Simon C.H. Yu

Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system : a study based on 926 patients

The current TNM staging system for patients with hepatocellular carcinoma (HCC) does not include liver function parameters and does not provide a precise prognosis for patients in different risk groups. The objectives of this study were to construct a new prognostic index for patients with hepatocellular carcinoma, the Chinese University Prognostic Index (CUPI), and to compare it with existing staging systems in terms of their ability to classify patients into different risk group.

Adjuvant intra-arterial lipiodol-iodine-131 for resectable hepatocellular carcinoma: a prospective randomised trial

Summary Background Resection of hepatocellular carcinoma is potentially curative, but local recurrence is common. In this prospective randomised trial, we aimed to find out if one dose of postoperative adjuvant intra-arterial iodine-131-labelled lipiodol could reduce the rate of local recurrence and increase disease-free and overall survival. Methods Patients who underwent curative resection for hepatocellular carcinoma and recovered within 6 weeks were randomly assigned one 1850 MBq dose of 131 I-lipiodol or no further treatment (controls). We compared rates of recurrence and disease-free and overall survival (the primary endpoints) between the two groups by intention to treat. We planned an interim analysis when 30 patients (both groups together) had been followed up for a median of 2 years, with the intention of stopping early if the between-group difference in disease-free survival was significant (p=0·029). Findings Between April, 1992, and August, 1997, we recruited 43 patients: 21 received intra-arterial 131 I-lipiodol and 22 received no adjuvant treatment. During a median follow-up of 34·6 (range 14·1–69·7) months, there were six (28·5%) recurrences among the 21 patients in the adjuvant treatment, compared with 13 (59%) in the controls (p=0·04). Median disease-free survival in the treatment and control groups was 57·2 (0·4–69·7) and 13·6 (2·1–68·3) months, respectively (p=0·037). 3-year overall survival in the treatment and control groups was 86·4% and 46·3%, respectively (p=0·039). The interim analysis showed a significant increase in disease-free survival in the treatment group compared with the controls (p=0·01), so we closed the trial early. 131 I-lipiodol had no significant toxic effects. Interpretation In patients with hepatocellular carcinoma, one 1850 MBq dose of intra-arterial 131 I-lipiodol given after curative resection significantly decreases the rate of recurrence and increases disease-free and overall survival.

A Novel, Self-Expanding, Nitinol Stent in Medically Refractory Intracranial Atherosclerotic Stenoses: The Wingspan Study

Background and Purpose— The purpose of this study was to assess the safety and performance of the Wingspan stent system and Gateway percutaneous transluminal angioplasty balloon catheter in the treatment of high-grade, intracranial atherosclerotic lesions in patients who had failed medical therapy. Methods— In this prospective, multicenter, single-arm study, medically refractory patients with a modified Rankin score ≤3 and recurrent symptoms attributable to angiographically demonstrated intracranial stenosis ≥50% in a vessel 2.5 to 4.5 mm in diameter were enrolled. Intracranial lesions were predilated with an undersized Gateway balloon catheter to 80% of the native vessel diameter, followed by deployment of the self-expanding Wingspan stent to facilitate further remodeling of the atherosclerotic plaque and to maintain vessel patency. Neurologic examinations and angiograms were performed at 6 months after the procedure. Results— Among the 45 patients enrolled, the degree of stenosis was reduced from a baseline of 74.9±9.8% to 31.9±13.6% after stenting and 28±23.2% at the 6-month follow-up. The 30-day composite ipsilateral stroke/death rate was 4.5% (2/44); at the 6-month follow-up, the ipsilateral stroke/death rate was 7.0%, the rate for all strokes was 9.7%, and all-cause mortality was 2.3%. Physician-reported follow-up in 43 patients (average of 13 months) conducted outside the study protocol (not adjudicated by the clinical event committee) reported 1 additional ipsilateral stroke. Conclusions— In medically refractory patients with high-grade intracranial atherosclerotic stenoses, a new treatment paradigm involving predilation with an undersized Gateway percutaneous transluminal angioplasty balloon catheter and placement of a self-expanding Wingspan stent system appears to be safe, may facilitate remodeling, and may contribute to favorable angiographic outcomes.

Percutaneous Local Ablative Therapy for Hepatocellular Carcinoma: A Review and Look Into the Future

ObjectiveTo review and compare treatment result for percutaneous local ablative therapy (PLAT) with surgical resection in the treatment of small hepatocellular carcinoma (HCC). Summary Background DataPLAT is indicated for small unresectable HCC localized to the liver. From the use of ethanol to the latest technology of radiofrequency ablation, ablative techniques have been refined and their role in the management of HCC established. This review aims to give an overview of various ablative methods, including their efficacy, indications, and limitations, and also tries to look into the future of clinical trials in PLAT. MethodsThe authors reviewed recent papers in the English medical literature about the use of local ablative therapy for HCC. Focus was given to the results of treatment in terms of local control, progression-free survival, and overall survival, and to compare treatment results with those of surgery. ResultsPLAT for small HCC (<5 cm) with thermal ablation (radiofrequency ablation or microwave coagulation) can achieve effective local control of disease and is superior to ethanol injection. Progressive disease in untreated areas is a common reason for failure. Overall progression-free survival is similar to that of surgical resection. ConclusionsThermal ablation gives good local control of small HCC, is superior to ethanol, and may be comparable to surgical resection in long-term outcome.

Multiple Roles for the Receptor Tyrosine Kinase Axl in Tumor Formation

A focus of contemporary cancer therapeutic development is the targeting of both the transformed cell and the supporting cellular microenvironment. Cell migration is a fundamental cellular behavior required for the complex interplay between multiple cell types necessary for tumor development. We therefore developed a novel retroviral-based screening technology in primary human endothelial cells to discover genes that control cell migration. We identified the receptor tyrosine kinase Axl as a novel regulator of endothelial cell haptotactic migration towards the matrix factor vitronectin. Using small interfering RNA-mediated silencing and overexpression of wild-type or mutated receptor proteins, we show that Axl is a key regulator of multiple angiogenic behaviors including endothelial cell migration, proliferation, and tube formation in vitro. Moreover, using sustained, retrovirally delivered short hairpin RNA (shRNA) Axl knockdown, we show that Axl is necessary for in vivo angiogenesis in a mouse model. Furthermore, we show that Axl is also required for human breast carcinoma cells to form a tumor in vivo. These findings indicate that Axl regulates processes vital for both neovascularization and tumorigenesis. Disruption of Axl signaling using a small-molecule inhibitor will hence simultaneously affect both the tumor and stromal cell compartments and thus represents a unique approach for cancer therapeutic development.

Treatment of pyogenic liver abscess: Prospective randomized comparison of catheter drainage and needle aspiration

This study aims to compare the therapeutic effectiveness of continuous catheter drainage versus intermittent needle aspiration in the percutaneous treatment of pyogenic liver abscesses. Over a 5‐year period, 64 consecutive patients with pyogenic liver abscess were treated with intravenous antibiotics (ampicillin, cefuroxime, and metronidazole) and randomized into two percutaneous treatment groups: continuous catheter drainage (with an 8F multi‐sidehole pigtail catheter); and intermittent needle aspiration (18G disposable trocar needle). There was no statistically significant difference between the two groups regarding patient demographics, underlying coexisting disease, abscess size, abscess number, number of loculation of abscess, the presenting clinical symptoms such as fever, abdominal pain, and pretreatment liver function test. Although not statistically significant, the duration of intravenous antibiotics treatment before percutaneous treatment was longer with the catheter group, and the change of antibiotics after the sensitivity test was more frequent with the needle group. The needle group was associated with a higher treatment success rate, a shorter duration of hospital stay, and a lower mortality rate, although this did not reach statistical significance. In conclusion, this study suggests that intermittent needle aspiration is probably as effective as continuous catheter drainage for the treatment of pyogenic liver abscess, although further proof with a large‐scale study is necessary. Due to the additional advantages of procedure simplicity, patient comfort, and reduced price, needle aspiration deserves to be considered as a first‐line drainage approach. (HEPATOLOGY 2004;39:932–938.)

Intracranial Aneurysms: Midterm Outcome of Pipeline Embolization Device—A Prospective Study in 143 Patients with 178 Aneurysms

PURPOSE To evaluate the midterm clinical and angiographic outcomes after pipeline embolization device (PED) placement for treatment of intracranial aneurysms. MATERIALS AND METHODS This prospective nonrandomized multicenter study was approved by the review boards of all involved centers; informed consent was obtained. Patients (143 patients, 178 aneurysms) with unruptured saccular or fusiform aneurysms or recurrent aneurysms after previous treatment were included and observed angiographically for up to 18 months and clinically for up to 3 years. Study endpoints included complete aneurysm occlusion; neurologic complications within 30 days and up to 3 years; clinical outcome of cranial nerve palsy after PED placement; angiographic evidence of occlusion or stenosis of parent artery and that of occlusion of covered side branches at 6, 12, and 18 months; and clinical and computed tomographic evidence of perforator infarction. RESULTS There were five (3.5%) cases of periprocedural death or major stroke (modified Rankin Scale [mRS] > 3) (95% confidence interval [CI]: 1.3%, 8.4%), including two posttreatment delayed ruptures, two intracerebral hemorrhages, and one thromboembolism. Five (3.5%) patients had minor neurologic complications within 30 days (mRS = 1) (95% CI: 1.3%, 8.4%), including transient ischemic attack (n = 2), small cerebral infarction (n = 2), and cranial nerve palsy (n = 1). Beyond 30 days, there was one fatal intracerebral hemorrhage and one transient ischemic attack. Ten of 13 patients (95% CI: 46%, 93.8%) completely recovered from symptoms of cranial nerve palsy within a median of 3.5 months. Angiographic results at 18 months revealed a complete aneurysm occlusion rate of 84% (49 of 58; 95% CI: 72.1%, 92.2%), with no cases of parent artery occlusion, parent artery stenosis (<50%) in three patients, and occlusion of a covered side branch in two cases (posterior communicating arteries). Perforator infarction did not occur. CONCLUSION PED placement is a reasonably safe and effective treatment for intracranial aneurysms. The treatment is promising for aneurysms of unfavorable morphologic features, such as wide neck, large size, fusiform morphology, incorporation of side branches, and posttreatment recanalization, and should be considered a first choice for treating unruptured aneurysms and recurrent aneurysms after previous treatments. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120422/-/DC1.

Epigenetic Therapy Using Belinostat for Patients With Unresectable Hepatocellular Carcinoma: A Multicenter Phase I/II Study With Biomarker and Pharmacokinetic Analysis of Tumors From Patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group

PURPOSE Epigenetic aberrations have been reported in hepatocellular carcinoma (HCC). In this study of patients with unresectable HCC and chronic liver disease, epigenetic therapy with the histone deacetylase inhibitor belinostat was assessed. The objectives were to determine dose-limiting toxicity and maximum-tolerated dose (MTD), to assess pharmacokinetics in phase I, and to assess activity of and explore potential biomarkers for response in phase II. PATIENTS AND METHODS Major eligibility criteria included histologically confirmed unresectable HCC, European Cooperative Oncology Group performance score ≤ 2, and adequate organ function. Phase I consisted of 18 patients; belinostat was given intravenously once per day on days 1 to 5 every 3 weeks; dose levels were 600 mg/m(2) per day (level 1), 900 mg/m(2) per day (level 2), 1,200 mg/m(2) per day (level 3), and 1,400 mg/m(2) per day (level 4). Phase II consisted of 42 patients. The primary end point was progression-free survival (PFS), and the main secondary end points were response according to Response Evaluation Criteria in Solid Tumors (RECIST) and overall survival (OS). Exploratory analysis was conducted on pretreatment tumor tissues to determine whether HR23B expression is a potential biomarker for response. RESULTS Belinostat pharmacokinetics were linear from 600 to 1,400 mg/m(2) without significant accumulation. The MTD was not reached at the maximum dose administered. Dose level 4 was used in phase II. The median number of cycles was two (range, one to 12). The partial response (PR) and stable disease (SD) rates were 2.4% and 45.2%, respectively. The median PFS and OS were 2.64 and 6.60 months, respectively. Exploratory analysis revealed that disease stabilization rate (complete response plus PR plus SD) in tumors having high and low HR23B histoscores were 58% and 14%, respectively (P = .036). CONCLUSION Epigenetic therapy with belinostat demonstrates tumor stabilization and is generally well-tolerated. HR23B expression was associated with disease stabilization.

Flow diverters for treatment of intracranial aneurysms: current status and ongoing clinical trials.

The ultimate treatment goal for intracranial aneurysms is to reconstruct the vessel wall and correct the hemodynamic disturbance. A flow diverter is a stent placed in the parent artery to reduce blood flow in the aneurysm sac to the point of stagnation, gradual thrombosis, and neointimal remodeling to maintain outflow in the side branches and perforators. Here, we review the two commercially available flow diverters, the Pipeline Embolization Device (PED) and the SILK flow diverter (SFD). The rates of severe hemorrhagic complications have been reported to be 2% for the PED and 0.8% for the SFD. The results of studies completed thus far show that endovascular reconstruction with flow diverters is an effective treatment of wide-necked, fusiform, large, and giant unruptured intracranial aneurysms, with 5% to 10% of patients experiencing permanent major morbidity and mortality. The results of ongoing studies may resolve whether flow diverters can replace coil embolization for the treatment of all, or selected, intracranial aneurysms.

Adjuvant intra-arterial iodine-131-labeled lipiodol for resectable hepatocellular carcinoma: a prospective randomized trial-update on 5-year and 10-year survival.

Objective:In this prospective randomized trial, we attempted to find out if 1 dose of postoperative adjuvant intra-arterial iodine-131-labeled lipiodol could reduce the rate of local recurrence, and increase disease-free and overall survival for patients with hepatocellular carcinoma (HCC). This study evaluated the long-term outcome. Background:Resection of HCC is potentially curative, but local recurrence is common. However, there is currently no effective adjuvant therapy. Early results after closing the trial (Lau et al. Lancet 1999;353:797–801) showed that 1 dose of intra-arterial 131I-lipiodol given after curative resection significantly decreased the rate of recurrence, and increased disease-free and overall survival. Methods:Patients who underwent curative resection for HCC and recovered within 6 weeks were randomly assigned one 1850 MBq dose of 131I-lipiodol or no further treatment (controls). We compared rates of recurrence, and long-term disease-free and overall survival (the primary endpoints) between the 2 groups by intention-to-treat. Results:Between April 1992 and August 1997, we recruited 43 patients: 21 were randomized to receive intra-arterial 131I-lipiodol and 22 to receive no adjuvant treatment. 131I-lipiodol had no significant toxic effects. During a median follow-up of 66 (range, 3–198) months, there were 10 (47.6%) recurrences among the 21 patients in the adjuvant treatment group, compared with 14 (63.6%) in the control group (P = 0.29). The actuarial 5-year disease-free survival in the treatment and control groups was 61.9% and 31.8%, respectively (P = 0.0397). The actuarial 5-year overall survival in the treatment and control groups was 66.7% and 36.4%, respectively (P = 0.0433). The actuarial 7-year disease-free survival in the treatment and control groups was 52.4% and 31.8%, respectively (P = 0.0224). The actuarial 7-year overall survival in the treatment and control groups was 66.7% and 31.8%, respectively (P = 0.0243). The actuarial 10-year disease-free survival in the treatment and control groups was 47.6% and 27.3%, respectively (P = 0.0892). The actuarial 10-year overall survival in the treatment and control groups was 52.4% and 27.3%, respectively (P = 0.0905). Conclusions:In patients with HCC, adjuvant intra-arterial 131I-lipiodol after curative liver resection provided survival benefit on the disease-free survival and overall survival, although the difference became statistically insignificant at 8 years after randomization.