Prostatic abscess with infected aneurysms and spondylodiscitis after transrectal ultrasound-guided prostate biopsy: a case report and literature review.

BACKGROUND: Transrectal ultrasonography (TRUS)-guided prostate biopsy is the conventional method of diagnosing prostate cancer. TRUS-guided prostate biopsy can occasionally be associated with severe complications. Here, we report the first case of a prostate abscess with aneurysms and spondylodiscitis as a complication of TRUS-guided prostate biopsy, and we review the relevant literature. CASE PRESENTATION: A 78-year-old man presented with back pain, sepsis, and prostate abscesses. Twenty days after TRUS-guided prostate biopsy, he was found to have a 20-mm diameter abdominal aortic aneurysm that expanded to 28.2 mm in the space of a week, despite antibiotic therapy. Therefore, he underwent transurethral resection of the prostate to control prostatic abscesses. Although his aneurysm decreased to 23 mm in size after surgery, he continued to experience back pain. He was diagnosed as having pyogenic spondylitis and this was managed using a lumbar corset. Sixty-four days after the prostate biopsy, the aneurysm had re-expanded to 30 mm; therefore, we performed endovascular aneurysm repair (EVAR) using a microcore stent graft 82 days after the biopsy. Four days after the EVAR, the patient developed acute cholecystitis, and he underwent endoscopic retrograde biliary drainage. One hundred and sixty days after the prostate biopsy, all the complications had improved, and he was discharged. A literature review identified a further six cases of spondylodiscitis that had occurred after transrectal ultrasound-guided prostate biopsy. CONCLUSIONS: We have reported the first case of a complication of TRUS-guided prostate biopsy that involved prostatic abscesses, aneurysms, and spondylodiscitis. Although such complications are uncommon, clinicians should be aware of the potential for such severe complications of this procedure to develop.

Transgenic expression of human CD47 reduces phagocytosis of porcine endothelial cells and podocytes by baboon and human macrophages.

BACKGROUND: Our initial studies utilizing a galactosyl-α1-3-galactosyltransferase gene knockout (GalTKO) pig-to-baboon renal transplant model demonstrated that the early development of nephrotic syndrome has been a significant obstacle to the long-term survival of baboon recipients. We have recently documented that sphingomyelin phosphodiesterase-3 (SMPDL3b) and CD80 expressed on podocytes in porcine kidney grafts contribute to this complication. We have hypothesized that one regulator of immune function is CD47 and that incompatibilities in CD47 between pig and baboon could potentially affect macrophage function, increasing the susceptibility of the kidney grafts to immunologically induced injury. METHODS: In order to address this hypothesis in vitro, we isolated and cultured porcine podocytes and ECs from GalTKO alone, human CD47 (hCD47)/hCD55 expressing transgenic (Tg) GalTKO swine, and GalTKO hCD46/hCD55 Tg swine along with baboon or human macrophages. RESULTS: We found that baboon macrophages phagocytosed porcine ECs in a similar manner to human macrophages, and this response was significantly reduced when porcine ECs and podocytes expressed hCD47/hCD55 but not hCD46/hCD55 without hCD47. Furthermore, masking hCD47 by anti-hCD47 antibody on hCD47/hCD55Tg ECs restored phagocytosis. These results are consistent with the hypothesis that CD47 incompatibility plays an important role in promoting macrophage phagocytosis of endogenous cells from the transplanted kidney. CONCLUSIONS: The similar levels of phagocytosis of porcine cells by baboon and human macrophages suggest that the expression of hCD47Tg on glomerular cells in donor porcine kidneys may prove to be a key strategy for preventing proteinuria following kidney xenotransplantation in a pig-to-human as well as a pig-to-baboon model.

Expression of epithelial-Mesenchymal transition related markers in Plasmacytoid Urothelial carcinoma of the urinary bladder.

BACKGROUND: Plasmacytoid urothelial carcinoma (PUC) of the urinary bladder is a variant of urothelial carcinoma that carries a poor prognosis. The epithelial-mesenchymal transition (EMT) has been demonstrated to contribute to tumor progression. As the cause of the increased aggressiveness of PUC is unknown, we investigated PUC and EMT-related marker expression. METHODS: A total of 633 bladder carcinoma cases diagnosed from 2006 to 2015 at the Nippon Medical School Hospital were analyzed. Twelve patients were found to have plasmacytoid histology and diagnosed with PUC. Slides were evaluated for percentage of plasmacytoid variant, and stained for E-cadherin, N-cadherin, Vimentin, Fibronectin and Snail expression. RESULTS: The incidence of PUC was 1.9% (12/633). The median patient age at diagnosis was 71 years (range, 60-80 years) and the male-female ratio was 11:1. All but three patients had stage T2b or higher. The median overall survival was 10 months. In 10/12 cases, Snail and N-cadherin were positive. Vimentin was positive in 9/12 cases. Fibronectin was positive in 8/12 cases. While E-cadherin was negative in 10/12 cases. Nine cases showed > 10% plasmacytoid component. Eight of the nine patients (88.9%) with > 10% plasmacytoid component died. CONCLUSIONS: The results indicate that PUC may induce EMT and may be associated with high invasion.

GalT-KO pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of hCD47 on porcine blood vessels.

BACKGROUND: Despite recent progress in survival times of xenografts in non-human primates, there are no reports of survival beyond 5 days of histologically well-aerated porcine lung grafts in baboons. Here, we report our initial results of pig-to-baboon xeno-lung transplantation (XLTx). METHODS: Eleven baboons received genetically modified porcine left lungs from either GalT-KO alone (n = 3), GalT-KO/humanCD47(hCD47)/hCD55 (n = 3), GalT-KO/hD47/hCD46 (n = 4), or GalT-KO/hCD39/hCD46/hCD55/TBM/EPCR (n = 1) swine. The first 2 XLTx procedures were performed under a non-survival protocol that allowed a 72-hour follow-up of the recipients with general anesthesia, while the remaining 9 underwent a survival protocol with the intention of weaning from ventilation. RESULTS: Lung graft survivals in the 2 non-survival animals were 48 and >72 hours, while survivals in the other 9 were 25 and 28 hours, at 5, 5, 6, 7, >7, 9, and 10 days. One baboon with graft survival >7 days, whose entire lung graft remained well aerated, was euthanized on POD 7 due to malfunction of femoral catheters. hCD47 expression of donor lungs was detected in both alveoli and vessels only in the 3 grafts surviving >7, 9, and 10 days. All other grafts lacked hCD47 expression in endothelial cells and were completely rejected with diffuse hemorrhagic changes and antibody/complement deposition detected in association with early graft loss. CONCLUSIONS: To our knowledge, this is the first evidence of histologically viable porcine lung grafts beyond 7 days in baboons. Our results indicate that GalT-KO pig lungs are highly susceptible to acute humoral rejection and that this may be mitigated by transgenic expression of hCD47.

Upregulation of CD80 on glomerular podocytes plays an important role in development of proteinuria following pig-to-baboon xeno-renal transplantation - an experimental study.

We have previously reported that co-transplantation of the kidney with vascularized donor thymus from α-1,3-galactosyltransferase gene knockout pigs with an anti-CD154 with rituximab-based regimen led to improved xenograft survival in baboons with donor-specific unresponsiveness. However, nephrotic syndrome emerged as a complication in which the glomeruli showed mild mesangial expansion with similarities to minimal change disease (MCD) in humans. Since MCD is associated with CD80 expression in glomeruli and elevated urinary excretion, we evaluated a potential role for CD80 in xenograft nephropathy. Study 1 confirmed high urinary CD80 excretion in nephrotic animals with renal xenografts showing CD80 expression in glomeruli. In Study 2, baboons receiving xenografts received CTLA4-Ig once a week from the second postoperative week or no CTLA4-Ig. The non-CTLA4-Ig group developed severe proteinuria with modest mesangial expansion with high urinary excretion of CD80 and documented CD80 expression in glomerular podocytes. All of the recipients in non-CTLA4-Ig groups had to be euthanized before POD 60. In contrast, CTLA4-Ig group showed a marked reduction in proteinuria and survived significantly longer, up to 193 days. These results demonstrate that anti-CD80 targeted therapy represents a promising strategy for reduction of proteinuria following renal xeno-transplantation with improved survival.

Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) as a novel marker in T1 high-grade and T2 bladder cancer patients receiving neoadjuvant chemotherapy.

BACKGROUND: To investigate associations between dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) expression and survival in T1 high-grade or T2 bladder cancer patients treated with neoadjuvant chemotherapy. METHODS: The cohort under investigation comprised 44 patients who underwent neoadjuvant chemotherapy for pT1 high-grade or pT2N0M0 bladder cancer at our institution between 2002 and 2011. Immunohistochemical analysis was used to determine expression of DYRK2 in bladder cancer specimens obtained by transurethral resection before chemotherapy. Relationships between DYRK2 expression and both response to chemotherapy and survival in these patients were analyzed. RESULTS: DYRK2 expression was positive in 21 of 44 patients (47.7 %) and negative in 23 patients (52.3 %). In total, 20 of 21 DYRK2-positive cases showed complete response to neoadjuvant chemotherapy, whereas 11 of 23 DYRK2-negative cases did not show complete response. Sensitivity and specificity were 62.5 % and 91.7 %, respectively (P = 0.0018). In addition, disease-specific survival rate was significantly higher for DYRK2-positive patients than for DYRK2-negative patients (P = 0.017). In multivariate analysis, DYRK2 expression level was identified as an independent prognostic factor for disease-specific survival (P = 0.029). We also showed that DYRK2 mRNA expression was significantly higher in DYRK2-positive samples by immunohistochemistry than DYRK2-negative samples (P = 0.040). CONCLUSIONS: DYRK2 expression level may predict the efficacy of neoadjuvant chemotherapy for T1 high-grade and T2 bladder cancer.

[Marked efficacy of multimodality therapy for ureteral cancer producing granulocyte colony-stmimulating factor].

A 69-year-old man was admitted with the chief complaint of macroscopic hematuria. Computerized tomography (CT) and ureteroscopy showed right ureter cancer. Right nephroureterectomy and partial cystectomy were performed. Histological examination revealed urothelial carcinoma of ureter (Grade3, pT3, INFbeta, ly1). The patient underwent two courses of adjuvant chemotherapy with gemcitabine and cisplatin. Three months later, abdominal CT showed a mass in his right obturatorius area. The patient's white blood cell count was 34,140 cells/microl. Additionally serum analysis revealed high value of granulocyte colony stimulating factor (G-CSF), 596 pg/ml with no obvious focus. After being diagnosed with recurrent ureteral cancer producing G-CSF, the patient underwent secondary chemotherapy with gemcitabine and docetaxel. After three courses of chemotherapy, CT revealed a marked decrease in tumor size, and the value of G-CSF declined at 31 pg/nl. Subsequently, radiotherapy (60 Gy) was administered. The patient has been alive for 16 months.

Snail expression and outcome in T1 high-grade and T2 bladder cancer: a retrospective immunohistochemical analysis.

BACKGROUND: Neoadjuvant chemotherapy has been shown to have benefit in T1 high-grade or T2 bladder cancer. However, neoadjuvant chemotherapy fails in some patients. Careful patient selection for neoadjuvant chemotherapy is therefore needed. Several reports show that Snail is associated with resistance to chemotherapy. We hypothesized that Snail expression could predict survival in T1 high-grade and T2 bladder cancer patients treated with neoadjuvant chemotherapy. METHODS: The participants were 44 patients with T1 high-grade and T2 bladder cancer receiving neoadjuvant chemotherapy. Immunohistochemical analysis was used to determine Snail expression in specimens of bladder cancer obtained by transurethral resection before neoadjuvant chemotherapy. The relationships between Snail expression and patients' outcomes were analyzed. RESULTS: Snail expression was positive in 15 of the 44 patients (34.1%) and negative in 29 (65.9%). Disease-free survival was significantly shorter for the Snail-positive group than for the Snail-negative group (p = 0.014). In addition, disease-specific survival was also significantly shorter for the Snail-positive group than for the Snail-negative group (p = 0.039). In multivariate analysis, Snail expression level was identified as an independent prognostic factor for disease-specific survival (p = 0.020). CONCLUSIONS: The results indicate that Snail expression may predict poor outcome in T1 high-grade and T2 bladder cancer patients treated with neoadjuvant chemotherapy.

[Plasmacytoid variant of urothelial carcinoma of urinary bladder: a case report].

We reported the experience with a case of plasmacytoid variant of urothelial carcinoma of urinary bladder. A 75-year-old woman complained of gross hematuria. She was hospitalized to be diagnosed as the bladder tumor on abdominal CT. TUR-BT was performed and pathological finding was invasive urothelial carcinoma. But she refused radical cystectomy. 2 months later, she was hospitalized again with worsening hematuria. Simple cystectomy was performed. Histological examination revealed a plasmacytoid appearance of the infiltrating tumor cells. Immunohistochemical stains for lymphoid markers were negative. Those findings lead to the diagnosis of plasmacytoid variant of urothelial carcinoma. She died due to local recurrence for 1.5 months after simple cystectomy.

[A CASE OF THROMBOSIS OF THE PAMPINIFORM PLEXUS TREATED WITH ANTICOAGULANT THERAPY].

We describe a patient with thrombosis of the pampiniform plexus cured using heparin. A 40-year-old man was referred to our hospital with pain in the left scrotum. A physical examination revealed a painful, 20-mm long, beaded mass in the upper left paratesticular region. Magnetic resonance imaging and ultrasonography revealed 10-mm long thrombosis in the left pampiniform plexus, so intravenous heparin was started. The patient recovered well and was discharged on oral anticoagulation therapy after five days of hospitalization. The patient was completely asymptomatic, and ultrasonographic findings of the left testicle were normal at six months after starting treatment. We found 19 patients with thrombosis of the pampiniform plexus including the present patient, in the English and Japanese literature to date. Here, we review these 19 patients and discuss their clinical features.

Treatment Results of Transurethral Resection of the Prostate by Non-Japanese Board-Certified Urologists for Benign Prostate Hyperplasia: Analysis by Resection Volume.

INTRODUCTION: Transurethral resection of the prostate (TURP) is the gold standard for surgical treatment of benign prostatic hyperplasia (BPH), but it has complications such as bleeding and transurethral resection syndrome. The treatment results of TURP performed by non-Japanese board-certified urologists were examined, and the results were analyzed according to the resection volume to determine how much resection volume was suitable for non-Japanese board-certified urologists. MATERIALS AND METHODS: A total of 72 cases that underwent TURP for BPH at our hospital were examined. The patients were divided into three groups by resection volume (<20 g, 20-30 g, >30 g). The operators were five non-Japanese board-certified urologists. Various clinical factors were examined among the three groups before and after TURP. RESULTS: The average operation time and resection volume were significantly different among the groups. There were more transfused cases with greater resection volume. The changes from before to after TURP in the International Prostate Symptom Score, total prostate volume, and maximum flow rate were significantly different among the three groups, but the rates of these changes were not. CONCLUSIONS: In this study, TURP performed by non-Japanese board-certified urologists was relatively safe and achieved sufficient efficacy. Cases with resection volume less than 20 g appear the most appropriate for non-Japanese board-certified urologists.