Childless Men at the Time of Vasectomy are Unlikely to Seek Fertility Restoration.

OBJECTIVE: To examine whether men who were childless at the time of vasectomy sought consultation for fertility restoration. METHODS: Retrospective chart review was performed to determine if patients without children at the time of vasectomy sought consultation for fertility restoration (defined as vasectomy reversal or sperm retrieval). If the patient had not been seen in our healthcare system within the previous 12 months, he was contacted by phone to determine whether he had sought consultation for fertility restoration. RESULTS: Of 1656 men, 68 men (4.1%) were childless at the time of vasectomy. Fifteen patients were excluded as they were not followed in our hospital system and were unreachable by phone. Zero patients sought consultation for fertility restoration. CONCLUSION: Our single institution study demonstrated that no men who were childless at the time of vasectomy sought consultation for fertility restoration. Given that there are no other FDA approved methods for nonbarrier sterilization for males, men with no children at the time of vasectomy should receive the same AUA guideline-recommended counseling that men with children receive.

Penile Prosthesis in Solid Organ Transplant Recipients-A Matched Cohort Study.

OBJECTIVE: To determine whether patients with solid organ transplant (SOT) are at higher risk of developing complications after inflatable penile prosthesis (IPP) implantation. METHODS: We retrospectively reviewed outcomes data for all patients with SOT who underwent IPP placement at our institution. A cohort of age-matched IPP recipients without SOT were used as controls. RESULTS: We identified 26 patients who underwent SOT and IPP between 1999 and 2015, and 26 controls. Transplants included heart (3), liver (2), kidney only (17), and kidney and pancreas (4). Mean follow-up time after IPP placement was 29.5 months (SOT group) and 13.5 months (controls). Age at IPP did not significantly differ between groups (53.7 + 8.1 vs 56.4 + 9.0, P = .26), nor did body mass index (30.3 + 5.5 vs 30.2 + 4.7, P = .92), history of prostatectomy (7.7% vs 15.4%, P = .39), rectal surgery (3.9% vs 3.9%, P = 1.00), hyperlipidemia (69.2% vs 69.2%, P = 1.00), hypertension (92.3% vs 76.9%, P = .25), or heart disease (57.7% vs 30.8%, P = .093). Peripheral vascular disease was more common in transplant patients (26.9% vs 3.9%, P = .021), as were stroke (19.2% vs 0.0%, P = .05) and diabetes (84.6% vs 53.6%, P = .016). No significant differences in IPP reoperation rates existed between patients with vs without SOT (11.5% vs 11.5%, P = 1.00), nor did they differ by organ transplanted (P = 1.00). No differences in IPP reoperation rate existed between 2-piece vs 3-piece IPP models (P = .47). CONCLUSION: Outcomes of IPP implantation in patients with SOT are similar to those of nontransplant patients. Patients with SOT should be considered suitable candidates for penile prosthesis.

Inflammatory Cytokines in the Papillary Tips and Urine of Nephrolithiasis Patients.

INTRODUCTION: Intrarenal inflammation has been implicated in the pathogenesis of nephrolithiasis, with prior work showing increased urine levels of IL-6, IL-8, and CCL-2 in stone patients. However, no studies have assessed for inflammation in the renal papillae. We sought to characterize novel papillary tip and urinary biomarkers in stone patients. MATERIALS AND METHODS: Ninety-two patients with nephrolithiasis undergoing percutaneous nephrolithotomy were enrolled. Papillary tip biopsies, kidney urine, and bladder urine were collected, as well as voided urine from eight healthy volunteers. Quantitative polymerase chain reaction was performed to measure inflammatory gene expression. RESULTS: Initial 84-gene polymerase chain reaction array revealed significant elevation of several cytokines in stone patients vs controls (fold change 2.3-694). Twenty-four genes were selected for final analysis. In 41 pairs of urine samples, levels of CCL5, CD40, FasL, RIPK2, SELE, TLR3, and IL-15 were significantly elevated in kidney vs bladder urine (p0.0001-0.04). In 23 triplets of samples, expression of these cytokines plus CCL2, CCL7, CCR2, CSF1, CXCL9, and CXCL10, was significantly greater in papillary tips vs urine samples (p0.001-0.05). Cytokine elevation was independent of maximum postoperative heart rate, respiratory rate, temperature, leukocyte count, urinary tract infection in the past year, presence or absence of antibiotics at the time of surgery, and stone composition (all p > 0.05). CONCLUSION: Expression of CCL-2, CCL-5, CCL-7, CCR-2, CD40, CSF1, CXCL-9, CXCL-10, Fas-L, RIPK2, SELE, and TLR-3 is markedly elevated in the papillary tips, kidney urine, and bladder urine of nephrolithiasis patients. Cytokine elevation was independent of signs of systemic inflammation. These findings further support the role of inflammation in nephrolithiasis and imply that the inflammatory process likely begins at the renal papillae. These may represent novel biomarkers of stone disease, which may be useful in basic nephrolithiasis research, disease diagnosis, and prognosis.

Testicular seminoma: oncologic rationale and role of surgery in treatment.

Seminomas account for approximately 50% of all cases of testicular cancer. Testicular cancer is a highly curable disease that can be broadly classified as either seminomatous or nonseminomatous; the management and treatment of the 2 forms vary widely. Although surgery plays a large role in the management of nonseminoma, its role in the management of seminoma is much more limited. Most clinicians in the United States choose orchiectomy followed by surveillance for patients with stage I seminomatous disease, and chemotherapy or radiation-followed by surgery for the management of residual masses-for patients with disease that is stage II and higher. Recently, clinicians have proposed a larger role for surgery in stage II seminoma to avoid the long-term toxic effects of chemotherapy and radiation therapy. In this review, we discuss the oncologic rationale for the treatment of seminoma, the role of surgery, and the use of minimally invasive operative techniques for retroperitoneal lymph node dissection.

Adenomatoid Tumor of the Testis Arising From the Tunica Albuginea.

Adenomatoid tumors are the most common paratesticular tumor. Although they primarily arise from the epididymis, they can rarely occur as an isolated intratesticular mass. These tumors are benign and surgical excision is curative. We present a case of a 36-year-old man diagnosed with an intratesticular adenomatoid tumor.

A compound heterozygous mutation in SLC34A3 causes hereditary hypophosphatemic rickets with hypercalciuria in a Chinese patient.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder inherited in an autosomal recessive fashion and characterized by hypophosphatemia, short stature, rickets and/or osteomalacia, and secondary absorptive hypercalciuria. HHRH was recently mapped to chromosome 9q34, which contains the gene SLC34A3 which encodes the renal proximal tubular sodium-phosphate cotransporter NaPi-IIc. Here we describe a 29-year-old man with a history of childhood rickets who presented with increased renal phosphate clearance leading to hypophosphatemia, hypercalciuria, low serum parathyroid hormone (PTH), elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and recurrent nephrolithiasis. We performed a mutation analysis of SLC34A3 (exons and adjacent introns) of the proband and his parents to determine if there was a genetic contribution. The proband proved to be compound heterozygous for two missense mutations in SLC34A3: one novel mutation in exon 7 c.571G>C (p.G191R) and one previously identified mutation in exon 13 c.1402C>T (p.R468W). His parents were both asymptomatic heterozygous carriers of one of these two mutations. We also performed an oral phosphate loading test and compared serum phosphate, intact PTH, and intact fibroblast growth factor 23 (iFGF23) in this patient versus patients with other forms of hypophosphatemic rickets, the results of which further revealed that the mechanism of hypophosphatemia in HHRH is independent of FGF23. This is the first report of HHRH in the Chinese population. Our findings of the novel mutation in exon 7 add to the list of more than 20 reported mutations of SLC34A3.

Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer.

Conventional treatment approaches have had little impact on the course of pancreatic cancer, which has the highest fatality rate among cancers. Gemcitabine, the primary therapeutic agent for pancreatic carcinoma, produces minimal survival benefit as a single agent. Therefore, numerous efforts have focused on gemcitabine combination treatments. Using a ratio design, this study established that combining pharmacologically achievable concentrations of ascorbate with gemcitabine resulted in a synergistic cytotoxic response in eight pancreatic tumor cell lines. Sensitization was evident regardless of inherent gemcitabine resistance and epithelial-mesenchymal phenotype. Our analysis suggested that the promiscuous oxidative actions of H(2)O(2) derived from pharmacologic ascorbate can culminate in synergism independent of the cancer cell's underlying phenotype and resistance to gemcitabine monotherapy. Gemcitabine-ascorbate combinations administered to mice bearing pancreatic tumor xenografts consistently enhanced inhibition of growth compared to gemcitabine alone, produced 50% growth inhibition in a tumor type not responsive to gemcitabine, and demonstrated a gemcitabine dose-sparing effect. These data support the testing of pharmacologic ascorbate in adjunctive treatments for cancers prone to high failure rates with conventional therapeutic regimens, such as pancreatic cancer.

Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects.

BACKGROUND: Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM) practitioners. The scale of such use in the U.S. and associated side effects are unknown. METHODS AND FINDINGS: We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U.S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA's Adverse Events Database. Of 199 survey respondents (out of 550), 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25 g/50 ml vials) were 318,539 in 2006 and 354,647 in 2008. Manufacturers' yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue. Of 9,328 patients for whom data is available, 101 had side effects, mostly minor, including lethargy/fatigue in 59 patients, change in mental status in 21 patients and vein irritation/phlebitis in 6 patients. Publications documented serious adverse events, including 2 deaths in patients known to be at risk for IV vitamin C. Due to confounding causes, the FDA Adverse Events Database was uninformative. Total numbers of patients treated in the US with high dose vitamin C cannot be accurately estimated from this study. CONCLUSIONS: High dose IV vitamin C is in unexpectedly wide use by CAM practitioners. Other than the known complications of IV vitamin C in those with renal impairment or glucose 6 phosphate dehydrogenase deficiency, high dose intravenous vitamin C appears to be remarkably safe. Physicians should inquire about IV vitamin C use in patients with cancer, chronic, untreatable, or intractable conditions and be observant of unexpected harm, drug interactions, or benefit.

Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice.

Ascorbic acid is an essential nutrient commonly regarded as an antioxidant. In this study, we showed that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogen-peroxide-dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells. To test this action in vivo, normal oral tight control was bypassed by parenteral ascorbate administration. Real-time microdialysis sampling in mice bearing glioblastoma xenografts showed that a single pharmacologic dose of ascorbate produced sustained ascorbate radical and hydrogen peroxide formation selectively within interstitial fluids of tumors but not in blood. Moreover, a regimen of daily pharmacologic ascorbate treatment significantly decreased growth rates of ovarian (P < 0.005), pancreatic (P < 0.05), and glioblastoma (P < 0.001) tumors established in mice. Similar pharmacologic concentrations were readily achieved in humans given ascorbate intravenously. These data suggest that ascorbate as a prodrug may have benefits in cancers with poor prognosis and limited therapeutic options.

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo.

Ascorbate (ascorbic acid, vitamin C), in pharmacologic concentrations easily achieved in humans by i.v. administration, selectively kills some cancer cells but not normal cells. We proposed that pharmacologic ascorbate is a prodrug for preferential steady-state formation of ascorbate radical (Asc(*-)) and H(2)O(2) in the extracellular space compared with blood. Here we test this hypothesis in vivo. Rats were administered parenteral (i.v. or i.p.) or oral ascorbate in typical human pharmacologic doses ( approximately 0.25-0.5 mg per gram of body weight). After i.v. injection, ascorbate baseline concentrations of 50-100 microM in blood and extracellular fluid increased to peaks of >8 mM. After i.p. injection, peaks approached 3 mM in both fluids. By gavage, the same doses produced ascorbate concentrations of <150 microM in both fluids. In blood, Asc(*-) concentrations measured by EPR were undetectable with oral administration and always <50 nM with parenteral administration, even when corresponding ascorbate concentrations were >8 mM. After parenteral dosing, Asc(*-) concentrations in extracellular fluid were 4- to 12-fold higher than those in blood, were as high as 250 nM, and were a function of ascorbate concentrations. By using the synthesized probe peroxyxanthone, H(2)O(2) in extracellular fluid was detected only after parenteral administration of ascorbate and when Asc(*-) concentrations in extracellular fluid exceeded 100 nM. The data show that pharmacologic ascorbate is a prodrug for preferential steady-state formation of Asc(*-) and H(2)O(2) in the extracellular space but not blood. These data provide a foundation for pursuing pharmacologic ascorbate as a prooxidant therapeutic agent in cancer and infections.