Outcome for patients treated with laparoscopic versus open resection of hepatocellular carcinoma: case-matched analysis.

INTRODUCTION: This is a case-matched analysis of patients undergoing laparoscopic versus open hepatectomy for hepatocellular carcinoma (HCC), with specific regard to margin status and survival. METHODS: Laparoscopic cases were matched with open controls by cirrhosis and tumor size (within 10%). Data were evaluated by logistic regression using the generalized estimating equation method. Mixed linear regression models were used to assess operative duration in the groups. Overall and disease-free survival were compared using a Cox proportional frailty model. RESULTS: Twenty laparoscopic cases were matched to 56 open resections. Thirty patients (39%) developed recurrence and 13 patients (17%) died, including one (1.3%) death within 30 days. There were no significant differences in age, gender, cirrhosis or tumor size. Paired univariate and multivariate analyses showed cases of laparoscopic resection had similar rates of transfusion and positive margins compared with open resection. Operative duration was similar in laparoscopic (mean 161 +/- 37 min) and open (mean 165 +/- 53 min) groups. The adjusted odds of length of stay > or = 6 days was significantly lower in patients with laparoscopic resection [odds ratio (OR) = 0.07, 95% confidence interval (CI) = 0.02-0.27]. Both unadjusted and adjusted analyses showed no significant association between type of resection and overall or disease-free survival. DISCUSSION: Neither margin status, nor recurrence, nor survival was significantly different between the two cohorts. Laparoscopic resection for malignancy is safe, with a similar operative time as open hepatectomy. If tumor location is amenable, laparoscopic resection for HCC is a reasonable alternative to open resection with the added benefits of improved cosmesis and sooner discharge home.

Effect of ischemia-reperfusion on the incidence of acute cellular rejection and timing of histologic hepatitis C virus recurrence after liver transplantation.

BACKGROUND: Because of a critical shortage of deceased donor (DD) livers, more extended criteria allografts are being utilized; these allografts are at increased risk for ischemia-reperfusion injury (IRI). We assessed whether, in a large cohort of patients transplanted for hepatitis C virus (HCV) either via a DD or live donor (LD), there was a relationship between the degree of IRI and the frequency and timing of acute cellular rejection (ACR) and histologic HCV recurrence. METHODS: During an 8-year study, patients were separated into four groups based on peak alanine aminotransferase (ALT) levels and three groups based on severity of IRI on postreperfusion liver biopsy. RESULTS: The mean follow-up time of 433 DD and 44 LD recipients was 1212 days. We noted a strong correlation in DD between peak ALT and the histologic degree of IRI (P = .01). There was no difference in the incidence or grade of ACR among the four groups. There was no correlation between the severity of IRI and the incidence or time to histologic recurrence of HCV. CONCLUSIONS: The magnitude of peak ALT correlated with the severity of IRI on postreperfusion liver biopsy. Among this large HCV cohort, there was no correlation between the severity of IRI and the incidence or timing of histologic HCV recurrence or incidence of ACR.

The Mount Sinai experience with orthotopic liver transplantation for benign tumors: brief report and literature review: case reports.

Orthotopic liver transplantation (OLT) is performed for benign hepatic lesions that are symptomatic, too large to be resected, have a malignant transformation potential, cause debilitating/life-threatening manifestations, or in patients experiencing posthepatectomy acute liver failure. Among benign tumors, polycystic liver disease (PLD) is the most common indication for OLT alone, or combined liver-kidney transplantation. Our 10-year experience with OLT for benign tumors includes two patients with PLD and one with a benign giant fibrous tumor. In this report, we present our experience with OLT for benign liver tumors, commenting on relevant published studies.

Treatment of HCC in patients awaiting liver transplantation.

Liver transplantation (LT) is the treatment of choice for many patients with unresectable hepatocellular carcinoma (HCC), but long waiting time due to the shortage of donor organs can result in tumor progression and drop-out from LT candidacy. Furthermore, even in candidates meeting the restrictive Milan criteria there is risk of HCC recurrence; this risk rises significantly when patients with more advanced HCC are included. In an effort to address these issues, treatment of HCC in patients awaiting LT has become widespread practice. In this review the various modalities employed in the pre-LT setting are presented, and the evidence for benefit with regard to (1) improvement of post-LT survival, (2) down-staging of advanced HCC to within Milan criteria and (3) preventing waiting list drop-out is considered. Chemoembolization, radiofrequency ablation and ethanol injection all have well-documented antitumor activity; however, there is no high level evidence that waiting list HCC treatment with these modalities is effective in achieving any of the three above-mentioned aims. Nevertheless, particularly in the United States, where continued waiting list priority depends on maintaining HCC within Milan criteria, use of nonsurgical HCC treatment will likely continue in an effort to forestall tumor progression and waiting list drop-out.

Graft function and survival depend primarily on host factors in compromised recipient models of orthotopic liver transplantation in the rat.

BACKGROUND: Experimental models of liver transplantation use normal recipients, although most patients undergoing liver transplantation suffer from acute or chronic liver failure. This study was designed to analyze the outcome of orthotopic liver transplantation in compromised rat hosts. METHODS: Recipient animals were either rats with D-galactosamine-induced acute or rats with chronic liver failure secondary to common bile duct ligation. Liver damage was evaluated by monitoring enzymes, bilirubin, ammonia levels, prothrombin, thrombin time, and cytokines. In vivo function of hepatocytes and sinusoidal endothelial cells were evaluated by indocyanine green and hyaluronic acid uptake. Transplantation was performed in normal, acute, and chronic liver failure rats at different time points using either freshly harvested or cold-preserved syngeneic livers. RESULTS: Survival with fresh grafts decreased significantly when transplants were performed 48 hr after the induction of acute liver failure. No rats with acute liver failure survived transplantation with grafts stored for 12 or 24 hr although in chronic failure survival was more 80%. Survival of acute liver failure rats receiving 6 hr preserved grafts was 16.6% compared with 83.3% observed with fresh grafts transplanted at the same time point after D-galactosamine injection. Elevated tumor necrosis factor-alpha and interleukin-1beta levels as well as impaired sinusoidal endothelial cell function were detected in acute liver failure rats with 6 h preserved grafts. CONCLUSION: These results suggest that preoperative status and different host factors have a significant effect on outcome and graft function after liver transplantation in rats.

Comparison of surgical outcomes for hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: a western experience.

BACKGROUND: We reviewed our experience in patients with hepatocellular carcinoma (HCC) and chronic hepatitis to determine if differences exist in preoperative status and postoperative survival between those with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. METHODS: We reviewed the records of 240 consecutive patients with HCC who underwent hepatic resection or liver transplantation at Mount Sinai Hospital between February 1990 and February 1998. Patients who tested negative for hepatitis B antigen and hepatitis C antibody (74 patients) as well as those who tested positive for both (2 patients) were excluded. Age as well as preoperative platelet count, prothrombin time (PT), albumin, and total bilirubin were measured in all patients. The presence of encephalopathy or ascites also was noted. Explanted livers and resection specimens were examined for size, number, and differentiation of tumors as well as the presence of vascular invasion and cirrhosis in the surrounding parenchyma. RESULTS: One hundred twenty-one patients with HCC tested positive for HCV, and 43 tested positive for HBV. A significantly higher proportion of patients with HCV required transplant for the treatment of their HCC when compared to those with HBV. In the resection group, patients with HCV were significantly older that those with HBV. They also had significantly lower mean preoperative platelet counts and albumin levels and higher mean PT and total bilirubin levels. Resected patients with HCV had significantly less-differentiated tumors and a higher incidence of vascular invasion and cirrhosis when compared to those with HBV. There was no statistical difference in the multicentricity and size of tumors between the two groups. The 5-year disease-free survival was significantly higher for HBV patients treated with resection when compared to those with HCV (49% vs. 7%, P = .0480). Patients with HCC and HCV had significantly longer 5-year disease-free survival with transplant when compared to resection (48% vs. 7%, P = .0001). Transplanted patients with HBV and HCC had preoperative status, pathological findings, and survival similar to those of patients with HCV. CONCLUSIONS: Based on preoperative liver function and tumor location, a much higher proportion of HCC patients with HBV were candidates for resection. Significant differences in preoperative status, tumor characteristics and disease-free survival exist between HCC patients with chronic HBV and HCV infection who have not yet reached end-stage liver disease. Serious consideration should be given to transplanting resectable HCC with concomitant HCV, especially in cases with small tumors.

Laparoscopic release of celiac artery compression syndrome facilitated by laparoscopic ultrasound scanning to confirm restoration of flow.

A 43-year-old woman presented with symptomatic mesenteric ischemia caused by median arcuate ligament compression of her celiac artery. Magnetic resonance angiography clearly demonstrated stenosis of the proximal celiac artery. She underwent laparoscopic decompression by division of the ligament and excision of the celiac plexus. Laparoscopic Doppler ultrasound scanning demonstrated markedly improved flow in the artery. She was discharged in 15 hours and reported complete resolution of her symptoms at the 3-month postoperative visit. Laparoscopy provides a less invasive but equally effective method for decompressing the celiac artery as well as assessing adequacy of flow after its release.

Cytokine profiles in early rejection following OKT3 treatment in liver transplant patients.

OKT3 , a murine monoclonal antibody specific to the human CD3 complex, induces immunosuppression by depletion of T cells. Administration of OKT3 results in significant release of proinflammatory cytokines, such as TNFalpha and IL1beta. Liver recipients who experience rejection within 3 weeks after transplantation with OKT3 prophylaxis recover their T cells by postoperative day 10 despite complete initial clearance. We sought to analyze the role of proinflammatory and Th-1 cytokines in T cell recovery and rejection after liver transplantation with OKT3 prophylaxis. In plasma samples from 32 patients, we measured TNFalpha, IL1beta and IL6 (before transplant and on postoperative days 1, 2 and 3) and IL2, IFNgamma, sIL2R and slCAM (postoperative days 5, 7 and 10) and examined possible correlations with T-cell recovery and occurrence of rejection within 3 weeks. TNFalpha, IL1beta, and IL6 did not correlate with T-cell recovery. In patients who rejected, IL2 and IFNgamma on postoperative days 5 and 7 correlated with degree of T-cell recovery by day 10; a significant rise in sIL2R over time also correlated with T-cell recovery in this group. Our results emphasize the role of Th-1 cytokines in rejection following OKT3 induction and suggest that markers of T cell activation may predict risk.

Hepatic epithelioid hemangioendothelioma: resection or transplantation, which and when?

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with an unpredictable course and prognosis. The aim of this study is to describe our experience with liver resection, as well as transplantation, in the treatment of this tumor. We retrospectively analyzed the clinical features, pathological findings, and postoperative results in a series of 11 patients presenting between 1990 and 1998. Five patients (45%) presented with abdominal pain, 3 patients (27%) with jaundice and ascites, and the rest were asymptomatic. Computed tomography or magnetic resonance imaging showed localized lesions in 2 patients (18%) and multifocal disease in the others. Seven patients (64%) had extrahepatic lesions, detected either by preoperative imaging or discovered at exploration. Two resections of apparently localized lesions were followed by rapid and aggressive recurrence. Five patients were treated with transplantation, including 1 patient who had previously undergone resection. Of these 5 patients, 2 patients are currently free of detectable disease, 1 patient who had severe ascites and jaundice is now asymptomatic with stable extrahepatic lesions, and 2 patients (including 1 who had previously undergone a resection) died of tumor recurrence. One patient with advanced tumor died while waiting for transplantation. The remaining 4 patients are free of symptoms and have stable hepatic and extrahepatic disease. HEHE is nearly always multifocal, and our results with resection were dismal. Because of the unpredictable nature of the tumor, the indications for transplantation in patients without liver-related symptoms should be carefully evaluated. Nevertheless, extrahepatic disease should not be an absolute contraindication for liver transplantation in patients with severe liver dysfunction.

Safety of preoperation endoscopic tattoo with india ink for identification of colonic lesions.

BACKGROUND: Colonic tattooing with india ink is a widely practiced technique regarded as safe, accurate, and reliable. In this series, the largest reported, the safety of this technique is studied. METHODS: A retrospective study of 8,125 consecutive patients who undersent colonoscopy over a 64-month period was conducted. India ink colonic mucosal tattooing was used for either preoperative marking or future endoscopic identification of a lesion. RESULTS: During the study, 195 patients underwent endoscopic injection of india ink. Of these, 50 patients were marked before surgery, and 145 underwent marking with the intent of facilitating future endoscopic localization. Patients were followed by either telephone interviews or physical examination. None of the patients developed fever, persistent abdominal pain, or abdominal tenderness on examination. All surgeons were interviewed. They uniformly reported the tattoo as intensely visible and of great utility in locating the lesions. CONCLUSIONS: Preoperative mucosal tattooing with india ink is recommended as a safe and necessary procedure.

Aggressive surgical treatment of intrahepatic cholangiocarcinoma: predictors of outcomes.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and constitutes 10% of primary liver malignancies. Surgery is the optimal therapy; the majority of the patients will require extensive resections that are associated with significant morbidity. METHODS: We retrospectively studied the records of 26 patients who underwent exploratory laparotomy for intrahepatic cholangiocarcinoma between June 1991 and December 1997 at the Mount Sinai Hospital. Patients with perihilar (Klatskin) tumors were excluded. All patients were considered resectable based on CT or MRI findings. Patients with positive margins or nodal invasion received adjuvant chemotherapy and radiation. RESULTS: Sixteen patients underwent 18 resections; in 10 patients the tumors were unresectable at laparotomy and only biopsy was performed. The mean age (62 versus 53 years) was significantly higher, and the mean total bilirubin level (0.71 versus 6.17 mg/dL) was significantly lower in the resected group (p=0.031 and 0.017, respectively). No patient with a total bilirubin over 1.2 mg/dL was found to be resectable. Median actuarial survivals were 42.9+/-8.9 months for resectable and 6.7+/-3.6 months for unresectable patients (p=0.005). Positive margins were associated with significantly shorter disease-free survival. But resected patients with positive margins survived significantly longer than those who were unresectable. Tumor size, presence of satellite nodules, and degree of tumor necrosis on histologic examination were significant predictors of outcomes. Survival among patients receiving adjuvant therapy was not significantly altered. CONCLUSIONS: We conclude that an aggressive surgical approach is warranted in patients with ICC because resection offers the only hope for longterm survival. Our findings emphasize the importance of achieving tumor-free margins. Noncurative resection offers a survival advantage over no resection. Histologic examination of resected specimens can help select patients with poor prognoses.

Differential in vivo recovery of sinusoidal endothelial cells, hepatocytes, and Kupffer cells after cold preservation and liver transplantation in rats.

BACKGROUND: The injury resulting from cold preservation/reperfusion primarily affects sinusoidal endothelial cells, while hepatocytes are thought to be less vulnerable; morphological changes and increased cytokine release suggest that Kupffer cells are activated. We evaluated the extent of functional damage to the different cell types in the liver after cold preservation and transplantation. Additionally, we analyzed in vivo the patterns of functional recovery of all three cell types over the first week after transplantation in Lewis rats. METHODS: We evaluated the in vivo uptake of hyaluronic acid, indocyanine green, and radio-labeled sulphur colloid to assess the function of sinusoidal endothelial cells, hepatocytes, and Kupffer cells, respectively. Measurements were performed immediately after transplantation using syngeneic grafts preserved in University of Wisconsin solution for different periods. Functional recovery was monitored in animals receiving grafts preserved for 24 hr over the first postoperative week. RESULTS: We found that hepatocyte were less affected compared with the profoundly damaged endothelial cells. The phagocytic ability of Kupffer cells was, however, also seriously compromised, which suggests a selective down-regulation. Functional recovery occurs in a differential manner during the first postoperative week starting with hepatocytes followed by sinusoidal endothelial cells. Phagocytic function further deteriorates after transplantation before showing improvement. CONCLUSIONS: In viable liver grafts, all cell types recover from preservation/reperfusion injury by the end of the first week after transplantation. The differential time courses of the recovery suggest that successful sinusoidal endothelial cell recovery may depend upon prior hepatocyte regeneration and may involve a paracrine interaction, via cytokines and growth factors.