Eradication of hepatitis C virus profoundly prolongs survival in hepatocellular carcinoma patients receiving transarterial chemoembolization.

Adjuvant pegylated interferon plus ribavirin treatment (PegIFN/RBV) reduces recurrence and prolongs survival in early stage hepatocellular carcinoma (HCC) patients with chronic hepatitis C (CHC) infection receiving resection or ablation. However, the impact of antiviral therapy in intermediate and advanced stage of CHC-HCC patients is uncertain. This study aimed to investigate the impact PegIFN/RBV treatment on recurrence-free interval and survival in patients with HCC receiving transarterial chemoembolization (TACE). From 2010 to 2013, 274 CHC patients from a 1073 patient-based cohort composed of freshly diagnosed HCC and receiving TACE treatment the Chang Gung Memorial Hospital, Linkou Medical Center were recruited. Propensity score matching (PSM) (age, gender, AST to Platelet Ratio Index (APRI), tumour size, tumour number and Child-Turcotte-Pugh score) with the ratio 1:2 for patients with and without PegIFN/RBV treatment was performed. Statistics were performed with SPSS V.20 (IBM, USA). After matching, 153 patients were analysed and 27 patients (17.6%) achieved sustained virologic response (SVR). The 2-year cumulative overall survival rate and recurrence-free survival rate among patients with SVR, non-SVR, and untreated were 85.2% vs 58.3% vs 69.6% (P=.001) and 73.3% vs 53.8% vs 58.5% (P=.013). By Cox regression analysis, non-SVR, untreated, increase CTP score and nonresponder to TACE were independent factors related to mortality. The SVR achieved by PegIFN/RBV treatment markedly improves survival and reduces tumour recurrence in CHC-HCC patients receiving TACE treatment after complete response.

IL28B genetic variations are associated with high sustained virological response (SVR) of interferon-α plus ribavirin therapy in Taiwanese chronic HCV infection.

Chronic hepatitis C virus (HCV) infection patients exhibit different sustained virological responses (SVRs) following the treatment with pegylated interferon-α (IFN-α) and ribavirin. Genome-wide association studies consistently linked SVR of IFN-α-based therapy to the IL28B single-nucleotide polymorphisms (SNPs) on chromosome 19q.13 in various populations. This study was undertaken to investigate the association of IL28B SNPs with SVR in a cohort of Taiwanese chronic HCV patients. Ten SNPs of IL28B were genotyped in 728 chronic HCV patients and 960 healthy controls. Genotype distributions, allele frequencies and haplotypes were tested for SVR and susceptibility in Taiwanese chronic HCV patients. Non-genotype 1 infection (adjusted P=3.3 × 10(-12), odds ratio (OR) 0.179; 95% confidence interval (CI): 0.110-0.290) and low HCV viral load (<400 000 IU ml(-1)) (adjusted P=3.5 × 10(-9), OR 0.299; 95% CI: 0.200-0.446) were two major factors identified for high SVR. Notably, eight IL28B SNPs including previously described disease-associated SNPs (Trend test P=0.005) were significantly associated with SVR. Our data indicate that IL28B polymorphisms are the essential contributing factors for high SVR in Taiwanese chronic HCV patients. Combination of virus genotyping and host genetic data may be used to select the optimal treatment regimes in IFN-based therapy.

A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients.

BACKGROUND: Human hepatocellular carcinoma (HCC) cells are largely deficient of argininosuccinate synthetase and thus auxotrophic for arginine. This study aims to investigate the efficacy and pharmacodynamics of pegylated arginine deiminase (ADI-PEG 20), a systemic arginine deprivation agent, in Asian HCC patients. METHODS: Patients with advanced HCC who were not candidates for local therapy were eligible and randomly assigned to receive weekly intramuscular injections of ADI-PEG 20 at doses of 160 or 320 IU m(-2). The primary end point was disease-control rate (DCR). RESULTS: Of the 71 accruals, 43.6% had failed previous systemic treatment. There were no objective responders. The DCR and the median overall survival (OS) of the intent-to-treat population were 31.0% (95% confidence interval (CI): 20.5-43.1) and 7.3 (95% CI: 4.7-9.9) months respectively. Both efficacy parameters were comparable between the two study arms. The median OS of patients with undetectable circulating arginine for more than or equal to and <4 weeks was 10.0 (95% CI: 2.1-17.9) and 5.8 (95% CI: 1.4-10.1) months respectively (P=0.251, log-rank test). The major treatment-related adverse events were grades 1-2 local and/or allergic reactions. CONCLUSIONS: ADI-PEG 20 is safe and efficacious in stabilising the progression of heavily pretreated advanced HCC in an Asian population, and deserves further exploration.

A liver slice culture-based ex vivo assay to predict the outcome of antiviral therapy for chronic hepatitis C.

A liver slice culture-based, ex vivo drug suppression assay was developed as a pre-therapeutic predictor for the outcome of antiviral therapy. To investigate its clinical application, 106 consecutive patients with chronic hepatitis C virus (HCV) infection were evaluated. Ex vivo drug suppression assay was performed before administrating a standard course of peginterferon plus ribavirin combination therapy. Stepwise logistic regression model was used to estimate sustained virological response (SVR) on the presence of various clinicopathological parameters. Suppression of HCV replication in the ex vivo assay was present in 32 patients, 29 (90.6%) of whom achieved SVR. Stepwise logistic regression analysis indicated that the presence of interferon suppression effect in the ex vivo assay (odds ratio [OR], 5.552; 95% confidence interval [CI], 1.114-27.673; P = 0.036), genotype 1 (OR; 0.045, 95% CI, 0.008-0.259; P = 0.001), HCV-RNA level (OR, 0.739; 95% CI, 0.617-0.885; P = 0.001), the presence of fatty metamorphosis (OR, 0.205; 95% CI, 0.053-0.793; P = 0.022), and albumin (OR, 9.687; 95% CI, 2.237-41.940; P = 0.002) were independent determinants of SVR. Categorical analysis revealed that 17 of 17 (100%) patients with genotype non-1 and positive ex vivo suppression test achieved SVR, while 20 of 40 (50%) with genotype 1 and negative ex vivo suppression test achieved SVR. In conclusion, the ex vivo drug suppression assay may serve as an independent pre-therapeutic predictor for the SVR in interferon-based antiviral therapy.

Sustained virological response to interferon reduces cirrhosis in chronic hepatitis C: a 1,386-patient study from Taiwan.

BACKGROUND: The long-term benefits of interferon-based therapy on preventing cirrhosis at non-cirrhotic stage in chronic hepatitis C patients are not fully clarified. AIM: To evaluate the effectiveness of interferon-based therapy regarding to cirrhosis prevention in non-cirrhotic chronic hepatitis C patients. METHODS: A total of 1386 biopsy-proven, non-cirrhotic chronic hepatitis C patients (892 received interferon-based therapy and 494 untreated) were enrolled. RESULTS: Fifty-six untreated and 51 treated (24 sustained virologic responders and 27 non-responders) patients developed cirrhosis during a mean follow-up period of 5.0 (1-16) and 5.1 (1-15.3) years, respectively. The annual incidences of cirrhosis in untreated and treated groups were 2.26 and 1.11% (non-responders: 1.99%, sustained responders: 0.74%), respectively. The 15-year cumulative incidence of cirrhosis was significantly lower in treated (9.9%) than untreated patients (39.8%, P = 0.0008, log-rank test). The 14.5-year cumulative incidence of cirrhosis was significantly lower in sustained responders (4.8%) compared with non-responders (21.6%, P = 0.0007) and untreated patients (36.6%, P < 0.0001). The difference was not significant between non-responders and untreated controls. Cox proportional hazards regression showed sustained virologic responders and younger age were independent negative factors for cirrhosis development. CONCLUSION: A sustained virologic response secondary to IFN-based therapy could reduce cirrhosis development in chronic hepatitis C patients.

Genome-wide hypomethylation in hepatocellular carcinogenesis.

Aberrant genome-wide hypomethylation has been thought to be related to tumorigenesis. However, its mechanism and implications in hepatocellular carcinogenesis remain to be elucidated. Samples of hepatoma (hepatocellular carcinoma, HCC) and paired non-HCC liver tissues were obtained from 17 HCC patients. Normal liver tissues obtained from three individuals were used as controls. Compared with the paired non-HCC liver tissues, genome-wide 5-methylcytosine content in HCC was reduced in all of the tested HCC samples (P < 0.001). Conversely, genome-wide 5-methylcytosine content did not significantly differ among normal, noncirrhotic, and cirrhotic liver tissues. Moreover, the degree of reduced DNA methylation was related to late histopathological HCC grade (P = 0.005) and large tumor size (P = 0.079). Compared with the paired non-HCC liver tissues, expression of DNA methyltransferases DNMT-1, DNMT-3A, and DNMT-3B and the DNA methyltransferase-like gene, DNMT-2, was up-regulated in 53, 41, 59, and 47% of the HCC samples, respectively. Surprisingly, small amounts of LINE-1 retrotransposon transcripts were detected in HCC and non-HCC as well as normal liver tissues, and the expression levels were not significantly different in HCC compared with the paired non-HCC or normal liver tissues. Of interest, the 3' ends of these LINE-1 transcripts were truncated. Our findings suggest that genome-wide hypomethylation in HCC is a continuing process that persists throughout the lifetime of the tumor cells rather than a historical event occurring in precancer stages or in cell origins for HCC. Up-regulation of DNA methyltransferases might simply be a result of increased cell proliferation in cancer. In addition, our results did not support the hypothesis of activation of transposable elements in HCC via genome-wide hypomethylation.

Response of patients with dual hepatitis B virus and C virus infection to interferon therapy.

Patients with dual infection with hepatitis B virus (HBV) and delta virus (HDV) responded poorly to interferon (IFN) therapy. Little is known about the effect of IFN therapy in patients with HBV and hepatitis C virus (HCV) dual infection. The patients in two randomized controlled trials with chronic HBV infection were retrospectively assayed for HCV markers. The HBV responses to IFN therapy in patients with and without HCV markers were compared. An open trial was conducted in 4 patients who had lost their serum HBV surface antigen (HBsAg) but had continuing HCV viremia and hepatitis. Of the 15 patients seropositive for HCV marker(s), only 1 (6.7%) responded with seroclearance of HBV DNA and HBV e antigen, as compared with 46 (28%) of 164 HCV-negative patients (p = 0.058). Icteric hepatitis developed in 1 patient on emergence of serum HCV RNA in association with seroclearance of HBV DNA. In contrast, good response was demonstrated in 3 of the 4 patients who had lost serum HBsAg before therapy. The results suggest that IFN therapy is not only of limited value in patients with dual infection with HBV and HCV but also has a potential risk of severe hepatitis if the clearance of one virus removes its suppressive effect on and facilitates the emergence of the other. However, patients with continuing HCV hepatitis after termination of the chronic HBsAg carrier state responded well to IFN therapy.

Treatment of chronic type B hepatitis in Southeast Asia.

In Southeast Asia, 15 to 20 percent of the population are hepatitis B surface antigen carriers. The majority of these carriers have chronic hepatitis and would progress to cirrhosis or hepatocellular carcinoma at an annual incidence of 2 percent and 1 percent, respectively. Previous studies from Southeast Asia suggested that immunosuppressive therapy could be harmful, or at best of no value, and antiviral treatment with vidarabine, picibanil, or even interferon was also unsatisfactory. Currently, a randomized controlled trial of human lymphoblastoid interferon, with or without prednisolone pretreatment, versus placebo in patients with hepatitis B core antigen in the liver and hepatitis B e antigen in the serum is being conducted. Forty-five patients (29 receiving interferon, 16 receiving placebo) have been entered in the trial for at least two months. Actuarial analysis shows that the response to interferon therapy was better than that to placebo. Although flu-like symptoms, hair loss, and body weight loss were seen, no side effect requiring specific treatment has been encountered. These preliminary results suggest that human lymphoblastoid interferon is effective and safe in Oriental patients.

A prospective randomized trial of colchicine in prevention of liver cirrhosis in chronic hepatitis B patients.

BACKGROUND: The clinical course of chronic hepatitis B is variable. Patients with hepatic decompensation, bridging necrosis or an alpha-fetoprotein level greater than 100 ng/mL during an exacerbation of hepatitis have a high risk of developing cirrhosis. This study was conducted to evaluate the effect of colchicine in the prevention of cirrhosis in such patients. METHODS: Patients with risk factor(s) were randomized to receive either colchicine 5 mg/week or no specific treatment, the end point being development of cirrhosis. RESULTS: After a follow up period of 4 years, the treatment group had a marked reduction in exacerbations of acute hepatitis (32% vs. 63%/patient/year, P < 0.005). Seven out of 38 patients in the treatment group and 10 out of 27 patients in the control group developed cirrhosis. The calculated cumulative incidence of cirrhosis by the end of first, second, third and fourth years in the treatment group was 8.7, 18.6, 32 and 32%, respectively. The corresponding figures in the control group were 30, 35.5, 46.3 and 73.2%, respectively, with a P-value of 0.057. CONCLUSIONS: The results suggest that colchicine may prevent cirrhosis in chronic hepatitis B patients with risk factor(s), possibly by suppressing exacerbations of hepatitis through an anti-inflammatory effect.

Hepatitis C virus in peripheral blood mononuclear cells.

RNA extracted from plasma and peripheral blood mononuclear cells of patients with chronic hepatitis C were used as the template for reverse transcription followed by double in vitro enzymatic amplification with nested primers. Hepatitis C virus was detected in 14 of 15 (93.3%) plasma specimens and in 8 of 15 (53.3%) peripheral blood mononuclear cell specimens obtained from patients with chronic hepatitis C and abnormal liver functions. The results suggest that hepatitis C virus could be found frequently in peripheral blood mononuclear cells of patients with chronic hepatitis C. Whether the presence of hepatitis C virus in peripheral blood mononuclear cells plays any role in the pathogenesis of diseases associated with hepatitis C virus infection remains to be determined.

Are expandable metallic stents better than conventional methods for treating difficult intrahepatic biliary strictures with recurrent hepatolithiasis?

BACKGROUND: Conventional methods for treating patients with recurrent hepatolithiasis associated with complicated intrahepatic biliary strictures include balloon dilatation of the intrahepatic biliary strictures, lithotripsy, and the clearance of difficult stones as completely as possible, with the placement of an external-internal stent for at least 6 months. After these modalities are used, symptomatic refractory strictures remain. Recently we used internal Gianturco-Rosch metallic Z stents to treat patients who had refractory strictures. OBJECTIVE: To compare therapeutic results and complications of an internal expandable metallic Z stent with those of repeated external-internal stent placement. STUDY DESIGN: Case-control study. SETTING: A referral center. PATIENTS: From January 1992 to December 1996, 18 patients with recurrent hepatolithiasis and complicated intrahepatic biliary strictures underwent percutaneous dilatation of stricture and transhepatic percutaneous cholangioscopic lithotomy for recurrent stones. After their stones were completely cleared, their biliary strictures failed to dilate satisfactorily. The patients were randomly enrolled into 2 groups: group A (7 patients), who received an expandable metallic Z stent, and group B (11 patients), who had repeated placement of external-internal stents. INTERVENTIONS: Percutaneous stricture dilatation, electrohydraulic lithotripsy, balloon dilatation, percutaneous transhepatic cholangioscopic lithotomy, and biliary stenting by a Silastic external-internal catheter or a modified Gianturco-Rosch expandable metallic Z stent (for an internal stent). MAIN OUTCOME MEASURES: The number of procedures, days in hospital, procedure-related complications, incidents of stone recurrence and recurrence of cholangitis, readmissions to the hospital, treatment sessions required, and mortality rate. Patients' limitations in ordinary activities were also compared. RESULTS: The follow-up period ranged from 28 to 60 (40.7+/-12.7 [mean +/- SD]) months in group A and from 28 to 49 (36.0+/-7.2) months in group B. Fewer group A patients (3 [43%]) than group B patients (8 [73%]) tended to have recurrent cholangitis and to require readmission to the hospital, but this was not statistically significant (P = .33). When their cumulative probability of a first episode of cholangitis during follow-up was compared, however, it was significantly lower in patients treated with a metallic stent (P = .04). Compared with group B patients, group A patients had less frequent recurrence of stones (0% vs 64%; P = .01), fewer procedures for the clearance of biliary stones or sludge (1.7+/-2.2 vs 6.4+/-4.3; P = .03), and shorter hospital stays (8.0+/-11.5 days vs 17.0+/-12.0 days; P = .07). No patients in group A experienced limitation in ordinary activities, whereas 7 patients in group B did (P<.02). CONCLUSIONS: Compared with the repeated placement of external-internal stents, the use of a metallic internal stent effectively decreases stone recurrence, simplifies further procedures, and is more convenient. Its use is suggested as an alternative choice in the treatment of recurrent hepatolithiasis with refractory intrahepatic biliary strictures.

Is the p53 gene mutation of prognostic value in hepatocellular carcinoma after resection?

HYPOTHESIS: Mutant p53 gene has lost its tumor suppression function and is considered to be a very important step in hepatocellular carcinoma development. We propose that the mutant p53 gene plays a role in its invasiveness and prognosis after resection. DESIGN: A case-controlled study. SETTING: A referral center. PATIENTS: Seventy-nine consecutive patients who underwent surgical resection for hepatocellular carcinoma entered this study. INTERVENTION: Tissue sections of resected hepatocellular carcinoma (deparaffinized and rehydrated from formalin-fixed and paraffin-embedded sections) were incubated with antihuman p53 monoclonal antibody and immunostained. The p53 result was scored without prior knowledge of the patients' status. A 10% immunopositivity was regarded as the threshold value. MAIN OUTCOME MEASURE: The immunopositive rate of p53 was 69.6% (55 of 79 patients). The clinical variables (age, sex, associated liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, serum alpha-fetoprotein, and Child-Pugh class); the histological variables (size, capsule, vascular permeation; grade of differentiation, and multinodularity); and postoperative course (recurrence, tumor-free interval, death, and survival period) were correlated with p53 immunopositivity. RESULTS: From univariate analysis, more patients with p53 positivity were male (92.7 vs 0%) (P<.001); had vascular permeation (80% vs 50%) (P =.007) (odds ratio [OR], 4.0); no complete capsule (83.6% vs 62.5%) (P =.04) (OR, 3.1); and daughter nodules (90.9% vs 70.8%) (P =.04) (OR, 4.1) than patients with negative p53 staining. From multivariate analysis, only sex and vascular permeation remained significant (P =.001 and P =.008, respectively). Although more patients with p53 positivity had tumor recurrence (78% vs 50%) (P =.01) and death (64% vs 33%) (P =. 01), the Cox proportional hazards model showed that p53 overexpression had only weak correlations with tumor-free interval and survival time (P =.09 and P =.08, respectively). CONCLUSIONS: Our results show that the biological behavior of the mutant p53 gene is strongly related to the invasiveness of hepatocellular carcinoma and may also influence the postoperative course. We suggest that the immunopositivity of the mutant p53 gene has a predictive role in the prognosis of patients with resected hepatocellular carcinoma.

Resolution of liver abscesses: comparison of pyogenic and amebic liver abscesses.

To examine the resolution of liver abscesses, a prospective ultrasonographic follow-up study was conducted in 51 patients, each with a solitary abscess (26 pyogenic and 25 amebic) which had been treated successfully by non-surgical measures. The rate of complete abscess resolution for each of the initial 6 months was 0%, 5%, 10%, 23%, 30%, and 30% in the amebic group; and 20%, 54%, 77%, 89%, 94%, and 94% in the pyogenic group. The absorption volume of the pyogenic group in the first month was also greater than that of the amebic group (3.0 +/- 5.0 ml/day vs. 1.1 +/- 0.8 ml/day, P less than 0.05). The resolution ratio of pyogenic and amebic liver abscesses in the first month was 74% +/- 38% and 36% +/- 23%, respectively. In 3 patients in the amebic group, the abscess was still detectable 2 years after treatment. These results suggest that pyogenic liver abscesses resolve more rapidly than amebic abscesses. These findings should be considered in the differential diagnosis of asymptomatic space-taking lesion in the liver.

The prognostic factors of severe amebic liver abscess: a retrospective study of 125 cases.

One hundred twenty-five cases of amebic liver abscess were diagnosed at Chang Gung Memorial Hospital in Taiwan from January 1981 to December 1989. An analysis of possible prognostic factors for severe amebic liver abscess was done retrospectively. The majority of the patients came from the southern part of Taiwan. Severe amebic liver abscess was defined as the rupture of an abscess that was resistant to 72 hr of medical treatment, or complicated by secondary bacterial infection. The results showed significant differences between patients with severe liver abscess and those with more moderate forms of amebic liver abscess in indices such as jaundice, hemoglobin and serum bilirubin levels, and dyspnea, as well as in pulmonary changes (right diaphragm elevation, right pleural effusion) seen on chest radiographs. Those patients with diabetes mellitus also had greater evidence of severe liver abscess. Moderate cases that were treated with amebicides showed excellent responses (no mortality). Severe cases required, in addition to amebicide therapy, either percutaneous or surgical drainage of pus, especially in those patients with ruptured abscesses. Those patients with abscesses that ruptured into the thoracic cavity were treated by either thoracostomy or needle aspiration, and all were cured. Three patients died of abscess rupture into the abdominal cavity, associated with secondary bacterial infection. The overall mortality rate was 2.4%. These symptoms and signs of severe liver abscess are indicators of the need for intensive treatment such as aspiration or surgical drainage.

Quantitative assessment of hepatitis C virus RNA by polymerase chain reaction and a digoxigenin detection system: comparison with branched DNA assay.

A method for quantifying hepatitis C virus (HCV) RNA in serum using reverse transcription-polymerase chain reaction (RT-PCR) followed by slot-blot hybridization with a specific, digoxigenin-labeled probe was developed. Using RNA synthesized from cloned HCV cDNA as a standard, serum concentration of HCV RNA above 10 copies/ml can be quantitatively determined. To compare this method with branched DNA (bDNA) assay, 45 serum samples from 26 patients with newly acquired acute hepatitis C (n = 16) or hepatitis C with acute exacerbation (n = 10) were submitted to both assays. HCV RNA in 30 (67%), 12 (27%) and three (6.7%) samples can be quantitatively determined by both, either and none of the two assays, respectively. Using a standardized qualitative HCV RNA detection test (Amplicor HCV test) as a reference, 1 and 0 false positive results were found by bDNA and this assay, respectively. This quantitative assay using RT-PCR and a digoxigenin detection system was comparable to bDNA assay. Since a false positive result was rarely found, this technique can be used as a first line test to screen a large number of samples rapidly and economically.

Percutaneous transhepatic cholangioscopy in the treatment of complicated intrahepatic biliary strictures and hepatolithiasis with internal metallic stent.

For recurrent hepatolithiasis coexisting with a complicated long-segment intrahepatic biliary stricture, repeated surgeries, balloon dilation of the stricture, and external-internal stenting may still fail to solve the problem. We tried using a Gianturco-Rosch metallic Z internal stent (Wilson-Cook Medical, Inc., Bloomington, IN, USA) with the aid of percutaneous transhepatic cholangioscopy (PTCS) to treat such patients. Eight patients had a Z stent placed through a percutaneous transhepatic biliary drainage tract. Immediately after stent placement, PTCS was inserted via the percutaneous transhepatic biliary drainage route and a part of the wire skirt not firmly anchored in one of the eight patients was detected. It was successfully repositioned using PTCS. Recurrent cholangitis developed in three patients 6, 7, and 30 months, respectively, after stent placement. PTCS was undertaken again through a reestablished percutaneous transhepatic biliary drainage route and revealed sludge in their stent lumens. We cleared it by PTCS. No further cases of cholangitis occurred in later follow-up. PTCS is useful in ensuring adequate stent position, diagnosing and treating the causes of recurrent cholangitis, and prolonging the function of stents.

The benefits of a second transhepatic route in failed percutaneous management of difficult intrahepatic biliary strictures with recurrent hepatolithiasis.

Percutaneous stricture dilatation and cholangioscopic lithotomy has become a mainstay in the treatment of patients with recurrent hepatolithiasis associated with intrahepatic biliary strictures. In a consecutive series of 125 patients who underwent percutaneous management of recurrent hepatolithiasis from 1987 to 1999, there were 15 patients in whom the procedure failed to clear the stones. A second percutaneous transhepatic route was established for subsequent treatment. A reappraisal of its indications and efficacy was done. Treatment through a second route was helpful for patients with bilateral strictures, angulated duct, difficult strictures, large impacted stones, a subcutaneous jejunal limb, or hemobilia developing in the first route. Strictures remained impacted in 1 of the 15 patients (failure rate, 7%), with the remaining having complete clearance of stones. Cholangitis occurred in two patients; no other complications were encountered. A second percutaneous route is very helpful for the management of complicated hepatolithiasis and biliary stricture.

Retroperitoneal neurilemoma: clinical features in 10 cases.

Neurilemoma is a rare tumor in the retroperitoneal cavity. Up to 1984, less than 50 cases had been reported in the English literature. We observed 10 cases of retroperitoneal neurilemoma with histologic proof at our hospital. The major symptoms were abdominal pain (80%) and body weight loss (40%). Physically palpable abdominal masses were found in 90% of the cases. The laboratory data were all within normal limits, except for a mild elevation of the eosinophil count in 4 cases. Radiologic examination demonstrated the tumor in most cases. Abdominal ultrasonography was very effective in the detection of these tumors. Surgical resection was the treatment of choice. Some patients suffered from leg numbness after the operation. Recurrent rate was high, up to 20% therefore, long-term follow-up is mandatory.

[A clinicopathological study in primary biliary cirrhosis].

Twenty-two patients with clinical, biochemical, immunological and pathological characteristics compatible with primary biliary cirrhosis were studied. There were 17 women and 5 men with a mean age of 57.4 +/- 15.2 years and a mean follow-up of 24.1 +/- 20.1 months. Four of them expired during the follow-up and eighteen patients now survive. The most common complaints were fatigue (63.6%) and itching (59.1%). Only one case (4.5%) was asymptomatic in this series. The major physical findings were jaundice (50%) and hepatomegaly (50%). The significant laboratory findings were: elevation of alkaline phosphatase (91% of the cases greater than 3 times the upper limit of normal), gamma-glutamyl transpeptidase (100% of the cases greater than 4 times the upper limit of normal), aspartate transaminase (95%) and alanine transaminase (100%), presence of anti-mitochondrial antibodies (91%), antinuclear antibodies (73%) and the elevation of IgM (88%). One case was associated with ulcerative colitis. Pathological staging in this series revealed 57.9% of stage II, 26% of stage III, 10% of stage IV and 5.3% of stage I. All patients with granuloma survived but 4 of the 5 patients with cholestasis died during follow-up. The results show that the features in this series of PBC were similar to those observed in western countries. The very high ALP and gamma-GT level as well as only one asymptomatic case in this series, suggest that our patients were diagnosed at a late stage. The reason(s) for the higher positivity of ANA, particularly the speckled type and a lower rate of associated auto-immune disease requires further study. Liver biopsy in predicting a prognosis is valuable.

Risk factors associated with fulminant amebic colitis.

Amebic colitis is associated with serious complications and a high fatality rate if it progresses to its fulminant form. The purpose of this retrospective study was to determine the risk factors associated with fulminant amebic colitis. From February 1978 to February 1993, 60 adults were diagnosed with intestinal amebiasis at Chang Gung Memorial Hospital. Sixteen patients with massive bloody diarrhea, persistent systemic toxicity or signs of peritonitis were classified as having fulminant colitis, five of whom progressed to fulminant colitis after admission to the hospital. Forty-four patients with good responses to amebicides and without complications were classified as having moderate colitis. There was no amebiasis-related mortality among patients with moderate colitis. In contrast, five patients with fulminant colitis died. Early diagnosis and surgical treatment significantly decreased mortality when compared with conservative treatment. Significant factors associated with the development of fulminant intestinal amebiasis in univariate analyses were being male, age over 60 years, having an associated liver abscess, progressive abdominal pain, signs of peritonitis, leukocytosis, hyponatremia, hypokalemia and hypoalbuminemia. Only the factors of being over 60 years of age and hypokalemia were important in multivariate analyses. We conclude that early and extensive surgical treatment is mandatory for patients with typical presentations of fulminant amebic colitis on admission to the hospital, such as progression to peritonitis, persistent systemic toxemia and explosive bloody diarrhea. For other patients, especially the elderly and those with low serum potassium levels, close monitoring and observation for signs of fulminant colitis is important.