Published papers

© 2018, The Author(s). Histological classification is essential in the clinical management of immunoglobulin A nephropathy (IgAN). However, there are limitations in predicting the prognosis of IgAN based on histological information alone, which suggests the need for better prognostic models. Therefore, we defined a prognostic model by combining the grade of clinical severity with the histological grading system by the following processes. We included 270 patients and explored the clinical variables associated with progression to end-stage renal disease (ESRD). Then, we created a predictive clinical grading system and defined the risk grades for dialysis induction by a combination of the clinical grade (CG) and the histological grade (HG). A logistic regression analysis revealed that the 24-h urinary protein excretion (UPE) and the estimated glomerular filtration rate (eGFR) were significant independent variables. We selected UPE of 0.5 g/day and eGFR of 60 ml/min/1.73 m 2 as the threshold values for the classification of CG. The risk of progression to ESRD of patients with CG II and III was significantly higher than that of patients with CG I. The patients were then re-classified into nine compartments based on the combination of CG and HG. Furthermore, the nine compartments were grouped into four risk groups. The risk of ESRD in the moderate, high, and super-high-risk groups was significantly higher than that in the low-risk group. Herein, we are giving a detailed description of our grading system for IgA nephropathy that predicted the risk of dialysis based on the combination of CG and HG.

© The Author(s) 2019. Clinical application of immune checkpoint inhibitors (CPIs) including nivolumab is expanding in the field of oncology treatment. Nivolumab is an anti-programmed death 1 protein (PD-1) antibody designed to augment an immunologic reaction against cancer cells. On the contrary, CPIs are known to cause a unique variety of side effects termed as immune-related adverse events, which can affect any organ including kidney. However, the characteristics of renal disorders by nivolumab treatment are poorly described. We describe two cases of acute kidney injury that were treated with nivolumab. Two patients, one with renal-cell carcinoma and the other with lung cancer, exhibited progressive renal dysfunction after the initiation of nivolumab treatment. By kidney biopsy, each case was diagnosed as acute interstitial nephritis (AIN). Of note, tubular epithelial cells enlarged with hyperchromatic nuclei were focally observed, and this finding was consistent with karyomegalic tubular epithelial cells. In immunostaining, most of the enlarged tubular epithelial cells were positive for Ki-67, which suggested regeneration of tubular epithelial cells. Clinically, in one case, re

An 80-year-old man was admitted because of appetite loss, mild proteinuria, and leg edema. A computed tomography examination revealed a tumor in his left kidney, and a left nephrectomy was performed. The tumor was histologically diagnosed as a clear cell type renal cell carcinoma, and hematoxylin eosin staining of the non-tumor region of the resected kidney showed an almost normal morphology. Three months later, he was readmitted because of the development of nephrotic syndrome with a urinary protein excretion of 4.2 g/day, a serum total protein concentration of 5.0 g/dL, a serum albumin concentration of 2.4 g/dL, a serum total cholesterol concentration of 214 mg/dL, and generalized edema. A full examination revealed no evidence of metastasis or recurrence of the renal cell carcinoma or any other malignant tumor. Congo red staining and immunohistochemical staining were performed using the non-tumor region of his resected kidney, and the presence of amyloid deposits in the microvascular walls and glomeruli that did not disappear when treated with potassium permanganate was disclosed. In this manner, the patient was diagnosed as having AL-type primary amyloidosis. Bence-Jones prot

BACKGROUND: Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease, characterized by increased concentrations of serum IgM and the presence of circulating anti-mitochondrial antibodies. Although bone diseases such as osteoporosis or osteodystrophy are commonly associated with PBC, osteomalacia which is caused by abnormal vitamin D metabolism, mineralization defects, and phosphate deficiency has not been recognized as a complication of PBC. CASE PRESENTATION: We report the case of a 49-year-old Japanese woman who complained of multiple fractures. Hypophosphatemic osteomalacia was diagnosed from a low serum phosphorus level, 1,25-dihydroxyvitamin D3 level, high levels of bone specific alkaline phosphatase and the findings of bone scintigraphy, although a bone biopsy was not performed. Twenty four hour urine demonstrated a low renal fractional tubular reabsorption of phosphate, increased fractional excretion of uric acid and generalized aminoaciduria. An intravenous bicarbonate loading test suggested the presence of proximal renal tubular acidosis (RTA). These biochemical data indicated Fanconi syndrome with proximal RTA. A kidney biopsy demonstrated t

Although drugs used in inflammatory bowel diseases (IBD) cause renal injury, glomerulopathies may also accompany IBD. We report a case with the rare association of ulcerative colitis (UC) and acute progressive interstitial nephritis. Although the kidney is acknowledged as a target organ for injury as a result of drug nephrotoxicity, our findings lend support to the novel recognition that the deranged autoimmune system emerging in UC causes interstitial nephritis as an extraintestinal manifestation. Overt renal failure due to interstitial nephritis has rarely been reported in UC patients. The case presented here therefore provides novel information on UC-associated nephropathy.

CONTEXT: For a precise and objective quantification of liver fibrosis, quantitative evaluations through image analysis have been utilized. However, manual operations are required in most cases for extracting fiber areas because of color variation included in digital pathology images. AIMS: The purpose of this research is to propose a color correction method for whole slide images (WSIs) of Elastica van Gieson (EVG) stained liver biopsy tissue specimens and to realize automated operation of image analysis for fibrosis quantification. MATERIALS AND METHODS: Our experimental dataset consisted of 38 WSIs of liver biopsy specimens collected from 38 chronic viral hepatitis patients from multiple medical facilities, stained with EVG and scanned at ×20 using a Nano Zoomer 2.0 HT (Hamamatsu Photonics K.K., Hamamatsu, Japan). Color correction was performed by modifying the color distribution of a target WSI so as to fit to the reference, where the color distribution was modeled by a set of two triangle pyramids. Using color corrected WSIs; fibrosis quantification was performed based on tissue classification analysis. STATISTICAL ANALYSIS USED: Spearman's rank correlation coefficients were calculated between liver stiffness measured by transient elastography and median area ratio of collagen fibers calculated based on tissue classification results. RESULTS: Statistical analysis results showed a significant correlation r = 0.61-0.68 even when tissue classifiers were trained by using a subset of WSIs, while the correlation coefficients were reduced to r = 0.40-0.50 without color correction. CONCLUSIONS: Fibrosis quantification accompanied with the proposed color correction method could provide an objective evaluation tool for liver fibrosis, which complements semi-quantitative histologic evaluation systems.

PURPOSE: In general, the index lesion of prostate cancer has the largest tumor volume, the highest Grade Group (GG), and the highest stage (concordant cases). However these factors sometimes do not coincide within one lesion (discordant cases). In such discordant cases, the largest tumor may not be of biological significance and the secondary tumor may more greatly impact the prognosis. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who underwent radical prostatectomy, and we identified 580 (85.3%) concordant cases and 100 (14.7%) discordant cases. The endpoint of this study was biochemical recurrence (BCR) and median follow-up was 4.2 years. RESULTS: Among discordant cases in which GGs of the largest tumor and the highest GG tumor differed, the majority (67 patients) had the largest tumor of GG 2 and we set them as the study cohort. On the other hand, we regarded 212 concordant cases with an index tumor of GG 2 as the control cohort. The study cohort comprised 48 (71.6%) patients with a secondary tumor of GG 3 and 19 (28.4%) with a secondary tumor of GG 4/5. Kaplan-Meier curves revealed that the 5-year BCR-free survival rates were 76%, and 67%, respectively. The 5-year BCR-free survival rate of the control cohort was 91%, which was significantly better than that of the study cohort (p=0.013 and 0.014, respectively). CONCLUSIONS: Our study suggested that the prognosis of discordant cases is better determined by the secondary cancer lesion with the highest GG instead of the largest lesion.

症例は48歳,女性.右乳房腫瘤を主訴に当院を受診した.既往歴として,25歳時に両側経腋窩的豊胸術(大胸筋下に生理食塩水バッグを挿入)を施行した.触診上,右乳頭直下に2cm大の腫瘤を触知した.画像検査では,乳癌が示唆された.確定診断のために針生検を提示するも,患者は拒否した.そこで,われわれは一期的な診断・手術治療を提示した.すなわち,全身麻酔下で切開生検・術中迅速病理組織検査を施行し,乳癌の場合には乳房切除+センチネルリンパ節生検+生理食塩水バッグ抜去+Tissue Expander挿入である.その方針に同意が得られた.結果は乳癌であった.センチネルリンパ節生検では転移陰性のため,腋窩リンパ節郭清は省略した.現在無再発生存中である.今後本邦では豊胸術施後の乳癌症例が増加してくることが予想される.その際のセンチネルリンパ節生検について若干の文献的考察を加えて報告する.(著者抄録)