Gaku Arai

Phase II study of personalized peptide vaccination for castration-resistant prostate cancer patients who failed in docetaxel-based chemotherapy.

Docetaxel‐based chemotherapy (DBC) showed limited clinical efficacy for castration‐resistant prostate cancer (CRPC) patients. To explore cancer vaccine as a new treatment modality, we conducted a phase II study of personalized peptide vaccine (PPV) for DBC‐resistant CRPC patients.

An Open-Label, Randomized Phase II Trial of Personalized Peptide Vaccination in Patients with Bladder Cancer that Progressed after Platinum-Based Chemotherapy

Purpose: The prognosis of platinum-based chemotherapy–resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity. Experimental Design: In this randomized, open-label, phase II study, patients ages ≥18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1:1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), immune response, and toxicity. Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4–1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34–0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5–12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8–6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions. Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results. Clin Cancer Res; 22(1); 54–60. ©2015 AACR.

Antioxidant cosupplementation therapy with vitamin C, vitamin E, and coenzyme Q10 in patients with oligoasthenozoospermia

OBJECTIVEnOverproduction of reactive oxygen species results in oxidative stress, a deleterious process that damages cell structure as well as lipids, proteins, and DNA. Oxidative stress plays a major role in various human diseases, such as oligoasthenozoospermia syndrome.nnnMATERIALS AND METHODSnWe evaluated the effectiveness of antioxidant co-supplementation therapy using vitamin C, vitamin E, and coenzyme Q10 in men with oligoasthenozoospermia. Overall, 169 infertile men with oligoasthenozoospermia received antioxidant therapy with 80 mg/day vitamin C, 40 mg/day vitamin E, and 120 mg/day coenzyme Q10. We evaluated spermiogram parameters at baseline and at 3 and 6 months of follow-up.nnnRESULTSnSignificant improvements were evident in sperm concentration and motility following coenzyme Q10 therapy. Treatment resulted in 48 (28.4%) partner pregnancies, of which 16 (9.5%) were spontaneous. Significant improvements in sperm cell concentration and sperm motility were observed after 3 and 6 months of treatment.nnnCONCLUSIONSnVitamin C, vitamin E, and coenzyme Q10 supplementation resulted in a significant improvement in certain semen parameters. However, further studies are needed to empirically determine the effect of supplementation on pregnancy rate.

Xanthogranulomatous pyelonephritis with a renocolic fistula caused by a parapelvic cyst

Abstractu2002 Fistula formation between the upper urinary tract and bowel is an uncommon complication in urogenital diseases. We present a rare case of focal xanthogranulomatous pyelonephritis with a renocolic fistula. This is the first case where a parapelvic cyst obstructs the caliceal outflow and leads to the formation of a renocolic fistula in renal inflammatory disease. It is difficult to make a preoperative diagnosis of focal xanthogranulomatous pyelonephritis with widespread involvement that is caused by non‐calculous urinary tract obstruction.

Inflammatory bowel disease in subfertile men and the effect of mesalazine on fertility

Abstract This study aimed to examine the effect of mesalazine on fertility. In this retrospective analysis of 1,225 male subfertile patients, we reviewed the cases of inflammatory bowel disease (IBD) in the medical records and evaluated the prevalence of the disease in our reproduction center. Specifically, we examined IBD patients who ceased mesalazine during male infertility treatment, and compared the seminogram of these patients before and after discontinuation of mesalazine. We also analyzed pregnancy outcome after discontinuation. The prevalence rate of Crohn’s disease and ulcerative colitis in our male infertile patients was 163 per 100,000 men and 490 per 100,000 men, respectively. Seven patients had taken mesalazine and six of them subsequently stopped the medication. The mean values of sperm concentration, sperm motility, percentage of normal formed sperm, semen volume, and total motile sperm count taken before discontinuation increased after discontinuation of mesalazine. Among these parameters, the sperm motility and total motile sperm count were significantly improved (pu2009<u20090.05) after discontinuation. Of the six patients who stopped the drug, four achieved pregnancy with their partners, with two of the four men showing significant improvement not only in the percentage of normal shaped sperm but also sperm motility and total motile sperm count. This study provides further insight into the rarely investigated relationship between male fertility and mesalazine.

Phase I trial of a cancer vaccine consisting of 20 mixed peptides in patients with castration-resistant prostate cancer: dose-related immune boosting and suppression

AbstractnThe heterogeneity expression of tumor-associated antigens (TAA) and variability of human T cell repertoire suggest that effective cancer vaccine requires induction of a wide breadth of cytotoxic T lymphocyte (CTL) specificities. This can be achieved with vaccines targeting multiple TAA. We evaluated the safety and immune dynamics of a cancer vaccine consisting of 20 mixed peptides (KRM-20) designed to induce CTLs against 12 different TAA in patients with castration-resistant prostate cancer (CRPC). Patients received each of three different randomly assigned doses of KRM-20 (6, 20, or 60xa0mg) once a week for 6xa0weeks. KRM-20 was applicable for patients with positive human leukocyte antigen (HLA) A2, A3, A11, A24, A26, A31 or A33 alleles, which cover the majority of the global population. To evaluate the minimum immunological effective dose (MIED), peptide-specific CTL and immunoglobulin G (IgG) responses, and immune suppressive subsets were evaluated during the vaccination. Total of 17 patients was enrolled. No serious adverse drug reactions were encountered. The MIED of KRM-20 in CTL or IgG response calculated by logistic regression model was set as 16 or 1.6xa0mg, respectively. The frequency of immune suppressive subsets was fewer in the 20xa0mg cohort than that in 6 or 60xa0mg cohort. Clinical responses determined by prostate-specific antigen levels were two partial responses (from the 20xa0mg cohort), five no changes and ten progressive diseases. Twenty milligrams of KRM-20 could be recommended for further studies because of the safety and ability to augment CTL activity.

Surgical treatment of urethral distraction defect associated with pelvic fracture: A nationwide survey in Japan

Objective:u2003 To survey practice patterns in surgical treatment for urethral distraction defect associated with pelvic fracture (PFUDD) and to analyze outcomes of the treatment in Japan.

Induction of spermatogenesis by rhFSH for azoospermia due to spermatogenic dysfunction with maturation arrest: five case series

Abstract When sperm cannot be retrieved from the testes of patients with azoospermia due to spermatogenic dysfunction (ASD), there is no rational way for the patient to become a biological father. We investigated the possibility of inducing spermatogenesis in such patients by hormonal therapy with recombinant human follicle-stimulating hormone (rhFSH) alone. Twenty-six ASD patients who could not obtain spermatozoa by microdissection testicular sperm extraction (micro-TESE) were confirmed to have arrested spermatogenesis at the late stage of maturation arrest. They were subsequently treated with 75–150 IU two times/week rhFSH alone for 12 months. The primary endpoint was the appearance of sperm in ejaculate, and we followed the patients to determine the outcome of inseminating their partners. After rhFSH treatment, mature spermatozoa were found in the ejaculate in five of 26 (19.2%) patients, all of whom showed histology of non-uniform type maturation arrest. Intracytoplasmic sperm injection of the mature spermatozoa resulted in two ongoing clinical pregnancies (insemination success rate, 40.0%). Recombinant human follicle-stimulating hormone treatment can be used as an advanced assisted reproductive technology to improve spermatogenesis in some azoospermic patients with maturation arrest of spermatogenesis and is a potential treatment option after unsuccessful micro-TESE.

Clinical efficacy and tolerability of Gosha-jinki-gan, a Japanese traditional herbal medicine, for nocturia.

We evaluated the efficacy and tolerability of Gosha-jinki-gan (GJG; 濟生腎氣丸 jì shēng shèn qì wán) in 30 cases of nocturia (夜尿 yè niào) unresponsive to α1-blockers or antimuscarinic drugs. All patients received GJG extract powder (2.5 g) three times a day for 12 weeks as an add-on therapy to α1-blockers or antimuscarinic drugs. Subjective outcomes assessed by the International Prostate Symptom Score—quality of life, and the benign prostatic hyperplasia impact index and objective outcomes assessed by urinary frequency and the urine production rate at night showed significant improvement after treatment. Moreover, other objective outcomes assessed by maximum flow rates, postvoid residual, serum human atrial natriuretic peptide levels, and urinary 8-hydroxy-2′-deoxyguanosine levels did not change. Adverse events were observed in 10% of cases; however, these events were mild. GJG appears to be a safe and effective potential therapeutic alternative for patients with nocturia unresponsive to α1-blockers or antimuscarinic drugs. Further clinical investigations are required to elucidate the precise pathophysiologic mechanisms of GJG in nocturia.

Prostate Cancer-Producing Granulocyte Colony-Stimulating Factor

An 86-year-old man with a serum prostate-specific antigen level of 93.33 ng/ml was diagnosed as having cT3aN0M0 prostatic adenocarcinoma of Gleason score 9. Although the serum prostate-specific antigen responded well to combined androgen blockade, the cancer spread and lead to death 6 months after diagnosis. The patient had leukocytosis during the clinical course with no sign of localized infection, especially after manipulation of the prostate. Enzyme immunoassay demonstrated elevated serum levels of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor. To our knowledge, this is the first case of prostate cancer with G-CSF production, which was confirmed immunohistochemically.