World J Surg DOI 10.1007/s00268-014-2610-3

Single-Port and Multi-Port Laparoscopic Left Lateral Liver Sectionectomy for Treating Benign Liver Diseases: A Prospective, Randomized, Controlled Study Minggen Hu • Guodong Zhao • Fei Wang Dabin Xu • Rong Liu



Ó Socie´te´ Internationale de Chirurgie 2014

Abstract Background The use of single-port laparoscopy for leftlateral liver sectionectomy (LLLS) has been reported in the literature, but the effectiveness and safety of LLLS has not been validated in randomized, controlled trials. This prospective randomized controlled trial compared the effectiveness and safety of single-port and multi-port laparoscopic LLLS for the surgical treatment of benign liver disease. Methods Altogether, 38 patients aged 17–65 years (16 men, 22 women) with benign liver diseases were hospitalized for elective laparoscopic LLLS between January 2010 and December 2012. Patients were randomly assigned to either single-port (n = 19) or multi-port (n = 19) laparoscopic LLLS. Main outcome measures were operative time, volume of intraoperative blood loss, complication rates, and postoperative hospitalization. Results Baseline characteristics of the two groups were comparable. Single-port and multi-port laparoscopies were successfully completed in all but one patient (1/19, 5.3 %) who required conversion from a single-port to a multi-port procedure. The two groups had similar mean operative times and volumes of intraoperative blood loss. There were no clinically significant postoperative complications or deaths. The single-port group had a significantly shorter

Minggen Hu and Guodong Zhao contributed equally to this study. M. Hu (&)  G. Zhao  F. Wang  D. Xu  R. Liu Department of Surgical Oncology, General Hospital of Chinese People’s Liberation Army, Fuxing Road 28, Beijing 100853, China e-mail: [email protected] R. Liu e-mail: [email protected]

postoperative hospitalization than the multi-port group (2.5 ± 1.7 vs. 4.0 ± 2.1 days; p \ 0.05). Conclusions Single-port laparoscopic LLLS is a technically feasible, effective, safe alternative to multi-port laparoscopy for the treatment of benign liver diseases in cautiously selected patients.

Introduction Laparoscopy is a minimally invasive surgical technique that has revolutionized current general, gastrointestinal, colorectal, gynecologic, and urologic surgery since it was introduced during the late 1980s [1–5]. Compared with conventional laparotomy, laparoscopy is associated with minimal invasiveness, less pain, expedited postoperative recovery, and shorter hospitalization [6]. With recent refinements in laparoscopic instrumentation and technique, the number of required incisions has been reduced, allowing multi-port laparoscopic surgery (MPLS) to evolve into single-port laparoscopic surgery (SPLS) [7], in which the single entry site is normally the umbilicus, a natural embryonic lumen remnant [8]. SPLS is now a viable procedure for cholecystectomy [9], appendectomy [10], hysterectomy [11], and even radical resection of gastrointestinal malignancies [12]. The use of fewer ports further shortens the operative time and minimizes scarring. However, SPLS is restricted by a limited linear view of the surgical field and difficulties in manipulating laparoscopic instruments via a single trocar site. For these reasons SPLS is used more often in minor rather than major operations. Improvements in laparoscopic liver surgery have made relatively slow progress compared with laparoscopy in other surgical subspecialties [13]. Types of laparoscopic

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liver surgery vary dramatically in complexity and difficulty, from simple biopsies and wedge resections to leftlateral sectionectomy [14] or even to hemihepatectomy or trisectionectomy for the treatment of hepatocellular carcinoma [15]. Currently acceptable indications for laparoscopic liver surgery consist mainly of solitary liver diseases that are B5 cm in size and located in liver segments II to VI [16]. Only experienced and specially trained surgeons should perform these procedures [16, 17]. SPLS has been reported for a variety of hepatobiliary procedures, including biliary exploration [18], liver biopsy [19], resection of biliary cyst, hydatid cyst, and metastatic liver tumors [20], and more frequently for laparoscopic left-lateral liver sectionectomy (LLLS) in the treatment of benign liver diseases [21] and for harvesting living donor liver [22]. Localized benign left-lateral liver disease is still the preferred candidate for SPLS because LLLS is technically less demanding. Also, resection specimens of benign liver diseases can be fragmented and retrieved without requiring the addition or extension of a trocar incision. The incorporation of SPLS into LLLS is expected to further reduce surgical morbidity and shorten postoperative hospitalization. Aldrighetti et al. [23] reported in a case–control study that SPLS was technically feasible and as safe as the conventional four-port procedure for selected patients in the scenarios of both benign and malignant liver diseases. The primary objective of this prospective randomized controlled study was to compare the effectiveness and safety of single-port laparoscopic LLLS with that of multiport laparoscopic LLLS for the treatment of benign liver disease.

Materials and methods Study protocol The institutional review board at the Chinese People’s Liberation Army General Hospital approved the study protocol. Between January 2010 and December 2012, a total of 64 patients with localized disease of the left-lateral liver segment were consecutively and prospectively hospitalized at the Department of Surgical Oncology. All patients voluntarily gave informed written consent prior to participation in this study and were subsequently screened for eligibility. The inclusion criteria were age C16 years; surgery was indicated for left-sided hepatolithiasis with complicating liver atrophy; symptomatic liver hemangioma or [10 cm; symptomatic focal nodular hyperplasia or [6 cm; or (a) symptomatic adenoma of any size localized to the leftlateral segment (Couinaud’s segment II and III) and not

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involving the hepatic hilum or the second hilum. The exclusion criteria were height [190 cm; body mass index [30 kg/m2; complicating clinically significant underlying liver conditions such as chronic hepatitis, liver cirrhosis, fibrosis, and steatosis; nonexcludable primary or metastatic liver cancer; concomitant gastrointestinal or extra-gastrointestinal malignancies; or a history of upper abdominal or hepatobiliary surgery. The possibility of liver malignancy was excluded based on a combination of upper abdominal ultrasonography, contrast-enhanced computed tomography (CE-CT) or magnetic resonance imaging scan, and positron emission tomography if applicable. Furthermore, all the included patients had normal serum a-fetoprotein (reference range 0–25 ng/ml), cancer antigen 19–9 (0–37 U/ml), normal coagulation, and sufficient cardiopulmonary/renal function reserve. Eligible patients (n = 38) were equally and randomly assigned to either the SPLS (n = 19) or MPLS (n = 19) group using a computerized random number table [24]. Operative technique A surgical team led by R. L. and consisting of resident surgeons, anesthesiologists, radiologists, clinical pathologists, surgical nurses, and research nurses performed the laparoscopic LLLSs. In each case, the patient was intubated under general anesthesia and placed in the French position (i.e., supine with the legs parted). The body was at a 20° head-up and feet-down tilt, with the left waist elevated 30° on soft cushion pads. The surgeon stood between the patient’s legs, with the first assistant holding the laparoscope on the right side, the second assistant on the left side, and the scrub nurse on the right-foot side. Continuous CO2 pneumoperitoneum was established at a pressure of 12 mmHg. In six patients scheduled for SPLS, the TriPort? Access System (Olympus, Tokyo, Japan) equipped with three 5-mm ports and one 10-mm port (reducible to 5 mm) was placed in a 2-cm subumbilical incision. In the other 13 patients, three conventional laparoscopic trocars (Ethicon Endo-surgery, Cincinnati, OH, USA), consisting of one 12-mm port in the middle and two 5-mm lateral ports, were placed through three adjoining subumbilical incisions. A Laparo-Angle L-hook with an Autonomy Comfort Handle (Cambridge Endo, Framingham, MA, USA) was used that allowed axial rotation and a complete 7° of freedom for unparalleled access to the surgical field. For MPLS, a standard set of four trocars was used. A 5-mm 30° electronic laparoscope (Olympus) was inserted through the 10-mm trocar located below the umbilicus. The primary access port (12 mm) was located on the left midclavicular line below the costal margin. The secondary

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access port (12 mm) was located on the lateral margin of the right rectus abdominis muscle. The third and fourth access ports (5 mm) were located 2 cm below the left costal margin and on the left anterior axillary line, respectively. Laparoscopic LLLS via single or multiple ports was performed as previously described [23]. Briefly, the diseased liver and the entire peritoneal cavity was examined using laparoscopy and intraoperative ultrasonography, if applicable, to delineate the gross pathology, number and size of the left-lateral segment disease, and its anatomical relation with the intrahepatic vessels. To fully mobilize the left-lateral segment, an ultrasonic scalpel (Ethicon EndoSurgery, Cincinnati, OH, USA) was used to sequentially transect the round, falciform, left coronary, left triangle, and hepatogastric ligaments. The proposed line of transection was demarcated by electrocauterization, and the liver parenchymal tissues bridging the left-lateral segment and the left-medial segment were transected using an ultrasonic scalpel. The vascular pedicle of the left-lateral segment was dissected using ultrasonic coagulation. An Endopath ETS-Flex 60-mm articulating linear cutter and stapler with 3.8 mm staples (Ethicon Endo-Surgery) was used to transect and seal the hepatic pedicle. The left hepatic vein root was divided using the ultrasonic scalpel and transected along with the surrounding liver tissue using an additional linear cutter-stapler. Oozing from the resection surface was appropriately controlled by bipolar electrocoagulation (EREB, Tu¨bingen, Germany) and argon beam coagulation (EREB). The peritoneal cavity was thoroughly irrigated with sterile normal saline to exclude any active bleeding or bile leak. No peritoneal drainage tube was placed in any patients. The resection specimen was placed in a disposable sterile endobag (Covidien, Mansfield, OH, USA), fragmented using a pair of oval forceps, and retrieved through the subumbilical port incision without extension. The resection margin was set at least 2 cm if the liver disease was suspected to be malignant during the operation. Frozen section biopsy of at least six randomly selected lesion specimens was performed to exclude the possibility of primary or metastatic liver cancer. The trocar incisions were closed with intradermal sutures. Postoperative care and follow-up The gastric tube and urethral catheter were removed after the patient recovered from general anesthesia. Patients were allowed to resume oral intake of clear liquid 6 hours after laparoscopy and semi-fluid diet on postoperative day (POD) 1. Antimicrobial prophylaxis and intravenous hydration were withdrawn on POD 2, and postoperative

analgesics were prescribed on demand. Follow-up routine hematology, liver biochemistry, and upper abdominal ultrasonography were subsequently performed. The patient was discharged from the hospital if he or she remained normothermic, showed normal results on the follow-up tests, and could tolerate oral intake of a normal diet. Patients were followed up at outpatient clinic visits at 1, 3, and 6 months after laparoscopy using routine hematology, liver biochemistry, upper abdominal ultrasonography, and computed tomography. Cosmetic outcome and quality of life were evaluated by the patients themselves and an independent investigator 6 months after laparoscopy. Follow-up visits were continued if any clinically significant adverse events occurred during the follow-up period. Statistical analysis SPSS 19.0 statistical software package (SPSS, Chicago, IL. USA) was used for statistical analysis. All continuous data are expressed as the mean ± SD and were compared using Student’s t-test for two independent samples. All categoric data are expressed as the number (%), and were compared using Fisher’s exact probability test. A value of p \ 0.05 was considered statistically significant.

Results Of 64 consecutive patients with localized left-lateral liver segment diseases treated at our hospital between January 2010 and December 2012, 38 patients (59.4 %) were eligible for laparoscopic LLLS (Table 1). The other 26 (40.6 %) were excluded from this study because of suspected malignant disease. Hence, 19 patients were assigned to each treatment arm. The two groups were comparable in age, sex, body mass index, the American Society of Anesthesiologists (ASA) physical status classification, location and size of liver tumor, concomitant medical conditions, and history of previous upper abdominal surgery. All patients underwent successful laparoscopic en bloc LLLS, and no patients required conversion to laparotomy (Table 2). In one patient undergoing SPLS with three conventional trocars, appropriate pressure pneumoperitoneum could not be maintained because of CO2 leakage from the trocar intervals. Therefore, the single-port procedure was uneventfully converted to a multi-port operation. The Pringle maneuver was not used in any patient. Patients in the SPLS group had an insignificantly longer mean operative time than those in the MPLS group (105 ± 22.5 vs. 90 ± 26.5 minutes; p [ 0.05). The two groups also had a similar volumes of intraoperative bleeding (75 ± 18 vs. 100 ± 12 ml; p [ 0.05). No

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uncontrollable massive bleeding or other clinically significant intraoperative incidents occurred, and none of patients required blood transfusion. No malignant tumors were reported on intraoperative frozen section biopsy. All patients had an uneventful postoperative recovery (Table 2). The SPLS group required significantly shorter postoperative hospitalization than the MPLS group (2.4 ± 1.7 vs. 4.0 ± 2.1 days; p \ 0.05), and SPLS was associated with slightly lower medical costs (2270 ± 11 vs. 2316 ± 9 USD; p [0.05). No clinically significant postoperative complications occurred in any patient prior to discharge from the hospital.

All left-lateral liver segment diseases were diagnosed as benign tumors or other disease (Table 2), with the results comparable between the two groups. All patients were followed up at outpatient clinics as scheduled, and no patient was lost to follow-up. No disease recurrence or residual was observed during the follow-up period. The two groups showed a favorable cosmetic outcome and a similar overall quality of life. However, compared with the MPLS group the SPLS group had a minimal, almost invisible incision scar.

Discussion Table 1 Baseline demographic and clinical characteristics of patients undergoing SPLS or MPLS for benign left-lateral liver disease Characteristic

SPLS

MPLS

p NS

Age (years)

49.0 ± 13.0

53.0 ± 11.0

Sex (M/F)

8/11

8/11

NS

BMI (kg/m2)

22.9 ± 4.8

23.6 ± 3.7

NS NS

ASA score Class A

16 (84.2 %)

15 (78.9 %)

Class B

3 (15.8 %)

4 (21.1 %)

6 (31.6 %)

6 (31.6 %)

Location of tumor Segment II

NS

Segment III

7 (36.8 %)

8 (42.1 %)

Segments II/III Lesion size (cm)

6 (31.6 %) 7.4 ± 2.5

4 (21.1 %) 6.8 ± 2.9

NS

Concomitant medical conditions

5 (26.3 %)

4 (21.1 %)

NS

Results are given as the mean ± SD, the number of patients, or the number and percent SPLS single-port laparoscopic surgery, MPLS multi-port laparoscopic surgery, BMI body mass index, ASA American Society of Anesthesiologists, NS not significant

Table 2 Operative, postoperative recovery, and pathologic results of patients undergoing SPLS or MPLS for benign left-lateral liver disease

Parameter

To the best of our knowledge, the present work is the first prospective, randomized, controlled study to compare the effectiveness and safety of SPLS and MPLS in laparoscopic LLLS for treating benign liver diseases. Our results showed that SPLS was equal to MPLS in terms of effectiveness and safety in the scenario of localized surgically treated benign liver disease. SPLS, also known as laparoendoscopic single-site surgery (LESS), was developed to further enhance the minimized invasiveness of laparoscopy. Using standard laparoscopic instruments, this procedure has been reported feasible for laparoscopic cholecystectomy and appendectomy [25, 26]. Prior to the present study, whether SPLS is superior to MPLS in terms of invasiveness and cosmetics could be considered undecided. Single-port laparoscopic cholecystectomy was shown to be superior [27, 28], equal [29], or even inferior [30] to the conventional multi-port procedure in terms of perioperative outcomes. In contrast, a case-matched analysis showed that SPLS was as safe as conventional laparoscopy for resecting localized benign or malignant left-

SPLS

MPLS

p

Operative time (min)

105 ± 23

90 ± 27

NS

Volume of blood loss (ml)

75 ± 18

100 ± 12

NS

Conversion to laparotomy

0

0

NS

Use of postoperative analgesics

2 (10.5 %)

3 (15.8 %)

NS

Postoperative hospitalization (days)

2.5 ± 1.7

4.0 ± 2.1

0.025

Overall medical costs (USD)

2270 ± 11

2316 ± 9

NS

Morbidity rate

0

0

NS

Pathology Hemangioma

7 (36.8 %)

8 (42.1 %)

NS

Adenoma

2 (10.5 %)

1 (5.3 %)

Results are the mean ± SD or the number and percent unless otherwise noted

Hepatolithiasis

6 (31.6 %)

5 (26.3 %)

Focal nodular hyperplasia

2 (10.5 %)

3 (15.8 %)

Cystadenoma

1 (5.3 %)

2 (10.5 %)

NS not significant, USD US dollars

Inflammatory pseudotumor

0

1 (5.3 %)

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lateral segment tumors in the hands of experienced hepatobiliary and laparoscopic surgeons [23]. The surgical indications of LLLS using SPLS are generally identical to those of LLLS using conventional laparoscopy. However, the performance of SPLS presents a few technical challenges [23]. The in-line laparoscopic view in SPLS compromises the operator’s ability to see the entire surgical field. The lack of a triangulating operating platform makes laparoscopic manipulation more complex and exhausting, even during simple laparoscopic procedures. The laparoscopic instruments are clustered through a single entry port and are likely to conflict with each other both intracorporeally and extracorporeally. Moreover, SPLS is thought to be less effective in controlling intraperitoneal bleeding. Therefore, SPLS is primarily used only for LLLS [23], marginal liver cyst fenestration [31], and wedge resections of segments II, III, or V with a size of B5 cm [32]. LLLS should be considered the gold standard surgical modality for benign or low-malignancy potential liver diseases localized in the left-lateral segment because it is less invasive than conventional laparotomy [33]. As laparoscopic LLLS is the best established laparoscopic procedure for the liver, it remains the preferred candidate for SPLS. Dissection of the left-lateral segment is relatively simple, and the ligaments suspending the liver also serve as traction to improve the surgeon’s view of the surgical filed. Diseased liver tissue of benign pathology can be fragmented and retrieved without extending the trocar incision or requiring an additional incision. Moreover, the use of laparoscopic stapler significantly shortened the operative time of SPLS from 195 min (range 125–330 min) in a previous single-center case-control study [23] to 105 min (range 60–150 min) in the present study. The TriPort access system, a multi-instrument access port for laparoscopic surgery, allows simultaneous use of up to three instruments through a single trocar incision [34]. This system is easy to manipulate but subject to high medical costs. We used an alternative approach with three conventional laparoscopic trocars, which resulted in similar surgical outcome and cosmetic effect with reduced medical expenses. However, one patient undergoing SPLS with conventional trocars required conversion to routine MPLS because of CO2 leakage. The TriPort system is especially designed to avoid CO2 leakage, thereby preventing the need for conversion to MPLS. Our study could be considered limited by a relatively small sample size due to strict patient selection criteria for safety concerns. More than 40 % of our screened patients were excluded because of suspected malignancies in the absence of preoperative pathology. Only 38 patients were finally determined eligible for laparoscopic LLLS. In addition, the exclusion of borderline or early-stage liver

cancers in our patient selection criteria might underestimate the role of SPLS in the treatment of localized leftlateral liver segment diseases. Finally, we did not perform a psychometric evaluation of patients’ psychological and social functioning, which might have disclosed additional benefits of SPLS.

Conclusions SPLS is technically feasible and as safe as conventional MPLS in selected patients undergoing laparoscopic LLLS for benign liver diseases involving segments II and III. The use of a single port in LLLS is also associated with expedited postoperative recovery and better cosmetic outcome, without compromising surgical effectiveness or safety. Conventional laparoscopic trocars can be a costeffective alternative to the TriPort access system used for establishing the single entry port. This technique is yet to be investigated for low-grade malignant or solitary metastatic tumors and underlying liver cirrhosis. Conflict of interest Drs. Minggen Hu, Guodong Zhao, Fei Wang, Dabin Xu, and Rong Liu have no conflicts of interest or financial ties to disclose.

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Single-port and multi-port laparoscopic left lateral liver sectionectomy for treating benign liver diseases: a prospective, randomized, controlled study.

The use of single-port laparoscopy for left-lateral liver sectionectomy (LLLS) has been reported in the literature, but the effectiveness and safety o...
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