Variant in C-terminal region of intestinal alkaline phosphatase associated with benign familial hyperphosphatasaemia.

BACKGROUND: A genetic diagnosis has been rarely performed in benign familial hyperphosphatasaemia, and molecular mechanism largely remains unclear. OBJECTIVES: We encountered a case with benign familial hyperphosphatasaemia of intestinal alkaline phosphatase (IAP). To elucidate the molecular mechanism, we performed ALPI gene sequencing and in vitro protein expression analysis. METHODS: ALPI gene was sequenced by long-range PCR and massively parallel sequencing. The soluble and membrane-bound ALP activities of the cultured cell line, transfected with the wild-type or variant-type ALPI gene were analysed by a glycosylphosphatidylinositol (GPI)-cleaving assay. RESULTS: We identified a deletion-insertion variant in the C-terminal end of the ALPI gene. This variant causes the attenuation of the hydrophobicity in GPI-anchor signal of IAP. An in vitro GPI-cleaving assay demonstrated that the membrane-bound IAP was greatly decreased, whereas the soluble IAP was increased, in the variant IAP. CONCLUSIONS: The C-terminal variant in ALPI causes the benign familial hyperphosphatasaemia of IAP by the attenuation of the membrane-binding capability.

[Intra-operative Acute Aortic Dissection during Aortic Root Reimplantation and Mitral Valve Reconstruction Surgery in a Patient with Marfan Syndrome;Report of a Case].

In patients with Marfan syndrome, cardiovascular complication due to aortic dissection represents the primary cause of death. Iatrogenic acute aortic dissection during cardiac surgery is a rare, but serious adverse event. A 51-year-old woman with Marfan syndrome underwent elective aortic surgery and mitral valve reconstruction surgery for the enlarged aortic root and severe mitral regurgitation. We replaced the aortic root and ascending aorta based on reimplantation technique. During subsequent mitral valve reconstruction, we found the heart pushed up from behind. Trans-esophageal echocardiography revealed a dissecting flap in the thoracic descending aorta. There was just weak signal of blood flow in the pseudolumen. We did not add any additional procedures such as an arch replacement. Cardio-pulmonary bypass was successfully discontinued. After protamine sulfate administration and blood transfusion, blood flow in the pseudolumen disappeared. The patient was successfully discharged from the hospital on 33th postoperative day without significant morbidities.

Efficacy of sorafenib in intermediate-stage hepatocellular carcinoma patients refractory to transarterial chemoembolization.

OBJECTIVE: We compared the benefits of sorafenib therapy with continued transarterial chemoembolization (TACE) in TACE-refractory patients with intermediate-stage hepatocellular carcinoma (HCC). METHODS: This retrospective study reviewed intermediate-stage HCC patients who underwent the first TACE. Patients were defined as TACE-refractory and divided into two cohorts: (1) patients who switched from TACE to sorafenib and (2) those who continued TACE. We evaluated the patient overall survival (OS) and time to disease progression (TTDP; the time patients reached Child-Pugh C or developed advanced-stage HCC). RESULTS: A total of 509 patients with HCC underwent TACE. Of 249 intermediate-stage HCC patients undergoing the first TACE, 122 were deemed refractory. At the time they were identified as refractory, 20 patients converted to sorafenib, whereas 36 patients continued TACE. We excluded patients with Child-Pugh scores of ≥ 8, those with advanced-stage HCC, those who had undergone hepatic arterial infusion chemotherapy or other systemic therapy, and those treated with best supportive care alone. The median TTDP and OS were 22.3 and 25.4 months, respectively, in the conversion group, and 7.7 and 11.5 months, respectively, in the continued group (p = 0.001 and p = 0.003, respectively). CONCLUSIONS: It is possible that sorafenib conversion might prolong OS and TTDP in TACE-refractory patients with intermediate-stage HCC.

A randomized phase II trial of intra-arterial chemotherapy using SM-11355 (Miriplatin) for hepatocellular carcinoma.

BACKGROUND: SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC) via administration into the hepatic artery as a sustained-release suspension in iodized oil. We conducted a multicenter phase II trial in patients with HCC to evaluate the efficacy and safety of SM-11355, using a Zinostatin stimalamer suspension in iodized oil as a reference. METHODS: Patients with unresectable HCC were randomized 2:1 to receive administration of the SM-11355 or Zinostatin stimalamer suspension into the hepatic artery. A second injection was given 4-12 weeks later. Efficacy was evaluated by CT 3 months after treatment and categorized as therapeutic effect (TE) V to I, where TE V was defined as disappearance or 100% necrosis of all treated tumors. RESULTS: A total of 122 patients were evaluated for efficacy and toxicity (SM-11355, n = 83; Zinostatin stimalamer, n = 39). Baseline characteristics were similar in the two groups. The TE V rates were 26.5% (22/83) and 17.9% (7/39) in the SM-11355 and Zinostatin stimalamer groups, respectively. In the SM-11355 group,the most frequent drug-related adverse events (AEs) of ≥ grade 3 were elevated AST, elevated ALT, thrombocytopenia, and hyperbilirubinemia. The AEs with the largest difference between the two groups (SM-11355 vs. Zinostatin stimalamer) were hepatic vascular injury (0 vs. 48.4%) and eosinophilia (84.3 vs. 41.0%). The 2-year and 3-year survival rates were 75.9% vs. 70.3% and 58.4% vs. 48.7%, respectively. CONCLUSIONS: The results suggest that SM-11355 in iodized oil has similar efficacy to Zinostatin stimalamer and that repeated dosing of SM-11355 is possible without hepatic vascular injury in cases of relapse.

Rikkunshito improves the symptoms in patients with functional dyspepsia, accompanied by an increase in the level of plasma ghrelin.

BACKGROUND/AIMS: Functional dyspepsia (FD) is a common disease but there is no established treatment. Rikkunshito is a traditional Japanese medicine that is widely used for treating upper gastrointestinal symptoms and its effect on ghrelin is of great interest. The aim of this study was to investigate the effect of rikkunshito on upper gastrointestinal symptoms and the levels of acylated ghrelin (AG) in patients with FD. METHODOLOGY: This study was a paralleled, randomized controlled trial. Patients were treated with either rikkunshito (group R) or domperidone (group D) for 4 weeks. The overall change in dyspeptic symptoms was evaluated by the GSRS (Gastrointestinal Symptom Rating Scale) questionnaire score. RESULTS: 27 patients were enrolled. There was a significant improvement in dyspeptic symptoms in both groups, based on the GSRS score. AG levels increased significantly in plasma in group R at 2 weeks after treatment (paired t-test, p<0.05). The improvements of reflux (Pearson's correlation test, r=-0.73, p=0.04) and indigestion (r=-0.76, p=0.03) symptoms in group R showed a good correlation with the increase of AG. CONCLUSIONS: Rikkunshito improves upper gastrointestinal symptoms in patients with FD, accompanied by an increase in the levels of AG.

Contrast-enhanced ultrasound with perflubutane microbubble agent: evaluation of differentiation of hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of contrast-enhanced ultrasound with a perflubutane microbubble agent in the assessment of cellular differentiation of hepatocellular carcinoma (HCC). SUBJECTS AND METHODS: Continuous harmonic imaging with a low mechanical index (0.21-0.30) was performed 1, 5, and 10 minutes after i.v. contrast injection (0.0075 mL/kg). Tumor enhancement was evaluated by both subjective reading and objective intensity analysis based on the signal distribution in the nontumor parenchyma. Tumor vascularity was assessed with CT during hepatic arteriography. RESULTS: Sixty-four patients with 77 histologically proved HCCs (mean greatest dimension, 19.1 ± 5.3 mm)--six poorly differentiated HCCs, 45 moderately differentiated HCCs, and 26 well-differentiated HCCs--were enrolled in this prospective study. Among 64 hyperenhancing lesions on peak enhancement sonograms, four poorly differentiated HCCs and eight moderately differentiated HCCs exhibited washout within 1 minute. In addition to these 12 lesions, 36 lesions exhibited washout 5 minutes after injection, resulting in a total of 48 washout lesions. Fifty-four lesions exhibited washout 10 minutes after contrast injection (six poorly differentiated, 38 moderately differentiated, and 10 well-differentiated HCCs). Washout was more frequent in poorly than in moderately differentiated HCC (p = 0.0117) and well-differentiated HCC (p = 0.0003) in the 1-minute phase and was more frequent in moderately differentiated than in well-differentiated HCC in the 5-minute (p = 0.0026) and 10-minute (p = 0.0117) phases. Thirteen lesions were isoenhancing or hypoenhancing on peak enhancement sonograms (three moderately differentiated and 10 well-differentiated HCCs). Contrast-enhanced ultrasound and CT during hepatic arteriography did not differ significantly with respect to rate of detection of hyperenhancing lesions. CONCLUSION: The findings at contrast-enhanced ultrasound with the perflubutane microbubble agent may be predictive of cellular differentiation of HCC without needle biopsy.

One-month biocompatibility evaluation of the pediatric TinyPump in goats.

The TinyPump is an extracorporeal, magnetically driven centrifugal blood pump with its impeller suspended magnetically and hydrodynamically to provide short-term mechanical circulatory support for children and infants. We have previously demonstrated that the in vivo experiments of the experimental TinyPump showed acceptable stable performance at pump flows averaging around 1.0 L/min with low hemolytic and thrombogenic properties for up to 2 weeks. We present here the 1-month in vivo evaluation of the TinyPump, whose design was modified further for more durable operation. The pump was implanted as a left ventricular assist device in five goats (12.5-26.7 kg), with inflow inserted into the left ventricular apex and outflow anastomosed to the descending aorta. Five animals were supported for 110 pump days, with mean pump flow of 1.19 ± 0.03 L/min at a pump speed of 2679 ± 97 rpm. Two animals reached the scheduled end point of 30 days without device failure, and mean plasma-free hemoglobin was 1.7 ± 0.8 mg/dL. Hematologic and biochemical data of these two animals showed no evidence of cardiovascular, renal, or hepatic dysfunction. Although further experiments are needed, the modified TinyPump offers promise as a short-term mechanical circulatory support device in pediatric population.

In vivo evaluation of the "TinyPump" as a pediatric left ventricular assist device.

Pediatric patients with end-stage heart failure require mechanical circulatory support (MCS) just as adults do. In order to meet the special requirements for neonates' and infants' MCS, pediatric circulatory support devices must be compact with low priming volume, easily controllable with low flow, less traumatic for blood cells and tissues, and biocompatible with minimum anticoagulation. We have designed and developed a miniature rotary centrifugal blood pump, "TinyPump," with a priming volume of 5 mL, which has already demonstrated its controllable performance for low flow and durability in vitro. To evaluate the feasibility of the TinyPump as a left ventricular assist device (LVAD) suitable for neonates and infants, we have examined the biocompatibility and hemodynamic performance of the TinyPump in a pediatric animal model using Shiba goats. The TinyPump is a miniaturized centrifugal pump weighing 150 g comprising a disposable pump head with a 30-mm diameter impeller having six straight-vanes and a reusable motor driver. The impeller in the pump head is supported by a hydrodynamic bearing at its center and is driven by radial magnetic force coupled to the motor driver. TinyPump implantations were performed in 22 Shiba goats (17 female and 5 male), with body weights ranging from 8.4 to 27.2 kg. Under gas anesthesia, via left lateral thoracotomy, a 22 Fr inflow cannula was inserted through the left ventricular apex, while a 6-mm outflow graft was anastomosed to the descending aorta, which were then connected to a TinyPump mounted on the animal's back. Postoperative hemodynamic monitoring included heart rate, arterial and central venous pressure, pump flow, and rotation speed. Target pump flow in all animals was maintained at 0.9 ± 0.1 L/min, which is approximately half the normal pulmonary artery flow measured in control animals. Blood samples were collected to evaluate peripheral organ functions, hemolysis, and thrombosis. Goats were divided into three groups-acute phase (6 h; n = 4), subchronic phase (6 h 2 postoperative days [POD]; n = 11), and chronic phase (3 POD-16 POD; n = 8)-based on their survival duration. In the early experiments, hemolysis and thrombi formation at the impeller bearing resulted in termination of the study. Subsequent modifications of the bearing design, pump housing design, and magnetic coupling force helped to minimize the hemolysis and thrombi formation, prolonging the survival duration of the Shiba goats to 2 weeks with minimum adverse effects on the blood components and organ functions. With further experiments and improvements in pump durability and hemocompatibility, the TinyPump can serve as a suitable circulatory support device for neonates and infants bridging to heart transplantation as well as to heart recovery.

Long-term effect of endoscopic injection therapy with combined cyanoacrylate and ethanol for gastric fundal varices in relation to portal hemodynamics.

BACKGROUND: The understanding on the long-term effect of endoscopic therapy for gastric fundal varices (FV) is still insufficient. The aim of this study was to evaluate the relationship between the long-term effect of the endoscopic injection therapy with combined cyanoacrylate (CA) and absolute ethanol (ET) for FV, and the portal hemodynamics. METHODS: The subjects of this retrospective study were ten consecutive cirrhotic patients with bleeding FV treated by endoscopic injection therapy with combined CA and ET. Percutaneous transhepatic portography was done after the completion of endoscopic treatment to assess portal hemodynamics. RESULTS: All the patients showed hemostasis by CA injection and complete obturation of FV by combined therapy of 5.6 +/- 2.1 (3-9) times without any severe complications except for gastric ulcer in one case. Five patients had recurrence (50%), and three of them showed rebleeding (30%). The other five patients had no recurrence during a mean observation period of 5.58 years (1190-2735 days). Although recurrence did not correlate with portal venous pressure, it was significantly frequent in patients without advanced portosystemic collateral vessels (5/7, P = 0.0384) compared to patients with them (0/3). CONCLUSIONS: Endoscopic injection therapy combining CA and ET may be effective for FV. Significant development of portosystemic collateral vessels would support long-term therapeutic effect after this treatment.

Ultrasound-guided treatments under low acoustic power contrast harmonic imaging for hepatocellular carcinomas undetected by B-mode ultrasonography.

BACKGROUND/AIMS: The aim was to examine the efficacy of contrast-enhanced ultrasound (US) with Sonazoid to demonstrate ultrasonically unrecognizable hypervascular hepatocellular carcinoma (HCC) and apply percutaneous US-guided treatments. METHODS: The subjects of this prospective study were 44 cirrhotic patients with 55 hypervascular lesions (12.7+/-4.5 mm) found by contrast-enhanced computed tomography but unrecognized by non-contrast US. Contrast-enhanced US was performed to demonstrate these hepatic lesions after an intravenous injection of Sonazoid (0.0075 ml/kg). The sonograms in both the early phase (for 1 min after injection) and the late phase (5-10 min after) were taken in the harmonic imaging mode under a low mechanical index (0.24-0.3). RESULTS: Fifty-three lesions were demonstrated by contrast-enhanced US, 52 with positive enhancement in the early phase and 44 with negative enhancement in the late phase. Percutaneous US-guided treatments were successfully performed for 42 lesions (ethanol injection in 20 and radiofrequency ablation in 22) in 32 patients with reference to contrast-enhanced US findings. Six patients were treated by transarterial chemoembolization alone because they had more than three lesions in the liver. In the remaining seven lesions in six patients, six were diagnosed as non-HCC lesions: five with vascular abnormalities such as arterioportal or arteriovenous communication and the other one with benign lesion in alcoholic liver disease. These six lesions and one HCC lesion with severe liver damage were followed up without any treatment. CONCLUSIONS: As the detectability of ultrasonically unrecognizable hypervascular HCC improved by contrast-enhanced US with Sonazoid, a wider application of percutaneous US-guided treatments may be possible.

Phase II study of hepatic arterial infusion of a fine-powder formulation of cisplatin for advanced hepatocellular carcinoma.

AIM: Intra-arterial cisplatin appears to have high therapeutic efficacy, but this has not been studied in detail. Accordingly, we developed a fine-powder cisplatin formulation and tested it in advanced hepatocellular carcinoma (HCC) patients in an open-label, uncontrolled study in which 27 institutions participated. METHODS: The patients in this study had inoperable advanced HCC without extrahepatic metastases. All received two infusions of high-concentration cisplatin (1.43 mg/mL) via the hepatic artery at a dose of 65 mg/m(2), with an intervening 4-6 week interval. RESULTS: Cisplatin efficacy and safety were assessed in 80 patients. We found partial responses in 27 cases, no change in 37, and progressive disease in 11 (five were not evaluated). The overall response rate was 33.8%. The 1-year survival rate was 67.5% and the 2-year survival rate was 50.8%. Severe adverse effects (>/=grade 3) included anorexia in 22.5%, vomiting in 6.3%, abdominal pain in 1.3%, thrombocytopenia in 25%, neutropenia in 13%, leukopenia in 1.3%, hypochromia in 1.3%, elevated serum aspartate aminotransferase in 32.5%, elevated serum alanine aminotransferase in 11.3%, elevated serum bilirubin in 3.8%, decreased serum albumin in 1.3%, elevated serum alkaline phosphatase in 1.3%, elevated gamma-glutamyltranspeptidase in 3.8%, and elevated serum creatinine in 2.5%. Death from myocardial infarction occurred as an incidental event in one case, and no other life-threatening, adverse events were observed. CONCLUSION: Although intra-arterial cisplatin has substantial local and systemic toxicity, high therapeutic efficacy suggests the potential usefulness of this agent in the treatment of advanced HCC.

How to characterize non-hypervascular hepatic nodules on contrast-enhanced computed tomography in chronic liver disease: feasibility of contrast-enhanced ultrasound with a microbubble contrast agent.

BACKGROUND AND AIM: Although hypervascular appearance is characteristic in hepatocellular carcinoma (HCC), hepatic nodules without hypervascular appearance are sometimes found in patients with chronic liver disease (CLD). The aim of the present study was to clarify the efficacy of contrast-enhanced ultrasound (CEUS) with Levovist to characterize small, non-hypervascular hepatic nodules on contrast-enhanced computed tomography (CECT) in patients with CLD. METHODS: The subject was 41 hepatic nodules (<30 mm, 18.5 +/- 5.6 mm) which showed non-hypervascular appearance on CECT in 35 patients with CLD; their histological results were 31 HCC (15 well, 14 moderate, and two poor) and 10 regenerative nodules (RN). CEUS with Levovist was performed under intermittent scanning (1-s interval) using APLIO at the early phase and the liver-specific phase, and the contrast enhancement of the nodule was assessed in comparison to that of the surrounding liver parenchyma. The contrast-enhanced findings with the time-intensity analysis were compared with the histological results. RESULTS: Twelve nodules with weak enhancement in the liver-specific phase were HCC, regardless of their early-phase appearances. The other 29 nodules with equivalent or weak enhancement in the early phase and equivalent enhancement in the liver-specific phase were 19 HCC and 10 RN. Among them, the maximum-intensity ratio of tumor to non-tumor in the early phase was significantly higher in HCC than in RN (P < 0.01, n = 16), and the receiver-operating characteristic analysis showed a sensitivity of 1.0 and a specificity of 0.83 for their characterization. CONCLUSION: CEUS with Levovist may be an alternative to biopsy to characterize small, non-hypervascular hepatic nodules on CECT in patients with CLD.

Current role of ultrasound for the management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a decisive influence on the prognosis of cirrhotic patients. Although alpha-fetoprotein (AFP) is a known and specific tumor maker for HCC, it is not suitable for the screening and surveillance of HCC because of its poor predictive value and low sensitivity. The use of imaging modalities is essential for the screening, diagnosis and treatment of HCC. Ultrasound (US) plays a major role among them, because it provides real-time and non-invasive observation by a simple and easy technique. In addition, US-guided needle puncture methods are frequently required for the diagnosis and/or treatment process of HCC. The development of digital technology has led to the detection of blood flow by color Doppler US, and the sensitivity for detecting tumor vascularity has shown remarkable improvement with the introduction of microbubble contrast agents. Moreover, near real-time 3-dimensional US images are now available. As for the treatment of HCC, high intensity focused ultrasound (HIFU) was developed as a novel technology that provides transcutaneous ablation effect without needle puncture. These advancements in the US field have led to rapid progress in HCC management, and continuing advances are expected. This article reviews the current application of US for HCC in clinical practice.

Multidetector helical CT plus superparamagnetic iron oxide-enhanced MR imaging for focal hepatic lesions in cirrhotic liver: a comparison with multi-phase CT during hepatic arteriography.

The aim of this study was to evaluate multidetector helical computed tomography (MDCT), superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging, and CT arterial portography (CTAP) and CT during hepatic arteriography (CTHA) for the detection and diagnosis of hepatocellular carcinomas (HCC). This included visual correlations of MDCT and SPIO-MR imaging in the detection of HCC using receiver operating characteristic (ROC) analysis. Twenty-five patients with 57 nodular HCCs were retrospectively analyzed. A total of 200 segments, including 49 segments with 57 HCCs, were reviewed independently by three observers. Each observer read four sets of images (set 1, MDCT; set 2, unenhanced and SPIO-enhanced MR images; set 3, combined MDCT and SPIO-enhanced MR images; set 4, combined CTAP and CTHA). The mean Az values representing the diagnostic accuracy for HCCs of sets 1, 2, 3, and 4 were 0.777, 0.814, 0.849, and 0.911, respectively, and there was no significant difference between sets 3 and 4. The sensitivity of set 4 was significantly higher than those of set 3 for all the lesions and for lesions 10 mm or smaller (p<0.05); however, for lesions larger than 10mm, the sensitivities of the two sets were similar. No significant difference in positive predictive value and specificity was observed between set 3 and set 4. Combined MDCT and SPIO-enhanced MR imaging may obviate the need for more invasive CTAP and CTHA for the pre-therapeutic evaluation of patients with HCC more than 10mm.

Relationship between therapeutic efficacy of arterial infusion chemotherapy and expression of P-glycoprotein and p53 protein in advanced hepatocellular carcinoma.

AIM: To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein (PGP) and p53 protein in advanced hepatocellular carcinoma (HCC). METHODS: The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the forty-one patients were treated with an anthracycline drug (epirubicin hydrochloride; anthracycline group), and the remaining 21 were treated with a non-anthracycline drug (mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group). The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups. RESULTS: Before the start of the treatment, PGP-positive rate was 90.2% (strongly-positive, 36.6%) and p53 protein-positive rate was 34.1% (strongly-positive, 19.5%). In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression (P=0.005), and their prognoses were poor (P=0.001). In the non-anthracycline group, the response rate was 42.9%, and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients (P=0.012), irrespective of the survival outcome. CONCLUSION: The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP expression. Similarly, immunostaining to evaluate p53 protein may be useful to predict the response in patients treated with an anthraquinone drug.

Prognostic Significance of Concurrent Hypovascular and Hypervascular Nodules in Patients with Hepatocellular Carcinoma.

BACKGROUND: Hypovascular nodules often occur together with hypervascular hepatocellular carcinoma (HCC). However, it remains controversial whether hypovascular nodules associated with hypervascular HCC have any prognostic value. This study evaluated the prognostic impact of hypovascular nodules co-existing with hypervascular HCC as diagnosed by computed tomography during arterial portography (CTAP) and computed tomography during hepatic arteriography (CTHA), which can sensitively capture the dynamic changes in blood flow through the portal vein and hepatic artery in patients with early stage HCC. METHODS: A total of 152 patients with hypervascular HCC (≤ 30 mm, ≤ 3 nodules), who underwent initial local ablation, were analyzed retrospectively. All patients received CTAP and CTHA prior to treatment. Overall survival (OS) was compared among group A (hypervascular HCC only, 107 patients) and group B (hypovascular nodules and hypervascular HCC, 45 patients). RESULTS: Among all hypovascular nodules, 81% (46 of 57) developed hypervascularization within the follow-up period. The 1- and 2-year hypervascularization rates were 17% and 51%, respectively. OS was significantly longer for group A than for group B (P < 0.001). A Cox proportional-hazards model identified the presence of hypovascular nodules concurrent with hypervascular HCC as an independent poor prognostic factor. CONCLUSION: The prognosis of hypervascular HCC patients with hypovascular nodules detected during CTAP and CTHA is poor. Clinical HCC categories seem to be dissimilar between patients with and without hypovascular nodules.

Thoracic aneurysm rupture due to graft perforation after endovascular stent-grafting via median sternotomy.

We performed emergency repeat surgery for aneurismal rupture due to graft perforation with mechanical stress of the Z stent in a kinking graft after frozen elephant trunk procedure. Graft kinking occurred due to cranial migration of the Z stent. It is important to prevent stent dislodgement in order to achieve long-term durability and reliability in the frozen elephant trunk procedure.

Arch-first technique performed under hypothermic circulatory arrest with retrograde cerebral perfusion improves neurological outcomes for total arch replacement.

OBJECTIVE: From 1998, we have adopted the arch first technique (reconstruction of arch vessels first and distal anastomosis second) instead of the distal anastomosis first technique for total arch replacement. The aim is to reduce the period of deep hypothermic circulatory arrest and the retrograde cerebral perfusion time. We evaluate the surgical results of the arch first technique. METHODS: The arch first technique was used in 50 cases (38 male and 12 female), of average age 68 years, from 1998 to 2003. There were 33 true aneurysms and 10 chronic and seven acute type A dissections. Clinical results were evaluated and compared with the distal first technique used in 24 cases operated on between 1992 and 1998. These were 14 males and 10 females, with an average age of 68 years. There were 16 true aneurysms, and three chronic and five acute aortic dissections. RESULTS: For the arch first technique there is a significantly shorter circulatory arrest time (32 vs. 72min, P<0.0001), but similar body ischemic times (76 vs. 72min, N.S.). With the arch first technique, all but two patients awoke within 24h, with an average delay of 9.3h. In the distal first technique, two patients did not awaken and three patients showed delayed awakening, with an average awakening time of 24h. The arch first technique led to one hospital death (2%), due to residual aneurysm rupture. Reversible ischemic neurological deficit (RIND) was complicated in three cases (6%), but no stroke occurred during operation. In the distal first technique there were four strokes, one RIND and three hospital deaths (12.5%). The arch first technique gave a significantly lower intra-operative stroke rate (P=0.0030) and smaller hospital mortality (P=0.0615). The arch first technique led to five late deaths, with an 84.5% 3 year survival rate, and the distal first technique led to six late deaths with a 59.1% 3-year survival rate. CONCLUSIONS: The arch first technique is clearly superior to the conventional distal first technique in surgical mortality and morbidity regarding neurological outcome, and provides a higher survival rate and better quality of life. The arch first technique is an excellent method for total arch replacement.

Successful treatment for ampullary submucosal bleeding-induced pancreatitis: a rare sequla of hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) is clinically characterized by the triad of mucocutaneous telangiectasia, recurrent epistaxis, and a familial history. We describe a 68-year-old woman with hereditary hemorrhagic telangiectasia undergoing transduodenal papillectomy for ampullary submucosal bleeding-induced pancreatitis. When she was 63 years old, she presented with abdominal pain due to acute pancreatitis, and from the age of 68, frequency of the symptom increased a couple of times a month. Gastrofiberscopy showed enlarged ampulla of Vater. Doppler ultrasonography showed rich and tortuous signals of bloodstream at submucosal region of the ampulla. Arteriogram revealed that hypervascular staining was fed by the inferior pancreaticoduodenal artery. Microcoil embolization was attempted and hypervascular staining disappeared. However, one week later, endoscopic papillotomy was unable to be performed due to risk of uncontrollable bleeding since Doppler ultrasonography showed signals of bloodstream at submucosal region of the ampulla again. Finally, she underwent open transduodenal papillectomy. She had an uneventful postoperative course, and has been free of pancreatitis for 20 months after surgery. We also review the literature and discuss the surgical indication for gastrointestinal and hepato-biliary-pancreatic involvement with hereditary hemorrhagic telangiectasia. To our knowledge, this is the first reported case of successful surgical treatment for pancreatitis due to sequla of hereditary hemorrhagic telangiectasia.

Feasibility of a miniature centrifugal rotary blood pump for low-flow circulation in children and infants.

In this study, a seal-less, tiny centrifugal rotary blood pump was designed for low-flow circulatory support in children and infants. The design was targeted to yield a compact and priming volume of 5 ml with a flow rate of 0.5-4 l/min against a head pressure of 40-100 mm Hg. To meet the design requirements, the first prototype had an impeller diameter of 30 mm with six straight vanes. The impeller was supported with a needle-type hydrodynamic bearing and was driven with a six-pole radial magnetic driver. The external pump dimensions included a pump head height of 20 mm, diameter of 49 mm, and priming volume of 5 ml. The weight was 150 g, including the motor driver. In the mock circulatory loop, using fresh porcine blood, the pump yielded a flow of 0.5-4.0 l/min against a head pressure of 40-100 mm Hg at a rotational speed of 1800-4000 rpm using 1/4" inflow and outflow conduits. The maximum flow and head pressure of 5.25 l/min and 244 mm Hg, respectively, were obtained at a rotational speed of 4400 rpm. The maximum electrical-to-hydraulic efficiency occurred at a flow rate of 1.5-3.5 l/min and at a rotational speed of 2000-4400 rpm. The normalized index of hemolysis, which was evaluated using fresh porcine blood, was 0.0076 g/100 l with the impeller in the down-mode and a bearing clearance of 0.1 mm. Further refinement in the bearing and magnetic coupler are required to improve the hemolytic performance of the pump. The durability of the needle-type hydrodynamic bearing and antithrombotic performance of the pump will be performed before clinical applications. The tiny centrifugal blood pump meets the flow requirements necessary to support the circulation of pediatric patients.