Atypical post-infectious glomerulonephritis with c-ANCA positivity followed by endocarditis.

Post-infectious glomerulonephritis (PIGN), an uncommon variety of glomerulonephritis (GN), is characterized by emergence of nephritic syndrome within a few weeks following an infectious event. PIGN typically presents as a mild condition and tends to resolve by the time of diagnosis for GN. Aggregatibacter actinomycetemcomitans belongs to the HACEK group of bacteria, which constitutes less than 3% of bacteria responsible for community-acquired infective endocarditis. We present a case of 29-year-old man suspected of lymphoma with B-symptoms along with severe splenomegaly and nephromegaly. Shortly after, he developed an episode of nephritic syndrome accompanied by acute kidney injury (AKI) and high titers of cytoplasmic ANCA (c-ANCA)-positivity. Kidney biopsy revealed PIGN with tubulointerstitial nephritis. Despite treatment with antibiotics and corticosteroid, he visited the emergency room due to worsening dyspnea and multi-organ failure. An echocardiogram showed a bicuspid aortic valve with vegetation unseen on previous echocardiogram. He underwent aortic valve replacement immediately without adverse events. Four months after valve replacement, his renal function and cardiac performance have remained stable. We report a case of PIGN with AKI and high titers of c-ANCA appearing later as an infective endocarditis due to Aggregatibacter actinomycetemcomitans. With careful clinical observation and appropriate and timely management, satisfactory outcomes for patient health are possible.

Implication of cystic fluid cytology of renal cell carcinoma on surgical practice.

OBJECTIVES: To evaluate the incidence of positive cystic fluid cytology and its risk factors in cystic renal cell carcinoma (RCC) addressing its implication on the current surgical practice. METHODS: All clinically diagnosed Bosniak III, IV cystic renal masses from March 2019 to August 2022 were studied prospectively. Database of patients' demographics and cystic tumor characteristics were recorded. Partial or radical nephrectomies were performed by either laparoscopic or robotic approach. Cystic fluid was collected right after specimen retrieval in the surgical field and examined by pathologist. Cytology results were compared to the demographic, perioperative variables using univariate and multivariate analysis. RESULTS: A total of 70 patients of histologically confirmed cystic RCC were included. Sixty seven patients underwent radical nephrectomy with laparoscopic or robotic approaches, while 3 patients underwent radical nephrectomy. There was no intraoperative cystic rupture or fluid spillage. Positive cystic fluid cytology findings were identified in 34 (48.6%) patients, while negative cystic fluid cytology were identified in 36 (51.4%) cases. Definite malignant cells were observed in 28 patients while the other six patients showed highly suspicious atypical cells. Histologically, 24 (70.8%) patients were proven clear cell RCC and 25 (73%) showed Fuhrman grade 1 or 2 in final histologic review in positive group. Univariate and multivariate regression analysis between positive and negative cytology groups showed that the presence of the malignant cells in cystic fluid was significantly associated with patients' age (> 55 years) and Bosniak grade of cystic tumor (p < 0.05). CONCLUSIONS: Definite malignant cells in cystic fluid cytology were observed through our study. Additionally, patients' age (> 55 years) and Bosniak grade were the significant risk factors of positive cytology in cystic RCC. Therefore, necessity of meticulous manipulation of cystic renal tumors, despite their clinical features, should not be underemphasized to avoid the least possible tumor cell seeding in case of cystic rupture when operating such high risk of positive cytology.

How Much Reliable Is the Current Belief on Grade Group 1 Prostate Cancer?

Objective: To evaluate the clinicopathological characteristics of grade group 1 (GG1) prostate cancer in Korean populations. Methods: We retrospectively analyzed 492 consecutive radical prostatectomy specimens from our institution, which included those from 322 men with clinical GG1 and 170 with clinical GG2 tumors between years 2009 and 2018. The incidence of Gleason score (GS) upgrading, extraprostatic extension (EPE), and seminal vesicle invasion (SVI) were evaluated in patients with clinical GG1. In pathological GG1 cases, the distribution of adverse pathological features including EPE, lymphovascular invasion (LVI), perineural invasion (PNI), and biochemical recurrence (BCR) was analyzed. Results: Altogether, 78 (24.2%) out of 322 men in the clinical GG1 group demonstrated upgrading of GS, including 19 men with pathological Gleason score 4 + 3 = 7 and 6 with ≥ pathological Gleason score 4 + 4 = 8 cases. EPE was found in 37 (11.5%) and 22 (8.9%) men in clinical GG1 and pathological GG1 group, respectively. The incidence of LVI and PNI in the pathological GG1 cases was 2.8% (n = 7) and 28.6% (n = 71), respectively. BCR was observed in 4 men in pathological GG1 T2 (n = 226) and 2 men in GG1 T3 (n = 22) group. When we compared the pathological features between pathological GG1 T3 vs. GG2 T2, there was no statistical differences in the incidence of LVI and PNI between the two groups. Conclusions: Contrary to the current concept that GG1 is almost always clinically insignificant, it seems that GG1 still possess its respectable position as a group of cancer with aggressiveness. These findings should be kept in mind when deciding on treatment options for prostate cancer patients in the Asian populations.

Genomic Landscape of Young-Onset Bladder Cancer and Its Prognostic Implications on Adult Bladder Cancer.

Due to the rare occurrence of young-onset bladder cancer (YBC), its genomic characteristics remain largely unknown. Twenty-nine biopsy-proven YBC cases were collected using a nation-wide search for bladder cancer diagnosed at 20 years or younger. Whole exome sequencing and RNA sequencing were carried out in 21 and 11 cases, respectively, and compared with those of adult bladder cancer (ABC) cases obtained from public databases. Almost all YBCs were low grade, non-invasive papillary tumors. YBC had a low mutation burden and less complex copy number alterations. All cases harbored putative driver mutations. Mutations were most commonly found in HRAS (10 cases), with a preference for exon 5. FGFR3 gene fusions were noted with various partner genes (7 cases). The alterations on HRAS and FGFR3 occurred in a mutually exclusive manner. Others included KRAS mutations (2 cases), chromosomes 4p and 10q arm-level deletions (1 case), and ERCC2 mutation (1 case). There were no point mutations in TP53 and FGFR3. The gene expression profiles of YBC were similar to those of the ABC group with good prognosis. None of the YBCs and ABCs with YBC-like mutations showed progression to muscle-invasive tumors. Our results suggest that bladder cancer with YBC-like mutations represents an indolent bladder tumor, regardless of age.

Amyloid light-chain amyloidosis presented as focal segmental glomerulosclerosis in a kidney transplant recipient.

Amyloid light-chain (AL) amyloidosis after kidney transplantation is a rare disease in the world, and only one case of systemic AL amyloidosis after kidney transplantation is reported in Korea. We here report a 46-year-old woman with AL amyloidosis developed after kidney transplantation. The underlying disease of our case was focal segmental glomerulosclerosis (FSGS), and was admitted to hospital for evaluation of proteinuria developed 2 years after kidney transplantation. The patient was initially diagnosed as recurrent FSGS on light microscopy. But, electron microscopic finding was suggestive of amyloidosis and systemic evaluation was consistent with systemic AL amyloidosis. This case provides the importance of differential diagnosis of proteinuria in kidney transplant recipients.

A bioprinted human-glioblastoma-on-a-chip for the identification of patient-specific responses to chemoradiotherapy.

Patient-specific ex vivo models of human tumours that recapitulate the pathological characteristics and complex ecology of native tumours could help determine the most appropriate cancer treatment for individual patients. Here, we show that bioprinted reconstituted glioblastoma tumours consisting of patient-derived tumour cells, vascular endothelial cells and decellularized extracellular matrix from brain tissue in a compartmentalized cancer-stroma concentric-ring structure that sustains a radial oxygen gradient, recapitulate the structural, biochemical and biophysical properties of the native tumours. We also show that the glioblastoma-on-a-chip reproduces clinically observed patient-specific resistances to treatment with concurrent chemoradiation and temozolomide, and that the model can be used to determine drug combinations associated with superior tumour killing. The patient-specific tumour-on-a-chip model might be useful for the identification of effective treatments for glioblastoma patients resistant to the standard first-line treatment.

Author Correction: Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer.

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.

High FOXM1 expression is a prognostic marker for poor clinical outcomes in prostate cancer.

Purpose: We aimed to investigate the expression of FOXM1 and to determine the relationships between FOXM1 expression and clinicopathologic characteristics in patients with PCa. Furthermore, we reconfirmed the prognostic impact of FOXM1 in different cohorts using already published data. Patients and Methods: Formalin-fixed, paraffin-embedded tissues were collected from patients with low- (n=17), intermediate- (n=36), and high-risk (n=29) disease, from patients with CRPC (n=2) and from patients with BPH (n=28). To analyze FOXM1 expression, we performed IHC analyses. Also, we analyzed gene expression data from cBioPortal to evaluate the associations between FOXM1 alteration and prognosis of PCa. Results: FOXM1 expression measured using Allred score differed between patients with BPH, and low-, intermediate-, and high-risk PCa (0.3, 1.5, 4.8, and 6.2, respectively; p<0.001). Patients with high FOXM1 expression had higher preoperative PSA levels (p=0.023), more advanced tumor stages (p=0.047), and higher pathologic Gleason score (p<0.001) than those with low FOXM1 expression. ROC curve analysis indicated that FOXM1 expression was a useful marker for discriminating PCa from BPH (AUC 0.851, 95% CI 0.783-0.920) and for discriminating high-risk PCa from low- and intermediate-risk PCa (AUC 0.807, 95% CI 0.719-0.894). In multivariate analyses, high FOXM1 expression was an independent predictor of BCR. Finally, in the TCGA dataset, FOXM1 alteration was associated with poor overall (p=4.521e-4) and disease-free survival (p=0.0108). Conclusions: In patients with PCa, high FOXM1 expression was associated with advanced tumor stages, high Gleason score, and poor prognosis. These data suggest a role of FOXM1 in biologically and clinically aggressive PCa.

Three-dimensional printing of a patient-specific engineered nasal cartilage for augmentative rhinoplasty.

Autologous cartilages or synthetic nasal implants have been utilized in augmentative rhinoplasty to reconstruct the nasal shape for therapeutic and cosmetic purposes. Autologous cartilage is considered to be an ideal graft, but has drawbacks, such as limited cartilage source, requirements of additional surgery for obtaining autologous cartilage, and donor site morbidity. In contrast, synthetic nasal implants are abundantly available but have low biocompatibility than the autologous cartilages. Moreover, the currently used nasal cartilage grafts involve additional reshaping processes, by meticulous manual carving during surgery to fit the diverse nose shape of each patient. The final shapes of the manually tailored implants are highly dependent on the surgeons' proficiency and often result in patient dissatisfaction and even undesired separation of the implant. This study describes a new process of rhinoplasty, which integrates three-dimensional printing and tissue engineering approaches. We established a serial procedure based on computer-aided design to generate a three-dimensional model of customized nasal implant, and the model was fabricated through three-dimensional printing. An engineered nasal cartilage implant was generated by injecting cartilage-derived hydrogel containing human adipose-derived stem cells into the implant containing the octahedral interior architecture. We observed remarkable expression levels of chondrogenic markers from the human adipose-derived stem cells grown in the engineered nasal cartilage with the cartilage-derived hydrogel. In addition, the engineered nasal cartilage, which was implanted into mouse subcutaneous region, exhibited maintenance of the exquisite shape and structure, and striking formation of the cartilaginous tissues for 12 weeks. We expect that the developed process, which combines computer-aided design, three-dimensional printing, and tissue-derived hydrogel, would be beneficial in generating implants of other types of tissue.

Clinical impact of complement (C1q, C3d) binding De Novo donor-specific HLA antibody in kidney transplant recipients.

INTRODUCTION: Complement binding activity of donor-specific HLA antibodies (DSA) has been suggested as a new tool to stratify immunologic risk in kidney transplantation (KT). The objective of this study was to evaluate the clinical implication of C1q/C3d binding activity of de novo DSA (dnDSA) in KT recipients. MATERIAL AND METHODS: A total of 161 pretransplant DSA-negative recipients were monitored for dnDSA at the time of biopsy. C1q/C3d binding activities of dnDSA were assessed using C1qScreen assay (One lambda, USA) and Lifecodes C3d detection assay (Immucor, USA), respectively. Clinical outcomes including biopsy-proven antibody mediated rejection (AMR), C4d detection and post-biopsy graft survival were investigated. RESULTS: De-novo DSAs were detected in fifty-four (33.5%) patients (HLA class I only, n = 19; class II only, n = 29; both class I and II, n = 6). Of them, complement binding activities were detected in 26 (48.1%) patients, including 17 C1q+ and 24 C3d+ patients. Both C1q and C3d positivity were associated with increased mean fluorescence intensity values of dnDSA. Complement binding activity of dnDSA enhanced the incidence of AMR (25.0% in C1q-C3d-, 36.4% in C1q+/C3d- or C1q-/C3d+, and 60.0% in C1q+/C3d+ patients) (P <0.001). The incidence of AMR was not different between patients with C1q+ and those with C3d+ dnDSA (64.7%, 11/17 versus 45.8%, 11/24, P = 0.238). In comparison between C1q and C3d assay according to HLA specificity, C1q+ HLA class I ± II dnDSA was the best predictor for AMR (odds ratio: 27.2). C1q+/C3d+ dnDSA was associated with more C4d deposition in allograft tissue and inferior post-biopsy graft survival. Clinical outcomes were not significantly different between C1q+ and C3d+ dnDSA-positive patients. CONCLUSION: Detection of complement binding activity using both C1q and C3d assays can be a further prognostic marker for predicting AMR and allograft outcome in dnDSA+ kidney transplant patients.

Clinical significance of the presence of anti-human leukocyte antigen-donor specific antibody in kidney transplant recipients with allograft dysfunction.

BACKGROUND/AIMS: This study investigated the clinical significance of detecting anti-human leukocyte antigen-donor specific antibody (HLA-DSA) in kidney transplant recipients (KTRs) requiring indication biopsy owing to allograft dysfunction. METHODS: We analyzed the presence of HLA-DSA in 210 KTRs who took indication biopsy. We divided these cases into two groups, HLA-DSA (+) (n = 52) and HLA-DSA (-) (n = 158) group, and compared the clinical characteristics, pathological findings, and clinical outcomes of the two groups. RESULTS: The rates of retransplant, pretransplant sensitization, and HLA-mismatch were significantly higher in HLA-DSA (+) group than in HLA-DSA (-) group (p < 0.05 for each comparison). In histologic finding, all types of rejections were more frequent in the former group. Besides, scores of both the T-cell injury markers such as tubulitis, interstitial inf lammation, and vasculitis and antibody-mediated injury markers such as peritubular C4d deposition and microvascular inflammation (glomerulitis plus peritubular capillaritis) were higher in HLA-DSA (+) group (p < 0.05 for each). Notably, allograft outcomes were worse in HLA-DSA (+) group. Further, multivariate analysis showed that presence of HLA-DSA, advanced interstitial fibrosis/tubular atrophy (interstitial fibrosis plus tubular atrophy ≥ 2), and allograft rejection in biopsy were independent risk factors for allograft failure. CONCLUSIONS: The results of this study showed that presence of HLA-DSA in a case of allograft dysfunction adversely influences allograft outcome, and its detection, irrespective of the result of the allograft biopsy, necessitates intensive monitoring and treatment.

Three-Dimensional Bio-Printed Scaffold Sleeves With Mesenchymal Stem Cells for Enhancement of Tendon-to-Bone Healing in Anterior Cruciate Ligament Reconstruction Using Soft-Tissue Tendon Graft.

PURPOSE: To investigate the efficacy of the insertion of 3-dimensional (3D) bio-printed scaffold sleeves seeded with mesenchymal stem cells (MSCs) to enhance osteointegration between the tendon and tunnel bone in anterior cruciate ligament (ACL) reconstruction in a rabbit model. METHODS: Scaffold sleeves were fabricated by 3D bio-printing. Before ACL reconstruction, MSCs were seeded into the scaffold sleeves. ACL reconstruction with hamstring tendon was performed on both legs of 15 adult rabbits (aged 12 weeks). We implanted 15 bone tunnels with scaffold sleeves with MSCs and implanted another 15 bone tunnels with scaffold sleeves without MSCs before passing the graft. The specimens were harvested at 4, 8, and 12 weeks. H&E staining, immunohistochemical staining of type II collagen, and micro-computed tomography of the tunnel cross-sectional area were evaluated. Histologic assessment was conducted with a histologic scoring system. RESULTS: In the histologic assessment, a smooth bone-to-tendon transition through broad fibrocartilage formation was identified in the treatment group, and the interface zone showed abundant type II collagen production on immunohistochemical staining. Bone-tendon healing histologic scores were significantly higher in the treatment group than in the control group at all time points. Micro-computed tomography at 12 weeks showed smaller tibial (control, 9.4 ± 0.9 mm2; treatment, 5.8 ± 2.9 mm2; P = .044) and femoral (control, 9.6 ± 2.9 mm2; treatment, 6.0 ± 1.0 mm2; P = .03) bone-tunnel areas in the treated group than in the control group. CONCLUSIONS: The 3D bio-printed scaffold sleeve with MSCs exhibited excellent results in osteointegration enhancement between the tendon and tunnel bone in ACL reconstruction in a rabbit model. CLINICAL RELEVANCE: If secure biological healing between the tendon graft and tunnel bone can be induced in the early postoperative period, earlier, more successful rehabilitation may be facilitated. Three-dimensional bio-printed scaffold sleeves with MSCs have the potential to accelerate bone-tendon healing in ACL reconstruction.

A cell-laden hybrid fiber/hydrogel composite for ligament regeneration with improved cell delivery and infiltration.

Ligament, a fibrous connective tissue between bones, is a unique tissue in human anatomy because it has complex viscoelastic properties and is very tough. Moreover, it is an important tissue for regeneration because frequent injuries occur, but there are limited types of substitutes that can be used as a tissue replacement. In this study, we present a stem cell-laden fiber/hydrogel composite structure with a layered fibrous structure, which can enhance cell infiltration, topographical cue and mechanical properties. It can promote cell viability, proliferation, and differentiation of the ligament phenotype with the help of a growth factor. The mechanical properties of the developed structure were experimentally identified using tensile tests, while cell viability and various functionalities were verified through culture tests using mesenchymal stem cells.

Level of mitoses in non-muscle invasive papillary urothelial carcinomas (pTa and pT1) at initial bladder biopsy is a simple and powerful predictor of clinical outcome: a multi-center study in South Korea.

BACKGROUND: Histologic grade is the most important predictor of the clinical outcome of non-muscle invasive (Ta, T1) papillary urothelial carcinoma (NMIPUCa), but its ambiguous criteria diminish its power to predict recurrence/progression for individual patients. We attempted to find an objective and reproducible histologic predictor of NMIPUCa that correlates well with the clinical outcome. METHODS: A total of 296 PUCas were collected from the Departments of Surgical Pathology of 11 institutions in South Korea. The clinical outcome was grouped into no event (NE), recurrence (R), and progression (P) categories. All 25 histological parameters were numerically redefined. The clinical pathology of each case was reviewed individually by 11 pathologists from 11 institutions based on the 2004 WHO criteria and afterwards blindly evaluated by two participants, based on our proposed parameters. Univariate and multivariate logistic regression analyses were performed using the R software package. RESULTS: The level of mitoses was the most reliable parameter for predicting the clinical outcome. We propose a four-tiered grading system based on mitotic count (> 10/10 high-power fields), nuclear pleomorphism (smallest-to-largest ratio of tumor nuclei >20), presence of divergent histology, and capillary proliferation (> 20 capillary lumina per papillary core). CONCLUSIONS: The level of mitoses at the initial bladder biopsy and transurethral resection (TUR) specimen appeared to be an independent predictor of the Ta PUCa outcome. Other parameters include the number of mitoses, nuclear pleomorphism, divergent histology, and capillary proliferation within the fibrovascular core. These findings may improve selection of patients for a therapeutic strategy as compared to previous grading systems.

Locally-applied 5-fluorouracil-loaded slow-release patch prevents pancreatic cancer growth in an orthotopic mouse model.

To obtain improved efficacy against pancreatic cancer, we investigated the efficacy and safety of a locally-applied 5-fluorouracil (5-FU)-loaded polymeric patch on pancreatic tumors in an orthotopic nude-mouse model. The 5-FU-releasing polymeric patch was produced by 3D printing. After application of the patch, it released the drug slowly for 4 weeks, and suppressed BxPC-3 pancreas cancer growth. Luciferase imaging of BxPC3-Luc cells implanted in the pancreas was performed longitudinally. The drug patch delivered a 30.2 times higher level of 5-FU than an intra-peritoneal (i.p.) bolus injection on day-1. High 5-FU levels were accumulated within one week by the patch. Four groups were compared for efficacy of 5-FU. Drug-free patch as a negative control (Group I); 30% 5-FU-loaded patch (4.8 mg) (Group II); 5-FU i.p. once (4.8 mg) (Group III); 5-FU i.p. once a week (1.2 mg), three times (Group IV). The tumor growth rate was significantly faster in Group I than Group II, III, IV (p=0.047 at day-8, p=0.022 at day-12, p=0.002 at day-18 and p=0.034 at day-21). All mice in Group III died of drug toxicity within two weeks after injection. Group II showed more effective suppression of tumor growth than Group IV (p=0.018 at day-12 and p=0.017 at day-21). Histological analysis showed extensive apoptosis in the TUNEL assay and by Ki -67 staining. Western blotting confirmed strong expression of cleaved caspase-3 in Group II. No significant changes were found hematologically and histologically in the liver, kidney and spleen in Groups I, II, IV but were found in Group III.

Henoch-Schönlein Purpura with Concurrent Cytomegalovirus Duodenitis.

Henoch-Schönlein purpura (HSP) is a systemic vasculitis involving the small vessels with distinct clinical features. The etiology of HSP is diverse, and viral infection is one of the many predisposing factors. Cytomegalovirus (CMV) infection mostly affects immune-suppressed patients, but rarely patients with normal immunity can also be affected. Authors experienced a case of HSP patient, with underlying small-cell lung cancer (SCLC) with CMV duodenitis. This is a rare case of HSP diagnosed in SCLC patient with predisposing factor of CMV infection.

Clinicopathologic Characteristics and Mutational Status of Succinate Dehydrogenase Genes in Paraganglioma of the Urinary Bladder: A Multi-Institutional Korean Study.

CONTEXT: - Because of the limited number of available primary bladder paraganglioma (PBPG) cases, the rates of succinate dehydrogenase (SDH) mutations and the clinicopathologic characteristics of SDH-deficient tumors have not been fully studied. OBJECTIVE: - To define the clinicopathologic and molecular characteristics of PBPGs. DESIGN: - A total of 52 PBPGs were collected retrospectively. SDHA and SDHB immunohistochemical stains were performed. In cases of SDHB expression loss, mutation analyses of SDHB, SDHC, and SDHD were performed. RESULTS: - The clinicopathologic features were analyzed for 52 cases (M:F = 27:25), with a mean age of 56 years (range, 22-79 years). Tumor sizes were 0.5 to 8 cm (mean, 2.4 cm). Tumor necrosis was present in 5 of 52 cases (10%), involvement of muscularis propria in 41 (79%), and lymphovascular tumor invasion in 6 (12%). During a mean follow-up period of 41 months (range, 1-161 months), 3 of 52 patients (6%) developed metastases, but no one died from the disease. Immunohistochemistry for SDHA and SDHB showed that all cases were SDHA intact. Among them, 43 cases had intact SDHB, whereas 9 cases were SDHB deficient. Compared with the SDHB-intact cases, the SDHB-deficient cases were characterized by large tumor sizes (4.5 versus 1.9 cm; P < .001), a higher number of mitoses per 10 high-powered fields (2.6 versus 0.1; P = .002), and frequent lymphovascular tumor invasion (33% versus 7%; P = .02) and metastases (22% versus 2%; P = .02). Mutational analyses for SDHB, SDHC, and SDHD were performed in 9 SDHB-deficient cases. Among them, 6 cases were successfully sequenced and revealed SDHB mutations only. CONCLUSIONS: - Large tumor size, a higher number of mitoses, and the presence of lymphovascular tumor invasion and SDHB mutations suggest malignant paraganglioma.

KRAS Mutation Test in Korean Patients with Colorectal Carcinomas: A Methodological Comparison between Sanger Sequencing and a Real-Time PCR-Based Assay.

BACKGROUND: Mutations in the KRAS gene have been identified in approximately 50% of colorectal cancers (CRCs). KRAS mutations are well established biomarkers in anti-epidermal growth factor receptor therapy. Therefore, assessment of KRAS mutations is needed in CRC patients to ensure appropriate treatment. METHODS: We compared the analytical performance of the cobas test to Sanger sequencing in 264 CRC cases. In addition, discordant specimens were evaluated by 454 pyrosequencing. RESULTS: KRAS mutations for codons 12/13 were detected in 43.2% of cases (114/264) by Sanger sequencing. Of 257 evaluable specimens for comparison, KRAS mutations were detected in 112 cases (43.6%) by Sanger sequencing and 118 cases (45.9%) by the cobas test. Concordance between the cobas test and Sanger sequencing for each lot was 93.8% positive percent agreement (PPA) and 91.0% negative percent agreement (NPA) for codons 12/13. Results from the cobas test and Sanger sequencing were discordant for 20 cases (7.8%). Twenty discrepant cases were subsequently subjected to 454 pyrosequencing. After comprehensive analysis of the results from combined Sanger sequencing-454 pyrosequencing and the cobas test, PPA was 97.5% and NPA was 100%. CONCLUSIONS: The cobas test is an accurate and sensitive test for detecting KRAS-activating mutations and has analytical power equivalent to Sanger sequencing. Prescreening using the cobas test with subsequent application of Sanger sequencing is the best strategy for routine detection of KRAS mutations in CRC.

Acute interstitial nephritis induced by Solanum nigrum.

Acute interstitial nephritis (AIN) is an important cause of reversible acute kidney injury and pathologically characterized by inflammatory infiltrate in the renal interstitium. Solanum nigrum (S. nigrum) is a medicinal plant member of the Solanaceae family. Although S. nigrum has been traditionally used to treat various ailments such as pain, inflammation, and fever, it has also been reported to have a toxic effect, resulting in anticholinergic symptoms. However, there have been no reports of AIN caused by S. nigrum. Here, we report the first case of biopsy-confirmed AIN after ingestion of S. nigrum. The patient was successfully treated using corticosteroid therapy.

Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer.

Extracellular vesicles (EVs) may play an important role in cancer development and progression. We aimed to investigate the prognostic potential of prostate-specific EVs in prostate cancer (PCa) patients. Plasma and prostate tissue were collected from patients who underwent surgery for PCa (n = 82) or benign prostatic hyperplasia (BPH, n = 28). To analyze the quantity of EVs in prostate, we performed transmission electron microscopy (TEM), immuno-TEM with CD63 and prostate-specific membrane antigen (PSMA), and immunofluorescence staining. After EV isolation from plasma, CD63 and PSMA concentration was measured using ELISA kits. PSMA-positive areas in prostate differed in patients with BPH, and low-, intermediate-, and high-risk PCa (2.4, 8.2, 17.5, 26.5%, p < 0.001). Plasma PSMA-positive EV concentration differed in patients with BPH, and low-, intermediate-, and high-risk PCa (21.9, 43.4, 49.2, 59.9 ng/mL, p < 0.001), and ROC curve analysis indicated that plasma PSMA-positive EV concentration differentiated PCa from BPH (AUC 0.943). Patients with lower plasma PSMA-positive EV concentration had greater prostate volume (50.2 vs. 33.4 cc, p < 0.001) and lower pathologic Gleason score (p = 0.025). During the median follow-up of 18 months, patients with lower plasma PSMA-positive EV concentration tended to have a lower risk of biochemical failure than those with higher levels of prostate-specific EVs (p = 0.085).