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PURPOSE: To assess the computed tomography (CT) findings of papillary renal neoplasm with reverse polarity (PRNRP) and develop a radiomics-based model to distinguish PRNRPs from papillary renal cell carcinomas (PRCCs). MATERIALS AND METHODS: We analyzed 31 PRNRPs and 68 PRCCs using preoperative kidney CT. We evaluated CT features that could discriminate PRNRPs from PRCCs. A radiomics signature was constructed using features selected through a least absolute shrinkage and selection operator algorithm. A radiomics-based model incorporating a radiomics signature and subjective CT parameters using multivariate logistic regression was developed. The diagnostic performance of the CT parameters, radiomics model, and their combination was evaluated using the area under the curve (AUC). RESULTS: Most of PRNRPs had a round shape (93.5%), well-defined margin (100%), and persistent enhancement (77.4%). Compared with PRCC, PRNRPs exhibited distinct CT features including small size (16.7 vs. 37.7 mm, P < 0.001), heterogeneity (64.5 vs. 32.4%, P = 0.004), enhancing dot sign (16.1 vs. 1.5%, P = 0.001), and high attenuation in pre-contrast CT (44.2 vs. 35.5 HU, P = 0.003). Multivariate analysis revealed smaller mass size (odds ratio [OR]: 0.9; 95% confidence interval [CI] 0.9-1.0, P = 0.013), heterogeneity (OR: 8.8; 95% CI 1.9-41.4, P = 0.006), and higher attenuation in pre-contrast CT (OR: 1.1; 95% CI 1.0-1.2, P = 0.011) as significant independent factors for identifying PRNRPs. The diagnostic performance of the combination model was excellent (AUC: 0.923). CONCLUSION: Smaller tumor size, heterogeneity, and higher attenuation in pre-contrast CT were more closely associated with PRNRPs than with PRCCs. Though the retrospective design, small sample size, and single-center data of this study may affect the generalizability of the findings, combining subjective CT features with a radiomics model is beneficial for distinguishing PRNRPs from PRCCs.
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TFE3-rearranged renal cell cancer (tRCC) is a rare form of RCC that involves chromosomal translocation of the Xp11.2 TFE3 gene. Despite its early onset and poor prognosis, the molecular mechanisms of the pathogenesis of tRCC remain elusive. This study aimed to identify novel therapeutic targets for patients with primary and recurrent tRCC. We collected 19 TFE3-positive RCC tissues that were diagnosed by immunohistochemistry and subjected them to genetic characterization to examine their genomic and transcriptomic features. Tumor-specific signatures were extracted using whole exome sequencing (WES) and RNA sequencing (RNA-seq) data, and the functional consequences were analyzed in a cell line with TFE3 translocation. Both a low burden of somatic single nucleotide variants (SNVs) and a positive correlation between the number of somatic variants and age of onset were observed. Transcriptome analysis revealed that four samples (21.1%) lacked the expected fusion event and clustered with the genomic profiles of clear cell RCC (ccRCC) tissues. The fusion event also demonstrated an enrichment of upregulated genes associated with mitochondrial respiration compared with ccRCC expression profiles. Comparison of the RNA expression profile with the TFE3 ChIP-seq pattern data indicated that PPARGC1A is a metabolic regulator of the oncogenic process. Cell proliferation was reduced when PPARGC1A and its related metabolic pathways were repressed by its inhibitor SR-18292. In conclusion, we demonstrate that PPARGC1A-mediated mitochondrial respiration can be considered a potential therapeutic target in tRCC. This study identifies an uncharacterized genetic profile of an RCC subtype with unique clinical features and provides therapeutic options specific to tRCC.
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BACKGROUND: Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease and end-stage kidney disease. Its diverse range of manifestations complicates the treatment approach for patients. Although kidney biopsy is considered the gold standard for diagnosis, it lacks precision in predicting the progression of kidney dysfunction. Herein, we addressed whether the presence of glomerular crescents is linked to the outcomes in patients with biopsy-confirmed type 2 DKD. METHODS: We performed a retrospective evaluation, involving 327 patients diagnosed with biopsy-confirmed DKD in the context of type 2 diabetes, excluding cases with other glomerular diseases, from nine tertiary hospitals. Hazard ratios (HRs) were calculated using a Cox regression model to assess the risk of kidney disease progression, defined as either ≥ 50% decrease in estimated glomerular filtration rates or the development of end-stage kidney disease, based on the presence of glomerular crescents. RESULTS: Out of the 327 patients selected, ten patients had glomerular crescents observed in their biopsied tissues. Over the follow-up period (median of 19 months, with a maximum of 18 years), the crescent group exhibited a higher risk of kidney disease progression than the no crescent group, with an adjusted HR of 2.82 (1.32-6.06) (P = 0.008). The presence of heavy proteinuria was associated with an increased risk of developing glomerular crescents. CONCLUSION: The presence of glomerular crescents is indeed linked to the progression of type 2 DKD. Therefore, it is important to determine whether there is an additional immune-mediated glomerulonephritis requiring immunomodulation, and it may be prudent to monitor the histology and repeat a biopsy.
Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Disease Progression , Kidney Glomerulus , Humans , Diabetic Nephropathies/pathology , Retrospective Studies , Male , Female , Middle Aged , Diabetes Mellitus, Type 2/complications , Kidney Glomerulus/pathology , Aged , Glomerular Filtration Rate , Cohort Studies , Biopsy , Kidney Failure, Chronic , Risk FactorsABSTRACT
Toxin- and drug-induced tubulointerstitial nephritis (TIN), characterized by interstitial infiltration of immune cells, frequently necessitates dialysis for patients due to irreversible fibrosis. However, agents modulating interstitial immune cells are lacking. Here, we addressed whether the housekeeping enzyme glutamyl-prolyl-transfer RNA synthetase 1 (EPRS1), responsible for attaching glutamic acid and proline to transfer RNA, modulates immune cell activity during TIN and whether its pharmacological inhibition abrogates fibrotic transformation. The immunological feature following TIN induction by means of an adenine-mixed diet was infiltration of EPRS1high T cells, particularly proliferating T and γδ T cells. The proliferation capacity of both CD4+ and CD8+ T cells, along with interleukin-17 production of γδ T cells, was higher in the kidneys of TIN-induced Eprs1+/+ mice than in the kidneys of TIN-induced Eprs1+/- mice. This discrepancy contributed to the fibrotic amelioration observed in kidneys of Eprs1+/- mice. TIN-induced fibrosis was also reduced in Rag1-/- mice adoptively transferred with Eprs1+/- T cells compared to the Rag1-/- mice transferred with Eprs1+/+ T cells. The use of an EPRS1-targeting small molecule inhibitor (bersiporocin) under clinical trials to evaluate its therapeutic potential against idiopathic pulmonary fibrosis alleviated immunofibrotic aggravation in TIN. EPRS1 expression was also observed in human kidney tissues and blood-derived T cells, and high expression was associated with worse patient outcomes. Thus, EPRS1 may emerge as a therapeutic target in toxin- and drug-induced TIN, modulating the proliferation and activity of infiltrated T cells.
Subject(s)
Amino Acyl-tRNA Synthetases , Nephritis, Interstitial , Renal Insufficiency , Animals , Humans , Mice , Amino Acyl-tRNA Synthetases/metabolism , CD8-Positive T-Lymphocytes , Cell Proliferation , Fibrosis , Homeodomain Proteins , Nephritis, Interstitial/chemically induced , Nephritis, Interstitial/genetics , Nephritis, Interstitial/drug therapyABSTRACT
OBJECTIVE: To develop a preliminary risk scoring system to predict the prognosis of patients with diabetic forefoot ulcers based on the severity of vasculopathy and infection, which are the major risk factors for amputation. METHODS: Forefoot was defined as the distal part of the foot composed of the metatarsal bones and phalanges and associated soft tissue structures. The degree of vasculopathy was graded as V0, V1, or V2 according to transcutaneous partial oxygen tension values and toe pressure. The degree of infection was graded as I0, I1, or I2 according to tissue and bone biopsy culture results. The risk scores were calculated by adding the scores for the degree of vasculopathy and infection and ranged from 0 to 4. Wound healing outcomes were graded as healed without amputation, minor amputation, or major amputation. The authors evaluated wound healing outcomes according to risk scores. RESULTS: As the risk score increased, the proportion of patients who underwent both major and minor amputations increased (P < .001). In the multivariate logistic analysis, the odds ratios of amputation also increased as the risk score increased. Patients with a risk score of 4 were 75- and 19-fold more likely to undergo major and minor amputations, respectively, than patients with a risk score of 0 (P = .006 and P < .001). CONCLUSIONS: The risk score can be used as an indicator to predict the probability of amputation in patients with diabetic forefoot ulcers.
Subject(s)
Diabetes Mellitus , Diabetic Foot , Humans , Diabetic Foot/diagnosis , Diabetic Foot/therapy , Ulcer , Foot , Wound Healing , Amputation, SurgicalABSTRACT
Mesangial proliferation is a diagnostic feature and a prognostic predictor of immunoglobulin A nephropathy (IgAN). We aimed to investigate the gene expression profiles of IgAN glomerulus according to the presence of mesangial proliferation. We performed spatial-specific transcriptomic profiling on kidney biopsy tissues using the GeoMx Digital Spatial Profiler. Twelve cases with three glomeruli for each case were profiled using direct pathologic classification (4 M1-IgAN, 4 M0-IgAN, and 4 donor controls). The results of enriched glom-specific genes demonstrated that M1-IgAN could be distinguished from controls (77 upregulated and 55 downregulated DEGs), while some DEGs were identified between M1-IgAN and M0-IgAN cases (24 upregulated and 8 downregulated DEGs) or between M0 and controls (1 upregulated and 16 downregulated DEGs). TCF21, an early podocyte damage marker, was the only differentially expressed gene (DEG) consistently upregulated in both M1-IgAN and M0-IgAN patients, whereas ATF3, EGR1, DUSP1, FOS, JUNB, KLF2, NR4A1, RHOB, and ZFP36 were consistently downregulated in IgAN cases. Glomeruli from M1-IgAN cases were significantly enriched for cell surface/adhesion molecules and gene expressions associated with vascular development or the extracellular matrix. Spatial transcriptomic analysis may contribute to dissecting structure-specific pathophysiology and molecular changes in IgAN.
Subject(s)
Glomerulonephritis, IGA , Podocytes , Humans , Glomerulonephritis, IGA/pathology , Kidney Glomerulus/pathology , Podocytes/metabolism , Gene Expression Profiling , Cell Adhesion Molecules/metabolism , Cell Proliferation , Basic Helix-Loop-Helix Transcription Factors/metabolismABSTRACT
Diabetes is the leading cause of kidney disease that progresses to kidney failure. However, the key molecular and cellular pathways involved in diabetic kidney disease (DKD) pathogenesis are largely unknown. Here, we performed a comparative analysis of adult human kidneys by examining cell type-specific chromatin accessibility by single-nucleus ATAC-seq (snATAC-seq) and analyzing three-dimensional chromatin architecture via high-throughput chromosome conformation capture (Hi-C method) of paired samples. We mapped the cell type-specific and DKD-specific open chromatin landscape and found that genetic variants associated with kidney diseases were significantly enriched in the proximal tubule- (PT) and injured PT-specific open chromatin regions in samples from patients with DKD. BACH1 was identified as a core transcription factor of injured PT cells; its binding target genes were highly associated with fibrosis and inflammation, which were also key features of injured PT cells. Additionally, Hi-C analysis revealed global chromatin architectural changes in DKD, accompanied by changes in local open chromatin patterns. Combining the snATAC-seq and Hi-C data identified direct target genes of BACH1, and indicated that BACH1 binding regions showed increased chromatin contact frequency with promoters of their target genes in DKD. Thus, our multi-omics analysis revealed BACH1 target genes in injured PTs and highlighted the role of BACH1 as a novel regulator of tubular inflammation and fibrosis.
Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Adult , Humans , Chromatin/genetics , Diabetic Nephropathies/genetics , Chromosomes , Kidney , Fibrosis , Inflammation , Diabetes Mellitus/geneticsABSTRACT
PURPOSE: This study aimed to evaluate the molecular features of clear cell adenocarcinoma (CCA) of the urinary tract and investigate its pathogenic pathways and possible actionable targets. MATERIALS AND METHODS: We retrospectively collected the data of patients with CCA between January 1999 and December 2016; the data were independently reviewed by two pathologists. We selected five cases of urinary CCA, based on the clinicopathological features. We analyzed these five cases by whole exome sequencing (WES) and subsequent bioinformatics analyses to determine the mutational spectrum and possible pathogenic pathways. RESULTS: All patients were female with a median age of 62 years. All tumors were located in the urethra and showed aggressive behavior with disease progression. WES revealed several genetic alterations, including driver gene mutations (AMER1, ARID1A, CHD4, KMT2D, KRAS, PBRM1, and PIK3R1) and mutations in other important genes with tumor-suppressive and oncogenic roles (CSMD3, KEAP1, SMARCA4, and CACNA1D). We suggest putative pathogenic pathways (chromatin remodeling pathway, mitogen-activated protein kinase signaling pathway, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Wnt/ß-catenin pathway) as candidates for targeted therapies. CONCLUSION: Our findings shed light on the molecular background of this extremely rare tumor with poor prognosis and can help improve treatment options.
Subject(s)
Adenocarcinoma, Clear Cell , Humans , Female , Middle Aged , Male , Adenocarcinoma, Clear Cell/genetics , Adenocarcinoma, Clear Cell/pathology , Kelch-Like ECH-Associated Protein 1/genetics , Urethra/pathology , Phosphatidylinositol 3-Kinases , Retrospective Studies , NF-E2-Related Factor 2/genetics , Mutation , DNA Helicases/genetics , Nuclear Proteins/genetics , Transcription Factors/geneticsABSTRACT
Papillary renal neoplasm with reverse polarity (PRNRP) is a renal tumor with frequent KRAS mutations. In this study, we aimed to report the clinical, histological, and immunohistochemical characteristics of PRNRP and the protein expression of various KRAS signaling pathway downstream effectors in PRNRP. PRNRP samples from patients who underwent surgical resection at Seoul National University Hospital over an 11-year period (January 2011 to December 2021) were analyzed. We identified 43 PRNRPs, defined as papillary renal tumors with a thin papillary architecture, eosinophilic finely granular cytoplasm, and apical nuclear position. Immunohistochemistry revealed typical characteristics of PRNRP, including exclusively positive GATA3 (43/43); highly positive L1CAM (43/43), PAX8 (43/43), and EMA (43/43); and low positive AMACR (4/43), RCC (1/43), and vimentin (1/43). KRAS signaling pathway effectors, such as p-ERK, RalA, and RalB, were highly expressed in PRNRP compared to papillary renal cell carcinoma (pRCC) with low or high nuclear grade (P < .001, all). Compared to pRCC with high nuclear grade, patients with PRNRP exhibited significantly longer progression-free survival (P < .001). PRNRP showed the best clinical outcome, with no disease progression in any of the cases. Our study analyzed the largest number of PRNRP cases and is the first to analyze the association between PRNRP and the KRAS downstream signaling pathway. PRNRP was found at a high frequency among all papillary renal tumors (43/207) and demonstrated a very good prognosis. PRNRP showed high GATA3, L1CAM, PAX8, and EMA protein expression as well as high p-ERK, RalA, and RalB protein expression.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neural Cell Adhesion Molecule L1 , Humans , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Kidney Neoplasms/pathology , Carcinoma, Renal Cell/pathology , Signal Transduction , Biomarkers, Tumor/geneticsABSTRACT
Diabetic nephropathy (DN) in the context of type 2 diabetes is the leading cause of end-stage renal disease (ESRD) in the United States. DN is graded based on glomerular morphology and has a spatially heterogeneous presentation in kidney biopsies that complicates pathologists' predictions of disease progression. Artificial intelligence and deep learning methods for pathology have shown promise for quantitative pathological evaluation and clinical trajectory estimation; but, they often fail to capture large-scale spatial anatomy and relationships found in whole slide images (WSIs). In this study, we present a transformer-based, multi-stage ESRD prediction framework built upon nonlinear dimensionality reduction, relative Euclidean pixel distance embeddings between every pair of observable glomeruli, and a corresponding spatial self-attention mechanism for a robust contextual representation. We developed a deep transformer network for encoding WSI and predicting future ESRD using a dataset of 56 kidney biopsy WSIs from DN patients at Seoul National University Hospital. Using a leave-one-out cross-validation scheme, our modified transformer framework outperformed RNNs, XGBoost, and logistic regression baseline models, and resulted in an area under the receiver operating characteristic curve (AUC) of 0.97 (95% CI: 0.90-1.00) for predicting two-year ESRD, compared with an AUC of 0.86 (95% CI: 0.66-0.99) without our relative distance embedding, and an AUC of 0.76 (95% CI: 0.59-0.92) without a denoising autoencoder module. While the variability and generalizability induced by smaller sample sizes are challenging, our distance-based embedding approach and overfitting mitigation techniques yielded results that suggest opportunities for future spatially aware WSI research using limited pathology datasets.
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BACKGROUND: Aquaporin (AQP) expression has been investigated in various malignant neoplasms, and the overexpression of AQP is related to poor prognosis in some malignancies. However, the expression of AQP protein in clear cell renal cell carcinoma (ccRCC) has not been extensively investigated by immunohistochemistry with large sample size. METHODS: We evaluated the AQP expression in 827 ccRCC with immunohistochemical staining in tissue microarray blocks and classified the cases into two categories, high and low expression. RESULTS: High expression of aquaporin-1 (AQP1) was found in 320 cases (38.7%), but aquaporin-3 was not expressed in ccRCC. High AQP1 expression was significantly related to younger age, low TNM stage, low World Health Organization/International Society of Urologic Pathology nuclear grade, and absence of distant metastasis. Furthermore, high AQP1 expression was also significantly associated with longer overall survival (OS; p<.001) and progression-specific survival (PFS; p<.001) and was an independent predictor of OS and PFS in ccRCC. CONCLUSIONS: Our study revealed the prognostic significance of AQP1 protein expression in ccRCC. These findings could be applied to predict the prognosis of ccRCC.
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Microsatellite instability (MSI) refers to alterations in the length of simple repetitive genomic sequences. MSI status serves as a prognostic and predictive factor in colorectal cancer. The MSI-high status is a good prognostic factor in stage II/III cancer, and predicts a lack of benefit to adjuvant fluorouracil chemotherapy in stage II cancer but a good response to immunotherapy in stage IV cancer. Therefore, determining MSI status in patients with colorectal cancer is important for identifying the appropriate treatment protocol. In the Pathology Artificial Intelligence Platform (PAIP) 2020 challenge, artificial intelligence researchers were invited to predict MSI status based on colorectal cancer slide images. Participants were required to perform two tasks. The primary task was to classify a given slide image as belonging to either the MSI-high or the microsatellite-stable group. The second task was tumor area segmentation to avoid ties with the main task. A total of 210 of the 495 participants enrolled in the challenge downloaded the images, and 23 teams submitted their final results. Seven teams from the top 10 participants agreed to disclose their algorithms, most of which were convolutional neural network-based deep learning models, such as EfficientNet and UNet. The top-ranked system achieved the highest F1 score (0.9231). This paper summarizes the various methods used in the PAIP 2020 challenge. This paper supports the effectiveness of digital pathology for identifying the relationship between colorectal cancer and the MSI characteristics.
Subject(s)
Colorectal Neoplasms , Microsatellite Instability , Humans , Artificial Intelligence , Prognosis , Fluorouracil/therapeutic use , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathologyABSTRACT
Background: The heterogeneous phenotype of diabetic nephropathy (DN) from type 2 diabetes complicates appropriate treatment approaches and outcome prediction. Kidney histology helps diagnose DN and predict its outcomes, and an artificial intelligence (AI)-based approach will maximize clinical utility of histopathological evaluation. Herein, we addressed whether AI-based integration of urine proteomics and image features improves DN classification and its outcome prediction, altogether augmenting and advancing pathology practice. Methods: We studied whole slide images (WSIs) of periodic acid-Schiff-stained kidney biopsies from 56 DN patients with associated urinary proteomics data. We identified urinary proteins differentially expressed in patients who developed end-stage kidney disease (ESKD) within two years of biopsy. Extending our previously published human-AI-loop pipeline, six renal sub-compartments were computationally segmented from each WSI. Hand-engineered image features for glomeruli and tubules, and urinary protein measurements, were used as inputs to deep-learning frameworks to predict ESKD outcome. Differential expression was correlated with digital image features using the Spearman rank sum coefficient. Results: A total of 45 urinary proteins were differentially detected in progressors, which was most predictive of ESKD (AUC=0.95), while tubular and glomerular features were less predictive (AUC=0.71 and AUC=0.63, respectively). Accordingly, a correlation map between canonical cell-type proteins, such as epidermal growth factor and secreted phosphoprotein 1, and AI-based image features was obtained, which supports previous pathobiological results. Conclusions: Computational method-based integration of urinary and image biomarkers may improve the pathophysiological understanding of DN progression as well as carry clinical implications in histopathological evaluation.
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OBJECTIVE: Lymphedema, especially in the advanced stage, is a growing challenge in extremity reconstruction, with few applicable surgical methods. Despite its importance, no consensus has been reached regarding a single surgical method yet. Herein, the authors introduce a novel concept of lymphatic reconstruction yielding promising results. METHODS: We included 37 patients with advanced-stage upper extremity lymphedema who underwent lymphatic complex transfers, consisting of both lymph vessel and node transfers, from 2015 to 2020. We compared the preoperative and postoperative (last visit) mean circumferences and volume ratios between the affected and unaffected limbs. Changes in the Lymphedema Life Impact Scale scores and complications were also investigated. RESULTS: The circumference ratio (affected to unaffected limbs) improved at all measuring points (P < .05), while the volume ratio showed a decrease from 1.54 to 1.39 (P < .001). The mean Lymphedema Life Impact Scale decreased from 48.1 ± 15.2 to 33.4 ± 13.8 (P < .05). No donor site morbidities, including iatrogenic lymphedema or any other major complications, were observed. CONCLUSIONS: A new technique for lymphatic reconstruction, lymphatic complex transfer, may be useful in cases of advanced stage lymphedema because of its effectiveness and the low possibility of donor site lymphedema.
Subject(s)
Lymphedema , Plastic Surgery Procedures , Humans , Lymph Nodes , Lymphedema/diagnostic imaging , Lymphedema/etiology , Lymphedema/surgery , Upper Extremity , Mastectomy/adverse effectsABSTRACT
Extensive inferomedial blow-out fractures involving the inferomedial orbit strut frequently result in severe ophthalmic complications. Therefore, anatomical reconstruction is essential but is still technically challenging. Thus, the authors have used a novel technique using a combination of single fan-shaped titanium-reinforced porous polyethylene (TR-PPE) implants and a bidirectionally extended transconjunctival approach. Herein, the authors describe our surgical technique and discuss its effectiveness. First, the transconjunctival approach was performed and was subsequently extended medially using the transcaruncular approach and laterally using lateral blepharotomy. After the origin of the inferior oblique muscle was identified, a trimmed fan-shaped TR-PPE implant was inserted into the orbital floor. It was subsequently rotated and bent at the site of origin of the IO muscle and moved upward to cover the superior bony ledge of the medial wall. Finally, the implant was fixed to the orbital rim. Anatomical orbital reconstruction was confirmed by a computed tomographic scan. The preoperative diplopia in 19 patients, resolved within 1 week in 16 patients and in 3 to 6 months in the remaining 3 patients. Preoperative enophthalmos >2 mm in all patients improved to <2 mm in 67 patients and 3 mm in 2 patients (>7 mm preoperatively). The postoperative course was uneventful, and no severe complications were observed. The authors believe that the placement of a fan-shaped TR-PEE implant into the orbit through the bidirectionally extended transconjunctival approach could be a viable option for the anatomical reconstruction of extensive inferomedial blow-out fractures involving the inferomedial orbital strut.
Subject(s)
Dental Implants , Enophthalmos , Orbital Fractures , Humans , Polyethylene , Orbital Fractures/diagnostic imaging , Orbital Fractures/surgery , Titanium , Treatment Outcome , Porosity , Orbit/surgery , Retrospective StudiesABSTRACT
OBJECTIVES: Urine cytology is the most widely used noninvasive screening tool for urothelial carcinoma diagnosis and surveillance. Although highly specific, urine cytology exhibits suboptimal sensitivity. This study aimed to determine whether hTERT immunocytochemistry (ICC) could be applicable as an ancillary test in routine cytology practice. METHODS: A total of 561 urinary tract samples were initially screened in this study. All of them were prepared using SurePath liquid-based cytology (LBC), while additional LBC slides were made and subsequently used for hTERT (SCD-A7) ICC. RESULTS: From the 561 samples screened, 337 were finally analyzed, all having an adequate cellularity and available follow-up histology. The hTERT ICC-positive rate was 95.9% (n = 208/217), 96% (n = 24/25), and 100% (n = 4/4) in cytology samples with high-grade urothelial carcinoma, carcinoma in situ, and low-grade urothelial carcinoma subsequent histology. Among the 64 atypical cytology cases histologically confirmed as urothelial carcinomas, 92.2% (n = 59/64) were immunoreactive to hTERT, whereas the two histologically benign cases were ICC-negative. 87/90 (96.7%) of the cytology cases confirmed to be benign in follow-up were hTERT-negative. The overall sensitivity and specificity of hTERT ICC were 96.3% and 98.8%, respectively (AUROC = 0.963; 95% CI = 0.960-0.967). CONCLUSIONS: The hTERT ICC test exhibited consistent and intense staining in malignant urothelial cells, suggesting its value as an ancillary test in liquid-based urine cytology.
Subject(s)
Carcinoma, Transitional Cell , Telomerase , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/pathology , Prospective Studies , Immunohistochemistry , Biomarkers, Tumor/urine , CytodiagnosisABSTRACT
BACKGROUND: Clear cell papillary renal cell tumor (CCPRCT) was first reported in 2006 a patient with end stage renal disease. After that it was discovered in the kidney without end stage renal disease in the 2010s and started to be mentioned in pathology and urology. The incidence of CCPRCT is low and most of it is discovered incidentally, so there is a lack of reports on clinical characteristics and surgical outcome. METHODS: This study used clinical data from the Seoul National University Prospectively Enrolled Registry for Renal Cell Carcinoma-Nephrectomy (SUPER-RCC-Nx). Between August 2016 and July 2022, patients who underwent radical or partial nephrectomy with clear cell papillary RCC with pathological finding were included in this study. All patients' pathologic reports were reviewed by 1 pathologist. Clinical characteristics and surgical outcomes were presented through descriptive statistics, and Kaplan-Meier curve used for survival analysis. RESULTS: Of the 2057 patients, CCPRCT was reported in 36 patients (1.8%). The median follow up period was 26.8 months. The median age was 67 years, and there were 10 females and 26 males. The median tumor size was 1.2 cm. Twenty-nine patients underwent partial nephrectomy. Seven patients with end-stage renal disease underwent radical nephrectomy. The median operative time for patients who underwent partial nephrectomy was 97.5 min and the estimated blood loss was 100 cc. The median hospital days was 4 and 30-day complications were 2 cases with clavien-dindo classification III or higher. During the follow-up period, there was no recurrence and cancer specific mortality. CONCLUSIONS: The size of CCPRCT was small and there was no advanced stage at that time of diagnosis. There was no recurrence or cancer specific mortality during the follow-up period. A multi-center study with a large scale is needed in the future. TRIAL REGISTRATION: Seoul National University Hospital (SNUH) Institutional Review Board (IRB) (approval number: 2210-126-1371).
Subject(s)
Carcinoma, Renal Cell , Kidney Failure, Chronic , Kidney Neoplasms , Male , Female , Humans , Aged , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Prospective Studies , Nephrectomy , Kidney Failure, Chronic/surgery , Treatment Outcome , Retrospective StudiesABSTRACT
Diabetic nephropathy (DN) in the context of type 2 diabetes is the leading cause of end-stage renal disease (ESRD) in the United States. DN is graded based on glomerular morphology and has a spatially heterogeneous presentation in kidney biopsies that complicates pathologists' predictions of disease progression. Artificial intelligence and deep learning methods for pathology have shown promise for quantitative pathological evaluation and clinical trajectory estimation; but, they often fail to capture large-scale spatial anatomy and relationships found in whole slide images (WSIs). In this study, we present a transformer-based, multi-stage ESRD prediction framework built upon nonlinear dimensionality reduction, relative Euclidean pixel distance embeddings between every pair of observable glomeruli, and a corresponding spatial self-attention mechanism for a robust contextual representation. We developed a deep transformer network for encoding WSI and predicting future ESRD using a dataset of 56 kidney biopsy WSIs from DN patients at Seoul National University Hospital. Using a leave-one-out cross-validation scheme, our modified transformer framework outperformed RNNs, XGBoost, and logistic regression baseline models, and resulted in an area under the receiver operating characteristic curve (AUC) of 0.97 (95% CI: 0.90-1.00) for predicting two-year ESRD, compared with an AUC of 0.86 (95% CI: 0.66-0.99) without our relative distance embedding, and an AUC of 0.76 (95% CI: 0.59-0.92) without a denoising autoencoder module. While the variability and generalizability induced by smaller sample sizes are challenging, our distance-based embedding approach and overfitting mitigation techniques yielded results that sugest opportunities for future spatially aware WSI research using limited pathology datasets.
ABSTRACT
BACKGROUND: This study aimed to evaluate whether mucous fistula refeeding (MFR) is safe and beneficial for the growth and intestinal adaptation of preterm infants with enterostomies. METHODS: This exploratory randomized controlled trial enrolled infants born before 35 weeks' gestation with enterostomy. If the stomal output was ≥ 40 mL/kg/day, infants were assigned to the high-output MFR group and received MFR. If the stoma output was < 40 mL/kg/day, infants were randomized to the normal-output MFR group or the control group. Growth, serum citrulline levels, and bowel diameter in loopograms were compared. The safety of MFR was evaluated. RESULTS: Twenty infants were included. The growth rate increased considerably, and the colon diameter was significantly larger after MFR. However, the citrulline levels did not significantly differ between the normal-output MFR and the control group. One case of bowel perforation occurred during the manual reduction for stoma prolapse. Although the association with MFR was unclear, two cases of culture-proven sepsis during MFR were noted. CONCLUSIONS: MFR benefits the growth and intestinal adaptation of preterm infants with enterostomy and can be safely implemented with a standardized protocol. However, infectious complications need to be investigated further. TRIAL REGISTRATION: clinicaltrials.gov NCT02812095, retrospectively registered on June 6, 2016.