Subgroup analysis of efficacy and safety of orantinib in combination with TACE in Japanese HCC patients in a randomized phase III trial (ORIENTAL).

A randomized, phase III trial of orantinib in combination with transcatheter arterial chemoembolization (TACE) did not prolong overall survival (OS) over placebo (ORIENTAL study). A subgroup analysis was conducted to evaluate the efficacy and safety of orantinib in Japanese patients enrolled in the ORIENTAL study. The data of Japanese patients from this study were analyzed. The overall survival (OS), time to progression (TTP), and time to TACE failure (TTTF) were compared between orantinib and placebo arms using stratified log-rank test. Since TTTF in patients with Barcelona Clinic Liver Cancer stage B (BCLC-B) showed favor outcome in this study, the OS and TTTF according to BCLC staging system were also analyzed. The subgroup analysis consisted of 219 and 213 patients in the orantinib and placebo arms. Median OS was 32.5 vs 33.0 months (p = 0.906), median TTP was 4.7 vs 3.1 months (p = 0.011), and median TTTF was 25.3 vs 18.2 months (p = 0.160) in the orantinib and placebo groups, respectively. Patients with BCLC-B in the orantinib and placebo groups showed a median OS of 33.7 and 30.1 months, respectively (p = 0.260), while the corresponding median TTTF were 25.3 and 14.0 months (p = 0.125). The Japanese population safety profile was similar to all over population in the ORIENTAL study. No significant differences were observed in the OS and TTTF though the TTP was significantly improved in the orantinib arm. The OS and TTTF showed a tendency to be prolonged following orantinib treatment of Japanese HCC patients with BCLC-B in the ORIENTAL study.

Autoimmune Hepatitis with Concomitant Idiopathic Thrombocytopenic Purpura Diagnosed by Transjugular Liver Biopsy.

Patients with autoimmune hepatitis (AIH) may sometimes have concomitant idiopathic thrombocytopenic purpura (ITP). Severe thrombocytopenia in ITP interferes with percutaneous liver biopsy for pathological diagnosis of AIH. Here, we report a case of AIH with ITP in a 63-year-old woman. The patient presented to our hospital with liver dysfunction and thrombocytopenia. For histological examination, transjugular liver biopsy (TJLB) was performed, leading to a diagnosis of AIH. Corticosteroids treatment led to an improvement in her liver enzyme levels and platelet count. In conclusion, patients with AIH may sometimes have concomitant ITP. TJLB was effective for making the diagnosis of AIH with severe thrombocytopenia due to ITP.

Which system is better to predict prognosis of patients with hepatocellular carcinoma treated by transcatheter arterial chemoembolization as initial therapy? Comparison between CLIP and JIS in a Japanese population.

Background There has been no consensus as to which system, either the Cancer of the Liver Italian Program (CLIP) or the Japan Integrated Staging (JIS) system, is suitable to predict the prognosis of hepatocellular carcinoma (HCC) patients who underwent transcatheter arterial chemoembolization (TACE) as initial therapy. Purpose To retrospectively compare the usefulness of CLIP and JIS in predicting and stratifying the prognosis of HCC patients treated by TACE. Material and Methods Between 1995 and 2005, consecutive 728 patients with untreated HCC who underwent TACE in our institute were selected for this study. The survival rate and its prognostic factors were assessed by multivariate analysis. Patients were stratified according to the two systems, and their survival rates between the scores were compared. Results The mean follow-up period was 1689 days. The 1-year, 3-year, 5-year, and 10-year survival rates were 83.1%, 55.1%, 34.7%, and 12.8%, respectively. Both systems stratified the prognosis of patients well, but was slightly better in CLIP as compared to in JIS. As for multivariate factor analysis, less severe Child-Pugh classification ( P < 0.001), simple tumor morphology ( P < 0.001), absence of portal vein invasion ( P < 0.001), and lower alpha-fetoprotein (AFP) level ( P < 0.001) were suggested to be independent indicators for favorable survival rate. All of these independent factors were included in CLIP, whereas JIS lacked AFP level. Furthermore, the likelihood χ2-test value was higher, and the Akaike information criterion value was lower for CLIP than for JIS. Conclusion CLIP is more suitable than JIS for predicting prognosis of patients with HCC who would undergo TACE in a Japanese population.

Upregulation of des-gamma-carboxy-prothrombin after portal vein embolization in a cirrhotic patient with hepatocellular carcinoma.

A 73-year-old female with hepatocellular carcinoma (HCC) received percutaneous transhepatic portal vein embolization (PTPE) before extensive right lobe hepatectomy. Serum levels of des-gamma-carboxy-prothrombin (DCP) were increased and remained at a high level until hepatectomy. Immunohistochemical examination revealed that an increased expression of DCP was demonstrated not only in HCC tissues, but also in the non-cancerous liver of the right lobe, where portal blood flow was blocked off as a result of PTPE. The serum level of DCP is known to be greatly increased in patients with HCC accompanied by portal vein invasion. We speculate that this increased DCP level is caused by both increased DCP production in HCC tissue and the surrounding non-cancerous liver, where portal flow is blocked off as a result of portal invasion by HCC.

Predictive factors related to the efficacy of pelvic arterial embolization for postpartum hemorrhage: a retrospective analysis of 21 cases.

OBJECTIVE: This retrospective study aimed to determine the predictive factors for the efficacy of pelvic arterial embolization for postpartum hemorrhage. MATERIALS AND METHODS: Twenty-one patients who underwent pelvic arterial embolization for postpartum hemorrhage of >1000 mL between September 2006 and September 2011 were enrolled in this study. The patients were divided into two subgroups according to the blood loss and time from the end of pelvic arterial embolization to complete hemostasis: good-response (16 patients) and poor-response groups (5 patients). The following predictive factors were compared between the groups: (1) patient characteristics; (2) blood loss; (3) time between delivery (or onset of bleeding) and pelvic arterial embolization; (4) obstetrical disseminated intravascular coagulation score comprising clinical background, clinical signs, and laboratory data; (5) individual disseminated intravascular coagulation score; (6) shock index; and (7) laboratory data including platelet count, prothrombin time-international normalized ratio, fibrinogen, fibrin degradation products, and antithrombin-III at the time of pelvic arterial embolization. RESULTS: In the poor-response group, the obstetrical and individual disseminated intravascular coagulation scores and prothrombin time-international normalized ratio were higher than those in the good-response group (p < 0.05). Platelet count, fibrinogen, and fibrin degradation products were lower than those in the good-response group (p < 0.05). All obstetrical disseminated intravascular coagulation scores in the poor-response group were >9 points. CONCLUSION: The efficacy of pelvic arterial embolization is related to the presence or absence of coagulation disorders. When the obstetrical disseminated intravascular coagulation score is high (>9 points), the efficacy may be poor.

Prognosis of patients with intermediate-stage hepatocellular carcinomas based on the Child-Pugh score: subclassifying the intermediate stage (Barcelona Clinic Liver Cancer stage B).

PURPOSE: Retrospective evaluation of intermediate-stage hepatocellular carcinoma (HCC) patient survival after undergoing chemoembolization based on the Child-Pugh score. MATERIALS AND METHODS: Data of intermediate-stage HCC patients undergoing chemoembolization were gathered from 43 centers in Japan. Overall survival rates were compared with Child-Pugh scores. RESULTS: Of the 329 patients examined in this study, Child-Pugh scores were 5 (CP-5) in 136 patients (41.3%), 6 (CP-6) in 101 patients (30.7%), 7 (CP-7) in 58 (17.7%), 8 (CP-8) in 22 (6.7%), and 9 (CP-9) in 12 (3.6%). Two-year survival rates were 77.5% in CP-5 patients (p = 0.047 vs. CP-6), 65.1% in CP-6 patients (p = 0.038 vs. CP-7), 51.3% in CP-7 patients (p = 0.30 vs. CP-8, p = 0.034 vs. CP-9), 50.3% in CP-8 patients (p = 0.0065 vs. CP-9), and 16.7% in CP-9 patients. Two-year survival rates were 77.2% in 139 patients meeting the 4 tumors of 7 cm criterion with Child-Pugh class A (B1) (p < 0.0001 vs. B2), 59.5% in 178 patients other than B1 and B3 (B2) (p = 0.0014 vs. B3), and 16.7% in 12 patients with Child-Pugh score 9 (B3). CONCLUSION: The Child-Pugh score is a useful prognostic factor to stratify intermediate-stage HCC patients.

The successful detection of postpartum unruptured vaginal pseudoaneurysm using ultrasonography: a case report.

INTRODUCTION: We report the first case of the successful detection of postpartum unruptured vaginal pseudoaneurysm using power- and pulsed-Doppler ultrasonography after delivery. CASE DESCRIPTION: A 38-year-old primiparous Japanese woman had a vaginal laceration with pulsatile bleeding after delivering by vacuum extraction. Transvaginal ultrasonography of the repaired vaginal wall showed an 18 × 20 mm hematoma within which a 6 × 7 mm pulsating anechoic mass was detected. Power-Doppler ultrasonography showed blood flow signals in the anechoic mass. Arterial waveforms detected in pulsed-Doppler mode were suggestive of unruptured pseudoaneurysm. Careful monitoring with contrast-enhanced computed tomography showed an increase in the size of the pseudoaneurysm on the fourth postpartum day. On the sixth postpartum day, massive vaginal bleeding occurred. Emergency angiography revealed strong staining with extravasation from the left vaginal artery, confirming the diagnosis of pseudoaneurysm. Embolization for hemostasis was successfully performed. DISCUSSION AND EVALUATION: As far as we know, our case is the first in which an unruptured vaginal pseudoaneurysm was diagnosed using ultrasonography. The differential diagnoses of pseudoaneurysm are arteriovenous malformations including arteriovenous fistula. This case had the typical ultrasonographic patterns of pseudoaneurysm in which the presence of one or two cystic masses in B-mode and color- and/or power-Doppler flow signals was demonstrated along with high-resistance arterial flow waveforms in pulsed-Doppler mode. Sequential examinations of contrast-enhanced CT showed ongoing development of the pseudoaneurysm. In retrospect, we could have performed angiography for embolization when the unruptured pseudoaneurysm was diagnosed, or at the latest when ongoing development of the pseudo-aneurysm was recognized, irrespective of whether symptoms were present. CONCLUSIONS: Ultrasonography is a non-invasive and clinically useful modality in the differential diagnosis of pseudoaneurysm. Contrast-enhanced computed tomography with or without ultrasonography can be useful for sequential monitoring of the size of unruptured pseudoaneurysms.

Focal fatty change in the liver that developed after cholecystectomy.

Focal fatty change of the segment IV of the liver has been attributed to local systemic venous inflow replacing the portal venous supply, which could develop or be accentuated after gastrectomy. However, focal fatty change due to aberrant pancreaticoduodenal vein that developed after cholecystectomy has never been reported. We report a 30-year-old man with such a rare lesion, which was initially misdiagnosed as a hepatocellular carcinoma, but was confirmed on computed tomography during selective gastroduodenal arteriography. The lesion disappeared 12 mo later without any intervention.

Pilot Study of Hepatic Arterial Infusion Chemotherapy with Interferon-beta and 5-fluorouracil: A New Chemotherapy for Patients with Advanced Hepatocellular Carcinoma.

BACKGROUND/AIMS: The present pilot study aimed to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) with interferon-beta (IFN-ß) and 5-fluorouracil (5-FU) in patients with advanced hepatocellular carcinoma (HCC). METHODOLOGY: We studied 10 patients with advanced HCC and who were unresponsive to previous HAIC using low-dose 5-FU and cisplatin. The median age was 67 years. Eight patients had portal vein tumor thrombosis and four patients had extrahepatic metastasis. Using a drug delivery system, patients were treated with HAIC of IFN-ß (600 MIU/body, three times/week) and 5-FU (250 mg/body, five times/week). Chemotherapy was repeated consecutively for 2 weeks every 4 weeks. RESULTS: Six (60%) patients had a decrease in tumor markers alpha-fetoprotein (APP) or des-gamma-carboxy prothrombin (DCP). The median overall survival was 108 days and the 1-year survival rate was 10.0%. Univariate analysis showed two significant prognostic factors related to long-term survival for more than 60 days: a decrease in APP or DCP 4 weeks after treatment (P = 0.035) and no extra hepatic metastasis (P = 0.035). Severe hepatic injury was not observed. CONCLUSIONS: HAIC with IFN-ß and 5-PU exerts modest antitumor effects and poses no particular safety concerns. This may be a new promising strategy for treatment of advanced HCC.

A randomised phase II study of TSU-68 in patients with hepatocellular carcinoma treated by transarterial chemoembolisation.

BACKGROUND: TSU-68 is an antitumour drug that acts by inhibiting angiogenesis. We evaluated the efficacy and safety of TSU-68 in combination with transarterial chemoembolisation (TACE) in patients with intermediate-stage hepatocellular carcinoma (HCC). PATIENTS AND METHODS: In this multicenter, open-label phase II study, we randomised patients with HCC who had been treated with a single session of TACE to receive either 200mg TSU-68 twice daily or no medication. The primary end-point was progression-free survival (PFS). RESULTS: A total of 103 patients were enrolled. Median PFS was 157.0days (95% confidence interval [CI], 124.0-230.0days) in the TSU-68 group and 122.0days (95% CI, 73.0-170.0days) in the control group. The hazard ratio was 0.699 (95% CI, 0.450-1.088). Fatigue, elevated aspartate aminotransferase (AST), elevated alkaline phosphatase, oedema and anorexia were more frequent in the TSU-68 group than in the control group. The most frequent grade 3/4 adverse events were AST elevation (46% of patients in the TSU-68 group and 12% of controls) and alanine aminotransferase elevation (26% of patients in the TSU-68 group and 8% of controls). Two deaths, grade 5 hepatic failure and melena were noted in the TSU-68 group. CONCLUSION: This exploratory study shows a trend towards prolonged PFS with TSU-68 treatment after a single session of TACE, but this observation was not statistically significant. The two deaths were related to the study treatment. These results suggest that further examination of the study design is necessary to determine whether TSU-68 has any clinical benefits when combined with TACE.

Warming effect on miriplatin-lipiodol suspension for potential use as a chemotherapeutic agent for transarterial chemoembolization of hepatocellular carcinoma: In vitro study.

AIM: To elucidate whether warming may reduce the viscosity of miriplatin-lipiodol suspension (MPT/LPD) and also the injection pressure through microcatheters, for potential use as a chemotherapeutic agent of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). METHODS: Viscosity of MPT/LPD prepared at on-label dose was measured in vitro at 25°C, 30°C, 40°C, 50°C and 60°C using capillary tube method. Reproducibility of viscosity change was also tested. Injection pressure through two different commercially available microcatheters was measured using a rheometer. Data sampling was performed at least twice for each measurement. RESULTS: Viscosity of MPT/LPD was significantly reduced as the temperature was elevated (R(2) = 0.9586, P < 0.0001, Pearson's correlation); at 40°C, it was almost half of that at room temperature (25°C). Repeated warming and cooling down of MPT/LPD revealed good reproducibility of viscosity change. Injection pressure through either microcatheter showed significant reduction when MPT/LPD was warmed (P < 0.05, Spearman's rank correlation coefficient). CONCLUSION: The viscosity and injection pressure through microcatheters of MPT/LPD was confirmed to reduce significantly as the temperature is elevated. MPT/LPD warmed to 40°C has half viscosity as that at room temperature and is considered suitable for clinical use. Warming MPT/LPD may have potential to facilitate the procedure of TACE for HCC.

Rupture of jejunal varices treated with balloon-occluded retrograde transvenous obliteration.

Bleeding from varices arising from outside of the gastroesophageal region is rare. We report a case of ruptured jejunal varices, successfully treated with B-RTO. Our patient was a 60-year-old man with alcoholic cirrhosis who had undergone total gastrectomy two years before he visited our clinic with tarry stool and hypotensive shock. Results of 3DMDCT clearly showed variceal formation at the jejunal loop around the anastomotic site and abdominal wall as well as the extensive epigastric outflow tract, which finally drained into the left femoral vein. B-RTO was carried out via right femoral approach, using a microcatheter system. The varices disappeared, and the patient remained asymptomatic 18 months after the treatment.

Pseudolesion of the liver on gadoxetate disodium-enhanced MR images obtained after transarterial chemoembolization for hepatocellular carcinoma: clinicoradiologic correlation.

OBJECTIVE: The purpose of this study was to elucidate the clinicoradiologic characteristics of pseudolesions of the liver in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) as observed on gadoxetate disodium-enhanced MR images. A particular interest was correlation between the pseudolesion characteristics and TACE-MRI interval, during which sequential changes in pseudolesions may be revealed after TACE. MATERIALS AND METHODS: Forty-eight patients with HCC who underwent gadoxetate disodium-enhanced MRI after TACE were retrospectively recruited. Pseudolesions were defined as areas of decreased signal intensity in treated areas on hepatocellular phase images that were confirmed to be nontumorous areas at follow-up. The prevalence and MRI features of pseudolesions were correlated with various clinical parameters, including TACE-MRI interval. RESULTS: Pseudolesions were found in 14 patients (29%). Within 1 month of TACE, the prevalence of pseudolesions was 83%. All of the pseudolesions had arterial enhancement, mimicking residual HCC. After 1 month, the prevalence of pseudolesions decreased, and these pseudolesions tended to exhibit no abnormality in any sequence other than the hepatocellular phase. Results of multivariate analysis suggested that size of HCC (p < 0.0001), duration of postembolization syndrome (p = 0.012), and TACE-MRI interval (p = 0.038) are independent indicators of the presence of pseudolesions. CONCLUSION: The prevalence and appearance of pseudolesions differ at different intervals from TACE. Radiologists need to recognize the clinicoradiologic characteristics to differentiate pseudolesions from true residual or recurrent HCC.

Papillary renal cell carcinoma with extensive paraaortic nodal metastasis mimicking malignant lymphoma.

A 52-year-old woman with abdominal distension underwent computed tomography (CT) that demonstrated extensive paraaortic lymphadenopathy and a right renal mass. Compared to the renal cortex, the lesions exhibited low signal intensity on T(1)- and T(2)-weighted images and high intensity on diffusion-weighted magnetic resonance (MR) images. We suspected malignant lymphoma and performed excisional biopsy, which revealed metastatic papillary renal cell carcinoma. Retrospectively, significantly reduced signal on in-phase chemical shift MR images compared to out-of-phase images suggested the presence of intratumoral hemosiderin, a characteristic finding of this entity.

Pseudolesion of the liver observed on gadoxetate disodium-enhanced magnetic resonance imaging obtained shortly after transarterial chemoembolization for hepatocellular carcinoma.

The purpose of this report was to describe pseudolesions of the liver that mimicked residual hypervascular hepatocellular carcinoma (HCC), as observed on gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) obtained shortly after transarterial chemoembolization (TACE). Between June 2008 and December 2008, three patients underwent MRI within 12 days after TACE to rule out remaining viable cancerous tissue or to assess the treatment effect. In all three patients, nontumorous liver tissue adjacent to the treated HCC exhibited focal arterial enhancement on dynamic phase and subsequent diminished uptake of gadoxetate disodium on hepatocellular phase images, which mimicked residual HCC. All three patients had mild postembolization syndrome at the time of EOB-MRI and showed no evidence of residual or recurrent tumors on follow-up. The findings of these areas may represent transient focal hyperemia and damage to the liver cell function caused by TACE. Radiologists should be aware that EOB-MRI obtained shortly after TACE may show pseudolesions around the treated tumors and should not mistake them for residual or recurrent tumors.

Clinico-roentogenologic findings in hepatocellular carcinoma fed by the right inferior phrenic artery at the initial chemoembolization.

BACKGROUND/AIMS: The purpose of this study was to investigate factors that may predict the development of the right inferior phrenic artery (RIPA) as a feeding artery in hepatocellular carcinoma (HCC) at the initial (first session) chemoembolization. METHODOLOGY: From January 1997 to June 2002, 538 patients with HCC were treated with a first session of transcatheter arterial chemoembolization (TACE). Twenty-six of these patients underwent TACE via both the Hepatic artery (HA) and RIPA at the initial TACE. We retrospectively analyzed the Child-Pugh's classification, macroscopic tumor type, location and size of the tumor, past history of intervention, complications and outcome in these 26 patients with HCC fed by the RIPA. RESULTS: The incidence of HCC fed by both the HA and RIPA at the initial TACE was 4.8% (26/538 patients). No hepatic arterial occlusion or attenuation was found in any of these 26 patients. All of the tumors abutted the diaphragm and were located at the surface of the liver. All of the tumors that were larger than 5 cm in diameter protruded from the surface of the liver. Seven of the 9 patients with HCC smaller than 5 cm in diameter had a defect in the liver capsule induced by previous intervention for the treatment of a different tumor, such as hepatic resection or percutaneous ablation therapy. There were no serious complications after TACE. CONCLUSION: The RIPA can be an extrahepatic feeding artery for HCC even at the initial TACE. A high incidence of HCC fed by the RIPA was recognized in cases in which a large tumor protruded from the surface of the liver, and when the liver capsule was damaged due to previous intervention such as hepatic resection or in ruptured HCC even at the initial TACE.

Successful embolization of pancreaticoduodenal artery pseudoaneurysm in a patient with common hepatic arterial occlusion after modified pancreatoduodenectomy with preservation of arteries in the head of pancreas.

Pancreaticoduodenectomy (PD) with preservation of the arcade in the head of the pancreas was performed in a 73-year-old male with ampullary adenocarcinoma associated with occlusion of the common hepatic artery (CHA) in another hospital. He developed active bleeding from his drain site, at 18 days after the operation. He was transferred to our hospital for emergent embolization. Celiac arteriogram showed complete occlusion of the CHA, posterior superior pancreaticoduodenal artery (PSPDA) pseudoaneurysm 1.7 cm in diameter and development of an enlarged tortuous dorsal pancreatic artery (DPA), posterior pancreatico-duodenal artery (PPDA), and gastroduodenal artery (GDA). Complete hemostasis was obtained without major complications by the transcatheter arterial embolization (TAE) with microcoils.

Multicenter evaluation of a whole-blood filter that saves platelets.

BACKGROUND: Whole-blood (WB) leukoreduction filters in current use retain the majority of PLTs. A new whole-blood filter, which retains significantly fewer of the PLTs (or saves PLTs [WB-SP]), has been developed. The performance characteristics of the WB-SP filter have been evaluated in a multicenter study. STUDY DESIGN AND METHODS: A total of 617 units of WB was collected into quadruple bag sets with an integrated WB-SP filter, leukoreduced, and processed into leukoreduced RBCs (LR-RBC), plasma (LR-PL), and buffy coats (LR-BC) from which, pooled, leukoreduced, PLT concentrates (LR-PCs) were produced. Recovery, yield, and residual WBCs were assessed in prepared blood components. RESULTS: The median residual WBC number in the LR-RBCs was 0.05 x 10(6) (range, <0.05-3.8), exceeding 1 x 10(6) in 0.6 percent of the units. Median Hb content in LR-RBC was 50 g (range, 34-72), reflecting a final RBC recovery of 81 +/- 6 percent. The median WBC content of the LR-PC was 0.05 x 10(6) (range, <0.05-0.28), with none exceeding 1 x 10(6). The median PLT content of the LR-PC, per individual donation, was 6.4 x 10(10) (range, 4.1-10.7), representing a final recovery of 62 +/- 10 percent. The mean FVIII activity was 104 +/- 25 percent and 83 +/- 11 percent in plasma separated from fresh or overnight stored WB, respectively. CONCLUSION: Use of the WB-SP filter makes it possible to obtain three leukoreduced blood components with only one filtration step. The WB-SP filter showed good leukoreduction performance and recovery of all blood components including PLTs.