Abstract
Background. Despite significant recent improvements in liver imaging, preoperative evaluation of the potentially resectable patient with viral Hepatitis and Hepatocellular Carcinoma (HCC) is often inaccurate. Diagnostic laparoscopy may change management for patients with under-appreciated nodular cirrhosis or intrahepatic metastases, preventing unnecessary open exploration. The purpose of this study is to determine the effectiveness of routine laparoscopy as a separate procedure prior to resection in the evaluation of patients with potentially resectable HCC. Methods. Patients with potentially resectable HCC were evaluated preoperatively with routine blood tests and axial imaging. All study patients also underwent diagnostic laparoscopy with laparoscopic ultrasonography. Laparoscopy was performed in an inpatient hospital setting, with 23 hour stays in most cases. Results. Among 65 patients evaluated with Hepatocellular Carcinoma between July 2001 and November 2003, 20 patients with potentially resectable disease were evaluated by diagnostic laparoscopy. All patients had viral Hepatitis: 16 with Hepatitis B and 4 with Hepatitis C. All study patients had cirrhosis; 18 classified as Child's-Pugh A and 2 as Child's-Pugh B. Diagnostic laparoscopy changed the management in 9/20 (45%) cases. Management was changed because of severe nodular cirrhosis in 4 cases, inaccurate assessment of intrahepatic metastases in 2 cases, inability to identify an HCC in 1 case, peritoneal carcinomatosis in 1 case, and inability to tolerate induction to general anesthesia in 1 case. Discussion. Diagnostic laparoscopy is useful in the evaluation of the potentially resectable patient with HCC. Information obtained from laparoscopy may change the clinical management in up to 45% of cases.
Keywords: Cirrhosis, hepatocellular carcinoma, laparoscopy, liver neoplasms, resection, surgery, viral hepatitis
Background
Accurate preoperative evaluation of the patient with viral Hepatitis and Hepatocellular Carcinoma (HCC) can pose a significant challenge for even the most experienced of hepatobiliary surgeons. The patient's hepatic functional status is determined according to preoperative clinical parameters and laboratory values, most often as specified by the Child's-Pugh classification system. Transabdominal Doppler ultrasound is often used as part of the evaluation of the patient with HCC, both in assessing the non-neoplastic liver parenchyma and the directional flow of portal venous blood. Unfortunately, transabdominal ultrasound of liver tumors performed within the setting of surrounding regenerative nodules, as is usually the case in patients with viral Hepatitis and cirrhosis, can be exceedingly difficult to interpret correctly. Thus further evaluation of the tumor and non-neoplastic liver with axial imaging, either by three-phase computerized tomography (CT) or magnetic resonance imaging (MRI), is an essential component of the preoperative workup. However, despite major recent advances in imaging technology, current limitations in the accuracy of information obtained upon axial imaging continue to pose difficulties in the preoperative workup of the HCC patient.
Characterization of the severity of cirrhosis can be difficult on axial imaging. Identifying patients with normal liver parenchyma is simple. Similarly, those with advanced cirrhosis are also easy to identify. This determination is based upon the presence of visible nodularity of the liver, which is often shrunken and has blunted angles. However, inaccuracies arise in the characterization of the patient with apparently mild cirrhosis. Although common imaging characteristics for cirrhosis may not be apparent, these patients often harbor severe nodular cirrhosis which is underappreciated by preoperative imaging.
Another important variable which is often difficult to determine accurately during the preoperative workup is the presence of satellite lesions or extrahepatic disease 1. This is a crucial variable as unnecessary open exploration is often avoidable if, for example, the unexpected presence of small intrahepatic metastases or peritoneal implants is definitively determined prior to a scheduled major hepatectomy or transplant 2,3. Many previous reports in the literature have advocated a role for diagnostic laparoscopy in the complete workup of a variety of gastrointestinal and hepato-biliary malignancies 4,5,6,7,8,9.
The purpose of this study was to determine the role for diagnostic laparoscopy and laparoscopic ultrasonography in the complete preoperative workup of the patient with viral Hepatitis and potentially resectable HCC.
Methods
Patients with viral Hepatitis and HCC newly diagnosed at Bellevue Hospital, a publicly-funded hospital in New York City which serves a large population of Asian immigrants to the United States, between July 2001 and November 2003 were evaluated with diagnostic laparoscopy and laparoscopic ultrasonography as part of the preoperative workup. Patients were selected for laparoscopic evaluation based on the pre-laparoscopy judgment that they met eligibility criteria for surgical resection, as assessed by an attending hepatobiliary surgeon. Eligibility for surgical resection was determined according to clinical evaluation of the patient, and by preoperative laboratory and imaging studies. All patients were evaluated with high-quality axial imaging: either three-phase CT with 5 mm cuts of the liver or MRI with intravenous contrast. Imaging studies were read and interpreted by an attending radiologist and dedicated liver surgeon in each case.
Laparoscopy was performed as a separate procedure, independent of a scheduled resection. Diagnostic laparoscopy was performed as either an ambulatory surgical procedure or with a 23 hour hospital stay. A three port approach was used, with a single 12 mm umbilical trocar and two 5 mm mid-abdominal trocars placed at the anterior axillary line. A 10 mm laparo-scope was used through the umbilical trocar when laparoscopic ultrasound was not being performed. During laparoscopic ultrasonography the camera in the umbilical port was replaced by a 10 mm flexible ultrasound probe (5–10 MHz frequency range), and a 5 mm laparoscope was placed through either of the two available lateral ports. The procedure was performed under general inhalational anesthesia, and lasted less than 60 minutes in all cases.
Data was collected prospectively to assess for any change in surgical management as a result of information obtained from laparoscopy. Change in patient management following diagnostic laparoscopy was decided upon according to the best judgment of an attending hepatobiliary surgeon. These decisions were primarily based upon an estimation of the patient's risk for subsequent major liver resection, or a perceived inability to clear all neoplastic disease. Surgeons were not blinded to the results of pre-laparoscopy imaging studies, as decisions ultimately dictating resectability were made.
Results
Among 65 patients with newly diagnosed HCC and viral Hepatitis seen at Bellevue Hospital during the study period, 20 patients were evaluated with diagnostic laparoscopy and laparoscopic ultrasonography as part of the preoperative workup. All study patients with HCC had positive serology for either Hepatitis B virus or Hepatitis C virus. Most patients were felt to have only mild cirrhosis according to laboratory values and physical examination; Child's-Pugh class A in the majority of cases (Table I). Preoperative imaging demonstrated features consistent with minimal or no hepatic functional compromise or nodularity in the majority of cases (Table II).
Table I. Viral Hepatitis status and Child's-Pugh classification of study patients.
| Viral Hepa atitis status | Child's-Pugh classification | ||
|---|---|---|---|
| HBV | HCV | A | B |
| 16 | 4 | 18 | 2 |
Table II. Imaging characteristics of study patients, based upon preoperative three-phase CT with 5 mm cuts of the liver or MRI with intravenous contrast.
| Yes | No | |
|---|---|---|
| Ascites | 3 | 17 |
| Multifocality | 8 | 12 |
| Nodular cirrhosis | 4 | 16 |
| Tumor >5 cm | 13 | 7 |
Surgical management was changed in 9/20 patients (45%) based on information obtained during diagnostic laparoscopy (Table III). In most cases management was changed from planned surgical resection to an alternative modality. This decision was based upon an attending surgeon's judgment on one of two primary factors: (1) the extent of neoplastic disease, and (2) the severity of nodular cirrhosis.
Table III. Appropriateness of surgical resection as deemed prior to and following diagnostic laparoscopy.
| Pre-laparoscopy resection candindidate |
|||
|---|---|---|---|
| Post-laparoscopy resection candidate | Yes | No | Total |
| Yes | 11 (58%) | 8 (42%) | 19 |
| No | 1 | 0 | 1 |
| Total | 12 | 8 | 20 |
In four cases laparoscopy demonstrated inaccuracy in the extent of tumor identified by preoperative imaging. Two patients were found to have more extensive tumor (peritoneal carcinomatosis or intrahepatic satellite metastases) than originally appreciated by imaging, and were referred for systemic chemotherapy (Table IV). In contrast, preoperative imaging led to incorrect over-estimation of the extent of tumor present in two patients, and the results obtained from laparoscopy decreased the clinical tumor stage. For example, in the case of a patient initially felt not to be an appropriate resection candidate based on the suspicion of a satellite lesion on preoperative imaging, surgical management was changed to resection after failure to identify the suspected satellite lesion during laparoscopy. Histopathologic examination of the resection specimen confirmed the presence of only a solitary HCC, validating the accuracy of laparoscopic evaluation in this particular patient.
Table IV. Patient table: changes in management according to information obtained upon diagnostic laparoscopy.
| Patient # | Pre-laparoscopy plan | Post-laparoscopy plan | Change in management | Reason for change in management |
|---|---|---|---|---|
| 1 | unresectable | resection | yes | suspected satellite not found on laparoscopy |
| 2 | resection candidate | resection | no | |
| 3 | resection candidate | resection | no | |
| 4 | resection candidate | systemic chemotherapy | yes | severe nodular cirrhosis |
| 5 | resection candidate | resection | no | |
| 6 | resection candidate | resection | no | |
| 7 | resection candidate | resection | no | |
| 8 | resection candidate | transplant | yes | severe nodular cirrhosis |
| 9 | resection candidate | radiofrequency ablation | yes | severe nodular cirrhosis |
| 10 | resection candidate | resection | no | |
| 11 | resection candidate | resection | no | |
| 12 | resection candidate | transplant | yes | severe nodular cirrhosis |
| 13 | resection candidate | observation | yes | HCC suspected by axial imaging not identified on laparoscopy |
| 14 | resection candidate | selective arterial embolization | yes | unable to tolerate anesthesia induction |
| 15 | resection candidate | resection | no | |
| 16 | resection candidate | resection | no | |
| 17 | resection candidate | selective arterial embolization | yes | satellite lesions |
| 18 | resection candidate | systemic chemotherapy | yes | carcinomatosis |
| 19 | resection candidate | resection | no | |
| 20 | resection candidate | resection | no |
In four cases management was changed because laparoscopy demonstrated the presence of severe nodular cirrhosis which was under-appreciated by pre-operative imaging, laboratory values, and clinical evaluation. Two of these patients were referred for liver transplantation, one was offered radiofrequency ablation instead of resection, and one was treated with systemic chemotherapy. Biopsy of the non-neoplastic liver was not routinely performed in an attempt to histologically grade the severity of a patient's cirrhosis. Instead, decisions regarding a change in operative management were based upon laparoscopic inspection of the liver and ultrasonography. The appropriateness of a major liver resection for the high-risk patient with very advanced nodularity of the liver was determined according to the best clinical judgment of an attending hepatobiliary surgeon.
Discussion
Despite ongoing improvements in imaging technology, accurate evaluation of the cirrhotic patient with HCC continues to pose a significant challenge. This is often due to difficulty in clearly determining the severity of nodular cirrhosis on imaging. Underestimation in the severity of cirrhosis is commonplace in patients felt to be only mildly cirrhotic according to imaging characteristics. Furthermore, one's ability to definitively exclude the presence of small intrahepatic metastases or extrahepatic sites of disease, such as peritoneal implants, also continues to be limited with current imaging technology 10.
Laparoscopy is a simple diagnostic procedure with minimal surgical risk to the patient 11. However, caution and common sense must be exercised during these procedures as any careless maneuver can lead to catastrophic consequences in cirrhotic patients. In our series only one patient experienced a complication as a result of laparoscopy (acute asthma exacerbation), for an operative morbidity of 5% and mortality of 0%.
The benefit of laparoscopy in the evaluation of the cirrhotic patient with HCC lies in the surgeon's ability to assess the patient's liver, peritoneal cavity, and tumor with a brief look through a camera 12,13,14,15. Minimal mobilization of the liver is necessary, and advanced laparoscopic skills are not required. Although intraoperative ultrasonography had initially been employed as a routine component of diagnostic laparoscopy, this imaging modality is actually of only marginal benefit in cirrhotic, viral Hepatitis patients. The limitation of intraoperative ultrasonography is due to several reasons including: difficulty in maintaining close probe contact with the surface of a highly nodular liver, and difficulty in delineating regenerative nodules from intrahepatic neoplasms in cirrhotic patients, among others. Given these limitations, we have currently abandoned laparoscopic ultrasonography, and perform only a simple diagnostic laparoscopy in cirrhotic patients.
In our series of viral Hepatitis patients with HCC, we have concluded that diagnostic laparoscopy is useful in the complete preoperative evaluation of the potentially resectable patient. This conclusion is based upon the fact that information obtained from laparoscopic evaluation has led to a change in surgical management in 45% of cases. Changes in surgical management have been made according to the best judgment of the hepatobiliary surgeon directing the care of the patient. Obviously, given the subjective nature of such clinical judgments, some inherent bias in studies such as this are unavoidable. Nonetheless, laparoscopy does appear to yield information which is useful in selecting the most appropriate treatment algorithm for patients who have a disease which can pose significant diagnostic and treatment dilemmas.
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