Annals of Surgical Oncology 15(3):800806

DOI: 10.1245/s10434-007-9749-1

Laparoscopic Liver Surgery for Patients with Hepatocellular Carcinoma

Hong-Yaw Chen, MD,1 Chung-Chou Juan, MD, PhD,1 and Chen-Guo Ker, MD, PhD, FACS2

Department of Surgery, Gastrointestinal Center, Yuan General Hospital, Kaohsiung, Taiwan Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, 100, Tz-You 1st Rd, Kaohsiung, 80756, Taiwan

Background: Laparoscopic hepatectomy is feasible for hepatocellular carcinoma (HCC) today. This is a retrospective study of the patients with HCC treated by liver resection with a totally laparoscopic approach. Methods: This study recruited 116 patients (92 male, 24 female) that underwent laparoscopic liver resection (LR) for HCC. Patients were divided into two groups: group I: (n = 97, 78 male,19 female) those with a volume of resection less than two segments; group II: (n = 19, 14 male, 5 female) those with a volume of resection of more than two segments. The distribution of the tumor-nodemetastasis (TNM) stage of patients in the two groups was not significantly different. Results: Patients resumed full diet on the second or third day after the operation, and the average length of hospital stay was 6 days. The operation time was 152.4 336.3 min and 175.8 57.4 min, while blood loss was 101.6 324.4 mL and 329.2 338.0 ml, for groups I and II, respectively. Five patients (5.2%) in group I and three patients (15.8%) in group II required blood transfusion (p = 0.122). The mortality rate was zero among our patients and complication rates were 6.2% and 5.2% for groups I and II, respectively. The 1-year, 3-year, and 5-year survival rates were 85.4%, 66.4%, and 59.4% for group I, and 94.7%, 74.2%, and 61.7% for group II, respectively, with no signicant difference between two groups (p = 0.1237). Conclusion: Laparoscopic liver resection is a procedure of signicant risk and is more technically demanding in comparison with traditional open method. There was no signicant difference in survival rates, based on the volume of resection. Laparoscopic surgery should be performed in selected patients as the postoperative quality of life of patients is better than that with open resection. Key Words: Liver cancerLaparoscopic surgeryHepatectomy.

Hepatocellular carcinoma (HCC) is a not infrequent disease in Taiwan. To date, literature on laparoscopic hepatic surgery is uncommon and we

Published online: December 29, 2007. Address correspondence and reprint requests to: Chen-Guo Ker, MD, PhD, FACS; E-mail: [email protected]
Published by Springer Science+Business Media, LLC 2007 The Society of Surgical Oncology, Inc.

believe this technique is an innovation.12 In 1998, we started to apply the laparoscopic approach to liver surgery for liver cancer.2 The laparoscopic approach has not yet been well developed for liver resection and only limited case series have been reported. Besides, laparoscopic examination and laparoscopic ultrasonography are indispensable to guarantee the precise determination of the segmental tumor location and the relationship of the tumor to adjacent vascular or biliary structures.36 Therefore, the tumor location 800

LAPAROSCOPIC LIVER SURGERY

801

and its spatial details are important during laparoscopic liver dissection in our experience. With improvements in laparoscopic techniques and the development of new technology and equipment, laparoscopic liver resection is safe when undertaken by experienced surgeons. In 2000, Descottes et al.7 reported its use for major operations, such as right liver lobectomy, and believed the use of this technical approach offers many advantages. In addition, the caudate lobe alone could be removed without sacricing other parts of the liver, as reported by Dulucg.8 Therefore, the laparoscopic technique has gradually become acceptance for application to liver resection, worldwide, in some institutions. Unlike laparoscopic cholecystectomy, laparoscopic hepatectomy has been slow to gain acceptance because of its associated technical diculties. Theoretically, laparoscopic liver surgery has advantages over the traditional open procedure. Therefore, the aim of this research is to perform a retrograde study of laparoscopic procedures for tumor resection in the patients of HCC. METHODS Patient Data One hundred and sixteen patients (92 male and 24 female) underwent laparoscopic liver resection between 1998 and 2006. Two groups were created; group I; (n = 97, 78 male,19 female) patients with a volume of resection of less than two segments: group II; (n = 19, 14 male, 5 female) patients with a volume of resection greater than two segments, including left lobectomy (removal of segments II and III) in seven patients, and left hepatectomy (removal of segments II, III, and IV) in four patients. The criteria for liver resection were HCC, with pathological diagnosis before operation, which was found to be resectable after imaging and clinical studies. The indications for a laparoscopic procedure were tumor located in the peripheral part of left liver or the anterior sector of right liver, and the size less than 5 cm in diameter, as shown in Fig. 1. Basic data regarding the patients are shown in Table 1. Laparoacopic Approach Procedures The patient was in supine position under general anesthesia and the trocar insertion sites depended on

FIG. 1. Schema of the location of tumors removed with totally laparoscopic liver resection or the hand-port-assisted technique.

the site of tumor. Usually, it was necessary to insert four trocars to have optimal operative manipulation. The abdominal pressure was maintained at the low level of 812 mmHg, in addition to abdominal lifting if necessary. The general condition of the liver could be evaluated directly from the laparoscopic examination, and then used to decide on the following procedure. The site and extension of the tumor, and its relationship to the vasculature, were conrmed by laparoscopic ultrasonography. The line of intended resection, tumor feeding vessels, and hepatic veins, were marked on the liver surface using diathermy. Microwave coagulation along the resection line was performed, before dissection of the liver parenchyma as shown in Fig. 2. With this technique, the risk of bleeding during dissection is reduced. All of the resection lines were punctured with laparoscopic microwave tissue coagulator to minimize bleeding during the liver dissection. Then, an ultrasonic dissector system (CUSA) was used, and branched vessels and ducts were clipped and then transected, as is commonly done in our patients, as shown in Fig. 3. The surgical eld was irrigated and checked for bleeding or bile leak, and residual uid was removed by suction. The electric coagulator was applied in order to ensure hemostasis of the resection surface. After dissecting the resected part of liver, the specimen was be removed by widening of the epigastric port wound. Finally, a drainage tube was placed to allow postoperative drainage.

Ann. Surg. Oncol. Vol. 15, No. 3, 2008

802

H.-Y. CHEN ET AL.

TABLE 1. Preoperative clinical data regarding the patients with hepatocellular carcinoma
Variable Sex Age Body mass index (kg/m2) HBsAG Anti-HCV Alpha-fetoprotein (ng/ml) GOT (U/L) GPT(U/L) Total bilirubin (mg/dl) Alkaline phosphatase (U/L) Albumin (g/dL) Platelet (103uL) UN (mg/dl) Serum creatinine (mg/dl) Prothrombin activity (%) ASA class Child-Pugh classication CLIP score TNM stage Male Female Total Male Female 25.0 3.4 No Yes No Yes <20 !20 <35 !35 <35 !35 <1 !1 Group I (n = 97) 78 19 57.6 12.6 55.9 12.5 64.7 10.8 24.8 3.5 31 66 64 33 51 46 20 77 33 64 54 43 107.5 60.0 3.6 0.6 43.0 30.4 18.2 10.6 1.2 0.5 0.906 0.092 84 13 79 18 48 49 92 5 Group II (n = 19) 14 5 61.6 13.1 63.1 8.4 57.4 22.7 0.806 11 8 11 8 13 6 5 14 4 15 16 3 72.1 41.1 3.8 0.5 30.6 28.6 18.3 5.5 1.1 0.3 0.963 0.060 18 1 19 0 15 4 19 0 P-value 0.540 0.219 0.043* 0.520 0.059 0.681 0.309 0.554 0.401 0.039* 0.016* 0.084 0.105 0.958 0.594 0.012* 0.461 0.041* 0.035* 0.590

1&2 3&4 A B&C <0.6 !0:6 I&II III&IV

* p < 0.05. ASA, Amercian Society of Anaesthesiologists; Anti-HCV, anti-hepatitis C virus antibodies; HBsAg, hepatitis B surface antigen; TNM, tumornodemetastasis; GOT, glutamic oxaloacetic transaminase; GPT, glutamic pyruvic transaminase; BUN, blood urea nitrogen; CLIP, Cancer of the Liver Italian program.

FIG. 2. Microwave coagulation along the intended resection line after laparoscopic ultrasonic examination.

FIG. 3. Dissecting the liver parenchyma with laparoscopic CUSA until the feeding vessels and bile ducts are exposed and can then be clipped and cut.

Postoperative Evaluation The surgical procedure, postoperative course, and follow-up were evaluated periodically. The following
Ann. Surg. Oncol. Vol. 15, No. 3, 2008

data were collected prospectively, including duration of surgery, blood loss, perioperative transfusions, surgical events, postoperative complications, hospital stay, and survival rate of patients.

LAPAROSCOPIC LIVER SURGERY

803

TABLE 2. Results, morbidity and mortality in the two groups

Variable Operation time (min) Blood loss (mL) Transfusion No Yes Blood transfused (mL) Complication No Yes Survival rate (%) 1 year 3 year 5 year * p < 0.05. Group I (n = 97) 152.4 336.3 101.6 324.4 92 5 36.1 148.7 91 6 85.4 66.4 59.4 Group II (n = 19) 175.8 57.4 329.2 338.0 16 3 105.3 267.7 18 1 94.7 74.2 61.7 P-value 0.764 0.006* 0.122 0.287 0.875 0.1237

RESULTS Intraoperative Results The laparoscopic procedure was totally completed in 116 patients. The lesions were located in the right liver in 61 patients and in the left liver in 55 patients. Conversion to laparotomy occurred in six patients (5.2%) due to anatomical limitations. Mean tumor size measured on the surgical specimen was 2.1 0.8 cm and 3.2 1.9 cm, for groups I and II, respectively. A margin of at least 1 cm beyond the tumor limit was obtained in all patients who underwent surgery for malignancy, except when the base of the tumor was adjacent to the main vessels. The results of laparoscopic liver resection are summarized in Table 2. Patients resumed a full diet on the second or third day after the operation, and the average length of hospital stay was six days, in total, for both groups I and II. The mean operation time was 152.4 336.3 min and 175.8 57.4 min, respectively, for groups I and II. The mean blood loss was 101.6 324.4 mL in group I and 329.2 338.0 mL in group II. Blood transfusion was necessary in ve patients (5.2%) in group I and three patients (15.8%) in group II (p = 0.122). There was no sign of postoperative gas embolism in any of our patients. Postoperative Results The operative mortality rate was zero among our patients, but complication rates were 6.2% and 5.2% for groups I and II, respectively. Transient postoperative ascites developed in two patients, but was well controlled with medication. There were no cases of postoperative bleeding or bile leak in our patients.

FIG. 4. The survival rates of patients with HCC who were treated by laparoscopic liver resection in groups I and II (p = 0.1237).

After a mean follow-up duration of 94 months, no port-site metastasis was observed in our patients. The 1-year, 3-year, and 5-year survival rates were 85.4%, 66.4%, and 59.4% in group I, and 94.7%, 74.2%, and 61.7% for group II, respectively. There was no signicant dierence in survival rates between the two groups (p = 0.1237), as shown in Table 2 and Fig. 4.

DISCUSSION With improvements in laparoscopic techniques, and the development of new and dedicated technologies, endoscopic liver surgery has been feasible since 1993.9 Far from being a routine technique in liver surgery, the laparoscopic approach to formal liver resections may be a promising procedure in selected cases where the tumor can be removed by minor and supercial resection. In 1996, Kaneko et al.10 reported that three patients underwent left lateral segmentectomy, and eight underwent partial hepatectomy. Kaneko and colleagues started to believe that notable differences were seen in blood loss, compared with open hepatectomy, and that postoperative pain was minimal. With the laparoscopic technique, postoperative recovery was swift and smooth. Wound pain was minimal, and the patient was satised with the operation.23,11 More recently, Chang et al. reported that the laparoscopic approach for left lateral sectorectomy was safe and could be considered routine in selected patients.12 If high-risk patients with HCC are selectively targeted, the additional benet of laparoscopy is inAnn. Surg. Oncol. Vol. 15, No. 3, 2008

804

H.-Y. CHEN ET AL.

creased and unnecessary laparotomy may be avoided.13 Despite signicant improvements in preoperative tumor staging, due to sophisticated new imaging and interventional techniques, peritoneal tumor spread and occult liver and lymph node metastases are only detected during surgery in some patients. Therefore, those patients could be given postoperative adjuvant therapy if occult tumor spread was found with the aid of diagnostic laparoscopy.14 Therefore, preventing patients with advanced tumors from undergoing unnecessary laparotomy is an important guiding principle in the staging of the cancer patient.15 In some situations, patients with potentially resectable hepatobiliary malignancy are found to have unresectable tumors at laparotomy. DAngelica et al. report that laparoscopic inspection could be completed in 291 (73%) patients, and 153 patients (38%) were found to have unresectable disease, 84 of whom were identied laparoscopically, increasing resectability from 62% to 78%.16 Therefore, laparoscopic liver resection is feasible in hepatocellular carcinoma if the tumor is singular, smaller than 5 cm, and located in the left lateral segments, or in the anterior or inferior sector of the right liver. Postoperative morbidity is low and long-term results seem to be similar to those of traditional laparotomy, based on our experience. Hence, we and Champault et al.17 believe that the laparoscopic surgery could be used as a procedure for staging and determining resectability in surgical oncology. Our experience strongly suggests that lesions of the left liver lobe (segments II and III), and the anterior sector (segments IVa, V, and VI), constitute a good indication for laparoscopic approach, whereas lesions of the posterior and superior liver segments (segment VII, VII, IVc, and I) are technically demanding and should only be approached with extreme caution or hand-port assisted procedures. Another important factor in laparoscopic surgery was the small tumor size (average diameter less than 5 cm) found in the most of the reported series. In comparing our results with the report of Morino,18 the mean postoperative hospital stay was 6.4 days (range, 216 days) in the laparoscopic group, 5.7 days for non-cirrhotic patients and 12.6 days for cirrhotic ones. In general, the hospital stay was shorter in those patients treated by a laparoscopic approach in our series and on literature review.1819 The mean operating time was 160.5 minutes and the conversion rate to open surgery was 8%, as reported by the National Registry in Spain20, and 5.2% in our series. We believe that the laparoscopic approach reduces blood loss and postoperative hospital stay, as
Ann. Surg. Oncol. Vol. 15, No. 3, 2008

well. Intraoperative bleeding is a topic of great concern in laparoscopic liver resection. In our series, eight patients (8/108), in total, needed blood transfusion. As in open surgery, management of bleeding during dissection of liver parenchyma requires technical experience, and adequate preoperative evaluation is important and offers the best guarantee. The microwave coagulator and CUSA were proved useful during laparoscopic resection, because they can coagulate and divide the hepatic parenchyma during dissection. However, one should be given enough time to operate, in order to achieve adequate homeostasis. In addition, the potential risk of gas embolism led some authors to use gasless suspension laparoscopy. When CO2, which is highly soluble, is used, this complication is rare. However, precautions, such as low abdominal pressure, monitored at the level of 68 mmHg, are warranted.2122 In the study of Belli et al., they suggest that laparoscopy was performed with a CO2 pneumoperitoneum at the level of 1214 mmHg.23 In our experience, it was safe if the pneumoperitoneum was set at a level of 610 mmHg. No port-site metastases were observed in patients of malignant disease, either in our series, or in the literature.24 Laparoscopic liver resection for peripheral or subcapsular hepatocellular carcinoma, in patients with chronic liver disease, is associated with lower morbidity than open resection.18,2527 However, based on our experience, the postoperative complication rate was 6.0%, in total, for laparoscopic liver resection, which was better than that observed in patients who underwent traditional resection in our department (unpublished data). A retrospective study was performed in 11 surgical centers in Europe, looking at their experience with laparoscopic resection of liver malignancies, and 37 patients with HCC were included.28 During a mean follow-up period of 14 months, the 2-year disease-free survival was 44% for patients with HCC. The 3-year overall and disease-free survival rates for patients with HCC (mean follow-up, 40 months) were 85% and 68%, respectively, as reported by Vibert27, and 93% and 64%, respectively, as reported by Cherqui.29 The 5-year overall cumulative survival rate for the 69 patients was 63.9%. 5 ve-year overall survival rate for patients with well differentiated HCC was 78.9%, whereas patients with moderately or poorly differentiated HCC had a 5-year overall survival rate of 38.9%. The 5-year cumulative survival rate for patients with HCCs of up to 2.0 cm in diameter was 76.0%, and 56.3% for patients with HCCs larger than 2.0 cm.29 To some extent, this shows that laparo-

LAPAROSCOPIC LIVER SURGERY

805

scopic procedures are best suited to the treatment of well-differentiated HCC.2930 In our series, the 5-year survival rates were found to be 59.7% and 61.7% for laparoscopic liver resection in groups I and II, respectively, and differences between the groups were nonsignicant (p = 0.1237). Due to the accumulation of experience and improvement of instruments, laparoscopic surgery is more frequently applied to right hepatectomy.31 Ultrasonically activated scissors and blades could decrease the blood loss during laparoscopic or open liver resections. The surgical technique is an important factor in preventing intraoperative and postoperative complications. Various techniques have been developed for safe and careful dissection of the liver parenchyma. Therefore, hand-assisted laparoscopic liver resection is a safe and feasible procedure for removal of two segments of liver.32 Although we have limited experience of hand-port procedure, direct feeling with the surgeons ngers makes possible a procedure that is almost identical to open surgery, in which there is better visualization of the surgical eld and transected margin, and immediate homeostasis is also achieved by manually depressing the bleeding point. From these reports, laparoscopic liver resection using the hand-port system is feasible in selected patients with lesions in the posterior portion of the right hepatic lobe requiring limited resection.3334 Individuals with small tumors may benet, because a large abdominal incision is not required, and the wound-related complication rate might be reduced. In conclusion, laparoscopic hepatectomy could avoid some of the disadvantages of open hepatectomy and is benecial for patient quality of life, as a minimally invasive procedure. Evolution of laparoscopic hepatectomies will probably continue and is worthy of encouragement, depending on the development of new techniques and instruments.

REFERENCES
1. Samama G, Chiche L, Brefort JL, et al. Laparoscopic anatomical hepatic resection. Report of four left lobectomies for solid tumors. Surg Endosc 1998; 12:768. 2. Ker CG, Chen HW, Juan CC, et al. Laparoscopic Sub-segmentectomy for Hepatocellular Carcinoma with Cirrhosis. Hepatogastroenterology 2000; 47:12603. 3. Chen HY, Ker CG, Juan C-C, et al. Laparoscopic left hepatectomy for liver tumor. Formosan J Surg 2002; 35:24652. 4. Lo CM, Lai EC, Liu CL, et al. Laparoscopy and laparoscopic ultrasonography avoid exploratory laparotomy in patients with hepatocellular carcinoma. Ann Surg 1998; 227:52732. 5. Lai EC, Lau WY. Spontaneous rupture of hepatocellular carcinoma: A systematic review. Arch Surg 2006; 141:1918.

6. Santambrogio R, Opocher E, Ceretti AP, et al. Impact of intraoperative ultrasonography in laparoscopic liver surgery. Surg Endosc 2007; 21:1818. 7. Descottes B, Lachachi F, Sodji M, et al. Early experience with laparoscopic approach for solid liver tumors: Initial 16 cases. Ann Surg 2000; 232:6415. 8. Dulucq JL, Wintringer P, Stabilini C, et al. Isolated laparoscopic resection of the hepatic caudate lobe: Surgical technique and a report of 2 cases. Surg Laparosc Endosc Percutan Tech 2006; 16:325. 9. Nord HJ, Brady PG. Endoscopic diagnosis and therapy of hepatocellular carcinoma. Endoscopy 1993; 25:12630. 10. Kaneko H, Takagi S, Shiba T. Laparoscopic partial hepatectomy and left lateral segmentectomy: Technique and results of a clinical series. Surgery 1996; 120:46875. 11. Azagra JS, Goergen M, Gilbart E, et al. Laparoscopic anatomical (hepatic) left lateral segmentectomy-technical aspects. Surg Endosc 1996; 10:75861. 12. Chang S, Laurent A, Tayar C, et al. Laparoscopy as a routine approach for left lateral sectionectomy. Br J Surg 2007; 94:58 63. 13. Kameda Y, Asakawa H, Shimomura S, et al. Laparoscopic prediction of hepatocellular carcinoma in cirrhosis patients. J Gastroenterol Hepatol 1997; 12:57681. 14. Weitz J, DAngelica M, Jarnagin W, et al. Selective use of diagnostic laparoscopy prior to planned hepatectomy for patients with hepatocellular carcinoma. Surgery 2004; 135:273 81. 15. Giger U, Schafer M, Krahenbuhl L. Technique and value of staging laparoscopy. Dig Surg 2002; 19:4738. 16. DAngelica M, Fong Y, Weber S, et al. The role of staging laparoscopy in hepatobiliary malignancy: Prospective analysis of 401 cases. Ann Surg Oncol 2003; 10:1839. 17. Champault A, Dagher I, Vons C, et al. Laparoscopic hepatic resection for hepatocellular carcinoma. Retrospective study of 12 patients. Gastroenterol Clin Biol 2005; 29:96973. 18. Morino M, Morra I, Rosso E, et al. Laparoscopic vs. open hepatic resection: A comparative study. Surg Endosc 2003; 17:19148. 19. Rau HG, Buttler E, Meyer G, et al. Laparoscopic liver resection compared with conventional partial hepatectomy A prospective analysis. Hepatogastroenterology 1998; 45:23338. 20. Cugat E, Olsina JJ, Rotellar F, et al. Initial results of the National Registry of laparoscopic liver surgery. Cir Esp 2005; 78:15260. 21. Watanabe Y, Sato M, Ueda S, et al. Laparoscopic hepatic resection: A new and safe procedure by abdominal wall lifting method. Hepatogastroenterology 1997; 44:1437. 22. Intra M, Viani MP, Ballarini C, et al. Gasless laparoscopic resection of hepatocellular carcinoma (HCC) in cirrhosis. J Laparoendosc Surg 1996; 6:26370. 23. Belli G, Fantini C, DAgostino A, et al. Laparoscopic liver resection without a Pringle maneuver for HCC in cirrhotic patients. Chir Ital 2005; 57:1525. 24. Cherqui D, Husson E, Hammoud R, et al. Laparoscopic liver resections: A feasibility study in 30 patients. Ann Surg 2000; 232:75362. 25. Laurent A, Cherqui D, Lesurtel M, et al. Laparoscopic liver resection for subcapsular hepatocellular carcinoma complicating chronic liver disease. Arch Surg 2003; 138:7639. 26. Buell JF, Thomas MJ, Doty TC, et al. An initial experience and evolution of laparoscopic hepatic resectional surgery. Surgery 2004; 136:80411. 27. Vibert E, Perniceni T, Levard H, et al. Laparoscopic liver resection. Br J Surg 2006; 93:6772. 28. Gigot JF, Glineur D, Azagra JS, et al. Laparoscopic liver resection for malignant liver tumors; Preliminary results of a multi-center European study. Ann Surg 2002; 236:907. 29. Cherqui D, Laurent A, Tayar C, et al. Laparoscopic liver resection for peripheral hepatocellular carcinoma in patients

Ann. Surg. Oncol. Vol. 15, No. 3, 2008

806

H.-Y. CHEN ET AL.

with chronic liver disease: Midterm results and perspectives. Ann Surg 2006; 243:499506. 30. Kawamoto C, Ido K, Isoda N, et al. Long-term outcomes for patients with solitary hepatocellular carcinoma treated by laparoscopic microwave coagulation. Cancer 2005; 103:98593. 31. ORourke N, Fielding G. Laparoscopic right hepatectomy: Surgical technique. J Gastrointest Surg 2004; 8:2136. 32. Fong Y, Jarnagin W, Conlon KC, et al. Hand-assisted laparoscopic liver resection: Lessons from an initial experience. Arch Surg 2000; 135:8549.

33. Huang MT, Lee WJ, Wang W, et al. Hand-assisted laparoscopic hepatectomy for solid tumor in the posterior portion of the right lobe: Initial experience. Ann Surg 2003; 238:6749. 34. Inagaki H, Kurokawa T, Nonami T, et al. Hand-assisted laparoscopic left lateral segmentectomy of the liver for hepatocellular carcinoma with cirrhosis. J Hepatobiliary Pancreat Surg 2003; 10:2958.

Ann. Surg. Oncol. Vol. 15, No. 3, 2008

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.