Hepatocellular carcinoma and octreotide: treatment results in prospectively assigned patients with advanced tumor and cirrhosis stage.

BACKGROUND AND AIM: Treatment of inoperable hepatocellular carcinoma (HCC) remains a major clinical problem. The only efficient treatment options are percutaneous ethanol injection (PEI), radiofrequency ablation (RF) and transarterial chemoembolization (TACE), but these therapies are only applicable to patients with limited tumor spread and sufficient liver function. For patients with advanced tumor and poor liver function a systemic therapy is required. Octreotide, a somatostatin analog with antimitotic activity, is a controversial treatment option. METHODS: In the current study we prospectively assigned a group of 41 HCC patients with advanced HCC and cirrhosis stage to treatment with octreotide. The clinical and laboratory parameters were monitored and survival was analyzed using a Cox regression model. RESULTS: The medium survival in the group of all patients was 571 days. Using the Cox regression there was a significant difference in survival for alpha-fetoprotein (P = 0.026) and Quick's test (P = 0.009) in consideration of the tumor dimension compared to the other characteristics. The tumor remained stable in 26 patients over a mean follow-up of 21 months and progressed in 14 patients. One patient showed a partial response. There was no incidence of severe side-effects (WHO grade 3-4). During the follow-up time, 14 patients died because of their underlying disease. CONCLUSIONS: Treatment with octreotide appears safe and patients show similar survival compared to a group of patients with advanced HCC treated with TACE. Further studies are necessary to investigate somatostatin receptor subtypes or receptor mutations of patients with advanced HCC in relation to their response.

Transcutaneous perianal sonography: a sensitive method for the detection of perianal inflammatory lesions in Crohn's disease.

AIM: Pelvic magnetic resonance imaging (MRI) and endoanal ultrasound which are established imaging methods for perianal inflammatory lesions in patients with Crohn's disease require expensive specialized equipments and expertise. We investigated the feasibility and sensitivity of transcutaneous perianal ultrasound (PAUS) using regular ultrasound probes in the imaging of perianal inflammatory lesions. The sonographic findings were correlated to pelvic MRI-scans. METHODS: We performed PAUS in 25 patients with Crohn's disease and clinical signs of perianal inflammatory disease. Within a median of 10 d (range 0-75) these patients underwent MRI of the pelvis. Regular convex and linear high resolution probes were used for PAUS. The sonographic findings were correlated to the MRI findings by blinded investigators. RESULTS: The sonographic investigations were well tolerated by all patients. Fistulae typically presented as hypoechoic tracks. Twenty-nine fistulae were detected in 22 patients. Abscesses were detected in 7 patients and presented as hypo- or anechoic formations. Twenty-six of 29 fistulae and 6 of 7 abscesses could be confirmed by MRI. Kappa statistics showed an excellent agreement (kappa>0.83) between the two imaging methods. CONCLUSION: PAUS is a simple, painless, feasible, real-time method that can be performed without specific patient preparation which is comparable in its sensitivity to pelvic MRI in the detection of perianal fistulae and/or abscesses. PAUS can especially be recommended as a screening tool in acute perianal disorders such as perianal abscess and for follow-up studies of perianal inflammatory disease.

Spontaneous tumor-specific humoral and cellular immune responses to NY-ESO-1 in hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is the fifth most common cancer around the world. Although several therapeutic approaches for treatment of HCC are available, survival rates for HCC patients are still very poor because of inefficient treatment options. For HCC, as well as other tumors, antigen-specific immunotherapy remains a viable approach that is dependent on the definition of tumor-associated antigens. NY-ESO-1, a member of the cancer testis antigen family, is one possible candidate for a tumor-specific antigen in HCC. The aim of this study was to show the relevance of NY-ESO-1 in hepatocellular carcinoma. EXPERIMENTAL DESIGN: Sera samples from 189 HCC patients were analyzed for NY-ESO-1-specific antibodies. Forty-nine HCC patients were screened for NY-ESO-1 mRNA expression in HCC tissue. Selected patients were followed for up to 3 years to correlate their immune response with their clinical course of events. NY-ESO-1-specific CD4+ and CD8+ T-cell responses from NY-ESO-1 seropositive patients were analyzed and a NY-ESO-1+ specific cytotoxic T-cell line was generated. RESULTS: Twelve of 49 analyzed tumor samples expressed NY-ESO-1 mRNA and 23 of 189 patients showed NY-ESO-1-specific antibody responses. These humoral immune responses were accompanied by NY-ESO-1-specific functional CD4+ and CD8+ T-cell responses. Finally, NY-ESO-1 humoral responses were dependent on the presence of NY-ESO-1-expressing tumors. CONCLUSIONS: This is the first report of a spontaneous immune response in HCC patients to a known tumor-specific antigen, NY-ESO-1 protein. Our data favor the possibility of immunotherapeutic strategies for the treatment of HCC.

Recurrence of Budd-Chiari syndrome after liver transplantation in paroxysmal nocturnal hemoglobinuria.

Venous thrombembolism is a major complication of paroxysmal nocturnal hemoglobinuria (PNH). Often, veins of atypical localization are afflicted, resulting in cerebral, mesenteric, or hepatic venous thrombosis. We present a patient who received an orthotopic liver graft for chronic Budd-Chiari syndrome in 1988. PNH was the only thrombophilic predisposition identified in this patient. After transplantation, he repeatedly suffered from hemorrhage. Subsequently, the patient discontinued prophylactic anticoagulation nearly 10 years after transplantation. Within 6 months Budd-Chiari syndrome recurred, but stabilized after anticoagulation therapy with low-molecular-weight heparin was reinstituted. The patient is clinically stable 14 years after receiving the liver graft. Eleven cases of relapsing Budd-Chiari syndrome have been reported in the literature. Of these, four patients suffered from PNH. All patients transplanted for PNH-associated Budd-Chiari syndrome in these reports suffered from either major bleeding or thrombosis. In conclusion, patients afflicted with PNH appear to be at high risk of incurring complications after liver transplantation.

Sonographic criteria for the diagnosis of hepatic involvement in hereditary hemorrhagic telangiectasia (HHT).

Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) is highly variable and may lead to severe clinical symptoms such as heart failure. This controlled, prospective study defined sonographic criteria for hepatic involvement in HHT. Color Doppler sonography and pulsed Doppler sonography were used to study 25 patients with HHT and liver involvement, 20 patients with HHT without liver involvement, 25 patients with cirrhosis, and 25 patients without liver disease. The diagnosis of hepatic manifestation was confirmed by computed tomography and/or angiography. Liver size, parenchymal changes of the liver, vessel diameters, and flow velocities of the portal vein and the hepatic artery were determined. Resistance index (RI) and pulsatility index (PI) were calculated. The diameter of the common hepatic artery was significantly dilated without overlap between HHT patients with liver involvement and the 3 control groups (mean 11.3 +/- 2.8 mm [HHT with liver involvement], 4.6 +/- 0.9 mm [HHT without liver involvement], 4.8 +/- 1.0 mm [cirrhosis], and 4.4 +/- 1.0 mm [healthy controls], P <.001). Doppler parameters of the proper hepatic artery differed significantly (all P <.001). In all patients with HHT and liver involvement, areas with intrahepatic hypervascularization caused by dilated intrahepatic arteries were observed in varying intensity. Cardiac output significantly correlated with the diameter of the common hepatic artery (r = 0.53, P =.007) and the portal vein (r = 0.42, P =.05). In conclusion, the diameter of the common hepatic artery (>7 mm) and intrahepatic hypervascularization are suitable sonographic diagnostic parameters of HHT with high sensitivity and specificity. Dilated diameters of the hepatic feeding vessels are indicators for systemic circulatory distress in these patients.

Successful treatment of fibrosing cholestatic hepatitis using adefovir dipivoxil in a patient with cirrhosis and renal insufficiency.

Fibrosing cholestatic hepatitis is a deleterious manifestation of hepatitis B virus infection in immunocompromised patients. Without treatment, this condition is usually fatal within weeks of onset. Liver retransplantation has not been successfully performed to date, and treatment intervention was generally unsuccessful before the advent of adefovir dipivoxil. However, concerns have been expressed about the use of this agent in patients who are renally compromised. A 40-year-old liver transplant recipient with hepatitis B virus reinfection, resistance to lamivudine, and fibrosing cholestatic hepatitis complicated by terminal renal impairment and spontaneous bacterial peritonitis was treated with adefovir dipivoxil 10 mg after every dialysis. Since initiating treatment with adefovir dipivoxil 10 mg, a dramatic virologic and clinical improvement was observed in this patient. The patient returned to work full-time within 6 months of starting adefovir dipivoxil without the need for liver retransplantation. Serum HBV DNA (Amplicor HBV; Roche Diagnostics, Basle, Switzerland) decreased by 6 log(10) copies/mL and became negative (< 400 copies/mL) within 8 weeks of treatment and remains negative at the last available assessment. The patient continues to require renal dialysis, but is generally well. Creatinine clearance improved from 8 mL/min to 16 mL/min during the course of treatment. No adverse events related to adefovir dipivoxil were observed. Adefovir dipivoxil resulted in significant clinical improvement in this patient with hepatitis B virus-induced fibrosing cholestatic hepatitis, despite the presence of renal impairment and lamivudine resistance.