Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: A case cohort study

Background and Aims:  A total of 967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death.
Methods:  Survival was the end-point for all analyses.
Results:  We found in our overall analysis, that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated alpha-fetoprotein (AFP) or bilirubin or alkaline phosphatases were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient subgroups based on poor liver function and aggressive tumor characteristics. In subgroup analysis based on these subsets, there was clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant, independent but modest risk factors. The results of this large dataset show that amongst nonsurgical HCC patients, there are clear subsets with longer survival than other subsets.
Conclusions:  This data also supports the concept of heterogeneity of HCC.     

The different biochemical course of HBsAg-negative and HBsAg-positive hepatitis (author's transl)]

In 73 patients with HBsAg negative hepatitis and in 94 patients with HBsAg positive hepatitis (hepatitis B) laboratory findings were compared: GOT, GPT, AP, gamma-GT, bilirubin, sedimentation rate and gamma-globulins. In the beginning of the disease there was little difference. But comparing the maximal values patients with hepatitis B showed significantly higher GOT, GPT, de-Ritis, and bilirubin levels than patients with HBsAg-negative hepatitis. There was a correlation between de Ritis quotient and bilirubin. The difference of HBsAg negative and HBsAg positive hepatitis might be due to different reactions of cellular mediated immunity.     

Transcatheter arterial embolization for hepatocellular carcinoma with portal vein thrombosis

Abstract In order to evaluate the possible benefits of transcatheter arterial embolization (TAE) in hepatocellular carcinoma (HCC) patients with peripheral portal vein thrombosis, 96 consecutive HCC cases with peripheral portal vein thrombosis were analysed. Of them, 35 cases received TAE and 61 cases did not. Most (77.8%) of the TAE-treated cases showed decreased α-fetoprotein (AFP) levels after treatment, but 57.1% of them suffered another rise in AFP levels and subsequently died. One patient (2.8%) developed progressive jaundice after TAE and died within 1 month, while four of the non-TAE cases died within 1 month after diagnosis. In general, TAE is safe for HCC patients with peripheral portal vein thrombosis. In addition, using Cox's regression model for multivariate survival analysis, serum total bilirubin (≤, > 2 mg/dL; P = 0.0254), AFP (≤ 3155 ng/mL, > 3155 ng/mL; P = 0.0002) and treatments (TAE, non-TAE; P = 0.0059) were found to affect their prognosis. There was significant difference in survival between TAE and non-TAE groups, the 6 month, 1 year and 2 year survival rates were 91.4 versus 62.3%, 51.4 versus 26.2% and 17.1 versus 4.9% ( P = 0.0017). The median survival times of TAE and non-TAE groups were 10.3 versus 3.7 months, respectively. Though TAE only provided palliative treatment, it did prolong survival in HCC patients with peripheral portal vein thrombosis.     

Predictive value of serum procollagen-III-peptide for the survival of patients with cirrhosis.

The value of the aminoterminal procollagen-III-peptide (P-III-P) in predicting death or survival was evaluated in a group of 43 patients with proven postnecrotic or alcoholic cirrhosis. Patients were followed-up prospectively for 2 years. The prognostic value of P-III-P was compared with the Child classification, fasting and postprandial serum bile acids, and standard laboratory tests such as bilirubin, prothrombin index, pseudocholinesterase, albumin, GOT, GPT, gamma-GT, and clinical findings such as ascites, encephalopathy (assessed with the number connection test = NCT), and nutritional status. Between patients who died and those who survived the following 2 years, there were significant differences in the following parameters at the time of inclusion in the study: encephalopathy judged by NCT (p = 0.001), serum albumin (p = 0.0012), postprandial serum bile acids (p = 0.0024), fasting serum bile acids (p = 0.0025), pseudocholinesterase (p = 0.0044), GOT (p = 0.015), bilirubin (p = 0.016), and prothrombin index (p = 0.01). None of the other parameters investigated, including SP-III-P (p = 0.46), revealed any statistically significant differences between patients who died and survivors. The prognostic significance of laboratory tests and recorded clinical findings was evaluated, either alone or in combination with life-table analysis using the Cox model. SP-III-P, alone or in combination with other parameters, failed to improve prediction of mortality in patients with cirrhosis. In comparison to the Child classification (p = 0.0004) the combination of NCT and postprandial serum bile acids showed a similar ability (p = 0.0003) to predict patient survival.     

Impact of pre-operative transarterial embolization on the treatment of hepatocellular carcinoma with liver transplantation

AIM: To determine the effectiveness of pre-liver transplant (LT) transarterial embolization (TAE) in treating hepatocellular carcinoma (HCC) and the patient categories, which are likely to have a good outcome after LT. METHODS: Twenty-nine patients with hepatitis-related cirrhosis and unresectable HCC after LT were studied over a 7-year period. The patients were divided into two groups: group A patients (19/29) received pre-LT TAE, whereas group B (10/29) underwent LT without prior TAE. According to Milan criteria, group A patients were further subdivided into: group A1(12/19) who met the criteria, and group A2 (7/19) who did not. Patient survivals were compared. RESULTS: In the explanted liver, CT images correlated well with pathological specimens showing that TAE induced massive tumor necrosis (>85%) in 63.1% of patients in group A and all 7 patients in group A2 exhibited tumor downgrading that met Milan criteria. The overall 5-year actuarial survival rate was 80.6%. The TAE group had a better survival (84% at 5 years) than the non-TAE (75% at 4 years). The 3-year survival of group A2 (83%) was also higher than that of group A1(79%). Tumor necrosis >85% was associated with excellent survival of 100% at 3 years, which was significantly better than the others who showed <85% tumor necrosis (57.1% at 3 years) or who did not have TAE (75% at 3 years). CONCLUSION: TAE is an effective treatment for HCC before LT. Excellent long-term survival was achieved in patients that did not fit Milan criteria. Our results broadened and redefined the selection policy for LT among patients with HCC. Meticulous pre-LT TAE helps in further reducing the rate of dropout from waiting lists and should be considered for patients with advanced HCC.     

Transcatheter arterial chemoembolization therapy for patients with hepatocellular carcinoma: a case-controlled study.

BACKGROUND & AIMS: Transcatheter arterial chemoembolization (TACE) currently is used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its efficacy still is debated. Our aim was to assess the impact of TACE on patient survival and to identify prognostic factors for survival. METHODS: Fifty-six cirrhotic patients with unresectable HCC undergoing at least 1 course of TACE were matched 1:1 for sex, age (in 5-year periods), parameters of Child-Pugh score, Okuda stage, and tumor type with a control group who had received only supportive care. RESULTS: The 2 groups were comparable for cause of cirrhosis, alpha-fetoprotein serum levels, and Cancer of the Liver Italian Program (CLIP) score. The 56 patients in the TACE group received a total of 123 treatment courses. The median follow-up period was 16 months (range, 1-67 mo) in the TACE group and 5 months (range, 1-77 mo) in the supportive care group. Survival rates at 12, 24, and 30 months in patients receiving TACE were 74.3%, 52.1%, and 38.8%, respectively, with a median survival time of 25 months, whereas in supportive care patients the rates were 39.4%, 25.4%, and 19%, respectively, with a median survival time of 7 months (P = .0004). At univariate analysis, TACE, tumor type, presence of ascites, alpha-fetoprotein serum level, CLIP score, and Okuda stage were associated significantly with survival. Only TACE and CLIP score proved to be independent predictors of survival at multivariate analysis. CONCLUSIONS: TACE is an effective therapeutic option for cirrhotic patients with unresectable HCC and a CLIP score of 3 or less.     

Radiation therapy for portal venous invasion by hepatocellular carcinoma

AIM: To clarify the efficacy and safety of three-dimensional conformal radiotherapy (3-D CRT) for this disease and to specify patient subgroups suitable for this treatment. METHODS: Fifty-two patients with HCC received PVI-targeted radiation therapy from January 1995 through December 2003. Portal venous invasion (PVI) was found in the second or lower order branches of the portal vein in 6 patients, in the first branch in 24 patients and in the main trunk in 22 patients. Child classifications of liver function before radiation therapy were A, B, and C for 19, 24 and 2 patients, respectively. All patients received three-dimensional conformal radiotherapy with a total dose ranging from 39 to 60 Gy (57.0 Gy in average). RESULTS: Overall survival rates at 1, 2, 3, 4, and 5 years were 45.1%, 25.3%, 15.2%, 10.1%, and 5.1%, respectively. Univariate analysis revealed that Child status, the number of tumor foci, tumor type, transcatheter arterial embolization (TAE) after radiation therapy were statistically significant prognostic factors. Multivariate analysis showed that the number of tumor foci and TAE after radiation therapy were statistically significant. CONCLUSION: The results of this study strongly suggest the efficacy of 3-D CRT as treatment for PVI in HCC. 3-D CRT is recommended in combination with post-radiation TAE for PVI of HCC with 5 tumor foci or less in the liver and with Child A liver function.     

Comparison between chemoembolization combined with radiotherapy and chemoembolization alone for large hepatocellular carcinoma

AIM: To investigate the efficacy of transcatheter arterial chemoembolization (TACE) combined with radiotherapy for unresectable large hepatocellular carcinoma (HCC). METHODS: From June 1994 to June 1999, a total of 76 patients with large unresectable HCC were treated with TACE followed by external-beam irradiation. 89 patients with large HCC, who underwent TACE alone during the same period, served as the control group. Clinical features, therapeutic modalities, acute effects and survival rates were analyzed and compared between TACE plus irradiation group and TACE alone group. A multivariate analysis of nine clinical variables and one treatment variable (irradiation) was performed by the Cox proportional hazards model. RESULTS: The clinical features and therapeutic modalities except irradiation between the two groups were comparable (P>0.05). The objective response rate (RR) in TACE plus irradiation group was higher than that in TACE alone group (47.4 % vs 28.1 %, P<0.05). The overall survival rates in TACE plus irradiation group (64.0 %, 28.6 %, and 19.3 % at 1, 3, 5 years, respectively) were significantly higher than those in TACE alone group (39.9 %, 9.5 %, and 7.2 %, respectively, P=0.0001). Cox proportional hazards model analysis showed that tumor extension and Child grade were significant and were independent negative predictors of survival, while irradiation was an independent positive predictor of survival. CONCLUSION: TACE combined with radiotherapy is more effective than TACE alone, and is a promising treatment for unresectable large HCC.     

Liver atrophy after transcatheter arterial embolization and percutaneous ethanol injection therapy for a minute hepatocellular carcinoma.

A 63-year-old male patient with compensated cirrhosis underwent transcatheter arterial embolization (TAE) and percutaneous ethanol injection therapy (PEIT) for a minute hepatocellular carcinoma (HCC). Although the HCC was successfully treated, esophageal varices worsened and refractory ascites developed 3 months after the TAE and PEIT. Liver atrophy progressed rapidly compared to the natural course of liver cirrhosis.     

Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with Child's grade A or B cirrhosis: a multivariate analysis of prognostic factors.

We evaluated factors affecting long-term survival after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) complicating cirrhosis. One hundred eighty-two patients with Child's class A or B cirrhosis and an HCC, not amenable to surgery or percutaneous ethanol injection, underwent 346 TACEs (mean 1.9) with epirubicin, iodized oil, and gelatin sponge. Many prognostic factors were subjected to univariate analysis and thereafter, when significant, to the Cox's hazard proportional model. Finally, the significant indices in the Cox's model were used to estimate the accuracy of the probability of death with computation of the area under the receiving operative characteristic (ROC) curve. The cumulative survival rates at 1, 2, 3, and 5 years were 0.83, 0.52, 0.40, and 0.16, respectively. According to Cox's model, the factors associated with significantly worse survival were the presence of ascites (p = 0.0027), elevated bilirubin levels (p = 0.0163), elevated alpha-fetoprotein (alphaFP) values (p = 0.0067), a tumor greater than 5 cm in diameter (p = 0.0001), and the absence of a tumor capsule-like rim (p = 0.0278). According to these parameters, the accuracy of the probability of death estimated with ROC analysis was 0.63. Minor and major complications occurred in 82 patients (45%) and caused death in 2 patients. Long-term prognosis after TACE for HCCs in patients with Child's class A or B cirrhosis depends on the presence of ascites, the bilirubin level, the alphaFP value, the diameter of the tumor, and the presence of a tumor capsule-like rim. However, when considered altogether, these variables are poor predictors to evaluate survival, and other factors should be investigated to identify subjects more responsive to TACE. Complications occur in a high percentage of patients, but they do not affect long-term prognosis.     

Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort

Currently there is no consensus as to which staging system is best in predicting the survival of patients with hepatocellular carcinoma (HCC). The aims of this study were to identify independent predictors of survival and to compare 7 available prognostic staging systems in patients with HCC. A total of 239 consecutive patients with cirrhosis and HCC seen between January 1, 2000, and December 31, 2003, were included. Demographic, laboratory, and tumor characteristics and performance status were determined at diagnosis and before therapy. Predictors of survival were identified using the Kaplan-Meir test and the Cox model. Sixty-two percent of patients had hepatitis C, 56% had more than 1 tumor nodule, 24% had portal vein thrombosis, and 29% did not receive any cancer treatment. At the time of censorship, 153 (63%) patients had died. The 1- and 3-year survival of the entire cohort was 58% and 29%, respectively. The independent predictors of survival were performance status (P < .0001), MELD score greater than 10 (P = .001), portal vein thrombosis (P = .0001), and tumor diameter greater than 4 cm (P = .001). Treatment of HCC was related to overall survival. The Barcelona Clinic Liver Cancer (BCLC) staging system had the best independent predictive power for survival when compared with the other 6 prognostic systems. In conclusion, performance status, tumor extent, liver function, and treatment were independent predictors of survival mostly in patients with cirrhosis and HCC. The BCLC staging system includes aspects of all of these elements and provided the best prognostic stratification for our cohort of patients with HCC.     

Prognostic factors and survival according to the Okuda stage in patients with hepatocellular carcinoma]

BACKGROUND/AIMS: There are several staging systems to decide the stage of hepatocellular carcinoma (HCC), but yet incomplete. Okuda stage which includes both tumor characteristics and liver function is widely used. The aims of this study were to assess the usefulness of known prognostic factors and Okuda staging system in 237 cases of HCC. METHODS: A retrospective analysis of 237 cases of HCC diagnosed from 2000 to 2002 was performed. We analyzed prognostic factors such as age, sex, liver cirrhosis, Child-Pugh classification, tumor size, albumin, bilirubin, alpha-FP, ascites, encephalopathy and Okuda stage. Prognostic analysis was performed for single variables and estimating survival distributions were analyzed by the Kaplan-Meier method, statistically compared by the log-rank test. RESULTS: Patients had a mean age of 57.5 years and were predominantly men (79.7%). Liver cirrhosis were noticed in 214 cases (90.3%). The overall median survival period was 25.7 months. The median survival period was correlated to bilirubin, ascites, alpha-FP, tumor size, and Child-Pugh classification, but not to age, sex, and pattern of viral infection. The median survival period of the Okuda stage I, II and III cases was 35.8, 11.9 and 8.5 months (p<0.001). CONCLUSIONS: The median survival period of patients with HCC is significantly correlated to Okuda staging system, and survival period has improved than the initial data when the Okuda staging system was published in 1985. However, in order to discriminate early staged HCC more accurately, other prognostic factors such as alpha-FP and tumor morphology should be included in future staging system for HCC.     

Noninvasive predictors of large varices in patients hospitalized with gastroesophageal variceal hemorrhage

Aim To identify noninvasive factors predicting the presence of large varices (LV) in patients hospitalized with gastroesophageal variceal hemorrhage (GEVH). Methods Case records of patients admitted with GEVH between January 1998 and June 2005 were retrospectively analyzed. Relevant clinical parameters assessed included Child-Pugh class, ascites (clinical and/or on ultrasound), portosystemic encephalopathy (PSE), splenomegaly (clinical and/or on ultrasound), and hemodynamic instability. The laboratory parameters assessed were hemoglobin level, platelet count, prothrombin time, serum bilirubin, and albumin. The ultrasonographic characteristics noted were splenic size, presence of splenic varices, and portal vein diameter. Results A total of 420 patients (264 men) presented with GEVH during the study period. The mean age, gender distribution, and presence of cirrhosis were similar in the two groups. Liver cirrhosis with hepatocellular carcinoma (HCC), Child-Pugh class C, presence of clinically detectable ascites, grade 3–4 PSE, detectable splenomegaly, previous history of GEVH, hemodynamic instability and platelet count <91,000 were more common in the LV group. The frequency of radiologically detected ascites, splenomegaly, and portal vein diameter were similar in both groups. On multivariate analysis, the independent predictors for the presence of LV were cirrhosis with HCC, clinically detectable splenomegaly, hemodynamic instability, a previous history of GEVH, platelet count <91,000, and splenic size ≥158 mm. Conclusion Cirrhosis with HCC, clinical splenomegaly, hemodynamic instability, a previous history of GEVH, thrombocytopenia (i.e., platelet count <91,000), and splenic size ≥158 mm are independent noninvasive predictors of large varices in patients hospitalized with gastroesophageal variceal hemorrhage.     

Evaluation of conservative therapeutic modalities for hepatocellular carcinoma--analysis of 206 cases

The clinical effectiveness of conservative therapeutic modalities for hepatocellular carcinoma (HCC) was evaluated in terms of extension of survival. The therapeutic methods included one-shot therapy (OST) using Mitomycin C (MMC), Adriamycin (ADM), simultaneous ADM & MMC, with or without transcatheter arterial embolization (TAE). Prior to estimating the effectiveness, the subjects were graded into three stages according to the pretreatment severity of their residual liver function, based on total bilirubin, aspartate aminotransferase/alanine aminotransferase ratio, and ascites as constituent factors. OST with or without TAE significantly prolonged the mean survival time in stage I cases in good condition and in stage II cases in fair condition, but not in stage III cases in poor condition. Concerning OST without TAE, the results of ADM were slightly better than MMC in terms of extension of survival. OST combined with TAE was far more effective than OST without TAE. Extension of survival by simultaneous ADM & MMC is now under observation, but the toxicity of the modality has so far not proved serious. The long-term influence of repeated TAE on liver function was revealed to be mild within an average observation period of approximately one year. This study confirmed the validity of the present staging system in evaluating the efficacy of OST and TAE in terms of extension of survival.     

Transjugular intrahepatic portosystemic shunt for palliative treatment of portal hypertension secondary to portal vein tumor thrombosis

AIM: To evaluate the palliative therapeutic effects of transjugular intrahepatic portosystemic shunt (TIPS) in portal vein tumor thrombosis (PVTT) complicated by portal hypertension. METHODS: We performed TIPS for 14 patients with PVTT due to hepatocellular carcinoma (HCC). Of the 14 patients, 8 patients had complete occlusion of the main portal vein, 6 patients had incomplete thrombosis, and 5 patients had portal vein cavernous transformation. Clinical characteristics and average survival time of 14 patients were analysed. Portal vein pressure, ascites, diarrhoea, and variceal bleeding and circumference of abdomen were assessed before and after TIPS. RESULTS: TIPS was successful in 10 cases, and the successful rate was about 71%. The mean portal vein pressure was reduced from 37.2 mmHg to 18.2 mmHg. After TIPS, the ascites decreased, hemorrhage stopped and the clinical symptoms disappeared in the 10 cases. The average survival time was 132.3 d. The procedure failed in 4 cases because of cavernous transformation in portal vein and severe cirrhosis. CONCLUSION: TIPS is an effective palliative treatment to control hemorrhage and ascites due to HCC complicated by PVTT.     

The AST/ALT ratio as an indicator of cirrhosis in patients with PBC.

OBJECTIVES: A non-invasive, simple and non-expensive test to predict cirrhosis would be highly desirable. The aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio has been proven to be such an indicator of cirrhosis in alcoholic liver disease, hepatitis C. AIM: To test whether the AST/ALT ratio is a marker of cirrhosis also in patients with primary biliary cirrhosis (PBC). METHODS: The study consisted of 160 patients. In 126 patients, we had clinical and laboratory data at the time of diagnosis and follow-up with outcome: liver-related death, liver transplantation and survival. In 121 patients, we had laboratory data and liver histology. RESULTS: We found that the AST/ALT ratio was significantly higher in cirrhotic patients than in non-cirrhotic patients. A high AST/ALT ratio was significantly associated with esophageal varices and ascites. In a multivariate analysis, bilirubin and ALP were predictors of poor prognosis. CONCLUSION: The AST/ALT ratio seems to be of clinical value as a hint to the diagnosis of cirrhosis in patients with PBC but not as a prognostic factor.     

Treatment and prognostic factors in patients with hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma is a leading cause of death from cancer worldwide. Survival of patients depends on tumor extension and liver function, but yet there is no consensual prognostic model. AIMS: To evaluate the influence on survival of pretreatment parameters (clinico-laboratorial, liver function, tumor extension, Okuda and Cancer of the Liver Italian program (CLIP) staging) and treatment modalities. METHODS: We retrospectively analyzed 207 patients, diagnosed between 1993 and 2003. The initial treatment was: surgery--six patients; radiofrequency ablation--21; percutaneous ethanol injection--29; transarterial chemoembolization--49; tamoxifen--49; supportive care alone--53. Factors determining survival were assessed by Kaplan-Meier method and Cox regression models. RESULTS: Median survival was 24 months. In univariate analysis, Child-Pugh classification and Model for end-stage liver disease (MELD) score, portal vein thrombosis (PVT), tumor size, number of lesions, Okuda and CLIP scores were all associated with prognosis (P < 0.001). Alpha-fetoprotein levels were not predictive of survival. Independent predictors of survival were ascites, bilirubin, PVT and therapeutic modalities (P < 0.001). In early stage hepatocellular carcinoma (HCC), survival was similar for both percutaneous ablation modalities, either radiofrequency or ethanol injection (P = NS). In advanced HCC, survival was better in patients receiving tamoxifen than supportive care alone (P < 0.001). CONCLUSION: This study reinforces the importance of baseline liver function (Child-Pugh classification and MELD score) in the survival of patients with HCC, although staging systems allowed the stratification of patients in different prognostic groups. Ascites, bilirubin and PVT were independent pretreatment predictors of survival. All treatments influenced the patient's outcome, whether in early or advanced stages.     

Gastric metastasis of hepatocellular carcinoma via a possible existing retrograde hematogenous pathway

Background and Aim: Hepatocellular carcinoma (HCC) tends to metastasize to extrahepatic organs. Stomach involvement has been seldom reported and has always been considered as direct invasion. This study aims to propose a possible existing pathway for the hematogenous metastasis of HCC to the stomach. Methods: Only seven cases with stomach involvement were found from 8267 HCC patients registered at our hospital between 2000 and 2007. Their laboratory data, the findings of computed tomography and upper endoscopy, therapeutic procedures, such as esophageal variceal banding ligation (EVL), and transhepatic arterial embolization (TAE) were further studied. Results: All seven patients were male. Liver cirrhosis was found in six patients (6/7 = 85.7%), HCC with portal vein thrombosis (PVT) in six patients (6/7 = 85.7%), splenomegaly in five patients (5/7 = 71.4%) and esophageal varices in five patients (5/7 = 71.4%). Six patients underwent TAE and one patient underwent EVL before the development of HCC in the stomach. Four patients had HCC at the cardia, one patient at the anterior wall of the high body and two patients at the greater curvature of the high body, far away from the original HCC. Six patients eventually developed distant metastasis. HCC with gastric metastasis developed 53–126 days after TAE in five patients and 74 days after EVL in one patient. Conclusions: When cirrhotic patients with portal hypertension have HCC with PVT, a hematogenous pathway can exist for gastric metastasis of tumor thrombi involving hepatofugal flow to the stomach after TAE or EVL apart from the major pathway of direct invasion.     

Differential diagnosis of jaundice by combined noninvasive diagnostic means using a logistic discriminant analysis

Using a logistic discriminant function we retrospectively evaluated the diagnostic value of laboratory features and abdominal sonography in 70 patients with jaundice. 18 patients had an extrahepatic obstruction of the common bile duct (EHO), 22 patients had metastatic liver disease (MLD) and 30 patients had an infectious or toxic hepatocellular disease (HCD). The sensitivity resp. specificity of the 5 laboratory values AP, GGT, GPT, GOT and bilirubin was 22% resp. 90% for diagnosing EHO, 82% resp. 79% for diagnosing MLD and 67% resp. 68% for diagnosing HCD. The diagnostic value determined by their Chi2-value was AP greater than GPT greater than bilirubin greater than GOT greater than GGT. An undoubtedly dilated common bile duct was seen in 56% of the patients with EHO and in none of the other patients. Metastatic lesions were seen exclusively in 81% of the patients with MLD. No distinct sonographic sign could be found for the patients with HCD. The combination of AP, GPT and bilirubin with the result of abdominal sonography in a logistic discriminant function led to a correct a posteriori classification of all patients. Using a mathematical classification model jaundiced patients can be diagnosed on the basis of noninvasive methods alone and invasive procedures should be restricted to therapeutic interventions.     

Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis

This study was undertaken to present data from a phase 2 study in which patients with unresectable hepatocellular carcinoma (HCC) with and without portal vein thrombosis underwent radioembolization with Yttrium ((90)Y) microspheres. Patients treated were stratified by Okuda, Child-Pugh, baseline bilirubin, tumor burden, Eastern Cooperative Oncology Group (ECOG), presence of cirrhosis and portal vein thrombosis (PVT) (none, branch, and main). Clinical and biochemical data were obtained at baseline and at 4-week intervals following treatment for up to 6 months. Tumor response was obtained using computed tomography (CT). Patients were followed for survival. One hundred eight patients were treated during the study period. Thirty-seven (34%) patients had PVT, 12 (32%) of which involved the main PV. The cumulative dose for those with and without PVT was 139.7 Gy and 131.9 Gy, respectively. The partial response rate using world Health Organization (WHO) criteria was 42.2%. Using European Association for the Study of the Liver (EASL), the response rate was 70%. Kaplan-Meier survival varied depending on location of PVT and presence of cirrhosis. The adverse event (AE) rates were highest in patients with main PVT and cirrhosis. There were no cases of radiation pneumonitis. Conclusion: The use of minimally embolic (90)Y glass microspheres to treat patients with HCC complicated by branch/lobar PVT may be clinically indicated and appears to have a favorable toxicity profile. Further investigation is warranted in patients with main PVT.