[A Long-Term Survival Case of Gastric Cancer with Pyloric Stenosis and Peritoneum Dissemination That Received Intravenous and Intraperitoneal Paclitaxel Combined with S-1 Therapy after Bypass Surgery].

Although a 74-year-old man with gastric cancer with pyloric stenosis(cT4aN[+]M0, Stage Ⅲ)had undergone surgery, he was diagnosed with peritoneum dissemination. He received bypass surgery, and an intraperitoneal access port was implanted in his subcutaneous space. Postoperatively, he received 4 courses of SOX therapy. In treatment effect, the primary tumor showed no change, and ascites developed. Therefore, we changed the chemotherapy regimen in intravenous and intraperitoneal paclitaxel combined with S-1 therapy. After starting this regimen, the primary tumor decreased in size, and the pyloric stenosis improved. Currently, the patient is alive without recurrence for 5 years and 8 months after intravenous and intraperitoneal paclitaxel combined with S-1 therapy and receiving this treatment regularly.

Plasma glucagon levels measured by sandwich ELISA are correlated with impaired glucose tolerance in type 2 diabetes.

Glucagon dysfunction as well as insulin dysfunction is associated with the pathogenesis of type 2 diabetes (T2DM). However, it is still unclear whether the measurement of plasma glucagon levels is useful in understanding the pathophysiology of T2DM. We recently reported that sandwich ELISA provides more accurate plasma glucagon values than conventional RIA in healthy subjects. Here we used sandwich ELISA as well as RIA to assess plasma glucagon levels, comparing them in T2DM patients and healthy subjects during oral glucose (OGTT) or meal tolerance tests (MTT). We confirmed that sandwich ELISA was able to detect more significant difference between healthy subjects and T2DM patients in the fasting levels and the response dynamics of plasma glucagon than RIA. We also found significant differences in the following glucagon parameters: (1) fasting glucagon, (2) the area under the curve (AUC) of glucagon in OGTT, and (3) the change in glucagon between 0 and 30 min (ΔGlucagon0-0.5h) in OGTT or MTT. Among these, the most apparent difference was ΔGlucagon0-0.5h in MTT. When we divided T2DM patients into two groups whose ΔGlucagon0-0.5h in MTT was either below or above the maximum value in healthy subjects, the group with higher ΔGlucagon0-0.5h showed more significant impairment of glucose tolerance. These results suggest that the assessment of plasma glucagon levels by sandwich ELISA might enhance our understanding of the pathophysiology of T2DM.

The prevalence of diffuse idiopathic skeletal hyperostosis in Japan - the first report of measurement by CT and review of the literature.

BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is prone to be accompanied by a spinal column fracture which is resistant to conservative therapy. This major characteristic of DISH is not recognized adequately by physicians, because the disease's detailed pathological condition has not yet been investigated. Therefore, the purposes of this study were to investigate the prevalence of DISH using computed tomography (CT), and to validate the reliability of CT interpretation. METHODS: Subjects were 558 patients (300 male and 258 female) who underwent both CT of chest to pelvis and x-ray of chest and abdomen from August 2011 to July 2012 at any department other than orthopedic surgery in our institution. The definition of DISH based on x-ray as well as CT was the presence of consecutive fused vertebral bodies according to Resnick's criteria. The prevalence of DISH based on both modalities was calculated in all subjects. For 107 subjects extracted at random, intra- (Cohen kappa) and inter-observer error (Fleiss kappa) were calculated and the levels of fused segments were investigated. RESULTS: Ninety-eight of 558 subjects (17.6%) were diagnosed as DISH by x-ray, and 152 (27.2%) by CT. Among males, 70 of 300 subjects (23.3%) were diagnosed by x-ray, and 116 (38.7%) by CT. Among females, 28 of 258 subjects (10.9%) were diagnosed by x-ray and 36 (14.0%) by CT. The levels of fused segments were presented from thoracic spine to lumbar spine, especially the middle and lower thoracic spine. Cohen kappa of x-ray was 0.587, and that of CT was 0.825. Fleiss kappa of x-ray was 0.552, and that of CT was 0.643. CONCLUSIONS: The prevalence of DISH based on CT was 27.1%, which was higher than that of x-ray. In addition, intra- and inter-observer error by review of CT was less than that of x-ray. CT evaluation would be a better method for precise understanding of the state of DISH.

New strategy for the treatment of type 2 diabetes mellitus with incretin-based therapy.

Incretin-based therapy was first made available for the treatment of type 2 diabetes mellitus (T2DM) in the US in 2006 and in Japan in 2009. Four DPP-4 inhibitors and two GLP-1 analog/receptor agonists are currently available. The effects of incretin-based therapy are assumed to be exerted mainly through the hormonal and neuronal actions of one of the incretins, GLP-1, which is secreted from L cells localized in the small intestine. The benefits of this therapy over conventional sulfonylureas or insulin injections, such as fewer hypoglycemic events and reduced body weight gain, derive from the glucose-dependent insulinotropic effect. The protective effects of this therapy on vulnerable pancreatic ß-cells and against micro/macroangiopathy in T2DM are also most welcome. Indications and/or contraindications for incretin-based therapy should be clarified by prospectively studying the experiences of Japanese T2DM patients undergoing this therapy in the clinical setting.

Effect of additional administration of acarbose on blood glucose fluctuations and postprandial hyperglycemia in patients with type 2 diabetes mellitus under treatment with alogliptin.

Acarbose was administered at 300 mg/day to patients with type 2 diabetes mellitus (T2DM) who had been taking 25 mg/day of alogliptin, and levels of blood glucose were analyzed by continuous glucose monitoring (CGM) for 3 days. The mean blood glucose level with acarbose (136.4 ± 30.7 mg/dL) did not differ significantly from that without acarbose (141.7 ± 28.3 mg/dL). However, in the condition of the combination therapy, there were significant decreases in the standard deviation of the mean blood glucose levels for the 24-hour period (27.6 ± 9.1 vs. 16.2 ± 6.9 mg/dL, p<0.001) and mean amplitude of glycemic excursions (MAGE) (65.8 ± 26.1 vs. 38.8 ± 19.2 mg/dL, p=0.010). In addition, a meal tolerance test was conducted to monitor changes in insulin secretion and active GLP-1 and total GIP values. Ten subjects (5 males, 5 females) of 54.9 ± 6.9 years with BMI 25.9 ± 5.2 kg/m² and HbAlc 9.2 ± 1.2% were enrolled. In the meal tolerance test, active GLP-1 values before and after acarbose administration were 17.0 ± 5.8 and 24.1 ± 9.3 pmol·hr/mL (p=0.054), respectively, showing an increasing tendency, and total GIP(AUC0-180) values were 685.9 ± 209.7 and 404.4 ± 173.7 pmol·hr/mL, respectively, showing a significant decrease (p=0.010). The results indicate that the combined administration of both inhibitors is effective not only in decreasing blood glucose fluctuations and preventing postprandial insulin secretion. The beneficial effects may also protect the endocrine pancreas and inhibit body weight gain.

Liposarcoma of the pleural cavity.

Liposarcoma rarely occurs in the pleura or thoracic cavity, and few reports appear in the literature. We hypothesized that combining clinicopathologic, immunohistochemical, and fluorescence in situ hybridization methods would allow definite diagnoses. Using formalin-fixed, paraffin-embedded blocks, we examined 6 atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLPS), 5 dedifferentiated liposarcomas (DDLPSs), 2 pleomorphic liposarcomas, and 1 myxoid liposarcoma (MLPS). We used the Kaplan-Meier method and the Wilcoxon test for survival analysis for prognostic factor evaluation. Histologically, ALT/WDLPS was composed of a relatively mature adipocytic proliferation, accompanied by some lipoblasts. DDLPS exhibited round-to-oval tumor cells with a high nucleus-to-cytoplasm ratio that had proliferated in nests, accompanied in case 10 by some giant cells but no fatty cells. The pleomorphic type contained a varying proportion of pleomorphic lipoblasts. MLPS displayed uniform round- to oval-shaped cells and small signet-ring lipoblasts in a myxoid stroma. Immunohistochemically, 11 (79%), 11 (79%), and 10 (71%) of 14 cases were positive for S-100, p16, and CDK4, respectively. Six of the 14 cases (43%) were positive for MDM2 and adipophilin. One case of ALT/WDLPS and 3 cases of DDLPS exhibited MDM2 amplification by fluorescence in situ hybridization (Vysis LSI MDM2 SpectrumGreen Probe plus Vysis CEP 12 SpectrumOrange probe). ALT/WDLPS was the most favorable type for survival, while adipophilin tended to be a negative prognostic factor for pleural liposarcoma. For a firm diagnosis of liposarcoma in the pleura, immunohistochemistry for CDK4, MDM2, and adipophilin together with MDM2 gene amplification by fluorescence in situ hybridization may be an important diagnostic tool.

Mid-term results of acetabular reconstruction using a Kerboull-type acetabular reinforcement device.

PURPOSE: The purpose of this study was to investigate the mid-term results of 32 acetabular reconstructions performed using a Kerboull-type acetabular reinforcement device and bone graft between June 1997 and January 2009. METHODS: The mean age of the patients at the time of surgery was 71.4 years (range 55-85). Patients were followed-up for a mean of 7.5 years (range 2.1-13.7). The acetabular bone defects according to the American Academy of Orthopaedic Surgeons system was type III for 29 hips and type IV for three hips. Bulk allografts were performed in 30 hips and morselised autografts (iliac bone) were performed in two hips. Clinical evaluations were made according to the criteria of Postel/Merle d'Aubigné. RESULTS: The mean pre-operative Postel/Merle d'Aubigné hip score was 7.0 ± 2.9, and the final follow-up hip score was 12.6 ± 2.8. Six hips showed radiographic loosening, and two hips required further revision. A Kaplan-Meier analysis showed that the five-year and ten-year survival rates were 96.9% and 92.3%, respectively, using further revision of the acetabular device as an end point. CONCLUSION: Acetabular reconstruction using a Kerboull-type acetabular reinforcement device and bone graft gives satisfactory mid-term results.

Analysis of entropy production in finitely slow processes between nonequilibrium steady states.

We investigate entropy production in finitely slow transitions between nonequilibrium steady states in Markov jump processes using the improved adiabatic approximation method, which has a close relationship with the slow driving perturbation. This method provides systematic improvement of the adiabatic approximation on infinitely slow transitions from which we obtain nonadiabatic corrections. We analyze two types of excess entropy production and confirm that the leading adiabatic contribution reproduces known results, and then obtain nonadiabatic corrections written in terms of thermodynamic metrics defined in protocol parameter spaces. We also numerically study the resulting excess entropy production in a two-state system.

Changes in the pleural cavity by pleurodesis using talc or OK-432: an experimental study.

PURPOSE: To define the changes in the pleural cavity after pleurodesis induced by talc or OK-432. METHODS: A total of 30 rats were divided into three groups: a normal saline group (control group, n = 10), a group administered 400 mg/kg talc (talc group, n = 10), and a group administered 0.3 KE/kg OK-432 (OK-432 group, n = 10). Pleural cavities were examined and scored on the 30th day after the intrapleural administration of each agent. RESULTS: Both the talc group and OK-432 group showed significantly higher macroscopic or microscopic pleurodesis scores than the control group (P < 0.05). Upon microscopic evaluation, the pleurodesis scores in the talc group were significantly higher than those in the OK-432 group (P < 0.01).The majority of the pleural thickness was found on the visceral pleura, and the parietal pleura was very thin. The thickness of the visceral pleura in the talc group was significantly higher than that in the OK-432 group (P < 0.005). Pathologically, the pleural thickening in the talc group consisted of fibrous tissue with injury of the pleural mesothelium, and talc particles were seen in the submesothelial fibrotic tissue and inside the alveoli. CONCLUSIONS: Talc pleurodesis induces more marked changes in the pleural cavity than OK-432-induced pleurodesis.

Association of time in range with hemoglobin A1c, glycated albumin and 1,5-anhydro-d-glucitol.

AIMS/INTRODUCTION: Hemoglobin A1c (HbA1c), glycated albumin (GA) and 1,5-anhydro-d-glucitol (1,5-AG) are used as indicators of glycemic control, whereas continuous glucose monitoring (CGM) is used to assess daily glucose profiles. The aim of this study was to investigate the relationships between CGM metrics, such as time in range (TIR), and glycemic control indicators. MATERIALS AND METHODS: We carried out retrospective CGM and blood tests on 189 outpatients with impaired glucose tolerance (n = 22), type 1 diabetes mellitus (n = 67) or type 2 diabetes mellitus (n = 100). RESULTS: In type 1 diabetes mellitus and type 2 diabetes mellitus patients, HbA1c and GA were negatively correlated with TIR, whereas 1,5-AG was positively correlated with TIR. In type 1 diabetes mellitus patients, a TIR of 70% corresponded to HbA1c, GA and 1,5-AG of 6.9% (95% confidence interval [CI] 6.5-7.2%), 20.3% (95% CI 19.0-21.7%) and 6.0 µg/mL (95% CI 5.1-6.9 µg/mL), respectively. In type 2 diabetes mellitus patients, a TIR of 70% corresponded to HbA1c, GA and 1,5-AG of 7.1% (95% CI 7.0-7.3%), 19.3% (95% CI 18.7-19.9%) and 10.0 µg/mL (95% CI 9.0-11.0 µg/mL), respectively. TIR values corresponding to HbA1c levels of 7.0% were 56.1% (95% CI 52.3-59.8%) and 74.2% (95% CI 71.3-77.2%) in type 1 diabetes mellitus and type 2 diabetes mellitus patients, respectively. CONCLUSIONS: The results of this study showed that the estimated HbA1c corresponding to a TIR of 70% was approximately 7.0% for both type 1 diabetes mellitus and type 2 diabetes mellitus patients, and that the estimated 1,5-AG calculated from the TIR of 70% might be different between type 1 diabetes mellitus and type 2 diabetes mellitus patients.

Sternal Metastasis of Brain Meningioma - A Case Report.

BACKGROUND: Metastases of meningiomas are infrequent and the site of extracranial metastasis such as the bone is extremely rare. CASE REPORT: A 75-year-old male had a history of five sessions of surgery and gamma-knife treatment for brain meningioma over a period of 29 years. He visited our hospital because he noticed a swelling in his anterior chest 2 years and 6 months after the final treatment. After an open biopsy, histopathological analysis revealed the mass to be a metastatic grade II meningioma. We resected the tumor along with the sternum, ribs, pleura, and pericardium. The patient had recurrences in the thoracic cavity and pericardium postoperatively and received radiation therapy. He also had metastasis in the abdominal cavity, which spread rapidly. CONCLUSION: We report on a rare instance of metastasis to the sternum in a case of atypical meningioma, showing rapid growth and invasion after long-term treatment.

Relationships between time in range, glycemic variability including hypoglycemia and types of diabetes therapy in Japanese patients with type 2 diabetes mellitus: Hyogo Diabetes Hypoglycemia Cognition Complications study.

AIMS/INTRODUCTION: Continuous glucose monitoring (CGM) metrics, such as times in range (TIR) and time below range, have been shown to be useful as clinical targets that complement glycated hemoglobin (HbA1c) for patients with type 2 diabetes mellitus. We investigated the relationships between TIR, glycemic variability and patient characteristics in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: We carried out continuous glucose monitoring in 281 outpatients with type 2 diabetes mellitus who participated in a multicenter cohort (Hyogo Diabetes Hypoglycemia Cognition Complications) study. RESULTS: The results are shown as the median (interquartile range). The age, disease duration and HbA1c were 68 years (62-71 years), 13 years (7-23 years) and 6.9% (6.5-7.5%), respectively. TIR and standard deviation obtained by continuous glucose monitoring worsened significantly with increasing disease duration. Multiple regression analyses showed that disease duration (standard partial regression coefficient, ß = -0.160, P = 0.003), diabetic peripheral neuropathy (ß = -0.106, P = 0.033) and urinary albumin excretion (ß = -0.100, P = 0.043) were useful explanatory factors for TIR. In contrast, HbA1c (ß = -0.398, P < 0.001) and the use of antidiabetic drugs potentially associated with severe hypoglycemia (ß = 0.180, P = 0.028), such as sulfonylureas, glinides and insulin, were useful explanatory factors for time below range in the elderly patients with type 2 diabetes mellitus. CONCLUSIONS: The results of this study suggest that disease duration and diabetic complications are associated with TIR deterioration. In addition, low HbA1c levels and the use of antidiabetic drugs potentially associated with severe hypoglycemia might worsen the time below range in the elderly.

Crossover sign after rotational acetabular osteotomy for dysplasia of the hip.

BACKGROUND: This study was performed to evaluate whether the radiographic crossover sign influences the painful femoroacetabular impingement or the radiographic progression of osteoarthritis after rotational acetabular osteotomy (RAO). METHODS: A total of 104 patients (115 hips) with preosteoarthritis (pre-OA) or early-stage OA of the hip due to dysplasia underwent RAO. Their mean age at the time of surgery was 34.7 years. The mean follow-up period was 13 years. Clinical follow-up was performed with the system of Merle d'Aubigne, and the impingement sign was evaluated. Radiographic analyses included the center-edge angle, acetabular roof angle, head lateralization index (HLI), joint congruency, crossover sign, posterior wall sign, acetabular index of depth to width, pistol grip deformity, and femoral head/femoral neck ratio. RESULTS: The mean clinical score improved significantly from 14.6 preoperatively to 17.0 at follow-up. The impingement sign at follow-up was observed in 14 hips (12.2%). The center-edge angle, acetabular roof angle, and head lateralization index (HLI) improved significantly after surgery. The crossover sign was observed in 8 hips (7.0%) preoperatively and in 49 hips (42.6%) postoperatively. The posterior wall sign was observed in 70 hips (60.9%) preoperatively and in 73 hips (63.5%) postoperatively. The impingement sign after RAO was positive significantly in the postoperative crossover sign-positive hips. Radiographic progression of OA was observed in 11 hips (crossover sign was positive in 7 hips and negative in 4 hips). The only factors significantly associated with radiographic progression after RAO were fair postoperative joint congruency and age at surgery. CONCLUSIONS: Although there was no significant radiographic progression of OA despite significant retroversion, anterior impingement and radiographic crossover sign after RAO are should be checked during the procedure. The goal of RAO should be correct alignment of the acetabulum including a correct version with a negative crossover sign.

Xanthine oxidoreductase activity correlates with vascular endothelial dysfunction in patients with type 1 diabetes.

AIMS: Xanthine oxidoreductase (XOR) is an enzyme regulating uric acid synthesis and generation of reactive oxygen species. Several studies suggested relationship between XOR and atherosclerotic diseases; however, few previous studies have directly examined the relationship between XOR and vascular endothelial dysfunction in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the relationship between XOR activity and vascular endothelial function in patients with T1DM. METHODS: Seventy-one patients with T1DM participated in the study and underwent assessments, including plasma XOR activity and flow-mediated dilation (FMD), to measure vascular endothelial function. RESULTS: The natural logarithm value of XOR activity (ln-XOR) was 3.03 ± 0.99 pmol/h/mL, and FMD was 5.5% ± 2.4%. FMD was inversely and significantly correlated with ln-XOR (correlation coefficient: r = - 0.396, P < 0.001), UA (r = - 0.252, P = 0.034), and asymmetric dimethylarginine (ADMA) (r = - 0.414, P < 0.001). ln-XOR showed positive correlation with HbA1c (r = 0.292, P = 0.013), ALT (r = 0.658, P < 0.001), and ADMA (r = 0.363, P = 0.002). Stepwise multiple regression analysis showed that ln-XOR (standard partial regression coefficient: ß = - 0.254, P = 0.018) was an independent explanatory variable of FMD. CONCLUSIONS: The results of this study showed for the first time that XOR activity is associated with glycemic control in patients with T1DM and that XOR activity is associated with vascular endothelial dysfunction.

Efficacy of a nitrogen-containing bisphosphonate, minodronate, in conjunction with a p38 mitogen activated protein kinase inhibitor or doxorubicin against malignant bone tumor cells.

PURPOSE: We recently reported the sarcoma-selective antitumor effects of a newly developed nitrogen-containing bisphosphonate, minodronate (MIN), on malignant bone tumors. The aim of this study was to develop efficient combination MIN therapy in malignant bone tumors. METHODS: We examined downstream molecular events of MIN in osteosarcoma and Ewing's sarcoma cells to search for a partner to combine with MIN. Furthermore, we evaluated the combined effects of MIN and clinically available Doxorubicin (DOX). RESULTS: We found that MIN inhibited Rap 1A prenylation, and extracellular signal-regulated kinase (ERK) or Akt phosphorylation in osteosarcoma (Saos-2) and Ewing's sarcoma (SK-ES-1) cells. Interestingly, MIN activated p38 mitogen activated protein kinase (MAPK) only in SK-ES-1 cells and a p38 MAPK inhibitor augmented MIN-induced growth inhibition in SK-ES-1 cells. Doxorubicin (DOX) exerted synergistic effects on Saos-2 and SK-ES-1 cell lines. Daily injection of MIN enhanced the growth inhibition of SK-ES-1 xenograft sarcoma treated by DOX in nude mice. CONCLUSIONS: These findings suggest that the inhibition of the p38 MAPK pathway may be attractive in overcoming cellular resistance against MIN. In the light of clinical settings, MIN may have a beneficial adjuvant role in the DOX treatment.

Scalp metastasis from malignant fibrous histiocytoma of bone.

Malignant fibrous histiocytoma (MFH) of bone is a relatively rare primary malignant neoplasm and an aggressive tumor, characterized by a high frequency of local recurrence and distant metastasis. The most common metastatic site is the lung (>80%), followed by bone and regional lymph node. Metastasis to other sites is extremely rare. In this report, we describe the skin as being the initial metastatic site for MFH of bone. A 42-year-old female presented with a bone tumor involving the right proximal tibia. She underwent tumor excision and knee joint reconstruction. Histologic examination confirmed a striform-pleomorphic type of MFH of bone. Six months postoperatively, the patient developed a scalp metastasis. Wide local excision was performed. Six months after the scalp operation, the patient was alive with no further relapse. We should keep the skin in mind as the possible initial site of metastatic MFH of bone.

Clinical outcomes of limb salvage surgery with postoperative intensity-modulated radiation therapy for soft-tissue sarcoma and metastasis.

OBJECTIVE: The primary aim of intensity-modulated radiation therapy (IMRT) for treating soft tissue sarcoma of an extremity is the reduction of morbidity and maintenance of local control. METHODS: We evaluated the outcomes and toxicity of adjuvant IMRT following function-preserving surgery to treat patients with soft tissue sarcoma and metastasis of the extremities. We retrospectively reviewed prospective databases at Kure Medical Center and Aichi Medical University between 2013 and 2016 and identified 10 patients with lower extremity soft tissue sarcoma who underwent both limb-sparing surgery and postoperative IMRT at one of our institutions. RESULTS: There were 7 men and 3 women (mean age, 67.2 years; range, 48-87 years) included in the study. Of these, four patients were continuously disease-free, two showed no evidence of disease, and four died due to disease. The average functional score was 82% (range, 53-100%). Among the 10 patients, 2 (22%) had grade 1-2 edema and 1 (11%) had grade 2 joint stiffness. Another patient developed grade 2 acute dermatitis. There were no severe complications such as infection, tissue necrosis, fracture, or nerve palsy. CONCLUSION: Although the number of patients in this study was small, our results show that adjuvant IMRT following function-preserving surgery for soft tissue sarcoma of the extremity can be valuable for treating unmanageable tumors.

Bizarre parosteal osteochondromatous proliferation of the femur: A case report.

A 54-year-old man initially presented with left distal thigh pain during walking. Imaging analysis revealed a diffuse calcified or ossified mass adjacent to the medial cortex of the distal femur and absence of continuity with the medulla. We performed resection biopsy. Histological examination revealed a large amount of hypercellular cartilage showing transformation to trabecular bone and BPOP was diagnosed. Postoperative course was uneventful and he remained free of recurrence. The method of resection should depend on the stage of reactive proliferation and whether the lesion is pathologically immature or mature. We also provide a brief review of the literature.