[Early Experience with MRI-Ultrasound Fusion-Guided Prostate Biopsy in Our Institution].

A total of 100 patients were retrospectively analyzed with magnetic resonance imaging-ultrasonography (MRI-US) fusion biopsy(KOELIS, TRINITY®) at our institution between October 2019 and May 2020. The median patient age was 71 years, median prostate specific antigen (PSA) level was 7.4 ng/ml, and median PSA-density was 0.183 mg/ml. Sixty-one of the patients were positive for cancer ; 14 of them were positive by targeted biopsy only, 9 were positive by systematic biopsy only, and 38 were positive by both. Clinically significant prostate cancer (CPSC ; Gleason Score ≥3＋4 and % core ≥50%) was detected by target biopsies in 46 patients and by systematic biopsies in 33 patients. The positive core detection rate for CSPC was 32.5% for targeted biopsies and 7.0% for systematic biopsies(P＜0.0001), with a significantly higher rate for targeted biopsies. These results indicate that in MRI-US fusion biopsy, targeted biopsy has a higher detection rate for cancer and a significantly higher detection rate for clinically significant prostate cancer compared with systematic biopsy.

Arteriovenous fistulas after ultrasound-guided needle biopsy of kidney allografts and treatment outcomes after transcatheter embolization: A single-center experience in Japan.

BACKGROUND: Arteriovenous fistula (AVF) is one of the vascular complications after allograft biopsy, and their reported incidence rates range widely. Transcatheter embolization (TE) is a common AVF treatment in kidney allografts. However, information on AVF incidence and features and TE outcomes in Japanese kidney transplant (KT) recipients is lacking. METHODS: This study investigated 270 protocol or clinically indicated kidney allograft biopsies in 129 KT recipients during 2010-2016 at a single-center using standardized methods (16-gauge needle and ultrasound guidance). We recorded the incidence and clinical features of AVF using currently recommended standardized methods of allograft biopsy and TE outcomes regarding allograft function up to 12 months after the procedure in Japanese KT recipients. RESULTS: AVF incidence was 2.6% (seven cases). The time from biopsy to AVF diagnosis was 7 (median, interquartile range: 5-117, range: 1-318) days. The time from biopsy to AVF diagnosis was significantly shorter in symptomatic cases (gross hematuria) than in asymptomatic cases (median 6 vs. 117 days, p = 0.034). Symptomatic patients underwent TE within a shorter time (0-6 days) than asymptomatic patients (25-104 days). There were no complications, and allograft function was stable up to 12 months after TE despite using contrast media and partial renal infarction. CONCLUSIONS: AVF does occur in certain probabilities. AVF formation can occur without apparent bleeding and exist for a long time after allograft biopsy. TE is a safe and immediate treatment for AVF in kidney allograft.

The pretreatment neutrophil-to-lymphocyte ratio is a novel biomarker for predicting clinical responses to pembrolizumab in platinum-resistant metastatic urothelial carcinoma patients.

PURPOSE: We investigated the relationship between pretreatment neutrophil-to-lymphocyte ratio (pre-NLR) levels just before the initiation of treatment with pembrolizumab and clinical outcomes in platinum-resistant metastatic urothelial carcinoma (UC) patients treated with pembrolizumab. METHODS: Our study population comprised 78 patients diagnosed with metastatic UC and treated with pembrolizumab after platinum-based chemotherapy at our institutions between December 2017 and April 2019. We examined the relationships between pre-NLR levels just before pembrolizumab treatment and clinical outcomes. A pre-NLR level of ≥3.35 was defined as elevated according to a calculation by a receiver-operating curve analysis. RESULTS: The high pre-NLR group consisted of 33 patients (42.3%). Overall, 29.5% of patients had a clinical response and the sum of the target lesion longest diameter was decreased in 18.8% of the high pre-NLR group, which was significantly lower than that in the low pre-NLR group (58.1%, P = 0.005). Six-month progression-free survival and cancer-specific survival rates for the high pre-NLR group were 9.1 and 58.0%, which were significantly lower than those for their counterpart (45.9 and 89.1%, P < 0.001 and P = 0.002, respectively). The pre-NLR level was an independent indicator of disease progression and cancer-specific death (P < 0.001 and P = 0.003). Furthermore, patients with a postpembrolizumab NLR level that had decreased ≥25% from the pre-NLR level had significantly lower disease progression and cancer-specific death rates than their counterparts (P = 0.01 and P = 0.022, respectively). CONCLUSIONS: Elevated pre-NLR may be a novel biomarker for identifying poor responders to pembrolizumab among platinum-resistant metastatic UC patients.

Automated acquisition of explainable knowledge from unannotated histopathology images.

Deep learning algorithms have been successfully used in medical image classification. In the next stage, the technology of acquiring explainable knowledge from medical images is highly desired. Here we show that deep learning algorithm enables automated acquisition of explainable features from diagnostic annotation-free histopathology images. We compare the prediction accuracy of prostate cancer recurrence using our algorithm-generated features with that of diagnosis by expert pathologists using established criteria on 13,188 whole-mount pathology images consisting of over 86 billion image patches. Our method not only reveals findings established by humans but also features that have not been recognized, showing higher accuracy than human in prognostic prediction. Combining both our algorithm-generated features and human-established criteria predicts the recurrence more accurately than using either method alone. We confirm robustness of our method using external validation datasets including 2276 pathology images. This study opens up fields of machine learning analysis for discovering uncharted knowledge.

Clinically useful limited sampling strategy to estimate area under the concentration-time curve of once-daily tacrolimus in adult Japanese kidney transplant recipients.

BACKGROUND: An extended-release, once-daily, oral formulation of tacrolimus is currently used after kidney transplantation as a substitute for the conventional twice-daily formulation. The purpose of this study was to provide a limited sampling strategy with minimum and optimum sampling points to predict the tacrolimus area under the concentration-time curve (AUC) after administration of once-daily tacrolimus in de novo adult kidney transplant patients. METHODS: A total of 36 adult Japanese kidney transplant patients receiving once-daily tacrolimus were included: 31 were allocated to a study group to develop limited sampling strategy (LSS) model equations based on multiple stepwise linear regression analysis, and 5 were allocated to a validation group to estimate the precision of the LSS equations developed by the study group. Twelve-hour AUC (AUC0-12) was calculated by the trapezoidal rule, and the relationship between individual concentration points and AUC0-12 were determined by multiple linear regression analysis. The coefficient of determination (R2) was used to assess the goodness-of-fit of the regression models. Three error indices (mean error, mean absolute error, and root mean squared prediction error) were calculated to evaluate predictive bias, accuracy, and precision, respectively. Quality of the statistical models was compared with Akaike's information criterion (AIC). RESULTS: A four-point model using C0, C2, C4 and C6 gave the best fit to predict AUC0-12 (R2 = 0.978). In the three- and two-point models, the best fits were at time points C2, C4, and C6 (R2 = 0.973), and C2 and C6 (R2 = 0.962), respectively. All three models reliably estimated tacrolimus AUC0-12, consistent with evaluations by the three error indices and Akaike's information criterion. Practically, the two-point model with C2 and C6 was considered to be the best combination, providing a highly accurate prediction and the lowest blood sampling frequency. CONCLUSIONS: The two-point model with C2 and C6 may be valuable in reducing the burden on patients, as well as medical costs, for once-daily tacrolimus monitoring.

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.

Hemorrhagic shock due to bleeding from an arteriovenous fistula after allograft biopsy in a kidney transplant recipient: a case report.

Arteriovenous fistula (AVF) after allograft biopsy occurs in 1.6-8.3% of kidney transplant patients and most cases remain asymptomatic. Here, we report a case of hemorrhagic shock in a kidney transplant recipient following bleeding from an AVF after graft biopsy. Immediate intensive care including angiographic embolization saved the patient and the allograft. A 62-year-old woman with end-stage renal disease caused by diabetic nephropathy underwent ABO-incompatible kidney transplantation. No complications occurred in the early postoperative period. However, serum creatinine levels did not decrease sufficiently and decreased graft diastolic blood flow was noted on ultrasound. Therefore, at 14 days after kidney transplantation, allograft biopsy was performed to elucidate the cause of allograft dysfunction. At 5 days after allograft biopsy, the patient developed hemorrhagic shock caused by bleeding from an AVF in the allograft. We immediately performed angiographic embolization, and her vital signs improved without deterioration in renal function. AVF can cause hemorrhagic shock, and angiographic embolization is effective for treating it.

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.

A bioinformatics-to-clinic sequential approach to analysis of prostate cancer biomarkers using TCGA datasets and clinical samples: a new method for precision oncology?

Biomarker-driven cancer therapy has met with significant clinical success. Identification of a biomarker implicated in a malignant phenotype and linked to poor clinical outcome is required if we are to develop these types of therapies. A subset of prostate adenocarcinoma (PACa) cases are treatment-resistant, making them an attractive target for such an approach. To identify target molecules implicated in shorter survival of patients with PACa, we established a bioinformatics-to-clinic sequential analysis approach, beginning with 2-step in silico analysis of a TCGA dataset for localized PACa. The effect of candidate genes identified by in silico analysis on survival was then assessed using biopsy specimens taken at the time of initial diagnosis of localized and metastatic PACa. We identified PEG10 as a candidate biomarker. Data from clinical samples suggested that increased expression of PEG10 at the time of initial diagnosis was linked to shorter survival time. Interestingly, PEG10 overexpression also correlated with expression of chromogranin A and synaptophysin, markers for neuroendocrine prostate cancer, a type of treatment-resistant prostate cancer. These results indicate that PEG10 is a novel biomarker for shorter survival of patients with PACa. Also, PEG10 expression at the time of initial diagnosis may predict focal neuroendocrine differentiation of PACa. Thus, PEG10 may be an attractive target for biomarker-driven cancer therapy. Thus, bioinformatics-to-clinic sequential analysis is a valid tool for identifying targets for precision oncology.

Paraneoplastic Dermatomyositis Associated with Metastatic Seminoma.

We report the first case in Japan of paraneoplastic dermatomyositis with pure seminoma, a tumor that extremely rarely accompanies dermatomyositis. The patient presented to the hospital with muscle weakness and erythema and was diagnosed with dermatomyositis from skin biopsy. Routine radiological screening revealed testicular tumor and massive lymph node metastases. We initially performed orchiectomy along with conventional immunotherapy. However, muscle weakness gradually worsened, and he eventually showed dysphagia and forced respiration and became bedridden. Although he seemed close to being too unstable to tolerate further treatment, we started carefully adjusted chemotherapy comprising 4 courses of etoposide plus cisplatin, which proved highly successful. Lymph node metastases completely disappeared and swallowing and respiration fully normalized after completing chemotherapy. We believe that this clinical success was due to our decision to initiate chemotherapy even in such a weak patient.

Solitary Fibrous Tumor of the Kidney Developing Local Recurrence.

Solitary fibrous tumor (SFT) of the kidney is a rare entity and usually displays a favorable prognosis. We herein report a second case of renal SFT developing local recurrence. A 50-year-old man was referred to our hospital because of a left renal mass. An abdominal CT detected a large renal tumor and radical nephrectomy was performed with a possible diagnosis of renal cell carcinoma. The resected tumor size was measured at 17 × 11 × 8 cm. Grossly, necrosis was observed in central lesion of the tumor but hemorrhage was not observed. Microscopically, the tumor consisted of spindle-shaped cells with scant cytoplasm accompanied by hyalinized collagenous tissue, which displayed hemangiopericytomatous patterns. The cellularity was normal and nuclear pleomorphism was not observed. Ki-67 labeling index was less than 3%. The pathological diagnosis of SFT was made without obvious malignant findings. Three years after the surgery, a follow-up CT scan detected a mass lesion in the tumor bed. Surgical resection was performed and the resected tumor was compatible with local recurrence of the SFT without obvious malignant findings. Renal SFT should be carefully monitored even in the absence of obvious malignant findings.

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.

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.

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.

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.

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.

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.

[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.

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.