Core outcome set for surgical trials in gastric cancer (GASTROS study): international patient and healthcare professional consensus.

BACKGROUND: Surgery is the primary treatment that can offer potential cure for gastric cancer, but is associated with significant risks. Identifying optimal surgical approaches should be based on comparing outcomes from well designed trials. Currently, trials report different outcomes, making synthesis of evidence difficult. To address this, the aim of this study was to develop a core outcome set (COS)-a standardized group of outcomes important to key international stakeholders-that should be reported by future trials in this field. METHODS: Stage 1 of the study involved identifying potentially important outcomes from previous trials and a series of patient interviews. Stage 2 involved patients and healthcare professionals prioritizing outcomes using a multilanguage international Delphi survey that informed an international consensus meeting at which the COS was finalized. RESULTS: Some 498 outcomes were identified from previously reported trials and patient interviews, and rationalized into 56 items presented in the Delphi survey. A total of 952 patients, surgeons, and nurses enrolled in round 1 of the survey, and 662 (70 per cent) completed round 2. Following the consensus meeting, eight outcomes were included in the COS: disease-free survival, disease-specific survival, surgery-related death, recurrence, completeness of tumour removal, overall quality of life, nutritional effects, and 'serious' adverse events. CONCLUSION: A COS for surgical trials in gastric cancer has been developed with international patients and healthcare professionals. This is a minimum set of outcomes that is recommended to be used in all future trials in this field to improve trial design and synthesis of evidence.

Decrescent intensity training concurrently improves maximal anaerobic power, maximal accumulated oxygen deficit, and maximal oxygen uptake.

This study aimed to investigate the effects of a gradually decreasing intensity training from that corresponding to maximal anaerobic power (MAnP) to that of near maximal oxygen uptake ([Formula: see text]) (decrescent intensity training) on MAnP, maximal accumulated oxygen deficit (MAOD), and [Formula: see text] in untrained young men. Seventeen untrained young men were randomly divided into either a training (TR; n = 9) group or a control (CON; n = 8) group. The TR group performed the decrescent intensity training, whereas the CON group did not perform any exercises. The mean training time per session throughout the training period was 275 ± 135 s. There was a Group × Time interaction for both absolute and relative (p < 0.01) values of [Formula: see text], MAOD, and MAnP. The TR group had significantly increased values for all variables after the 8-week training program, and the relative values of all variables were significantly higher in the TR group than in the CON group. Muscle thicknesses in the anterior and posterior aspects of the thigh and maximal isokinetic knee extension and flexion strengths improved only in the TR group (p < 0.05). A single-exercise training with gradually decreasing intensity from that corresponding to the MAnP to that of approximately 100% [Formula: see text] improves MAnP, MAOD, and [Formula: see text] concurrently, despite the short training time per session.

Spike-monitoring of anaesthesia for corpus callosotomy using bilateral bispectral index.

During corpus callosotomy for intractable epilepsy, the electrocorticogram is commonly recorded from electrodes placed on the brain surface to monitor of epileptic activity and assess the synchronisation of epileptic signals between the left and the right hemispheres. We evaluated the usefulness of bilateral bispectral index monitoring using two monitors and two sensors placed above the frontal region. Spikes were readily detected on the electroencephalogram on the bispectral index monitor, and the frequency of their occurrence increased or decreased in response to adjustment of the sevoflurane concentration. The disappearance of synchronisation between the left and the right hemispheres was observed with use of the bispectral index - in concordance with the electrocorticogram. Thus, 'spike-monitoring anaesthesia' using bilateral bispectral index was useful in assessing both the effect of anaesthetics on the electroencephalogram signals and the surgical therapeutic effect.

Paracetamol absorption test with Wagner-Nelson analysis for safe and accurate measurements of gastric emptying in women.

The physiological and pharmacological aspects of gastric emptying in fertile or pregnant women have been studied. Scintigraphy is the reference method for measuring gastric emptying. However, it should be applied very cautiously to women of childbearing age because of the risk of substantial irratiation. In such a population, paracetamol absorption has been used safely as an index of gastric emptying, but its accuracy has been challenged. The Wagner-Nelson method is a traditional tool used to precisely evaluate drug absorption kinetics. To clarify whether the absorption kinetics of paracetamol assessed by the Wagner-Nelson method is as accurate as scintigraphy in evaluating gastric emptying in young women, gastric emptying of a 200-kcal liquid meal was measured simultaneously by scintigraphy and the paracetamol test in 10 healthy young female volunteers. Paracetamol absorption systemically overestimated the rate of gastric emptying measured by scintigraphy. By introducing a correction factor into the paracetamol test, the overestimation could be adjusted. The paracetamol test with Wagner-Nelson analysis can be a safe and accurate method for measuring gastric emptying in women of childbearing age.

Influence of the numbers of islets on the models of rat syngeneic-islet and allogeneic-islet transplantations.

One of the main barriers to widespread application of islet transplantation is the limited availability of human pancreatic islets. The reduction of graft islet mass for transplantation to a recipient is one of the strategies in islet transplantation. However, transplantation of only a small number of islets may result in primary nonfunction. To optimize the sites and numbers of islets for transplantation, we analyzed these factors using pancreatic islets from Lewis or F344 rats transplanted into rats rendered diabetic by streptozotocin (50 mg/kg IV) and confirmed as such prior to transplantation (>300 mg/dL blood glucose). Approximately 500 to 1500 islets were injected via the portal vein or under the renal capsule into the diabetic F344 rats. The blood glucose level of all animals bearing 1500 syngeneic or allogeneic islets transplanted to the liver or under the kidney capsule exhibited restored normoglycemia (<200 mg/dL) at 1 day after transplantation. Graft function deteriorated after only 3 days in three animals (5.8%). The loss of graft function after 3 days occurred in 10 of 28 rats transplanted with 1000 to 1200 syngeneic islets, 4 of 19 rats transplanted with 800 to 900 syngeneic islets, and 7 of 17 rats transplanted with 500 to 600 syngeneic islets. There was no significant difference in the loss of graft function between the sites of transplantation via portal vein or under the kidney capsule. In conclusion, higher frequencies of primary nonfunction occurred with less than 1500 islets transplanted. They were independent of the sites in the rat-islet transplantation model.

Characteristic alterations of cutaneous neurogenic factors in photoaged skin.

BACKGROUND: Although it has been recognized that photoageing and chronological ageing differ in various morphological and biological aspects, the characteristic alterations of cutaneous neurogenic factors in photoaged skin are poorly characterized. OBJECTIVES: To characterize cutaneous neurogenic factors, including innervation, neuropeptides, nerve growth factor and interactions of mast cells, in photoaged skin. SUBJECTS AND METHODS: Paired biopsy specimens were obtained from sun-exposed volar forearm skin and from sun-protected dorsal upper arm skin of 20 elderly subjects. Various cutaneous neurogenic factors, including innervation, neuropeptides, neurokinin receptor, nerve growth factor, neurogenic inflammation and morphology of mast cells, were compared in sun-exposed vs. sun-protected skin quantitatively and qualitatively. RESULTS: Cutaneous neurogenic factors associated with photoageing were characterized by a significant increase in the densities of dermal and intraepidermal nerve fibres, a correlation between epidermal innervation and the severity of photodamage, increases in the number of neuropeptidergic sensory nerve fibres in the dermis and in tissue levels of sensory neuropeptides, increases in the content of nerve growth factor, reduced expression of neurokinin receptor 1 by epidermal keratinocytes and by vascular endothelial cells and a tachykinin-specific reduction of cutaneous neurogenic inflammation. Mast cells in photodamaged skin showed several characteristic morphological features, including various degrees of activation and an intimate association with fibroblasts, which were distinct from those in sun-protected skin. Furthermore, mast cells in photodamaged skin possessed larger amounts of substance P within their granules than did those in sun-protected skin. CONCLUSIONS: These findings document for the first time characteristic alterations of cutaneous neurogenic factors in photodamaged skin and suggest that the cutaneous nervous system may be involved in photoageing processes.

Hand-assisted laparoscopic and thoracoscopic surgery (HALTS) in radical esophagectomy with three-field lymphadenectomy for thoracic esophageal cancer.

AIM: To prove the feasibility of hand-assisted laparoscopic and thoracoscopic surgery (HALTS) for radical esophagectomy with three-field lymphadenectomy to thoracic esophageal cancer. METHODS: Esophagectomy with three-field lymphadenectomy was performed using HALTS in 19 patients with thoracic esophageal cancer without distant metastasis. Five patients had chemo-radiotherapy prior to surgery. RESULTS: All operations were completed successfully without the need for open surgery. Mean surgical time was 476+/-58 min, and mean blood loss during surgery was 343+/-184 mL. All patients started tube feeding and were moved from the intensive care unit to the general surgery ward the day after surgery. Discharge occurred a median of 10 days after surgery. Fifteen patients could return to full time jobs from 8 to 62 days after surgery (median 22 days) and from 1 to 35 days after discharge (median 9 days). Other three could return to daily activities at home soon as well. No major complications occurred, except one anastomotic leak. In terms of lung function, %FEV(1) was not changed whereas %VC was reduced significantly 1 month after surgery. All but two recurrences have been healthy without a relapse for a mean of 289 days. CONCLUSIONS: These results suggest that HALTS may be a useful surgical technique to reduce the invasiveness of conventional radical esophagectomy with three-field lymphadenectomy for thoracic esophageal cancer.

Ileosigmoid knot: case report and CT findings.

Ileosigmoid knot (ISK) is an unusual clinical entity of small bowel obstruction in which the ileum wraps around the base of the sigmoid colon and forms a pseudo-knot. We present the case of a 75-year-old male in whom ISK was the definitive computed tomographic finding. ISK should be considered in differential diagnosis of patients who present with ileus.

Preparation and pharmaceutical evaluation for clinical application of high specific activity S-(-)[11C]CGP-12177, a radioligand for beta-adrenoreceptors.

BACKGROUND: Although S-(-)[C]CGP-12177 is a useful positron emission tomography (PET) ligand for beta-adrenoreceptors, the difficulty in radiolabelling the compound has prevented its extensive clinical application. Recently, we have developed a simple synthesis method for S-(-)[C]CGP-12177. In the present study, we attempted to prepare S-(-)[C]CGP-12177 with a high specific activity for intravenous injection which is feasible for the clinical evaluation of beta-adrenoreceptors. METHODS: The [C]methane produced during irradiation of a N2--H2 (95/5) mixture with an 18 MeV proton beam (20 microA, 30 min) was chlorinated using Cl2 to yield [C]carbon tetrachloride. S-(-)[C]CGP-12177 was synthesized by reacting the diamino precursor with [C]phosgene produced by oxidizing [C]carbon tetrachloride on a Fe--Fe2O3 column. The product was purified by using reversed phase, high-performance liquid chromatography (RP-HPLC) and the radioactive fraction containing S-(-)[C]CGP-12177 was collected and evaporated to dryness. S-(-)[C]CGP-12177 dissolved in physiological saline was sterilized through a 0.22 microm membrane filter. The radiochemical purity and the mass of the compound were determined with RP-HPLC. The residual organic solvents were determined with GC. Tests for sterility and the presence of bacterial endotoxins were also performed. RESULTS: S-(-)[C]CGP-12177 for intravenous injection was prepared in 25 min after the end of bombardment with a yield of 1.5+/-0.2 GBq. Specific activity was found to be 385.4+/-133.0 GBq/ micromol at the end of synthesis (EOS) (n=3). Radiochemical purity was found to be more than 99%. Toluene was not detected in the solution. The ethanol concentration was determined to be 60.3+/-52.5 ppm. Tests for sterility and bacterial endotoxins showed negative results. CONCLUSION: We successfully prepared S-(-)[C]CGP-12177 formulated for intravenous injection with high purity and high specific activity, which is feasible for the clinical evaluation of beta-adrenoreceptors.

Effect of steroids on [18F]fluorodeoxyglucose uptake in an experimental tumour model.

BACKGROUND: It is well known that blood glucose level affects the uptake of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in tumours. Thus, the action of steroids on glucose metabolism may alter blood glucose levels and may affect FDG uptake in tumours in patients treated with steroids. To clarify this point, we determined the effects of steroids on FDG uptake in tumours in a rat model of a malignant tumour. METHODS: Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle. They were fasted overnight and divided into three groups (n=5 in each group): (1) dexamethasone (DEX) pretreated (0.8 mg.kg(-1) body weight, i.m. injection 4 h before FDG i.v. injection); (2) prednisolone (PRE) pretreated (8 mg.kg(-1) body weight, i.m. injection 20 h before FDG i.v. injection); and (3) control (untreated) groups. Radioactivity in tissues was determined 1 h after i.v. injection of FDG. FDG uptake in the tumour was expressed as the percentage of injected dose per gram of tissue after normalization to animal's weight (%ID/g tissue/kg body weight). RESULTS: DEX and PRE pretreatments significantly increased the blood glucose levels to 128% and 145% of the control value. The levels of FDG uptake in the tumour were not significantly affected by DEX and PRE pretreatment (90% and 87% of the control value, respectively) (P=NS). CONCLUSIONS: These results demonstrate that FDG uptake in the tumour was not affected by pretreatment with steroids, in spite of a slight elevation in blood glucose level.

High proliferative potential colony-forming cells (HPP-CFCs) in the peripheral blood of rheumatoid arthritis patients with interstitial lung disease.

OBJECTIVE: To examine the presence of high proliferative potential colony-forming cells (HPP-CFCs) in the peripheral blood of rheumatoid arthritis (RA) patients with and without interstitial lung disease (ILD). METHODS: Peripheral blood mononuclear cells from 35 RA patients with and without ILD, 12 patients with infectious pulmonary diseases, 10 patients with idiopathic pulmonary fibrosis (IPF), and 20 healthy volunteers, were assayed for in vitro colony formation. RESULTS: HPP-CFCs were detected significantly more frequently in the peripheral blood of patients with ILD (11/14: 78%, p<0.05) than in that of patients without ILD (4/21: 19%). HPP-CFCs were not detected in the peripheral blood of patients with infectious pulmonary diseases, those with IPF or healthy volunteers. CONCLUSIONS: HPP-CFCs were frequently found in the peripheral blood of RA patients with ILD compared with those without ILD, suggesting the mobilization of HPP-CFCs from the bone marrow into the peripheral blood in association with ILD in RA.

Endothelin protein expression as a significant prognostic factor in oesophageal squamous cell carcinoma.

The aim of this study was to investigate if the expression of endothelin (ET), a vasoactive peptide, in cancerous oesophageal lesions, adjacent dysplastic tissue and normal mucosa might be prognostic. Tissue samples from a total of 101 patients with oesophageal squamous cell carcinoma were obtained and stained with ET antibody in an immunohistochemical analysis. High staining levels of ET within normal mucosa were related to lymph vessel invasion, regional lymph node metastasis and distant metastasis, as well as a reduced relapse-free survival (log-rank test; P=0.0066). After adjustment for several histological prognostic risk factors and each component of the TNM classification system, high ET expression within dysplastic tissue more than doubled the hazard ratio of relapse with significant model improvement. These results suggest that, in addition to known histological risk factors and TNM classification criteria, measurement of ET expression with a simple immunohistochemical analysis might further help in predicting the prognosis of patients with oesophageal squamous cell carcinoma.

[The effect of intra-aortic balloon pumping on the graft of coronary artery bypass grafting].

The effect of intra-aortic balloon pumping (IABP) on the graft of coronary artery bypass grafting (CABG) was examined. These patients needed IABP when they were weaned from cardiopulmonary bypass. The flow wave pattern in the graft was acquired and analyze by the slope, peak flow rate and area of systolic phase and diastolic phase. The flow wave pattern different between graft to a left anterior branch and the graft to the right coronary artery. IABP was significantly effective for the flow to the left anterior branch. However, the effect of IABP on the graft flow to the right coronary artery was not significant. In the natural heart, the flow rate of the left coronary artery predominates during the diastolic phase. However this predominance is not clear in the right coronary artery. Our results suggested that this phenomenon in the natural state caused a difference the flow wave pattern between graft of left coronary artery and that of the right coronary artery.

An analog CMOS central pattern generator for interlimb coordination in quadruped locomotion.

This paper proposes a neuromorphic analog CMOS controller for interlimb coordination in quadruped locomotion. Animal locomotion, such as walking, running, swimming, and flying, is based on periodic rhythmic movements. These rhythmic movements are driven by the biological neural network, called the central pattern generator (CPG). In recent years, many researchers have applied CPG to locomotion controllers in robotics. However, most of these have been developed with digital processors and, thus, have several problems, such as high power consumption. In order to overcome such problems, a CPG controller with analog CMOS circuit is proposed. Since the CMOS transistors in the circuit operate in their subthreshold region and under low supply voltage, the controller can reduce power consumption. Moreover, low-cost production and miniaturization of controllers are expected. We have shown through computer simulation, such circuit has the capability to generate several periodic rhythmic patterns and transitions between their patterns promptly.

Fluorodeoxyglucose uptake and glucose transporter expression in experimental inflammatory lesions and malignant tumours: effects of insulin and glucose loading.

The expression of glucose transporters (GLUTs) and its relationship to fluorodeoxyglucose accumulation in malignant tumours have been well investigated, while such a relation has not been studied in inflammatory lesions. The aim of the present study was to investigate the effects of insulin and glucose loading on the expression of GLUTs in inflammatory lesions and compare them with those in malignant tumours in relation to fluorodeoxyglucose accumulation. All tissue specimens used in this study were obtained in our previous study, in which rats were inoculated with allogenic hepatoma cells (KDH-8), Staphylococcus aureus, or turpentine oil into the left calf muscle and divided into three subgroups: insulin loaded, glucose loaded, and control groups. The expression of glucose transporters (GLUT-1 to GLUT-5) was investigated by immunostaining the lesions (n=5-6, for each group). In all control groups, the expression levels of GLUT-1 and GLUT-3 were significantly higher than those of GLUT-2, GLUT-4 and GLUT-5. Insulin loading did not significantly affect the expression levels of GLUT-1 and GLUT-3 in these lesions except for a significant but slight decrease in the GLUT-1 expression level in the inflammatory lesion of non-infectious origin (89% of the control value). Glucose loading significantly decreased the expression level of GLUT-1 in the inflammatory lesion of non-infectious origin (70% of the control value, P<0.01), and that of GLUT-3 in the inflammatory lesion of infectious origin (70% of the control value, P<0.05), while the expression levels of GLUT-1 and GLUT-3 in the tumour were not significantly affected. These results demonstrate the effects of insulin and glucose loading on the expression level of a molecule (GLUT proteins). The decreased GLUT-1 and GLUT-3 expression levels induced by glucose loading may partly explain the impaired FDG uptake observed in our previous study.

Is enteral administration of fluorine-18-fluorodeoxyglucose (F-18 FDG) a palatable alternative to IV injection? Pre-clinical evaluation in normal rodents.

To establish effective methods of enteral 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) administration, the efficiency of FDG absorption in the gastrointestinal tracts following enteral administrations was evaluated using the FDG biodistribution in normal rodents, in combination with various fasting conditions and FDG diluents. The blood FDG curve using hypotonic solution showed a rapid increase, while that in iso- and hypertonic groups showed slow rises. Brain FDG uptake had a close positive correlation with blood AUC (area under curve) and an inverse relationship with the stomach contents.

Dramatic efficacy of cyclophosphamide pulsed therapy combined with double-filtration plasmapheresis for treating severe massive pulmonary hemorrhage associated with systemic lupus erythematosus.

Abstract Pulmonary hemorrhage (PH) is a rare but fatal complication of systemic lupus erythematosus (SLE). We report a patient with SLE and a massive PH who was treated with double-filtration plasmapheresis synchronized with cyclophosphamide pulsed therapy. The patient showed dramatic improvement immediately and was followed for 3 years without recurrence. Prompt treatment during the acute phase of PH with this short-term intensive combination therapy may offer the best chance of success. There are few reports of long-term followup, especially in Japan.

Mito-mice: animal models for mitochondrial DNA-based diseases.

We have successfully produced "Mito-mice" harbouring a pathogenic mtDNA mutation. We generated the mice by introducing mitochondria with a 4696 base-pair mtDNA deletion (Delta mtDNA4696) into mouse embryos. This deletion encompasses nucleotides 7759-12 454 and includes six tRNA genes and seven structural genes. In Mito-mice, the Delta mtDNA4696 is transmitted maternally, and induces mitochondrial dysfunction in various tissues. Most of the Mito-mice with high proportions of the Delta mtDNA4696 died at about age 6 months due to renal failure. Mito-mice are the first animal model for mtDNA-based diseases and will be valuable for studying pathogenesis and for identifying effective drug and gene therapies.

Immunohistochemical detection of inhibin-alpha, -betaB, and -betaA chains and 3beta-hydroxysteroid dehydrogenase in canine testicular tumors and normal testes.

Immunohistochemical detection of inhibin-alpha, -betaA and -betaB chains and 3beta-hydroxysteroid dehydrogenase (HSD) was carried out on primary testicular tumors from 15 dogs and normal testes from three adult dogs. Histopathologically, the tumors were composed of three types: Leydig cell tumors in five dogs, Sertoli cell tumors in five dogs, and seminoma in five dogs. In normal testes, immunostaining against inhibin-alpha, -betaA, and -betaB chains and 3beta-HSD revealed positive reactivity in the cytoplasm of Leydig cells. In testicular tumors, immunoreactive cells against inhibin-alpha, -betaA, and -betaB chains and 3beta-HSD were localized in all Leydig cell tumors but not in any Sertoli cell tumors or seminomas. The results of radioimmunoassay for plasma inhibin in dogs with Leydig cell tumors showed higher concentrations than those in dogs with Sertoli cell tumors and seminomas and those in normal dogs. The concentration of inhibin in the plasma was markedly decreased by the surgical removal of the Leydig cell tumor in one dog. Our findings suggest that inhibin is synthesized by normal and neoplastic Leydig cells in the canine testis, and the secreted inhibin may be inhibin A and inhibin B.

Interaction theory of mammalian mitochondria.

We generated mice with deletion mutant mtDNA by its introduction from somatic cells into mouse zygotes. Expressions of disease phenotypes are limited to tissues expressing mitochondrial dysfunction. Considering that all these mice share the same nuclear background, these observations suggest that accumulation of the mutant mtDNA and resultant expressions of mitochondrial dysfunction are responsible for expression of disease phenotypes. On the other hand, mitochondrial dysfunction and expression of clinical abnormalities were not observed until the mutant mtDNA accumulated predominantly. This protection is due to the presence of extensive and continuous interaction between exogenous mitochondria from cybrids and recipient mitochondria from embryos. Thus, we would like to propose a new hypothesis on mitochondrial biogenesis, interaction theory of mitochondria: mammalian mitochondria exchange genetic contents, and thus lost the individuality and function as a single dynamic cellular unit.