The androgen receptor (AR) plays a critical role in the progression of prostate cancer. At present, the only established treatment for metastatic castration-resistant prostate cancer (CRPC) is monotherapy with docetaxel. However, several studies have shown that the majority of CRPC express AR and androgen-responsive genes, indicating that the AR signaling pathway is still functional under androgen-depleted conditions. The main mechanisms underlying the progression of prostate cancer into a castrate-resistant state are hypersensitivity to AR, promiscuous AR activity and outlaw AR pathways that bypass the need for androgens. Therefore, understanding these mechanisms has promoted the development of new anti-androgens and androgen-depleting agents. Recently, several therapies targeting the androgen signaling pathway have come to market. Notably, promising results have been obtained in clinical trials with enzaltamide, a small-molecule AR antagonist that prevents nuclear translocation and DNA binding without agonist activity, and with abiraterone acetate, a prodrug, low molecular weight inhibitor of a rate-limiting enzyme in androgen biosynthesis. Herein, we review the androgen signaling pathway and novel drugs targeting this pathway for the management of CRPC.
Rheumatoid arthritis (RA) is characterized by chronic inflammatory synovitis that causes pain, loss of function and disability, and can significantly reduce health-related quality of life. Improved understanding of the disease pathogenesis has led to the development of new biologic treatments that target specific cytokines. Large randomized controlled trials (RCTs) have been conducted to show the efficacy of anti-TNF and IL-6. However, despite these treatments, some patients fail to respond to these therapies. Recently, novel anti-cytokine treatments have been developed and introduced. Certolizumab pegol treatment with and without non-MTX disease-modifying anti-rheumatic drugs (DMARDs) in Japanese patients, to whom MTX cannot be administered, resulted in rapid, sustained reductions in RA signs and symptoms. Drug-based treatments, such as DMARDs and biologic agents, have evolved markedly over the past 2 decades and have reduced the need for joint replacements. Thus, surgical treatment of RA using joint replacements has decreased dramatically. In particular, the decline was greater for lower-limb and spinal operations than for upper-limb operations.
Though carcinomatous metastasis to various organs, such as the lung and liver, occurs frequently in the end stage of cancer, gastric metastasis is relatively rare. We examined the endoscopic findings and pathological analyses of 16 metastatic gastric cancers from our hospital during the past twenty years. Out of 16 cases, there were a total of 10 primary organs, of which lung and breast cancers were the most frequent sources. In endoscopic diagnosis of the 16 gastric lesions, there were 7 (44%) cases of suspected metastatic tumor, compared with 4 (25%) and 5 (31%) primary and non-tumor lesions, respectively. There were 5 multiple and 11 single lesions of the stomach. There were 5 (31%) cases of metastasis to the stomach alone. Eight cases (50%) were found to be primary cancer and gastric metastasis during the same period. The longest term from the onset of primary cancer to the detection of gastric metastasis was 8 years 4 months. It is difficult to distinguish gastric metastasis from primary gastric cancer and benign ulcerative lesion endoscopically. Strict follow-up observation and pathological assessment of both primary site gastric lesions were important.
In recent years, assisted reproductive technology (ART) has developed remarkably, and many infertile couples can now have babies using these approaches. In addition to ART, cancer therapies have also developed and survival rates have improved greatly. Cancer therapies may be harmful to spermatogenesis. Recently, cryopreservation of sperm has been recommended for men of reproductive age with malignancies before undergoing cancer treatment. Thus, we attempted to perform in vitro fertilization (IVF) using cryopreserved sperm for the purpose of future preservation of fertility of cancer-bearing male patients at Nihon University Itabashi Hospital. We report two cases of sperm cryopreservation. Neither case could provide prepare fresh sperm on the day of oocyte retrieval due to work commitments away from their partner. Sperm cryopreservation was performed with the slow-freezing method. Both cases obtained multiple good embryos and blastocysts and led to pregnancies. The technique of cryopreserved sperm is also available in Nihon University Itabashi Hospital. However it is necessary to cooperate with oncologists or the physician in charge when fertility preservation technologies are performed for patients with malignancies.
Objective: Cardiac resynchronization therapy (CRT) is known to be effective for left ventricular dysfunction associated with left bundle branch block. However, CRT does not necessarily decrease the risk of sudden cardiac death. Recent studies have shown that epicardial left ventricular pacing may lead to prolongation of the QT interval and the development of torsades de pointes. Microvolt T-wave alternans (TWA) has been associated with increased susceptibility to ventricular tachyarrhythmias. We compared the influence of right atrial pacing, right ventricular pacing, left ventricular pacing and biventricular pacing (RAP, RVP, LVP and BVP) on TWA. Methods: TWA was measured per pacing mode during incremental pacing from 70 to 120 bpm in 18 CRT patients with a mean ejection fraction of 32±5%. TWA was considered positive if alternans voltage (Valt)>1.9 μV and alternans ratio (AR)>3.0 were observed for at least 1 minute. The incidence of TWA is reported as the percentage of impulse applications during which it was observed. Results: TWA was observed as follows: BVP, 73%; RVP, 50%; LVP, 60%; and RAP, 60%. Mean Valt (μV) was 2.44±0.35, 0.36±0.11, 1.44±0.65, and 1.95±0.45, respectively (P<0.01 BVP vs. RVP). Mean alternans ratio during BVP, RVP, LVP, and RAP was 8.21±2.4, 4.28±1.3, 5.66±2.3, and 7.36±2.0, respectively (P<0.05 BVP vs. RVP). Conclusion: BVP may increase the temporal inhomogeneity of ventricular repolarization, which may lead to the development of ventricular tachyarrhythmia.
Gangrenous ischemic colitis is one of the abdominal emergency diseases, which has a poor prognosis. This report presents a case of gangrenous ischemic colitis. A 62-year-old man came to our hospital with the complaint of loss of appetite for 2 days prior. Rebound tenderness appeared upon abdominal examination, and abdominal computer tomography showed free air on the ventral side of the liver. Therefore, we performed an emergency laparotomy under the diagnosis of perforation of the colon. Consecutive necrosis of the large intestine from the cecum to the ascending colon was discovered, and we performed right hemicolectomy. Based on the histological findings, the patient was ultimately diagnosed as having gangrenous-type ischemic colitis.