Stereotactic body radiation therapy (SBRT) for inoperable hepatocellular carcinoma (HCC) offers excellent local control rates. This study retrospectively analyzed the influence of different tumor ...size on treatment outcomes after SBRT.Between December 2008 and February 2014, 141 HCC patients were treated with Cyberknife SBRT. Patients were divided into 3 groups namely small tumors (≤4 cm), intermediate-sized (>4-<10 cm), and large (≥10 cm) tumors. Treatment outcomes, prognoses, and safety at each tumor size were compared and analyzed.A total of 52 patients with small tumors, 55 with intermediate tumors, and 34 patients with large tumors were retrospectively analyzed with a median follow-up of 16 months. Objective responses were achieved at 96.15%, 90.90%, and 76.47% for small, intermediate, and large tumors, respectively (P ≤ .0001) and the 3-year local control rates were 97.85%, 71.99%, and 82.14%, respectively (P = .0035). The 3-year overall survival rates were 50.26%, 45.29%, and 33.38% for small, intermediate, and large tumors, respectively (P = .3757). No significant differences were found in overall-survival, intra-hepatic recurrence free survival, disease-progression free survival, or distant metastasis-free survival.SBRT offers the best effective local control rate and response rate for small HCCs. However, tumor size did not significantly affect the overall survival rate, intra-hepatic recurrence free rate, or disease-progression free rate.
AIM: To study the manifestations of perihepatic lymph nodes during the episode of acute hepatitis flare by point-of-care ultrasonography.METHODS: One hundred and seventy-six patients with an episode ...of acute hepatitis flare(ALT value > 5 × upper normal limit) were enrolled retrospectively. Diagnosis of etiology of the acute hepatitis flare was based on chart records and serological and virological assays. The patients were categorized into two groups(viral origin and non-viral origin) and further defined into ten subgroups according to the etiologies. An ultrasonograpy was performed within 2 h to 72 h(median, 8 h). The maximum size of each noticeable lymph node was measured. Correlation between clinical parameters and nodal manifestations was analyzed RESULTS: Enlarged lymph nodes(width ≥ 5mm)were noticeable in 110(62.5%) patients, mostly in acute on chronic hepatitis B(54.5%). The viral group had a higher prevalence rate(89/110 = 80.9%) and larger nodal size(median, 7 mm) than those of the non-viral group(21/66 = 31.8%; median, 0 mm)(P < 0.001 for both). Meanwhile, there were significant differences in the nodal size between acute and chronic viral groups(P < 0.01), and between acute hepatitis A and non-hepatitis A viral groups(P < 0.001). In logistical regression analysis, the nodal width still showed strong significance in multivariate analysis(P < 0.0001) to stratify the two groups. The area under the curve of ROC was 0.805, with a sensitivity of 80.9%, a specificity of 68.2%, positive predictive value of 80.92%, negative predictive value of 68.18%, and an accuracy of 76.14%. CONCLUSION: Point-of-care ultrasonography to detect perihepatic nodal change is valuable for clarifying the etiologies in an episode of acute hepatitis flare.
In this study, a high-sensitivity colorimetric membrane array method was used to detect circulating tumor cells (CTC) in the peripheral blood of colorectal cancer (CRC) patients with normal ...perioperative serum carcinoembryonic antigen (CEA) levels. This membrane array method was evaluated as a potential diagnostic and postoperative surveillance tool.
Membrane arrays consisting of a panel of mRNA markers that include human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and CEA mRNA were used to detect CTCs in the peripheral blood of 157 postoperative CRC patients with normal perioperative serum CEA levels and in 80 healthy individuals. Digoxigenin-labeled cDNA were amplified by reverse transcription-PCR from the peripheral blood samples, which were then hybridized to the membrane array. The sensitivity, specificity, and accuracy of membrane arrays for the detection of CTCs were then calculated.
Using the four markers in combination, expression of any three markers or all the four markers in this panel was significantly correlated with the clinicopathologic characteristics, including depth of tumor invasion, lymph node metastasis, tumor-node-metastasis stage, and postoperative relapse (all P < 0.05). The interval between the detection of all four positive molecular markers and subsequent elevated CEA ranged from 3 to 8 months (median 6 months). The expression of all four mRNA markers was an independent predictor for postoperative relapse. CRC patients with all four mRNA markers expression showed a significantly poorer survival rate than those with less than four positive markers.
The constructed membrane array method was helpful in the early prediction of postoperative relapse in CRC patients with normal perioperative serum CEA levels.
Up-regulation of Wnt-1 protein has been reported in hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) tissues and cell lines. It is known to play a ...fundamental role in signaling cancer progression, whereas its prognostic role in HCC remains unexplored.
As a prognostic biomarker, this study analyzed Wnt-1 protein expression in 63 histology-verified HCC patients receiving curative resection. In each paired tumor and nontumor specimen, Wnt-1 levels were semiquantitatively measured by Western blotting and expressed by tumor/nontumor ratio. The data were further correlated with quantitative real-time PCR as well as with beta-catenin and E-cadherin expression by immunohistochemistry. Cumulative tumor recurrence-free survival curves were constructed using the Kaplan-Meier method and compared by the log-rank test.
The results showed that 26 (group I) and 37 (group II) HCC patients had an expression ratio of Wnt-1 > or =1.5 and <1.5, respectively. The amount of Wnt-1 estimated by tumor/nontumor ratio correlated with the results by quantitative real-time PCR. High tumor Wnt-1 expression correlated with enhanced nuclear beta-catenin accumulation, diminished membranous E-cadherin expression, and increased tumor recurrence after curative tumor resection.
These results suggest that Wnt-1 may be used as a predisposing risk factor for HCC recurrence. The use of tumor Wnt-1 as prognostic biomarker may identify patients with HBV- and/or HCV-related HCC patients with a high risk of tumor recurrence who may then benefit from further intensive therapy after surgery.
Autoimmune hepatitis (AIH) is rare in Asian countries compared to the West, and an exceptionally low prevalence was noted previously in Taiwan. Using the revised criteria of the IAIHG, 48 cases of ...AIH patients were diagnosed. All patients were consecutively diagnosed over a period of 5 years. Detailed medical histories including disease onset, hepatitis B and C, alcohol, drugs, blood transfusion, and family history of autoimmune disease were recorded. Clinical manifestations, result of steroid therapy, outcome, and survival rate were investigated and analyzed. Clinical data on AIH patients with cirrhosis and without cirrhosis were compared and analyzed for their outcome. The statistical methods used were Fisher's exact test, Wilcoxon rank sum test, and Kaplan-Meier curve. Forty-eight patients were diagnosed as AIH type 1, with a median age of 58 years and a female:male ratio of 37:11. The most common clinical features at presentation were fatigue, jaundice, and anorexia. Ninety-eight percent of patients were ANA positive, and most of the patients showed elevated values of AST, ALT, serum globulin, and bilirubin. A substantial proportion of patients presented with poor liver function at entry and 35% of patients had liver cirrhosis, with relatively prolonged PT (P=0.001) and poorer outcome (P=0.005) compared to the noncirrhotics. As a whole there was a favorable treatment response and the overall survival rate was 85%. We conclude that the incidence of AIH in Taiwan is much higher than previously presumed and AIH type 1 is the predominant type of the disease. Although a substantial proportion of AIH patients presented with poor hepatic function at entry, as a whole there was a favorable clinical outcome.
This study was designed to determine if existing methods of grading liver function that have been developed in non-Asian patients with cirrhosis can be used to predict mortality in Asian patients ...treated for refractory variceal hemorrhage by the use of the transjugular intrahepatic portosystemic shunt (TIPS) procedure.
Data for 107 consecutive patients who underwent an emergency TIPS procedure were retrospectively analyzed. Acute physiology and chronic health evaluation (APACHE II), Child-Pugh and model for end-stage liver disease (MELD) scores were calculated. Survival analyses were performed to evaluate the ability of the various models to predict 30-day, 60-day and 360-day mortality. The ability of stratified APACHE II, Child-Pugh, and MELD scores to predict survival was assessed by the use of Kaplan-Meier analysis with the log-rank test.
No patient died during the TIPS procedure, but 82 patients died during the follow-up period. Thirty patients died within 30 days after the TIPS procedure; 37 patients died within 60 days and 53 patients died within 360 days. Univariate analysis indicated that hepatorenal syndrome, use of inotropic agents and mechanical ventilation were associated with elevated 30-day mortality (p < 0.05). Multivariate analysis showed that a Child-Pugh score > 11 or an MELD score > 20 predicted increased risk of death at 30, 60 and 360 days (p < 0.05). APACHE II scores could only predict mortality at 360 days (p < 0.05).
A Child-Pugh score > 11 or an MELD score > 20 are predictive of mortality in Asian patients with refractory variceal hemorrhage treated with the TIPS procedure. An APACHE II score is not predictive of early mortality in this patient population.
Background: The aims of the study were to compare (i) the effects of transcatheter arterial embolization on initial hemostasis and the control of rebleeding in the treatment of hemorrhage due to ...hepatic artery injury; and (ii) the outcomes of embolization by different locations.
Methods: Subjects were 32 patients with suspected hepatic artery injury who were transferred to Chi‐Mei Foundation Medical Center for hepatic angiography and embolization. The causes of arterial injury included liver trauma (n = 15) and iatrogenic injury (n = 17). The sites of embolization were classified into four groups: group 1 (n = 8) was classified as ‘combined outlet, target and inlet control’ with embolization of the vascular lesion (target) and hepatic artery distal (outlet) and proximal (inlet) to the vascular lesion simultaneously; group 2 (n = 11) as ‘combined target and inlet control’; group 3 (n = 8) as ‘combined outlet and inlet control’; group 4 (n = 5) as ‘inlet control’ only.
Results: Successful initial hemostasis was achieved in 30 of the 32 patients (93.8%), with two failures, both of which were caused by liver injury and occurred in subjects in group 4. Rebleeding was seen in three patients who had successful initial hemostasis: two of them in group 4 (66.7%) and one in group 1 (12.5%). All rebleedings were successfully managed by repeat embolization. Abscess formation was found in two group 1 patients, and both were successfully managed by percutaneous drainage.
Conclusions: Transcatheter arterial embolization is an effective method for hemostasis in hepatic artery hemorrhage for both patients with liver trauma and patients with iatrogenic injuries to the hepatic artery. Based on this experience, embolization of the vascular lesion and/or the arterial lumen distal to the vascular lesion combined with inlet control is recommended for preventing recurrent hemorrhage, but studies with larger sample sizes will be required to validate this conclusion.
Abstract Acute exacerbations (AEs) of chronic hepatitis B (CH-B) are thought to be the result of breakdown of immune tolerance on the natural history of chronic hepatitis B virus (HBV) infection. ...Immune tolerance to HBV maintained in CH-B patients without hepatitis is under the control of the host's forkhead box p3-expressing regulatory T cells (Tregs). Its breakdown mimics the occurrence of autoimmune diseases. Severe AEs may lead to liver decompensation and mortalities. Consequently, AEs are currently the major therapeutic targets in patient treatment. In this study, we employed the SYFPEITHI scoring system to identify epitopes on HBV core antigen (HBcAg) for the construction of human leukocyte antigen class II tetramers to measure HBcAg-specific Treg frequencies (Tregf). Upregulation of Treg gene profiling accompanied by increased HBcAg-specific Tregf was detected in AE patients with sustained remission (SR) to anti-HBV therapy. Depletion of Tregs from peripheral blood mononuclear cells enhanced proliferation to HBcAg. HBcAg-specific Treg clones inhibited the killing capacity of cytotoxic T lymphocyte clones in an antigen-independent manner. A greater posttherapy increase in HBcAg-specific Tregf correlated with a higher SR rate to anti-HBV therapy. These results suggest that HBcAg-specific Tregs function as suppressor effectors and confer SR to anti-HBV therapy.
Sporadic cases of acute hepatitis E virus (HEV) infection with production of anti-HEV IgM have been reported occasionally in Taiwan despite no reported outbreaks in the past. This study was ...undertaken to determine whether serological markers correlated with virus detection. From 2002 to 2006, 72 reported cases of acute hepatitis E seropositive for anti-HEV IgM in Taiwan were enrolled for investigation. Acute phase serum samples were collected for detection of HEV RNA, HBV DNA, HCV RNA, and GBV-C RNA by PCR. The results showed that viral sequences of HEV, HBV, HCV and GBV-C were detected in 54 (75%), 21 (29.2%), 9 (12.5%), and 22 (30.6%) of cases, respectively. Acute hepatitis A co-infection was excluded in all patients because none were seropositive for anti-HAV IgM and, nine patients (12.5%) did not seroconvert to anti-HEV IgG. These results suggest that serum markers did not correlate completely with viremia in the diagnosis of acute HEV infection. Multiple viruses may co-infect with acute hepatitis E virus in Taiwan. Detection of hepatitis E viremia together with seropositivity for anti-HEV IgM and followed by seroconversion to anti-HEV IgG should be included in the diagnostic criteria for HEV infection. J. Med. Virol. 81:1734-1742, 2009.
A 66-year-old female presented with acute illness of severe hepatic dysfunction. She had a past history of chronic hepatitis of low disease activity. After admission and clinical investigation ...including liver biopsy, it showed an underlying chronic liver disease suggestive of autoimmune hepatitis (AIH) with early liver cirrhosis. Together with other clinical features, this patient was diagnosed as definite AIH type 1 by using the IAIHG (International Autoimmune Hepatitis Group) criteria. During this episode, superinfection by Epstein-Barr virus (EBV) was evidenced by positive PCR (polymerase chain reaction) test, and serial changes of EBV VCA IgM and IgG tests. Severe hepatic impairment was evidenced by markedly elevated AST level 3090 IU/L, high bilirubin level 26.4 mg/dL, and presence of ascites. The patient gradually recovered and liver function improved in agreement with the decline of EBV VCA titers. Immunosuppressive therapy resulted in further improvement of the aminotransferases levels. This is an unusual case of EBV superinfection on pre-existing AIH with early cirrhosis, which caused enhancement of the autoimmune disease process and resulted in severe hepatic decompensation and jaundice. We herein describe the case and briefly review the literature.
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