Laparoscopic liver resection of hepatocellular carcinoma

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1 The American Journal of Surgery 189 (2005) Laparoscopy Laparoscopic liver resection of hepatocellular carcinoma Hironori Kaneko, M.D.*, Sumito Takagi, M.D., Yuichiro Otsuka, M.D., Masaru Tsuchiya, M.D., Akira Tamura, M.D., Toshio Katagiri, M.D., Tetsuya Maeda, M.D., Tadaaki Shiba, M.D. Department of Surgery, Omori Hospital, Toho University School of Medicine, Omorinishi, Ota-ku, Tokyo , Japan Manuscript received March 9, 2004; revised manuscript September 11, 2004 Abstract Background: We have continued to develop laparoscopic hepatectomy as a means of surgical therapy for hepatocellular carcinoma (HCC). Methods: We evaluated the degree of invasiveness and analyzed the outcomes of laparoscopic hepatectomy compared with open hepatectomy for HCC. Results: There were notable differences with respect to blood loss and operating time compared with open hepatectomy cases. Patients started walking and eating significantly earlier in the laparoscopic hepatectomy group, and these more rapid recoveries allowed shorter hospitalizations. On the Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system, there was no difference in preoperative risk. However, a significant difference was seen in the surgical stress and comprehensive risk scores between the open hepatectomy and laparoscopic hepatectomy groups. Concerning the survival rate and disease-free survival rate, there were no significant differences between procedures. Conclusions: Laparoscopic hepatectomy avoids some of the disadvantages of open hepatectomy and is beneficial for patient quality of life (QOL) as a minimally invasive procedure if the operative indications are appropriately based on preoperative liver function and the location and size of HCC Excerpta Medica Inc. All rights reserved. Keywords: Liver surgery; Endoscopic surgery; Laparoscopic liver resection; Hepatocellular carcinoma; Minimally invasive surgery The majority of hepatocellular carcinomas (HCCs) progress from chronic hepatitis or cirrhosis due to hepatitis B (HBV) or hepatitis C (HCV) viral infections and exhibit a variety of developmental patterns. In particular, HCCs are associated with a high frequency of intrahepatic metastasis and multicentric occurrence accompanied by underlying chronic liver disease caused by HBV or HCV. Hepatectomy is the standard therapy with the highest cure rate, although postoperative recurrence rates are still high [1 4]. If there is a risk of postoperative liver failure, the choice of treatment for HCC depends on the underlying chronic liver disease. Nonsurgical treatments, such as percutaneous ethanol [5 7] or ablation (microwave or radiofrequency) therapy [8 13] and transcatheter arterial embolization [14,15], have been widely used in view of the superior quality of life (QOL) and minimal invasiveness they allow, thus provoking controversy between these options and hepatectomy. * Corresponding author. Tel.: ; fax: address: hironori@med.toho-u.ac.jp Endoscopic surgery, a rapidly adopted minimally invasive surgery, has been applied to the treatment of HCC. We have actively performed laparoscopic hepatectomies for hepatic tumors, especially HCCs, since 1993 [16 19]. Recent experience has persuaded us that there are great potential benefits in laparoscopic hepatectomy. However, few reports exist regarding the usefulness, morbidity, and mortality of laparoscopic hepatectomy for HCC [20]. In this study, we address the indications, evaluate the degree of invasiveness, and analyze the outcomes of laparoscopic hepatectomy for HCC based on our 10 years experience. Patients and Methods From 1993 to January 2003, laparoscopic hepatectomies were performed on 40 cases, including 30 cases of HCC. The stages of HCC were as follows: Child A, 20; Child B, 8; and Child C, 2 cases. HBV and HCV positively was noted in 4 and 21 cases, respectively. Twelve cases had chronic hepatitis, while 13 had liver cirrhosis. The localiza /05/$ see front matter 2005 Excerpta Medica Inc. All rights reserved. doi: /j.amjsurg

2 H. Kaneko et al. / The American Journal of Surgery 189 (2005) tion of HCC by Couinaud s classification was as follows: segment II, 6; segments II and III, 8; segment IV, 4; segment V, 6; segment VI, 5; and segment VIII, 1 case. All HCCs were localized in the left lobe or lower segment, except for 1 case. During this same time period ( ), 144 open hepatectomies were performed. Thirty patients elected conventional open hepatectomy over laparoscopic hepatectomy at the time of informed consent. Twenty-eight cases (left lateral segmentectomy, 8; partial hepatectomy, 20) were retrospectively selected by the same criteria: tumor was solid, located in the left lateral segment or lower segment, and tumor size was less than 6 cm. All operations were performed by the authors. The patients undergoing laparoscopic hepatectomy were compared to those who underwent open hepatectomy with respect to operation time, blood loss, and blood chemistry. To evaluate less invasive surgery, we utilized the Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system, which predicts postoperative morbidity and mortality by quantifying the patient s reserve and surgical stress [21,22]. For statistical analysis, the Student t test, Kaplan-Meier method (for survival rates), and log-rank test were used. s less than.05 were considered statistically significant. Surgical procedure The technique of laparoscopic hepatectomy has been described elsewhere. Briefly, patients were generally anesthetized according to the same protocol. Each patient s position and trocar placement were decided based on the location of the tumor. Laparoscopic hepatectomies were performed with the 4- or 5-trocar technique. Exploration of the extent of the tumor and its relationship with the vascular anatomy and with other tumors in the liver was performed by intraoperative ultrasonography (Aloka Inc, Tokyo, Japan). What should be noted most in laparoscopic hepatectomy is the possibility of CO 2 embolism by pneumoperitoneum during transection of the liver parenchyma and vessels [23]. Therefore, the pneumoperitoneum was shifted using abdominal wall lifting (Mizuho Inc, Tokyo, Japan), particularly during liver parenchymal transection. The line of the intended liver parenchymal transection was marked on the liver surface using diathermy or microwaves. After the liver was punctured by the microwave scalpel (Azwel Inc, Osaka, Japan) along the line of the transection, it was irradiated with microwaves (average power 75 W) for a 30-second interval. Ultrasonic dissection of the liver was performed using an ultrasonic surgical system (Olympus Inc, Tokyo, Japan). The branched vessels were clipped and transected. In recent cases, laparoscopic coagulating shears (Ethicon Endo Surgery Inc, Cincinnati, OH) have been actively employed, and an endoscopic linear stapler has been applied for the liver transection if the tumor was pedunculated. In addition, the use of an endolinear Table 1 Clinicopathologic features stapler (Ethicon Endo Surgery Inc) has allowed surgeons to achieve rapid dissection and transection of Glisson s sheath, as well as the hepatic veins, in a left lateral segmentectomy. The resected liver was maneuvered into a plastic bag. Extraction of the undivided specimen was performed in all patients through the slightly enlarged trocar incision, thus enabling histologic review. In 4 cases (including 3 cases of large resected liver and 1 case involving a tumor located in the posterior segment VI), laparoscopy-assisted hepatectomies were also performed [24]. An approximately 7-cm incision was made on the upper abdomen, and with the abdominal wall lifting technique, surgery was performed with instruments used for open procedures and endoscopic surgery with hand manipulation by both endoscopic and direct views. Results L-Hr (n 30) O-Hr (n 28) Age (y) NS Gender (male:female) 18:12 18:10 NS Child (A:B:C) 22:7:1 22:6:0 NS T-Bil (mg/dl) NS ALT (IU/L) NS CRP (mg/dl) NS ICG R15 (%) NS Platelet ( 10 4 ) NS Tumor size (cm) NS L-Hr laparoscopic hepatectomy; O-Hr open hepatectomy; T-Bil total bilirubin; ALT alanine aminotransferase; CRP C-reactive protein; ICG indocyanine green dye retention rate at 15 minutes; NS not significant. Demographic data of the clinicopathologic features in the open hepatectomy and laparoscopic hepatectomy groups are shown in Table 1. We found no differences in any of the preoperative background variables between the 2 groups, including tumor size. Laparoscopic hepatectomy was successful except for 1 early case that was converted to open laparotomy. In the left lateral segmentectomy cases and the partial hepatectomy cases, there were notable differences with respect to operating time compared to the open hepatectomy cases (Table 2). However, when the laparoscopic hepatectomy groups were divided into early period ( 1997) and late period (1998 ), there was a significant difference with respect to operative time between the early period groups and the late period groups in both the partial hepatectomy and left lateral segmentectomy groups. Blood loss also differed, although not significantly (Table 3). Postoperatively, the peak values of total bilirubin, alanine aminotransferase, and C-reactive protein did not sta-

3 192 H. Kaneko et al. / The American Journal of Surgery 189 (2005) Table 2 Clinicopathologic features L-Hr (n 30) O-Hr (n 28) Partial hepatectomy Left lateral segmentectomy 10 8 Operation time (min) NS Blood loss (g) NS POD1 T-Bil (mg/dl) NS POD1 ALT (IU/L) NS POD1 CRP (mg/dl) NS Drain off (POD) NS Ambulation (POD) Oral intake (POD) Hospital stay Postoperative complication 3 (10%) 5 (18%) Bile leakage 1 2 Liver failure 0 1 L-Hr laparoscopic hepatectomy; O-Hr open hepatectomy; POD postoperative day; T-Bil total bilirubin; ALT alanine aminotransferase; CRP C-reactive protein; NS not significant. Fig. 1. Estimation of physiologic ability and surgical stress. L-Hr laparoscopic hepatectomy; O-Hr open hepatectomy; *P.0001, **P.005. PRS (preoperative risk score) X X X X X X 6 ;X 1 age; X 2 presence (1) or absence (0) of severe heart disease; X 3 presence (1) or absence (0) of severe pulmonary disease; X 4 presence (1) or absence (0) of diabetes mellitus; X 5 performance status index (0 4); X 6 American Society of Anesthesiologists physiologic status classification (1 5). SSS (surgical stress score) X X X 3 ;X 1 blood loss/body weight (g/kg); X 2 operation time(h); X 3 extent of skin incision (0 minor incision for laparoscopic or thoracoscopic surgery including scope-assisted surgery; 1 laparotomy or thoracotomy alone; 2 both laparotomy and thoracotomy). CRS (comprehensive risk score) (PRS) 0.976(SSS). tistically differ between the 2 procedure groups. The patients started walking and eating significantly earlier in the laparoscopic hepatectomy group, and these more rapid recoveries consequently allowed shorter hospitalizations. The laparoscopic hepatectomy group had a 10% complication rate, while the open hepatectomy group had a complication rate of 18%, although this difference did not reach statistical significance (Table 2). There were no hospital deaths in either group. According to the E-PASS scoring system, there was no difference in preoperative risk. However, a significant difference was seen in the surgical stress and comprehensive risk scores between the open hepatectomy and laparoscopic hepatectomy groups (Fig. 1). No recurrences related to laparoscopy, such as peritoneal dissemination and port-site recurrences, were observed. Concerning the survival rate and disease-free survival rate, there were no significant differences between procedures, although more clinical cases and longer follow-up periods are needed to reach definitive conclusions. The 5-year survival rate and the survival rate without recurrences were 61% and 31%, respectively, by endoscopic procedure and 62% and 29%, respectively, by conventional partial hepatectomy (Fig. 2). Discussion Laparoscopic surgery for liver resection is a highly specialized field, because the liver, given its unique anatomical features, presents technical difficulties for surgery such as control of bleeding and bile leakage from the intrahepatic vessels. However, important technologic developments and improved endoscopic procedures are being established. Equipment modifications such as intraoperative ultrasonography, ultrasonic dissection, microwave coagulators, and argon beam coagulators have all been recognized for their efficacy in liver surgery, as have the introduction of endoscopic linear staplers and laparoscopic coagulation shears. Table 3 Comparison of operation results of laparoscopic hepatectomy in early ( 1997) and late (1998 ) periods Early period ( 1997) (n 14) Late period (1998 ) (n 16) Partial hepatectomy 9 11 Operation time (min) Blood loss (g) NS Left lateral segmentectomy 5 5 Operation time (min) Blood loss (g) NS NS not significant. Fig. 2. Prognosis (survival rate and disease-free survival rate). L-Hr laparoscopic hepatectomy; O-Hr open hepatectomy; N.S. not significant.

4 H. Kaneko et al. / The American Journal of Surgery 189 (2005) Thus, laparoscopic partial hepatectomy has been more actively performed recently. There have been reports of laparoscopic right and left lobectomy [25 28], and laparoscopic surgery has also been applied to left lateral segmentectomy of the living donor s liver for transplant [29]. We have accumulated laparoscopic hepatectomy case experience for 10 years, and the operative time has been shortened with less bleeding in recent cases. The operative times for laparoscopic partial hepatectomy and left lateral segmentectomy have been shortened to less than 2 hours and less than 4 hours, respectively, indicating that our technique has been improving with increasing clinical experience. Most important point is good judgment during the operation. Therefore, we would like to emphasize that a well-experienced endoscopic surgeon and well-experienced liver surgeon should collaborate for safe performance of laparoscopic hepatectomy. It is generally difficult to evaluate minimally invasive surgery. We chose to evaluate the procedures with the E-PASS scoring system because it relates to postoperative clinical course. The E-PASS scoring system is believed to predict the morbidity and mortality of postsurgical risk by quantifying the patient s reserve and surgical stress [20,21]. Laparoscopic hepatectomy was found to be less invasive than conventional hepatectomy according to both the E- PASS scoring system for surgical stress and postoperative clinical course. However, this procedure requires the surgeon to master the technical difficulties inherent in laparoscopic hepatectomy. The most important issue regarding laparoscopic hepatectomy for HCC is appropriate knowledge of, and adherence to, the procedure s indications. It is dangerous to broaden the indications without evidence because such expansion could jeopardize the twin goals of laparoscopic surgery:- minimal invasiveness and safety. The indications for laparoscopic hepatectomy are essentially identical to those for open hepatectomy in terms of preoperative assessment of liver function. However, cirrhotic patients with relatively poor liver function can tolerate laparoscopic hepatectomy if the tumor resides in a location affording easy access. Therefore, in determining whether laparoscopic hepatectomy is indicated, the size, type, and location of the tumor must be evaluated. Nodular tumors smaller than 4 cm or pedunculated tumors smaller than 6 cm are proper indications [19]. Concerning location, tumors in the lower segment and the left lateral segment are good candidates. As for tumors located in the upper segment, thoracoscopic hepatectomy may be feasible. However, it would be difficult to obtain a free surgical margin for the inferior portion of the tumor. Moreover, if accidental bleeding is encountered, meticulous bleeding control is required. Thus, thoracoscopic hepatectomy is not acceptable except in cases involving pedunculated tumors. With respect to the operative method, laparoscopic hepatectomy involving partial hepatectomy and left lateral segmentectomy is a feasible and less invasive operation, in our experience. If relatively large livers have to be resected, laparoscopic-assisted hepatectomy is considered to be one option [24], because it is easy to mobilize the liver, obtain good exposure, diagnose the tumor location by palpation, and achieve hemostasis by immediate compression. However, patients who require anatomical resection such as right lobectomy would most likely be poor candidates for laparoscopic liver surgery [25], although we have had no direct experience. Because the required operative time would be protracted without significant operative exposure, a skin incision of at least 15 cm would be required to remove the large amount of liver tissue, and the conversion rate to standard open hepatectomy would be high. The overarching principle of laparoscopic surgery is to achieve minimal invasiveness with optimal safety; thus, laparoscopic right lobectomy is too invasive to provide the expected benefits of laparoscopic surgery at present. The indications for surgical resection and ablation therapy in HCC remain controversial. The treatment of HCC and, more specifically, the indications for hepatectomy are very limited, and nonsurgical ablation therapy, an alternative method to surgery, has been advocated by some for its advantage in yielding improved QOLs for the patients, provoking controversy over curability [30]. However, the Liver Cancer Study Group of Japan has reported that patients who underwent hepatic resection had a higher survival rate than a nonsurgical treatment group, even for small-sized HCCs [4]. Under such circumstances, laparoscopic hepatectomy represents an intermediate option between ablation therapy and conventional hepatectomy; ablation therapy is less invasive than surgical resection, but laparoscopic hepatectomy is superior in its ability to completely resect the tumor, and in allowing optimal pathologic evaluation from the resected specimen. While laparoscopic surgery is less invasive than standard hepatectomy, laparoscopic hepatectomy is inferior to open hepatectomy in terms of anatomical resection. Laparoscopic systematic resection is currently considered a contraindication except for left lateral segmentectomy because of its technical difficulties. A recent report demonstrated the safety associated with more limited blood loss for laparoscopic left lateral segmentectomies in a case-control study [31]. Due to the specific characteristics of HCCs, including their high recurrence rate accompanied by underlying chronic hepatitis and cirrhosis caused by HBV or HCV, the most important goals in HCC treatment are curability and minimal invasiveness. However, achieving both of these goals may not always be possible. Laparoscopic hepatectomy can avoid the disadvantages of standard hepatectomy and ablation, and is beneficial for patient QOL due to its minimal invasiveness. Prospective randomized trials are required to confirm those results. This procedure is expected to develop further in the future as a new surgical method for HCC, a method that improves patients QOL as long as the indications are strictly followed based on preoperative liver function, as well as the location and size of tumors. While

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