Search

Myeloid sarcoma (MS) is a rare neoplastic condition that is often described in association with acute myeloid leukemia (AML). MS in childhood has received little attention, particularly in Japan. We carried out a nationwide retrospective analysis of Japanese children diagnosed with MS without bone marrow involvement. Inclusion criteria were diagnosis of MS at younger than 20 years of age between January 1, 2000 and December 31, 2013. There was a predominance of males (8:2), and the median age at MS diagnosis was 4 years. Sites of involvement varied and included skin (n = 3), head and/or neck (n = 2), and multiple sites (n = 2). Karyotypes were evaluated in seven patients, with one individual carrying t(8;21) and t(9;11). Four patients developed bone marrow involvement 2-55 months after diagnosis of MS. All patients received chemotherapy for de novo AML and two individuals received HSCT in first remission. Seven of ten patients survived for 50-152 months (median, 93 months) without disease after initial chemotherapy. This retrospective study confirmed that pediatric MS without bone marrow involvement in Japan is a very rare disease. MS patients responded favorably to therapies for de novo AML, and HSCT in first remission was not indicated for all patients. [ABSTRACT FROM AUTHOR]

Purpose: Self-expandable metallic stents (SEMSs) may be used to effectively palliate malignant gastric outlet obstructions (GOOs), but their utility and efficacy in patients under best supportive care (BSC) have not been explored.Method: In this multicenter retrospective study, we reviewed data on patients under BSC who underwent endoscopic SEMS placement to treat malignant GOO without chemotherapy. We evaluated the safety and efficacy of the procedure.Results: We enrolled a total of 208 patients. SEMS placement was technically successful in 207 (99.5%) and clinically successful in 164 (78.8%). The mean procedure time was 25.6 ± 2.8 min. Stent dysfunction later developed in 30 (14.4%) patients, of whom 90% (27/30) underwent reintervention. The procedure-related mortality rate was 1.44%; all deaths were due to pneumonia. Subgroup analysis by Karnofsky performance status (KPS) revealed that neither technical success, stent dysfunction, reintervention rate, procedure-related pneumonia or death, nor death within 14 days differed between patients with good and poor KPS. However, the clinical success rate and the median survival time were significantly lower and shorter, respectively, in those with poor KPS (p < 0.001).Conclusions: Duodenal SEMS placement is an effective palliative treatment for malignant GOO in BSC patients. Although the GOO score did not dramatically improve in patients with poor KPS, the procedure was safe and palliatively feasible. Procedure-related pneumonia was fatal; thus, it is essential to proceed with great caution.Trial Registration: Clinical trial registration number: UMIN000028367. [ABSTRACT FROM AUTHOR]

Background: We evaluated the efficacy and safety of 5-weekly S-1 and cisplatin combined with trastuzumab, a monoclonal antibody against human epidermal growth factor receptor type 2 (HER2) for HER2-positive advanced gastric cancer (AGC).Methods: This phase II study treatment consisted of S-1 (80-120 mg per day) orally on day 1-21, cisplatin (60 mg/m(2)) intravenously on day 8, and trastuzumab (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) intravenously. The primary end point was 1-year survival rate. The secondary end points included overall survival, progression-free survival (PFS), response rate (RR), and safety.Results: A total 22 patients from seven centers were enrolled. In the 20 patients evaluable for analysis, the 1-year survival rate was 70 % (95 % confidence interval (CI) 49.9-90.1 %), and median survival time, PFS, and RR were 15.3, 7.5 months and 41.2 %, respectively. Major grade 3/4 adverse events were neutropenia (30 %), anorexia (30 %), leukopenia (25 %), fatigue (20 %), and anemia (15 %).Conclusions: Five-weekly S-1 and cisplatin combined with trastuzumab showed effective with favorable safety profile in patients with HER2-positive AGC. [ABSTRACT FROM AUTHOR]

A 59-year-old man with bloody stools, and previously diagnosed with sigmoid colon carcinoma, visited our hospital. Preoperative abdominal ultrasonography (US) showed another tumor, with an uneven irregular surface, measuring about 9 × 5 cm, below the left hypochondrium. The tumor consisted of several cysts. Abdominal computed tomography (CT) showed a multicystic tumor attached to the stomach, and its septum and marginal region were intensely stained on contrast imaging. On magnetic resonance imaging (MRI), low and markedly high signals were revealed in the tumor on T1-weighted and T2-weighted sequences, respectively. Contrast imaging of the upper digestive tract showed extramural compression of the greater curvature of the antral stomach by the tumor. The tumor was partially imaged by endoscopic ultrasonography (EUS), but continuity to the stomach was not confirmed. On abdominal angiography, the tumor was slightly stained via the gastroepiploic arteries. Surgical treatment was performed to excise both the gastric tumor and the sigmoid colon carcinoma. The gastric tumor was removed with gastric wall tissue where the tumor was attached to a 2-cm pedicle. It was multicystic, contained watery fluid, and had a smooth outer surface. Histologically, the tumor consisted of multiple irregular cysts without epithelial lining, and solid epitheloid cell nests in between. The tumor cells had clear or eosinophilic cytoplasm and round nuclei. No mitotic figures were seen. The tumor cells in the pedicle were connected with the muscularis propriae of the stomach. Immunohistochemistry showed c-kit-positive, CD34-positive smooth muscle actin (SMA)-negative, and S-100-negative staining of tumor cells. The final diagnosis was gastrointestinal stromal tumor (GIST). [ABSTRACT FROM AUTHOR]

Hypertensive cardiac hypertrophy is associated with the accumulation of collagen in the myocardial interstitium. Previous studies have demonstrated that this myocardial fibrosis accounts for impaired myocardial stiffness and ventricular dysfunction. Although cardiac fibroblasts are responsible for the synthesis of fibrillar collagen, the factors that regulate collagen synthesis in cardiac fibroblasts are not fully understood. We investigated the effects of angiotensin II on cardiac collagen synthesis in cardiac fibroblasts. Cardiac fibroblasts of 10 week old spontaneously hypertensive rats and age-matched Wistar-Kyoto rats were prepared and maintained in culture medium supplemented with 10% fetal calf serum. The expression of mRNA of the renin-angiotensin system (renin, angiotensinogen, angiotensin converting enzyme) was determined by using a ribonuclease protection assay. Basal collagen synthesis in cardiac fibroblasts from spontaneously hypertensive rats was 1.6 fold greater than that in the cell of Wistar-Kyoto rats. Angiotensin II stimulated collagen synthesis in cardiac fibroblasts in a dose-dependent manner. The responsiveness of collagen production to angiotensin II was significantly enhanced in cardiac fibroblasts from spontaneously hypertensive rats (100 nM angiotensin II resulted in 185 ± 18% increase above basal levels, 185 ± 18 versus 128 ± 19% in Wistar-Kyoto rats p < 0.01). This effect was receptor-specific, because it was blocked by the competitive inhibitor saralasin and MK 954. These results indicate that collagen production was enhanced in cardiac fibroblasts from spontaneously hypertensive rats, that angiotensin II had a stimulatory effect on collagen synthesis in cardiac fibroblasts, and that cardiac fibroblasts from spontaneously hypertensive rats were hyper-responsive to stimulation by angiotensin II. Level of angiotensin and renin mRNA expressed in ventricles, and angiotensinogen mRNA expressed in fibroblasts from SHR were higher than those from WKY. These findings suggest that the cardiac renin-angiotensin system may play an important role in collagen accumulation in hypertensive cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

It is known that inositol (1, 4, 5)-trisphosphate (IP) stimulates Ca release from sarcoplasmic reticulum (SR) in several tissues, but in cardiac myocytes this phenomenon has not been confirmed. The purpose of the present study was to confirm the effect of (1, 4, 5)-IP on Ca release from SR in cardiac myocytes. The effect of IP on Ca release from SR in hypertrophic cardiac cells was also determined. We examined the effects of IP on Ca release from cardiac myocyte SR by the bigital-image method in a single cell. We also determined the effect of IP on calcium release from isolated SR. SR was prepared from spontaneous hypertensive rat hearts and Wistar kyoto rat hearts. The SR was prelabeled withCa+, and then incubated with the indicated concentrations of IP for 1 min at 37°C. In cardiac myocytes treated with saponin, Ca release stimulated by 10 μM (1, 4, 5)-IP was detected by fura-2. InCa prelabeled SR, the maximal Ca release was achieved at 10 μM IP incubated for 1 min. The release of Ca was higher in Sr of SHR than in the SR of WKY. IP stimulates Ca release from cardiac SR, and this release is greater in SHR than in WKY. However, it is uncertain whether this phenomenon plays a role in cardiac hypertrophy. [ABSTRACT FROM AUTHOR]