ANNALS OF SURGERYVol. 227, No. 4, 527-532C) 1998 Lippincott-Raven Publishers

Laparoscopy and Laparoscopic UItrasonographyAvoid Exploratory Laparotomy in Patients WithHepatocellular CarcinomaChung-Mau Lo, MBBS, FRCS, FRACS, FACS, Edward C. S. Lai, MS, FRCS, FRACS, FACS,Chi-Leung Liu, MBBS, FRCS (Edin), Sheung-Tat Fan, MS, FRCS, FACS, John Wong, PhD, FRCS, FRACS, FACS

From the Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China

ObjectiveThis prospective study evaluates the value of laparoscopy andlaparoscopic ultrasonography (USG) in avoiding exploratorylaparotomy in patients with hepatocellular carcinoma (HCC).

Summary Background DataLaparotomy and intraoperative USG is the gold standard todetermine the resectability of HCC. No palliation can be of-fered to patients found to have unresectable disease, and thesurgical exploration causes morbidity.

MethodsFrom June 1994 to June 1996, 1 10 of 370 patients (30%)with HCC were considered candidates for possible hepaticresection. Preoperative liver function was assessed usingChild-Pugh grading and indocyanine green retention test. Theextent of disease was evaluated with radiologic studies, in-cluding percutaneous USG, computerized tomography scan,and hepatic angiogram. Nineteen patients were excludedfrom the study because of previous upper abdominal surgery(n = 12), ruptured tumors (n = 4), refusal by patients (n = 2),and instrument failure (n = 1). Laparoscopy and laparoscopicUSG was performed on 91 patients immediately before aplanned laparotomy aiming at hepatic resection. Laparotomywas aborted when definite evidence of unresectable disease

was found on laparoscopic examination.

ResultsThe median time required for laparoscopy and laparoscopicUSG was 30 minutes (range, 10 to 120 minutes). Fifteen pa-tients had evidence of unresectable disease on laparoscopicexamination. Among the remaining 76 patients who under-went laparotomy, 9 had exploration only and 67 underwenthepatic resection. Thus, exploratory laparotomy was avoidedin 63% of patients with unresectable disease. The laparo-scopic examination failed to confirm unresectable diseasemore often when the tumor was >10 cm in diameter. Theprocedure accurately assessed the adequacy of the liver rem-nant and the presence of intrahepatic metastases, but it wasless sensitive in determining the presence of tumor thrombi inmajor vascular structures and the extent of invasion of adja-cent organs. When unresectable disease was detected with-out the need for a laparotomy, the postoperative recoverywas faster, and the nonoperative treatment for the tumorcould be initiated earlier.

ConclusionsLaparoscopy with laparoscopic USG avoids unnecessary lap-arotomy in patients with HCC and should precede a plannedlaparotomy aiming at hepatic resection.

Hepatocellular carcinoma (HCC) carries a poor progno-sis, and hepatic resection offers the best chance of survival.Nonetheless, surgical resection is possible only in 9% to40% of these patients1-6 because of liver cirrhosis and

advanced stages of the disease. Selection of patients forlaparotomy with the intent of curative hepatic resectioninvolves an accurate assessment of the liver function and theextent of disease. Various special liver function studiesincluding the bromsulphthalein test,7'8 indocyanine greenretention test,9'10 oral glucose tolerance test, and arterialketone body ratio11 are performed to assess the global liverfunction. However, the final judgment as to the risk ofpostoperative liver failure often depends on the surgeon's

527

Address for correspondence and reprint requests: Dr. C. M. Lo, Depart-ment of Surgery, The University of Hong Kong, Queen Mary Hospital,Hong Kong, China.

Accepted for publication November 20, 1997.

528 Lo and Others

assessment of the severity of the liver cirrhosis and the sizeof the liver remnant at laparotomy. Despite advances inimaging techniques, significant discrepancies between thefindings of preoperative investigations and those at explor-atory laparotomy are not uncommon. Depending on thepatient population, extent of preoperative investigations andthe criteria for resectability, up to 64% of patients withHCC, are subjected to laparotomy without hepatic resec-tion.2 6"2-5 While it is true that exploratory laparotomy andintraoperative ultrasonography (USG) remain the gold stan-dard before the final decision to proceed to hepatic resec-tion, no surgical palliation can be offered to those withunresectable disease. Surgical exploration to confirm unre-sectability not only entails unnecessary hospital expensesand substantial morbidity for the patient, but it may alsodelay the initiation of nonoperative treatment.

Laparoscopy with laparoscopic USG combines the powerof a detailed visual assessment of the liver with that of highresolution intraoperative contact ultrasound examination.Recent studies have yielded encouraging results with thisminimally invasive technique in staging of liver tumors andother gastrointestinal malignancies.' 6-19 Therefore, we con-ducted a prospective study to ascertain the value of lapa-roscopy and laparoscopic USG performed immediately be-fore a planned laparotomy in patients with potentiallyresectable HCC.

PATIENTS AND METHODSFrom June 1994 to June 1996, 370 patients with newly

diagnosed HCC were seen in the Department of Surgery atthe University of Hong Kong at Queen Mary Hospital. Thepossibility of hepatic resection was assessed according to astandard protocol. All patients had a chest radiograph andpercutaneous USG. Laboratory blood tests including hepa-titis B surface antigen, serum alpha-fetoprotein, serum al-bumin, serum total bilirubin, aspartate aminotransferase,alanine aminotransferase, and prothrombin time were ob-tained and the Pugh's modification of Child's criteria20 wasdetermined. The indocyanine green retention test was per-formed to assess the liver function with a maximum reten-tion of 14% at 15 minutes as the guideline for majorhepatectomy in patients with cirrhosis.9 Patients with po-tentially resectable lesions underwent a computed tomogra-phy (CT) scan of the abdomen and a hepatic angiogram. ALipiodol-CT scan was performed in selected patients. Fur-ther investigations, such as CT scan of the thorax, or radio-isotope bone scand were performed only when there wasclinical suspicion of extrahepatic metastases.

Using such criteria, 110 patients (30%) were consideredcandidates for possible hepatic resection and underwentsurgery. Nineteen patients were excluded from this studyand had an exploratory laparotomy directly to assess resect-ability. The reasons for exclusion were previous upper ab-dominal surgery (12 patients), ruptured tumors (4 patients),refusal by patients (2 patients), and instrument failure (1

patient). Laparoscopy with laparoscopic USG was at-tempted in 91 patients immediately before a planned lapa-rotomy that aimed at hepatic resection. There were 77 menand 14 women who had a mean age of 53.2 years (range, 18to 82 years). Serum hepatitis B surface antigen was positivein 82 patients (90%). Eighty-five patients were of Child-Pugh class A, 5 of class B, and 1 of class C. The mean ±SDpreoperative indocyanine green retention at 15 minutes was12.5% ± 9.1%. Fifty-three patients (58.2%) had large tu-mors >5 cm in diameter.

Laparoscopy and Laparoscopic USGThe patient was prepared as for a planned hepatic resec-

tion and was put under general anesthesia with endotrachealintubation. A subumbilical cutdown technique was used toinsert a 12-mm laparoscopic port, and pneumoperitoneumwas established with carbon dioxide insufflation to a max-imum pressure of 12 mmHg. Using a 300 laparoscope, theperitoneal cavity and surface of the liver was inspected.Under direct visual guidance, a second 12-mm port wasinserted in the right lower quadrant at the mid-clavicularline. The laparoscopic ultrasound probe was insertedthrough this port and was placed in contact with the liverunder the guidance of the laparoscope. In the early part ofthe study, a rigid 7.5 M-Hz linear array probe (AlokaUST-5526-7.5, Tokyo, Japan) was used in conjunction witha portable ultrasound monitor (Aloka SSD-500). Thesewere subsequently replaced by another ultrasound monitor(Aloka SSD-2000) and a flexible 7.5 M-Hz probe (AlokaUST-5536-7.5), which could be steered upward and down-ward for better contact with the surface of the liver. Sys-temic examination of the liver was performed by slowlymoving and rotating the probe over the entire liver. Lapa-roscopic inspection of the undersurface of the left lobe wascompleted by using the laparoscopic ultrasound probe todisplace the liver. The examination was repeated after thesites of insertion for the laparoscope and laparoscopic ul-trasound probe were interchanged. A guided biopsy withfrozen section was performed to examine suspicious lesionsthat would preclude curative resection if found positive.However, for fear of dissemination, a biopsy for potentiallyresectable tumors was not performed. The decision forunresectability was based on the finding of disease notamenable to curative resection or an inadequate liver rem-nant, using the same criteria as at laparotomy and intraop-erative USG. When definite evidence of unresectable dis-ease was manifest on laparoscopic examination, laparotomywas not performed. Otherwise, if unresectability was notobvious or only was suspected but not confirmed, openexploration and intraoperative USG using a 7.5 M-Hz T-shaped probe was performed immediately. A further biopsywith frozen section was done for suspicious lesions. Whenresectability was determined, hepatic resection was carriedout using the technique previously described.5 All proce-dures, including laparoscopy, laparoscopic USG, intraoper-

Ann. Surg. * April 1998

Laparoscopic Ultrasonography for Hepatocellular Carcinoma 529

Hepatocellular carcinoma(n=370)

II

Surey(n- I 10)

Laparoscopic u rng y Laparotomy(n-91) (n=19)

Hepatic resection Unresectable Unrese[able(n=67) (n-9) (n=I5) Unresectable Hepatic resection

RES group LAP group LUS goup (n=6) (n=13)

Figure 1. Study design and results of laparoscopic ultrasonography.

ative USG, and hepatic resection were undertaken by thesame surgical team. All the surgeons have had extensiveexperience in laparoscopic surgery and intraoperative USG.

Statistical Analysis

Continuous variables were expressed as median (range)and compared using the Mann-Whitney U test. Categoricalvariables were compared using either the chi-square test or

the Fisher's Exact test, where appropriate. Statistical anal-ysis was performed with the help of SPSSPC+ (SPSS,Chicago, Illinois) and a p value < 0.05 was taken as

statistically significant.

RESULTS

Laparoscopy with laparoscopic USG was successfullyperformed in all 91 patients. The median time for theprocedure was 30 minutes (range, 10 to 120 minutes). Theexamination demonstrated definite features of unresectabledisease and thus laparotomy in 15 patients (LUS group) wasavoided. The remaining 76 patients underwent laparotomy.Sixty-seven patients had hepatic resection (RES group)while 9 patients were unresectable on exploration (LAPgroup). Thus, the use of laparoscopy and laparoscopic USGavoided exploratory laparotomy in 15 of 24 patients (63%)with unresectable disease, which increased the resectabilityrate at laparotomy from 74% to 88%. During the same

period, 19 patients who were excluded from this study hadlaparotomy without laparoscopy and laparoscopic USG. Sixpatients had exploration only without hepatic resection,giving a resectability rate of 68% (Figure 1).

Duration of ProcedureThe median time required for completion of laparoscopy

and laparoscopic USG was 45 minutes (range, 30 to 120minutes) for the LUS group, 20 minutes (range, 15 to 35minutes) for the LAP group, and 25 minutes (range, 10 to 90minutes) for the RES group (p < 0.001, LUS group vs. LAPgroup or RES group). The significantly longer time requiredin the LUS group was related to the need for laparoscopic orlaparoscopic ultrasonographically guided biopsy to confirmunresectable disease without performing a laparotomy.

Demographic Data, Liver Function, andTumor SizeThe demographic data of (Table 1) the three groups of

patients were comparable, and there was no difference in thepreoperative liver function with reference to Child-Pughgrading or indocyanine green retention test. However, pa-tients who underwent hepatic resection had significantlysmaller tumors than those with unresectable disease (p <0.05, RES group vs LUS group; p < 0.001, RES group vsLAP group). Patients with unresectable disease not detectedby the laparoscopic examination, but found only at laparot-omy, tended to have a larger tumor size than those identifiedby laparoscopy and laparoscopic USG (p = 0.06). Thelaparoscopic examination failed to confirm unresectable dis-ease in 7 of 12 patients with tumors >10 cm and in only 2of 12 patients with tumors ' 10 cm.

Major Findings of UnresectabilityThe major findings that precluded hepatic resection in 24

patients of LUS and LAP groups are shown in Table 2. Onlaparoscopic examination alone, 8 of the 24 patients hadevidence of unresectable disease including an inadequateliver remnant (6 patients), visible bilobar disease (5 pa-tients) and peritoneal metastasis (1 patient). After laparo-scopic USG, another 7 patients had additional features ne-gating hepatic resection. These included bilobar intrahepaticmetastases (6 patients) and tumor infiltration of main portalvein or inferior vena cava (3 patients). The remaining ninepatients of the LAP group required exploratory laparotomyto detect (five patients) or to confirm unresectable disease(four patients). Thus, laparoscopy and laparoscopic USGwas able to detect 6 of 7 patients with inadequate liverremnant, 11 of 13 patients with bilobar intrahepatic metas-tases, and the 1 patient with peritoneal metastasis. However,the procedure failed to confirm the presence of main portalvein tumor thrombi in three of five patients, inferior venacava tumor thrombi in one of two patients, and invasion ofadjacent organs in all three patients.

Postoperative CourseThere was no complication related to the laparoscopic

examination itself. Two of nine patients in whom unresect-

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530 Lo and Others

Table 1. DEMOGRAPHIC DATA, LIVER FUNCTION, AND TUMOR SIZE OF 91 PATIENTSWITH HEPATOCELLULAR CARCINOMA UNDERGOING LAPAROSCOPY AND

LAPAROSCOPY ULTRASONOGRAPHY

LUS Group (n = 15) LAP Group (n = 9) RES Group (n = 67)

Sex (M:F)Age (yr)*Child-Pugh gradingABC

ICG retention at 15 min (%)*Tumor size (cm)*>105.1-102.1-5<2

12:351 (32-77)

140

111 (3.8-26.9)8 (2.5-15)5550

8:153 (45-72)

7

20

14 (5-33.5)11.6 (5.2-1 5)t720

0

57:1052 (18-82)

6430

10.5 (1.6-66.9)5.8 (1.5-15.2)

1123276

LUS group = unresectable disease detected by laparscopic examination; LAP group = unresectable disease detected by laparotomy; RES group = resectable disease;ICG = Indocyanine green.* Median (range).t p <0.001 LAP group vs. RES group; p = 0.06 LAP group vs. LUS group.

able disease was discovered at exploratory laparotomy de-veloped postoperative complications: one developed pneu-

monia and another had pleural effusion which requiredtapping. There was no complication in patients who under-went laparoscopy and laparoscopic USG alone. Patients ofthe LUS group were able to resume their diet earlier (O dayvs. 1.5 days; p < 0.05) and also had a shorter hospital stay(5 days vs. 9 days; p < 0.005) when compared with those ofthe LAP group (Table 3).

Eight patients of the LUS group and five of the LAPgroup subsequently received transarterial chemoemboliza-tion. Two patients of each group were treated with oral

Table 2. MAJOR FINDINGS PRECLUDINGHEPATIC RESECTION IN 24 PATIENTSWITH HEPATOCELLULAR CARCINOMA

LUP Group LAP Group(n = 15) (n = 9)

Inadequate liver remnant/severecirrhosis

Peritoneal metastasisBilobar intrahepatic metastatsisMain portal vein tumor thrombusInferior vena cava tumorthrombus

Invasion of adjacent organs

61

1 12

1

0

1 (1)0

2 (1)3 (2)

1

Some patients had more than one feature precluding hepatic resection. Values inparentheses are number of patients with findings suspected on laparoscopicexamination.LUS group = findings at laparoscopy and laparoscopic ultrasonography; LAPgroup = findings at laparotomy.* Invasion of colon and duodenum in one patient and invasion of the diaphragmclose to the inferior vena cava in two patients.

tamoxifen and one of the LUS group received ultrasound-guided intralesional alcohol injection. The remaining fourpatients of the LUS group and two of the LAP group hadsymptomatic treatment only. The time from surgery to theperformance of nonoperative treatment was less in the LUSgroup (11 patients) than in the LAP group (7 patients) (6days vs. 23 days; p < 0.05). The median survival, however,was not significantly different (Table 3). For the 67 patientswho underwent hepatic resection, the 1-year survival ratewas 76%, and there was no evidence of metastasis at thelaparoscopic port-sites or laparotomy wounds in any patientat a median follow-up of 10 months (range, 1 to 30 months).

DISCUSSIONDespite recent advances in hepatic resection techniques,

surgical resection for HCC should be offered only to se-

Table 3. POSTOPERATIVE COURSE OF24 PATIENTS WITH UNRESECTABLEHEPATOCELLULAR CARCINOMA

LUS Group LAP Group(n = 15) (n = 9)

Tolerate normal diet (days)* 0 (0-2) 1.5 (0-4)tPostoperative complications 0 2Hospital stay (days)* 5 (0-16) 9 (4-31)tTime from surgery to nonoperative

treatment (days)* 6 (0-79) 23 (2-91)tMedian survival (mo) 5 5.7

* Median (range).t p <0.05.t p < 0.005.

Ann. Surg. * April 1998

Laparoscopic Ultrasonography for Hepatocellular Carcinoma 531

lected patients with sufficient liver function and unilateraldisease amenable to curative treatment.21 Hepatectomy inthe presence of poor hepatic reserve will often result inpostoperative liver failure which carries a greater mortalityrate.22 Likewise, palliative resection for patients with bilo-bar or metastatic disease offers no meaningful survivaladvantage.'3'23 The ultimate goal of various modalities ofpreoperative assessment is the selection of the appropriatecandidates suitable for hepatic resection. Nonetheless, withthe use of preoperative indocyanine green retention test,percutaneous USG, contrast-enhanced CT scan, and hepaticangiography, more than 25% of our patients subjected tosurgery were on exploration not resectable. Because thesurvival time of these patients with unresectable disease islimited, an exploratory laparotomy would entail significantsuffering and morbidity. Thus, an accurate but less invasivetechnique for determining resectability is needed.

Diagnostic laparoscopy, as a staging technique for he-patic malignancy, is sensitive in identifying underlying livercirrhosis, peritoneal metastasis, and satellite lesions on thesurface of the liver. Babineau et al.24 reported that 14 of 29patients with hepatic malignancies had laparoscopy evi-dence of unresectable disease. Most of their patients suf-fered from metastatic liver cancer, and peritoneal seedlingswere the most common laparoscopic finding that precludedhepatic resection. Autopsy studies, however, showed thatHCC had a much lower incidence of peritoneal metastasesthan other hepatic malignancies.4 In a clinical series of 48patients who were subjected to surgery for HCC,6 only 1 ofthe 14 patients who was not resectable had peritoneal me-

tastasis. In the present series, concomitant liver cirrhosiswith inadequate liver remnant, bilobar intrahepatic metas-tases, and tumor thrombi in major vascular structures were

the three most common findings that precluded hepaticresection in patients with HCC. Intrahepatic metastasis andtumor thrombus are often not visible or palpable and can

readily be detected by intraoperative USG only.25 Thus, thevalue of diagnostic laparoscopy alone was limited in pa-

tients with HCC and the procedure could detect only 8 of 24patients with unresectable disease in this series.

Recent advances in minimal access surgery has promotedthe development of laparoscopic ultrasonograpic transduc-ers. Laparoscopy with laparoscopic USG combines the lessinvasive advantage of minimal access surgery with thegreater accuracy of intraoperative contact USG. The sensi-tivity of laparoscopic USG in detecting intrahepatic lesionswas comparable to that of open contact USG in a bench topmodel of hepatic metastases.26 The clinical use of laparos-copy and laparoscopic USG in staging liver tumors was

recently reported. Timothy et al.16 described their experi-ence of the technique in a heterogenous group of patientswith different types of liver tumors, including benign le-sions. In some cases, however, the purpose of the procedurewas diagnostic rather than staging, and the laparoscopicexamination was not always performed after full preopera-tive radiologic assessment had been completed. In a retro-

spective study of 13 patients with liver metastases,17 theaccuracy of laparoscopic USG was compared with that ofCT portography. Laparoscopy and laparoscopic USG sharethe objectives of other modalities of preoperative assess-ment in selecting the appropriate candidates for hepaticresection. However, the procedure itself is an operationunder general anesthesia and is invasive when comparedwith other radiologic investigations. Hence, we tend toreserve this procedure only for those patients with poten-tially resectable HCC after less invasive investigations hadbeen completed. To ascertain whether this minimally inva-sive technique can replace open exploration for determina-tion of resectability, its accuracy should be compared withintraoperative USG at laparotomy.Our data show that laparoscopy with laparoscopic USG is

highly accurate in assessing the adequacy of the liver rem-nant and the presence of intrahepatic metastases. However,the procedure is less accurate than laparotomy and intraop-erative USG in determining the presence of tumor thrombiin major vascular structures and the extent of invasion ofadjacent organs. When compared with intraoperative USGat laparotomy, the definite limitations of the laparoscopictechnique are: 1) palpation of a lesion is not possible underthe laparoscope; 2) when direct invasion of adjacent organsis suspected, a trial of dissection cannot be performed; 3) theangle and direction of ultrasound scanning under the lapa-roscope is limited by the position of the laparoscopic ports;and 4) preliminary mobilization and manipulation of theliver to improve the angle of scanning cannot be performed.Such limitations are most obvious in patients with largetumors and account for the lower accuracy of the laparo-scopic examination in determining resectability when thetumors are >10 cm in diameter. Thus, bulky tumors inter-fere with the angle and direction of the laparoscopic ultra-sound probe and limit the adequacy of scanning. In addition,invasion of adjacent organs tends to occur more often withthese large tumors. To assess whether the tumor is adherentto or infiltrating the colon or the duodenum, a careful trial ofdissection is necessary. Similarly, invasion of the dia-phragm can only be detected after mobilization of the liver'sright lobe. Such a trial of dissection for a large tumor ispotentially dangerous under the laparoscope and onlyshould be attempted at laparotomy.With the use of laparoscopy with laparoscopic USG, we

were able to avoid exploratory laparotomy in more than60% of our patients with unresectable disease. By success-fully avoiding the need for open exploration in these 15patients, the morbidity rate was reduced, the hospital staywas shortened, and nonoperative treatments could be startedearlier. For the 76 patients who subsequently underwentlaparotomy and did not benefit from the laparoscopic ex-amination, although the procedure caused an extra operatingtime of 20 to 25 minutes, there was no procedure-relatedcomplication. The report of port-site metastases after lapa-roscopic surgery in patients with occult malignancy27 raisesconcerns about this important complication after diagnostic

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532 Lo and Others

laparoscopy. The incidence was 1.6% in a retrospectivestudy of 250 patients who underwent staging laparoscopyfor gastrointestinal malignancy.28 To avoid tumor seedling,biopsy should be performed only for unresectable tumors orfor suspicious metastases that would preclude curative re-section. Biopsy should be avoided in patients with poten-tially resectable disease. In this series, no laparoscopicport-site or laparotomy wound metastasis developed in pa-tients who underwent hepatic resection with curative intent,and the laparoscopic examination did not seem to jeopardizethe outcome of these patients.

In conclusion, laparoscopy with laparoscopic USG avoidsthe morbidity associated with exploratory laparotomy in pa-tients with HCC. Although the technique may be less accuratefor tumors > 10 cm in diameter, we would recommend that theprocedure should be performed in all cases before a plannedlaparotomy aiming at hepatic resection.

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