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10.1245/s10434-006-9278-3
Annals of Surgical Oncology 14:1347-1355 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Contrast-Enhanced Intraoperative Ultrasonography During Surgery for Hepatocellular Carcinoma in Liver Cirrhosis: Is It Useful or Useless? A Prospective Cohort Study of Our Experience

Guido Torzilli, MD, PhD, Angela Palmisano, MD, Daniele Del Fabbro, MD, Matteo Marconi, MD, Matteo Donadon, MD, Antonino Spinelli, MD, Paolo Pietro Bianchi, MD and Marco Montorsi, MD

3rd Department of Surgery, Istituto Clinico Humanitas, IRCCS, University of Milan, Via Manzoni, 56, I-20089, Rozzano, Milan, Italy

Correspondence: Address correspondence and reprint requests to: Guido Torzilli, MD, PhD; E-mail: guido.torzilli{at}unimi.it


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Preliminary results showed that contrast-enhanced intraoperative ultrasonography (CEIOUS) could provide information not obtainable with conventional IOUS during surgery for hepatocellular carcinoma (HCC). The aim of the study was to prospectively validate the role of CEIOUS on the basis of a larger experience and to establish a new classification that takes into account its findings.

Methods: Eighty-seven consecutive patients underwent hepatecomies for HCC. Those patients with new lesions at IOUS underwent CEIOUS: for that patients received intravenously 4.8 mL sulphurhexafluoride microbubbles. Pattern of enhancement was classified in 4 categories: A1 (full enhancement in the arterial phase and wash-out in the delayed phases), A2 (intralesional signs of neovascularization during all phases), A3 (no nodular enhancement but detectability during the liver enhancement), and B (undetectability during the liver enhancement). Resection was recommended for A1-3 nodules and no treatment for B nodules.

Results: Twenty-nine patients (33%) had 59 new lesions at IOUS and underwent CEIOUS. Twenty-seven nodules showed a B pattern at CEIOUS and were not removed; 32 nodules were classified as A1 in 5 patients, A2 in 11 patients, and A3 in 16 patients. The nodules were removed, and by histology, five A1, nine A2, and six A3 nodules were confirmed to be HCC. CEIOUS modified the operative decision making in 79% of these patients.

Conclusions: CEIOUS is useful during surgery for HCC; it complements the accuracy of IOUS and affects the radicalness of the surgical. Specificity of CEIOUS has to be further improved, although intrinsic drawbacks exist in the diagnostic criterion of tumor vascularity.

Key Words: Intraoperative ultrasonography • Hepatocellular carcinoma • Liver cirrhosis • Liver tumors • Diagnosis • Staging • Surgery • Laparoscopic ultrasonography • Contrast-enhanced ultrasound • Contrast-enhanced intraoperative ultrasound


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Today, intraoperative ultrasonography (IOUS) is still the most accurate diagnostic technique for detecting focal liver lesions (FLLs).1,2 However, IOUS has a few drawbacks. One of them is that in patients with cirrhosis and hepatocellular carcinoma (HCC), few nodules detected by IOUS are neoplastic (20% to 30%),3,4 which results in the likely overstaging of the disease. Currently, IOUS, unlike computed tomography (CT) or magnetic resonance imaging, does not provide information about tumor vascularity and tissue microcirculation. However, the introduction of intravenous contrast agent during transcutaneous ultrasonography (US) of the liver has been shown to improve US characterization for HCC.5 Conversely, contrast-enhanced US (CEUS) does not seem to affect nodule detection in the cirrhotic liver. Indeed, HCC is typically enhanced in the arterial phase, which lasts 10 to 40 seconds.5 This fact limits the possibility of checking for the presence (or absence) of new lesions in the liver with CEUS, but it permits the detailed study of nodules identified by unenhanced US.

We have previously reported that contrast-enhanced intraoperative ultrasonography (CEIOUS) is feasible.6 It may provide further information to IOUS for patients who undergo surgery for HCC,6,7 and it improves IOUS staging in patients who undergo surgery for colorectal cancer liver metastases.6,8 These last results have been recently confirmed by other authors.9 However, our preliminary experience with CEIOUS in patients operated for HCC was based on a small sample size, and for that reason, we could not provide definite results concerning the real impact of this technique in aiding nodule differentiation among the new lesions detected by IOUS. Furthermore, our experience with CEIOUS and HCC was not followed by reports of similar experiences from other groups, as it was for colorectal cancer liver metastases.

It is therefore necessary to more comprehensively evaluate the role of CEIOUS during surgery for HCC. For this purpose, we developed a new classification for the pattern of enhancement of the new lesions detected by IOUS, which was a simplified version of that released in the published studies about CEUS.5 This study aims to prospectively validate this approach on a cohort of patients operated on for HCC. We compared their long-term results with those of patients with HCC who underwent surgery before CEIOUS was introduced.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
From September 2003 to January 2006, a total of 87 consecutive patients, 64 men and 23 women, underwent liver resection that used IOUS and CEIOUS for imaging of HCC in liver cirrhosis. Mean patient age was 67.8 years (median, 69 years; range, 36–87 years). The imaging diagnostic workup for FLLs for the patients included abdominal US and contrast-enhanced spiral CT (5-mm slice thickness) in all cases; magnetic resonance imaging, CEUS, 18-FDG–positron emission tomography, angiography, and fine-needle biopsy were carried out in eight, five, one, three, and one patient, respectively. Seventy-five patients had associated cirrhosis, and twelve had chronic hepatitis. Informed consent was obtained from all patients.

IOUS was performed in all cases with an Aloka SDD 5500 (Aloka, Tokyo, Japan); for IOUS, a microconvex probe of 7.5 to 10 MHz frequency was adopted, whereas for CEIOUS a convex probe of 3 to 6 MHz frequency and a 1.88 to 3.76 MHz harmonic frequency transducer was used. In all patients, 4.8 mL of sulfur-hexafluoride microbubbles (SonoVue, Bracco Imaging, Italy) was injected intravenously through a peripheral vein by the anesthesiologist. After laparotomy, IOUS exploration was performed to confirm the presence and location of the FLLs diagnosed preoperatively, and to find adjunctive nodules. When we found additional FLLs by IOUS, we used CEIOUS to study their vascularity.

Interpretation of the findings of CEIOUS was performed according to the following classification, and related treatments were adopted (Fig. 1Go). A hypoechogenic or hyperechogenic nodule was considered malignant and then removed when: (1) CEIOUS showed a full enhancement (hyperechogenic appearance) in the arterial phase, becoming hypoechogenic in the delayed portal and late phases (A1); (2) CEIOUS showed only intralesional signs of neovascularization during the arterial and delayed phases (A2) (Fig. 2Go); (3) CEIOUS did not show any early enhancement or any intralesional sign of neovascularization, but the lesion seemed fully hypoechogenic in comparison with the surrounding liver parenchyma during all the phases (A3) (Fig. 3Go); or (4) if a hypoechogenic or hyperechogenic nodule was no longer visible compared with the surrounding liver parenchyma in all the phases, it was considered to be a nonneoplastic lesion. These last FLLs were not removed, and their benignity was confirmed after at least 6 months of follow-up if there was no tumor growth or if they were still not detectable by spiral CT.


Figure 1
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  		FIG. 1. Schema showing different patterns of enhancement and illustrating our classification scheme. (a) A1 is pattern in which nodule (1) is fully enhanced in arterial phase (2) and unenhanced in late phases (3). (b) A2 is pattern in which nodule (1) shows intranodular neovascularization in arterial phase (2), which remains evident in late phases (3). (c) A3 is pattern in which nodule (1) remains unenhanced in both arterial (2) and late phases (3). (d) B is pattern in which nodule (1) has same enhancement of surrounding liver parenchyma in all the phases.

 

Figure 2
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  		FIG. 2. Nodule (arrows) enhanced with pattern A2 in arterial (a) and delayed (b) phases. Arrowheads indicate intranodular signals indicating neovascularization.

 

Figure 3
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  		FIG. 3. Nodule (arrows) appear with pattern A3 in arterial (a) and delayed (b) phases.

 
If a new nodule showed a mosaic pattern at IOUS, it was considered malignant3,4 and removed without performing CEIOUS for characterization. On the basis of a previous study, intraoperative fine-needle biopsy was not considered adequate to differentiate these nodules.10 The results of IOUS and CEIOUS were compared with those of histology for the nodules that were removed, and with the CT findings at a follow-up of at least 6 months for nodules that were not resected. Assuming that any new nodule found by IOUS was a potentially malignant lesion, a new finding at CEIOUS was defined as any nodule detected by IOUS that showed a pattern of enhancement at CEIOUS not indicating malignancy; therefore, pattern B at CEIOUS was considered a new finding. Inversely, those nodules with A1 to A3 pattern of enhancement at CEIOUS were considered to be a confirmation of IOUS findings.

Operative decision making was considered modified for either of the following two conditions: (1) CEIOUS confirmed the new lesions detected by IOUS as malignant, and their removal modified the surgical strategy by adding a new area of resection or modifying the extension of the planned one; or (2) CEIOUS did not confirm the new lesions detected by IOUS to be malignant, and as a result of this finding, the surgeon did not add new resection areas or did not modify the planned one.

Overall, disease-free, and hepatic-free survival times were calculated for the considered cohort of patients and were compared with the same survival-time curves obtained for the group of patients belonging to the pre-CEIOUS group. This group comprised 10 consecutive patients who underwent surgery from June 2000 to July 2002. These patients, who were the first to undergo surgery for HCC since we started our work, also underwent hepatectomies with IOUS guidance. Patients who underwent CEIOUS from August 2002 to September 2003, but who were considered in previously published studies,6,7 were not included in the present analysis.

Statistical Analysis
Accuracy, sensitivity, specificity, and positive and negative predictive values were calculated for IOUS and CEIOUS. False-positive findings were based on histological findings of the resected specimens. False-negative findings were evaluated on the basis of imaging studies performed during postoperative follow-up. In particular, any new lesion detected at any time during follow-up that occurred in the site where a B-pattern lesion was detected during surgery was considered to be a false-negative finding of CEIOUS. Conversely, any new lesion detected within the first 12 months of follow-up after surgery that did not correspond to any B-pattern lesion at CEIOUS was considered as a false-negative finding of IOUS.

Survival time for the group of patients in the pre-CEIOUS group and of the cohort of patients studied with CEIOUS was calculated from the date of hepatic resection until death. Disease-free and hepatic-free survivals were calculated from the date of hepatic resection until diagnosis of recurrence overall or limited to the liver, respectively. The survival rates were obtained by the Kaplan-Meier method and compared by the log rank test. A bilateral Student’s t-test for unpaired data was used to compare the mean tumor size and the number of tumors in the two groups. The {chi}2 test was used to match the groups in terms of background liver features and rate of macrovascular invasion. All significance tests were two-tailed, and P < .05 was considered statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Preoperatively, the total number of detected lesions was 106 (mean, 1.3; median, 1; range, 1–4), with a mean tumor diameter of 4.9 cm (median, 3.9 cm; range, 1.1–20 cm). At IOUS, the 106 lesions were all confirmed, and in 29 patients (33%), an additional 59 nodules were detected (mean, .7; median, 0; range, 0–5). Of these 59 nodules, 51 were hypoechogenic (mean, .9 cm; range, .4–1.4 cm) and 8 were hyperechogenic (mean, .8 cm; range, .7–.9 cm). CEIOUS was performed in 29 patients found to have new FLLs at IOUS, and the total number of injections was 46 (mean, 1.6; median, 2; range, 1–3). No adverse effects were observed.

Figure 4Go shows the distribution of the different pattern of enhancement by CEIOUS among these new FLLs. Twenty-seven (46%) of 59 new FLLs detected by IOUS showed the contrast enhancement previously classified as B, and thus, they were not considered malignant. In accordance with our protocol, none of them was removed (Fig. 4Go); instead, the FLLs were monitored at follow-up. The remaining 32 new FLLs (54%) found by IOUS showed contrast enhancement pattern A1 in 5 (16%), A2 in 11 (34%), and A3 in 16 (50%). All the A1 to A3 new FLLs were diagnosed as HCC nodules and then removed. As shown in Fig. 4Go, all the nodules with A1 pattern were proved by histology to be HCC, all but two of those with A2 pattern (80%); only 6 (38%) of 16 nodules with A3 pattern were HCC. The two false-positive nodules with A2 pattern at CEIOUS were, respectively, a regenerative nodule and a low-grade dysplastic nodule. The 10 false-positive FLLs showing an A3 pattern by CEIOUS at histology were as follows: four regenerative nodules, three biliary hamartomas, two low-grade dysplastic nodules, and one necrotic lesion. No new FLLs showed a mosaic pattern at IOUS.


Figure 4
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  		FIG. 4. Distribution among new focal liver lesions at intraoperative ultrasonography (IOUS) of the different pattern of enhancement at contrast-enhanced intraoperative ultrasonography (CEIOUS).

 
Figure 5Go shows the impact of CEIOUS on operative decision making for 29 patients with new FLLs found by IOUS. As a result of CEIOUS, 11 patients with new B-pattern FLLs did not undergo additional resection. For this subgroup of patients, the mean follow-up was 24 months (median, 16 months; range, 6–34 months), and the mean disease-free survival was 17 months (median, 11 months; range, 2–34 months). The six new liver lesions discovered during follow-up in these patients were all confirmed by contrast-enhanced CT, but none of them occurred in the segments where the B-pattern lesions had been detected.


Figure 5
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  		FIG. 5. Schema indicating how operative decision making was modified in accordance with contrast-enhanced intraoperative ultrasonography findings and histological results.

 
Among the 18 patients with new A1 to A3 FLLs at CEIOUS, 11 had all the FLLs properly removed, 1 had seven new FLLs removed (only five of which were HCC), and 6 had tumors that had been wrongly upstaged, which led to improper additional surgery. In this subgroup of patients, eight patients had also 13 new B-pattern FLLs, which were not removed. In all the patients, according to our policy,11,12 a conservative surgical approach was the planned surgical strategy, and despite the upstaging, none of them shifted to a stage that would require major removal of liver parenchyma. The modified operations consisted of 10 patients who required 13 additional limited subsegmental resections, 7 patients who required an extension of the planned resection area, and both limited subsegmental resection and extension of the planned resection area in 1 patient. All but 2 of these 18 patients had no recurrence at a mean follow-up of 19 months (median, 18 months; range, 7–32 months). The mean disease-free survival was 14 months (median, 11 months; range, 6–32 months). In two patients, a total of eight new liver lesions were discovered at follow-up, and all were confirmed by contrast-enhanced CT. One of these two patients was found by intraoperative CEIOUS to have two B-pattern lesions, but neither of the new lesions occurred in the segments where the B-pattern lesions had been detected.

Among the remaining 58 patients in whom IOUS and CEIOUS found no additional lesions, 7 patients had 19 totally new lesions in the liver 8, 12, 26, 26, 27, 34, and 34 months later, and 3 patients had extra-hepatic disease (left adrenal gland, lymph node, and bone metastases) at 19, 16, and 12 months, respectively. Globally, there were no new lesions during follow-up that corresponded to the B-pattern lesions defined at CEIOUS. Conversely, 14 (42%) of 33 new lesions detected during follow-up appeared within 12 months after surgery and were considered to be false-negative findings of IOUS. Sensitivity, specificity, and positive and negative predictive values of IOUS and CEIOUS are listed in Table 1Go.


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  		TABLE 1. Sensitivity, specificity, positive and negative predictive values, and accuracy of IOUS and CEIOUS in patients who underwent surgery for hepatocellular carcinoma
 
Overall 1- and 3-year survival times in the 307 CEIOUS and pre-CEIOUS groups were 92% to 83% and 80% to 60% (P = .100), respectively (Fig. 6Go). Disease-free 1- or 3-year survival times in the CEIOUS and pre-CEIOUS groups were 81% to 32% and 80% to 40% (P = .746), respectively (Fig. 7Go). Hepatic-free 1-and 3-year survival times in the CEIOUS and pre-CEIOUS groups were 84% to 38% and 89% to 63% (P = .261), respectively (Fig. 8Go). Table 2Go shows that there were no statistically significant differences between the 2 groups in terms of tumor size, number, rate of macrovascular invasion, and rate or cirrhotic patients.


Figure 6
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  		FIG. 6. Overall 1- and 3-year survival times of patients with hepatocellular carcinoma treated in the contrast-enhanced intraoperative ultrasonography (CEIOUS) and pre-CEIOUS eras.

 

Figure 7
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  		FIG. 7. Disease-free 1- and 3-year survival times of patients with hepatocellular carcinoma treated in contrast-enhanced intraoperative ultrasonography (CEIOUS) and pre-CEIOUS eras.

 

Figure 8
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  		FIG. 8. Hepatic-free 1- and 3-year survival times of patients with hepatocellular carcinoma treated in contrast-enhanced intraoperative ultrasonography (CEIOUS) and pre-CEIOUS eras.

 

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  		TABLE 2. Tumor and background liver features of patients with HCC who underwent surgery in CEIOUS and pre-CEIOUS eras
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In patients with cirrhosis with HCC, new liver nodules detected by IOUS are estimated to not be malignant in 70% to 80%. In particular, previous reports show that only 24% to 30% of hypoechogenic nodules and 0% to 18% of those that are hyperechogenic are malignant, whereas most of the nodules showing a mosaic pattern are HCC.3,4 Today, the risk is to overestimate the tumor stage with IOUS and to overcome this problem even when fine-needle biopsy seems inadequate.

Tumor vascularity as a criterion for differentiating the regenerative or dysplastic nodules from the HCC correlates well with the histological evidence of a progressive increase in unpaired arteries from dysplastic to neoplastic nodules in a cirrhotic liver.13 The pattern of vascular enhancement is not sufficient for differentiating malignant from nonmalignant nodules in a cirrhotic liver with 100% specificity. However, some improvements compared with conventional IOUS may be expected. For this reason, in early 1990s, attempts were made to use CEIOUS with carbon dioxide as contrast material for IOUS, but the need for arterial catheterization made this technique too invasive.14 In our preliminary experience, CEIOUS provided remarkable findings; the procedure provided extra information on nodular vascularity in patients with HCC and detected nodules that were not visible at IOUS in patients with colorectal cancer liver metastases.6 Our preliminary experience, which focused on patients operated for HCC, showed encouraging results.7 However, there were very few patients, and data did not support our too-optimistic expectations. CEIOUS was able to differentiate with 100% specificity all the new FLLs detected by IOUS in a series of 16 patients. We classified the pattern of enhancement of new FLLs at CEIOUS on the bases of both our preliminary experience and that reported in the literature about CEUS,5 and we prospectively recruited the present series of consecutive patients to validate the results we obtained in the initial experience.

On the bases of a large series of 87 patients and a systematic classification of the pattern of enhancement, we showed that 33% of patients had new FLLs found by IOUS and thus underwent CEIOUS. Among these patients, 18 of 29 had new FLLs that were partially or fully confirmed as suspicious for HCC at CEIOUS. Specificity in differentiating these lesions was 69% (Table 1Go), which is certainly closer to the true performance of CEIOUS, rather than the 100% obtained at the initial experience.7 This value is probably not that high, especially when compared with the 95% reported for CEUS.5 However, the small size of the lesions targeted for CEIOUS study compared with those studied with CEUS could explain this discrepancy. The neovascularity of these tiny nodules as a criterion for differentiation between malignant and benign lesions has limits that are independent of the methods used to study them. Therefore, CEIOUS can be helpful in certain nodules, but not in all. From this perspective, a 69% rate of specificity is encouraging because it means that we can provide proper information with this new technique in approximately 7 of 10 lesions that we detect at the time of laparotomy. For the remaining three, even histology may be lacking because there is no common agreement between western and eastern pathologists on the definition of early HCC and dysplastic lesions.13,15

Operative decision making was properly affected by new findings at CEIOUS in 22 (76%) of 29 patients with new FLLs found by IOUS (Fig. 5Go), which accounted for 25% of the whole series. If we add to these patients the one who had partially proper operative decision making modified by CEIOUS, the rate raises to 79% (26% of the whole series). Twenty-one percent of patients underwent additional surgery for lesions that were not confirmed histologically. However, of the 12 nonmalignant nodules we removed, 3 were dysplastic nodules and were therefore likely to progress.16

Over the last two decades, the impact of IOUS on operative decision making, when compared with those of preoperative imaging techniques, has decreased from 49% to 51%17,18 to 4% to 7%.1,19,20 This is in part the result of progress in preoperative imaging. However, the low rates shown in the latest reports1,18,19 are also partially motivated by surgeons’ surgical policies. However, in our study, because quite a few patients underwent major hepatectomies, new nodules detected by IOUS in the same hemiliver would have not modified the surgical strategy. In our experience, major hepatectomies are performed in a minority of patients11,12 simply because of the extensive use of IOUS guidance for achieving parenchymal-sparing resections, so detection of new nodules is more suitable for changing the surgical strategy. However, CEIOUS clearly enhances the value of IOUS on operative decision making for liver tumors by both extending and reducing the resection foci. The expected introduction of probes fitted for laparoscopic exploration may enable CEIOUS without laparotomy, which could be particularly useful in patients with HCC and in candidates for liver transplants.

The impact of more effective treatments on operative decision making could explain the better long-term prognosis for patients treated in the CEIOUS era compared with those operated before CEIOUS was introduced. Many other factors may play a role in explaining this difference, such as biases existing in any retrospective comparison, surgeon experience, the technology of the US machines that were used, and the small size of the group of patients belonging to the pre-CEIOUS group. Furthermore, the differences were not large, and if the disease-free survival times were similar, the hepatic-free survival times seemed slightly better for the patients in the pre-CEIOUS group. However, patients in the CEIOUS group had tumors with a higher rate of macrovascular invasion, even though they had better overall survival times and similar tumor-free survival times. We think that the good long-term results, together with the objective improvement in nodule differentiation obtained with CEIOUS, provide enough evidence to justify further studies for confirming our impression of the valuable role this modality can play in affecting the treatment of HCC. In evaluating of the results of CEIOUS, this technique should be considered not as an alternative to IOUS, but as its complement: it provides new findings that are based on IOUS, but that IOUS itself could not obtain.

Some authors have raised some concerns concerning the safety of CEIOUS.21 As has already been pointed out,22 the European Medicine Agency temporarily withdrew approval for use of SonoVue in echocardiography. This temporary withdrawal has now been suspended, with the recommendation that it be used with caution in patients with severe cardiac diseases. Patients who undergo liver resection are strictly selected patients who undergo routine anesthetic, respiratory, and cardiac evaluations specifically to exclude major cardiovascular and respiratory diseases. Furthermore, CEIOUS is performed in patients who are under real-time monitoring by the anesthesiologist. We therefore think that CEIOUS is safe in our patient population because our patients are not in the at-risk category for the use of SonoVue, and they are constantly monitored during the procedure. We did not observe any adverse effects in this experience or in our previously reported experiences.6–8

In summary, the present study addresses some important aspects regarding the role of CEIOUS during surgery for HCC and represents a practical guideline for its use, as follows:

  1. CEIOUS helps characterize new lesions detected during surgery for HCC, and in this sense, it complements IOUS. It does not enhance the detection power of IOUS, and it is therefore useless in patients who had no new nodules found by IOUS.
  2. The proposed classification of CEIOUS findings shows high sensitivity and good specificity (Table 1Go).
  3. Nodules with B pattern remained undetectable at follow-up, and therefore they could be left untreated until further confirmation can be obtained.
  4. Lesions with the A1 and A2 patterns are likely to be malignant, and they should be removed.
  5. A3 nodules are the most common among the suspicious new FLLs encountered found by IOUS exploration. However, this pattern of enhancement is the least accurate, which accounts for the intrinsic limit of vascularity as the single criterion for differentiating borderline lesions.13,15 In these situations, even analysis of frozen sections is not helpful. Conversely, a false-negative result may lead to a less strict follow-up program, which could result in delay of diagnosis and treatment. Therefore, we recommend that nodules with an A3 pattern by CEIOUS be removed until further experience adds new information that allow us to improve the specificity of this modality. In the present series, we were able to avoid major hepatectomy in all patients despite additional lesions found by IOUS and CEIOUS. We think that this is the result of the conservative policy we have systematically adopted that is based on IOUS guidance of resection, which has allowed us to avoid major hepatectomies in patients with tumors with complex vascular relations.11,12 Exceptional conditions in which the removal of an A3 lesion would require a major extension of the hepatectomy should be considered on a case-by-case basis, both to secure remnant liver for the patient and to ensure treatment of the nodule. Considering the small size of any A3 lesion (less than 2 cm), if major hepatectomy were the only resective solution but it was thought to be too risky, intraoperative thermal ablation could also be considered.
  6. Overall survival times of patients in the CEIOUS group were better than those of the pre-CEIOUS group. Although biases of a comparison with historical data are compounded by our small series of patients, the results suggest that CEIOUS permits decision making that results in longer patient survival.
  7. Disease-free and hepatic-free survival times were not different between the pre-CEIOUS and CEIOUS groups (Figs. 7Go, 8Go), but the higher rate of macrovascular invasion in the patients of the CEIOUS group (Table 2Go) suggest, that treatment decisions made using this new diagnostic tool may affect disease-free survival (Fig. 6Go).

In conclusion, CEIOUS allows more precise staging and more effective surgical treatment of HCC, and it should be considered a useful technique that permits new treatment scenarios in these patients.


   ACKNOWLEDGMENTS
 
The authors wish to thank Rosalind Roberts for her assistance with the manuscript

Received for publication September 10, 2006. Accepted for publication October 31, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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