[AFP and PIVKA-â ¡ Producing Gastric Cancer with Metachronous Liver Metastasis after Gastrectomy-A Case Report].

A 67-year-old man visited his doctor because of anorexia and was diagnosed with gastric cancer based on endoscopic findings. Endoscopy revealed a 0-Ⅰ type tumor, 6 cm in size, at the gastric angle. Preoperative CT showed no apparent lymph node or distant metastases. Distal gastrectomy was performed for gastric cancer with Billroth Ⅰ reconstruction. He had no complications and was discharged on postoperative day 11. The pathological Stage was pT2N0M0, pStage ⅠB, and he underwent no adjuvant chemotherapy. Four months postoperatively, serum CA19-9, AFP, and PIVKA-Ⅱ were elevated, and CT revealed multiple liver tumors. A liver biopsy was performed for the definitive diagnosis. The patient was diagnosed with liver metastases from gastric cancer. It is considered that AFP and PIVKA-Ⅱ were produced by the liver metastasis from gastric cancer. He received chemotherapy for liver metastasis and died 1 year after the recurrence.

Osteoblast-like cell responses to ion products released from magnesium- and silicate-containing calcium carbonates.

BACKGROUND: Inorganic ions released from bioceramics and bioactive glasses have been reported to influence osteogenic cell functions. Cell responses depend on types of the ions provided, for example, silicate ion has been found to up-regulate their proliferation, differentiation and mineralization. OBJECTIVE: Mouse osteoblast-like cells (MC3T3-E1) were cultured in media containing silicate and calcium ions with/without magnesium ion to evaluate their combined effects on the cell's functions. METHODS: The cells were cultured in the media containing the extract of silicate-containing vaterite (SiV) and magnesium- and siloxane-containing one (MgSiV) and normal medium and then their adhesion, proliferation, differentiation and mineralization were evaluated. RESULTS: The adhesion of the cells was enhanced when they were cultured in the medium containing MgSiV-extract. Their proliferation and differentiation were up-regulated in both media containing MgSiV-extract and SiV-extract. In particular, the MgSiV-extract significantly enhanced their differentiation than the SiV-extract. This was supported by the mineralization test's results, which showed a large amount of mineral deposit was observed in the cells cultured in the MgSiV-extract medium. CONCLUSIONS: Providing the three kinds of ions was effective for up-regulating the cell's mineralization compared to providing silicate and calcium ions without magnesium ion.

Development of Magnesium and Siloxane-Containing Vaterite and Its Composite Materials for Bone Regeneration.

Development of novel biomaterials with Mg(2+), Ca(2+), and silicate ions releasability for bone regeneration is now in progress. Several inorganic ions have been reported to stimulate bone-forming cells. We featured Ca(2+), silicate, and especially, Mg(2+) ions as growth factors for osteoblasts. Various biomaterials, such as ceramic powders and organic-inorganic composites, that release the ions, have been developed and investigated for their cytocompatibilities in our previous work. Through the investigation, providing the three ions was found to be effective to activate osteogenic cells. Magnesium and siloxane--containing vaterite was prepared by a carbonation process as an inorganic particle that can has the ability to simultaneously release Ca(2+), silicate, and Mg(2+) ions to biodegradable polymers. Poly (l-lactic acid) (PLLA)- and bioactive PLLA-based composites containing vaterite coatings were discussed regarding their degradability and cytocompatibility using a metallic Mg substrate as Mg(2+) ion source. PLLA/SiV composite film, which has a releasability of silicate ions besides Ca(2+) ion, was coated on a pure Mg substrate to be compared with the PLLA/V coating. The degradability and releasability of inorganic ions were morphologically and quantitatively monitored in a cell culture medium. The bonding strength between the coatings and Mg substrates was one of the key factors to control Mg(2+) ion release from the substrates. The cell culture tests were conducted using mouse osteoblast-like cells (MC3T3-E1 cells); cellular morphology, proliferation, and differentiation on the materials were evaluated. The PLLA/V and PLLA/SiV coatings on Mg substrates were found to enhance the proliferation, especially the PLLA/SiV coating possessed a higher ability to induce the osteogenic differentiation of the cells.

The measurement of axillary moisture for the assessment of dehydration among older patients: a pilot study.

PURPOSE: Dry axilla can sometimes be found among dehydrated older patients. In this study, we measured the axillary moisture and assessed it as possible marker for dehydration. METHODS: Twenty-nine older patients admitted with acute medical conditions participated in this study. Dehydration was diagnosed by the calculated serum osmolality of greater than 295 mOsm/L. The moisture of axilla was measured by a skin moisture impedance meter which was applied at the center of axilla of patients. RESULTS: 11 patients (7 males and 4 females) were diagnosed as dehydrated and 18 patients (10 males and 8 females) were diagnosed as non-dehydrated. The mean axillary moisture (33%) in the dehydrated group was significantly lower than that (42%) in the non-dehydrated group (p<0.05). The axillary moisture ≥50% showed the sensitivity of 88%. The axillary moisture <30% showed the specificity of 91%. Use of a single cutoff value of 40% moisture produced the sensitivity of 59% and the specificity of 9%. As for the physical signs, dry axilla had also moderate sensitivity and excellent specificity to detect dehydration. CONCLUSIONS: The measurement of the axillary moisture could help assess dehydration. Dehydration could be ruled out when the axillary moisture ≥50%, while it could be ruled-in when the axillary moisture is <30%.

Physical signs of dehydration in the elderly.

OBJECTIVE: Dehydration is a common condition and frequent cause of hospitalization in older people, despite the caregiver's high attention in attempt to avoid its occurrence. In this study, various physical signs were examined as clinical signs of dehydration in elderly. METHODS: A prospective observational study was conducted in an acute care teaching hospital. Consecutive elderly patients who were admitted to the Department of Medicine were evaluated. Dehydration was defined as a calculated serum osmolality above 295 mOsm/L. The patients diagnosed as dehydrated or not dehydrated were observed for physical signs of dehydration. Data of blood and urine chemistry analysis were also compared between the two groups. RESULTS: A total of 27 elderly patients admitted with acute medical conditions were included in this study. For the physical signs, dry axilla had moderate sensitivity (44%) and excellent specificity (89%) to detect dehydration. Sunken eyes and delayed capillary refill time also showed relatively good specificity (83%). For laboratory data, the mean concentrations of serum sodium of the dehydrated group (146 mEq/L) was significantly higher (p<0.01) than those of the non-dehydrated group (134 mEq/L). CONCLUSION: Physical signs of dehydration in elderly showed relatively good specificity but poor sensitivity. The evaluation of the axillary moisture could help assess dehydration as well as laboratory data analysis such as serum sodium concentration.

Siloxane-poly(lactic acid)-vaterite composites with 3D cotton-like structure.

Trace amounts of ionic calcium and silicon species have been reported to stimulate the proliferation, differentiation, and mineralization of bone-forming cells. Composite materials comprising siloxane-doped calcium carbonate (vaterite) particles and poly(L-lactic acid) have been developed [siloxane-poly(lactic acid)-vaterite hybrid-composite, SiPVH] so far; they were designed such that calcium and silicate ions are gradually released from SiPVH and they show the chronic effects of ions on cellular activities. In the present work, SiPVH with a 3D cotton-like structure was prepared by electrospinning to obtain the major advantages of excellent bioactivity and ease of handling for bone filling surgery. The diameter of the fibrous skeletons that form structure of the cotton-like SiPVH was controlled to ~10 µm to achieve cellular migration into the spaces between fibers. The resulting cotton-like SiPVH showed good flexibility. The fiber surface was coated rapidly with numerous particles of several hundred nanometers in size by alternate soaking in CaCl(2) and Na(2)HPO(4). The treated cotton-like material, which released calcium and silicate ions gradually, showed good cellular migration behavior into the 3D structure in cell culture tests using murine osteoblast-like MC3T3-E1 cells.

Prostaglandin synthases influence thyroid follicular cell proliferation but not carcinogenesis in rats initiated with N-bis(2-hydroxypropyl)nitrosamine.

To clarify roles of prostaglandin synthases in rat thyroid follicular carcinogenesis, effects of an antithyroid agent, sulfadimethoxine (SDM), and two prostaglandin H synthase (COX) inhibitors, indomethacin and nimesulide, on prostaglandin synthase expression, follicular cell proliferation, and tumor induction in thyroids of rats with or without N-bis(2-hydroxypropyl)nitrosamine (DHPN) initiation were examined. In experiment 1, F344 male rats were allowed free access to drinking water containing SDM (0.1%), SDM + indomethacin (0.0025% in diet), or SDM + nimesulide (0.04% in diet) for 4 weeks. Both COX inhibitors suppressed goitrogenic activity of SDM, but they did not significantly affect microsomal prostaglandin E synthase-2 (mPGES-2) expression levels enhanced by SDM. In experiment 2, all rats received an injection of DHPN (2800 mg/kg body weight), and starting 1 week later, they were treated as in experiment 1 for 4 or 10 weeks. Cell proliferation was suppressed or showed a tendency for suppression by the COX inhibitors in the follicular preneoplastic/neoplastic lesions and surrounding parenchyma, and this was obviously thyroid stimulating hormone independent at least at week 4. However, neither of the COX inhibitors altered the incidence or multiplicity of preneoplastic/neoplastic lesions. Immunohistochemistry revealed significant reduction and elevation of COX-2 and mPGES-2 expression, respectively, in the lesions, but these were also not changed by the COX inhibitors. These results suggest that COX-2 and PGES, and in turn PGE(2), might play important roles in follicular cell proliferation but do not affect tumor induction in this rat thyroid carcinogenesis model. Further studies are needed to clarify the significance of the reduction of COX-2 expression in preneoplastic/neoplastic lesions.

[The significance of chemoradiation therapy for TNM cStage II - III esophageal squamous cell carcinoma].

UNLABELLED: The value of chemoradiation therapy (CRT) followed by surgery is unknown in Japan. PATIENT AND METHOD: Thirty Patients with TNM cStage II - III squamous cell carcinoma (SCC) of the esophagus were divided into CRT (40 Gy) followed by surgery( arm A) and definitive CRT( 60 Gy()arm B). The correlations between several clinicopathological factors and survival time were examined. RESULTS: The effective rate (CR+PR) of CRT was 75% in arm A versus 88.9% in arm B (p= 0.32). There was no significant difference about the median survival time (arm A: 17. 4 months, arm B: 12. 6 months, p= 0.18). The two-year survival rate was 40 . 4% in arm A versus 41 . 6% in arm B (p=0.35). CONCLUSION: Our retrospective study showed no significant difference in prognosis between CRT followed by surgery and definitive CRT. Definitive CRT might be a choice of therapy for curative esophageal carcinoma.

[Preoperative chemoradiotherapy with S-1 for advanced low rectal cancer].

We reviewed the patients with neoadjuvant chemoradiotherapy (CRT) with S-1 to evaluate the feasibility and effectiveness for locally advanced lower rectal cancer. The CRT regimen consisted of pelvic irradiation (45 Gy in fractions of 1.8 Gy), five days a week. A treatment of oral S-1 (80 mg/m2 per day) on days 1-14 and 22-35 was given during radiotherapy. Patients underwent a curative resection with lateral lymph node resection at 6-8 weeks intervals after neoadjuvant CRT. The response rate on pathological study was 60% (all were grade 2), and no patients had lateral lymph node metastases. Grade 1 or 2 adverse effects occurred in all patients during CRT, but the CRT was achieved in all patients. We found two patients had surgical complications with wound infection and one patient with anastomotic leakage. All complications were improved by conservative treatment. The neoadjuvant CRT was feasible and effective treatment for all patients with locally advanced rectal cancer. We have started a phase II study of the neoadjuvant CRT.

Effect of preparation route on the degradation behavior and ion releasability of siloxane-poly(lactic acid)-vaterite hybrid nonwoven fabrics for guided bone regeneration.

Two types of nonwoven fabric, consisting of siloxane-doped vaterite (SiV) and poly(lactic acid) (PLA), for guided bone regeneration (GBR) were prepared by an electrospinning. One of the fabrics, SiV-PLA(M), was derived from PLA mixed with the solution of SiV dispersed in chloroform. Another one, SiV-PLA(K), was derived from a composite prepared by kneading SiV and PLA while heating at 200°C. The SiV-PLA(K) fabric shows higher degradability in dilute NaOH aq. than the SiV-PLA(M) fabric. To improve the cellular compatibility of the fabric, the fibers were coated with hydroxyapatite (HA) by soaking in simulated body fluid. The HA-coated SiV-PLA(K) fabric showed the release of silicate ions; the amount was reduced by 1/5 to 1/8 compared with that of the HA-coated SiV-PLA(M) fabric, and the excessive release was controlled. The preparation route of kneading at 200°C led to formation of a fabric with degradation behavior and ion releasability effective for bone regeneration.

[A case report of locally advanced rectal carcinoma effectively treated with preoperative chemoradiotherapy].

The patient was an 80-year-old woman who was diagnosed with locally advanced low rectal cancer. It was unresectable and we performed chemoradiotherapy combined with S-1 (S-1 80 mg/m2, RT 1.8 Gy × 25, total 45 Gy). An effective reduction of primary region resulted in curative resection (super low anterior resection, D3 lymph node dissection, covering ileostomy) with preserving the anal sphincter. Histopathologically, therapeutic efficacy was Grade 2. Preoperative chemoradiation has been a standard therapy in Western countries and would control local recurrence. This case indicated that CRT could improve a rate of curative resection in patients with locally advanced rectal carcinomas.

Electrospun microfiber meshes of silicon-doped vaterite/poly(lactic acid) hybrid for guided bone regeneration.

Silicon-releasable microfiber meshes consisting of silicon-doped vaterite (SiV) particles and poly(lactic acid) (PLA) hybrids were prepared by electrospinning. Due to their flexibility and porosity they formed ideal membranes or scaffolds for guided bone regeneration. In addition, a trace amount of silicon species has been reported to stimulate osteogenic cells to mineralize and enhance bone formation. We propose a new method of preparation of silicon-releasing microfiber meshes by electrospinning. Their structure and hydroxyapatite (HA)-forming abilities in simulated body fluid were examined. In addition, we studied their stimulatory effects on osteoblast-like cells in vitro and bone-forming ability in vivo, with a special emphasis on their ability to release silicon. The meshes consisted of a hybrid of carboxy groups in PLA and amino groups in siloxane, derived from aminopropyltriethoxysilane or calcium ions on the SiV surface. This hybrid exhibited an enhanced ability to form HA. The meshes coated with HA released 0.2-0.7 mg l(-1) silicon species into the culture medium over 7 days. Enhanced proliferation of osteoblast-like cells was observed using the meshes and new bone formed on the meshes when implanted into the calvaria of rabbits. These meshes, therefore, provide an excellent substrate for bone regeneration and exhibit enhanced bone-forming ability under both in vitro and in vivo conditions.

Inhibitory effects of aminoguanidine on thyroid follicular carcinoma development in inflamed capsular regions of rats treated with sulfadimethoxine after N-bis(2-hydroxypropyl)nitrosamine-initiation.

We have reported that thyroid capsular thickening with inflammation induced by an antithyroidal agent, sulfadimethoxine (SDM), might play a role in the development of invasive follicular carcinomas in rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Inducible nitric oxide synthase (iNOS) expressed in the inflamed capsular regions further appeared to be implicated in the tumor progression. In the present study, the effects of an iNOS inhibitor, aminoguanidine (AG), on thyroid carcinogenesis were examined. F344 male rats were treated with SDM in drinking water (0.1%) with or without concomitant dietary administration of AG (0.2%) for 4 and 10 weeks after subcutaneous injection of DHPN at 2800 mg/kg bodyweight. At week 4, thyroid capsular thickening with inflammation was observed and iNOS-positive foci were found in the inflamed regions. In addition, single-strand DNA-positive inflammatory cells were scattered among neighboring follicular cells, indicating some cellular damage, at least partly in association with iNOS induction. Concurrent dietary administration of AG with SDM treatment slightly decreased the number of single-strand DNA-positive cells but did not alter the incidence and multiplicity of iNOS-positive foci in the inflamed capsular regions at week 4. At week 10, however, invasive follicular carcinomas predominantly arose in the thickened capsule in the DHPN-SDM-treated rats, and AG administration decreased (P < 0.05) their multiplicity. The carcinoma cells were partly positive for iNOS. These results thus suggested that iNOS induction in both inflammatory and tumor cells might play pivotal roles in tumor progression in this DHPN-SDM rat model.

A 55-week chronic toxicity study of dietary administered kojic acid (KA) in male F344 rats.

A chronic toxicity study of kojic acid (KA) was performed using male F344 rats by dietary administration at concentrations of 0 (control), 0.5 and 2.0% for 55 weeks. Body weight gain was suppressed in the 2.0% group. The major hematological findings were decreased red blood cell (RBC) count and hematocrit (Ht) values at both 0.5 and 2.0%. In serum biochemistry, increased aspartate transaminase (AsT), alanine transaminase (AlT), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) levels were detected in the 0.5 and 2.0% groups. Histopathologically, single cell necrosis of hepatocytes and proliferation of bile ductules in both treatment groups, and hypertrophy of hepatocytes, granulomas and proliferation of bile ducts in the 2.0% group were increased in incidence, and numbers and areas of glutathione-S-transferase placental-form (GST-P) positive foci were increased in the liver of the 2.0% group. In the thyroids, diffuse follicular cell hyperplasia at 0.5 and 2.0% and focal follicular cell hyperplasia and follicular adenoma at 2.0% were increased. A thyroid follicular carcinoma was also observed at 2.0%. Additionally, increased incidences of hyaline casts and basophilic tubules in the kidneys at 2.0% and microgranulomas containing crystals in the lung in both treatment groups were noted. At 2.0%, hypertrophy of cortical cells in zona fasciculata was also increased in the adrenals. In conclusion, no observed adverse effect level of KA was below 0.5%, which is equivalent to 227 mg/kg body weight/day in male rats.

A new medium-term rat colorectal bioassay applying neoplastic lesions as end points for detection of carcinogenesis modifiers effects with weak or controversial modifiers.

We have established a two-stage, medium-term rat colorectal carcinogenesis model featuring induction of neoplastic lesions within ten weeks. In the present study, we examined the ability of this model to detect weak modifiers. F344 male rats were given three subcutaneous (sc) injections of 1,2-dimethyl-hydrazine (DMH, 40 mg/kg b.w.) in one week followed by drinking water containing 1% dextran sodium sulfate (DSS) for a second week. One week after this regimen, basal diet alone, or diets containing 10% perilla oil, 10% corn oil, 10% dextrin, or 0.1% indole-3-carbinol (I3C) were supplied. The perilla oil and corn oil groups did not show significant differences in the numbers of aberrant crypt foci (ACF) and incidences or multiplicity of proliferative lesions as compared to the controls at either time point. In the dextrin group, the total number of ACF at week ten was significantly increased. With I3C, the total number of ACF and incidence and multiplicities of adenocarcinomas at week ten and the incidence of invasive tumors at week twenty were significantly increased. These data essentially correspond with earlier reported results, except in the vegetable oil cases. Thus, the system is suitable for detection of colorectal carcinogenesis modifiers with advantages over previous models using ACF alone as end points.

Significance of inflammation-associated regenerative mucosa characterized by Paneth cell metaplasia and beta-catenin accumulation for the onset of colorectal carcinogenesis in rats initiated with 1,2-dimethylhydrazine.

Short-term dextran sodium sulfate (DSS) treatment has been shown to notably accelerate colorectal tumor development in rats initiated with 1,2-dimethylhydrazine (DMH). In the present study, to clarify mechanisms underlying the DSS influence, time-course studies of histopathological and immunohistochemical characteristics and beta-catenin gene mutations in colorectal mucosa in early stages of this model were conducted. F344 males were given three subcutaneous injections of DMH (40 mg/kg body wt) within a week, followed by free access to drinking water containing 1% DSS for a week. At weeks 1, 4, 6 and 8 after the DSS treatment, rats were euthanized and colorectal samples were collected. At week 1, the colorectal mucosa demonstrated extensive erosion along with significant inflammatory cell infiltration and neighboring reactive hyperplasia. By week 4, the mucosal damage was repaired and regenerative mucosa, partly characterized by Paneth cell metaplasia and altered subcellular localization of beta-catenin, was apparent. Areas with Paneth cells/beta-catenin accumulation were significantly more likely to be accompanied by interstitial inflammation and 17 of 24 dysplastic foci were found in regenerative mucosa with Paneth cells. Furthermore, adenomas/carcinomas frequently featured various degrees of Paneth cell differentiation. Point mutations mainly in codons 34 and 41 of beta-catenin gene were detected in 6 of 27 samples of regenerative mucosa with Paneth cells and four of nine dysplastic foci/adenomas/carcinomas. These findings indicate that inflammation-associated regenerative mucosa with Paneth cell metaplasia and alteration in the APC/beta-catenin/Tcf signal transduction pathway are possibly involved in the acceleration of colorectal carcinogenesis in this DMH-DSS rat model.

Bone formation following implantation of fibrous calcium compounds (beta-Ca(PO3)2, CaCO3(aragonite)) into bone marrow.

Bone formation around three types of fibrous calcium-containing crystals has been examined histologically using rats. The implanted materials are (i) calcium metaphosphate (beta-Ca(PO(3))(2)) fibers having aspect ratios of 15-80 with 2-20 microm in diameter, (ii) beta-Ca(PO(3))(2)) fibers surface-modified using dilute NaOH and (iii) calcium carbonate (CaCO(3); aragonite phase) whiskers having aspect ratios of 15-40 with 0.5-3 microm in diameter. Beta-Ca(PO(3))(2) fibers show a mechanically high strength with a low modulus of elasticity, and the surface-modified fibers have a thin layer consisting of a calcium orthophosphate phase. CaCO(3) whiskers were used for comparison reasons. The materials were implanted for 4, 8, and 12 weeks into bone defects created in the bone marrow of rat tibiae. Cancellous bone formation was observed around beta-Ca(PO3)2 fibers, the surface-modified fibers and CaCO(3) whiskers after implantation for 12, 4 and 4 weeks, respectively. CaCO(3) whiskers were scarcely observed after 12 weeks for resorbing. The calcium phosphate fibrous materials show combined advantages of mechanically high strength for toughening a matrix phase and biological activities; thus, these materials may prove to be useful for novel applications in the biomedical field.