Staging laparoscopy leads to rapid induction of chemotherapy for unresectable pancreatobiliary cancers

Preoperatively evaluating the resectability of pancreatobiliary cancers is difficult. The aim of this study was to investigate the benefit of staging laparoscopy in unresectable pancreatobiliary cancers. Between 2010 and 2013, 25 patients with pancreatobiliary cancers underwent staging laparoscopy after conventional tumor staging; they were compared with 10 patients who had unresectable or metastatic tumors that were found during laparotomy. Staging laparoscopy did not show unresectable factors in 11 patients, and resections were performed in these patients. Unresectable factors were found in other 14 patients who underwent staging laparoscopy. In these patients, chemotherapy was started after median postoperative day 3 (range, 2–10 days). This period was significantly longer in patients who received unnecessary laparotomy; chemotherapy was started after median postoperative day 11 (range, 6–15 days). These results suggest that staging laparoscopy, while avoiding laparotomy with unsuccessful resection, can lead to rapid induction of chemotherapy for unresectable pancreatobiliary cancers.     

Evaluation of the Optimal Visceral Branch Configuration in Open Thoracoabdominal Aortic Repair by Computed Tomography

Background: In thoracoabdominal aneurysm (TAAA) repair, our technical modification of visceral reconstruction using longer cut pre-sewn side branches has provided good surgical outcomes. Here, we assessed the long-term durability and patency of revascularized branches using computed tomography (CT) to confirm the validity of our approach.Methods: Early and late CT evaluations were performed in 11 TAAA patients (males: 5; mean age: 60.6 years) using the Coselli graft to evaluate the position of main graft and the diverging pattern and patency of side branches. Seven of 11 were sutured in an extra-anatomical fashion using longer cut side branches.Results: In Anatomical (n = 4) and Extra-anatomical (n = 7) groups, the early patency of side branches was not significantly different. Although the late patency of right renal artery (RA) was 100% in both groups, the one of left RA was 60% in Extra-anatomical, while 100% in Anatomical. Furthermore, the main graft in Extra-anatomical was significantly posterior and leftward to the spine with left RA side branch diverging at an acute angle.Conclusions: When a pre-sewn branched graft designed for TAAA is used, the graft should be sutured in a fashion similar to normal patient anatomy to minimize the possibility of kinking of RA side branch for the patency.     

Combination of vitamin K2 and the angiotensin-converting enzyme inhibitor, perindopril, attenuates the liver enzyme-altered preneoplastic lesions in rats via angiogenesis suppression

BACKGROUND/AIMS: Chemoprevention should be a promising approach to improve the prognosis of the patients with hepatocellular carcinoma (HCC). Angiogenesis is now recognized as a crucial step not only in tumor growth, but also in early carcinogenesis. The aim of this study was to elucidate the combination effect of the clinically used vitamin K(2) (VK) and the angiotensin-converting enzyme inhibitor, perindopril (PE), on hepatocarcinogenesis, especially in conjunction with angiogenesis. METHODS: In a diethylnitrosamine-induced rat hepatocarcinogenesis model, the effects of VK and PE on the development of liver enzyme-altered preneoplastic lesions and angiogenesis were examined. RESULTS: Treatment with both VK and PE markedly inhibited the development of preneoplastic lesions in association with suppression of neovascularization in the liver. The combination treatment with VK and PE exerted a more potent inhibitory effect as compared with the single agent treatments. The in vitro study demonstrated that VK and PE inhibited the endothelial cell (EC) tubular formation. VK also suppressed the EC proliferation in a dose-dependent manner. CONCLUSIONS: The combination of VK and PE exerted a chemopreventive effect against rat liver carcinogenesis via suppression of angiogenesis. Since both agents are widely used in the clinical practice, this combination therapy may represent a potential new strategy for chemoprevention against HCC in the future.     

A case of invasive Langerhans cell histiocytosis localizing only in the lung and diagnosed as pneumothorax in an adolescent female

In infants, Langerhans cell histiocytosis (LCH) is associated with poor clinical outcomes as Langerhans cells invade and damage multiple organs, a presentation that is different from that in adults. Here, we present a case of a 15-year-old female who visited ourclinic complaining of right chest pain and dyspnea. She was diagnosed with right pneumothorax by chest X-ray. Chest computed tomography showed multiple cystic changes in the bilateral lung. Additionally, bullous lesions occupying the upper lobe and multiple white tiny nodules on the surface of the lung were observed by thoracoscopy. These nodules comprised proliferating atypical CD1a/S-100-positive cells invading the pulmonary parenchyma, leading to the diagnosis of LCH. Because of the extensive invasion into the pulmonary parenchyma, chemotherapy was administered. This case of LCH was unique in that the age of onset was atypical and the tumor cells occupied a single organ, despite their malignant behavior.     

Quantifying the atomic-level mechanics of single long physisorbed molecular chains

Individual in situ polymerized fluorene chains 10–100 nm long linked by C–C bonds are pulled vertically from an Au(111) substrate by the tip of a low-temperature atomic force microscope. The conformation of the selected chains is imaged before and after manipulation using scanning tunneling microscopy. The measured force gradient shows strong and periodic variations that correspond to the step-by-step detachment of individual fluorene repeat units. These variations persist at constant intensity until the entire polymer is completely removed from the surface. Calculations based on an extended Frenkel–Kontorova model reproduce the periodicity and magnitude of these features and allow us to relate them to the detachment force and desorption energy of the repeat units. The adsorbed part of the polymer slides easily along the surface during the pulling process, leading to only small oscillations as a result of the high stiffness of the fluorenes and of their length mismatch with respect to the substrate surface structure. A significant lateral force also is caused by the sequential detachment of individual units. The gained insight into the molecule–surface interactions during sliding and pulling should aid the design of mechanoresponsive nanosystems and devices.Ever since the invention of the atomic force microscope (AFM) (1) and the first imaging applications, force spectroscopy has been applied to study the mechanical behavior of polymers (2); more complex chain-like biomolecules, e.g., DNA complementary strands (3); and proteins, subject to controlled extension (2) or applied force (4), mostly in solution and at room temperature. Reactive groups are chemically inserted at the ends and/or along each molecule to firmly bind some of them to suitably functionalized tips and sample surfaces. Irreversible jumps in curves of force vs. vertical separation may be associated in this way with the rupture of bonds or the unfolding of coiled subunits. If reproducible, the lowest peak in the histogram of the forces attained just before each jump is attributed to such an event in a single molecular chain or complementary pair. In the case of homogeneous polymers or protein segments, simulations based on two-state rate theory combined with a standard model of polymer nonlinear elasticity can reproduce such events, whereas reversible plateaus or continuous rises in the force may be associated with fast binding–rebinding processes or with large thermal fluctuations (2). Attention thus has focused on conformational changes strongly influenced by pulling speed or imposed force jumps (4) and also by external stimuli, e.g., optical excitation of inserted chromophores (5) or specific reactants or enzymes (6). Furthermore, mechanical forces recently were discovered by chemists as a unique stimulus to induce specific chemical reactions. In this so-called mechanochemistry, sonication typically is applied to polymer systems and is believed to result in a strong force acting on the weakest link in the chain, where the reaction takes place (7, 8). Regardless of the direct or indirect exposure to force, it is clear that the mechanics of polymer chains constrained in their surrounding environment is of utmost importance for a variety of biophysical and chemical processes as well as self-healing materials applications (9, 10).A few pulling studies have been conducted on polyelectrolytes unspecifically adsorbed on self-assembled monolayers via tunable electrostatic interactions (11), including DNA (12). They merely revealed noisy force plateaus, interpreted as continuous partial desorption of single chains, terminated by a drop to zero upon complete detachment from the surface. Despite the undisputed merit of these studies, little is known about the mechanical behavior of single molecular chains pulled off a surface, both defined and characterized on the atomic scale, in the absence of significant thermal fluctuations and drifts. Measurements at low temperature reduce the diffusion of adsorbates and provide an opportunity to determine the energetic landscape of specific molecules interacting with a surface under controlled conditions. As demonstrated here, the sliding and detachment mechanisms of individual polymer repeat units can then be inferred from the analysis of pulling experiments. A detailed interpretation of our results, based on a modified Frenkel–Kontorova (FK) model (13), also is presented.     

Impact of Renal Artery Stent Implantation on Hypertension in Patients with Hemodialysis

The benefit from renal artery stent implantation to treat atherosclerotic renal artery stenosis (ARAS) is not well understood in hemodialysis patients. We sought to evaluate the effects of renal artery stenting on hypertension of hemodialysis patients. Renal artery stent implantation was successfully performed on eight hypertensive hemodialysis patients with ARAS (mean ± SD, 66 ± 10 years; men 6, women 2). Blood pressure was measured by automated oscillometric recordings just before hemodialysis. Mean values of the blood pressure, measured 12 times a month, were used for blood pressure analysis. Values of systolic blood pressure decreased at 6 months after renal artery stent implantation (162.6 ± 29.7 to 121.1 ± 23.3 mm Hg, p = 0.0015). Values of diastolic blood pressure also decreased from 77.6 ± 13.6 to 65.6 ± 7.2 mm Hg (p = 0.02). Renal artery stent implantation for ARAS had a beneficial effect on hypertension in hemodialysis patients.     

Aβ neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-D-aspartate receptors

N-methyl-d-aspartate receptors (NMDARs) mediate critical CNS functions, whereas excessive activity contributes to neuronal damage. At physiological glycine concentrations, NMDAR currents recorded from cultured rodent hippocampal neurons exhibited strong desensitization in the continued presence of NMDA, thus protecting neurons from calcium overload. Reducing copper availability by specific chelators (bathocuproine disulfonate, cuprizone) induced nondesensitizing NMDAR currents even at physiologically low glycine concentrations. This effect was mimicked by, and was not additive with, genetic ablation of cellular prion protein (PrP(C)), a key copper-binding protein in the CNS. Acute ablation of PrP(C) by enzymatically cleaving its cell-surface GPI anchor yielded similar effects. Biochemical studies and electrophysiological measurements revealed that PrP(C) interacts with the NMDAR complex in a copper-dependent manner to allosterically reduce glycine affinity for the receptor. Synthetic human Aβ(1-42) (10 nM-5 μM) produced an identical effect that could be mitigated by addition of excess copper ions or NMDAR blockers. Taken together, Aβ(1-42), copper chelators, or PrP(C) inactivation all enhance the activity of glycine at the NMDAR, giving rise to pathologically large nondesensitizing steady-state NMDAR currents and neurotoxicity. We propose a physiological role for PrP(C), one that limits excessive NMDAR activity that might otherwise promote neuronal damage. In addition, we provide a unifying molecular mechanism whereby toxic species of Aβ(1-42) might mediate neuronal and synaptic injury, at least in part, by disrupting the normal copper-mediated, PrP(C)-dependent inhibition of excessive activity of this highly calcium-permeable glutamate receptor.     

Measurement of vaporization cavity after CO2 laser irradiation on bovine dentin

Lasers are used for various clinical applications in dental practices, and many studies have examined the effects of lasers with different applications on enamel and dentin. The CO₂ laser was introduced into the dental clinic for the removal of caries and for cavity preparation of hard tissues, in anticipation of replacing air turban and micromotor devices. The aim of this study was to examine dentin structural changes by measuring 3-dimensional diameter, depth, and volume in bovine teeth irradiated with a CO₂ laser at 1, 3, or 5 W. According to our measurements, a vaporization depth of 400 μm was created by irradiation for a mere 100 ms in the case of 3 W irradiation and 500 μm in the case of 5 W irradiation. Further, at the same output power, the pulse mode transmitted energy to deeper layers of the tooth as compared with the continuous wave mode, indicating that the pulse mode has more penetrating power than the continuous wave mode. Moreover, the depth of cavity that after laser irradiated was > 500 μm at output power 5 W. Thus, irradiation at high output power and the influence of pulse mode on the pulp tissue cannot be disregarded. That is to say, it is important to consider irradiation output power, mode, direction, and distance when lasers are used for adjacent to pulp of tooth that primary incisors and deep cavities.