblin, and Geller. Study supervision: Tsung and Geller.
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