High-dose mizoribine combined with calcineurin inhibitor (cyclosporine or tacrolimus), basiliximab and corticosteroids for renal transplantation: A Japanese multicenter study.

OBJECTIVE: To evaluate the utility and safety of high-dose mizoribine combination therapy using cyclosporine and tacrolimus as calcineurin inhibitors in patients undergoing kidney transplant. METHODS: The present study enrolled 156 patients who received kidney transplants in 18 institutions between 2009 and 2013. ABO-incompatible and/or pre-sensitized recipients were excluded. Immunosuppression used cyclosporine (88) or tacrolimus (68) as a calcineurin inhibitor, and the dosage was adjusted based on blood concentrations. Mizoribine was started at 6 mg/kg/day, and the target trough level was 1-2 ng/mL. Primary efficacy end-points of this study were 2-year patient survival, 2-year graft survival and the acute rejection rate within 2 years after transplantation. RESULTS: The 2-year patient and graft survival rates in the cyclosporine group were 98.9% and 94.3%, respectively, whereas those in the tacrolimus group were 100% and 98.5%, respectively, with no significant difference between groups. Rates of onset of rejection during the observation period were also equivalent, at 22.7% in the cyclosporine group and 17.6% in the tacrolimus group. Furthermore, groups showed no significant differences in transplanted renal function. No notable differences in adverse events were observed between groups. CONCLUSIONS: A regimen of high-dose mizoribine in combination with calcineurin inhibitors basiliximab, and corticosteroids can provide effective immunosuppression while lowering the rate of cytomegalovirus infection in kidney transplant patients.

Significance of baseline bone markers on disease progression and survival in hormone-sensitive prostate cancer with bone metastasis.

PURPOSE: This study evaluated the baseline patient characteristics associated with the time to biochemical progression and overall survival in patients who participated in a phase II trial on zoledronic acid combined with the initial androgen-deprivation therapy for treatment-naïve bone-metastatic prostate cancer. METHODS: Patients received zoledronic acid 4 mg intravenously every 4 weeks for up to 24 months, concomitantly started with bicalutamide 80 mg orally every day and goserelin acetate 10.8 mg subcutaneously every 12 weeks. RESULTS: A total of 53 Japanese patients were enrolled between July 2008 and April 2010, and 52 patients were evaluable. Median follow-up period was 41.6 months. Updated median time to biochemical progression was 25.9 months (95 % confidence interval 14.5-49.9). Higher serum bone-specific alkaline phosphatase was an independent risk factor for time to biochemical progression based on multivariate analysis (hazard ratio 6.51; 95 % confidence interval 2.71-15.62; P < 0.001). Median time to biochemical progression for patients with serum bone-specific alkaline phosphatase level higher than 26 µg/L was 12.7 months. Multivariate analysis indicated that higher serum C-terminal telopeptide of type I collagen independently increased the risk of death (hazard ratio 9.62; 95 % confidence interval 2.11-43.89; P = 0.003). Median overall survival for patients with serum C-terminal telopeptide of type I collagen level higher than 8.0 ng/ml was 31.1 months. CONCLUSIONS: Baseline bone markers can be useful as predictors for disease progression and survival time in patients with bone metastasis from treatment-naïve prostate cancer treated with upfront zoledronic acid concomitantly started with androgen-deprivation therapy.

[Cyst of the tunica albuginea testis : a case report].

This report concerns a case of cyst of the tunica albuginea testis in a 74-year-old man, who presented with a painful swelling of right scrotal contents. Magnetic resonance imaging (MRI) and ultrasonography revealed a cystic mass on the surface of the right testicle. We performed resection of the cystic wall. The histological findings indicated cyst of the tunica albuginea testis. In this series, we collected 30 cases in the Japanese literature.

Phase II trial of zoledronic acid combined with androgen-deprivation therapy for treatment-naïve prostate cancer with bone metastasis.

BACKGROUND: The efficacy of zoledronic acid in patients with treatment-naïve prostate cancer is unclear. We conducted a phase II study to investigate the benefits of combined zoledronic acid and androgen deprivation therapy in treatment-naïve prostate cancer with bone metastasis. The primary endpoint was skeletal-related event-free survival at 24 months. METHODS: Subjects were treatment-naïve patients with histologically confirmed adenocarcinoma of the prostate and radiological evidence of bone metastasis. Treatment consisted of bicalutamide 80 mg daily, goserelin acetate 10.8 mg every 12 weeks, and zoledronic acid 4 mg every 4 weeks. Zoledronic acid was continued for 24 months. RESULTS: Of the patients enrolled between July 2008 and April 2010, 52 were included in the analyses. The median age of the patients was 72 years. The median baseline prostate-specific antigen level was 249.4 ng/mL. The median follow-up period was 33.3 months. The 24-month skeletal-related event-free survival rate was 84.4 % (95 % confidence interval 71.2-91.9). The median time to prostate-specific antigen progression was 25.9 months (95 % confidence interval 14.7-36.3). The median overall survival time was not reached. Improvement in pain or maintenance of no pain during the first 12 weeks was observed in 70 % of patients and the extent of bone disease was decreased in 10 % of patients at 12 months. Grade 3 osteonecrosis of the jaw was observed in three patients (5.8 %). CONCLUSION: Zoledronic acid concomitant with androgen deprivation therapy as initial treatment in patients with treatment-naïve prostate cancer with bone metastasis resulted in an encouraging skeletal-related event-free survival rate at 24 months.

[Metastatic tumor of the spermatic cord from gastric cancer: a case report].

A 66-year-old man presented with a painless swelling of left scrotal contents. We performed left inguinal orchiectomy and left inguinal lymphnode dissection. Histopathological examination revealed spermatic cord metastases from gastric carcinoma. We collected 44 cases of metastatic tumor of the spermatic cord from gastric cancer in the Japanese literature.

[Granulocyte-colony stimulating factor-producing urothelial carcinoma of the renal pelvis : a case report].

A 43-year-old woman was referred to our hospital for fever, general fatigue and left flank abdominal pain during the last two weeks. A blood test showed severe inflammation, and computed tomography (CT) study of the abdomen with intravenous contrast revealed swelling and irregular enhancement in the upper left kidney. Initially, we diagnosed it as xanthogranulomatous pyelonephritis and treated it with antibiotics. A percutaneous renal biopsy was performed because the white blood cell count remained elevated after the treatment. Histopathologic examination revealed a carcinoma. Therefore, we performed left nephroureterectomy. The diagnosis was high grade urothelial carcinoma of the renal pelvis, and it stained positive by immunohistochemical staining using anti-granulocyte-colony stimulating factor (G-CSF). The serum G-CSF level was also elevated on the same day. The patient received chemotherapy but, died 9 months after surgery. A G-CSF-producing urothelial carcinoma of the renal pelvis is known to have a poor prognosis in the Japanese literature. It is important to closely monitor a G-CSF producing tumor, when a patient shows severe inflammation, but no infection.

Giant adrenal pseudocyst removed using robot-assisted surgery.

Introduction: Adrenal cysts are relatively rare and often asymptomatic. Surgical treatment is indicated for symptomatic cases with cysts >6 cm, suspected bleeding, and those that cannot be distinguished from malignant illness based on imaging findings. There have often been cases of giant cysts that were difficult to treat using laparoscopic surgery. Case presentation: A 39-year-old woman presented with fever and upper abdominal pain. Abdominal computed tomography and magnetic resonance imaging revealed a 95 × 80-mm left adrenal cyst. As malignant disease could not be ruled out, and the patient was symptomatic, we opted for robot-assisted left adrenalectomy. The pathological findings indicated an adrenal pseudocyst. Conclusions: This is the second report of the successful robot-assisted removal of a giant adrenal cyst.

Prognosis of Patients Receiving Chemotherapy for Metastatic Upper Tract Urothelial Carcinoma Compared With Metastatic Urinary Bladder Cancer.

BACKGROUND/AIM: The treatment strategy for metastatic upper tract urothelial carcinoma (mUTUC) is currently based on the evidence from metastatic urinary bladder cancer (mUBC). However, some reports have shown that the outcomes of UTUC differ from those of UBC. Therefore, we retrospectively analyzed the prognosis of patients with mUBC and mUTUC treated with first-line platinum-based chemotherapy. PATIENTS AND METHODS: Patients who underwent platinum-based chemotherapy at the Kindai University Hospital and affiliated hospitals between January 2010 and December 2021 were included in the study. There were 56 patients with mUBC and 73 with mUTUC. Kaplan-Meier curves were used to estimate progression-free (PFS) and overall (OS) survival. Multivariate analyses were performed using Cox proportional hazards model to predict prognostic factors. RESULTS: The median PFS was 4.5 and 4.0 months for the mUBC and mUTUC groups, respectively (p=0.094). The median OS was 17.0 months for both groups (p=0.821). The multivariate analysis showed no prognostic factor for PFS. The multivariate analysis for OS showed that younger age at the initiation of chemotherapy and immune checkpoint inhibitor use after first-line therapy were significantly associated with better OS. CONCLUSION: Platinum-based chemotherapy had a similar effect on patients with mUTUC and mUBC.

Carvedilol protects tubular epithelial cells from ischemia-reperfusion injury by inhibiting oxidative stress.

OBJECTIVES: Renal ischemia-reperfusion injury (IRI), leading to acute kidney injury, is a frequent complication with renal transplantation and it is associated with graft function. Its pathogenesis involves ischemia, vascular congestion and reactive oxygen metabolites. Carvedilol is an antihypertensive drug with potent anti-oxidant properties. In this study we investigated the protective effects of carvedilol in a rat renal IRI model. METHODS: Twenty-four rats were randomized into sham, untreated control and carvedilol (2 mg/kg 30 min before surgery and 12 hr after reperfusion) treatment groups and were subjected to 60 min of left renal ischemia followed by reperfusion at 24, 48, 96 and 168 hr. RESULTS: Treatment with carvedilol significantly decreased plasma creatinine levels after IRI (up to 168 hr) compared to controls (P < 0.001), suggesting an improvement in renal function. Histopathological analysis revealed decreased IRI-induced damage in kidneys from carvedilol-treated rats. A significant increase in the expression levels of Cu/Zn superoxide dismutase and reduction of 8-hydroxydeoxyguanosine and apoptosis levels (P < 0.005) suggested a protective effect after treatment with carvedilol. CONCLUSIONS: Our findings suggest that carvedilol ameliorates IRI resulting in improved renal function.

Pathological Findings in Male Patients With Anti-N-methyl-d-Aspartate Receptor Encephalitis.

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune encephalitis. The disease predominantly affects women (1:5-1:10), with only 3 reports of autopsy findings in women being published to date. The present study reports findings from the first autopsy performed on a man with anti-NMDAR encephalitis. The patient had some scattered lesions in the limbic system with neuronal loss, gliosis, and microglial activation. The temporal and frontal cortices showed additional patchy demyelination. T-lymphocyte infiltration was detectable in the fusiform gyrus lesion. These findings were partly similar to those reported in female patients. Although clinical differences based on the sex of the patient are reported for this disease, the observed pathological similarities potentially help to establish common therapeutic strategies for all patients. Severe testicular damage was additionally observed in the male patient in this study. Biopsy-proven severe testicular damage was also confirmed in another, previously fertile man who became azoospermic. Moreover, serum follicle-stimulating hormone levels, which often increased in response to disturbed spermatogenesis, were elevated, and testosterone/luteinizing hormone ratio reflecting Leydig cell function was low in all 5 male patients in this study. Overall, these findings suggest similar brain pathology in patients of both sexes and severe testicular damage in male patients.

Organic and functional evaluation of atherosclerosis in renal transplant recipients.

We evaluated atherosclerotic lesions in 18 renal transplant recipients in whom the grafts remained functional after transplantation from living donors at the Sakai Hospital, Kinki University School of Medicine. In each patient, the mean intima-media thickness of the bilateral common carotid arteries (mIMT) was measured by ultrasonography. In the pulse wave test, the ankle brachial index (ABI) and the brachial-ankle pulse wave velocity (ba-PWV) were measured. In 12 (66.7%) of the 18 renal transplant recipients examined, the mean value of ba-PWV was higher than the mean plus 1 standard deviation (SD) in the corresponding Japanese age group. A significant correlation was noted between mIMT (an organic indicator of atherosclerosis) and ba-PWV (a functional indicator of atherosclerosis). The age at the time of test, blood pressure and the pre-transplant duration of hemodialysis had a significant positive correlation with both mIMT and ba-PWV. Thus in renal transplant recipients, organic evaluation of atherosclerosis correlated significantly with its functional evaluation. Both evaluations were proven to be reliable. Many of the renal transplant recipients had complications from atherosclerosis, and several factors seemed to be involved in the onset of atherosclerosis in these patients. Among others, the duration of hemodialysis before transplant correlated particularly closely with post-transplant onset of atherosclerosis, and it seems likely that persistent uremia can stimulate the progression of atherosclerosis.

Zoledronic acid combined with androgen-deprivation therapy may prolong time to castration-resistant prostate cancer in hormone-naïve metastatic prostate cancer patients - A propensity scoring approach.

OBJECTIVE: To clarify the oncological benefit of zoledronic acid for hormone-naïve metastatic prostate cancer, patient outcome of androgen deprivation therapy with zoledronic acid (ADT + Z) and androgen deprivation therapy alone (ADT) was compared. METHODS: Fifty-two patients with pathologically confirmed metastatic prostate cancer were prospectively enrolled and treated with combined androgen blockade (goserelin and bicalutamide) with zoledronic acid (4 mg every 4 weeks for 24 months). A propensity score-match with logistic regression analysis was applied to select 50 pair-matched cohorts (both from ADT + Z and from historical control cohorts who had undergone ADT alone), and patient outcomes were compared. RESULTS: Patients with ADT + Z had significantly longer time to progression (TTP) than those with ADT (median TTP; 24.2 vs. 14.0 months, p = 0.0092), while no significant difference of overall survival between two groups (p = 0.1502). Multivariate analysis for biochemical recurrence revealed treatment with ADT was the sole independent prognostic factor (HR: 1.724, 95% CI: 1.06-2.86, p = 0.0297). CONCLUSION: Combination of zoledronic acid with ADT may prolong time to castration resistant prostate cancer.

A pilot study of acotiamide hydrochloride hydrate in patients with detrusor underactivity.

AIM: To investigate the clinical efficacy of acotiamide hydrochloride hydrate in patients with detrusor underactivity. METHODS: We measured the post-void residual urinary volume in 19 patients with underactive bladders. All these patients had been under treatment with distigmine bromide and were prescribed acotiamide hydrochloride hydrate at a dose of 100 mg three times daily for 2 weeks. RESULTS: Compared with the post-void residual urinary volume value at baseline (161.4±90.0 mL) a statistically significant reduction was observed at the end of treatment (116.3±63.1 mL) (P=0.006). The drug was generally well tolerated by the majority of patients. CONCLUSION: Maybe, acotiamide hydrochloride hydrate showed clinical efficacy in patients with underactive bladders and may, therefore, be used alternatively in patients who do not respond sufficiently to distigmine bromide.

[Evaluation of the management of blunt renal trauma and indication for surgery].

OBJECTIVES: Appropriate management of renal trauma is still controversial. Many of the patients have minor injuries and conservative treatment can achieve excellent outcomes without any complications. For major injuries of deep lacerations or ruptures, we have been performing early surgical treatment to salvage the kidney in the selected cases after the precise evaluation of the injury. To obtain the optimal management options, we evaluated the clinical results of our procedures. PATIENTS AND METHODS: We conducted a retrospective study, which included 106 cases of blunt renal trauma with evident etiology over the past 22 years and 9 months. The severity of the injury was evaluated mainly by CT scanning. The indication of renal exploration included persistent renal bleeding, large hematoma around the kidney, dislocated fragments, nonviable tissue, massive urinary extravasation and vascular injury. With the patients who required an operation, we first controlled the bleeding by clamping the hilar vessels. Then, the final decision whether to repair or remove the kidney was made based on the direct inspection of the injured kidney after the complete removal of the hematoma. The severity of renal trauma was classified by the classifications found in The Organ Injury Committee of the American Association for the Surgery of Trauma. RESULTS: Sixty-three patients were managed conservatively without any interventions, while 22 surgical repairs and 21 nephrectomies were performed. Of the 63 patients, 35 patients (81.4%) were operated on within 2 days after the injury. Judging from systolic blood pressure, red cell count, blood loss during surgery and transfusion requirements, surgically treated patients were more severely injured than conservatively treated patients. And nephrectomized patients than surgically repaired patients. All the surgically repaired cases were confirmed to have preserved renal functions postoperatively. In all of the 50 patients with Grade I injuries, conservative treatment was successful. Eight out of the 19 Grade II and III cases, who were indicated for kidney exploration because of multiple lacerations or considerable bleeding, were also successfully repaired. Localized hematoma with no urine leakage, even when it was large, settled spontaneously without complication. For the 37 Grade IV and V injuries, including 4 cases with hilar injuries, we implemented conservative procedures on 2 patients, surgical repair on 14 patients and nephrectomy on 21 patients. In the conservatively treated cases, one deep laceration with relatively large, but localized, hematoma, and minimal urine extravasation healed spontaneously. Atrophy of the segment and hypertension developed in the other ruptured kidney with dislocated fragments, large hematoma and urine leakage. This kidney, which also required later surgical exploration, did have good parenchymal blood flow. Hilar injury cases were all resulted in nephrectomy. CONCLUSION: In most of our cases the indication for surgical exploration or nephrectomy based on our criteria seemed to be properly decided. Several cases, though, might have received overtreatment. Recent advances in evaluations and strategies of renal trauma have decreased the need for surgical exploration. This may have overreached the indication for conservative management. Severely injured kidneys may be managed conservatively because in most cases bleeding settles after the full formation of large hematoma within the Gerota's fascia. In such cases, though, no one can predict whether the injury will heal spontaneously or not, and, moreover, whether a complication will develop or not. We think that the optimal management of the patient requires an accurate evaluation of the injured kidney. Therefore the indication for surgical exploration should be made based on the degree of the injury.

Procalcitonin as a useful marker to decide upon intervention for urinary tract infection.

BACKGROUND: Because the use of procalcitonin has been advocated as a marker of bacterial infection, this study was carried out to determine the usefulness of serum PCT as an early marker to decide upon intervention for urinary tract infection. METHODS: The subjects were 68 patients with urinary tract infection (UTI) in whom we measured serum procalcitonin concentration at the start of treatment. RESULTS: There were 47 patients with nonobstructed UTI and 21 with obstructed UTI. All patients with obstructed UTI were subjected to intervention. There were significant differences in procalcitonin, white blood cells, and creatinine levels between patients with nonobstructed and obstructed UTI (P < 0.05). CONCLUSION: Although this retrospective study comprised a small number of patients, we found that procalcitonin was a useful marker to decide upon urinary intervention.

Clinical outcome of incidentally discovered small renal cell carcinoma after delayed surgery.

BACKGROUND: This study was undertaken to investigate the growth rate and clinical outcome of patients with a small renal mass (SRM) after delayed surgery. METHODS: We reviewed the clinical records of 34 patients with SRMs ≤ 4 cm at diagnosis, who underwent delayed surgical intervention during surveillance from January 2000 to December 2011. Radiographic evaluations using computed tomography (CT) scan and magnetic resonance imaging (MRI) were performed at least every 6 months, and the tumor size was determined at least twice. RESULTS: The mean follow-up time was 26.6 ± 18.6 months and mean tumor doubling time was 23.4 ± 16.0 months. Histopathological analysis revealed that 32 of the 34 patients were malignant in pT1aN0M0. Only one patient showed tumor recurrence, who subsequently died due to tumor progression. CONCLUSION: The growth rate of the small renal mass was slow in the majority of our patients. Delayed intervention does not have a detrimental effect on cancer-specific outcomes.

Clinical Outcome of Small Renal Cell Carcinoma after Delayed Surgery versus Immediate Surgery.

BACKGROUND: This study was undertaken to investigate the growth rate and clinical outcome of patients with a small renal mass (SRM) after delayed surgery versus immediate surgery. METHODS: We reviewed the clinical records of 328 patients with SRM ≦ 4cm at diagnosis, who underwent delayed or immediate surgical intervention from January 2000 to December 2011. Radiographic evaluation using CT scan and MRI were performed at least every 6 months and the tumor size was determined at least twice in the delayed surgery group. RESULTS: A total of 292 RCC patients with pT1aN0M0 were identified; among them, 32 patients had been managed with delayed surgery intervention. No statistically significant difference was observed in overall survival rate (OSR) and cancer recurrence-free rate (CRFR). But cancer-specific survival rate (CSSR) was significantly lower in the delayed surgery group (p=0.0002). CONCLUSIONS: The overall survival rate of delayed surgery was not inferior compared with that after immediate surgery. Delayed surgery intervention for SRMs is a treatment option in the current study.

A case of severe ganciclovir-induced encephalopathy.

BACKGROUND: Ganciclovir, a drug against cytomegalovirus (CMV) infection, is generally well tolerated, but can cause neurotoxicity such as encephalopathy. Although ganciclovir-induced encephalopathy has been described in several reports, a literature search revealed that ganciclovir concentrations in the blood or cerebrospinal fluid were previously measured in only 3 patients with encephalopathy. Symptoms usually include confusion and disturbed consciousness, which mimic CMV encephalitis. Prompt and accurate diagnosis is thus sometimes difficult, and is derived solely from accumulated clinical information of definite cases, since ganciclovir concentrations, not routinely measured, become available after several days or a few weeks. CASE PRESENTATION: Here, we summarize clinical information of all patients with definite ganciclovir-induced encephalopathy including our own patient, who had severe symptoms, with the highest reported trough concentration of ganciclovir in the blood, and underwent therapeutic dialysis with complete recovery. CONCLUSION: Our summary of patients with definite encephalopathy could lead to prompt and accurate diagnoses.

Survey on lower urinary tract symptoms and sleep disorders in patients treated at urology departments.

OBJECTIVES: This study examined the association between sleep disorders and lower urinary tract symptoms in patients who had visited urology departments. METHODS: This was an independent cross-sectional, observational study. Outpatients who had visited the urology departments at the Kinki University School of Medicine or the Sakai Hospital, Kinki University School of Medicine, between August 2011 and January 2012 were assessed using the Athens Insomnia Scale and the International Prostate Symptom Score. RESULTS: In total, 1174 patients (mean age, 65.7 ± 13.7 years), with 895 men (67.1 ± 13.2 years old) and 279 women (61.4 ± 14.6 years old), were included in the study. Approximately half of these patients were suspected of having a sleep disorder. With regard to the International Prostate Symptom Score subscores, a significant increase in the risk for suspected sleep disorders was observed among patients with a post-micturition symptom (the feeling of incomplete emptying) subscore of ≥1 (a 2.3-fold increase), a storage symptom (daytime frequency + urgency + nocturia) subscore of ≥5 (a 2.7-fold increase), a voiding symptom (intermittency + slow stream + hesitancy) subscore of ≥2 (a 2.6-fold increase), and a nocturia subscore of ≥2 (a 1.9-fold increase). CONCLUSION: The results demonstrated that the risk factors for sleep disorders could also include voiding, post-micturition, and storage symptoms, in addition to nocturia.