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Teleradiology is recognized for fostering collaboration between regional and tertiary hospitals. However, its application in gastroenterological diseases remains underexplored. This study aimed to assess the effectiveness of teleradiology in improving gastroenterological care. This retrospective study analyzed patients with gastroenterological diseases in a tertiary hospital who were referred from a regional hospital using a cloud-based radiology image-sharing system between July 2020 and June 2023. Our primary focus was to conduct a descriptive statistical analysis to evaluate patient characteristics and the referral process and analyze the timeframes from referral to transfer and from the start of treatment to discharge and the outcomes. We analyzed 56 patients, with 45 (80.4%) presenting hepatobiliary pancreatic disease. The most frequent condition was common bile duct stones (17 cases). Forty-nine cases were transferred for inpatient treatments, four underwent endoscopic examinations as outpatients, and two had imaging consultation without subsequent hospital visits. On referral day, 16 patients were transferred, and the remaining 33 (67.3%) were placed on a waiting list starting from the subsequent day. The median time from referral to admission was 1 day (range: 0-14 days), and the median time from referral to treatment was 2 days (range: 0-14 days). Remote image-sharing systems ensure accurate imaging at referral, preventing care delays. In collaboration with regional and tertiary hospitals, teleradiology may also be useful for gastroenterological diseases., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Saffman-Taylor instability exhibits a stepwise unstable morphology from a stable interface to viscous fingering, eventually leading to tip splitting. The nonlinear dynamics of the destabilized interface depends on various flow properties. However, the physicochemical mechanism that determines the transition point of the flow state is unclear. We studied the interfacial instability transition in miscible displacement from a thermodynamic perspective by calculating the momentum transport and entropy production. Using numerical analysis based on Darcy's law coupled with the convection-diffusion equation, the observed flux-dependent flow state transitions were attributed to the selection of the flow state with a higher entropy production.

Background and Aim: Convolutional neural network (CNN) systems that automatically detect abnormalities from small-bowel capsule endoscopy (SBCE) images are still experimental, and no studies have directly compared the clinical usefulness of different systems. We compared endoscopist readings using an existing and a novel CNN system in a real-world SBCE setting., Methods: Thirty-six complete SBCE videos, including 43 abnormal lesions (18 mucosal breaks, 8 angioectasia, and 17 protruding lesions), were retrospectively prepared. Three reading processes were compared: (A) endoscopist readings without CNN screening, (B) endoscopist readings after an existing CNN screening, and (C) endoscopist readings after a novel CNN screening., Results: The mean number of small-bowel images was 14 747 per patient. Among these images, existing and novel CNN systems automatically captured 24.3% and 9.4% of the images, respectively. In this process, both systems extracted all 43 abnormal lesions. Next, we focused on the clinical usefulness. The detection rates of abnormalities by trainee endoscopists were not significantly different across the three processes: A, 77%; B, 67%; and C, 79%. The mean reading time of the trainees was the shortest during process C (10.1 min per patient), followed by processes B (23.1 min per patient) and A (33.6 min per patient). The mean psychological stress score while reading videos (scale, 1-5) was the lowest in process C (1.8) but was not significantly different between processes B (2.8) and A (3.2)., Conclusions: Our novel CNN system significantly reduced endoscopist reading time and psychological stress while maintaining the detectability of abnormalities. CNN performance directly affects clinical utility and should be carefully assessed., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Phase separation is ubiquitous in nature and technology. So far, the focus has primarily been on phase separation occurring in the bulk phase. Recently, phase separation taking place in interfacial areas has attracted more attention - in particular, a combination of interfacial phase separation and hydrodynamics. Studies on this combination have been conducted intensively in this past decade; however, the detailed dynamics remain unclear. Here, we perform fluid displacement experiments, where a less viscous solution displaces a more viscous one in a radially confined geometry and phase separation occurs at the interfacial region. We demonstrate that a finger-like pattern, due to the viscosity contrast during the displacement, can be suppressed by the phase separation. We also claim that the direction of a body force, the so-called Korteweg force, which appears during the phase separation and induces convection, determines whether the fingering pattern is suppressed or changed to a droplet pattern. The change of the fingering pattern to the droplet pattern is enhanced by the Korteweg force directed from the less viscous solution to the more viscous one, whereas the fingering is suppressed by the force directed in the opposite direction. These findings will contribute directly to the higher efficiency of processes such as enhanced oil recovery and CO 2 sequestration, where interfacial phase separation is considered to occur during the flow.

A chemical reaction in the flow field affects the physical property of fluids, resulting in changing flow dynamics. The effect of the reaction on the flow dynamics is normally evaluated by comparison between the physical properties of the fluid between pre- and post-reaction. However, our group found a polymeric reacting flow in which a comparison between pre- and post-reaction fluid properties is insufficient to evaluate the influences of the reaction on the flow dynamics (T. Ueki et al. , J. Phys. Chem. B , 2019, 123 , 4587-4593). In the study, we examined the stirred flow by an impeller in a beaker with a chemical reaction between partially hydrolyzed polyacrylamide (HPAM) solution and Fe(NO 3 ) 3 solution. We found that a so-called Weissenberg effect, where the stirred solution climbs up the stirring shaft because of an increase in the viscoelasticity of the mixed solution, transiently appeared in only the halfway of the reaction, although the reaction slightly decreased the solution's viscosity at the final stage under a certain pH and we proposed the mechanism for the temporal increase in the viscoelasticity. In the present study, we conducted similar experiments as our previous study using HPAM solution at various pH and two concentrations of Al(NO 3 ) 3 solutions. The unpredictable flow dynamics by comparison between pre- and post-reaction fluid properties, i.e. , the appearance and disappearance of the Weissenberg effect, has been observed under a certain pH and Al(NO 3 ) 3 concentration. We investigated the mechanism by means of the simultaneous measurement of pH and the stirring torque and the identification of the dominant species of aluminum aqua complexes by the Henderson-Hasselbalch equation. As a result, we proposed two mechanisms of dissapearance of the Weissenberg effect: one is the same for the Fe(NO 3 ) 3 case but the other is unique and novel for the Al(NO 3 ) 3 case. This study can contribute to the comprehensive understanding of the conditions for the occurrence of the unpredictable dynamics of polymeric reacting flow by comparison between the pre- and post-reaction fluid properties.

The effects of countercations and coexisting compounds on the molecular structure of the [M(α-PW 11 O 39 ) 2 ] n - polyanion were analyzed in terms of the repulsion and twisting of two [α-PW 11 O 39 ] 7- units. More specifically, it was found that two [α-PW 11 O 39 ] 7- ions approached one another upon reducing the ionic radius of M in [M(α-PW 11 O 39 ) 2 ] n - . The interactive twisting of the [α-PW 11 O 39 ] 7- units prevented mutual repulsion of the units containing terminal O atoms, and the tendency for approach and twisting of the [α-PW 11 O 39 ] 7- units varied as a function of the type of countercation and the presence of coexisting compounds. Overall, this study demonstrated that some interactions between the counteraction and coexisting compounds with [M(α-PW 11 O 39 ) 2 ] n - determined the molecular conformation and the isolated form of the polyanion., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background/aim: Despite evidence of an association between pulmonary diseases and periodontopathic bacteria, the molecular mechanisms remain unknown. Matrix metalloproteinase-9 (MMP9) plays important roles in pneumonia, chronic obstructive pulmonary disease, and asthma; therefore, we assessed the effects of Fusobacterium nucleatum on MMP9 expression in mouse lung and A549 human alveolar epithelial cells., Materials and Methods: Heat-killed F. nucleatum was administered to the trachea of mice or added to A549 cell cultures. MMP9 expression was determined using real-time PCR and western blotting. The involvement of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) in MMP9 expression was examined., Results: F. nucleatum induced expression of MMP9 in mouse lung and bronchoalveolar lavage fluid. In A549 cells, F. nucleatum induced production of MMP9 protein and mRNA in a density-dependent manner; this was inhibited by inhibitors of extracellular-regulated kinase 1/2 and NF-κB, but not of p38 and Jun N-terminal protein kinase., Conclusion: F. nucleatum may contribute to the onset of pulmonary diseases via MMP9 expression through extracellular-regulated kinase 1/2 and NF-κB activation., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Exacerbation of chronic obstructive pulmonary disease (COPD) is associated with disease progression and increased mortality. Periodontal disease is a risk factor for exacerbation of COPD, but little is known about the role of periodontopathic bacteria in this process. Here, we investigated the effects of intratracheal administration of Fusobacterium nucleatum, a periodontopathic bacteria species, on COPD exacerbation in elastase-induced emphysematous mice. The administration of F. nucleatum to elastase-treated mice enhanced inflammatory responses, production of alveolar wall destruction factors, progression of emphysema, and recruitment of mucin, all of which are symptoms observed in patients with COPD exacerbation. Hence, we propose that F. nucleatum may play a role in exacerbation of COPD., (© 2022 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The displacement of one fluid by another is an important process, not only in industrial and environmental fields, such as chromatography, enhanced oil recovery, and CO 2 sequestration, but also material processing, such as Lost Foam Casting. Even during hydrodynamically stable fluid displacement where a more viscous fluid displaces a less viscous fluid in porous media or in Hele-Shaw cells, the growing interface fluctuates slightly. This fluctuation is attributed to thermodynamic conditions, which can be categorized as the following systems: fully miscible, partially miscible, and immiscible. The dynamics of these three systems differ significantly. Here, we analyze interfacial fluctuations under the three systems using Family-Vicsek scaling and calculate the scaling indexes. We discovered that the roughness exponent, α, and growth exponent, β, of the partially miscible case are larger than those of the immiscible and fully miscible cases due to the effects of the Korteweg convection as induced during phase separation. Moreover, it is confirmed that fluctuations in all systems with steady values of α and β are represented as a single curve, which implies that accurate predictions for the growing interface with fluctuations in Hele-Shaw flows can be accomplished at any scale and time, regardless of the miscibility conditions.

Herein, we report on the hydrodynamic interfacial instability controlled by a thermodynamic parameter driving the liquid-liquid phase separation during fluid displacement in a Hele-Shaw cell. This instability remains even when the solution is guaranteed to be hydrodynamically stable. Adjusting the salt concentration helps control the miscibility of the solutions and change the pattern of the interface. We observe stable circular, fingering, and droplet formation patterns as the salt concentration is decreased from equilibrium. In addition, we analyze this interfacial instability using thermodynamic flux, which is determined from the growth rate of the interface, and provide a theoretical framework to quantitatively predict the transition points between the patterns. We find that the patterns transition to a state having higher entropy production.

Phase separation is important in biology, biochemistry, industry, and other areas and is divided into two types: a spinodal decomposition type and a nucleation and growth type. The spinodal decomposition type phase separation occurs under the thermodynamically unstable conditions, and the nucleation and growth type phase separation occurs under thermodynamically metastable conditions. On the other hand, when a less viscous fluid displaces a more viscous one in porous media, the interface of the two fluids becomes hydrodynamically unstable and forms a finger-like pattern. The coupling of the hydrodynamic instability with the thermodynamic instability has been studied. It is reported that the hydrodynamic instability under thermodynamically unstable conditions, where spinodal decomposition type phase separation occurs, creates multiple moving droplets with a radius of 3-4 mm because of the spontaneous convection induced by the Korteweg force, which is driven by a compositional gradient during phase separation. However, the hydrodynamic instability under metastable conditions, where the phase separation of nucleation and growth type occurs, is still unrevealed. In this study, we applied fingering instability (hydrodynamic instability) under the metastable conditions, where the patterns are changed from fingering or droplets to anomalous patterns such as tip-widening or needle-like (top-pointed) fingering patterns when the initial concentration is metastable, which is considered near a binodal curve. These patterns are ubiquitous in nature, similar to dendrite crystals (snowflakes) or our body's cells. Thus, the patterns created can be controlled through hydrodynamic conditions such as the injection flow and thermodynamic conditions such as spinodal decomposition (thermodynamically unstable conditions) and metastable conditions.

Porphyromonas gingivalis (Pg) is a periodontopathic pathogen that may affect MUC5AC-related mucus hypersecretion along airway epithelial cells. Here, we attempted to establish whether Pg virulence factors (lipopolysaccharide, FimA fimbriae, gingipains) affect MUC5AC in immortalized and primary bronchial cells. We report that MUC5AC gene expression and protein levels are affected by Pg culture supernatant, but not by lipopolysaccharide or FimA fimbriae. Cells treated with either Pg single (Kgp or Rgp) or double (Kgp/Rgp) mutants had altered levels of MUC5AC gene expression and protein levels, and MUC5AC staining of double mutant-treated mouse lung cells showed that MUC5AC protein levels were unaffected. Taken together, we propose that Pg gingipains may be the primary virulence factor that influences both MUC5AC gene expression and protein levels., (© 2020 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global public health emergency. Periodontitis, the most prevalent disease that leads to tooth loss, is caused by infection by periodontopathic bacteria. Periodontitis is also a risk factor for pneumonia and the exacerbation of chronic obstructive pulmonary disease, presumably because of the aspiration of saliva contaminated with periodontopathic bacteria into the lower respiratory tract. Patients with these diseases have increased rates of COVID-19 aggravation and mortality. Because periodontopathic bacteria have been isolated from the bronchoalveolar lavage fluid of patients with COVID-19, periodontitis may be a risk factor for COVID-19 aggravation. However, the molecular links between periodontitis and COVID-19 have not been clarified. In this study, we found that the culture supernatant of the periodontopathic bacterium Fusobacterium nucleatum (CSF) upregulated the SARS-CoV-2 receptor angiotensin-converting enzyme 2 in A549 alveolar epithelial cells. In addition, CSF induced interleukin (IL)-6 and IL-8 production by both A549 and primary alveolar epithelial cells. CSF also strongly induced IL-6 and IL-8 expression by BEAS-2B bronchial epithelial cells and Detroit 562 pharyngeal epithelial cells. These results suggest that when patients with mild COVID-19 frequently aspirate periodontopathic bacteria, SARS-CoV-2 infection is promoted, and inflammation in the lower respiratory tract may become severe in the presence of viral pneumonia.

Triglyceride (TG) and cholesterol accumulation are known to occur in the liver of rats fed a histidine-excess (5%) diet, but there are few studies reporting histochemical and molecular biological analyses of the rat liver. The aim of this study was to elucidate the molecular basis of this lipid-accumulation mechanism. Lipid accumulations, tissue section images, and gene expression levels were compared in the livers of rats fed a control or histidine-excess diet for 5 wk (n=8/group). Serum levels of TGs, free fatty acids, total cholesterol, high-density lipoprotein cholesterol, glucose, albumin, and the enzyme activities of aspartate aminotransferase and alanine aminotransferase were also analyzed. In the livers of rats fed a histidine-excess diet, histochemical analyses showed what appeared to be a preliminary stage of nonalcoholic fatty liver, characterized by lipid accumulation around the central vein area and minor fibrosis. However, there were no changes in serum TG or free fatty acid levels. Quantitative PCR analyses showed the up-regulation of FAT/CD36, which is related to the uptake of fatty acids into cells, and the downregulation of two apolipoprotein genes, ApoC3 and ApoE. The mRNA levels of PPARγ, LXRα, and AMPKα in the liver were also reduced by excess histidine intake. The results of this study suggest that steatosis caused by excess histidine intake may be the result of an imbalance between lipid transport from the liver and the uptake of free fatty acids into hepatocytes.

Introduction: Cervical spinal cord injury with the C3 neurological level may cause respiratory failure and require long-term mechanical ventilation. Conventional weaning of spontaneous breathing trials is difficult to perform outside of intensive care or spinal cord units., Case Presentation: An 80-year-old man presented with total tetraplegia and restrictive respiratory failure that required assisted ventilation after a falling accident. Cervical spine magnetic resonance imaging showed cervical cord compression that was worst at the C3-C4 intervertebral level. He experienced unexpected cardiac arrest during the conventional weaning process of trials of intermittent spontaneous breathing in the intensive care unit. The automated weaning protocol utilizing a closed-loop ventilation mode (IntelliVent ® -ASV ® ) was introduced 131 days after injury in our ward for chronically ill patients. The patient was successfully weaned 39 days after the introduction of the weaning protocol., Discussion: An automated weaning protocol utilizing a closed-loop ventilation mode could be an optional procedure in patients with cervical cord injury on long-term mechanical ventilation, even in a ward for chronically ill patients where sufficient staff is not available. The efficacy and safety, and the cost-effectiveness of the procedure should be examined in larger spinal cord units., Competing Interests: Compliance with ethical standardsThe authors declare that they have no conflict of interest.

Objective: Crush syndrome (CS) is a serious medical condition characterized by muscle cell damage resulting from pressure. CS has a high mortality, even when patients receive fluid therapy. We examined whether administration of NaNO2-containing fluid can improve survival in a rat model of CS., Design: The CS model was generated by subjecting anesthetized rats to bilateral hind limb compression with a rubber tourniquet for 5 h. Rats were then randomly divided into six groups: sham; CS with no treatment; CS with normal saline treatment; CS with normal saline + 25 mEq/L bicarbonate treatment; and CS with normal saline + 200 or 500 μmol/kg NaNO2., Measurements and Main Results: Blood and tissue samples were collected for histological and biochemical analyses at predetermined time points before and after reperfusion. Ischemic compression of rat hind limbs reduced nitrite content in the crushed muscle, and subsequent reperfusion resulted in reactive oxygen species-induced circulatory dysfunction and systemic inflammation. Rats treated with 200 μmol/kg NaNO2 showed increased nitric oxide (NO) levels, blood circulation, and neoangiogenesis, decreased generation of reactive oxygen species, and suppression of the inflammatory response, leading to complete recovery., Conclusions: Treatment with 200 μmol/kg NaNO2 prevents muscle damage induced by ischemia reperfusion via the protective effects of NO and suppression of systemic inflammation, thereby increasing survival rates in CS.

Shrub Chaste Tree Fruit (SCTF) is defined as the fruits of Vitex rotundifolia L. f. and V. trifolia L. and has been used as a component of some traditional Japanese medicines (Kampo formulations). Agnus Castus Fruit (ACF) is defined as the dried ripe fruits of V. agnus-castus L.; it is used in traditional European medicines, but is becoming popular in Japan as both an over-the-counter drug and as an ingredient in health foods for treating premenstrual syndrome (PMS). To ensure the efficacy and safety of both SCTF and ACF products, it is important to precisely authenticate their botanical origins and to clearly distinguish between SCTF and ACF. Therefore, we tried to identify SCTF-specific marker compounds based on LC/MS metabolic analysis. The multivariate analysis of LC/MS data from SCTF and ACF samples furnished candidate marker compounds of SCTF. An SCTF-specific marker was isolated from SCTF crude drugs and identified as 3-O-trans-feruloyl tormentic acid on the basis of spectroscopic data from NMR and MS. Since avoiding contamination from closely related species is a significant requirement for pharmaceuticals of natural origin, this information will be valuable for the quality control of both SCTF and ACF products from the viewpoint of regulatory science.

Agnus Castus Fruit is defined in the European Pharmacopoeia as the dried ripe fruit of Vitex agnus-castus. In Europe it is used as a medicine targeting premenstrual syndrome and climacteric disorder. In Japan, Agnus Castus Fruit is becoming popular as a raw material for over-the-counter drugs and health food products, though its congenic species, Vitex rotundifolia and Vitex trifolia, have been used as Shrub Chaste Tree Fruit in traditional medicines. Therefore, it is important to discriminate these Vitex plants from the viewpoint of regulatory science. Here we tried to identify putative marker compounds that distinguish between Agnus Castus Fruit and Shrub Chaste Tree Fruit. We analyzed extracts of each crude drug by liquid chromatography-mass spectrometry, and performed differential analysis by comparison of each chromatogram to find one or more peaks characteristic of Agnus Castus Fruit. A peak was isolated and identified as an equilibrium mixture of new compounds named chastol (1) and epichastol (1a). The planar structures of 1 and 1a were determined spectroscopically. Their relative configurations were revealed by nuclear Overhauser effect spectroscopy and differential nuclear Overhauser effect-NMR data. Since avoiding contamination from closely related species is needed for the quality control of natural pharmaceuticals, this information will be valuable to establish a method for the quality control of both, Agnus Castus Fruit and Shrub Chaste Tree Fruit products., (Georg Thieme Verlag KG Stuttgart · New York.)

Sinodielide A (SA) is a naturally occurring guaianolide, which is isolated from the root of Sinodielsia yunnanensis. This root, commonly found in Yunnan province, is used in traditional Chinese medicine as an antipyretic, analgesic and diaphoretic agent. A number of studies have reported that agents isolated from a species of Umbelliferae (Apiaceae) have antitumor activities. We previously reported, using combined treatments with this medicinal herb and hyperthermia at various temperatures, an enhanced cytotoxicity in the human prostate cancer androgen‑independent cell lines, PC3 and DU145, and analyzed the related mechanisms. In the present study, we investigated the effects of treatment with SA prior to hyperthermia on the thermosensitivity of DU145 cells, and the mechanisms related to the induction of apoptosis and G(2)/M cell cycle arrest via the activation of extracellular-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathways, as well as the phosphoinositide 3-kinase (PI3K)/Akt signaling pathways. Cells were exposed to hyperthermia alone (40-44˚C) or hyperthermia in combination with SA. Lethal damage to cells treated with mild hyperthermia (40 or 42˚C) for up to 6 h was slight; however, hyperthermia in combination with SA synergistically enhanced thermosensivity. Lethal damage to cells treated with acute hyperthermia (43 or 44˚C) was more severe, but these effects were also enhanced and were more significant by the combined treatment with SA. The kinetics of apoptosis induction and cell cycle distribution were analyzed by flow cytometry. In addition, the levels of ERK1/2, JNK and Akt were determined by western blot analysis. The incidence of apoptotic cells after treatment with SA (20.0 µM) at 37˚C for 4 h, hyperthermia (44˚C) alone for 30 min, and the combination in sequence were examined. The sub-G1 division (%) in the diagram obtained by flow cytometry was applied to that assay. The percentage of apoptotic cells (10.53±5.02%) was higher at 48 h as compared to 0, 12 and 24 h after treatment. The distribution of DU145 cells in the G2/M cell cycle phase was markedly increased after 24 h of heating at 44˚C and after the combined treatment with heating and SA. The phosphorylation of ERK1/2 was reduced following treatment with heating and SA, while the levels of phosphorylated JNK (p-JNK) were markedly increased immediately after heating at 44˚C and when heating was combined with SA. By contrast, the levels of phosphorylated Akt (p-Akt) were immediately increased only after heating at 44˚C. Thus, we concluded that SA exerts its thermosensitizing effects on DU145 cells by inhibiting the activation of the MAPK/ERK1/2 and PI3K/Akt signaling pathways.

We experimentally examined the propagation of temporally square modulated optical pulses through a coupled ring resonator. Sharp transient spikes appeared as the square pulses entered the system. The main signal gradually grew up through coupled-resonator-induced transparency (CRIT), with the time constant determined by a second resonator. Transient spikes were attributed to the higher and lower spectral components of the incident pulse, to which the resonators cannot respond; hence, they were interpreted as optical precursors. The experiments, therefore, demonstrated that precursors and the main signal can be observed separately, with amplitudes comparable to that of the incident step in CRIT.

Context: Pancreatic neuroendocrine tumor (pNET) secretes various peptide hormones; however, calcitonin hypersecretion is rare. Its clinicopathological significance and treatment is still controversial., Case Report: A 43 year-old Japanese man presented severe watery diarrhea and a large mass in the pancreatic tail. Blood concentration of VIP was elevated to 649 pg/mL (reference range: 0-100 pg/mL), and calcitonin to 66,700 pg/mL (reference range: 15-86 pg/mL). There was no tumor in other endocrine organs. The resected tumor was composed of 80% calcitonin-positive cells and 10% VIP-positive cells. After the operation, the levels of VIP and calcitonin were decreased to 44 and 553 pg/mL, respectively, and diarrhea was improved. The mRNA of somatostatin receptor (SSTR) subtypes 2, 3 and 5 in the tumor tissue were increased 22.8, 25.1, and 37.0-fold of those of normal pancreas, respectively. At 19 months after the operation, blood calcitonin was again raised to 3,980 pg/mL, and metastatic tumors were found in the liver. With the treatment of long-acting somatostatin analogue, calcitonin was reduced to 803 pg/mL. The patient does not present endocrine symptom, and the size of the metastatic tumors appears stable., Conclusion: From the world literature to date, co-secretion of VIP and calcitonin was documented in only 10 cases of pNET including the current case. Although VIP is a primary cause of diarrhea in these cases, high level of calcitonin may also influence on the clinical symptoms. Somatostatin analogue suppresses the levels of VIP and calcitonin, and the control proliferation is also expected when tumor cells express SSTRs.

Parthenolide (PTL), a nuclear factor-κB (NF-κB) inhibitor, has a significant thermo-enhancement effect. Modification of thermosensitivity by treatment with PTL prior to hyperthermia was investigated in the human prostate cancer androgen-independent cell lines PC3 and DU145. In addition, we analyzed the mechanisms related to induction of apoptosis or G₂/M cell-cycle arrest via the effects of ERK1/2, p38 and SAPK/JNK signaling on mitogen-activated protein kinase (MAPK). Lethal damage caused by mild hyperthermia at 41.0˚C or 42.0˚C in both cell lines resulted in a low level of thermosensitivity, while sequential combination with PTL showed significant thermosensitization. Step-up hyperthermia (SUH) (42˚C for 30 min, 43.0˚C or 43.5˚C for various periods) reduced the thermosensitivity of the cells to second heating. However, PTL given as pre-treatment prior to SUH prevented SUH-induced thermal tolerance and resulted in significant thermosensitization. Induction of apoptosis by the combination of PTL and hyperthermia at 44.0˚C was determined by the ratio of sub-G1 division cells using flow cytometry, which was increased significantly in comparison with single treatment, and was more effective in PC3 than DU145 cells. The behavior of ERK1/2, p38, and SAPK/JNK signaling in the MAPK cascade by treatment with PTL and hyperthermia were examined by Western blotting. As for PC3 cells, ras-downstream p-ERK1/2 was activated and p-p38 slightly activated by combined treatment with PTL and hyperthermia in comparison with each alone. As for DU145 cells, ERK1/2 was not changed, while p38 and SAPK/JNK were slightly activated by combination treatment. These results were related to increases in the induction of apoptosis, G₂/M cell cycle arrest, and lethal damage of cells via the MAPK cascade. Together, our findings demonstrate that PTL is an effective thermosensitizing agent for multidisciplinary therapy for human prostate cancer.

Fifty patients with localized prostate cancer, clinical stage T1-T2N0M0 were studied. The therapy started with androgen deprivation therapy for 3 months to reduce the volume of prostate about 35%. High-energy transurethral microwave thermotherapy (TUMT) was then performed. Transurethral resection of the prostate (TURP) was performed in radical fashion at least 3 months after TUMT to confirm the treatment effect. Thorough pathological study of all the TURP chips revealed no cancer cells in 39 of the 50 patients. Among 11 patients who revealed remnant of cancer cells, 4 patients were with viable cancer cells, and 7 were with devitalized cancer cells.

The hyper-vascular form of solitary fibrous tumors (SFTs) is rare and there have been few therapeutic evaluations of this entity. We encountered a hyper-vascular SFT and had difficulty removing it surgically. Following radiotherapy, both tumor size and feeder vessels were reduced and we could proceed with gross total removal. A 29-year-old woman was admitted with a 1-year history of decreasing visual acuity on the right side. Magnetic resonance imaging with gadolinium enhancement showed a homogenous enhancing mass (6x5x5 cm) which expanded the superior and inferior tentorium cerebelli. The tumor was fed by the left posterior cerebral artery, bilateral middle meningeal arteries and the right occipital artery. The first operation employed an occipital transtentorial approach and a highly vascular tumor was found. Tumor resection was limited due to severe bleeding. Histologically, the tumor showed focal hypercellularity with spindle cells and numerous capillaries. Immunohistochemically, the tumor was diffusely positive for CD34 and a diagnosis of SFT, hyper-vascular subtype, was made. After the first operation, local irradiation of a total of 40 Gy was performed. Both the tumor size and vascularity decreased dramatically. At the second operation, gross total removal was able to be performed. Radiotherapy appears effective in reducing the hyper-vascular subtype of SFT and would be one possible therapy to deal with these tumors, given their propensity of excessive bleeding during initial surgery.

Various materials have been used for cranioplasty; however, these materials frequently produce artifacts that appear when examined with conventional radiography. Computed tomography (CT), in particular, detects high density artifacts near artificial bones, which is manipulated by increased noise, and limits diagnostic performance. The purpose of this study was to evaluate the extent and shape of the artifacts due to artificial cranial bones and to consider CT imaging parameters necessary for accurate recognition of structures under the materials. Four different artificial bone materials were evaluated in this study: hydroxyapatite with 1) 40% or 2) 50% porosity, 3) titanium plate, and 4) hydroxyapatite-polymethylmethacrylate composite (HA-PMMA). CT scanning was performed with standard clinical settings. Sample specimens were placed on the right side, under the artificial bones, and CT was performed to evaluate specimen visibility. We compared the artifacts created by the four bone types listed above, and measured the CT values of those materials. With ordinary scan settings, all the artificial bones revealed high-density artifact surrounding the materials, including the inability to accurately measure specimen thickness. The upper part of the specimen in contact with the artificial bones could not be distinguished from the artifact. The CT value in the medial aspect of the artificial bones increased more than the actual CT values. Of the four artificial bone materials studied, HA-PMMA produced the fewest artifacts. Description of the structures under the artificial bones can be improved by extending the window width to approximately twice that of normal settings.

A 67-year-old man who had twice previously undergone operations for a tuberculum sellae meningioma was admitted to hospital for further treatment. After the third surgical intervention, the patient developed persistent low-grade fever and impaired consciousness. Computed tomography, 1 week after surgery, showed postsurgical hydrocephalus. Cerebrospinal fluid (CSF) studies revealed high intracranial pressure (above 30 cm H2O), and increased cell count (1232/3). One week after the ventricular drainage, coagulase-negative Staphylococcus epidermidis was recovered from his CSF, and antimicrobial susceptibility results indicated that the organism was methicillin-resistant. After 14 days of intravenous vancomycin (VCM) administration failed, linezolid (LZD) was initialized intravenously, resulting in a resolution of the meningitis. After a ventriculoperitoneal shunt procedure was performed, LZD was continued orally, which resulted in a cure. CSF penetration by VCM is reported to be poor, i.e., approximately 10% of serum concentration, which may explain its lack of efficacy. In this case, the penetration of LZD into the CSF was 58.9% of the peak value and 133% of the trough value of serum concentrations. LZD must be considered one of the first-line treatments against surgical-site infection in neurosurgery caused by methicillin-resistant Staphylococci.

To date, reports about the macroscopic appearance of ventriculitis have been rare, consisting only of a few autopsy cases. A patient in our hospital had ventriculitis caused by coagulase-negative staphylococci, and under neuroendoscopy we obtained clear findings of granular ependymitis. A 44-year-old man was admitted for disturbance of consciousness caused by progressive hydrocephalus. He had experienced subarachnoid hemorrhage (SAH) from a left vertebral dissecting aneurysm, and had subsequently received a ventriculoperitoneal shunt against post-SAH hydrocephalus. After admission, he was found to have retrograde shunt infection from peritonitis caused by cholecystitis. Coagulase-negative staphylococci were detected in cerebrospinal fluid (CSF), and the infection persisted even with intrathecal administration of gentamycin, and intravenous administration of vancomycin and arbekacin. Endoscopic rinsing was performed, and multiple small yellowish microgranulations, less than 1 mm in diameter, were observed in the lateral ventricles and the third ventricle. Rinsing of the CSF after intensive antimicrobial treatment resulted in a cure. Because there have been no reports of endoscopic observations of bacterial ventriculitis, we were unable to be certain about the origin or significance of the microgranulations. However, whether or not the microgranulations were bacterial colonies, infection did not recur during a 2-year follow-up period.

The pathogenesis and clinical treatment of dural arteriovenous fistulas (DAVF) has been well established. However, only 15 cases of spontaneous closure of DAVFs have been reported. We describe a case of spontaneous closure of a DAVF. A 60-year-old male presented with pulsatile tinnitus. Selective cerebral angiography revealed a left posterior DAVF fed by the left occipital artery and the middle meningeal artery, which drained into the left transverse sinus and sigmoid sinus. Following the initial angiography, the patient exhibited vomiting with transient disorientation and amnesia. These symptoms, along with the tinnitus, disappeared by the following day. Seven days after the initial angiography, a second angiography was performed that revealed the complete disappearance of the DAVF. Previous reports have described a long period of closure for DAVFs following initial diagnosis. Possible mechanisms for spontaneous closure of DAVFs include the development of scar tissue or a sinus thrombosis that leads to occlusion of the DAVF In this case, the DAVF closure may have been due to a sinus thrombosis induced by sinus stenosis, since occlusion of the draining sinuses coincided with the spontaneous closure of the DAVF. In cases of non-traumatic DAVF without cortical venous reflex that do not present severe symptoms, a prudent course of treatment is necessary since there is a chance of spontaneous closure of the DAVF occuring.

Meningioma usually grows and expands into the brain, but invasion into the brain parenchyma is relatively rare. Meningioma arises from arachnoid cap cells, and infiltration into dura mater is the main growth pattern of meningiomas. However, little is known about the mechanism of meningioma invasion into the dura mater. In this study, seven specimens, including dural attachments, from seven cases of meningioma were used for immunohistochemical analysis. Matrix metalloproteinase (MMP)-1, -2, -9, urokinase-type plasminogen activator (uPA), vascular endothelial growth factors (VEGF), flt-1, E-cadherin, estrogen receptor (EgR), progesterone receptor (PgR), and aquaporin (AQP)-1, -4 were used as primary antibodies. There were several patterns of meningioma invasion into the dura mater: papillary-shaped invasion with destruction of dural structure, infiltration along the fibers of the dura mater, and invasion of several tumor cell units with fibroblast infiltration. Strong immunostaining was obtained with MMP-1, followed by AQP-1 and uPA, within the invading tumor cells. Neovasculature and extravasated erythrocytes, which stained with AQP-1, were also occasionally observed around the invading tumor cells. Simpson grade II removal of meningiomas results in high recurrence rates, and the inhibition of meningioma growth via dural invasion will facilitate improved remission in many cases with meningioma. In this study, MMP-1, AQP-1, and uPA are considered to have some role in the dural infiltration of meningioma cells. The fact that AQP-1 was highly expressed at the dural attachment and invading front of meningioma may indicate that dural invasion of the meningioma may be facilitated by AQP-1-induced water flow and neovascularization.

An interventional-radiology computed-tomography (IVR-CT)/angio system is a combination of an angiographic unit and a CT scanner. This system allows patient's movement in and out of the two imaging units, on the same table. Since June 2003, we have applied our conventional protocol for evaluation of cerebral blood perfusion during interventional radiology (IVR) procedures. We reviewed our experience using the IVR-CT/angio system and investigated the efficacy and limitations of this technique. No complications relating to radiation exposure, contrast medium use, or IVR procedures were observed. CT perfusion was useful for detecting cerebral perfusion impairment during IVR procedures. This was helpful in deciding the postoperative management. Because patients do not need to be transported to another radiographic suite to evaluate cerebral blood perfusion, the IVR-CT/angio system is ideal for safely and simply detecting cerebral perfusion defects during IVR procedures. However, it is important to consider whether there is sufficient indication for the procedure, because radiation exposure and the amount of contrast medium use are increased if the IVR procedures become difficult.

Purpose: The 2nd generation transurethral microwave thermotherapy (TUMT), equipped with high energy microwave generator and urethral cooling device is widely accepted as an less invasive effective modality to treat benign prostatic hyperplasia. For prostatic cancer, however, it is generally estimated as insufficient because of limitation in penetration of microwave into deep prostatic tissue. In this study, we examined histopathologic changes after androgen deprivation theraphy (ADT) and TUMT., Patients and Methods: Ten patients with localized prostate cancer underwent ADT for 3 months, and then TUMT was proceeded using Urowave (Dornier MedTech GmbH). Additional 3 months after TUMT and continued ADT, TURP in radical fashion was performed in all the patients, and all the resected chips were submitted for pathological study., Results: Significant reduction in prostate volume was noted after NHT for 3 months from 37.4 +/- 9.6 ml to 22.0 +/- 5.6 ml. The pathological study of resected chips revealed progressive fibrotic changes without viable cancer cells in 9 of 10 patients. In 1 patient, however, some remnant of carcinomatous foci were noted in a resected chip from the middle lobe of the prostate., Conclusion: Although the number of patient is limited and longer follow-up is needed, the results in present series was interested and worth considering.

Presented herein is a case of combined small cell and squamous cell carcinoma in a polypoid bronchial tumor, showing a histologically unique progression, in a 76-year-old Japanese man. A bronchofiberscopic examination revealed that the bronchus (left B3) was occluded by the polypoid tumor. Biopsies were performed, and the pathological diagnosis was poorly differentiated squamous cell carcinoma. The patient consequently underwent a left upper lung lobectomy. The surgical specimen was described as a 24 x 8 x 8 mm soft tumor, emanating from the bronchial wall (left B3). Histologically, the tumor had two distinct components: (i) nearly the entire tumor was composed of atypical small round cells, with a high nuclear-cytoplasmic ratio, in the lamina propria, under the basement membrane; and (ii) the surface of the tumor was composed of poorly differentiated squamous cell carcinoma that had proliferated primarily above the basement membrane but there was also some proliferation, seen as island-like formations, below the basement membrane. The histological diagnosis was combined small cell and squamous cell carcinoma. It was suspected that poorly differentiated squamous cell carcinoma, generated in the bronchial epithelium, had caused small cell carcinoma resulting from neuroendocrine differentiation during its invasion into the lamina propria.

Prophylactic administration of antibiotics is prevalent for traumatic patients including head injury, when the patients have contaminated wounds, CSF leakage, and multiple injuries. In cases with prolonged fever and inflammatory signs, other antibiotics must be selected without confirming the infections by cultures. Usually, 1st or 2nd generation cefalosporins are selected as empiric therapy for traumatic patients, but, successive antibiotics are usually selected according to the situation. In this study, we analyzed 60 cases of head injured patients with Glasgow Coma Scale under 12, in terms of the selection of antibiotics and the reasons for the antibiotic selections. CEZ > PIPC > FMOX were used for initial treatment without any culture results. The second selection was made without any positive culture results in 85.7%, and tertiary selection without culture results in 50% of the patients. CPR > CFSL > FMOX > PAPM/BP were mainly used as second selection, and IPM/CS > CPR = PIPC were mainly used as tertiary selection. In cases with traumatic brain injuries, it is important to prevent antibiotic resistances. 1) by selecting appropriate antibiotics, 2) by using antibiotics after excluding catheter related infections, 3) by not using antibiotics and performing frequent cultures when no apparent infection focuses are detected.

Pituitary carcinomas are very rare. The diagnosis of pituitary carcinoma is defined by evidence of craniospinal and/or systemic metastasis, rather than by histological malignancies. We report a case of prolactin-secreting pituitary macroadenoma invading the cavernous sinuses at the time of initial treatment, which later metastasized to the cerebellum, medulla oblongata, and spinal axis. The patient survived approximately nine years following the initial diagnosis of a pituitary tumor and two years following the diagnosis of metastatic disease. Histological examination of the metastatic cerebellar tumor showed an adenoma with high cellularity and hyperchromasia, but no mitoses.

Object: Transsphenoidal surgery for the removal of macroadenomas has some disadvantages, including the risk of performing procedures without adequate visualization, difficulties in estimating the amount of residual tumor, and the risk of injuring major vessels. To overcome these disadvantages, the authors have developed transcranial echo-guided transsphenoidal surgery., Methods: Three patients with large macroadenomas and two patients with irregularly shaped macroadenomas were selected for this operation. In addition to standard preparations for transsphenoidal surgery, in each case the right frontal bone was trephined and an echo probe was inserted transdurally through the trephination hole. During tumor removal, brightness-mode echo images and Doppler color flow images were obtained. The echo images allowed for real-time visualization of the tumor and surrounding brain structures including major arteries and the cisterns; histological heterogeneities of the tumor could also be appreciated. The tumors were removed safely and maximal tumor removal was achieved., Conclusions: Transcranial echo-guided transsphenoidal surgery provides real-time visualization of tumor removal. The method enhances the safety of this surgery, maximizes the removal of the tumor, and is inexpensive.

Thallium (Tl)-201 single-photon emission computed tomography (SPECT) is a useful tool for detecting brain tumors. In this study, we evaluated the utility of Tl-201 SPECT for determining the effect of maintenance chemotherapy with ACNU (nimustine hydrochloride)/VCR (vincristine sulfate) against malignant gliomas. The cases were comprised of 16 glioma cases; 6 astrocytomas, 2 anaplastic astrocytomas, and 8 glioblastomas. We first analyzed the correlation between Tl-201 uptake ratio and proliferative activity of the tumor, using Ki-67 immunohistochemistry in 13 cases of glioma. The uptake ratio of Tl-201 correlated with the Ki-67 staining indices (SI), and a closer correlation was obtained using Tl-201 delayed images than with the early images. We also analyzed the chronological changes of Tl-201 uptake ratio and volume of abnormal area evaluated by MRI T2-weighted imaging (MRI T2WI), in 10 cases of malignant glioma during maintenance chemotherapy. The Tl-201 uptake ratio gradually decreased with the effect of maintenance chemotherapy, and the sensitivity was superior to MRI findings. Together with MRI, Tl-201 SPECT is considered to be a useful indicator for evaluating the effect of maintenance chemotherapy against malignant gliomas.

Objective: The purpose of this study was to establish selection criteria for intentional limited resection in patients with peripheral lung cancer., Methods: Six hundred eighty-nine cases of cT1N0M0 peripheral non-small cell lung cancer were divided into groups according to maximum tumor diameter. The cases in each group were examined for histopathological invasive factors, and the results of a pilot study of intentional limited resection were assessed., Results: The positive rate of invasive factors was 30.8% among the patients with tumors 2 cm or less in diameter, and significantly lower than the 44.0% noted in those whose tumor diameter was in the 2.1-3.0 cm range. The positive rate was significantly lower in 90 patients with type A or B adenocarcinoma, and none of these patients developed postoperative recurrence. In 24 of these 90 patients, the tumor diameter was in the 2.1-3.0 cm range. The 5-year survival rate in the 74 patients with pT1N0M0 and tumors 2 cm or less in diameter who underwent limited resection was 89.1%., Conclusions: We attempted to establish selection criteria for limited resection, with the aim of obtaining survival rates that was comparable to those obtained after lobectomy. The selection criteria established in this study are: 1, cT1N0M0 peripheral non-small cell lung cancer; 2, maximum tumor diameter 2 cm or less on diagnostic images, but a tumor diameter in the range of 2-3 cm in adenocarcinoma of Noguchi type A or B cases; 3, limited resection feasible based on tumor location.

A 73-year-old woman evidencing an abnormal shadow on chest X-ray film since 1993 was admitted after a tumor of the left 8th rib was diagnosed in 2001. Computed tomography showed a low-density mass with coarse calcification arising from the left 8th rib and protruding into the abdominal cavity. The tumor was diagnosed as low-grade chondrosarcoma by incision biopsy and was resected together with the left 7th, 8th, and 9th ribs. The chest wall was reconstructed using Marlex mesh. Histological findings were compatible with Grade I chondrosarcoma. The patient had a long clinical course without distant metastasis thanks to the tumor's low malignancy.

Objective: The present study was undertaken to demonstrate that limited pulmonary resection for peripheral small-sized lung cancer yields outcomes not inferior to those of lobectomy., Methods: During the 9-year period from 1992 to 2000, patients with cT1 N0 M0 peripheral non-small cell lung cancer whose maximum tumor diameter was 2 cm or less on diagnostic imaging and in whom lobectomy was determined to be feasible were treated with limited resection if the patient consented to the procedure and with lobectomy if consent to limited resection was not obtained. The survival and clinical outcome of the patients whose tumors were postoperatively staged as pT1 N0 M0 were compared between the limited resection group (n = 74) and the lobectomy group (n = 159)., Results: The limited resection group consisted of 60 patients treated with segmentectomy and 14 patients treated with wedge resection. Among patients followed up for a mean period of 52 months after the operation, neither the 3-year nor 5-year survivals differed significantly between the limited resection group (3-year survival, 94.0%; 5-year survival, 89.1%) and the lobectomy group (3-year survival, 97.0%; 5-year survival, 90.1%). Postoperative tumor recurrence was noted in 5 patients after limited resection and in 9 patients after lobectomy, and the difference in the incidence of postoperative recurrence between the 2 groups was not significant., Conclusions: The results of this study indicate that in patients with peripheral T1 N0 M0 non-small cell lung cancer whose maximum tumor diameter was 2 cm or less, the outcome of limited pulmonary resection is comparable with that of pulmonary lobectomy.

To investigate the mechanisms of proteolysis within the glioma, and tissue reactions against glioblastoma, immunohistochemical detection both outside and inside of the tumor was performed using seven brains with glioblastoma that were obtained from autopsies. Immunohistochemistry was performed to detect vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-1,-2,-9, membrane-type matrix metalloproteinase (MT-MMP), interleukin (IL)1-beta, and IL-6. The data were translated into color graphics and the localization of these proteins was analyzed. In glial cells around the tumor, GFAP, VEGF, MMP-2, and MT-MMP were strongly expressed. Moreover, IL1-beta was also expressed strongly in the glial cells at the periphery of the tumor. IL-6 was recognized outside of the tumor, but was expressed only in the swollen astrocytes and normal pyramidal cells. These data suggest that in the periphery of the tumor, tissue reconstruction processes take place with concomitant degradation of the matrix by MMP-2 and MT-MMP, as well as vascular remodeling promoted by VEGF. The fact that IL1-beta, but not IL-6, was expressed strongly in the glial cells around the tumor, may indicate that these proteins expressed outside of the tumor are not utilized for tumor growth, but may be used to guard the tumor against invasions, such as immune response.

A 53-year old female presented with paresis of the left upper extremity. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) disclosed a single high-flow vertebral arteriovenous fistula (AVF) with vertebral artery (VA) transection. The AVF was also fed by steal flow from the contralateral VA. The left posterior inferior cerebellar artery (PICA) branched just distal to the fistula. The fistula drained into the neighboring paravertebral veins and refluxed into the intradural venous systems. The dilated drainers compressed the spinal cord. Embolization was attempted at the drainer just behind the fistula orifice using platinum coils. The fistula was still fed slightly by right VA after the embolization, but spontaneous complete obliteration was achieved after one week. The clinical symptoms and signs disappeared. Although, detachable balloon embolization is the quickest and most effective procedure to obliterate a fistula, stepwise embolization using GDC can be considered, and may avoid the normal pressure perfusion break-through phenomenon. Spontaneous obliteration of the fistula after partial embolization in our case may result from intravenous embolization just behind the fistula orifice. It may therefore be a useful approach to the embolization of an AVF to begin the embolization at the venous side of the fistula.