Circulating miRNA panels for specific and early detection in bladder cancer.

Bladder cancer is the 9th leading cause of cancer death worldwide. The major problem in bladder cancer is primarily the high recurrence rate after drug treatment and resection. Although conventional screening methods, such as cystoscopy, urinary cytology and ultrasound sonography, have become widely used in clinical settings, the diagnostic performance of these modalities is unsatisfactory due to low accuracy or high invasiveness. Because circulating micro RNA (miRNA) profiles have recently been reported as an attractive tool for liquid biopsy in cancer screening, here, we performed global miRNA profiling of 392 serum samples of bladder cancer patients with 100 non-cancer samples and 480 samples of other types of cancer as controls. We randomly classified the bladder cancer and control samples into 2 cohorts, a training set (N = 486) and a validation set (N = 486). By comparing both controls, we identified specific miRNA, such as miR-6087, for diagnosing bladder cancer in the training and validation sets. Furthermore, we found that a combination of 7 miRNA (7-miRNA panel: miR-6087, miR-6724-5p, miR-3960, miR-1343-5p, miR-1185-1-3p, miR-6831-5p and miR-4695-5p) could discriminate bladder cancer from non-cancer and other types of tumors with the highest accuracy (AUC: .97; sensitivity: 95%; specificity: 87%). The diagnostic accuracy was high, regardless of the stage and grade of bladder cancer. Our data demonstrated that the 7-miRNA panel could be a biomarker for the specific and early detection of bladder cancer.

Kidney autotransplantation for the treatment of renal artery occlusion after endovascular aortic repair: a case report.

BACKGROUND: Unintentional renal artery occlusion after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm remains one of the most unfavorable complications. Renal salvage options include percutaneous transluminal renal artery angioplasty (PTRA) and open hepatosplenorenal bypass. However, the usefulness of kidney autotransplantation (AutoTx) remains unclear. CASE PRESENTATION: A 76-year-old woman with a right solitary kidney attributable to a left renal thromboembolism had previously undergone EVAR with a stent graft for an infrarenal aortic aneurysm, which led to ostial occlusion of the right renal artery. In addition, she had undergone PTRA and stenting. Two days before admission, she developed leg edema and hypertension, leading her to visit the hospital. Her serum creatinine level was 2.4 (baseline, 1.0) mg/dL. Acute kidney injury due to renal artery in-stent restenosis was suspected; re-angioplasty was attempted on day 2 of hospitalization, but was unsuccessful. Her renal function did not improve and anuria persisted; thus, hemodialysis was initiated on the same day. The right kidney size (8.6 cm) was preserved relative to her body size, with only mild cortical atrophy. Doppler ultrasonography and mercaptoacetyltriglycine scintigraphy revealed minimal but significant perfusion of the right kidney. Therefore, we considered that kidney perfusion was sustained and renal function could be reversed. On day 25 of hospitalization, right kidney AutoTx to the right iliac fossa was performed to reestablish adequate renal perfusion and reverse the need for dialysis. Soon after the procedure, the patient started passing urine. Her renal function improved; her serum creatinine level decreased to 1.0 mg/dL on day 33 of hospitalization. Hemodialysis was discontinued after the surgery. Zero-hour kidney biopsy showed only mild tubular injury, with neither tubular necrosis nor glomerular abnormalities. CONCLUSIONS: Kidney AutoTx can be performed for patients with renal artery in-stent occlusion after unsuccessful PTRA who previously underwent EVAR. Our case showed successful recovery of renal function nearly 1 month after renal artery occlusion, indicating that revascularization should be considered even if it is delayed, as the kidney might be perfused through collateral circulation.

Early post-transplant diagnosis of cytomegalovirus esophagitis in an ABO-incompatible kidney transplant recipients: A case report.

Cytomegalovirus (CMV) is a common infectious pathogen in kidney transplant patients. Here, we present a case of CMV esophagitis with antigenemia, that developed within 3 days of kidney transplantation, a timeline generally considered to be too early for development of a CMV infection. Intense immunosuppressive therapy for desensitization in ABO-incompatibility or in the presence of donor-specific antibody can increase the risk for significant opportunistic infection immediately after or even before transplantation.

Embryonic kidney function in a chronic renal failure model in rodents.

BACKGROUND: Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. METHODS: Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. RESULTS: We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. CONCLUSION: The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

Serum Aberrant N-Glycan Profile as a Marker Associated with Early Antibody-Mediated Rejection in Patients Receiving a Living Donor Kidney Transplant.

We determined if the serum N-glycan profile can be used as a diagnostic marker of antibody-mediated rejection (ABMR) in living donor kidney transplant (LKTx) recipients. Glycoblotting, combined with mass spectrometry, was used to retrospectively examine N-glycan levels in the postoperative sera of 197 LKTx recipients of whom 16 recipients had ABMR with or without T-cell-mediated rejection (TCMR), 40 recipients had TCMR, and 141 recipients had no adverse events. Multivariate discriminant analysis for prediction of ABMR was performed by inputting an ABMR event as an explanatory variable and sex, age, and serum N-glycan level as objective variables. The N-glycan score was calculated by multiplying the level of candidate objective variables by objective function values. The ABMR predictive performance of the N-glycan score was assessed by receiver operator characteristic curve and Kaplan-Meier curve analyses. The N-glycan score discriminated ABMR with 81.25% sensitivity, 87.85% specificity, and an area under the curve (AUC) of 0.892 that was far superior to that of preformed donor-specific antibody status (AUC, 0.761). Recipients with N-glycan-positive scores >0.8770 had significantly shorter ABMR survival than that of recipients with N-glycan-negative scores. Although the limitations of our study includ its small sample size and retrospective nature, the serum N-glycan score may contribute to prediction of ABMR.

Vascular endothelial growth factor-D-mediated blockade of regulatory T cells within tumors is induced by hematopoietic stem cell transplantation.

Lymphopenia-induced homeostatic proliferation of T cells after autologous hematopoietic stem cell transplantation (HSCT) skews the T cell repertoire by engaging tumor-associated Ags, leading to an induction of antitumor immunity. However, how HSCT alters the immunosuppressive microenvironment in the tumors is unknown. In this study, we first analyzed the kinetics of regulatory T cells (Tregs) in the tumors after syngeneic HSCT. Unexpectedly, the frequency of CD4⁺ cells expressing Foxp3 was increased in the spleens, whereas the frequency was clearly decreased in the tumors after HSCT. The origin of reconstituted CD4⁺ and Foxp3⁺ cells in the tumors was mainly from the expansion of transferred splenic T cells. Then, to examine the mechanism of Treg suppression after HSCT, we isolated CD11c⁺ cells from tumors. A large amount of Treg-inhibitory cytokine IL-6 was secreted from the CD11c⁺ cells in the tumors, but not in the spleens in the recipient mice. Furthermore, to understand what factor affects the activity of CD11c⁺ cells in the tumors after HSCT, we analyzed the expression of various cytokines/chemokines with mouse cytokine Ab arrays, and noticed that VEGF-D concentration was increased in the tumors in the early period after HSCT. The CD11c⁺ cells produced IL-6 in response to VEGF-D stimulation, and an administration of VEGF receptor-3 neutralizing Ab significantly suppressed the production of IL-6 from CD11c⁺ cells accompanied with the increase of Tregs in the tumors of HSCT recipients. Autologous HSCT creates an environment that strongly supports the enhancement of antitumor immunity in reconstituted lymphopenic recipients through the suppression of Tregs.

Pharmacokinetic analysis of cyclosporine in a renal transplant recipient with congenital absence of the portal vein.

Here we report therapeutic drug monitoring of cyclosporine in a kidney transplant recipient lacking enterohepatic circulation. The patient developed steroid-resistant nephrotic syndrome at age 14 years, and was medicated with an oral cyclosporine microemulsion. However, her cyclosporine trough level was unexpectedly elevated, and subsequent investigations showed that she was deficient in drug metabolism as a result of the congenital absence of the portal vein. Her renal function gradually decreased and she became dialysis-dependent at the age of 21 years, and kidney transplantation was planned. Based on pretransplant therapeutic drug monitoring, we started cyclosporine microemulsion at half of the conventional dosage. After transplantation, the dosage was successfully adjusted to achieve a target trough level. The post-transplant course was stable with no symptoms of rejection or cyclosporine-associated nephrotoxicity.

Suppression of Tregs by anti-glucocorticoid induced TNF receptor antibody enhances the antitumor immunity of interferon-α gene therapy for pancreatic cancer.

We have reported that interferon (IFN)-α can attack cancer cells by multiple antitumor mechanisms including the induction of direct cancer cell death and the enhancement of an immune response in several pancreatic cancer models. However, an immunotolerant microenvironment in the tumors is often responsible for the failure of the cancer immunotherapy. Here we examined whether the suppression of regulatory T cells (Tregs) within tumors can enhance an antitumor immunity induced by an intratumoral IFN-α gene transfer. First we showed that an intraperitoneal administration of an agonistic anti-glucocorticoid induced TNF receptor (GITR) monoclonal antibody (mAb), which is reported to suppress the function of Tregs, significantly inhibited subcutaneous tumor growth in a murine pancreatic cancer model. The anti-GITR mAb was then combined with the intratumoral injection of the IFN-α-adenovirus vector. The treatment with the antibody synergistically augmented the antitumor effect of IFN-α gene therapy not only in the vector-injected tumors but also in the vector-uninjected tumors. Immunostaining showed that the anti-GITR mAb decreased Foxp3(+) cells infiltrating in the tumors, while the intratumoral IFN-α gene transfer increased CD4(+) and CD8(+) T cells in the tumors. Therefore, the combination therapy strongly inclined the immune balance of the tumor microenvironment in an antitumor direction, leading to a marked systemic antitumor effect. The CCR5 expression on Tregs was downregulated in the antibody-treated mice, which may explain the decrease of tumor-infiltrating Tregs. The combination of Treg-suppression by GITR mAb and the tumor immunity induction by IFN-α gene therapy could be a promising therapeutic strategy for pancreatic cancer.

Therapeutic effects of microRNA-582-5p and -3p on the inhibition of bladder cancer progression.

Many reports have indicated that the abnormal expression of microRNAs (miRNAs) is associated with the progression of disease and have identified miRNAs as attractive targets for therapeutic intervention. However, the bifunctional mechanisms of miRNA guide and passenger strands in RNA interference (RNAi) therapy have not yet been clarified. Here, we show that miRNA (miR)-582-5p and -3p, which are strongly decreased in high-grade bladder cancer clinical samples, regulate tumor progression in vitro and in vivo. Significantly, the overexpression of miR-582-5p or -3p reduced the proliferation and invasion of UM-UC-3 human bladder cancer cells. Furthermore, transurethral injections of synthetic miR-582 molecule suppressed tumor growth and metastasis in an animal model of bladder cancer. Most interestingly, our study revealed that both strands of miR-582-5p and -3p suppressed the expression of the same set of target genes such as protein geranylgeranyltransferase type I beta subunit (PGGT1B), leucine-rich repeat kinase 2 (LRRK2) and DIX domain containing 1 (DIXDC1). Knockdown of these genes using small interfering RNA (siRNA) resulted in the inhibition of cell growth and invasiveness of UM-UC-3. These findings uncover the unique regulatory pathway involving tumor suppression by both strands of a single miRNA that is a potential therapeutic target in the treatment of invasive bladder cancer.

Asymptomatic post-transplant lymphoproliferative disorder diagnosed at one year protocol renal allograft biopsy.

Post-transplant lymphoproliferative disorder (PTLD) is a neoplastic complication with a potentially fatal outcome that develops as a consequence of immunosuppression, and is mainly associated with Epstein-Barr virus (EBV) infection. A 70-year-old woman underwent a live unrelated, ABO-incompatible renal transplant for end-stage renal disease. One year after transplantation, protocol biopsy revealed pathological changes indicative of the histological subtype of 'early lesions of PTLD' according to the World Health Organization classification, while the patient showed no clinical signs or symptoms. The patient was finally diagnosed with EBV-positive PTLD by in situ hybridization for EBER (EBV-encoded RNA), and was successfully treated based on the reduction of immunosuppression. Protocol biopsy within the first post-transplant year is the only diagnostic measure to detect asymptomatic early PTLD, which allows for early intervention and leads to better outcomes.

Subcutaneous pathway diversion for peritoneal dialysis catheter salvage.

Peritoneal dialysis (PD) catheter-related infection is still is the most troublesome problem for continuation of PD without the need to switch to hemodialysis. We have been performing subcutaneous pathway diversion (SPD) as a surgical treatment for refractory exit-site and tunnel infection (ESTI). To clarify the efficacy and safety of SPD, we conducted a retrospective study. From August 2008 to August 2013, 30 SPDs were performed in 26 patients (16 men, 10 women; mean age: 58 +/- 13 years; 54% with diabetes; mean body mass index: 23.9 +/- 3.5 kg/ m2). The reasons for the SPDs were ESTI in 25 patients, and outer cuff extrusion in 1 patient. All patients resumed PD immediately after SPD, and the duration of hospitalization was 11.7 +/- 10.1 days. After SPD, one patient experienced a dialysate leak, and another patient experienced a mild subcutaneous hematoma. Another 4 patients developed exit-site infection (ESI) and underwent a second SPD. Of those 4 patients, 3 presented with another ESI unrelated to the first episode, and all developed an ESI after 6 months or more. The remaining 20 patients experienced no such complications. Furthermore, catheter survival after SPD was 17.4 +/- 13.4 months. To eradicate ESTTI we suggest that SPD, which does not require catheter removal or interruption of PD, is useful compared with the unroofing technique or catheter removal.

Risk factors associated with inadequate veins for placement of arteriovenous fistulas for hemodialysis.

An arteriovenous fistula (AVF) between the radial artery and cephalic vein at the wrist is the preferred type of hemodialysis vascular access. However, in the practice of access placement, we are aware that some patients fail to form the standard forearm radial-cephalic AVF, owing to naturally small veins or acquired abnormal lesions of the veins. To identify the risk factors for failure to form the standard AVF, we examined 305 consecutive patients who underwent first-time access surgery at our hospital from January 2006 to December 2010. We compared the patients' characteristics between those having normal vessels and successfully forming the standard AVF, and those having apparently abnormal vessels and thus forming alternative types of access instead. Histories of major and minor surgery were specifically evaluated, assuming that surgical procedures in the past could potentially damage the superficial veins. We created 207 standard and 98 alternative accesses during the period and found that significantly more patients with alternative accesses (31 %) had undergone major surgery of a variety of specialties, in comparison with those with the standard AVF (15.0 %). Multivariate logistic analysis revealed that a history of major surgery (OR = 2.39, 95 %CI 1.29-4.47, p = 0.006) and female gender (OR = 1.87, 95 %CI 1.10-3.20, p = 0.02) were independent risk factors associated with failure to construct the standard AVF. Our results indicate that previous surgery can damage the superficial veins and cause venous abnormality, which makes construction of the standard AVF difficult. We propose that care should be taken to preserve the superficial veins when patients for whom dialysis therapy is a future possibility undergo surgical procedures, especially invasive ones.

Irreversible immunoexpression of matrix metalloproteinase-9 in proximal tubular epithelium of renal allografts with acute rejection.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is the most important member of the MMP family responsible for the development and progression of various renal diseases. Our study aims to investigate the localization of MMP-9 in human renal allografts and to assess whether MMP-9 immunostaining is contributory to detect pathological change in renal biopsy. METHODS: We examined 150 renal allograft biopsies (48 baseline and 102 follow-up) from 49 transplants and analyzed the associations of clinical and histopathological data with the MMP-9 staining intensity using a semi-quantitative scoring. RESULTS: MMP-9 immunostaining in proximal tubule epithelium was negative before transplantation, but positive in biopsies with episodes, particularly with acute cellular rejection (ACR) and acute calcineurin inhibitor (CNI) toxicity. Tubulitis was the most significant association factor (p < 0.0001) with increased MMP-9 staining intensity. The expression in proximal tubules remained augmented in allografts recovered from ACR episodes, while it was disappeared or diminished in those recovered from acute CNI toxicity or ischemia/reperfusion effects. CONCLUSION: These findings suggest the necessary participation of MMP-9 in the pathogenesis of tubulitis and the subsequent stage of pathogenesis in ACR. Up-regulation of MMP-9 expression in the proximal tubule could be a new indicator of tubular injury and a predictive factor for the prognosis of renal allograft.

Kidney function, albuminuria and cardiovascular risk factors in post-operative living kidney donors: a single-center, cross-sectional study.

BACKGROUND: Mortality and renal or cardiovascular prognosis in living kidney donors (LKDs) has been reported to be as same as the general population; however, it is known that the prevalence of hypertension, albuminuria and metabolic syndrome increases after donation. At present, data from Japanese donors are scarce and as a result the actual medical status of LKDs remains unclear. To evaluate cardiovascular disease (CVD) risk factors in Japanese LKDs, we conducted a cross-sectional study on LKDs at our tertiary care hospital and clinic. METHOD: Thirty-six out of 63 LKDs who underwent kidney donation at the kidney disease center of the St. Marianna University Hospital were enrolled. The kidney function, albuminuria, and CVD risk factors including hypertension, dyslipidemia, hyperuricemia, glucose intolerance (GI) and obesity were cross-sectionally investigated. RESULTS: The kidney function by inulin clearance was 55.2 ± 10.3 ml/min/1.73 m(2) on average, indicating that 63.9% of LKDs were categorized into chronic kidney disease (CKD) stage 3 after donation. Albuminuria developed in 16.7%. Blood pressure (BP) was not elevated after donation, but ambulatory BP monitoring revealed that 39.4% of LKDs were categorized as having non-dipper type BP. GI was shown in 25% of LKDs. Prevalence of dyslipidemia and hyperuricemia were 41.7% and 27.8%, respectively. Body mass index was not significantly changed after donation. Seven LKDs (19.4%) were diagnosed with metabolic syndrome. CONCLUSION: Many Japanese LKDs were experiencing decreased kidney function corresponding to CKD stage 3. They also had a significant but not lower prevalence of albuminuria and CVD risk compared to the general Japanese population. LKDs should be followed closely with special attention to the management of renal and CVD risk factors.

Synchronous bilateral urothelial cancer in a kidney recipient.

Synchronous bilateral urothelial cancer is very rare. We report a 25-year-old male kidney recipient with Alport syndrome who developed bilateral synchronous urothelial cancer after transplantation. At the age of 16 this patient was referred to our clinic for a kidney transplantation. A living related donor kidney transplantation was performed with cyclosporin-based quadruple immunosuppression. He experienced no acute rejection and his graft function was excellent after transplantation. Nine years after transplantation, he complained of asymptomatic gross hematuria and was diagnosed as having a bilateral urothelial cancer in the native upper urinary tracts. A bilateral total nephroureterectomy was undertaken, and the postoperative pathological diagnosis was advanced bilateral urothelial carcinoma. The patient received adjuvant gemcitabine plus cisplatin chemotherapy at a cisplatin dosage reduced by 50%. After 4 years of follow-up, he is alive with a functioning graft and no evidence of recurrence.

[Case of renal parenchymal malakoplakia presenting as sepsis and treated with nephrectomy].

Malakoplakia is a rare chronic inflammatory condition characterized by defective macrophage function, most of which involve the genitourinary tract, and renal parenchymal involvement is uncommon. We present a case of malakoplakia affecting renal parenchyma. A 46-year-old woman with pyrexia and jaundice was referred to our department. Abdominal enhanced CT scan revealed a left pyelonephritis with ureteral stone and bilateral renal abscesses. Despite the insertion of a left ureteral stent and administration of antibiotics, the patient showed persistent high fever and elevated CRP, and no obvious improvement in clinical and imaging data. In view of the limited effectiveness of the conservative treatment in this case, we decided to perform left nephrectomy. The diagnosis of malakoplakia was made based on the histopathological findings of von Hansemann cells and Michaelis-Guttmann bodies detected in the nephrectomy specimen. She is clinically healthy up to the present (50 months after surgery) with normal clinical indicators and CT findings.

Mycophenolate mofetil-induced agranulocytosis in a renal transplant recipient.

A 27-year-old woman underwent living kidney transplantation from her mother. She received basiliximab, tacrolimus, mycophenolate mofetil (MMF), and a corticosteroid. Before transplantation, her complete blood count and white cell differential were normal. On about the 70th postoperative day (POD 70), her white blood cell (WBC) count began to decrease. On POD 113, her WBC count was 2800/µL. There was no evidence of viral infection, other systemic infection or malignancy. Drug-induced neutropenia, especially MMF-induced neutropenia, was suspected, and the dosage of MMF was reduced. However, the neutrophil count fell to 0/µL within 2 weeks. We further reduced the dosage of MMF and administered granulocyte-colony stimulating factor (G-CSF), which only temporarily increased the neutrophil count. Then, MMF was discontinued and switched to azathioprine, resulting in recovery of neutrophil count without subsequent rejection. MMF-induced neutropenia frequently occurs and should be monitored not only by WBC count but also by white cell differential count, since early discontinuation is the key to successful resolution of neutropenia. Switching from MMF to azathioprine or administration of G-CSF with or without MMF discontinuation might be options for treatment to avoid subsequent rejection.

Internal filtration in dialyzers with different membrane permeabilities.

Over the last decade, hemodialysis with enhanced internal filtration (IF) has been investigated as an alternative to conventional dialysis. Several factors affect IF, including the geometry and permeability of hollow-fiber dialyzers. Although various studies have been performed, the association between IF and membrane permeability has not been fully examined because of the difficulty in measuring IF. Therefore, in this study, we set up an experimental circuit and attempted to directly measure IF as well as membrane permeability in five dialyzers. In the circuit, we placed two dialyzers of the same type in series, and a special sampling port between them, thereby making it possible to determine IF by measuring the extent to which blood was concentrated between the two dialyzers. We showed that a significant amount of IF occurred in this tandem-dialyzer circuit, ranging from 23.5 to 100 ml/min, which increased linearly with increasing membrane permeability. We also showed that membrane permeability was reduced in the first dialyzer to a greater extent than in the second one after four hours of circulation, suggesting that filtration caused substantial membrane fouling. In this study we practically demonstrated that membrane permeability is highly relevant to the phenomenon of IF.

Brachial-brachial autogenous arteriovenous fistula in a dialysis patient with Staphylococcus aureus bacteremia.

As the number of patients on hemodialysis increases, there will also be an increase in the number of patients with inadequate superficial veins for the creation of an autogenous arteriovenous fistula (AVF). In those patients, medical devices such as vascular prostheses or tunneled-cuffed catheters are necessary to maintain dialysis access. However, these devices are frequently associated with bacterial infection. We recently encountered a dialysis patient who underwent tunneled-cuffed catheter insertion because of the lack of usable superficial veins for autogenous access, and this patient subsequently developed catheter-related Staphylococcus aureus bacteremia with multiple metastatic infections. Despite immediate removal of the catheter, the infection persisted over an extended period, which was a condition precluding the further use of catheters or other prosthetic materials. To handle this situation, we utilized the deep brachial vein to construct an autogenous AVF. After ligating numerous branches, the vein was anastomosed to the brachial artery and then transposed to the subcutaneous space. The newly constructed autogenous AVF, which successfully kept the patient free from foreign materials, greatly contributed to the relief of persistent infection. Although the brachial vein is rarely used for AVF creation, we suggest that it can serve as an option to create an alternative AVF in a patient with inadequate superficial veins.

A case report: primary extragonadal yolk sac tumor of penile shaft in a 2-year-old child.

A 2-year-old boy, who had the chief complaints of penile swelling and pain, was brought to the hospital by his mother. Penile contusion/trauma was suspected and he was admitted the same day to undergo emergency surgery to eliminate hematoma. The surgery revealed that the origin of the bleeding was not trauma but a tumor lesion of the penile shaft. It was histopathologically identified as a yolk sac tumor and no tumorous lesions were found except that in the penis. Therefore the patient was diagnosed as definitely having a yolk sac tumor originating in the penis. The patient received four cycles of cisplatin, etoposide and bleomycin treatment as adjuvant chemotherapy. Although it was impossible to completely resect the tumor, cisplatin, etoposide and bleomycin chemotherapy was effective and a complete response was achieved. We plan to carefully monitor the patient in the future.