Search

Objective: Bulbar urethral necrosis is a rare and devastating complication of anastomotic urethroplasty for pelvic fracture urethral injury, which manifests as bulbar urethral loss due to inadequate retrograde blood supply after transection of the bulbar urethra. In this accompanying video, we demonstrate a case of bulbar urethral necrosis successfully salvaged using penile skin tube flap urethroplasty. Patient and surgical procedure: A 67-year-old male underwent anastomotic urethroplasty for a pelvic fracture urethral injury; however, he experienced urinary retention 3 months after urethroplasty. Urethrography revealed a long (40 mm) urethral defect, suggesting bulbar urethral necrosis. Salvage urethroplasty using a penile skin flap was performed 12 months after failure of the initial urethroplasty. A midline perineal incision was made and the necrotic bulbar urethral segment was excised entirely, exposing the healthy distal and proximal urethral ends. A transverse circular penile skin flap 3 cm wide was harvested and transposed to the perineum. Subsequently, a skin flap tube was created using a 5–0 polydioxanone running suture over a 14 Fr Foley catheter and was anastomosed to both urethral ends to fill the bulbar urethral defect. Results: The postoperative course was uneventful. Four weeks after salvage urethroplasty, the urethral catheter was removed and the patient resumed voiding. Postoperative cystourethroscopy revealed no recurrent stenosis and the flap was healthy with a wide urethral lumen. Two years after surgery, the patient continued to have a good voiding status. Conclusion: Penile skin tube flap urethroplasty may be a viable option for the repair of bulbar urethral necrosis.

A 54-year-old male patient presented with pneumaturia. Right scrotal swelling was observed. CT showed an intrascrotal abscess with gas formation. MRI showed a fistula extending from the sigmoid colon to the seminal vesicles. Since there are many diverticula in the sigmoid colon, an abscess caused by diverticulitis may have formed a fistula. The scrotal abscess was drained; however, the pus discharge did not decrease. A colostomy was then performed, and the scrotal infection rapidly improved. Sigmoidectomy and fistula transection were performed 11 months after the colostomy. Prompt diagnosis of a sigmoid coloseminal fistula using imaging has led to optimal treatment.

Summary: We describe a patient haploinsufficient for the neuronal RNA binding protein NOVA1 who developed a behavioral motor hyperactivity disorder, suggesting a role of NOVA1 in postnatal motor inhibition. To investigate Nova1’s action in adult Gad2+ inhibitory neurons, we generated a conditional Nova1-null mouse (Nova1-cKOGad2-cre). Strikingly, the phenotypes of these mice show many similarities to the NOVA1 haploinsufficient patient and identify a function of Nova1 in the hypothalamus. Molecularly, Nova1 loss in Gad2-positive neurons alters downstream expression of Impact mRNA, along with a subset of RNAs encoding electron transport chain-related factors and ribosomal proteins. NOVA1 stabilizes Impact mRNA by binding its 3′ UTR, antagonizing the actions of miR-138 and miR-124. Together, these studies demonstrate actions of NOVA1 in adult hypothalamic neurons, mechanisms by which it functions in translation and metabolism, including through direct binding to Impact mRNA, and illuminate its role in human neurologic disease.

Objective: Accumulating evidence indicates that high uric acid (UA) is strongly associated with obesity and metabolic syndrome and drives the development of nonalcoholic fatty liver disease (NAFLD) and insulin resistance. Although urate transporter-1 (URAT1), which is primarily expressed in the kidneys, plays a critical role in the development of hyperuricemia, its pathophysiological implication in NAFLD and insulin resistance remains unclear. We herein investigated the role and functional significance of URAT1 in diet-induced obese mice. Methods: Mice fed a high-fat diet (HFD) for 16–18 weeks or a normal-fat diet (NFD) were treated with or without a novel oral URAT1-selective inhibitor (dotinurad [50 mg/kg/day]) for another 4 weeks. Results: We found that URAT1 was also expressed in the liver and brown adipose tissue (BAT) other than the kidneys. Dotinurad administration significantly ameliorated HFD-induced obesity and insulin resistance. HFD markedly induced NAFLD, which was characterized by severe hepatic steatosis as well as the elevation of serum ALT activity and tissue inflammatory cytokine genes (chemokine ligand 2 (Ccl2) and tissue necrosis factor α (TNFα)), all of which were attenuated by dotinurad. Similarly, HFD significantly increased URAT1 expression in BAT, resulting in lipid accumulation (whitening of BAT), and increased the production of tissue reactive oxygen species (ROS), which were reduced by dotinurad via UCP1 activation. Conclusions: In conclusion, a novel URAT1-selective inhibitor, dotinurad, ameliorates insulin resistance by attenuating hepatic steatosis and promoting rebrowning of lipid-rich BAT in HFD-induced obese mice. URAT1 serves as a key regulator of the pathophysiology of metabolic syndrome and may be a new therapeutic target for insulin-resistant individuals, particularly those with concomitant NAFLD.

We report a case of unusually aggressive behavior of a mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney with no sarcomatoid changes. A 43-year-old man was referred to our hospital for a mass on his left kidney. Computed tomography revealed a tumor at the upper pole of the kidney and swollen lymph nodes. Left radical nephrectomy with lymph node dissection was performed and the tumor was diagnosed as MTSCC. Peritoneal dissemination was detected 4 months after the surgery. The patient received systemic treatments, which were not effective. He finally died of the disease 12 months after the surgery.

Pazopanib, a multityrosine kinase inhibitor used for treating malignant soft tissue tumors, rarely causes adverse events associated with the respiratory system. We report a case of a 73-year-old male with leiomyosarcoma treated with pazopanib. Four months after treatment initiation, chest computed tomography showed bilateral patchy consolidation and ground-glass opacities. Bronchoscopy revealed increased lymphocytes in the bronchoalveolar lavage fluid. Histological analysis of lung tissue demonstrated intraluminal fibrotic changes in alveolar spaces. According to these findings, we diagnosed the patient with pazopanib-induced organizing pneumonia. To best of our knowledge, this is the first report of such a case.

Renal cell carcinoma (RCC) is the most lethal urological malignancy with high risk of recurrence; thus, new prognostic biomarkers are needed. In this study, a new RCC antigen, PTPL1 associated RhoGAP1 (PARG1), was identified by using serological identification of recombinant cDNA expression cloning with sera from RCC patients. PARG1 protein was found to be differentially expressed in RCC cells among patients. High PARG1 expression is significantly correlated with various clinicopathological factors relating to cancer cell proliferation and invasion, including G3 percentage (P = .0046), Ki-67 score (p expression is also correlated with high recurrence of N0M0 patients (P = .0084) and poor prognosis in RCC patients (P = .0345). Multivariate analysis has revealed that high PARG1 expression is an independent factor for recurrence (P = .0149) of N0M0 RCC patients. In in vitro studies, depletion of PARG1by siRNA in human RCC cell lines inhibited their proliferation through inducing G1 cell cycle arrest via upregulation of p53 and subsequent p21Cip1/Waf1, which are mediated by increased RhoA-ROCK activities. Similarly, PARG1 depletion cells inhibited invasion ability via increasing RhoA-ROCK activities in the RCC cell lines. Conversely, overexpression of PARG1 on human embryonic kidney cell line HEK293T promotes its cell proliferation and invasion. These results indicate that PARG1 plays crucial roles in progression of human RCC in increasing cell proliferation and invasion ability via inhibition of the RhoA-ROCK axis, and PARG1 is a poor prognostic marker, particularly for high recurrence of N0M0 RCC patients.

Pazopanib is an orally bioavailable tyrosine kinase inhibitor anticancer drug approved worldwide for the treatment of metastatic renal cell carcinoma and advanced soft tissue sarcoma. Here we report the case of a patient whose recurrent retroperitoneal soft tissue sarcoma showed a drastic reduction immediately after pazopanib administration accompanied by severe liver dysfunction. His liver function was restored conservatively by giving him hepatoprotectors and having him stop taking pazopanib. The recurrent tumor disappeared but by 4 months later had regrown. Keywords: Liver toxicity, Pazopanib, Recurrent soft tissue sarcoma

The present case underwent right laparoscopic radical nephrectomy for collecting duct carcinoma (CDC). Recurrence occurred in the lung and the bone (skull and lumber vertebra) in 2011. Gemcitabine plus cisplatin (GC) chemotherapy and monthly zoledronic acid (ZA) was then started. The massive skull bone metastases were prominently reossified after several courses of the therapy. The patient received 16 courses of GC chemotherapy and monthly ZA, and pulmonary metastases and reossified skull bone metastases were stable for 23 months. Although we cannot verify the adoptive effect of ZA on the reossification, this combination may be effective for CDC bone metastases.

Renal replacement lipomatosis (RRL) is a rare condition that occurs at the end of the spectrum of renal tissue replacement by fat. Xanthogranulomatous pyelonephritis (XGP) is a granulomatous inflammation characterized by destruction of renal parenchyma and replacement by lipid-laden macrophages. We present the case of a 75-year-old man who complained of severe anemia 34 years after right nephrolithotomy. Computed tomography revealed a huge low-density mass with renal parenchyma atrophy on the right side of horseshoe kidney. Right nephrectomy was performed. Pathological diagnosis was RRL with XGP. This is the first report of RRL with XGP in a horseshoe kidney.