Primary Lymphangiosarcoma of the Urinary Bladder in a Dog.

Abdominal ultrasonographical and computed tomography examinations of a 12-year-old neutered female toy poodle revealed a protruding mass, approximately 2 cm in diameter, at the apex of the bladder. The mass was firm and haemorrhagic with a homogeneously brownish-yellow cut surface. Microscopically, it was unencapsulated and located in the muscle layer with invasion of the extra-muscular layer. It was composed of spindloid to oval neoplastic cells that formed irregular clefts and diffuse sheets that dissected bundles of collagen. Immunohistochemically, the neoplastic cells were positive for vimentin and lymphatic vessel endothelial hyaluronan receptor 1 antigens, but negative for cytokeratin AE1/AE3, factor VIII-related antigen, CD31, CD34, Prox-1, S100, desmin, α-smooth muscle actin and MyoD1. Negative immunolabelling for laminin antigen supported the absence of evidence of a basal lamina on ultrastructural examination. Based on these findings, this tumour was identified as a lymphangiosarcoma. To the best of our knowledge, this case is the first report of lymphangiosarcoma arising from the bladder in a dog.

Association between dexamethasone treatment and alterations in serum concentrations of trace metals.

Previously, a significant elevation in the serum levels of iron (Fe) was observed within a few days after the initiation of cisplatin (CDDP)-based chemotherapy. To clarify the underlying mechanisms, the serum concentration of hepcidin, a negative regulator of Fe release, was determined in the clinical samples obtained from six patients with cancer. The result showed that the serum concentration of hepcidin in patients receiving CDDP-based chemotherapy was significantly increased after 4-6 days of treatment, in comparison to the baseline level, suggesting that aforementioned excessive systemic Fe was not explained by the change of serum hepcidin level. All these patients received antiemetic premedication. We next evaluated of the effects of Pt-containing drugs and prophylactic antiemetic dexamethasone medication on the serum concentration of trace metals in mice, and on the hepatic and renal concentration of trace metals. The serum concentrations of Fe, Cu, and Zn in the CDDP-treated and oxaliplatin-treated mice were not significantly altered in comparison to those of the vehicle-treated control group. The serum concentrations of Fe, Cu, and Zn were increased after 24 h of dexamethasone treatment, compared to those of the control group (P < 0.05). The hepatic concentration of Mn was significantly reduced, whereas those of Fe and Cu inclined to diminish. The present findings suggest that dexamethasone can partly contribute to the changes in the serum concentrations of trace metals during anticancer chemotherapy.

Effects of intermittent Pringle's manoeuvre on cirrhotic compared with normal liver.

BACKGROUND: Although patients with liver cirrhosis are supposed to tolerate ischaemia-reperfusion poorly, the exact impact of intermittent inflow clamping during hepatic resection of cirrhotic compared with normal liver remains unclear. METHODS: Intermittent Pringle's manoeuvre was applied during minor hepatectomy in 172 patients with a normal liver, 59 with chronic hepatitis and 97 with liver cirrhosis. To assess hepatic injury, delta (D)-aspartate aminotransferase (AST) and D-alanine aminotransferase (ALT) (maximum level minus preoperative level) were calculated. To evaluate postoperative liver function, postoperative levels of total bilirubin, albumin and cholinesterase (ChE), and prothrombin time were measured. RESULTS: Significant correlations between D-AST or D-ALT and clamping time were found in each group. The regression coefficients of the regression lines for D-AST and D-ALT in patients with normal liver were significantly higher than those in patients with cirrhotic liver. Irrespective of whether clamping time was 45 min or less, or at least 60 min, D-AST and D-ALT were significantly lower in patients with cirrhosis than in those with a normal liver. Parameters of hepatic functional reserve, such as total bilirubin, prothrombin time, albumin and ChE, were impaired significantly after surgery in patients with a cirrhotic liver. CONCLUSION: Patients with liver cirrhosis had a smaller increase in aminotransferase levels following portal triad clamping than those with a normal liver. However, hepatic functional reserve in those with a cirrhotic liver seemed to be affected more after intermittent inflow occlusion.

[Metastatic lung cancer origin from osteosarcoma of mandible invading tracheal lumen].

A 52-year-old woman underwent the surgical treatment for osteosarcoma of the left mandible in 2003 and was followed up afterward. She suffered from dry cough and bloody sputum, and was admitted to our hospital in April 2007. Computed tomography (CT) revealed several nodules in bilateral lung, and bronchofiberscopy showed the endobronchial tumor obstructing in the right main bronchus. The metastatic tumor progressed in the right main bronchus from the right S6 lung segment. The tumor rapidly progressed in the right bronchus in comparison with the CT findings in about 2 weeks, and the possibility of the tracheal obstruction was considered. She underwent the right middle and lower lobectomy, and the endobronchial tumor was pulled through the right main bronchus. The postoperative course was uneventful, the patient was discharged on 14th postoperative day, and the chemotherapy using cisplatin (CDDP) and adriamycin (ADR) is on-going.

[Thymic carcinoma involving aortic arch; report of a case].

Adenocarcinoma of the thymus is a very rare malignant tumor. The standard treatment for advanced thymic carcinoma has not yet been established, and the prognosis is poor. We report a case of thymic carcinoma that involving the aortic arch and the innominate vein. A 78-year-old woman was admitted to our hospital complaining of hoarseness in April 2007. The computed tomography (CT) scan showed an anterior mediastinal tumor contiguous to the aortic arch and the innominate vein with swelling lymphnodes. Microspcopic examinations of specimens obtained by CT-guided needle biopsy revealed poorly differenciated adenocarcinoma. The carcinoembryonic antigen (CEA) level of serum elevated at 54.9 ng/ml. Thymic carcinoma was diagnosed. The chemoradiotherapy [concurrent, carboplatin (CBDCA) + paclitaxel(TXL)-->vinorelbine (NVB), 60 Gy] was performed, but the effect of the therapy was limited. The resection of the tumor with a part of aortic arch and other peripheral tissues was performed in Augast 2007. The postoperative course was uneventful and the CEA level of serum lowered to the normal. She was discharged 30 days after surgery.

[Right lung cancer with right aortic arch].

An abnormal shadow was detected on chest X-ray mass screening in an asymptomatic 63-year-old man. The further examinations revealed the shadow to be primary lung cancer (Rt. S6. adenocarcinoma, cT2N0M0, c-stage IB) with right aortic arch. We used 3 dimentional-computed tomography (3D-CT) to assess an anatomical feature of vessels in detail. The right lower lobectomy and the dissection of medi astinal lymph nodes was performed. We confirmed no abnormal anatomy of pulmonary artery and vein at surgery, and it was possible to perform right lower lobectomy with the common procedure. Since lymph node was found by intraopetrative pathological examination, since no metastasis from interlobar to subcarinal lymph node was found, we did not perform dissection of upper mediastinal dissection, which was equivalent to ND2a lymph nodes dissection of the left lung cancer in General Rule for Clinical and Pathological Record of Lung Cancer. The patient with right aortic arch is known to have variant anatomy of other intrathoracic vessels occasionally. 3D-CT was quite useful in assessing anatomical feature, and enabled us to perform safe operation.

Impact of a left-lobe graft without modulation of portal flow in adult-to-adult living donor liver transplantation.

In adult-to-adult living donor liver transplantation (LDLT), left-lobe grafts can sometimes be small-for-size. Although attempts have been made to prevent graft overperfusion through modulation of portal inflow, the optimal portal venous circulation for a liver graft is still unclear. Hepatic hemodynamics were analyzed with reference to graft function and outcome in 19 consecutive adult-to-adult LDLTs using left-lobe grafts without modulation of graft portal inflow. Overall mean graft volume (GV) was 398 g, which was equivalent to 37.8% of the recipient standard liver volume (SV). The GV/SV ratio was less than 40% in 13 of the 19 recipients. Overall mean recipient portal vein flow (PVF) was much higher than the left PVF in the donors. The mean portal contribution to the graft was markedly increased to 89%. Average daily volume of ascites revealed a significant correlation with portal vein pressure, and not with PVF. When PVP exceeds 25 mmHg after transplantation, modulation of portal inflow might be required in order to improve the early postoperative outcome. Although the study population was small and contained several patients suffering from tumors or metabolic disease, all 19 patients made good progress and the 1-year graft and patient survival rate were 100%. A GV/SV ratio of less than 40% or PVF of more than 260 mL/min/100 g graft weight does not contraindicate transplantation, nor is it necessarily associated with a poor outcome. Left-lobe graft LDLT is still an important treatment option for adult patients.

Laparoscopy-assisted right hepatic lobectomy using a wall-lifting procedure.

This article describes a new technique for performing a laparoscopy-assisted right hepatic lobectomy using a hanger wall-lifting procedure. The patient is placed in the left semi-lateral position. A cholecystectomy and hemi-hepatic vascular inflow control are then performed through a midline incision, through which the resected liver can be removed. Next, the right lower chest and right upper abdominal wall are lifted by two wires vertical to the abdominal wall. Two ports, a 5-mm port in right lateral abdomen for forceps and a 12-mm port just right of the umbilicus for the laparoscope, are inserted. The obtained view of the operative field in the right upper abdominal cavity is thus excellent. The laparoscopy-assisted mobilization of the right hepatic lobe is done with the assistance of a hand inserted through the midline incision, including a dissection of the hepato-renal ligament, the right triangular ligament, and the right coronary ligament. A parenchymal dissection is then performed using the Cavitron Ultrasonic Surgical Aspirator (CUSA) and the resected specimen is passed through the midline incision without any morcellation of the liver. This procedure can minimize the length of the wound, while avoiding the lethal complications associated with pneumoperitoneum.

Conversion of elective laparoscopic to open cholecystectomy between 1993 and 2004.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the standard treatment for symptomatic gallbladder disease. The identification of factors that reliably predict the likely need to convert LC to an open procedure would provide short-term benefits in terms of patient education and postoperative expectations. METHODS: Between 1993 and 2004, 1179 elective LCs were attempted from a total of 1339 elective cholecystectomies. The change in conversion rate between 1993-1999 and 2000-2004 was analysed. Factors predictive of higher risk for conversion were also identified. RESULTS: Eighty-nine LCs (7.5 per cent) required conversion. Gallbladder wall thickness and a history of common bile duct (CBD) stones, treated by preoperative endoscopic sphincterotomy, were predictors of conversion. The proportion of patients who underwent LC was the same in 1993-1999 (87.5 per cent) and 2000-2004 (88.8 per cent), but the conversion rate increased significantly from 5.3 to 10.6 per cent in these two time intervals. In addition, the proportion of patients with a history of CBD stones rose significantly, from 6.4 per cent in 1993-1999 to 11.0 per cent in 2000-2004. CONCLUSION: The conversion rate increased over the 12-year interval of the study. A history of preoperative endoscopic sphincterotomy and a thickened gallbladder wall contributed to the likelihood of conversion.

Clinical significance of immunohistochemically detectable lymph node metastasis in adenocarcinoma of the ampulla of Vater.

BACKGROUND: The aim of this study was to assess the impact of immunohistochemically identified lymph node metastasis on survival in patients with carcinoma of the ampulla of Vater. METHODS: Three hundred and twenty-six regional lymph nodes dissected from pancreatoduodenectomy specimens from 25 patients with ampulla of Vater carcinoma were immunostained with anticytokeratin antibody (CAM 5.2). The clinicopathological significance of immunohistochemically detectable lymph node metastasis was evaluated and compared with that of other potential prognostic factors. RESULTS: The frequency of lymph node involvement in relation to the total number of dissected lymph nodes increased from 5.5 per cent (18 of 326) using haematoxylin and eosin staining to 9.5 per cent (31 of 326) using cytokeratin immunostaining (P < 0.001). Lymph node involvement was revealed by haematoxylin and eosin staining in eight of 25 patients and by cytokeratin immunostaining in 11 of 25 patients (P = 0.006). Absence of immunohistochemically detectable lymph node metastasis was identified as an independent predictor of improved postoperative survival. CONCLUSION: Immunostaining of dissected lymph nodes adds additional information to data obtained by conventional haematoxylin and eosin staining when determining the prognosis of patients with carcinoma of the ampulla of Vater.

[Effectiveness of high-dose, intermittent 5'-DFUR therapy for advanced gastric cancer].

We report a case of advanced gastric cancer with multiple liver metastases and peritoneal dissemination. The patient was effectively treated with high-dose 5'-DFUR. A 52-year-old patient with advanced gastric cancer and multiple liver metastases, who showed a high serum level of CEA and CA19-9 underwent simple D1 gastrectomy. Thereafter, he received per os 1,200 mg/day of 5'-DFUR intermittently (5 days a week) and TAI every four months postoperatively. The serum levels of both CEA and CA19-9 fell dramatically to within the normal range and were maintained thereafter until the present. The size and number of the liver metastases dramatically decreased, judging from CT and angiography findings.

Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis.

A major hallmark of apoptosis is normotonic shrinkage of cells. Here, we studied the relation between apoptotic cell shrinkage and apoptotic cell death. Induction of the apoptotic volume decrease (AVD) under normotonic conditions was found to be coupled to facilitation of the regulatory volume decrease (RVD), which is known to be attained by parallel operation of Cl(-) and K(+) channels, under hypotonic conditions. Both the AVD induction and the RVD facilitation were found to precede cytochrome c release, caspase-3 activation, DNA laddering, and ultrastructural alterations in three cell types after apoptotic insults with two distinct apoptosis inducers. Also, the AVD was not prevented by a broad-spectrum caspase inhibitor. When the AVD induction and the RVD facilitation were prevented by blocking volume-regulatory Cl(-) or K(+) channels, these cells did not show succeeding apoptotic biochemical and morphological events and were rescued from death. Thus, it is concluded that the AVD, which is caused by disordered cell volume regulation, is an early prerequisite to apoptotic events leading to cell death.

A role for p27/Kip1 in the control of cerebellar granule cell precursor proliferation.

During development, control of proliferation of neuronal precursor cells plays a crucial role in determining the number of neurons. Proliferation is driven by mitogens, but how it is terminated remains a mystery. In this study, we examined the role of cyclin-dependent kinase inhibitors in the control of proliferation of cerebellar granule cell precursors (GCPs). Among the inhibitors we examined, only p27/Kip1 (p27) was expressed at significant levels in cells of the granule cell lineage in the developing and adult cerebellum. In developing cerebella, p27 was expressed in the external germinal layer (the deeper regions), the molecular layer, and the granule layer. In adult cerebella, p27 was expressed in the cells of the granule layer. We isolated and purified GCPs from cerebella of developing mice and examined their bromodeoxyuridine (BrdU) uptake and p27 expression at various times. We found that there was an inverse correlation between BrdU uptake and p27 expression. Even in the presence of saturating amounts of Sonic hedgehog, a potent mitogen, the cells eventually stopped dividing and differentiated, expressing p27 strongly. We also examined mice in which one or both copies of the p27 gene have been inactivated by targeted gene disruption and found that their cerebella were larger than those of wild-type mice. In cell cultures, GCPs prepared from p27-deficient mice showed enhanced proliferation compared with GCPs from wild-type mice. Taken together, these results suggest that there is an intracellular mechanism that stops GCP division and causes GCPs to differentiate and that p27 is part of this mechanism.

Effect of pranlukast on bronchial inflammation in patients with asthma.

BACKGROUND: Pranlukast (8-[p-(4-phenylbutyloxy) benzol] amino-2-[tetrazol-5-yl]-4-oxo-4H-1-benzopyran hemihydrate), a selective cysteinyl leukotriene receptor antagonist, has been reported to exhibit not only antileukotrine activity but also pharmacological activity including antieosinophilic effects. OBJECTIVE: This study was designed to investigate whether the antiasthmatic activity of pranlukast is associated with a reduction in eosinophilic inflammation. METHODS: A double-blind, randomized, crossover design was used. Subjects received 225 mg of pranlukast or placebo orally twice daily for 4 weeks and then, after a washout period of at least 4 weeks, crossed over to receive the alternative treatment. We assessed the effects of pretreatment with pranlukast on bronchoconstriction precipitated by inhalation of methacholine in 32 adult patients with mild or moderate bronchial asthma; those who were in stable clinical condition were allocated to this study. Blood and sputum samples were taken the morning of the methacholine provocation test. Eosinophil counts and measurement of eosinophilic cationic protein (ECP) were performed. RESULTS: After the 4 weeks of treatment with pranlukast, patients' symptoms, blood eosinophils, serum ECP, sputum eosinophils, and sputum ECP were significantly decreased. Furthermore, values of PC20-methacholine significantly improved in the treatment with pranlukast. CONCLUSION: Our results suggest that pranlukast has an anti-inflammatory effect on bronchial eosinophilic infiltration. This study raises further interesting therapeutic possibilities and argues for further trials of new approaches to the treatment of bronchial asthma.

Immobilization on the day 14th does not disrupts the basic diurnal rhythm of bone resorption.

Weight bearing and physical activity are important mechanical stimuli to bone growth and metabolism, and microgravity, such a space flight and/or bed rest, induces bone resorption and bone loss. An increased excretion of urinary Ca, an increased bone resorption and a decreased bone mineral density (BMD) have been observed in bed rest experiment of healthy subjects. Bone resorption markers show the specific circadian rhythms in human. Cross-linked carboxyl-terminal telopeptide of type I collagen (ICTP) and the urinary excretion of deoxypyridinoline (Dpy) are the highest in the early morning and the lowest late at night. Bed rest immobilization might influence these rhythms, due to no mechanical loading with loss of daily life activity. Bone resorption markers in healthy subjects had been compared between before and during bed rest to determine disruption of diurnal rhythms of bone resorption.

Efficacy of leukotriene receptor antagonist in bronchial hyperresponsiveness and hypersensitivity to analgesic in aspirin-intolerant asthma.

BACKGROUND: Albeit its exact pathogenesis is still ambiguous; aspirin-intolerant asthma is one of several types of asthma for which antileukotriene therapy is useful, because it is widely accepted that bronchial over-production of leukotrienes may be involved in its pathogenesis. Pranlukast (8-[p-(4-phenylbutyloxy) benzol] amino-2-(tetrazol-5-yl)-4-oxo-4H-1-benzopyran hemihydrate), a selective cysteinyl leukotriene receptor antagonist, is now widely used in the treatment of asthma. OBJECTIVE: This study was designed to investigate the protective effect of pranlukast on airway sensitivity to sulpyrine provocation testing, bronchial responsiveness to methacholine provocation testing, and to investigate whether this protective activity is associated with a reduction in aspirin-induced excretion of urinary LTE4 (uLTE4), a marker of the cysteinyl leukotriene (LT) overproduction that participates in the pathogenesis of aspirin-induced asthma. METHODS: We assessed the effects of pretreatment with pranlukast on bronchoconstriction precipitated by inhalation of methacholine and sulpyrine in 16 adult patients with mild or moderate aspirin-intolerant asthma; those who were in stable clinical condition and were hypersensitive to sulpyrine provocation testing were allocated to this study. A double-blind, randomized, crossover design was used. uLTE4 was measured using combined reverse-phase high-performance liquid chromatography (rp-HPLC)/enzyme immunoassay. RESULTS: Pranlukast protected against analgesic-induced bronchoconstriction through mechanisms that were not related to the bronchodilator property, but were related to the improvement both of bronchial hyperresponsiveness and hypersensitivity to analgesic (P < 0.005 and P < 0.0001). Pranlukast showed little effect on excretion of uLTE4. CONCLUSION: These results support the hypothesis that cysteinyl leukotriene is one of the most important components in the pathogenesis of aspirin-intolerant asthma. Pranlukast improves not only hypersensitivity to analgesic, but also bronchial hyperresponsiveness in aspirin-intolerant asthma. It is also possible that pranlukast has another anti-asthmatic effect besides that of a leukotriene receptor antagonist.

Possible involvement of a chloride-bicarbonate exchanger in apoptosis of endothelial cells and cardiomyocytes.

We examined the role of ion movement in staurosporine-induced apoptosis of vascular endothelial cells. Cultured vascular endothelial cells from bovine carotid arteries were used. Apoptosis was determined by propidium iodide assay. Treatment of the endothelial cells with staurosporine (10 nmol/l-1 micromol/l) for 6 h induced nuclear fragmentation in a dose-dependent manner. Staurosporine (1 micromol/l) elicited apoptosis in 70.5+/-1.5% of cells. Concomitant treatment of endothelial cells with 1 mmol/l of 4, 4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), a chloride-bicarbonate exchange blocker, completely inhibited staurosporine-induced apoptosis. Other ion transporter inhibitors such as dimethyl amiloride and anthracene-9 carboxylic acid were less effective inhibitors of staurosporine-induced apoptosis of endothelial cells. DIDS prevented staurosporine-induced apoptosis of endothelial cells as well as cardiomyocytes. Next, we determined whether chloride ions or bicarbonate are involved in apoptosis. Incubation with a chloride ion removal buffer did not inhibit staurosporine-induced apoptosis of endothelial cells. However, endothelial cell apoptosis was completely suppressed by an inhibitor of caspase, benzyloxycarbonyl-Asp-CH(2)-O(C)O-dichlorobenzene (zD-dcb, 50 micromol/l). Staurosporine (1 micromol/l) increased the intracellular pH of endothelial cells, and DIDS (1 mmol/l), but not a caspase inhibitor, inhibited this increase in pH caused by staurosporine. Our findings suggest that endothelial cell apoptosis induced by staurosporine may be associated with the Cl(-)and bicarbonate (HCO-3) ions. Thus, Cl(-)efflux from cells or HCO-3 influx to cells (which increases pH) may play an important role in signal transduction leading events such as activation of caspase in staurosporine-induced apoptosis.

Evaluation of local excision for sessile-type lower rectal tumors.

BACKGROUND/AIMS: A study was undertaken to evaluate the surgical morbidity and risk of recurrence in patients undergoing local excision for rectal carcinoma. METHODOLOGY: Twenty patients with well or moderately differentiated lesions less than 6 cm in diameter, which were difficult to remove endoscopically but had no clinically involved regional nodes, were eligible for local excision. RESULTS: The transanal approach was simple and had few complications. After posterior parasacral excision, 3 patients developed rectocutaneous fistulas, and 1 of them died. None of the 12 patients with cancer extension limited to the lesser depth of the submucosa died of rectal cancer. Among 8 patients with cancer invasive into the greater depth of the submucosa or deeper, 5 underwent additional radical resection, and regional lymph node metastasis was revealed in 2. CONCLUSIONS: Transanal excision is suitable for curative resection of lower rectal tumors when the cancer extends only to the lesser depth of the submucosa. The procedure should be defined as a total excisional biopsy until the results of histologic examination are obtained.

Clinical evaluation of 3D-CT cholangiography for preoperative examination in laparoscopic cholecystectomy.

Three-dimensional-computed tomography (3D-CT) cholangiography is a 3D shaded surface display image of the biliary tract obtained by using helical CT after intravenous cholangiography or cholangiography per percutaneous transhepatic cholangio-drainage tube. We investigated whether 3D-CT cholangiography could provide a useful image, for preoperative examination in laparoscopic cholecystectomy. Sixty-five patients with biliary diseases were examined by 3D-CT cholangiography. Helical scanning was performed on a Proceed Accell (GE Medical Systems, Waukesha, WI, USA). Three-dimensional images were created using an independent workstation. A clear image of the common bile duct was obtained for all patients (100%) by 3D-CT cholangiography. The gallbladder was well visualized in 54 (93%) and the cystic duct was shown to be opacified in 55 (95%) of the 58 patients with a gallbladder. Thirty-one patients were diagnosed as having gallstones by 3D-CT cholangiography (sensitivity. 72.1%; specificity, 100%; accuracy, 79.3%), while 43 were diagnosed as having cholecystolithiasis by ultrasonography. The advantages of 3D-CT cholangiography were a low level of invasiveness, easily obtained images compared to those obtained with endoscopic retrograde cholangiography (ERC), good opacification, and provision of a three-dimensional understanding of the biliary system, especially of the cystic duct. When combined with ultrasonography and routine liver function tests, 3D-CT cholangiography was considered very useful for obtaining information before laparoscopic cholecystectomy. It allowed the omission of ERC in many patients who were considered to have no common bile duct stone, by employment of 3D-CT cholangiography.