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.

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.

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.

Expression Level of Urinary MicroRNA-146a-5p Is Increased in Patients With Bladder Cancer and Decreased in Those After Transurethral Resection.

BACKGROUND: Bladder cancer is the most prevalent malignancy involving the urinary system and exhibits a markedly high recurrence rate. Therefore, reliable and noninvasive diagnostic and surveillance methods are desperately needed. PATIENTS AND METHODS: Candidate microRNAs (miRNAs) were selected from the miRNAs that were differentially expressed in bladder cancer cell lines (T24 and RT4) compared to normal ureteral epithelial tissue using miRNA-microarray analysis. The candidate miRNAs were validated by quantitative reverse transcription polymerase chain reaction assay using voided urine samples. RESULTS: We identified 3 miRNAs (miR-301b, -563, and -146a-5p) that demonstrated > 2-fold higher expression levels in cancer cell lines than in the normal ureteral epithelial tissue. Of these, only miR-146a-5p was consistently and significantly higher in urine samples from the patients with bladder cancer than in those from the normal individuals (P = .0014). The patients with high-grade tumors exhibited significantly higher urinary miR-146a-5p levels than those with low-grade tumors, and the patients with invasive tumors tended to show higher urinary miR-146a-5p levels than those with noninvasive tumors. Elevated urinary miR-146a-5p levels in patients with bladder cancer were decreased to the normal level after transurethral resection of the tumors (P = .0214). CONCLUSION: Our study suggested that urinary miR-146a-5p might be useful as a new noninvasive diagnostic marker, therapeutic target, or anticancer agent for bladder cancer, as well as for increasing our understanding of cancer biology.

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.

Induction of macrophage-like immunosuppressive cells from mouse ES cells that contribute to prolong allogeneic graft survival.

Recent progress in regenerative medicine has enabled the utilization of pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) as a donor resource for transplantation. However, immune suppression is still needed when the donor-recipient combination is allogeneic. Protection of ESCs-derived grafts from host immune response might be achieved thought the utilization of immunosuppressive cells generated from ESCs. In the present study, we show that a certain fraction of immunosuppressive cells can be generated from ESCs and help to suppress immune response against allogeneic grafts. ESCs-derived suppressor cells (ES-SCs) resembled macrophages in terms of cell surface molecule and gene expressions. Furthermore, gene expression analysis including microarray showed that ES-SCs have M1/M2 hybrid phenotype with high expression of genes correlated to immunosuppression of T cell response. Indeed, ES-SCs were effective to block allogeneic T cell proliferation in a nitric oxide-dependent manner, and prolonged the survival of ESCs-derived embryoid bodies or cardiomyocytes grafts transplanted into mouse kidney capsule. Thus, we consider the potential use of these ESCs-derived macrophage-like immunosuppressive cells as cellular therapies to promote long-term graft survival in future therapies.