Parenchymal Loss Research Articles

S2660 Imatinib Mesylate (Gleevec)-Induced Acute Liver Failure Successfully Treated With Prednisolone Therapy

INTRODUCTION: Imatinib mesylate (Gleevec) is an FDA approved tyrosine-kinase inhibitor for treatment of resected, high-risk and advanced gastrointestinal stromal tumors (GISTs) and chronic myeloid leukemia.1-4% of patients on imatinib therapy develop drug-induced liver injury (DILI) with a minority developing acute liver failure, or even death. We report a clinical case of imatinib-induced acute liver failure in a 46-year-old woman with a GIST of the esophagus/mediastinum successfully treated with corticosteroids. CASE DESCRIPTION/METHODS: A 46-year-old woman with stage IIIa posterior mediastinal GIST at the gastroesophageal junction status post-surgical resection with pathology showing 38 mitosis per high power field on adjuvant imatinib therapy since October 2019 presented in December 2019 with emesis, jaundice and encephalopathy. On exam, she had jaundice and grade 3 hepatic encephalopathy with no focal neurological deficit. The liver associated enzymes revealed elevated ALP 165U/I, ALT 694U/I, AST 635U/I and total bilirubin of 3.0 mg/dL. The ammonia level was 65 uMol/L and INR was 2.3 prompting discontinuation of imatinib.During the hospital course, liver enzymes trended up. Serum assessment for viral hepatitis, autoimmune hepatitis, metabolic liver disease and toxicology testing was negative. Liver ultrasound and abdominal MRI were unremarkable. Liver biopsy revealed extensive inflammation of the liver parenchyma consisting primarily of neutrophils and a few lymphocytes with foci of parenchymal loss and bridging necrosis (Figure 1). A diagnosis of DILI likely secondary to imatinib was made. After initiation of prednisolone, her encephalopathy and jaundice improved. The liver enzymes and total bilirubin also trended down over a 6 week period (Figure 2,3). DISCUSSION: Imatinib therapy can cause serious side effects, such as acute hepatitis and rarely acute liver failure and death. Liver injury is thought onset varies from 6 days to several years after the initiation of treatment. However, in most cases, acute liver injury develops within a period of 2 to 6 months. Hepatotoxicity usually resolves with either dosage reduction or discontinuation of imatinib. The mechanism of imatinib-induced hepatotoxicity is unknown, however, it has been proposed that imatinib causes immune stimulation. In this case, we successfully employed prednisolone as a novel therapy to treat imatinib induced acute liver failure.This supports the notion that liver injury by imatinib is due to systemic inflammation and direct hepatocyte injury.Figure 1.: extensive inflammation of the liver parenchyma consisting primarily of neutrophils and a few lymphocytes with foci of parenchymal loss and bridging necrosis.Figure 2.: Liver enzymes trend after initiation of prednisolone therapy.Figure 3.: Biliribin trend.

Renal infarction as an uncommon cause of abdominal pain. A case report

Renal infarction is a rare cause of abdominal pain whose diagnosis is often misunderstood or severely delayed. The difficulty in identifying this time-dependent condition greatly limits the possibilities of therapeutic intervention and determines the loss of renal parenchyma that could have been saved with prompt diagnosis. It is, therefore, essential to include renal infarction in the differential diagnosis in case of abdominal pain and to identify this pathology beforehand. We present a case of a 65-yearold male with atrial fibrillation in therapy with Edoxaban who was admitted to the hospital for acute onset of widespread abdominal pain with nausea, vomit, and a worsening of renal function according to the laboratory tests. An abdominal computed tomography with contrast confirmed the presence of a bilateral renal infarction. The patient developed chronic kidney disease and was discharged on anticoagulant therapy. The aim of this paper is, therefore, to increase physician awareness towards this condition, the best opportunity to diagnose early renal infarction and to establish acute and long-term therapy.

Hepatotoxicity and biochemical evaluation of a novel breakfast food produced from the blend of fonio (Digitaria iburua Stapf) and pigeon pea (Cajanus cajan (L.) Millspaugh) in albino rats

BackgroundThe production of novel foods from underutilized nutritious tropical crops is increasing; however, the toxicological studies are sparse. In this study, the safety of the breakfast food produced from the blend of fonio and pigeon pea was examined by evaluating the biochemical and toxicological parameters of the breakfast food using Wistar albino rats. Twenty male Wistar albino rats subdivided into 4 groups of 5 were separately fed with four food samples (100% fonio, 80:20 fonio:pigeon pea, standard rat feed (control) and a commercial brand of corn flake) for 28 days after which the animals were sacrificed and blood samples collected for analyses. Body weight, blood glucose, biochemical, and hematological parameters were examined during the experimental period.ResultsThe feeding of rats with the four diets did not cause mortality and adverse toxicity during the experimental period. Steady body weight gain was observed in fonio-pigeon pea fed rats, and slight changes were obtained in percentage blood glucose. There was no significant difference in the levels of white blood cells, lymphocytes, mean corpuscular volume, platelet, high-density lipoprotein, catalase, SOD, and malondialdehyde of the group fed with fonio-pigeon pea diet as compared with the control group. Furthermore, significant (p < 0.05) lower levels of density lipoprotein, triacylglyceride, and cholesterol were observed in the fonio-pigeon pea-fed rats than the control group. The liver function marker of fonio-pigeon pea-fed-rat and the control showed no significant difference.ConclusionThe study showed no severe toxicity in the test animals, although a mild loss of liver parenchyma and variation in size and shape of nuclei were observed in the group fed with the fonio-pigeon pea diet.

Low serum trypsinogen levels in chronic pancreatitis: Correlation with parenchymal loss, exocrine pancreatic insufficiency, and diabetes but not CT-based cambridge severity scores for fibrosis

BackgroundChronic pancreatitis (CP) is a complex inflammatory disorder of the pancreas affecting acinar cells, duct cells, islet cells and inflammatory cells including fibrosis-producing stellate cells. Serum trypsinogen is a biomarkers of acinar cell function. AimTo define the degree of correlation between low trypsinogen levels as a marker of acinar cell function and variable features of CP. MethodsSerum samples from previously ascertained and well phenotyped case and control subjects from the North American Pancreatitis Study II (NAPS2) were used to measure serum trypsinogen levels in a commercial laboratory. Control samples were used to define normal ranges and compared with levels in CP patients with defined features. ResultsA final cohort of 279 CP patients and 262 controls from the NAPS2 studies were evaluated. In controls trypsinogen had a mean of 34.96 ng/ml and SD = 11.99. Cut-off values for low trypsinogen ranged from <20 to 10 ng/ml and very low trypsinogen at <10 ng/ml. Compared to controls, CP was associated with very low trypsinogen levels (p < 0.0001). Within CP, very low trypsinogen levels correlated with parenchymal loss (pancreatic surgery [p < 0.05]; atrophy with calcifications, [p < 0.001]), EPI (p < 0.01, trend p < 0.001) and diabetes (trend p < 0.01) but not CT-based criteria for fibrosis (pancreatic duct dilation, irregularity, strictures). ConclusionsVery low serum trypsinogen levels correlate with measures of acinar cell loss including surgical resection, atrophic-calcific CP, diabetes and functional symptoms EPI but not duct morphology criteria. Serum trypsinogen levels correlate with decreased acinar cell function and therefore have biomarker utility clinical management.

Quantitative contrast-enhanced ultrasound of the brain on twin fetal lambs maintained by the extrauterine environment for neonatal development (EXTEND): initial experience.

With the development of an artificial environment to support the extremely premature infant, advanced imaging techniques tested in this extrauterine system might be beneficial to evaluate the fetal brain. We evaluated the feasibility of (a) performing contrast-enhanced ultrasound (CEUS) and (b) quantifying normal and decreased brain perfusion in fetal lambs maintained on the extrauterine environment for neonatal development (EXTEND) system. Twin premature fetal lambs (102days of gestational age) were transferred to the EXTEND system. Twin B was subjected to sub-physiological flows (152mL/kg/min) and oxygen delivery (15.9mL/kg/min), while Twin A was maintained at physiological levels. We administered Lumason contrast agent into the oxygenator circuit and performed serial CEUS examinations. We quantified perfusion parameters and generated parametric maps. We also recorded hemodynamic parameters, serum blood analysis, and measurements across the oxygenator. Postmortem MRIs were performed. No significant changes in hemodynamic variables were attributable to CEUS examinations. On gray-scale images, Twin B demonstrated ventriculomegaly and progressive parenchymal volume loss culminating in hydranencephaly. By CEUS, Twin B demonstrated decreased peak enhancement and decreased overall parenchymal perfusion when compared to Twin A by perfusion parameters and parametric maps. Changes in perfusion parameters were detected immediately following blood transfusion. Postmortem MRI confirmed ultrasonographic findings in Twin B. In this preliminary experience, we show that CEUS of the brain is feasible in fetal lambs maintained on the EXTEND system and that changes in perfusion can be quantified, which is promising for the application of CEUS in this extrauterine system supporting the premature infant.

Grading of Hydronephrosis: An Ongoing Challenge

The crucial point for prompt diagnostics, ideal therapeutic approach, and follow-up of hydronephrosis associated with UPJ anomalies in children is the severity of hydronephrosis. Such many hydronephrosis grading systems as AP diameter, SFU, radiology, UTD, and Onen have been developed to evaluate hydronephrosis severity in infants. Unfortunately, it is still an ongoing challenge and there is no consensus between different disciplines. AP diameter is a very dynamic parameter and is affected by many factors (hydration, bladder filling, position, respiration). More importantly, its measurement is very variable and misleading due to different renal pelvic configurations. The radiology grading system has the same grades 1, 2, and 3 as the SFU grading system with addition of the AP diameter for the first 3 grades. This grading system divides parenchymal loss into two different grades. Grade 4 represents mild parenchymal loss while grade 5 suggests severe parenchymal loss. However, it is operator dependent, is not decisive, and does not differentiate grades 4 and 5 clearly. All grades of SFU are very variable between operators and clinicians. UTD classification aims to put all significant abnormal urinary findings together including the kidney, ureter, and bladder and thus determines the risk level for infants with any urinary disease. Different renal deterioration risks occur depending on the mechanism of hydronephrosis. Therefore, SFU and UTD classification may result in significant confusion and misleading in determining the severity of hydronephrosis. SFU-4 and UTD-P3 represent a considerable range of severity of hydronephrosis. Both represent minimal thinning of the medullary parenchyma and severe thinning of the cortical parenchyma (cyst-like hydronephrotic kidneys) at the same grade. The wide definition of SFU-4 and UTD-P3 fails to indicate accurately the severity of hydronephrosis and thus significantly misleads from a prompt treatment. They do not suggest who need surgical treatment and who can safely be followed non-operatively. The anatomy and physiology of the 4 suborgans of the kidney (renal pelvis, calices, medulla, and cortex) are completely different from each other. Therefore, each part of the kidney affect and behave differently as a response to UPJ-type hydronephrosis (UPJHN) depending on the severity of hydronephrosis. The upgraded Onen hydronephrosis grading system has been developed based on this basic evidence both for prenatal and post-natal periods. The Onen grading system determines specific detailed findings of significant renal damage, which clearly show and suggest who can safely be followed conservatively from who will need surgical intervention for UPJHN. Neither AP diameter nor radiology, SFU, or UTD classification is the gold standard in determining the severity of hydronephrosis. All these grading systems are based on subjective parameters and are affected by many factors. They do not determine the exact severity of UPJHN and thus cause permanent renal damage due to a delay in surgical decision in some infants while they may cause an unnecessary surgery in others. The Onen grading system has resolved all disadvantages of other grading systems and promises a safer follow-up and a prompt treatment for UPJHN. It is an accurate and easily reproducible grading that has high sensitivity and specificity.

Extent and characteristics of carotid plaques and brain parenchymal loss in asymptomatic patients with no indication for revascularization.

Extent of subclinical atherosclerosis has been associated with brain parenchymal loss in community-dwelling aged subjects. Identification of patient-related and plaque-related markers could identify subjects at higher risk of brain atrophy, independent of cerebrovascular accidents. Aim of the study was to investigate the relation between extent and characteristics of carotid plaques and brain atrophy in asymptomatic patients with no indication for revascularization. Sixty-four patients (aged 69±8years, 45% females) with carotid stenosis <70% based on Doppler flow velocity were enrolled in the study. Potential causes of cerebral damage other than atherosclerosis, including history of atrial fibrillation, heart failure, previous cardiac or neurosurgery and neurological disorders were excluded. All subjects underwent carotid computed tomography angiography, contrast enhanced ultrasound for assessment of plaque neovascularization and brain magnetic resonance imaging for measuring brain volumes. On multivariate regression analysis, age and fibrocalcific plaques were independently associated with lower total brain volumes (β=-3.13 and β=-30.7, both p<0.05). Fibrocalcific plaques were also independently associated with lower gray matter (GM) volumes (β=-28.6, p=0.003). On the other hand, age and extent of carotid atherosclerosis were independent predictors of lower white matter (WM) volumes. WM and GM have different susceptibility to processes involved in parenchymal loss. Contrary to common belief, our results show that presence of fibrocalcific plaques is associated with brain atrophy.

Measuring volumetric segmentation changes in the ipsilateral and contralateral kidney postpartial nephrectomy

ObjectiveTo analyze the volumetric changes of the ipsilateral and contralateral kidneys and their effect on functional outcome post partial nephrectomy using segmentation analysis. Patients and methodsWe have analyzed the data of 119 patients from a single surgeon series of partial nephrectomy patients. Median follow-up was 11.40 months. Patients with bilateral tumors, and solitary kidney were excluded from analysis. Volumetric measurements were performed using a semiautomated tissue segmentation tool. A simple linear regression model to assess the predictors for parenchymal volume loss (PVL). A multivariable linear regression model was used to evaluate the association between PVL and warm ischemia time (WIT), controlling for other factors. ResultsMean WIT was 12.09 ± 4.40 minutes and the mean percentage decrease in the volume of the operated kidney was 16.99 ± 13.49%. WIT (β = 1.24, P < 0.001) and tumor complexity (simple vs. intermediate, β = 0.06, P = 0.984; simple vs. high, β = 11.62,P = 0.007) were associated with PVL. A 1 minute increase in WIT was associated with an increase in the percentage volume loss in the operated kidney by 1.38% (β = 1.20, P < 0.001). Patients with high tumor complexity (β = 11.17, P = 0.009) had a significantly higher percentage volume loss compared to patients with simple tumor complexity. Ipsilateral PVL (β = −0.35, P = 0.015) and male gender (β = −9.89, P = 0.021) were associated with change in eGFR. After adjusting for confounders, % volume loss (β = −0.32, P < 0.001) remained a significant predictor for contralateral hypertrophy. ConclusionTumor complexity results in higher WIT and increased PVL as measured by volumetric segmentation. PVL is a key factor associated with functional outcome, and is directly linked to WIT. Increased PVL is also associated with decreased contralateral hypertrophy. Prospective studies with larger samples sizes will be required to validate our findings.

Arsenic induces dose-dependent structural and ultrastructural pathological remodeling in the heart of Wistar rats

AimArsenic, an environmental contaminant, represents a public health problem worldwide. Studies have shown its association with molecular mechanisms related to cardiomyocytes redox balance. However, the microstructure and ultrastructure of cardiac tissue, as well as the activity of its antioxidant defenses front of disturbances in the mineral bioavailability induced by arsenic are still scarce. Thus, the aim of this study was to evaluate if arsenic exposure might induce structural and ultrastructural damages in cardiac tissue, including pathological remodeling of the parenchyma and stroma. Moreover, its impact on micromineral distribution and antioxidant enzymes activity in heart tissue was also evaluated. Main methodsAdult male Wistar rats were divided into three groups that received 0, 1 and 10 mg/L sodium arsenite in drinking water for eight weeks. The hearts were collected and subjected to structural and ultrastructural analysis, mineral microanalysis and antioxidant enzymes quantification. Functional markers of cardiac damages were evaluated using serum samples. Key findingsArsenic exposure induced dose-dependent structural and ultrastructural remodeling of cardiac tissue, with parenchyma loss, increase of stroma components, collagen deposition, and pathological damages such as inflammation, sarcomere disorganization, mitochondria degeneration and myofilament dissociation. Moreover, this metalloid was bioaccumulated in the tissue affecting its micromineral content, which resulted in antioxidant imbalance and increased levels of oxidative stress and cardiac markers. SignificanceTaken together, our findings indicate that the heart is a potential target to arsenic toxicity, and long-term exposure to this metalloid must be avoided, once it might induce several cardiac tissue pathologies.

PT188 - Hypertension and cardiovascular morbidity following radical nephrectomy are only sustained by renal parenchyma loss and cardiovascular morbidity

PT188 - Hypertension and cardiovascular morbidity following radical nephrectomy are only sustained by renal parenchyma loss and cardiovascular morbidity

Pancreatitis crónica

Chronic pancreatitis is a chronic inflammatory disease of the pancreas that is accompanied by parenchymal fibrosis and loss of functional tissue, which in advanced phases leads to the onset of exocrine and endocrine pancreatic insufficiency. There are various causes that are currently summarised in the TIGAR-O classification, the most common of which is toxic-metabolic (alcohol and tobacco). The most common clinical manifestations are abdominal pain and symptoms resulting from exocrine pancreatic insufficiency. The diagnosis of chronic pancreatitis is based on detecting a) morphological abnormalities (with endoscopic ultrasonography and cholangiopancreatography by magnetic resonance imaging with secretin and magnetic resonance imaging with gadolinium) and/or b) functional abnormalities (with the secretin test). Exocrine pancreatic insufficiency is analysed through the faecal elastase test, combined with a complete nutritional study or with methods such as the 13C-mixed triglyceride breath test. Treatment for the disease is focused on treating the cause, controlling the symptoms (mainly pain) and managing its functional (e.g., exocrine and endocrine pancreatic insufficiency) and morphological complications (e.g., pseudocyst, pseudoaneurysm and pancreatic cancer).

Surgical details and renal function change after robot-assisted partial nephrectomy.

To investigate whether differences in surgical details during robot-assisted partial nephrectomy impact postoperative renal function. Patient, tumor and perioperative characteristics of 751 patients who underwent robot-assisted partial nephrectomy were analyzed with respect to the difference in ipsilateral glomerular filtration rate measured by diethylenetetramine pentaacetic acid renal scan. Detailed surgical methods defined for tumor excision (cutting vs splitting), hemostasis (suturing vs clipping) and renorrhaphy (continuous vs interrupted) were analyzed for early glomerular filtration rate decline and long-term recovery. The glomerular filtration rate of the entire cohort decreased by 9.8mL/min/1.73m2 (22%) at 3months postoperatively, gradually increasing thereafter. The recovery slope was 1.7mL/min/1.73m2 /year during a median follow-up period of 23.0months. Early glomerular filtration rate decline was more pronounced in the cutting group (23.5 vs 20.1%, P=0.009). Clipping was associated with less glomerular filtration rate decline throughout the observation period, and the recovery slope was also significantly higher (2.7 vs 1.1mL/min/1.73m2 /year). In multivariate analysis, early decline was associated with age, preoperative glomerular filtration rate, parenchymal volume loss and ischemia >25min. With respect to long-term recovery, suturing had the greatest adverse impact (β=-5.060, P<0.0001, 95% confidence interval -7.709, -2.411) in addition to parenchymal volume reduction and early decline. In the propensity-matched cohort accounting for differences in tumor size and complexity, suturing was persistently associated with a significant glomerular filtration rate decline until >2years after surgery. Hemostatic sutures during robot-assisted partial nephrectomy might interfere with long-term renal function recovery irrespective of parameters that determine the initial function change. As the splitting method reduces the use of sutures, modifying these details might help preserve renal function.

Effect of Gallic acid and Myricetin on ovarian cancer models: a possible alternative antitumoral treatment

BackgroundOvarian cancer is the leading cause of mortality among malignant gynecological tumors. Surgical resection and chemotherapy with intravenous platinum/taxanes drugs are the treatments of choice, with little effectiveness in later stages and severe toxicological effects. Therefore, this study aimed to evaluate the antineoplastic activity of gallic acid (GA) and myricetin (Myr) administrated peritumorally in Nu/Nu mice xenotransplanted with SKOV-3 cells.MethodsBiological activity of GA and MYR was evaluated in SKOV-3 and OVCAR-3 cells (ovarian adenocarcinomas) by confocal/transmission electron microscopy, PI-flow cytometry, H2-DCF-DA stain, MTT, and Annexin V/PI assays. Molecular targets of compounds were determined with ACD/I-Labs and SEA. Antineoplastic activity was performed in SKOV-3 cells subcutaneously xenotransplanted into female Nu/Nu mice treated peritumorally with 50 mg/kg of each compound (2 alternate days/week) for 28 days. Controls used were paclitaxel (5 mg/kg) and 20 μL of vehicle (0.5% DMSO in 1X PBS). Tumor lesions, organs and sera were evaluated with NMR, USG, histopathological, and paraclinical studies.ResultsIn vitro studies showed a decrease of cell viability with GA and Myr in SKOV-3 (50 and 166 μg/mL) and OVCAR-3 (43 and 94 μg/mL) cells respectively, as well as morphological changes, cell cycle arrest, and apoptosis induction due to ROS generation (p ≤ 0.05, ANOVA). In silico studies suggest that GA and MYR could interact with carbonic anhydrase IX and PI3K, respectively. In vivo studies revealed inhibitory effects on tumor lesions development with GA and MYR up to 50% (p ≤ 0.05, ANOVA), with decreased vascularity, necrotic/fibrotic areas, neoplastic stroma retraction and apoptosis. However, toxicological effects were observed with GA treatment, such as leukocyte infiltrate and hepatic parenchyma loss, hypertransaminasemia (ALT: 150.7 ± 25.60 U/L), and hypoazotemia (urea: 33.4 ± 7.4 mg/dL), due to the development of chronic hepatitis (p ≤ 0.05, ANOVA).ConclusionGA and Myr (50 mg/kg) administered by peritumoral route, inhibit ovarian tumor lesions development in rodents with some toxicological effects. Additional studies will be necessary to find the appropriate therapeutic dose for GA. Therefore, GA and Myr could be considered as a starting point for the development of novel anticancer agents.

PD49-08 HYPERTENSION AND CARDIOVASCULAR MORBIDITY FOLLOWING RADICAL NEPHRECTOMY ARE ONLY SUSTAINED BY RENAL PARENCHYMA LOSS AND CARDIOVASCULAR MORBIDITY

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy V (PD49)1 Apr 2020PD49-08 HYPERTENSION AND CARDIOVASCULAR MORBIDITY FOLLOWING RADICAL NEPHRECTOMY ARE ONLY SUSTAINED BY RENAL PARENCHYMA LOSS AND CARDIOVASCULAR MORBIDITY Alessandro Nini*, Chiara Re, Fabio Muttin, Alberto Martini, Giuseppe Rosiello, Villa Luca, Francesco Trevisani, Daniela Canibus, Francesco Montorsi, Andrea Salonia, Alberto Briganti, Roberto Bertini, Alessandro Larcher, and Umberto Capitanio Alessandro Nini*Alessandro Nini* More articles by this author , Chiara ReChiara Re More articles by this author , Fabio MuttinFabio Muttin More articles by this author , Alberto MartiniAlberto Martini More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Villa LucaVilla Luca More articles by this author , Francesco TrevisaniFrancesco Trevisani More articles by this author , Daniela CanibusDaniela Canibus More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Roberto BertiniRoberto Bertini More articles by this author , Alessandro LarcherAlessandro Larcher More articles by this author , and Umberto CapitanioUmberto Capitanio More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000943.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In patients with no history of preoperative hypertension or major cardiovascular event, the onset of hypertension after radical nephrectomy (RN) is an early event, due probably to the acute loss of renal parenchyma and cardiovascular modifications. The aim of the present study was to test if the removal of adrenal gland during RN, together with acute loss of renal parenchyma, is associated with higher risk of hypertension or major cardiovascular events. METHODS: Within a single institution database, we identified 1,783 patients treated with RN for renal tumour from a prospectively collected database of 3,645 patients between 1990 and 2019. Exclusion criteria were represented by single kidney, metachronous and synchronous kidney tumours. Descriptive statistics were used to report patients´ characteristics. Frequencies and proportions were used for categorical variables. Means, medians, and interquartile ranges (IQR) were used for continuously coded variables. Cox-regression models were used to predict hypertension or major cardiovascular events at follow-up. RESULTS: Median age resulted 62 years (Interquartile range 53-71 years). Overall, 62% underwent RN with adrenalectomy. Preoperative, 44% (199) of patients presented with hypertension, 11% (139) with diabetes, 8% (139) with acute myocardial infarction, 1.9% (33) with heart failure and 3.5% (60) with nephropathy. At discharge, the serum creatinine was over the cut-off in 41% of female patients (1.1 mg/dl) and 77% of male patients (1.2 mg/dl). At a median follow-up of 3 years, 7% (125/1783) of patients had hypertension or major cardiovascular events, one-fourth (31/125) before discharge. At Cox-regression models, predictors of hypertension or major cardiovascular events at follow-up, were age (HR 1.01, CI95% 1.02-1.06, p-value <0.001), nephropathy (HR 2.8, CI95% 1.4-5.6, p-value=0.003) and acute myocardial infarction (HR 1.9, CI95% 1.1-3.2, p=0.01). The removal of adrenal gland was not associated with an increased risk of hypertension or major cardiovascular events at follow-up (p>0.05). CONCLUSIONS: In patients undergoing RN, the risk of hypertension or major cardiovascular events is predicted by presence of nephropathy, heart failure or history of myocardial infarction, but not by the removal of adrenal gland at surgery. The first observation underlines the role of renal parenchyma loss and cardiovascular abnormalities in exposing patients to higher risk of hypertension or major cardiovascular events. The latter may be explained by compensation mechanism of the contralateral adrenal gland. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1003-e1004 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alessandro Nini* More articles by this author Chiara Re More articles by this author Fabio Muttin More articles by this author Alberto Martini More articles by this author Giuseppe Rosiello More articles by this author Villa Luca More articles by this author Francesco Trevisani More articles by this author Daniela Canibus More articles by this author Francesco Montorsi More articles by this author Andrea Salonia More articles by this author Alberto Briganti More articles by this author Roberto Bertini More articles by this author Alessandro Larcher More articles by this author Umberto Capitanio More articles by this author Expand All Advertisement PDF downloadLoading ...

MP80-19 IS RENAL VOLUME AND FUNCTION COMPROMISED IN ONCOCYTOMA PATIENTS ON ACTIVE SURVEILLANCE?

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging/Surveillance III (MP80)1 Apr 2020MP80-19 IS RENAL VOLUME AND FUNCTION COMPROMISED IN ONCOCYTOMA PATIENTS ON ACTIVE SURVEILLANCE? Amandip Cheema*, Arun Menon, Tashionna White, Gaybrielle James, and Eric Kauffman Amandip Cheema*Amandip Cheema* More articles by this author , Arun MenonArun Menon More articles by this author , Tashionna WhiteTashionna White More articles by this author , Gaybrielle JamesGaybrielle James More articles by this author , and Eric KauffmanEric Kauffman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000972.019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The oncologic safety of active surveillance in renal oncocytoma is well reported. However concern remains at the hypothetical possibility of renal functional deterioration due to mechanical effects of an enlarging tumor on normal renal parenchyma. Here we tested this hypothesis by evaluating renal functional outcomes of oncocytoma tumors on AS, including 3-dimension (3-D) imaging software to measure ipsilateral renal parenchymal volumetric changes in patients with large and/or actively growing oncocytoma tumors. METHODS: A renal tumor AS database at Roswell Park Comprehensive Cancer Center was queried to identify all renal oncocytoma patients with at least 18 months follow up on AS. Renal functional outcomes (Cr, GFR) were retrospectively reviewed to determine changes during AS. Tumor volume was calculated using the formula 0.5362*x*y*z when 3 dimensions were available and 0.5362*x*y*(x+y/2) when two dimensions were available. Oncocytoma patients with an estimated volume increase on AS of at least 10 cm3 were selected for automated 3-D volumetric assessment of the tumor and ipsilateral renal parenchyma using CT images with Myrian ® software. Ipsilateral renal parenchymal volume and tumor volume were compared between first and last available CT images. RESULTS: Among a total of 32 oncocytoma patients on AS, 22 with at least 18 months follow up were identified (median 33, mean 37.5, range 19-95 months). Median (mean) estimated tumor volume for these 22 patients was 8.5 cm3 (27.3 cm3) at AS initiation compared to 16.8 cm3 (42.73 cm3) at last follow up. Median (mean) Cr and GFR for these 22 patients was 1.02 mg/dl and 70.9 ml/min/1.73m2 (1.0 and 68.6) at AS initiation compared to 0.89 mg/dl and 79.5 ml/min/1.73m2 (0.9 and 74.2) at last follow up. A total of 9 patients were identified with estimated volume increase of at least 10 cc on AS, most of whom had tumor size >5 cm at last follow up. Tumor volumes calculated for these 9 patients using 3-D imaging software (range 11.3-222) correlated well with estimated tumor volumes (range 9.2-232). The median change in 3-D tumor volume on AS was 26.1 cm3 (mean 40.5, range 12.2-108), while the median change in normal renal parenchymal volume was 4.0 cm3 (mean -1.6, range -35-23). 6/9 (67%) tumors had minimal-to-no decrease (10 cm3 or more) in 3-D renal parenchymal volume on AS. CONCLUSIONS: Loss of renal parenchyma and function may be uncommon in oncocytoma patients regardless of tumor growth and size. This result supports the renal functional safety of AS for oncocytoma, however larger studies with longer follow up and larger tumor volume increases are needed. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1233-e1234 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amandip Cheema* More articles by this author Arun Menon More articles by this author Tashionna White More articles by this author Gaybrielle James More articles by this author Eric Kauffman More articles by this author Expand All Advertisement PDF downloadLoading ...

MP21-06 FACTORS ASSOCIATED WITH PARENCHYMAL VOLUME LOSS FOLLOWING PARTIAL NEPHRECTOMY

INTRODUCTION AND OBJECTIVE:Functional renal parenchymal loss (RPL) is associated with functional outcome following partial nephrectomy (PN). We sought to analyze the association between these facto...

Estimating brain volume loss after radiation therapy in children treated for posterior fossa tumors (Corpus callosum and whole brain volume changes following radiotherapy in children)

More than half of pediatric tumors of central nervous system (CNS) primarily originate in the posterior fossa and are conventionally treated with radiation therapy (RT). The objective of this study was to establish whether corpus callosum volumes (CCV) and whole brain volumes (WBV) are correlated and to determine the impact of whole-brain lowvs high-dose RT on brain parenchymal volume loss as assessed using each technique. Of the 30 identified children (6-12 years) with newly diagnosed posterior fossa tumors treated with cranial RT, including focal and whole-brain RT, suitable imaging was obtained for 23. Radiotherapy regimens were the following: no whole-brain RT (Group 1, n = 7), low-dose whole-brain RT (<30 Gy, Group 2, n = 9) and high-dose whole-brain RT (>30 Gy, Group 3, n = 7) in addition to focal boost. Magnetic resonance images (MRIs) were analyzed at baseline and follow-up (median 14 months). The CCVs were manually segmented on midline sagittal slice (n = 23), while WBVs were segmented semi-automatically using Freesurfer (n = 15). This was done twice (6-month interval) for all baseline CCV measurements and 5 randomly selected WBV measurements to establish measurement reproducibility. Correlations between CCV and WBV were investigated and percentage of children demonstrating reduction in CCV or WBV noted. Correlation between baseline CCV and WBV was not significant (p = 0.37). Measurement reproducibility was from 6% to -9% for CCV and from 4.8% to -1.2% for WBV. Among the children studied, 30.4% (7/23) had >9% reduction in CCV at follow-up, while 33.3% (5/15) had >1.2% reduction in WBV. Five of 7 patients with CCV loss were not picked up by WBV measurements. Similarly, 3 of 5 patients with WBV loss were not picked up by CCV measurements. The CCV and the WBV are unrelated and may indicate different brain parenchymal losses following RT. Up to a third of posterior fossa tumors treated with RT have measurable CCV or WBV loss; incidence was equivalent in lowvs high-dose whole-brain RT.

Targeting the progression of chronic kidney disease.

Chronic kidney disease (CKD) is a devastating condition that is reaching epidemic levels owing to the increasing prevalence of diabetes mellitus, hypertension and obesity, as well as ageing of the population. Regardless of the underlying aetiology, CKD is slowly progressive and leads to irreversible nephron loss, end-stage renal disease and/or premature death. Factors that contribute to CKD progression include parenchymal cell loss, chronic inflammation, fibrosis andreduced regenerative capacity of the kidney. Current therapies have limited effectiveness and only delay disease progression, underscoring the need to develop novel therapeutic approaches to either stop or reverse progression. Preclinical studies have identified several approaches that reduce fibrosis in experimental models, including targeting cytokines, transcription factors, developmental and signalling pathways and epigenetic modulators, particularly microRNAs. Some of these nephroprotective strategies are now being tested in clinical trials. Lessons learned from the failure of clinical studies of transforming growth factor β1 (TGFβ1) blockade underscore the need for alternative approaches to CKD therapy, as strategies that target a single pathogenic process may result in unexpected negative effects on simultaneously occurring processes. Additional promising avenues include preventing tubular cell injury and anti-fibrotic therapies that target activated myofibroblasts, the main collagen-producing cells.

Physiological and Pathological Alterations in the Mammary Gland of Holstein Cows during Transition Period

Background: Physiological and immunological adaptations occurred in peripartum period may be responsible for susceptibility to intramammary infections during colostrogenesis. Increase in blood flow and hormones cause physiological edema by accumulation of lymphatic fluid in interstitial space. Specific composition of mammary secretion increases the susceptibility to mastitis. So, the study of physical, cellular and microbiological changes in the mammary gland in this period are fundamental for understanding, diagnosing and adopting prophylactic measures for bovine mastitis. This study aimed to characterize physiological and pathological changes that occur in the mammary gland during transition period.Materials, Methods &amp; Results: Thirteen cows, in second to fourth lactation were followed from 3 weeks pre-calving to 3 weeks post-calving. Cows were submitted weekly to physical examination of mammary gland, strip cup test, California Mastitis Test (CMT), Microscopic Somatic Cell Count (MSCC), and bacteriological examination of mammary secretion. Mammary quarters were divided into two groups: BAC-: samples that did not present bacteriological growth throughout transition period; BAC+: samples that presented bacteriological growth in at least two isolates of the same bacterial genus. Regarding physical examination of mammary gland, the parameters localized or generalized alteration in volume, asymmetry, reddish color, reduced skin elasticity, increased temperature, and swollen consistency presented higher frequencies in the BAC- group. On the other hand, infection in mammary quarters of cows from BAC+ group promoted a decrease in frequencies of increased volume, decreased elasticity, and elevated temperature in the mammary gland, in addition to a higher positivity to CMT and higher cellularity. Overall rate of intramammary infection was 25.82%, with non-aureus Staphylococci (NAS) being the predominant agent (69.2%). Maximum peak of bacterial isolates occurred immediately after calving (33.3%). Differences were observed between groups (P = 0.021) for CMT, showing a higher frequency of positive tests in BAC+ group (36.5%) compared to BAC- group (18%). MSCC varied between weeks (P = 0.001), groups (P = 0.001), and between the interaction of the two variables (P = 0.019). Highest median value of MSCC was observed at calving (1.5 × 106 cells/mL), being different (P = 0.001) from the +1, +2, and +3 weeks and the lowest median value of MSCC (0.08×106 cells/mL) was observed in +3 compared to previous weeks (P &lt; 0.05).Discussion: NAS was predominantly isolated in mammary secretions of cows during peripartum, it is commonly found in the skin and canal of the teat and are associated with subclinical mastitis. Peak of mammary infection was observed on calving, probably by the cortisol peak resulting in a stress leucogram and decrease in the functional activity of immune cells. Changes observed in the physical examination of mammary gland of cows from BAC- group are compatible with physiological edema caused by circulatory changes that occurs with the proximity of calving, increasing blood flow necessary for production of colostrum. Alterations in the mammary quarters of cows from BAC+ group may be associated with functional loss of mammary parenchyma or persistent infectious process, characterizing clinical findings of pathological changes during transition period. Mammary quarters of the BAC+ group presented higher percentages of positive reactions to CMT in weeks +1 and +2, and higher MSCC values and are associated with infection of the mammary gland.

Treatment of an Atypical Case of Bilateral Nephrolithiasis in a Canine

Background: Less than 5% of canine uroliths are found in the kidney and ureter. The decision to remove a nephrolith is controversial and should be considered in cases of refractory infection, hematuria, presence of obstructive uropathy and compression of the renal parenchyma. The aim of this report is to describe an unusual presentation of bilateral nephrolithiasis in a dog, occupying almost the entire renal parenchyma, its clinical and imaging findings, in addition to surgical treatment and its evolution.Case: A 10-year-old male Basset Hound was evaluated at the Veterinary Medical Teaching Hospital (HCV) of the Federal University of Rio Grande do Sul (UFRGS), presenting prostration, anorexia, vomiting, diarrhea and severe hematuria for three days. On physical examination the patient was dehydrated, with pale mucous membranes, uremic breath and abdominal pain. Blood tests showed mild anemia and azotemia. In both kidneys, abdominal ultrasonography exhibited a large hyperechoic structure with deep acoustic shadowing. These same structures were observed in abdominal radiographic examination as radiopaque structures, confirming the diagnosis of bilateral nephrolithiasis. Urine culture was positive for coagulase-negative Staphylococcus sp. The patient was stabilized with fluid therapy, antiemetic, analgesics, antibiotics and whole blood transfusion. Unilateral nephrotomy of the right kidney was performed to remove the urolith. After three months, nephrotomy of the left kidney was performed to remove the other urolith. The patient was clinically stable and with no macroscopic hematuria 12 h after surgery. Two days after discharge, the patient returned prostrated in lateral recumbency, however with no alteration of parameters in physical examination. Blood tests showed anemia, thrombocytopenia, hypoalbuminemia, azotemia and hyperphosphatemia. The dog presented a convulsive episode and died shortly, eight hours later. In the necropsy examination, extensive loss of renal parenchyma was seen in both kidneys and the presence of thrombosis and areas of infarction in several organs such as spleen, liver, lungs and central nervous system.Discussion: Complications of nephrotomy include perirenal hemorrhage, hydronephrosis due to obstruction of blood clots or urine leakage to the abdominal cavity. From the necropsy findings, the surgical site did not present these complications, justifying that the surgical procedure was not directly related to death. Correction of dehydration, blood transfusion, and antibiotic therapy based on urine culture and susceptibility testing was important for initial stabilization, before surgery. However, the presence of advanced chronic kidney disease may have contributed to deterioration of the patient's clinical condition and death. The presence of thrombus and hemorrhagic areas, observed during necropsy, associated with acute onset of clinical signs and the presence of severe hypoalbuminemia, may suggest that the patient died due to a thromboembolic event, as a consequence of nephrotic syndrome. Studies show that nephrotomy can be performed with few adverse effects on renal function if the surgical technique and anesthetic management are adequate. In this case, nephrotomy was the best option for the treatment of the patient, since it enabled a rapid intervention, controlled the hematuria and allowed the removal of both uroliths without complications related to surgery.