New clinical evidence of silodosin,an α1A selective adrenoceptor antagonist,in the treatment for lower urinary tract symptoms

Lower urinary tract symptoms associated with benign prostatic hyperplasia are highly prevalent in older men. Pharmacological treatment is the first‐line treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia. The first choice in the pharmacological treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia is the α₁‐adrenoceptor antagonists. Many α₁‐adrenoceptor antagonists are available in the world. Silodosin is an α₁‐adrenoceptor antagonist developed by Kissei Pharmaceutical, and has a specific selectivity for the α_1A‐adrenoceptor subtype. By antagonizing α_1A‐adrenoceptor in the prostate and urethra, silodosin causes smooth muscle relaxation in the lower urinary tract. As a result of the high affinity for the α_1A‐adrenoceptor than for the α_1B‐adrenoceptor, silodosin minimizes the propensity for blood pressure‐related adverse effects caused by blockade of α_1B‐adrenoceptor. The efficacy and safety of silodosin for treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia was first reported by Japanese investigators in 2006. At present, silodosin is used in many countries. In the present review, we summarize the new clinical evidence for lower urinary tract symptoms associated with benign prostatic hyperplasia and introduce the data supporting the new clinical indications of silodosin.     

Does Primary or Secondary Chondrocalcinosis Influence Long-term Survivorship of Unicompartmental Arthroplasty?

Background  

Coexistence of degenerative arthritis and calcium pyrophosphate dihydrate (CPPD) crystals (or radiological chondrocalcinosis) with osteoarthritis (OA) of the knees is frequent at the time of arthroplasty. Several studies suggest more rapid clinical and radiographic progression with CPPD than with OA alone. However, it is unclear whether chondrocalcinosis predisposes to higher risks of progression of arthritis in other compartments.     

FGF and ERK signaling coordinately regulate mineralization-related genes and play essential roles in osteocyte differentiation

To examine the roles of FGF and ERK MAPK signaling in osteocyte differentiation and function, we performed microarray analyses using the osteocyte cell line MLO-Y4. This experiment identified a number of mineralization-related genes that were regulated by FGF2 in an ERK MAPK-dependent manner. Real-time PCR analysis indicated that FGF2 upregulates Ank, Enpp1, Mgp, Slc20a1, and Dmp1 in MLO-Y4 cells. Consistent with this observation, the selective FGF receptor inhibitor PD173074 decreased Ank, Enpp1, Slc20a1, and Dmp1 mRNA expression in mouse calvaria in organ culture. Since Dmp1 plays a central role in osteocyte differentiation and mineral homeostasis, we further analyzed FGF regulation of Dmp1. Similar to FGF2, FGF23 upregulated Dmp1 expression in MLO-Y4 cells in the presence of Klotho. Furthermore, increased extracellular phosphate levels partially inhibited FGF2-induced upregulation of Dmp1 mRNA expression, suggesting a coordinated regulation of Dmp1 expression by FGF signaling and extracellular phosphate. In MLO-Y4 osteocytes and in MC3T3E1 and primary calvaria osteoblasts, U0126 strongly inhibited both basal expression of Dmp1 mRNA and FGF2-induced upregulation. Consistent with the in vitro observations, real-time PCR and immunohistochemical analysis showed a strong decrease in Dmp1 expression in the skeletal elements of ERK1 ^−/− ; ERK2 ^flox/flox ; Prx1-Cre mice. Furthermore, scanning electron microscopic analysis revealed that no osteocytes with characteristic dendritic processes develop in the limbs of ERK1 ^−/− ; ERK2 ^flox/flox ; Prx1-Cre mice. Collectively, our observations indicate that FGF signaling coordinately regulates mineralization-related genes in the osteoblast lineage and that ERK signaling is essential for Dmp1 expression and osteocyte differentiation.     

One and a half ventricle repair for Ebstein’s anomaly

The surgical strategy for patients having Ebstein’s anomaly and hypoplastic right ventricle is controversial. An 11-year-old boy patient having such condition, with estimated end-diastolic volume index of the atrialized and functional right ventricle being 70% of normally expected values, underwent biventricular repair. Immediately after the surgery, however, he developed right heart failure with the central venous pressure of 11 mmHg. He consequently underwent additional bidirectional cavopulmonary anastomosis, thereby converting the biventricular repair into one and a half ventricle repair. He recovered uneventfully and is doing well 2 years after the surgery.     

Distinct Recurrence Pattern and Outcome of Adenocarcinoma of the Gastric Cardia in Comparison with Carcinoma of Other Regions of the Stomach

Background Carcinoma arising in the cardioesophageal junction is a distinct clinical entity compared with tumors located in other regions of the stomach. The prognosis for adenocarcinoma of the upper stomach is considered to be relatively poorer than carcinomas of the more distal stomach. We have therefore investigated patients with carcinoma of the gastric cardia in order to evaluate the underlying cause of this poor prognosis. Materials and Methods Clinicopathologic features and postoperative prognosis of 101 patients with carcinoma of the cardia were evaluated and compared with findings on 1884 patients with tumors in other regions of the stomach. Results Tumors of the cardia had a mean size of 6.8 cm, which was significantly larger than the mean size of 5.9 cm for tumors found in the middle- and lower third of the stomach. The incidence of serosal invasion, lymph node metastasis, and lymphatic and blood vessel invasion was higher in association with adenocarcinoma of the cardia than with adenocarcinoma in remaining parts of the stomach. In the analysis of patients who had undergone curative resection, the 5-year survival rates were 61.6, 79.1, and 82.6% in patients with carcinoma of the cardia, upper one-third, and remaining middle- and lower one-third of the stomach, respectively, and the differences were statistically significant. Multivariate analysis indicated that adenocarcinoma of the gastric cardia is an independent prognostic factor. With regard to the site of recurrence, both lymph node and hematogenous recurrence were observed more frequently in the cardia than in the remaining parts of the stomach. Conclusions Our data indicate that the prognosis of patients with adenocarcinoma of the gastric cardia is extremely poor. To improve their prognosis, new treatments in addition to gastrectomy with extensive lymph node dissection are needed.     

Feasibility of a new approach for creating a preperitoneal space in transabdominal preperitoneal repair inguinal hernia repair: using a sandwich approach

Purpose

In Japan, transabdominal preperitoneal (TAPP) inguinal hernia repair is performed by firmly pulling the peritoneum inwards to lift it from the underlying deep layer of subperitoneal fascia. It decreases the postoperative pain and discomfort in the inguinal area. The aim of this study was to evaluate the feasibility of the sandwich approach, which is a new technique for creating a preperitoneal space.

Methods

The operation was performed via the sandwich approach. We made sure to protect the preperitoneal fascia areolar layer when making the preperitoneal space.

Results

We performed TAPP in 745 patients (876 hernias) treated between October 2006 and April 2015 at Himeji Medical Center and Kurashiki Central Hospital. Before October 2010, we did not use the sandwich approach, and recurrence was observed in three patients. From October 2010, we always used the sandwich approach and never experienced any cases of recurrence. Clavien–Dindo classification Grade 3 or higher postoperative complications occurred in 6 patients (0.8%) between October 2006 and April 2015. Mesh-related ileus was the most frequently observed morbidity. There were no cases of vas differentia or spermatic vessel injury, postoperative chronic pain, or urinary retention.

Conclusion

The sandwich approach is feasible as another standard dissective procedure for TAPP.

     

The cardiothoracic ratio and all-cause and cardiovascular disease mortality in patients undergoing maintenance hemodialysis: results of the MBD-5D study

Background

The cardiothoracic ratio (CTR) is a non-invasive left ventricular hypertrophy index. However, whether CTR associates with cardiovascular disease (CVD) and mortality in hemodialysis (HD) populations is unclear.

Methods

Using a Mineral and Bone disorder Outcomes Study for Japanese CKD Stage 5D Patients (MBD-5D Study) subcohort, 2266 prevalent HD patients (age 62.8 years, female 38.0%, HD duration 9.4 years) with secondary hyperparathyroidism (SHPT) whose baseline CTR had been recorded were selected. We evaluated associations between CTR and all-cause death, CVD death, or composite events in HD patients.

Results

CTR was associated significantly with various background and laboratory characteristics. All-cause death, CVD-related death, and composite events increased across the CTR quartiles (Q). Adjusted hazard risk (HR) for all-cause death was 1.4 (95% confidential interval, 0.9–2.1) in Q2, 1.9 (1.3–2.9) in Q3, and 2.6 (1.7–4.0) in Q4, respectively (Q1 as a reference). The corresponding adjusted HR for CVD-related death was 1.8 (0.8–4.2), 3.1 (1.4–6.8), and 3.5 (1.6–7.9), and that for composite outcome was 1.2 (1.0–1.6), 1.7 (1.3–2.2), and 1.8 (1.5–2.3), respectively. Exploratory analysis revealed that there were relationships between CTR and age, sex, body mass index, comorbidity of CVD, dialysis duration, dialysate calcium level and intact parathyroid hormone, phosphorus, hemoglobin, and usage of phosphate binder.

Conclusion

CTR correlated with all-cause death, CVD death, and composite events in HD patients with SHPT.

     

Preoperative Serum Carcinoembryonic Antigen Level as a Predictive Factor of Recurrence After Curative Resection of Colorectal Cancer

Background  We evaluated the prognostic value of the preoperative serum carcinoembryonic antigen (CEA) level in patients with colorectal cancer (CRC). Patients and Methods  The study group comprised 638 patients. The optimal cutoff value for the preoperative serum CEA level was determined. Predictive factors of recurrence were evaluated using multivariate analyses. The relapse-free time was investigated according to the CEA level. Results  All patients underwent potentially curative resection for CRC without distant metastasis, classified as stage I, II, or III. The optimal cutoff value for preoperative serum CEA level was 10 ng/ml. Elevated preoperative serum CEA level was observed in 92 patients. Multivariate analysis identified tumor–node–metastasis (TNM) stage and preoperative serum CEA level as independent predictive factors of recurrence. The relapse-free survival between CEA levels >10 ng/ml and <10 ng/ml significantly differed in patients with stage II and III. However, there was no significant difference in relapse-free survival between CEA levels >10 ng/ml and <10 ng/ml in patients with stage I. Conclusion  Preoperative serum CEA is a reliable predictive factor of recurrence after curative surgery in CRC patients and a useful indicator of the optimal treatment after resection, particularly for cases classified as stage II or stage III.     

High incidence of microbleeds in hemodialysis patients detected by T2*-weighted gradient-echo magnetic resonance imaging

The incidence and characteristics of microbleeds in hemodialysis (HD) patients were investigated to elucidate the clinical significance with T(2)(*)-weighted gradient-echo magnetic resonance (MR) imaging. The 57 patients with chronic renal failure maintained by HD had no previous history of stroke. The control group consisted of 53 patients without previous history of stroke or chronic renal failure. The incidence and the number of microbleeds were assessed in the HD and control groups. The findings of microbleeds with T(2)(*)-weighted gradient-echo MR imaging were compared with those of T(1)- and T(2)-weighted MR imaging in HD patients. The incidence of microbleeds was significantly greater in the HD patients compared with the control patients. T(2)(*)-weighted gradient-echo imaging revealed a total of 44 microbleeds in 11 HD patients. T(2)-weighted imaging demonstrated 13 of 44 microbleeds as hyperintensity, whereas T(1)-weighted imaging demonstrated 12 lesions as hypointensity. T(2)- and T(1)-weighted imagings did not demonstrate any findings in 31 and 32 lesions, respectively. T(2)(*)-weighted gradient-echo MR imaging is effective to detect microbleeds which may be a predictor of intracerebral hemorrhage in HD patients and should be included in the protocol for the study of cerebrovascular disease, because T(2)- and T(1)-weighted MR imaging recognizes microbleeds as lacunar infarction.