Hepatocellular carcinoma in a mouse model fed a choline-deficient, L-amino acid-defined, high-fat diet.

Hepatocellular carcinoma (HCC) is a common cancer worldwide and represents the outcome of the natural history of chronic liver disease. The growing rates of HCC may be partially attributable to increased numbers of people with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). However, details of the liver-specific molecular mechanisms responsible for the NAFLD-NASH-HCC progression remain unclear, and mouse models that can be used to explore the exact factors that influence the progression of NAFLD/NASH to the more chronic stages of liver disease and subsequent HCC are not yet fully established. We have previously reported a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) as a dietary NASH model with rapidly progressive liver fibrosis in mice. The current study in C57BL/6J mice fed CDAHFD provided evidence for the chronic persistence of advanced hepatic fibrosis in NASH and disease progression towards HCC in a period of 36 weeks. When mice fed CDAHFD were switched back to a standard diet, hepatic steatosis was normalized and NAFLD activity score improved, but HCC incidence increased and the phenotype of fibrosis-associated HCC development was observed. Moreover, when mice continued to be fed CDAHFD for 60 weeks, HCC further developed without severe body weight loss or carcinogenesis in other organs. The autochthonous tumours showed a variety of histological features and architectural patterns including trabecular, pseudoglandular and solid growth. The CDAHFD mouse model might be a useful tool for studying the development of HCC from NAFLD/NASH, and potentially useful for better understanding pathological changes during hepatocarcinogenesis.

Hybrid procedures for an infant with hypoplastic left heart syndrome with intact atrial septum.

A boy, prenatally diagnosed as hypoplastic left heart syndrome (HLHS) with intact atrial septum (IAS) was successfully treated by hybrid procedures. He underwent emergent catheter atrial septostomy and stent insertion in the atrial septum on Day 1 and then underwent bilateral pulmonary artery banding, ductal stent insertion, modified Norwood operation, bidirectional Glenn's operation and finally Fontan type operation at 2 years of age. Considering the presence of decompression pathway from the left atrium in HLHS with IAS, we should organize a treatment team for collaborative work and plan an appropriate treatment strategy before delivery. Although his clinical course has been uneventful until now, closer medical observation is warranted because he may have coexisting pulmonary disease.

The expression of groups IIE and V phospholipase A2 is associated with an increased expression of osteogenic molecules in human calcified aortic valves.

AIM: Eicosanoids play various pathogenic roles in aortic valve calcification. Eicosanoids are derived from the arachidonic acid generated by phospholipase A2 (PLA2). We therefore sought to determine whether PLA2s are expressed in human aortic valves and, if so, whether the expression of PLA2s is related to the expression of osteogenic molecules in these tissues. METHODS: Histological and gene expression analyses of 38 non-rheumatic aortic valves obtained at the time of cardiac valve replacement surgery were conducted. Moreover, gene expression analyses were performed using valve interstitial cells (VICs) obtained from human aortic valves. RESULTS: Among the PLA2s examined, the degree of immunoreactivity for PLA2s-IIE and -V was found to significantly correlate with the grade of calcification in the aortic valves. The degree of immunoreactivity and gene expression levels of PLA2s-IIE and -V significantly correlated with those of bone morphogenetic protein (BMP)-2, osteopontin and alkaline phosphatase (ALP). In addition, immunoreactivity for cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase, downstream enzymes of PLA2 in the arachidonic acid cascade, was co-localized with that for PLA2s-IIE and -V in cells expressing α-smooth muscle actin and macrophages expressing CD68. Furthermore, in the in vitro experiments using cultured VICs, the mRNA expression levels of BMP-2, osteopontin and ALP were suppressed by the inhibition of the expression of PLA2s-IIE or -V with specific siRNAs. CONCLUSIONS: The expression of PLA2s-IIE and -V correlates with the development of calcification as well as the expression of pro-osteogenic molecules in human aortic valves, and inhibiting the expression of PLA2s-IIE and -V suppresses the induction of osteogenic molecules in cultured cells. Therefore, PLA2s-IIE and -V may play a role in the pathogenesis of valve calcification.

Successful thoracoscopic removal of a giant teratoma following extraction of cystic conponents: a case report.

Video-assisted thoracoscopic surgery is a type of minimal-access surgery. The nature of the surgery means that there are limitations on the size of a tumor that can be removed through an access incision. Herein, we report our experience removing a giant teratoma (16 × 14 × 13 cm in size) from the anterior mediastinum of a young girl. We employed video-assisted thoracoscopic surgery to remove the teratoma through a mini-thoracotomy following the extraction of the cystic components.

Surgical techniques for implanting implantable cardioverter defibrillators in children and infants.

Implantable cardioverter defibrillators (ICDs) are now being used in children. ICDs can be used to prevent sudden cardiac death caused by not only congenital heart defects, but also various non-structural diseases, such as long QT syndrome. However, a standard implantation technique for children, especially infants, has not yet been established. As the surgical implantation in infants is not amenable to transvenous lead placement, it was necessary to choose from epicardial, subcutaneous and pericardial ICD systems. However, many of these systems are associated with high rates of late complications. Lead fracture, insulation breakage, migration, buckling or crinkling of the patch lead and constrictive pericarditis have been reported as the most common lead-related complications. An increase in the defibrillation threshold is another issue that must be considered when using an ICD in a child or infant. Further studies on the outcomes, psychosomatic impact and other specific complications in the pediatric population need to be considered. The clinical use of ICDs in infants is still limited. Therefore, it is important to have many surgical options available so that the treatment can be custom-tailored to suit individual patients.

Atypical membrane-embedded phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2)-binding site on p47(phox) Phox homology (PX) domain revealed by NMR.

The Phox homology (PX) domain is a functional module that targets membranes through specific interactions with phosphoinositides. The p47(phox) PX domain preferably binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P(2)) and plays a pivotal role in the assembly of phagocyte NADPH oxidase. We describe the PI(3,4)P(2) binding mode of the p47(phox) PX domain as identified by a transferred cross-saturation experiment. The identified PI(3,4)P(2)-binding site, which includes the residues of helices α1 and α1' and the following loop up to the distorted left-handed PP(II) helix, is located at a unique position, as compared with the phosphoinositide-binding sites of all other PX domains characterized thus far. Mutational analyses corroborated the results of the transferred cross-saturation experiments. Moreover, experiments with intact cells demonstrated the importance of this unique binding site for the function of the NADPH oxidase. The low affinity and selectivity of the atypical phosphoinositide-binding site on the p47(phox) PX domain suggest that different types of phosphoinositides sequentially bind to the p47(phox) PX domain, allowing the regulation of the multiple events that characterize the assembly and activation of phagocyte NADPH oxidase.

Intracardiac varix of the left atrium.

A 68-year-old female patient with a history of hyperlipidaemia and fatty liver was referred for evaluation of an incidentally detected asymptomatic cardiac mass. Computed tomographic scan imaging showed a large calcified mass in the left atrium. Echocardiography revealed a 2.4 1.5 cm, well-circumscribed, round, high echoic mass with severe calcification and low mobility attached to the lower rim of the fossa ovalis. The cardiac mass along with part of the fossa ovalis and left atrial wall were excised. Histological diagnosis was compatible with intracardiac varix.

Non-small cell lung carcinoma therapy using mTOR-siRNA.

Molecular targeting agents play important roles in non-small-cell lung cancer (NSCLC) therapy. Published studies have investigated new drugs categorized as molecular targeting agents that inhibit the mammalian target of rapamycin (mTOR). We focused on a small interfering RNA (siRNA) that specifically inhibits mTOR and has fewer side effects. To evaluate the antitumor effects of the siRNA, cell proliferation, apoptosis, and migration were assessed. In the study group, the siRNA was transfected into NSCLC cells. The number of cells present after 6 days of culture was counted to determine changes in cell proliferation. The level of apoptosis was evaluated by the detection of DNA-histone complexes in the cytoplasmic fraction using an absorption spectrometer. Changes in migration were evaluated by calculating the number of cells that passed through a specific filter using a commercial chemotaxis assay kit. mTOR-siRNA transfection inhibited cell proliferation as indicated by 37.3% (p = 0.034) decrease in the number of cells compared with the control cells. Analysis of the level of apoptosis in NSCLC cells revealed 16.7% (p = 0.016) increase following mTOR-siRNA transfection, and mTOR-siRNA transfection significantly inhibited cell migration by 39.2% (p = 0.0001). We confirmed that mTOR-siRNA induces apoptosis and inhibits the proliferation and migration of NSCLC cells in vitro. Further studies using mTOR-siRNA may aid in the development of an alternative therapy that maximizes the antineoplastic effect of mTOR inhibition.

Successful staged management of simultaneous abdominal aortic aneurysm and renal tumor: the novel minimally invasive treatment with endovascular aneurysm repair and retroperitoneal laparoscopic radical nephrectomy in an elderly and high-risk case.

The association between abdominal aortic aneurysm (AAA) and renal tumor is becoming more frequent, and the increasing incidence of this synchronous diseases raised questions about the procedures of treatment. In most of the previous cases, open nephrectomy and AAA surgery have been reported, however in high risk and elderly patients, the procedure is life threatening. We present a successful staged treatment of AAA and renal tumor using novel minimally invasive treatment with endovascular aneurysm repair and retroperitoneal laparoscopic radical nephrectomy in an elderly and high-risk case.

Two-staged treatment strategy in patients with severe carotid or cerebrovascular diseases undergoing coronary artery bypass grafting.

PURPOSE: There is no clear consensus on how to treat patients undergoing coronary artery bypass grafting (CABG) who have severe concomitant carotidcerebral artery stenosis. The aim of this study was to evaluate our surgical results in patients with severe carotid and/or cerebrovascular disease undergoing CABG. METHODS: Between October 2003 and April 2009, a total of 47 such patients were treated at our institution with the following strategies: (1) protective carotid artery stenting for severe carotid stenosis performed either before (n = 20) or after (n = 5) CABG or (2) a superficial temporal artery-middle cerebral artery anastomosis procedure followed by CABG if indicated (n = 4). Off-pump CABG was performed in 75% of the patients. RESULTS: There were no major perioperative strokes or in-hospital deaths; however, three patients had transient ischemic attacks and two had minor strokes during the early post-CABG period. All of the patients with postoperative cerebrovascular events had had unilateral carotid artery occlusion. There were no late deaths during the follow-up period (up to 6 years, with a mean of 27 months). However, major adverse cardiocerebrovascular events (MACCE) occurred in seven patients (14.9%). The rates of freedom from MACCE at 1 and 3 years were 92% and 74%, respectively. CONCLUSION: It appears that our two-staged approach is safe and may reduce the risk of postoperative cerebrovascular events.

Aortic regurgitation due to perforation of the right coronary cusp 10 years after implantation of a freestyle stentless bioprosthesis.

Valve deterioration following aortic valve replacement using the Freestyle stentless bioprosthesis is related to cusp tear, operative injury, or infection. We report a patient with aortic regurgitation due to perforation of the right coronary cusp 10 years after implantation of a Freestyle stentless bioprosthesis in the absence of endocarditis.

Treatment of prosthetic valve endocarditis complicated by destruction of the aortic annulus.

PURPOSE: It has been reported that surgical treatment for prosthetic valve endocarditis complicated by destruction of the aortic annulus is associated with high mortality and morbidity. The aim of this study was to evaluate the efficacy of our surgical strategy for this situation. METHODS: Between October 2003 and April 2009, eight patients (mean age 68.6 years) with prosthetic valve endocarditis complicated by destruction of the aortic annulus were surgically treated at our hospital. We use a relatively simple procedure consisting of a patch plasty of the abscess cavity in addition to complete removal of the infected tissue of the abscess cavity followed by standard aortic valve replacement. All patients had active endocarditis and were in New York Heart Association functional class III or IV. Preoperative echocardiography revealed that four patients had moderate or severe aortic regurgitation, and two had mitral valve endocarditis as well. RESULTS: There were no operative deaths (≤30 days). Cardiac complications included paroxysmal atrial fibrillation in three patients and transient atrioventricular block in one. One patient died of multiple organ failure 66 days after the surgery. The overall in-hospital mortality was 12.5%. Patients were followed-up for 6-49 months (mean 31 months). There was no recurrent prosthetic valve endocarditis. One patient required reoperation (mitral annuloplasty and redo aortic valve replacement). There were two late deaths: lung cancer in one and multiple organ failure related to pneumonia after the aforementioned redo operation in the other. CONCLUSION: Our simple procedure for complicated prosthetic valve endocarditis yielded excellent early and midterm outcomes.

Contained rupture of an inflammatory abdominal aortic aneurysm into the iliopsoas muscle: report of a case.

A 72-year-old man with a history of old myocardial infarction was admitted to our hospital for surgical treatment of a ruptured abdominal aortic aneurysm. His hemodynamics was stable. He had left lumbar pain on moving his left leg and constipation for ten days without abdominal pain and high fever. Elevation of fat density around the aneurysm and ureter involvement were noted on the computed tomography. These characteristic image findings indicated inflammatory aortic aneurysm. During operation, an infrarenal abdominal aortic aneurysm with an 8 cm maximum diameter was noted. This aneurysm was firm and thick and adhered to some organs due to inflammation. An 5 × 5 cm punched-out defect was found on the lateral wall of the aneurysm. We replaced the ruptured aneurysm with a Dacron graft. Histological examination showed that the aneurysm wall had an infiltrate of inflammatory cells, lymphoid follicles and thickened adventitia. From these findings, the diagnosis was inflammatory aortic aneurysm.

Surgical treatment of aortic valve papillary fibroelastoma with neurofibromatosis (von Recklinghausen's disease).

A 69-year-old man with a medical history of neurofibromatosis was transferred to our hospital for the treatment of an aortic valve mass. His workup identified an aortic valve papillary fibroelastoma based on the absence of signs of infection, thrombus in the left atrium, and valvular destruction or abnormal valvular function. A tumor was excised under cardiopulmonary bypass. The pathology of the mass was a papillary fibroelastoma. Neurofibromatosis with cardiac tumor is extremely rare. This is the first report of a case of papillary fibroelastoma associated with neurofibromatosis.

An atypical cause of aortic valve prolapse.

We encountered a surgical case of aortic valve prolapse caused by a fissure formed in the commissural region and coronary cusp, and we achieved a favorable outcome. On pathologic examination, the fissured valve was found to be myxoid degeneration with ruptured elastic fibers and clustering of foamy macrophages, and it was diagnosed as an atherosclerotic change not associated with rheumatic change. The fissure appeared to develop because of hypertensive stress in a region rendered vulnerable by atherosclerosis. Although this mechanism is atypical, it should be recognized that poorly controlled hypertension can cause aortic valve prolapse and induce acute heart failure.