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Purpose@#Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT. @*Materials and Methods@#The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT. @*Results@#Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976). @*Conclusion@#The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.
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Background@#Both neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) exhibit neuroendocrine differentiation and are classified as neuroendocrine neoplasms (NENs).NECs and nonneuroendocrine neoplasms (non-NENs), such as adenocarcinoma, have similar mutational profiles. The purpose of this study was to identify differences in metastatic patterns and to identify the key factor causing these differences by simultaneously comparing the metastatic patterns of NETs, NECs and non-NENs from various primary organs. @*Methods@#We retrieved data for 4,223 patients with NENs and 41,637 patients with non-NENs arising at various primary sites from an institutional database and then compared NET, NEC, and non-NEN metastatic patterns. @*Results@#NETs and NECs showed generally similar metastatic patterns. Most NEN patients had a higher liver organotrophic metastasis rate, lower lung organotrophic metastasis rate, and lower pleural/peritoneal organotrophic metastasis rate than non-NEN patients. Some differences were characteristics of specific organs. Some of these site-specific differences were not caused by NENs but by non-NENs, including a higher bone organotrophic metastasis rate for medullary thyroid carcinoma and a lower bone organotrophic metastasis rate for pulmonary NEN. Other differences were probably caused by NENs, including a higher bone organotrophic metastasis rate for colorectal NETs. Uterine cervical NEC showed unique patterns of metastasis compared to NEN from other sites. @*Conclusion@#Significant differences between the metastatic patterns of NENs and non-NENs were detected. The multigene program that causes neuroendocrine differentiation might be associated with organotropic metastasis.
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Purpose@#The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC). @*Materials and Methods@#In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety. @*Results@#Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates. @*Conclusion@#Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).
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Purpose@#We aimed to investigate the risk factors and patterns of locoregional recurrence (LRR) after radical nephrectomy (RN) in patients with locally advanced renal cell carcinoma (RCC). @*Materials and Methods@#We retrospectively analyzed 245 patients who underwent RN for non-metastatic pT3-4 RCC from January 2006 to January 2016. We analyzed the risk factors associated with poor locoregional control using Cox regression. Anatomical mapping was performed on reference computed tomography scans showing intact kidneys. @*Results@#The median follow-up duration was 56 months (range, 1 to 128 months). Tumor extension to renal vessels or the inferior vena cava (IVC) and Fuhrman’s nuclear grade IV were identified as independent risk factors of LRR. The 5-year actuarial LRR rates in groups with no risk factor, one risk factor, and two risk factors were 2.3%, 19.8%, and 30.8%, respectively (p < 0.001). The locations of LRR were distributed as follows: aortocaval area (n=2), paraaortic area (n=4), retrocaval area (n=5), and tumor bed (n=11). No LRR was observed above the celiac axis (CA) or under the inferior mesenteric artery (IMA). @*Conclusion@#Tumor extension to renal vessels or the IVC and Fuhrman’s nuclear grade IV were the independent risk factors associated with LRR after RN for pT3-4 RCC. The locations of LRR after RN for RCC were distributed in the tumor bed and regional lymphatic area from the bifurcation of the CA to that of the IMA.
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Background@#We recently discovered the presence of specialized nail mesenchyme below the nail matrix and designated it as onychomatricodermis. @*Objective@#We did further research to characterize the histologic, histochemical, immunohistochemical and ultrastructural features of the onychomatricodermis containing onychofibroblasts in the nail unit. @*Methods@#Ten polydactyly nail unit specimens and 8 nail matrix biopsies were included. H&E-stained slides were reviewed. We did Alcian blue staining and Masson Trichrome staining, as well as immunohistochemical staining for type Ⅰ collagen, CD10, CD13 and CD34. In addition, polydactyly nail units were examined by transmission electron microscopy. @*Results@#In H&E staining, the specialized mesenchyme called onychomatricodermis was observed to be slightly distant from the undersurface of the nail matrix and be less eosinophilic area. Onychomatricodermal onychofibroblasts showed light purple abundant cytoplasm.Masson Trichrome staining revealed fewer collagen fibers within the onychomatricodermis. In Alcian blue staining the onychomatricodermis showed mucin deposition within the onychofibroblasts and around them. Immunohistochemically, type Ⅰ collagen was expressed much less in the onychomatricodermis while it was strongly expressed elsewhere in the nail unit. In nail matrix biopsy specimens onychomatricodermal onychofibroblasts expressed CD10 and CD13 strongly, and expressed CD34 as well. Ultrastructurally, collagen fibrils were found sparsely within the onychomatricodermis, whereas collagen fibrils were densely distributed in the dermis of other parts of the nail unit. @*Conclusion@#We demonstrated that there was less collagen expression in the onychomatricodermis containing onychofibroblasts. In addition, we found morphological and immunohistochemical features of onychomatricodermal onychofibroblasts (onychofibroblasts of Dongyoun). These findings support the presence of onychomatricodermis containing onychofibroblasts in the nail unit.
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Objective@#To compare the diagnostic performance between Prostate Imaging-Reporting and Data System version 2.0 (PIRADSv2.0) and version 2.1 (PI-RADSv2.1) for clinically significant prostate cancer (csPCa) in the peripheral zone (PZ). @*Materials and Methods@#This retrospective study included 317 patients who underwent multiparametric magnetic resonance imaging and targeted biopsy for PZ lesions. Definition of csPCa was International Society of Urologic Pathology grade ≥ 2 cancer. Area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for csPCa were analyzed by two readers. The cancer detection rate (CDR) for csPCa was investigated according to the PI-RADS categories. @*Results@#AUC of PI-RADSv2.1 (0.856 and 0.858 for reader 1 and 2 respectively) was higher than that of PI-RADSv2.0 (0.795 and 0.747 for reader 1 and 2 respectively) (both p < 0.001). Sensitivity, specificity, PPV, NPV, and accuracy for PI-RADSv2.0 vs. PI-RADSv2.1 were 93.2% vs. 88.3% (p = 0.023), 52.8% vs. 76.6% (p < 0.001), 48.7% vs. 64.5% (p < 0.001), 94.2% vs. 93.2% (p = 0.504), and 65.9% vs. 80.4% (p < 0.001) for reader 1, and 96.1% vs. 92.2% (p = 0.046), 34.1% vs. 72.4% (p < 0.001), 41.3% vs. 61.7% (p < 0.001), 94.8% vs. 95.1% (p = 0.869), and 54.3% vs. 78.9% (p < 0.001) for reader 2, respectively. CDRs of PI-RADS categories 1–2, 3, 4, and 5 for PI-RADSv2.0 vs. PI-RADSv2.1 were 5.9% vs. 5.9%, 5.8% vs. 12.5%, 39.8% vs. 56.2%, and 88.9% vs. 88.9% for reader 1; and 4.5% vs. 4.1%, 6.1% vs. 11.1%, 32.5% vs. 53.4%, and 85.0% vs. 86.8% for reader 2, respectively. @*Conclusion@#Our data demonstrated improved AUC, specificity, PPV, accuracy, and CDRs of category 3 or 4 of PI-RADSv2.1, but decreased sensitivity, compared with PI-RADSv2.0, for csPCa in PZ.
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Objective@#To compare the diagnostic performance between Prostate Imaging-Reporting and Data System version 2.0 (PIRADSv2.0) and version 2.1 (PI-RADSv2.1) for clinically significant prostate cancer (csPCa) in the peripheral zone (PZ). @*Materials and Methods@#This retrospective study included 317 patients who underwent multiparametric magnetic resonance imaging and targeted biopsy for PZ lesions. Definition of csPCa was International Society of Urologic Pathology grade ≥ 2 cancer. Area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for csPCa were analyzed by two readers. The cancer detection rate (CDR) for csPCa was investigated according to the PI-RADS categories. @*Results@#AUC of PI-RADSv2.1 (0.856 and 0.858 for reader 1 and 2 respectively) was higher than that of PI-RADSv2.0 (0.795 and 0.747 for reader 1 and 2 respectively) (both p < 0.001). Sensitivity, specificity, PPV, NPV, and accuracy for PI-RADSv2.0 vs. PI-RADSv2.1 were 93.2% vs. 88.3% (p = 0.023), 52.8% vs. 76.6% (p < 0.001), 48.7% vs. 64.5% (p < 0.001), 94.2% vs. 93.2% (p = 0.504), and 65.9% vs. 80.4% (p < 0.001) for reader 1, and 96.1% vs. 92.2% (p = 0.046), 34.1% vs. 72.4% (p < 0.001), 41.3% vs. 61.7% (p < 0.001), 94.8% vs. 95.1% (p = 0.869), and 54.3% vs. 78.9% (p < 0.001) for reader 2, respectively. CDRs of PI-RADS categories 1–2, 3, 4, and 5 for PI-RADSv2.0 vs. PI-RADSv2.1 were 5.9% vs. 5.9%, 5.8% vs. 12.5%, 39.8% vs. 56.2%, and 88.9% vs. 88.9% for reader 1; and 4.5% vs. 4.1%, 6.1% vs. 11.1%, 32.5% vs. 53.4%, and 85.0% vs. 86.8% for reader 2, respectively. @*Conclusion@#Our data demonstrated improved AUC, specificity, PPV, accuracy, and CDRs of category 3 or 4 of PI-RADSv2.1, but decreased sensitivity, compared with PI-RADSv2.0, for csPCa in PZ.
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Background@#Non-HLA antibodies, anti-angiotensin II type 1 receptor antibodies (anti-AT1R) and anti-endothelial cell antibodies (AECA), are known to play a role in allograft rejection. We evaluated the role of both antibodies in predicting post-transplant outcomes in low-risk living donor kidney transplantation (LDKT) recipients. @*Methods@#In 94 consecutive LDKT recipients who were ABO compatible and negative for pre-transplant HLA donor-specific antibodies, we determined the levels of anti-AT1Rs using an enzyme-linked immunosorbent assay and the presence of AECAs using a flow cytometric endothelial cell crossmatch (ECXM) assay with pre-transplant sera. Hazard ratio (HR) was calculated to predict post-transplant outcomes. @*Results@#Pre-transplant anti-AT1Rs (≥11.5 U/mL) and AECAs were observed in 36 (38.3%) and 22 recipients (23.4%), respectively; 11 recipients had both. Pre-transplant anti-AT1Rs were a significant risk factor for the development of acute rejection (AR) (HR 2.09; P=0.018), while a positive AECA status was associated with AR or microvascular inflammation only (HR 2.47; P=0.004) throughout the follow-up period. In particular, AECA (+) recipients with ≥11.5 U/mL anti-AT1Rs exhibited a significant effect on creatinine and estimated glomerular filtration rate (P<0.001; P=0.028), although the risk of AR was not significant. @*Conclusions@#Pre-transplant anti-AT1Rs and AECAs have independent negative effects on post-transplant outcomes in low-risk LDKT recipients. Assessment of both antibodies would be helpful in stratifying the pre-transplant immunological risk, even in low-risk LDKT recipients.
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Purpose@#There remains a lot of unmet need to increase understanding of node-positive (ypN+) muscle invasive bladder cancer (MIBC) after neoadjuvant chemotherapy and radical cystectomy to decide the appropriate therapeutics. @*Materials and Methods@#In a retrospective study using the center cancer chemotherapy registry, we found 113 MIBC patients who were treated with neoadjuvant chemotherapy involving gemcitabine and cisplatin (GP) followed by radical cystectomy between 2010 and 2014. Disease-free survival (DFS) and overall survival (OS) were compared according to the pathologic node positivity (ypN- vs. ypN+). Among a total of 165 patients with MIBC who received neoadjuvant chemotherapy involving GP, 118 underwent radical cystectomy. In 46 patients with ypN+ disease, DFS and OS were evaluated according to administration of adjuvant GP. @*Results@#After neoadjuvant chemotherapy and radical cystectomy, 41% of patients had ypN+ disease, which showed significantly shorter DFS (median, 7.4 months; 95% confidence interval [CI], 5.3–9.6 months) and OS (median, 20.0 months; 95% CI, 13.4–26.6 months) compared to those with ypN- disease. The patients with ypN+ disease had a high risk of recurrence or death, regardless of the administration of adjuvant chemotherapy or adjuvant regimen. @*Conclusions@#Within the limitations of this retrospective study, MIBC patients with ypN+ disease despite neoadjuvant chemotherapy and radical cystectomy had a poor prognosis. Further studies involving novel, effective adjuvant treatment including immunotherapy agents are needed to reduce the high risk of recurrence or death in these patients.
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Purpose@#There remains a lot of unmet need to increase understanding of node-positive (ypN+) muscle invasive bladder cancer (MIBC) after neoadjuvant chemotherapy and radical cystectomy to decide the appropriate therapeutics. @*Materials and Methods@#In a retrospective study using the center cancer chemotherapy registry, we found 113 MIBC patients who were treated with neoadjuvant chemotherapy involving gemcitabine and cisplatin (GP) followed by radical cystectomy between 2010 and 2014. Disease-free survival (DFS) and overall survival (OS) were compared according to the pathologic node positivity (ypN- vs. ypN+). Among a total of 165 patients with MIBC who received neoadjuvant chemotherapy involving GP, 118 underwent radical cystectomy. In 46 patients with ypN+ disease, DFS and OS were evaluated according to administration of adjuvant GP. @*Results@#After neoadjuvant chemotherapy and radical cystectomy, 41% of patients had ypN+ disease, which showed significantly shorter DFS (median, 7.4 months; 95% confidence interval [CI], 5.3–9.6 months) and OS (median, 20.0 months; 95% CI, 13.4–26.6 months) compared to those with ypN- disease. The patients with ypN+ disease had a high risk of recurrence or death, regardless of the administration of adjuvant chemotherapy or adjuvant regimen. @*Conclusions@#Within the limitations of this retrospective study, MIBC patients with ypN+ disease despite neoadjuvant chemotherapy and radical cystectomy had a poor prognosis. Further studies involving novel, effective adjuvant treatment including immunotherapy agents are needed to reduce the high risk of recurrence or death in these patients.
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PURPOSE: Treatment targeting immune checkpoint with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has demonstrated efficacy and tolerability in the treatment of metastatic urothelial carcinoma (mUC). We investigated the efficacy and safety of atezolizumab in mUC patients who failed platinum-based chemotherapy. MATERIALS AND METHODS: A retrospective study using the Samsung Medical Center cancer chemotherapy registry was performed on 50 consecutive patients with mUC treated with atezolizumab, regardless of their PD-L1(SP142) status, as salvage therapy after chemotherapy failure between May 2017 and June 2018. Endpoints included overall response rate (RR), progression-free survival (PFS), and safety. RESULTS: Among 50 patients, men constituted 76% and the median age was 68 years (range, 46 to 82 years). Twenty-three patients (46%) received atezolizumab as second-line therapy. PD-L1 (SP142) status IC0/1 and IC2/3 were found in 21 (42%) and 21 (42%) of patients, respectively; in eight patients (16%), PD-L1 (SP142) expression was not available. Atezolizumab was generally well tolerated, with pruritus and fatigue being the most commonly observed toxicities. As a result, partial response was noted in 20 patients (40%), with 12 (24%) stable diseases. RRwas higherin IC2/3 (62%) than in IC0/1 patients (24%, p=0.013). The median PFS was 7.4 months (95% confidence interval, 3.4 to 11.4 months). As expected, PFS also was significantly longer in IC2/3 patients than in IC0/1 (median, 12.7 vs. 2.1 months; p=0.005). PFS was not significantly influenced by age, sex, performance status, number of previous chemotherapy, site of metastases, or any of the baseline laboratory parameters. CONCLUSION: In this retrospective study, atezolizumab demonstrated clinically efficacy and tolerability in unselected mUC patients who failed platinum-based chemotherapy.
Subject(s)
Humans , Male , Disease-Free Survival , Drug Therapy , Fatigue , Neoplasm Metastasis , Pruritus , Retrospective Studies , Salvage TherapyABSTRACT
PURPOSE: The efficacy of nivolumab in metastatic renal cell carcinoma (mRCC) has been proven. However, the nivolumab experience in Korean patients with mRCC is still poorly reported. We report initial experiences with the efficacy and safety of nivolumab in patients with mRCC. MATERIALS AND METHODS: We retrospectively reviewed records for 25 patients with mRCC who had failed targeted therapy and were treated by nivolumab (2 mg/kg, every 2 weeks) at a single institution. The primary endpoint was objective response rate (ORR), and secondary endpoints were progression-free survival (PFS), safety profiles, and ORR in a programmed cell death receptor ligand 1 (PD-L1) expression subgroup. RESULTS: The median age was 60 years and 16 patients (64%) were male. Objective responses were achieved in 8 patients (32.0%) (complete response, 1; partial response, 7). Median PFS was 3.0 months (95% confidence interval, 1.46–4.53). Treatment-related adverse events (AEs) of any grade were observed in 19 patients (76.0%) with 6 (24.0%) experiencing grade 3 to 4 treatment-related AEs. In subgroups by PD-L1 expression levels classified as 1% or greater and less than 1%, ORR was 50% and 0%, respectively. CONCLUSIONS: This study showed the efficacy and safety of initial experiences with nivolumab in Korean patients with mRCC who had failed targeted therapy. Our results were comparable to recent clinical trials on nivolumab in mRCC.
Subject(s)
Humans , Male , B7-H1 Antigen , Carcinoma, Renal Cell , Cell Death , Disease-Free Survival , Neoplasm Metastasis , Retrospective Studies , Treatment OutcomeABSTRACT
Renal artery stenosis (RAS) is commonly presented with hypertension and chronic kidney disease. We report a rare case of RAS occurring in a 78-year-old man who presented with nephrotic-range proteinuria. Renal biopsy on the left side was performed, and results showed mesangiopathic glomerulonephritis, which was not compatible with the cause of nephrotic-range proteinuria. Proteinuria was decreased by angiotensin receptor blocker, but azotemia was aggravated. Therefore, angiotensin receptor blocker was discontinued inevitably and thorough evaluation for the possibility of RAS was performed. Computed tomography angiography revealed significant RAS on the left side and a renal artery stent was inserted. After stenting, aortic dissection developed and progressed despite tight control of blood pressure. After inserting another stent graft through the true lumen of the left renal artery, the patient's renal function and proteinuria improved markedly.
Subject(s)
Aged , Humans , Angiography , Angioplasty , Angiotensins , Azotemia , Biopsy , Blood Pressure , Blood Vessel Prosthesis , Glomerulonephritis , Hypertension , Proteinuria , Renal Artery Obstruction , Renal Artery , Renal Insufficiency, Chronic , StentsABSTRACT
Crystalline nephropathy is a rare yet well-known condition associated with multiple myeloma and other light chain–secreting disorders. Paraproteins that are resistant to proteolysis crystallize within proximal tubular cells and cause light-chain proximal tubulopathy, which presents clinically as Fanconi syndrome. Podocytes are rarely affected, and the crystalline inclusions within podocytes are typically precipitated, yielding significant glomerular proteinuria. Here we report a case of extensive crystalline inclusions primarily within podocytes and proximal tubules that presented only with Fanconi syndrome and renal insufficiency. Despite the presence of extensive crystalline inclusions in podocytes and diffuse foot process effacement, the patient had no clinical evidence suggestive of podocyte injury.
Subject(s)
Humans , Crystallins , Fanconi Syndrome , Foot , Multiple Myeloma , Paraproteins , Podocytes , Proteinuria , Proteolysis , Renal InsufficiencyABSTRACT
Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a ligand-activated transcription factor has been investigated as the target for cancer treatment as well as metabolic disorders. Recent studies have demonstrated that PPAR-gamma ligands are anti-tumorigenic in prostate cancer due to anti-proliferative and pro-differentiation effects. The aim of this study was to validate PPAR-gamma expression in malignant and benign prostate tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). A total of 730 prostatic adenocarcinomas (PCAs) including 63 whole sections from radical prostatectomy specimens and tissue microarrays containing 667 PCAs were subject to immunostaining for two PPAR-gamma antibodies. Twenty-five benign prostate tissues and PCAs were selected for investigating mRNA expression by quantitative real-time PCR. 10.7% of PCAs (78/730) showed cytoplasmic immunoreactivity of PPAR-gamma and no nuclear immunoreactivity was noted in PCAs. Most benign prostatic glands showed negative immunoreactivity of PPAR-gamma except for variable weak cytoplasmic staining in some glands. Nuclear immunoreactivity of PPAR-gamma was noted some central zone and verumontanum mucosal epithelium. The constitutive PPAR-gamma mRNA showed significantly lower level in PCAs compared to that in the benign tissues. There was no difference of PPAR-gamma mRNA expression between low (7) Gleason score groups. There was no association of PPAR-gamma mRNA level or cytoplasmic immunostaining with Gleason grade or pathologic stage. Our study supported the evidence of extra-nuclear localization and nongenomic actions of PPAR-gamma. Further studies are needed to assess the functional role of PPAR-gamma and to validate its therapeutic implication in prostate cancer.
Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Adenocarcinoma/metabolism , Gene Expression Regulation, Neoplastic , Immunohistochemistry , Neoplasm Staging , PPAR gamma/genetics , Prostate/pathology , Prostatectomy , Prostatic Neoplasms/metabolism , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Tissue Array AnalysisABSTRACT
Megalocytic interstitial nephritis is a rare form of kidney disease caused by chronic inflammation. We report a case of megalocytic interstitial nephritis occurring in a 45-yrold woman who presented with oliguric acute kidney injury and acute pyelonephritis accompanied by Escherichia coli bacteremia. Her renal function was not recovered despite adequate duration of susceptible antibiotic treatment, accompanied by negative conversion of bacteremia and bacteriuria. Kidney biopsy revealed an infiltration of numerous histiocytes without Michaelis-Gutmann bodies. The patient's renal function was markedly improved after short-term treatment with high-dose steroid.
Subject(s)
Female , Humans , Middle Aged , Acute Disease , Acute Kidney Injury/complications , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Bacteremia/drug therapy , Cefotaxime/therapeutic use , Creatinine/blood , Escherichia coli , Escherichia coli Infections/drug therapy , Kidney/pathology , Methylprednisolone/therapeutic use , Nephritis, Interstitial/drug therapy , Pyelonephritis/complications , Renal Dialysis , Shock, Septic/drug therapyABSTRACT
Kidney is rarely an involved organ of graft-versus-host disease (GVHD). Here, we report on a case of membranous nephropathy and interstitial nephritis after allogenic hematopoietic stem cell transplantation (HSCT) in a 44-year-old female patient with acute lymphoblastic leukemia. The patient received GVHD prophylaxis with low dose steroid, cyclosporin, and short course methotrexate. Cyclosporine was tapered out 17 months after allogeneic HSCT. Thereafter, the patient developed kidney impairment and nephrotic range proteinuria. Kidney biopsy revealed membranous nephropathy concurrent with interstitial nephritis.
Subject(s)
Adult , Female , Humans , Biopsy , Cyclosporine , Glomerulonephritis, Membranous , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Kidney , Methotrexate , Nephritis, Interstitial , Precursor Cell Lymphoblastic Leukemia-Lymphoma , ProteinuriaABSTRACT
OBJECTIVE: To retrospectively determine the optimal b value of diffusion-weighted imaging (DWI) for predicting the presence of localized prostate cancer, and to evaluate the utility of DWI under different b values in differentiating between cancers and benign prostatic tissues. MATERIALS AND METHODS: Eighty patients with suspected prostate cancer underwent MRI including DWI at 3T, followed by radical prostatectomy. DWI was examined under different b values. Apparent diffusion coefficient (ADC) maps were generated by using b = 0, and other b values of 300, 700, 1000 or 2000 s/mm2. For predicting the presence of cancers, four different ADC maps were analyzed independently by two blinded readers. ADCs were measured in benign and malignant tissues. RESULTS: For predicting the presence of 110 prostate cancers, the sensitivity and area under the curve (AUC) for an experienced reader was significantly greater at b = 1000 (85% and 0.91) than b = 300, 700 or 2000 s/mm2 (p < 0.01). For a less-experienced reader, the AUC was significantly greater at b = 700, 1000 or 2000 than b = 300 s/mm2 (p < 0.01). Mean ADCs of the cancers in sequence from b = 300 to 2000 s/mm2 were 1.33, 1.03, 0.88 and 0.68 x 10(-3) mm2/s, which were significantly lower than those of benign tissues (p < 0.001). CONCLUSION: The optimal b value for 3T DWI for predicting the presence of prostate cancer may be 1000 s/mm2.
Subject(s)
Aged , Aged, 80 and over , Humans , Male , Middle Aged , Area Under Curve , Biopsy , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging/methods , Neoplasm Staging , Predictive Value of Tests , Prostate-Specific Antigen/blood , Prostatectomy , Prostatic Neoplasms/diagnosis , Retrospective Studies , Sensitivity and SpecificityABSTRACT
Familial juvenile hyperuricemic nephropathy (FJHN; OMIM 162000) is an autosomal dominant disorder characterized by hyperuricemia and gouty arthritis due to reduced kidney excretion of uric acid and progressive renal failure. Gradual progressive interstitial renal disease, with basement membrane thickening and glomerulosclerosis resulting from fibrosis, starts in early life. In most cases of FJHN, uromodulin gene (UMOD) is responsible for the disease; however, there has been only one report of a genetically confirmed FJHN family in Korea. Here we report another Korean family with FJHN, in which three male members. a father and 2 sons.developed gout and progressive renal insufficiency. The clinical, laboratory, and radiological findings were consistent with FJHN, and renal biopsy showed chronic parenchymal damage, which can be found in FJHN but is not specific to this disease. In order to confirm the diagnosis, sequence analysis of the UMOD was performed, and a novel heterozygous missense variant (c.187T>C; p.Cys63Arg) in exon 3 was identified. We assume that this variant is likely to be the causative mutation in this family, as the variant segregated with the disease. In addition, approximately two-thirds of the known mutations lead to a cysteine amino acid change in uromodulin, and all such variants have been shown to cause UMOD-associated kidney disease. In summary, we report a Korean FJHN family with three affected members by genetic analysis of the UMOD, and provide the first report of a novel heterozygous missense mutation.