Phase II trial of preoperative S-1 plus cisplatin followed by surgery for initially unresectable locally advanced gastric cancer.

BACKGROUND: The aim of this study was to evaluate the efficacy and feasibility of preoperative chemotherapy with S-1 plus cisplatin in patients with initially unresectable locally advanced gastric cancer. METHODS: We enrolled patients with initially unresectable locally advanced gastric cancer because of severe lymph node metastases or invasion of adjacent structures. Preoperative chemotherapy consisted of S-1 at 80 mg/m(2) divided in two daily doses for 21 days and cisplatin at 60 mg/m(2) intravenously on day 8, repeated every 35 days. If a tumor decreased in size, patients received 1 or 2 more courses. Surgery involved radical resection with D2 lymphadenectomy. RESULTS: Between December 2000 and December 2007, 27 patients were enrolled on the study. No CR was obtained, but PR was seen in 17 cases, and the response rate was 63.0%. Thirteen patients (48.1%) had R0 resections. There were no treatment related deaths. The median overall survival time (MST) and the 3-year overall survival (OS) of all patients were 31.4 months and 31.0%, respectively. Among the 13 patients who underwent curative resection, the median disease-free survival (DFS) and the 3-year DFS were 17.4 months and 23.1%, respectively. The MST and the 3-year OS were 50.1 months and 53.8%, respectively. The most common site of initial recurrence after the R0 resection was the para-aortic lymph nodes. CONCLUSIONS: Preoperative S-1 plus cisplatin can be safely delivered to patients undergoing radical gastrectomy. This regimen is promising as neoadjuvant chemotherapy for resectable gastric cancer. For initially unresectable locally advanced gastric cancer, new trials using more effective regimens along with extended lymph node dissection are necessary.

Combination therapy of an anticancer drug with the FNIII14 peptide of fibronectin effectively overcomes cell adhesion-mediated drug resistance of acute myelogenous leukemia.

We investigated whether FNIII14, a 22-mer peptide derived from fibronectin (FN) that potently impairs interaction of FN with beta1-integrin, could overcome cell adhesion-mediated drug resistance (CAM-DR) induced by very late antigen (VLA)-4-to-FN interaction in acute myelogenous leukemia (AML). Two AML cell lines, U937 cells and HL-60 cells, and fresh leukemic cells from six AML patients with high alpha4-integrin expression exhibited CAM-DR to cytosine arabinoside (Ara C) through VLA-4-to-FN interaction, while fresh leukemic cells from two AML patients with low alpha4-integrin expression did not display CAM-DR to Ara C. FNIII14 impaired VLA-4-to-FN interaction and restored sensitivity to Ara C in the CAM-DR leukemic cells. In these CAM-DR leukemic cells, upregulation of Bcl-2, which was induced through the focal adhesion kinase/Akt signal pathway upon VLA-4-to-FN interaction, was inhibited by FNIII14 treatment. In a mouse model of minimal residual disease (MRD) in bone marrow, 100% survival was achieved by combining FNIII14 with Ara C, whereas Ara C alone prolonged survival only slightly. The myelosuppression induced by Ara C was not augmented by the combination of FNIII14 in mouse experiments. Thus, the combination of anticancer drugs and FNIII14 holds promise to eradicate MRD in bone marrow after chemotherapy.

Calculation of energy distributions of charged particles produced by neutrons from 0.14 to 65 MeV in tissue substitutes.

Energy distributions of secondary charged particles were calculated in tissue substitutes irradiated by neutrons from 0.14 to 65 MeV, using the Particle and Heavy Ion Transport code System. The calculations were compared with experimental data measured by tissue equivalent proportional counters (TEPC). It is found that the calculated distributions of the lineal energy, y, generally agree well with the measured ones for neutrons from several 100 keV to 15 MeV. In the case of 40 and 65 MeV neutron irradiations, wall effects of TEPC should be considered and the fluence of alphas is underestimated by the calculations. Integrated dose contributions of the secondary charged particles are generally in good agreement with those of the measured ones.

Development of a quasi-monoenergetic neutron field using the 7Li(p,n)7Be reaction in the energy range from 250 to 390 MeV at RCNP.

A quasi-monoenergetic neutron field using the (7)Li(p,n)(7)Be reaction has been developed at the ring cyclotron facility at the Research Center for Nuclear Physics (RCNP), Osaka University. Neutrons were generated from a 10-mm-thick Li target injected by 250, 350 and 392 MeV protons and neutrons produced at 0 degrees were extracted into the time-of-flight (TOF) room of 100-m length through the concrete collimator of 10 x 12 cm aperture and 150 cm thickness. The neutron energy spectra were measured by a 12.7-cm diam x 12.7-cm long NE213 organic liquid scintillator using the TOF method. The peak neutron fluence was 1.94 x 10(10), 1.07 x 10(10) and 1.50 x 10(10) n sr(-1) per muC of 250, 350 and 392 MeV protons, respectively. The neutron spectra generated from various thick (stopping length) targets of carbon, aluminium, iron and lead, bombarded by 250 and 350 MeV protons, were also measured with the TOF method. Although these measurements were performed to obtain thick target neutron yields, they are also used as a continuous energy neutron field. These neutron fields are very useful for characterising neutron detectors, measuring neutron cross sections, testing irradiation effects for various materials and performing neutron shielding experiments.

The current status of treatment strategies for cerebral aneurysms in nagoya university and affiliated hospitals based on a questionnaire survey.

SUMMARY: We investigated differences in the treatment strategies for ruptured aneurysms among 26 hospitals affiliated with Nagoya University and any changes in those strategies based on responses to a questionnaire.We also surveyed the data concerning patients with a ruptured aneurysm collected from our affiliated hospitals between 2001 and 2002. In half of the institutes, angiography is performed immediately after an urgent medical examination, there are only five hospitals (20%) which have a basic policy of terminating the angiography within three to six hours after onset. In half of the institutes, the timing of the treatment also depends on the location of the aneurysm. In particular, the treatment for vertebro-basilar aneurysms tends to be done the next day or later. Low-grade subarachnoid hemorrhage (SAH) patients with mild symptoms tended not to be given any sedative drugs (46%), while patients with SAH in some institutes were sedated without informed consent regardless of the severity. The main treatment method for most anterior circulation aneurysms was clipping. Concerning aneurysms located in the posterior circulation and the origin of the ophthalmic artery, clipping and coiling were equally selected. Almost all the hospitals (92%) responded that their treatment strategy had not changed even after the report of the International Subarachnoid Aneurysm Trial (ISAT). There is a great deal of difference in treatment strategies and indications among institutions. In particular, institutions without neuroendovascular interventionists (NETists) frequently persist in the conventional policy, making it urgently necessary to bring NETists up-to-date on the latest advance in endovascular treatment.

Radiation safety design for the J-PARC Project.

The High-Intensity Proton Accelerator Project, named J-PARC, is in progress, with the aim of enabling studies on the latest basic science and the advancement of nuclear technology. In the project, a high-energy proton accelerator complex with the world's highest instantaneous intensity is under construction. In order to establish a reasonable shielding design, both simplified and detailed design methods were used in the shielding design of J-PARC. This paper reviews the present status of the radiation safety design study for J-PARC.

Characteristic response of plastic track detectors to 40-80 MeV neutrons.

This paper investigates the characteristic response of plastic track detectors to high-energy neutrons. Three types of plastic nuclear track detector (PNTD), Baryotrak made of pure CR-39, TD-1 made of CR-39 containing an antioxidant and TNF-1 made of a copolymer of CR-39/N-isopropylacrylamide, were exposed in quasi-monoenergetic neutron fields generated by p-Li reactions. The total efficiencies for TD-1 and TNF-1 were more than double and triple that of Baryotrak respectively. In addition, the species of particles were classitied into three groups, i.e. proton relatives, alpha particles and heavy ions, by analysing the etch-pit growth curve obtained by step-by-step etching. In a 65 MeV neutron field about half of the tracks recorded in pure CR-39 were due to heavy ions, whereas the TNF-1 detector could effectively register the protons, accounting for 70% of the tracks. The results could be explained by the difference in the sensitivity to high-energy protons.

Histopathological grading does not affect survival after R0 surgery for gastric cancer.

AIM: It is unclear whether Histopathological Grading (UICC, TNM Classification) affects survival after resection for gastric cancer. METHODS: To investigate the prognostic significance of Histopathological Grading after gastrectomy, 1455 patients who underwent gastric resection for gastric adenocarcinoma were reviewed. RESULTS: The R0 (UICC, R Classification) resection rate was inversely correlated with the grade (86.5% for Grade 1, 79.7% for Grade 2 and 69.2% for Grade 3) and the R1 and R2 resection rates increased with the grade. The Histopathological Grading did not influence survival in the 1119 patients who underwent R0 resection (71.0% for Grade 1, 65.7% for Grade 2 and 66.7% for Grade 3). When multivariate analysis was performed for the 1119 cases undergoing R0 resection, the Histopathological Grading was not a determinant prognostic factor. CONCLUSION: We conclude that the UICC Histopathological Grading affects R0 resection rates, but does not affect survival independently.

Measurement of lineal-energy distributions for neutrons of 8 keV to 65 MeV by using a tissue-equivalent proportional counter.

The lineal-energy spectra for monoenergetic and quasi-monoenergetic neutrons of 8 keV to 65 MeV were obtained using a tissue-equivalent proportional counter (TEPC). The frequency-mean lineal energy, the dose-average lineal energy and mean quality factor were estimated from the measured data. The neutron absorbed doses obtained with this TEPC were compared with the kerma coefticient for A-150 plastic defined by ICRP 26 and the mean quality factors were compared with the data of ICRP 74. respectively. These comparisons indicated good agreement between them.

Length of the antral segment in pylorus-preserving gastrectomy.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) has the advantages of preventing dumping syndrome and duodenogastric reflux. However, time was required to reduce symptoms of gastric fullness or to improve food intake after surgery. The aim of this study was to investigate whether the length of the retained antral segment influenced the postoperative symptoms in patients who underwent PPG. METHODS: Thirty patients with early gastric cancer who underwent PPG were divided into two groups according to the length of the retained antrum. In group 1 (n = 20) the transection was 1.5 cm and in group 2 (n = 10) it was 2.5 cm proximal to the oral edge of the pyloric ring. The subjects were interviewed and examined periodically to assess symptoms, food intake, body-weight and serum nutritional variables. Endoscopy and a radioisotope gastric emptying test were performed 1 year after the operation. RESULTS: In group 1 gastric fullness after meals was common, resulting in poor food intake and poor recovery of body-weight. A high incidence of food residue in the remnant stomach was found in group 1. With regard to gastric emptying, seven of 20 patients in group 1 and one of ten in group 2 had a delayed emptying curve 1 year after operation. CONCLUSION: Group 2 was superior to group 1 in terms of postprandial symptoms, food intake, recovery of body-weight and gastric emptying. The length of the retained antrum may play an important role in the motility of the pyloric ring following PPG.

An experimental study on radiation streaming through a labyrinth in a proton accelerator facility of intermediate energy.

A radiation streaming experiment has been carried out at the Takasaki Ion Accelerator Facility for Advanced Radiation Application at the Japan Atomic Energy Research Institute in a room housing a Cu target irradiated with 68 MeV protons and in a labyrinth of three-legs having a total length of 29 m. In the experiment, neutron and gamma ray energy spectra, neutron reaction rates, and neutron and gamma ray dose equivalent rates were measured using various counters and dosimeters. The experimental data show the applicability of some empirical formulas for estimating the thermal neutron flux in a room and neutrons streaming in a labyrinth designed for a proton accelerator operating in the intermediate energy region. The data suggest that it is mandatory to estimate the gamma ray dose equivalent rate in a labyrinth, which is dominated by the secondary gamma rays due to the neutron capture reaction.

[The concept of mood disorder in ICD-10].

The classification of 'Manic-depressive illness(MDI)' has been changing in this several years greatly. MDI is recently named as a 'mood(affective) disorder' according to the ICD and DSM diagnostic system. Since 1990, with ICD-10(WHO), and 1994, with DSM-IV(APA), practitioners have had at their disposal two(practically compatible) classifications of mental disorders containing operational criteria for diagnosis, and helpful in guiding clinical and therapeutic approach. In ICD-10, mood disorder belongs to the F3 category, and there are seven subcategories which were divided in to subclasses. The two other subclasses of 'F06.3 organic mood disorder' 'F41.2 mixed anxiety and depressive disorders' were set up additionally.

A randomized clinical trial of pouch reconstruction after total gastrectomy for cancer: which is the better technique, Roux-en-Y or interposition?

BACKGROUND/AIMS: To determine the optimum pouch reconstruction after total gastrectomy, we conducted a randomized trial to compare the usefulness between PR and PI in terms of quality of life. METHODOLOGY: Thirty patients younger than 70 years of age were selected and randomly classified into the following 2 groups: pouch and Roux-en-Y (PR; n = 15) and pouch and interposition (PI; n = 15). In each subject, the postoperative symptoms, food intake in a single meal, body weight, serum nutritional parameters, endoscopy, emptying time of the gastric substitute, and gallstone formation were evaluated. RESULTS: There were no significant differences in terms of the postprandial symptoms, food intake, body weight, and serum nutritional parameters until 2 years postoperative. Endoscopy showed a tendency of food stasis in the PR group, although this was not significant. The gastric emptying test in the PR group indicated that the retention capacity was slightly superior to that in the PI group. CONCLUSIONS: The impact of the duodenal passage on symptoms and nutrition could not be ascertained.

Recovery from psychotic illness: a 15- and 25-year international follow-up study.

BACKGROUND: Poorly defined cohorts and weak study designs have hampered cross-cultural comparisons of course and outcome in schizophrenia. AIMS: To describe long-term outcome in 18 diverse treated incidence and prevalence cohorts. To compare mortality, 15- and 25-year illness trajectory and the predictive strength of selected baseline and short-term course variables. METHODS: Historic prospective study. Standardised assessments of course and outcome. RESULTS: About 75% traced. About 50% of surviving cases had favourable outcomes, but there was marked heterogeneity across geographic centres. In regression models, early (2-year) course patterns were the strongest predictor of 15-year outcome, but recovery varied by location; 16% of early unremitting cases achieved late-phase recovery. CONCLUSIONS: A significant proportion of treated incident cases of schizophrenia achieve favourable long-term outcome. Sociocultural conditions appear to modify long-term course. Early intervention programmes focused on social as well as pharmacological treatments may realise longer-term gains.

Billroth I gastrectomy using a circular stapler to treat gastric cancer.

We describe herein our technique of performing gastrectomy followed by side-to-end gastroduodenostomy. Because the clamp is removed at the resection line of the greater curvature, there is no need to perform an additional gastrotomy for insertion of the instrument. This feature differentiates our technique from previous methods of anastomosis using the circular stapler. We believe that our technique is superior in simplicity and security to the traditional hand-sewn anastomosis. Moreover, it allows for a shorter operative time. This technique is recommended for practical surgery over conventional techniques.

Comparison of in-phantom dose distributions for coronary angiography using an x-ray machine and synchrotron radiation.

Coronary cineangiography using synchrotron radiation is anticipated, owing to the high intensity and availability of monoenergy. To investigate allowable dose levels in clinical application, absorbed dose distribution in a tissue substitute phantom for a conventional x-ray machine was measured with thermoluminescent dosimeters at the University of Tsukuba under the practical conditions used for digital angiography. The dose rate at a 0.5-cm depth was 0.145 Gy/s, and the dose per frame was 0.725 mGy for the irradiation period of 5 ms per frame. For synchrotron radiation, the dose distribution measurement was made at a 5-GeV AR (Accumulation Ring) of the High Energy Accelerator Research Organization, in which a polymethylmethacrylate (PMMA) phantom was irradiated with the strongest beam available at the facility, which was 33.32 keV, 5.2 x 6.2 cm2 beam. Using this beam, a 1-mm-diameter coronary artery has been visualized at 1% iodine concentration at the AR. Nonhomogeneous strength distribution in the beam was observed in the vertical direction. The maximum dose rate was 0.556 Gy/s, and it attenuated to 1/3000 at a 30-cm depth in the beam center. At the deep positions, the doses were influenced by the high harmonics, which was confirmed with an EGS4 Monte Carlo calculation. Outside the beam, beam contamination on both sides of the main beam affected the doses. For comparison to the x-ray machine, the measured dose was analytically converted to that needed for a 5.2 x 16 cm2 beam that is used for clinical application. The dose rate at 0.5-cm depth was found to be 0.215 Gy/s, which is 1.48 times larger than that for x-rays. Moreover, the attenuation rate in the phantom was significantly greater than that of the x-ray machine, because of the difference of the energy spectra between the x-rays and synchrotron radiation used.

Negative effect of transforming growth factor-beta-1 on intestinal anastomotic tissue regeneration.

To examine the involvement of transforming growth factor-beta(1 )(TGF-beta(1)) in intestinal anastomotic repair, we administered a TGF-beta(1)-neutralizing antibody to rats after operation, and then examined its influence on the healing process and interaction with other peptide growth factors. Thirty male Sprague-Dawley rats were subjected to primary anastomosis after transection of the small intestine (n = 30) and treated by intraperitoneal administration of IgG (n = 15) or the TGF-beta(1) neutralizing antibody (n = 15). Treatment with the antibody against TGF-beta(1) resulted in more definite mucosal growth and increased vascularity on day 5 after surgery. Augmented mRNA expression of epidermal growth factor and vascular endothelial growth factor, and an increased number of cells that expressed these peptides in granulation tissue were demonstrated by RT-PCR and immunohistochemical staining. Taken together it was indicated that TGF-beta(1) has negative effects on regeneration of the bowel wall mucosa and angiogenesis in the course of intestinal anastomotic wound healing.