Activities of Ca2+-related ion channels during the formation of kidney stones in an infection-induced urolithiasis rat model.

Bacterial infection has long been recognized to contribute to struvite urinary stone deposition; however, its contribution to the development of chronic kidney stones has not been extensively investigated. In the present study, we hypothesized another possible method of bacteria contributing to the formation of calcium oxalate (CaOx) that accounts for the biggest part of the kidney stone. Bacteria may play important roles by influencing renal Ca2+-related ion channel activities, resulting in chronic inflammation of the kidney along with rapid aggregation of stones. We examined the correlation among infection-promoted CaOx kidney stones and alterations in Ca2+-related ion channels in an animal model with experimentally induced Proteus mirabilis and foreign body infection. After the bladder was infected for 7 days, the data demonstrated that stones were presented and induced severe renal tubular breakage as well as altered levels of monocyte chemoattractant protein-1, cyclooxygenase-2, osteopontin, and transient receptor potential vanilloid member 5 expression, reflecting responses of kidney ion channels. Monocyte chemoattractant protein-1, osteopontin, and transient receptor potential vanilloid member 5 expression was significantly downregulated over time, indicating the chronic inflammation phase of the kidney and accelerated aggregation of CaOx crystals, respectively, whereas cyclooxygenase-2 exhibited no differences. These results indicated that bacterial infection is considerably correlated with an alteration in renal Ca2+-related ion channels and might support specific and targeted Ca2+-related ion channel-based therapeutics for urolithiasis and related inflammatory renal damage.

Emodin modulates epigenetic modifications and suppresses bladder carcinoma cell growth.

The deregulation of epigenetics was involved in early and subsequent carcinogenic events. Reversing cancer epigenetics to restore a normal epigenetic condition could be a rational approach for cancer treatment and specialized prevention. In the present study, we found that the expression levels of two epigenetic markers, histone H3K27 trimethylation (H3K27me3), was low but histone H3S10 phosphorylation (pH3Ser10) was high in human bladder cancer tissues, which showed opposite expression patterns in their normal counterparts. Thus, we investigated whether a natural product, emodin, has the ability to reverse these two epigenetic modifications and inhibit bladder cancer cell growth. Emodin significantly inhibited the cell growth of four bladder cancer cell lines in a dose- and time-dependent manner. Emodin treatment did not induce specific cell cycle arrest, but it altered epigenetic modifications. Emodin treatment resulted in the suppression of pH3Ser10 and increased H3K27me3, contributing to gene silencing in bladder cancer cells. Microarray analysis demonstrated that oncogenic genes including fatty acid binding protein 4 (FABP4) and fibroblast growth factor binding protein 1 (HBP17), RGS4, tissue inhibitor of metalloproteinase 3 (TIMP3), WNT5b, URB, and collagen, type VIII, alpha 1 (COL8A1) responsible for proliferation, survival, inflammation, and carcinogenesis were significantly repressed by emodin. The ChIP assays also showed that emodin increased H3K27me3 but decreased pH3Ser10 modifications on the promoters of repressed genes, which indicate that emodin reverses the cancer epigenetics towards normal epigenetic situations. In conclusion, our work demonstrates the significant anti-neoplastic activity of emodin on bladder cancer cells and elucidates the novel mechanisms of emodin-mediated epigenetic modulation of target genes. Our study warrants further investigation of emodin as an effective therapeutic or preventive agent for bladder cancer.

Renal infarction secondary to ketamine abuse.

Renal infarction is an uncommon condition that resulted from inadequate perfusion of the kidney and is easily missed diagnosed due to its nonspecific clinical presentations. Major risk factors for renal infarction are atrial fibrillation, previous embolism, and ischemic and valvular heart disease. Progressive decrease in renal function or even death can occur if renal infarction is not diagnosed accurately and promptly. Ketamine abuse may cause variable urinary tract injury. However, renal infarction caused by ketamine abuse has never been reported. To our knowledge, this is the first documented case of renal infarction following nasal insufflation of ketamine.

Calcified, minimally fat-contained angiomyolipoma clinically indistinguishable from a renal cell carcinoma.

BACKGROUND: Angiomyolipomas are benign tumors of the kidney. Typical angiomyolipomas are usually recognized by identifying fat components before any intervention. On the contrary, solid renal masses without evident fatty components but containing calcifications on the computed tomography scan are suspicious for malignancy. However, as in this rare case, rules of diagnostic imaging are of exceptions. CASE PRESENTATION: A 40-year-old man presented with left flank pain. The plain X-ray showed multiple coarse calcifications of 4.0x3.2 cm in diameter on the left upper quadrant abdomen. Computed tomography scan further revealed a solid renal mass and inside the mass there were calcifications. The size of the tumor was 5.6×5.5×6.3 cm. We performed a radical nephrectomy, and the histopathology showed a minimally fat-contained angiomyolipoma of multiple calcifications. The patient was free of recurrence or metastases after a follow-up period of 3 years. CONCLUSION: An angiomyolipoma containing calcification is rare. An angiomyolipoma with minimal fat concomitant with calcifications is an even rarer presentation. It is very difficult to differentiate a minimal-fat angiomyolipoma with calcifications from a renal cell carcinoma preoperatively. In such a circumstance, a well-planned partial nephrectomy may be optimal for the patient, regardless of the tumor size.

Germanium-Titanium-π Polymer Composites as Functional Textiles for Clinical Strategy to Evaluate Blood Circulation Improvement and Sexual Satisfaction.

By continuously enhancing the blood flow, far-infrared (FIR) textile is anticipated to be a potential non-pharmacological therapy in patients with peripheral vascular disorders, for instance, patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) and experiencing vasculogenic erectile dysfunction (VED). Hence, we manufactured a novel polymer composite, namely, germanium-titanium-π (Ge-Ti-π) textile and aimed to evaluate its characteristics and quality. We also investigated the immediate and long-term effects of the textile on patients with ESRD undergoing HD and experiencing VED. The Ge-Ti-π textile was found to have 0.93 FIR emissivity, 3.05 g/d strength, and 18.98% elongation. The results also showed a 51.6% bacteria reduction and negative fungal growth. On application in patients receiving HD, the Ge-Ti-π textile significantly reduced the limb numbness/pain (p < 0.001) and pain score on the visual analog scale (p < 0.001). Moreover, the Doppler ultrasound assessment data indicated a significant enhancement of blood flow in the right hand after 1 week of Ge-Ti-π textile treatment (p < 0.041). In VED patients, the Ge-Ti-π underpants treatment significantly improved the quality of sexual function and increased the average penile blood flow velocity after 3 months of the treatment. Our study suggests that the Ge-Ti-π textile could be beneficial for patients with blood circulation disorders.

Ketamine-associated bladder dysfunction.

OBJECTIVE: To assess the impact of ketamine abuse on genitourinary tract dysfunction. METHODS: Eleven patients with urinary tract symptoms and a history of ketamine abuse in recent years were studied. Urinalysis, urine culture, renal function tests, abdominal sonography and urodynamic studies were done. Bladder biopsies were carried out in selected cases. RESULTS: The most common complaints were lower urinary tract symptoms, including dysuria, frequency, urgency and gross hematuria. Urinalyses showed nonbacterial pyuria and were negative for tuberculosis. All biopsy specimens showed infiltrations of granulocytes (mostly eosinophils) and mast cells within the bladder tissue. Medications produced only slight clinical improvements. Intravesical instillation of hyaluronan solution was performed for some patients and a significant improvement of lower urinary tract symptoms was observed. CONCLUSIONS: Although the dosage and duration of ketamine abuse causing severe side-effects are still unclear, some patients develop irreversible histological changes in the urinary tract. Therefore, clinicians should be aware of the negative effects of ketamine abuse on genitourinary tract function.

Comparison of Different Treatment Schedules of Mitomycin C Intravesical Instillation in High-Risk Superficial Bladder Cancer Patients.

ZIEL: Diese Studie erfolgte zum Vergleich der Wirksamkeit einer intravesikalen Instillation von Mitomycin C (MMC) zur Prävention eines nicht muskelinvasiven Ta- oder T1-High-Risk-Harnblasenkarzinoms (NMIBC) unter Verwendung verschiedener Schemata. MATERIAL UND METHODEN: Diese retrospektive Kohortenstudie wurde bei 152 Patienten durchgeführt, die zwischen April 2009 und September 2016 mit einer intravesikalen MMC-Injektion behandelt wurden. Der mittlere Nachbeobachtungszeitraum lag bei 32,67 Monaten. Alle Patienten unterzogen sich einer vollständigen transurethralen Resektion des Blasentumors (TURBT), an die sich innerhalb von 24 Stunden eine postoperative Instillation von MMC anschloss. Die Patienten wurden in 4 Behandlungsgruppen unterteilt: Bei Gruppe 1 erfolgte die Nachbeobachtung ohne MMC-Erhaltungsdosis; Gruppe 2 erhielt in den ersten 8 Wochen einmal pro Woche eine MMC-Instillation; Gruppe 3 erhielt in den ersten 8 Wochen einmal pro Woche und in den darauffolgenden 6 Monaten einmal pro Monat eine MMC-Instillation; Gruppe 4 erhielt in den ersten 8 Wochen einmal pro Woche und in den darauffolgenden 12 Monaten einmal pro Monat eine MMC-Instillation. ERGEBNISSE: Die allgemeine Rezidivrate lag bei 27,6 %. Gruppe 1 zeigte eine signifikant hohe (p < 0,05) Rezidivrate von 50 %, während sich bei den Rezidivraten der übrigen 3 Schemata kein Unterschied fand (Gruppe 2: 15 %; Gruppe 3: 24,1 %; Gruppe 4: 27,2 %). Darüber hinaus zeigte sich zwischen diesen Patientengruppen kein statistischer Unterschied bei den Rezidivraten von Ta- oder T1-Tumoren sowie niedrig- oder hochgradigen Tumoren. SCHLUSSFOLGERUNG: Unser Vergleich der verschiedenen Schemata einer intravesikalen MMC-Instillation ergab bei einer einzigen MMC-Instillation nach TURBT eine signifikant höhere Rezidivrate als bei Patienten, die nach 8 Wochen, 6 Monaten und 12 Monaten eine Erhaltungsdosis erhielten. Zeitlich fanden sich beim MMC-Erhaltungsschema keine signifikanten Unterschiede zwischen der 8. Woche und dem 12. Monat. Daraus folgern wir, dass bei T1- oder Ta-High-Risk-NMIBC nach TURBT einmalig eine MMC-Instillation mit anschließender Erhaltungstherapie mit einmal wöchentlicher Verabreichung über 8 Wochen durchgeführt werden kann.

Laparoscopic radical prostatectomy: initial experience of robotic surgery in Taiwan.

BACKGROUND: The incidence of prostate cancer is lower in Taiwan compared to Europe and North America. Only a few urologists have been trained to perform laparoscopic radical prostatectomies (LRP). The initial experience of robotic LRP in Taiwan is reported. PATIENTS AND METHODS: Twenty-four patients with localized prostate carcinomas underwent robotic LRP between November 2004 and December 2006. Data collection included basic demographics, prostate specific antigen (PSA), stages, Gleason scores, operative time, estimated blood loss (EBL), catheterization time, pathology, complications and return of continence. RESULTS: The mean operative time was 310 minutes, the mean EBL was 234 mL and the average urethral catheterization time was 7.1 days. Three patients had a total of three complications. Continence was 20.8% at one week, 59.1% at six weeks and 75% at three months postoperatively. CONCLUSION: Our initial experience with robotic LRP indicated that the procedure was safe and effective. Six case experiences were required to establish a standard operating procedure. Eighteen operations were needed to complete the learning curve and achieve stable results.

Kidney Transplantation from an extracorporeal membrane oxygenation-supported brain-dead donor: A case report.

RATIONALE: Extracorporeal membrane oxygenation (ECMO) can deliver effective respiratory and circulatory maintenance to organ donors, improve organ function, and shorten warm ischemic time before harvesting. However, ECMO-supported brain-dead donors (DBDs) still have a high risk of acute kidney injury related to decreased renal oxygen delivery and inflammatory damage, which may cause early graft failure. PATIENT CONCERNS: Kidney transplantation from an ECMO-supported DBD. DIAGNOSES: We found an extremely abnormal "very dark blue" appearance of the graft kidneys from an ECMO-supported DBD during kidney procurement. INTERVENTIONS: Rather than discarding the graft kidneys, we performed an on-table biopsy. Pretransplant biopsy results revealed minimal interstitial fibrosis in the section of these graft kidneys. OUTCOMES: Two candidates received graft kidneys, and the two grafts remained functional until the 8-month follow-up. LESSONS: Currently, there is no standard method for evaluating graft kidney function of ECMO-supported DBDs. Regardless of the donors' preoperative serum creatinine (SCr) level, estimated glomerular filtration rate (eGFR), or gross appearance of the graft kidney, we believe that it is more reliable to include pretransplant biopsy as a criterion in clinical practice to safely accept kidneys from ECMO-supported DBDs.

Spondylodiscitis with Epidural and Psoas Muscle Abscesses as Complications After Transrectal Ultrasound-guided Prostate Biopsy: Report of a Rare Case.

A 71-year-old man presented with spondylodiscitis with epidural and psoas muscle abscesses following transrectal ultrasound (TRUS)-guided prostate biopsy. These rare complications were detected by computed tomography of the abdomen and magnetic resonance imaging of the lumbar spine. The patient was successfully treated with antibiotics and underwent neurosurgery. Awareness of presentations such as backache and weakness of the lower limbs after prostate biopsy is important as these symptoms are usually mistaken for bone or muscle problems and often not recognized as being related to infection. LEARNING POINTS: We describe the case of a patient who experienced two major complications (spondylodiscitis with epidural abscess and psoas muscle abscess) following prostate biopsy.Awareness of these potential complications following prostate biopsy is essential to prevent life-threatening consequences.

Unusual presentation of direct intraperitoneal metastases complicated with massive ascites from plasmacytoid variant of bladder cancer and adenocarcinoma of colon: A case report and literature review.

BACKGROUND: Plasmacytoid urothelial carcinoma (PUC) is a distinct variant of urinary bladder cancer, with a high propensity for invasion and poor prognosis. These tumors occur most commonly in male patients with the age of reported cases ranging from 46 to 87 years. CASE REPORT: We present a case of a 74-year-old male patient having massive ascites and bilateral lower leg edema. Colonoscopy showed a 3-cm lesion in the sigmoid colon and an edematous nonpapillary tumor was found by cystoscopy in the bladder. Histopathology analysis of the biopsies showed adenocarcinoma of colon and PUC of bladder. The diagnosis of PUC with peritoneal carcinomatosis was then confirmed by immunohistochemical stain. CONCLUSION: The diagnostic dilemmas of the unusual variant of urothelial malignancy, the origin of peritoneal metastasis, and its clinical impact are discussed in the present case.

Limited Wegener's granulomatosis of the epididymis and testis.

A case is presented of Wegener's granulomatosis limited to the testis and epididymis, simultaneously, in a 69-year-old man. Orchiectomy was carried out through an inguinal incision under the presumptive diagnosis of a right testicular tumor. A hard, irregular mass occupied the upper testicle and a portion of the epididymal head was visualized. Histopathologic examination of the specimen showed granulomatous inflammation of the testis and epididymis with prominent angiocentric granulomata in the walls of arteries, veins and foci of fibrinoid necrosis, surrounded by palisading inflammatory cells with a few giant cells. The diagnosis of limited Wegener's granulomatosis was considered, although antineutrophil cytoplasmic antibody (c-ANCA) test was negative 2 weeks after orchiectomy. The patient showed an excellent response after local complete excision. He remains free of disease 18 months after orchiectomy.

The Risk of Nephrolithiasis Among Patients With Ankylosing Spondylitis: a Population-Based Cohort Study.

OBJECTIVES: This study aims to investigate the correlation of ankylosing spondylitis (AS) with nephrolithiasis by performing a nationwide population- based cohort study. PATIENTS AND METHODS: The data used in this retrospective cohort study were collected from the Taiwan National Health Insurance Research database. The study included a total of 3,334 AS patients (1,914 males, 1,420 females; mean age 44.51±16.83 years; range 22 to 79 years) and 13,336 non-AS patients (7,656 males, 5,680 females; mean age 44.27±17.01 years; range 21 to 78 years) who had been followed-up on an average of 6.78 years and 6.75 years, respectively, between January 2000 and December 2008. RESULTS: The percentage of newly diagnosed nephrolithiasis was 4.8% in all study subjects. However, the percentages of newly diagnosed nephrolithiasis were 5.76% and 4.58% in the AS and non-AS cohorts, respectively. After adjusting the patients' sex, age, urbanization level, and comorbidities, the hazard ratio obtained from our multivariable Cox model was 1.19. CONCLUSION: Our study findings indicate that patients with AS are more likely to develop nephrolithiasis than non-AS patients.

An Unexpected Clinical Feature of Zinner's Syndrome - A Case Report.

We present a case of a healthy 43-year-old man who experienced right lower abdominal mass with gastrointestinal upset for 6 months. A series of imaging studies revealed a large lobulated cyst in the right pelvis and retroperitoneum. Because of the persistent symptom, surgical intervention was performed to remove the cystic lesion. The final pathology report demonstrated a large seminal vesicle cyst with agenesis of kidney. It is compatible with the diagnosis of Zinner's syndrome. However, right lower abdominal mass is a rare manifestation of this syndrome. This case reminds us a unique differential diagnosis of a right lower abdominal mass.

Novel Cancer Therapeutics with Allosteric Modulation of the Mitochondrial C-Raf-DAPK Complex by Raf Inhibitor Combination Therapy.

Mitochondria are the powerhouses of cells. Mitochondrial C-Raf is a potential cancer therapeutic target, as it regulates mitochondrial function and is localized to the mitochondria by its N-terminal domain. However, Raf inhibitor monotherapy can induce S338 phosphorylation of C-Raf (pC-Raf(S338)) and impede therapy. This study identified the interaction of C-Raf with S308 phosphorylated DAPK (pDAPK(S308)), which together became colocalized in the mitochondria to facilitate mitochondrial remodeling. Combined use of the Raf inhibitors sorafenib and GW5074 had synergistic anticancer effects in vitro and in vivo, but targeted mitochondrial function, rather than the canonical Raf signaling pathway. C-Raf depletion in knockout MEF(C-Raf-/-) or siRNA knockdown ACHN renal cancer cells abrogated the cytotoxicity of combination therapy. Crystal structure simulation showed that GW5074 bound to C-Raf and induced a C-Raf conformational change that enhanced sorafenib-binding affinity. In the presence of pDAPK(S308), this drug-target interaction compromised the mitochondrial targeting effect of the N-terminal domain of C-Raf, which induced two-hit damages to cancer cells. First, combination therapy facilitated pC-Raf(S338) and pDAPK(S308) translocation from mitochondria to cytoplasm, leading to mitochondrial dysfunction and reactive oxygen species (ROS) generation. Second, ROS facilitated PP2A-mediated dephosphorylation of pDAPK(S308) to DAPK. PP2A then dissociated from the C-Raf-DAPK complex and induced profound cancer cell death. Increased pDAPK(S308) modification was also observed in renal cancer tissues, which correlated with poor disease-free survival and poor overall survival in renal cancer patients. Besides mediating the anticancer effect, pDAPK(S308) may serve as a predictive biomarker for Raf inhibitors combination therapy, suggesting an ideal preclinical model that is worthy of clinical translation.

Ischemic glans penis after circumcision.

A 33-year-old male receiving dorsal penile nerve block (DPNB) for circumcision exhibited a postoperative ischemic change over the glans penis. The event occurred nearly 24 hours after the procedure. The patient was treated with intravenous pentoxifyllin and hyperbaric oxygenation. Total reverse of the ischemia was observed. The complications associated with circumcision and DPNB were reviewed and discussed.

Is Urodynamic Study a Good Witness to the Progression of Ketamine-Associated Cystitis?

OBJECTIVES: Ketamine abuse may cause variable lower urinary tract symptoms and severe cystitis. In this study, we evaluated the relevance of urodynamic parameters according to the dose and duration of ketamine use and investigate the value of urodynamic studies in determining the severity of ketamine-associated cystitis (KC). METHODS: The urodynamic study results of 30 patients with KC between January 2009 and December 2012 were analyzed retrospectively. All patients had been diagnosed based on their history and clinical features before urodynamic investigations. Cystoscopy was performed to confirm the diagnosis and measure the maximum anesthetic bladder bladder capacity (MBC) (under spinal anesthesia). RESULTS: The mean (± standard deviation) age of patients with KC was 22.0 ± 3.3 years. The mean duration of ketamine abuse was 39.0 ± 20.8 months. Maximum cystometric capacity was 115 ± 66.6 mL. Seventy-five percent of patients had a high maximal urethral closure pressure (MUCP) (> 90 cmH2 O). There was no significant difference of urodynamic parameters between the high-dose (≥ 5 gm/day) and low-dose groups (< 5 gm/day) or the long-duration (≥ 3 years) and short-duration (< 3 years) groups. However, the MBC was significantly lower in high-dose and long-duration groups compared to the low-dose and short-duration groups (191.3 ± 68.5 vs. 299.0 ± 99 mL; P = 0.01; 219.0 ± 59.7 vs. 325.5 ± 104.5 mL; P = 0.002). CONCLUSIONS: The urodynamic test results help diagnose KC, but may not be useful in determining the severity of the disease. The MBC measured under anesthesia may be a better predictor of the disease progression in KC.