Paraneoplastic neurological syndrome due to burned-out testicular tumor showing hot cross-bun sign.

BACKGROUND: Paraneoplastic neurological syndromes (PNS) are rare remote effect of cancer. The antibodies and tumors associated with PNS have been well described, but there are still many clinically suspected cases in which no tumor or antibody can be identified. This is the first report of PNS showing hot cross-bun sign and caused by exceptionally rare underlying malignancy, such as burned-out testicular tumor. CASE PRESENTATION: A 42-year-old man presented subacute progression of hearing loss and cerebellar ataxia. Cerebrospinal fluid showed continuous inflammation and magnetic resonance imaging (MRI) revealed cerebellar atrophy and hot cross-bun sign. Resection of tumors improved both laboratory findings and neurological signs and their pathology was seminoma. CONCLUSION: Seminoma can cause PNS showing 8th cranial nerve palsy, cerebellar, and brainstem atrophy with hot cross-bun sign on MRI study. Extensive screening for onconeural antibodies was negative and thereby suggested that unknown antibodies worked for both antitumor immunity and induction of PNS.

Clinical features and outcomes of delayed perforation after endoscopic submucosal dissection for early gastric cancer.

Perforation is a major complication of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). However, there have been no reports on delayed perforation after ESD for EGC. We aimed to elucidate the incidence and outcomes of delayed perforation after ESD. Clinical courses in 1159 consecutive patients with 1329 EGCs who underwent ESD were investigated. Delayed perforation occurred in six patients (0.45 %). All these patients had complete en bloc resection without intraoperative perforation during ESD. Five of six perforations were located in the upper third of the stomach, while one lesion was found in the middle third. Symptoms of peritoneal irritation with rebound tenderness presented within 24 h after ESD in all cases. One patient did not require surgery because the symptoms were localized, and recovered with conservative antibiotic therapy by nasogastric tube placement. The remaining five patients required emergency surgery. There was no mortality in this case series.

Add-on combination therapy with adefovir dipivoxil induces renal impairment in patients with lamivudine-refractory hepatitis B virus.

Combination therapy with adefovir dipivoxil (ADV) and lamivudine (LAM) is recommended for patients infected with LAM-refractory hepatitis B virus (HBV). However, the effects of such therapy on renal function and serum phosphorus levels have not been fully evaluated. Combination therapy with ADV and LAM was given to 37 patients infected with LAM-refractory HBV, including 17 with hepatic cirrhosis. Serum HBV DNA levels decreased to below 2.6 log(10) copies/mL in 23 (62%) of 37 patients at 12 months, 25 (78%) of 32 patients at 24 months, and 16 (84%) of 19 patients at 36 months. Except for one cirrhotic patient, serum alanine aminotransferase levels were below 50 IU/L in all patients during combination therapy. Serum creatinine levels increased in 14 (38%) of 37 patients, and serum phosphate levels decreased to below 2.5 mg/mL in 6 (16%) of 37 patients during combination therapy. Patients who received combination therapy for 36 months or longer had a significantly incidence of elevated serum creatinine levels. Fanconi syndrome occurred in a 57-year-old woman with cirrhosis after ADV was added to LAM. Combination therapy with ADV and LAM can maintain biochemical remission in patients with LAM-refractory HBV. However, the dosing interval of ADV should be adjusted according to renal function and serum phosphate levels in patients receiving long-term treatment.

[Evaluation of a new portable device for measuring prothrombin time-internatinal normalized ratio; comparison between the conventional method and the new CoagCheck XS].

We evaluated a new portable device (CoaguCheck XS) for measuring the prothrombin time-international normalized ratio (PT-INR) in 63 patients after cardiac surgery, and compared the results with those of the conventional method. There was a good correlation between the PT-INR values measured conventionally and those obtained with the CoaguCheck XS. This new device was easy to use, data were obtained rapidly, and the results were reliable. The CoaguCheck XS will be particularly useful for outpatients. PT-INR self-management is expected to be introduced as soon as health insurance coverage is obtained.

Development of hepatocellular carcinoma in patients with chronic hepatitis C who had a sustained virological response to interferon therapy: a multicenter, retrospective cohort study of 1124 patients.

BACKGROUND: Interferon (IFN) improves hepatic inflammation/fibrosis and reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CH-C). However, HCC develops in some patients who have a sustained virological response (SVR) to IFN therapy. We designed this study to establish a follow-up protocol for patients with CH-C who have SVR to IFN therapy. METHODS: We retrospectively studied 1124 patients with CH-C who received IFN. RESULTS: HCC developed in 3.5% of patients with SVR to IFN. As compared with SVR patients without HCC, SVR patients with HCC were predominantly male (P=0.003), older at the initiation of IFN therapy (P=0.002), and at a more advanced histologic stage of disease (P<0.001). However, three of the 13 SVR HCC patients had mild fibrosis. The mean interval from IFN therapy to the detection of HCC in SVR HCC patients was 5.8 years and did not differ significantly from that in non-SVR HCC patients (P=0.304). Although most patients with HCC received curative therapy, the prognosis of some SVR HCC patients was poor, probably because of insufficient follow-up, resulting in delayed detection of HCC. CONCLUSIONS: SVR patients with CH-C who are elderly, male, or have an advanced histologic stage are at a high risk for the development of HCC after IFN therapy. We recommend that SVR patients should be observed carefully for more than 10 years after the completion of IFN therapy, even if they only have early fibrosis.

Gene expression during chemically induced liver fibrosis: effect of halofuginone on TGF-beta signaling.

Hepatic fibrosis is associated with the activation of stellate cells (HSCs), the major source of extracellular matrix (ECM) proteins. Transforming growth factor-beta (TGF-beta), signaling via Smad3, is the most profibrogenic cytokine and the major promoter of ECM synthesis. Halofuginone, an inhibitor of liver fibrosis, inhibits TGF-beta-dependent Smad3 phosphorylation in human HSCs in culture. We have used transcriptional profiling to evaluate the effect of halofuginone on gene expression during the progression of thioacetamide (TAA)-induced liver fibrosis in the rat and have focused on genes that are associated with TGF-beta. TAA treatment causes alterations in the expression of 7% of liver genes. Halofuginone treatment prevents the changes in the expression of 41% of these genes and results in the inhibition of HSC activation and collagen synthesis. During the early stages of the disease, halofuginone affects genes involved in alcohol, lipid, protein, and phosphate metabolism and cell adhesion and, at later stages, in the cell cycle (cell development, differentiation, cell proliferation, and apoptosis). The activation of TGF-beta-dependent genes, such as tartrate-resistant acid phosphatase, its putative substrate osteopontin, stellate cell activation-association protein, and fibrillin-1, during chemically induced fibrosis is prevented by halofuginone. This study thus highlights the role of TGF-beta signaling in liver fibrosis and especially its potential for pharmacological intervention. Halofuginone, which has demonstrated efficacy and tolerance in animals and humans, could become an effective and novel therapy for liver fibrosis.

[Nicks operation for aortic valve dysfunction with pannus formation; report of a case].

A 58-year-old female who underwent an aortic valve replacement 3 years ago was admitted to our hospital. She developed dyspnea in a month. Urgent reoperation was scheduled because an echocardiography demonstrated severe aortic valve regurgitation, and because a cinefluoroscopy showed that a leaflet of the prosthetic valve was restricted. Pannus formation from left ventricular outflow tract caused prosthetic valve insufficiency. An ATS 18 aortic prosthesis was replaced after removing old sewing cuff and surrounding tissue of the aortic annulus as much as possible. However, the coronary orifices were partially covered with the prosthesis. The leaflet rubbed onto the left ventricular outflow muscle specially in opening position. Therefore, an annular enlargement was required. In case of re-replacement of prosthetic valve for small aortic annulus, the annulus was at most same size or smaller than it of the previous operation. It was harmful for the patient whose body surface area was 1.74 m2 to utilize smaller prosthesis because of patient-prosthesis mismatch. We conclude that annular enlargement is useful for reoperarion of small aortic annulus associate with left ventricular outflow hypertrophy.

[Delayed repair for blunt injury of the thoracic aorta complicated with the spinal cord injury; report of a case].

Blunt aortic injury is a major cause of death from blunt trauma and it generally accompanies with the other multiple serious injuries. A 67-year-old man sustained a blunt aortic injury and a fracture of 5th cervical vertebrae complicated with a spinal cord injury. A neurological examination showed a complete paralysis of the limbs. However, his respiratory status and circulatory status were stable. On admission, the paralysis improved resulting from high dose steroid injection and a cervical traction. An orthopedic operation was required before a cardiovascular operation even though computed tomography (CT) showed that a pseudo aortic aneurysm on the distal arch tended to enlarge in the short period. As a result, the aorta was repaired about 5 months after the injury. Delayed repair was performed in safe after careful and serial CT follow-up.

[Successful repair of the left ventricular wall rupture after mitral valve replacement of an octogenarian; report of a case].

The left ventricular wall rupture is not only a rare complication after mitral valve replacement, but also a high mortality disease. We have encountered a case of this complication after removal of the extracorporeal circulation in an octogenarian female after mitral valve replacement with Carpentier-Edwards (25 mm). It could be successfully repaired from outside the heart on the cardiopulmonary bypass without second cardiac arrest. Repair from inside the heart using extracorporeal circulation and cardioplesia is generally recommended because of the accuracy. However, second cardiac arrest might be a risk of postoperative complications in octogenarians. Hence, prevention is the most important. And operative strategy for the repair is also important in these patients.

[A successful surgical treatment for original Taussig-Bing malformation 13 years after banding of the pulmonary artery].

A 13-year-old girl with original Taussig-Bing malformation underwent successful intraventricular rerouting. In this congenital heart disease, the large pulmonary flow elevates pulmonary arterial pressure and progress the pulmonary vascular diseases in early infancy. Banding of the pulmonary artery helps to prevent the irreversible vascular changes, while that may result in further hypertrophy of the right ventricle. Ideally, radical repair should be performed as soon as possible after definitive diagnosis. Although, she had banding operation of the pulmonary artery at 8 months of age, there was no difference between the right ventricle and the aortic pressure. The subpulmonary space was large enough to make the tunnel with an internal conduit. Additionally, right ventricle outflow tract reconstruction was performed by a Dacron patch. The postoperative cathetherization demonstrated no stenotic region in both left and right ventricular outflow tract. The Kawashima intraventricular rerouting can be applied to the patients without the subaortic stenosis if banding of the pulmonary artery have been performed long before.

An arming yeast with the ability to entrap fluorescent 17beta-estradiol on the cell surface.

We constructed a novel surface-engineered yeast displaying the ligand-binding domain of the rat estrogen receptor (ERLBD). ERLBD, display of which on the yeast cell surface was confirmed by immunofluorescence, possessed strong binding activity to fluorescent 17beta-estradiol - an analogue of the natural ligand of the estrogen receptor - that was comparable to the activity of the native receptor. Environmental homeostasis has recently been disturbed by endocrine disruptors, which cause confusion in the hormone secretion system. It is therefore very important to identify chemical compounds with hormone-like activity and remove them from the environment. The present results demonstrate that the new arming yeast displaying ERLBD on its cell surface will be capable of screening, entrapping, and removing estradiol-like compounds from the environment.

[Exchange transfusions in sepsis after the pediatric open heart surgery].

We experienced 2 cases of septic children after open heart surgery. Both of them recovered by using exchange blood transfusion technique. We use irradiated and dialysed fresh blood for exchange blood transfusion. After this procedure, they recovered from sepsis, as the datas improving, white blood cell reduced from 19,700 +/- 3,710 to 8,200 +/- 2,360, CRP reduced from 5.46 +/- 1.65 to 1.89 +/- 0.70, T-Bil reduced from 7.61 +/- 2.66 to 3.02 +/- 0.89, and BUN reduced from 525.92 +/- 6.64 to 19.76 +/- 5.34. Furthermore, blood pressure and urine volume were stable between exchange blood transfusion, although after open heart surgery. Therefore this procedure has benefits for the compromised, septic patients, performed open heart surgery, because of its stability of the circulating circumstances. And using the irradiated and dialysed fresh blood provides stable condition eventhough under high dose catecholamine use.

[Right ventricular outflow tract reconstruction with PTFE mono-cusped transannular patch for tetralogy of Fallot].

Conotruncal repair for tetralogy of Fallot consists of (1) precise closure of the VSD with the membranous flap and (2) reconstruction of the right ventricular outflow tract (RVOT) by a short transannular patch (< 30% of the RV length) with a wide PTFE monocusp. This report describes the mid-term results in 46 patients with tetralogy of Fallot who underwent conotruncal repair with PTFE monocusped transannular patch and have been followed up for 4 years or more. There was no early and late death and no patient required reoperation. No patient has had a significant residual defect or tricuspid regurgitation (> II). The right and left ventricular pressure ratio was 0.41 +/- 0.12 and the pressure gradient across RVOT was 10.5 +/- 5.9 mmHg, signifying sufficient relief of RVOT obstruction. The mobility of the PTFE monocusp was echocardiographically detected in 86% over a mean follow-up period of 84 +/- 34 months and % freedom from pulmonary regurgitation (> II) was 85.9% at 10 years postoperatively. Excellent long-term durability of the PTFE monocusp provided the normal right vent performance with RVEDV of 91.8 +/- 29.5% of normal and a central venous pressure of 5 +/- 1 mmHg. In conclusion, conotruncal repair with a wide and short transannular patch has provided good mid-term results with the excellent long-term durability of PTFE monocusp.

Regulation of cell growth by redox-mediated extracellular proteolysis of platelet-derived growth factor receptor beta.

Redox-regulated processes are important elements in various cellular functions. Reducing agents, such as N-acetyl-l-cysteine (NAC), are known to regulate signal transduction and cell growth through their radical scavenging action. However, recent studies have shown that reactive oxygen species are not always involved in ligand-stimulated intracellular signaling. Here, we report a novel mechanism by which NAC blocks platelet-derived growth factor (PDGF)-induced signaling pathways in hepatic stellate cells, a fibrogenic player in the liver. Unlike in vascular smooth muscle cells, we found that reducing agents, including NAC, triggered extracellular proteolysis of PDGF receptor-beta, leading to desensitization of hepatic stellate cells toward PDGF-BB. This effect was mediated by secreted mature cathepsin B. In addition, type II transforming growth factor-beta receptor was also down-regulated. Furthermore, these events seemed to cause a dramatic improvement of rat liver fibrosis. These results indicated that redox processes impact the cell's response to growth factors by regulating the turnover of growth factor receptors and that "redox therapy" is promising for fibrosis-related disease.

Right ventricular dynamic cardiomyoplasty for the univentricular heart with pulmonary hypertension.

OBJECTIVES: We conducted an acute experimental study to test the feasibility of dynamic cardiomyoplasty in a setting of modified Fontan procedure for univentricular heart with pulmonary hypertension to obtain a possible proxy for high-risk Fontan candidates. METHODS: After electrical preconditioning of the left latissimuss dorsi for 6 weeks in 8 dogs, the right ventricular cavity was totally obliterated with concomittent closure of the tricuspid valve and right pulmonary artery. Modified Fontan circulation was established with the aortic homograft anastomosed between the right atrium and pulmonary trunk, incorporated with a pericardial pouch as a compression chamber (neoright ventricle) fixed onto the epicardial surface of the ventricle. After cardiopulmonary bypass termination, a latissimus dorsi was applied to wrap the pericardial pouch and ventricle clockwise and stimulated with a trained-pulse (25 Hz) at 1:1 synchronization ratio with cardiac beats. RESULTS: Profound right heart failure was noted during Fontan circulation in increased pulmonary vascular resistance (11 +/- 3.2 Wood units), whereas graft pacing showed significant augmentation of systolic pulmonary pressure by 54 +/- 12%, the mean pulmonary flow by 68 +/- 23%, and aortic pressure by 23 +/- 5% at a physiological range of central venous pressure (13.2 +/- 0.7 mmHg). Right heart function curve analysis confirmed marked augmentation of right heart performance, restoring almost normal pulmonary circulation. These functional benefits were sustained up to 4 hours in 4 animals until experiments were terminated. CONCLUSIONS: Dynamic cardiomyoplasty in a modified Fontan procedure is a viable surgical option for univentricular heart, not a Fontan candidate.

In vivo and in vitro interactions between human colon carcinoma cells and hepatic stellate cells.

Stromal reaction is important for the growth of cancer both in primary and metastatic sites. To demonstrate this reaction during the hepatic metastasis of human colon carcinoma, we histologically investigated alterations to the distribution and phenotype of hepatic stellate cells (HSCs), the only mesenchymal cells in the liver parenchyma, using a nude mouse model. Intrasplenically injected colon carcinoma LM-H3 cells migrated into the space of Disse and underwent proliferation, in close association with hepatocytes and HSCs, at 2 days. At 14 days, HSCs were accumulated around the tumor mass and expressed alpha-smooth muscle actin, a marker for HSC activation. We next investigated in vitro the growth factors involved in the interactions between LM-H3 cells and HSCs. Conditioned medium of rat HSCs which underwent culture-induced activation contained platelet-derived growth factor (PDGF)-AB, hepatocyte growth factor (HGF) and transforming growth factor (TGF)-beta, and could augment LM-H3-cell proliferation and migration. Neutralizing antibodies against PDGF-AA and PDGF-BB and those against PDGF-BB and HGF inhibited proliferation and migration, respectively, of LM-H3 cells, whereas antibody against TGF-beta had no effect. LM-H3 cells expressed PDGF receptors-alpha and -beta and c-met. Conditioned medium of LM-H3 cells contained PDGF-AB, and could enhance HSC proliferation and migration. This augmenting effect was suppressed by treatment with anti-PDGF-AB antibody. The present study has demonstrated that bidirectional interactions involving PDGF and HGF take place in vitro between colon carcinoma cells and HSCs, raising the possibility that similar interactions might be involved in the stromal reaction during hepatic metastasis.

Inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP-470 in rats.

Proliferation and activation of hepatic stellate cells (HSCs) are critical steps for the development of postnecrotic fibrosis in the liver. The present study aimed to reveal the inhibitory effect of the semisynthetic analogue of fumagillin TNP-470 on these events for its possible use as an antifibrogenic agent. Rat models of carbon tetrachloride (CCl(4))- and dimethylnitrosamine-induced hepatic fibrosis were used for an in vivo study. In both models, the fibrotic area was considerably decreased by concurrent repetitive subcutaneous injections of 30 mg/kg body weight of TNP-470. In CCl(4)-induced fibrosis, factor VIII-related antigen-positive blood vessels, desmin-, or alpha-smooth muscle actin (alphaSMA)-positive mesenchymal cells, bromodeoxyuridine (BrdU)-positive mesenchymal cells also decreased in number by treatment with TNP-470. In in vitro experiments, a supplement of 1,000 ng/mL TNP-470 suppressed BrdU incorporation and cyclins D1, D2, and E expression by cultured HSCs in the absence and/or presence of platelet-derived growth factor (PDGF). Expression of HSC activation markers, i.e., alphaSMA and PDGF receptor beta, was also suppressed. The present results indicate that TNP-470 inhibits HSC proliferation by blocking the cell-cycle transition from G1 to S and HSC activation, and, as the consequence, prevents the progression of hepatic fibrosis, probably being coupled with its antiangiogenic effect.

Outcomes of dysplastic nodules in human cirrhotic liver: a clinicopathological study.

The number of dysplastic nodules detected clinically has increased since patients with hepatitis virus-associated cirrhosis, who are at increased risk for hepatocellular carcinoma (HCC), began to undergo regular cancer surveillance. Although it is potentially important to determine which type(s) of nodule may be prone to progress to HCC, outcomes of dysplastic nodules have not been fully investigated. This prompted us to examine the outcomes of dysplastic nodules in cirrhotic patients clinicopathologically. We studied 33 dysplastic nodules of <20 mm in maximum diameter, diagnosed by fine needle aspiration biopsy under ultrasonography (US). These nodules were clinically followed, mainly by US examination, for up to 70 months. When the nodules enlarged or exhibited changes on US, they were histologically reexamined by second biopsy. Surprisingly, 15 of the 33 nodules (45.5%) disappeared, 14 nodules (42.4%) remained unchanged, and only 4 nodules (12.1%) progressed to HCC. The latter 4 nodules were all hyperechoic on US and were composed of clear cells with fatty change or small cells with increased nuclear density, and in all 4 patients serum was positive for hepatitis C virus antibody. Univariate analyses revealed that, although not significant, the hyperechoic nodules or nodules with small cell change showed a higher HCC progression rate in comparison with the hypoechoic nodules or the nodules without small cell change. In summary, most of the dysplastic nodules we followed disappeared or remained unchanged, but some progressed to HCC. Hyperechoic nodules in patients with hepatitis C virus-associated cirrhosis, which show small cell change with increased nuclear density, may be prone to progress to HCC.