Publications by authors named "Korosh Khalili"

74 Publications

The Renal Vasculature: What the Radiologist Needs to Know.

Radiographics 2021 Sep-Oct;41(5):1531-1548. Epub 2021 Jul 30.

From the Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, and Women's College Hospital, University of Toronto, 200 Elizabeth St, Toronto, ON, Canada M5G 2C4 (A.L., M.J.T., K.K., S.K.); Department of Radiology, University of Iowa, Iowa City, Iowa (S.N.); and Department of Medical Imaging, Ottawa Hospital, University of Ottawa, Ottawa, Ont, Canada (N.S.).

The physiologic role of the kidneys is dependent on the normal structure and functioning of the renal vasculature. Knowledge and understanding of the embryologic basis of the renal vasculature are necessary for the radiologist. Common anatomic variants involving the renal artery (supernumerary arteries and prehilar branching) and renal vein (supernumerary veins, delayed venous confluence, retroaortic or circumaortic vein) may affect procedures like renal transplantation, percutaneous biopsy, and aortic aneurysm repair. Venous compression syndromes (anterior and posterior nutcracker syndrome) can be symptomatic and can be diagnosed with a combination of radiologic features. Renal artery stenosis is commonly atherosclerotic and is diagnosed with Doppler US, CT angiography, or MR angiography. Fibromuscular dysplasia, the second most common cause of renal artery narrowing, has a characteristic string-of-beads appearance resulting from multifocal stenoses and dilatations. Manifestations of renal vasculitis differ depending on whether the affected vessels are large, medium, or small. Renal vascular injury is graded according to the American Association for the Surgery of Trauma (AAST) renal injury scale, which defines and in renal injuries. Both renal arteries and veins are affected by primary neoplasms or secondarily by neoplasms from adjacent structures. Differentiation between bland thrombus and tumor thrombus and the extent of involvement dictate management in malignancies, especially renal cell carcinoma. Aneurysms, pseudoaneurysms, arteriovenous malformations, and arteriovenous fistulas can affect renal vessels and can be diagnosed with specific imaging features. The radiologist has a critical role in identification of specific imaging characteristics and establishing the diagnosis in the varied pathologic conditions affecting the renal vasculature, which is critical for directing management. Thus, the renal vasculature should be an integral part of radiologists' checklist. RSNA, 2021.
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http://dx.doi.org/10.1148/rg.2021200174DOI Listing
July 2021

Autologous Hematopoietic Stem Cell Transplantation for Liver Transplant Recipients With Recurrent Primary Sclerosing Cholangitis: A Pilot Study.

Transplantation 2021 May 25. Epub 2021 May 25.

Multi Organ Transplant Program, University Health Network, Toronto, ON, Canada. Blood and Marrow Transplant Program, The Ottawa Hospital, Ottawa, ON, Canada. Department of Pathology, University of Pittsburgh, Pittsburgh, PA. Department of Medical Imaging, University Health Network, Toronto, ON, Canada. Ottawa Stem Cell Program, Canadian Blood Services, Ottawa, ON, Canada.

Background: Primary sclerosing cholangitis (PSC) is an indication for liver transplantation, but recurrence after liver transplantation is associated with poor outcomes often requiring repeat transplantation. We investigated whether autologous hematopoietic stem cell transplantation (aHSCT) could be used to stop progression of recurrent PSC and promote operational tolerance.

Methods: Twelve patients with recurrent PSC were fully evaluated and 5 were selected for aHSCT. Autologous hematopoietic stem cells were collected, purified by CD34 immunomagnetic selection and cryopreserved. Immunoablation using busulfan, cyclophosphamide and rabbit anti-thymocyte globulin was followed by aHSCT. The primary endpoint of the study was the establishment of operational tolerance defined as lack of biochemical, histologic and clinical evidence of rejection while off immunosuppression at 2 years post-aHSCT.

Results: Two of the 5 patients achieved operational tolerance with no clinical or histological evidence of PSC progression or allo-rejection. A third patient developed sinusoidal obstruction syndrome following aHSCT requiring repeat liver transplantation but has no evidence of PSC recurrence while on sirolimus monotherapy now more than 3 years after aHSCT. A fourth patient was weaned off immunosuppression but died 212 days after aHSCT from pericardial constriction. A fifth patient died from multiorgan failure. Immunosuppression-free allograft acceptance was associated with deletion of T cell clones, loss of autoantibodies and increases in regulatory T cells, transitional B cells, and programmed cell death protein-1 expressing CD8+ T cells in the 2 long-term survivors.

Conclusions: Although operational tolerance occurred following aHSCT, the high morbidity and mortality observed renders this specific protocol unsuitable for clinical adoption.
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http://dx.doi.org/10.1097/TP.0000000000003829DOI Listing
May 2021

The added value of contrast-enhanced ultrasound in evaluation of indeterminate small solid renal masses and risk stratification of cystic renal lesions.

Eur Radiol 2021 Apr 29. Epub 2021 Apr 29.

Toronto Joint Department of Medical Imaging, University Health Network, Sinai Health System and Women's College Hospital, University of Toronto, Toronto, ON, Canada.

Objectives: To investigate accuracy of contrast-enhanced ultrasound (CEUS) to characterize indeterminate small solid renal masses (sSRMs), excluding lipid-rich AMLs, and cystic renal masses (CRMs) according to the proposed Bosniak Classification 2019 MATERIALS AND METHODS: CEUS of pathology-proven CRMs and sSRMs (without definite enhancement or macroscopic fat on CT/MRI), and CRMs with ≥18 months follow-up were retrospectively reviewed. Two radiologists blindly categorized CRMs according to new Bosniak Classification on CT/MRI. On CEUS, two other radiologists evaluated arterial-phase enhancement of sSRMs relative to renal cortex and categorized CRMs following new Bosniak Classification. Fisher's exact/chi-squared test was used to compare categorical variables, and Cohen κ statistics for inter-observer agreement RESULTS: A total of 237 patients had 241 lesions: 161 pathology-proven sSRMs (122 malignant and 39 benign), 29 pathology-proven CRMs, 51 CRMs with adequate follow-up. Arterial-phase enhancement < renal cortex predicted malignancy with specificity of 97.4% (38/39) (CI 85.6-99.9%), and positive predictive value (PPV) of 98.2% (54/55) (CI 90.4-99.9%). Inter-observer kappa was 0.95. In pathology-proven CRMS, sensitivity of CEUS vs CT/MRI was 100% (15/15) (CI 79.6-100%) vs 60% (9/15) (CI 35.8-80.1%) (p value = .002) and negative predictive value (NPV) 100% (2/2) (CI 17.8-100%) vs 25% (2/8 ) (CI 4.4-59.1%) (p value < 0.0001), with similar specificity (50%) and PPV- 88.2% (15/17) (CI 65.7-97.9%) vs 81.8% (9/11) (CI 52.3-96.8%) ( p value = 0.586). Bosniak Classification inter-observer kappa was 0.92 for CEUS vs 0.68 for CT/MRI (p value = 0.009).

Conclusion: In our cohort, CEUS had high specificity and PPV to diagnose RCC in sSRMs excluding lipid-rich AML. CEUS had significantly higher sensitivity/NPV to diagnose malignancy in CRMs as compared to CT/MRI.

Key Points: • Once lipid-rich AML is excluded by the other modalities, sSRM arterial phase hypo-enhancement relative to renal cortex on CEUS yielded high specificity (97.4%) and PPV (98.2%) to diagnose RCC. • When applying the proposed Bosniak Classification 2019, CEUS showed higher sensitivity compared to CT/MRI (100% vs 60%), p value=.0024, in the stratification of cystic renal masses to diagnose malignancy. • CEUS may reduce the number of CT/MRI Bosniak IIF lesions by assigning them to either II or III/IV categories.
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http://dx.doi.org/10.1007/s00330-021-07964-0DOI Listing
April 2021

Patients with Protein-Truncating Mutations and Mild ADPKD.

Clin J Am Soc Nephrol 2021 03 18;16(3):374-383. Epub 2021 Feb 18.

Division of Nephrology, University Health Network and University of Toronto, Toronto, Ontario, Canada

Background And Objectives: Progression of autosomal dominant polycystic kidney disease (ADPKD) is highly variable. On average, protein-truncating mutations are associated with the most severe kidney disease among all mutation classes. Here, we report that patients with protein-truncating mutations may also have mild kidney disease, a finding not previously well recognized.

Design, Setting, Participants, & Measurements: From the extended Toronto Genetic Epidemiologic Study of Polycystic Kidney Disease, 487 patients had and sequencing and typical ADPKD imaging patterns by magnetic resonance imaging or computed tomography. Mayo Clinic Imaging Classification on the basis of age- and height-adjusted total kidney volume was used to assess their cystic disease severity; classes 1A or 1B were used as a proxy to define mild disease. Multivariable linear regression was performed to test the effects of age, sex, and mutation classes on log-transformed height-adjusted total kidney volume and eGFR.

Results: Among 174 study patients with typical imaging patterns and protein-truncating mutations, 32 (18%) were found to have mild disease on the basis of imaging results (., Mayo Clinic Imaging class 1A-1B), with their mutations spanning the entire gene. By multivariable analyses of age, sex, and mutation class, they displayed mild disease similar to patients with mutations and Mayo Clinic Imaging class 1A-1B. Most of these mildly affected patients with protein-truncating mutations reported a positive family history of ADPKD in preceding generations and displayed significant intrafamilial disease variability.

Conclusions: Despite having the most severe mutation class, 18% of patients with protein-truncating mutations had mild disease on the basis of clinical and imaging assessment.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_02_18_CJN11100720_final.mp3.
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http://dx.doi.org/10.2215/CJN.11100720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011025PMC
March 2021

Recognizing the Role of the Reticuloendothelial System in the Late Phase of US Contrast Agents.

Radiology 2021 Feb 8;298(2):287-291. Epub 2020 Dec 8.

From the Department of Medical Imaging, University of Toronto, 610 University Ave, Room 3-964, Toronto, ON, Canada M5G 2M9; and Joint Department of Medical Imaging, University Health Network, Sinai Health System, Women's College Hospital, Toronto, Canada.

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http://dx.doi.org/10.1148/radiol.2020203245DOI Listing
February 2021

Convolutional neural networks versus radiologists in characterization of small hypoattenuating hepatic nodules on CT: a critical diagnostic challenge in staging of colorectal carcinoma.

Sci Rep 2020 09 17;10(1):15248. Epub 2020 Sep 17.

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.

Our objective was to compare the diagnostic performance and diagnostic confidence of convolutional neural networks (CNN) to radiologists in characterizing small hypoattenuating hepatic nodules (SHHN) in colorectal carcinoma (CRC) on CT scans. Retrospective review of CRC CT scans over 6-years yielded 199 patients (550 SHHN) defined as < 1 cm in diameter. The reference standard was established through 1-year stability/MRI for benign or nodule evolution for malignant nodules. Five CNNs underwent supervised training on 150 patients (412 SHHN). The remaining 49 patients (138 SHHN) were used as testing-set to compare performance of 3 radiologists to CNN, measured through ROC AUC analysis of confidence rating assigned to each nodule by the radiologists. Multivariable modeling was used to compensate for radiologist bias from visible findings other than SHHN. In characterizing SHHN as benign or malignant, the radiologists' mean AUC ROC (0.96) was significantly higher than CNN (0.84, p = 0.0004) but equivalent to CNN adjusted through multivariable modeling for presence of synchronous ≥ 1 cm liver metastases (0.95, p = 0.9). The diagnostic confidence of radiologists and CNN were analyzed. There were significantly lower number of nodules rated with low confidence by CNN (19.6%) and CNN with liver metastatic status (18.1%) than two (38.4%, 44.2%, p < 0.0001) but not a third radiologist (11.1%, p = 0.09). We conclude that in CRC, CNN in combination with liver metastatic status equaled expert radiologists in characterizing SHHN but with better diagnostic confidence.
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http://dx.doi.org/10.1038/s41598-020-71364-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499427PMC
September 2020

Foam Sclerotherapy for Cyst Volume Reduction in Autosomal Dominant Polycystic Kidney Disease: A Prospective Cohort Study.

Kidney Med 2019 Nov-Dec;1(6):366-375. Epub 2019 Oct 18.

Division of Nephrology, University Health Network and University of Toronto, Toronto, Ontario, Canada.

Rationale & Objective: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder. Progressive increase in cyst number and size leads to kidney failure in a majority of patients. Large kidney cysts, although few, can be especially deleterious by impeding kidney blood flow and obstructing urine flow over a large region. Foam sclerotherapy is a minimally invasive procedure that may be used to ablate large cysts. We examined the effectiveness and safety of foam sclerotherapy for kidney volume reduction in patients with ADPKD.

Study Design: Prospective cohort study.

Setting & Participants: Adults with ADPKD at a tertiary referral center in Toronto.

Predictor: Foam sclerotherapy.

Outcomes: Volume of treated kidneys and adverse events.

Analytical Approach: Treated and nontreated kidney volume, kidney function, tolerability, and symptoms were analyzed within each patient.

Results: We performed 77 foam sclerotherapy treatment sessions in 66 patients. Foam sclerotherapy was associated with a 21.8% volume reduction of the treated kidneys (n = 95; median, 1,138 [IQR, 801-1,582] mL before vs 891 [IQR, 548-1,450] mL after;  < 0.001), while the volume of the nontreated kidneys increased by 3.4% during the same time frame (n = 37; median, 655 [IQR, 352-998] mL before vs 677 [IQR, 371-1,164] mL after;  < 0.001). 4 (6%) patients had a higher measured creatinine clearance by at least 10 mL/min at least 12 months after foam sclerotherapy. 9 (14%) patients experienced self-limiting pain at the procedure site and 2 (3%) had cyst or urinary tract infection. Most patients with flank/back pain, abdominal pain, and abdominal distension had improvement in their symptoms.

Limitations: Small sample, observational data.

Conclusions: Foam sclerotherapy is a safe and effective procedure for kidney volume reduction and amelioration of compressive symptoms in select patients with ADPKD. Further studies are needed to assess its effects on kidney blood flow and kidney function and determine the subgroups of patients most likely to benefit.
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http://dx.doi.org/10.1016/j.xkme.2019.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380421PMC
October 2019

Hepatocellular carcinoma surveillance: the often-neglected practice.

Hepatobiliary Surg Nutr 2020 Feb;9(1):77-79

Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.21037/hbsn.2019.08.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026797PMC
February 2020

Imaging and implications of tumor thrombus in abdominal malignancies: reviewing the basics.

Abdom Radiol (NY) 2020 04;45(4):1057-1068

Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women's College Hospital, University of Toronto, Toronto, ON, Canada.

Extension of tumor tissue within a vein is a recognized prognostic factor in abdominal malignancy because of its influence on tumor staging and selection of therapeutic management. With the advent of newer surgical techniques, and variable treatment strategies, imaging plays a crucial role in categorizing patients according to the tumor resectability and vascular reconstruction techniques during surgery. Understanding the clinical impact of tumor thrombus increases the awareness of the radiologist about the key findings in tumor staging and decision-making of surgical approach. Ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) can be used individually and in combination to accurately assess the tumor thrombus. In our pictorial review, we will discuss the imaging findings and clinical consequences of tumor thrombosis in abdominal malignancies, including hepatocellular carcinoma, pancreatic neuroendocrine tumor, renal cancer, and adrenal cortical carcinoma.
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http://dx.doi.org/10.1007/s00261-019-02282-yDOI Listing
April 2020

Negative Predictive Value of Contrast-Enhanced Ultrasound of Liver and Kidney Thermal Ablation Sites for Local Tumour Progression During Long-term Follow-up: A Retrospective Consecutive Study.

Can Assoc Radiol J 2019 Nov 2;70(4):434-440. Epub 2019 Oct 2.

Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada.

Purpose: To determine negative predictive value (NPV) of contrast-enhanced ultrasound (CEUS) to demonstrate local tumour progression (LTP) at thermal ablation (TA) sites.

Methods: Our institutional review board approved this retrospective study; acquisition of consent was waived. Consecutive CEUS examinations performed between 2004-2014 for TA site evaluation on patients who could not undergo enhanced computed tomography (CT) or magnetic resonance imaging (MRI), or had inconclusive CT or MRI, were retrospectively reviewed. Those reported as no abnormal enhancement in or surrounding TA site were included. CEUS examination was considered true-negative based on stability or lack of enhancement/washout on follow-up imaging for at least 1 year, and false-negative (FN), if there was an arterially enhancing focus with wash-out at or surrounding TA site on subsequent follow-up imaging.

Results: Study population included 56 tumours in 54 patients, 11 women, 43 men; mean age 71 years. Two patients had TA of two different hepatocellular carcinomas. Thirty-six examinations were for hepatic TA and twenty for renal TA. Lesion sizes ranged from 1 cm to 7 cm (mean 3.1 ± 1.2). Mean diameter of 7 recurrences was 13.8 mm. Overall FN rate was 12.5% (7/56). Corresponding numbers were 0% (0/20) for renal TA and 19.4% (7/36) for hepatic TA. Overall NPV of CEUS was 87.5% (49/56) (confidence interval [CI]: 78.8%-96.2%). NPV for renal TA was 100% (20/20) (CI: 100%-100%) and for hepatic TA 81.5% (29/36) (CI: 67.6 %-93.5%).

Conclusion: In this cohort, CEUS showed high NPV for exclusion of LTP at renal TA sites. NPV for hepatic TA sites was high but lower than renal TA.
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http://dx.doi.org/10.1016/j.carj.2019.06.011DOI Listing
November 2019

Diagnostic imaging of hepatocellular carcinoma at community hospitals and their tertiary referral center in the era of LI-RADS: a quality assessment study.

Abdom Radiol (NY) 2019 12;44(12):4028-4036

Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.

Purpose: To assess guideline compliance and quality of hepatocellular carcinoma, (HCC) diagnostic imaging within community hospitals (CH) and their Tertiary referral center (TRC) in a moderately high incidence region.

Methods: Initial diagnostic workup CT/MRI scans of 251 patients (122 CH, 112 TRC, 17 Non-TRC academic) with HCC over a 15-month period were assessed for Liver reporting and Data System (LI-RADS) guideline compliance. 269 scans (182 CT, 87 MRI) were qualitatively evaluated by 2 independent blinded radiologists for arterial timing, overall image quality, noise and sharpness, with quantification of interobserver variability. The contrast enhancement ratio (CER) for the largest HCC on each scan was calculated using pre- and post-contrast images.

Results: 103/104 (99%) of TRC and 44/78 (56%) of CH CTs adhered to LI-RADS imaging guidelines (P < 0.0001). Lack of delayed phase accounted for 32/34 (94%) of noncompliant CH CTs. Regarding MRI, 19/19 (100%) of TRC and 60/68 (88%) of CH scans were adherent (P = 0.12). For both modalities, overall image quality, noise and sharpness were rated significantly higher for TRC than CH. There was moderate interobserver agreement with intraclass correlation coefficient of 0.73, 0.70 and 0.63, respectively. Arterial-phase timing was rated adequate for CT in 75/104 TRC (72%) and 10/68 (14%) CH scans (P < 0.0001) and for MRI in 8/19 (42%) TRC and 23/68 (33%) CH scans (P = 0.17). The CER was significantly higher for TRC versus CH (2.9 vs. 1.9, P < 0.001) and MRI (0.9 vs. 0.7, P = 0.03).

Conclusions: Community hospital HCC diagnostic scans significantly lag in critical quality parameters of tumor enhancement, arterial phase timing, perceived image quality, and LI-RADS CT technique compliance compared to a TRC.
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http://dx.doi.org/10.1007/s00261-019-02237-3DOI Listing
December 2019

Crawling Into View.

Clin Infect Dis 2019 08;69(6):1079-1081

Department of Medicine, University of Toronto, Canada.

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http://dx.doi.org/10.1093/cid/ciy950DOI Listing
August 2019

CT and MR imaging findings of the livers in adults with Fontan palliation: an observational study.

Abdom Radiol (NY) 2020 01;45(1):188-202

Joint Department of Medical Imaging, Toronto General Hospital, University of Toronto, 585 University Avenue, Toronto, ON, M5G 2N2, Canada.

Purpose: To describe liver imaging findings and complications on computed tomography (CT) or magnetic resonance imaging (MRI) in adults with Fontan palliation and investigate whether imaging features show correlations with clinical and physiological parameters.

Methods: Our Institutional Review Board approved this retrospective study. Two blinded abdominal radiologists reviewed abdominal CT (n = 21) and MRI (n = 16) images between September 2011 and October 2017 in 37 adults (median age 27 years, interquartile range 21-36 years, 14 males [38%]) with a Fontan palliation (median post-Fontan duration 22 years, interquartile range 19-28 years). Correlation between CT/MRI findings and clinical parameters including laboratory results within 6 months of CT/MRI examinations was assessed by Spearman's rank correlation coefficient.

Results: Lobulated hepatic surface and blunt hepatic edge were seen in 92% (34/37) and 95% (35/37) of patients, respectively. Surface nodularity was noted in 32% (12/37). In 7 patients, there were 11 hepatic nodules which showed arterial-phase hyperenhancement and washout. Among them, 2 were biopsy-proven hepatocellular carcinomas (HCCs), and the remaining 9 were focal nodular hyperplasia (FNH)-like nodules. Suprahepatic inferior vena cava (IVC) diameter showed positive correlations with post-Fontan duration (p < 0.01), serum gamma-glutamyl transferase (p < 0.01), and total bilirubin (p < 0.01).

Conclusion: The livers in post-Fontan adults show a unique morphology of blunt edge and lobulating surface with occasional nodularity. There is a diagnostic challenge in distinguishing HCCs from FNH-like nodules in post-Fontan population due to overlapping imaging findings. Suprahepatic IVC diameter is a potentially useful imaging marker that reflects hepatic dysfunction in Fontan palliation.
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http://dx.doi.org/10.1007/s00261-019-02119-8DOI Listing
January 2020

Parasitic Liver Infections: Imaging Findings and Strategies for Timely Diagnosis.

Curr Probl Diagn Radiol 2020 Nov - Dec;49(6):447-451. Epub 2019 Aug 7.

Department of Radiology, McMaster University, St. Joseph's Healthcare, Hamilton, ON, Canada.

There are a number of parasitic infections that can affect the liver and biliary tree. These infections can be primarily related to the liver or can include secondary hepatic involvement. Imaging can narrow down the differential diagnosis in the appropriate clinical setting, and can even clinch the diagnosis with some pathognomonic findings. The various imaging modalities can also identify disease extent, help guide management, and demonstrate response to treatment. This pictorial essay will give an overview of parasitic liver infections, and will discuss the best imaging strategies and the key imaging features to help make a timely accurate diagnosis.
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http://dx.doi.org/10.1067/j.cpradiol.2019.08.002DOI Listing
June 2021

Prognostic Performance of Kidney Volume Measurement for Polycystic Kidney Disease: A Comparative Study of Ellipsoid vs. Manual Segmentation.

Sci Rep 2019 07 29;9(1):10996. Epub 2019 Jul 29.

Division of Nephrology and University Health Network and University of Toronto, Toronto, Ontario, Canada.

Total kidney volume (TKV) is a validated prognostic biomarker for risk assessment in autosomal dominant polycystic kidney disease (ADPKD). TKV by manual segmentation (MS) is the "gold standard" but is time-consuming and requires expertise. The purpose of this study was to compare TKV-based prognostic performance by ellipsoid (EL) vs. MS in a large cohort of patients. Cross-sectional study of 308 patients seen at a tertiary referral center; all had a standardized MRI with typical imaging of ADPKD. An experienced radiologist blinded to patient clinical results performed all TKV measurements by EL and MS. We assessed the agreement of TKV measurements by intraclass correlation(ICC) and Bland-Altman plot and also how the disagreement of the two methods impact the prognostic performance of the Mayo Clinic Imaging Classification (MCIC). We found a high ICC of TKV measurements (0.991, p < 0.001) between EL vs. MS; however, 5.5% of the cases displayed disagreement of TKV measurements >20%. We also found a high degree of agreement of the individual MCIC risk classes (i.e. 1A to 1E) with a Cohen's weighted-kappa of 0.89; but 42 cases (13.6%) were misclassified by EL with no misclassification spanning more than one risk class. The sensitivity and specificity of EL in distinguishing low-risk (1A-B) from high-risk (1C-E) MCIC prognostic grouping were 96.6% and 96.1%, respectively. Overall, we found an excellent agreement of TKV-based risk assessment between EL and MS. However, caution is warranted for patients with MCIC 1B and 1C, as misclassification can have therapeutic consequence.
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http://dx.doi.org/10.1038/s41598-019-47206-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662759PMC
July 2019

Intrafamilial Variability of ADPKD.

Kidney Int Rep 2019 Jul 7;4(7):995-1003. Epub 2019 May 7.

Division of Nephrology, University Health Network, Toronto, Ontario, Canada.

Introduction: Discordance in kidney disease severity between affected relatives is a recognized feature of autosomal dominant polycystic kidney disease (ADPKD). Here, we report a systematic study of a large cohort of families to define the prevalence and clinical features of intrafamilial discordance in ADPKD.

Methods: The extended Toronto Genetic Epidemiology Study of Polycystic Kidney Disease (eTGESP) cohort includes 1390 patients from 612 unrelated families with ADPKD ascertained in a regional polycystic kidney disease center. All probands underwent comprehensive and mutation screening. Total kidney volume by magnetic resonance imaging (MRI) was available in 500 study patients.

Results: Based on (i) rate of estimated glomerular filtration rate (eGFR) decline, (ii) age at onset of end-stage renal disease (ESRD), and (iii) Mayo Clinic Imaging Classification (MCIC), 20% of patients were classified as having mild disease, and 33% as having severe disease. Intrafamilial ADPKD discordance with at least 1 mild and 1 severe case was observed in 43 of 371 (12%) families, at a similar frequency regardless of the responsible gene (no mutation detected) or mutation type (protein-truncating versus nontruncating). Intrafamilial discordance was more common in larger families and was present in 30% of families with more than 5 affected members. The heritability of age at onset of ESRD was similar between different mutation types.

Conclusion: Extreme kidney disease discordance is present in at least 12% of families with ADPKD, regardless of the underlying mutated gene or mutation class. Delineating genetic and environmental modifiers underlying the observed intrafamilial ADPKD variability will provide novel insights into the mechanisms of progression in ADPKD.
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http://dx.doi.org/10.1016/j.ekir.2019.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611955PMC
July 2019

Contrast-enhanced ultrasound approach to the diagnosis of focal liver lesions: the importance of washout.

Ultrasonography 2019 Oct 17;38(4):289-301. Epub 2019 Mar 17.

Joint Department of Medical Imaging, University of Toronto, Toronto, Canada.

Contrast-enhanced ultrasound (CEUS) is a powerful technique for differentiating focal liver lesions (FLLs) without the risks of potential nephrotoxicity or ionizing radiation. In the diagnostic algorithm for FLLs on CEUS, washout is an important feature, as its presence is highly suggestive of malignancy and its characteristics are useful in distinguishing hepatocellular from nonhepatocellular malignancies. Interpreting washout on CEUS requires an understanding that microbubble contrast agents are strictly intravascular, unlike computed tomography or magnetic resonance imaging contrast agents. This review explains the definition and types of washout on CEUS in accordance with the 2017 version of the CEUS Liver Imaging Reporting and Data System and presents their applications to differential diagnosis with illustrative examples. Additionally, we propose potential mechanisms of rapid washout and describe the washout phenomenon in benign entities.
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http://dx.doi.org/10.14366/usg.19006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769186PMC
October 2019

Historical Data Are Not Relevant to the Diagnostic Performance of Ultrasound in Surveillance for Hepatocellular Carcinoma.

Authors:
Korosh Khalili

Gastroenterology 2019 09 17;157(3):899-900. Epub 2019 May 17.

Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1053/j.gastro.2018.12.051DOI Listing
September 2019

Metastatic low-grade endometrial stromal sarcoma of uterus presenting as a primary pancreatic tumor: case presentation and literature review.

Diagn Pathol 2019 Apr 22;14(1):30. Epub 2019 Apr 22.

Department of Anatomical Pathology, Laboratory Medicine Program, University Health Network, Toronto General Hospital, 200 Elizabeth Street, 11th Floor, Eaton Wing, Toronto, Ontario, M5G 2C4, Canada.

Background: Metastatic tumors to the pancreas are uncommon, accounting for approximately 2% of pancreatic malignancies. The most common primary tumors to give rise to pancreatic metastases are carcinomas.

Case Presentation: A 50-year old female patient was investigated for a cause of abdominal discomfort. She had a 2-year history of menorrhagia and dysmenorrhea which was ascribed to a fibroid uterus. On imaging, she was found to have a large solid and cystic mass in the tail of the pancreas. Imaging also confirmed a fibroid uterus. A distal pancreatectomy and splenectomy showed a 9 cm circumscribed mass within, and grossly confined to, the parenchyma of the pancreatic tail. Microscopically, the pancreatic lesion was lobulated, and well-circumscribed, but focally infiltrative. It comprised sheets of uniform spindled to epithelioid cells with round to oval nuclei, coarse to vesicular chromatin, visible nucleoli, nuclear grooves and clear to eosinophilic cytoplasm. Prominent arterioles were identified. The stroma was collagenized in areas. Occasional hemosiderin-laden macrophages were seen, and focal cystic change was present. There was no evidence of nuclear pleomorphism, mitotic activity or necrosis, and there was no evidence of endometriosis despite multiple sections being taken. Immunohistochemistry showed that the tumor cells were positive for CD10, estrogen receptor (ER), progesterone receptor (PR), Wilms tumor-1 (WT-1) and smooth muscle actin (SMA). RNA sequencing detected a PHF1 rearrangement. The morphological, immunohistochemical and molecular features were of a low-grade endometrial stromal sarcoma (LG-ESS). Subsequent total hysterectomy and bilateral salpingo-oophorectomy 3 months later, showed uterine fibroids and a 5 cm low-grade endometrial stromal sarcoma confined to the uterus, with lymphatic invasion.

Conclusions: To the best of our knowledge, this is the first documented case of metastatic endometrial stromal sarcoma of uterus presenting as a primary pancreatic neoplasm. An unexpected extra-uterine location and unusual presentation of ESS may make the diagnosis challenging, despite classic histological features. Morphological, immunohistochemical and molecular findings must be combined to render the correct diagnosis.
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http://dx.doi.org/10.1186/s13000-019-0807-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477712PMC
April 2019

Reproducibility of 2 Liver 2-Dimensional Shear Wave Elastographic Techniques in the Fasting and Postprandial States.

J Ultrasound Med 2019 Jul 11;38(7):1739-1745. Epub 2018 Dec 11.

Departments of Medical Imaging, Toronto, Ontario, Canada.

Objectives: The purpose of this study was to compare the reliability and agreement of 2 methods of 2-dimensional (2D) shear wave elastography (SWE) on liver stiffness in healthy volunteers. We also assessed effects of the prandial state and operator experience on measurements.

Methods: Two operators, 1 experienced and 1 novice, independently examined 20 healthy volunteers with 2D SWE on 2 ultrasound machines (Aixplorer [SuperSonic Imagine, Aix-en-Provence, France] and Aplio 500 [Canon Medical Systems Corporation, Otawara, Japan]). Volunteers were scanned 8 times by the operators using both machines in fasting and postprandial states. Agreement was evaluated by a Bland-Altman analysis, and the correlation was assessed by the Pearson correlation and intraclass correlation coefficients (ICCs). An analysis of variance was conducted to determine the contribution of the machine, prandial state, and operator experience to the variability.

Results: Agreement assessed by Bland-Altman plots showed no statistically significant difference in measured liver stiffness between the machines (mean difference, -0.8%; 95% confidence interval, -3.7%, 2.1%), with a critical difference of 1.36 kPa. The correlation was good to excellent for both the crude overall Pearson coefficient and the ICC, both measuring 0.88 (95% confidence interval, 0.82, 0.92). Subclass ICCs for the fasting state, postprandial state, novice operator, and experienced operator were 0.89, 0.88, 0.90, and 0.86, respectively. The 2-way mixed effect analysis of variance showed that the volunteers accounted for 86.3% of variation in median liver stiffness, with no statistically significant contribution from operator experience, the prandial state, or the machine (P = .108, .067, and .296, respectively).

Conclusions: Our study showed that the 2D SWE techniques had a high degree of reliability and agreement in measurement of liver stiffness in a healthy population. Operator experience and the prandial state did not impart significant variability to stiffness measurements.
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http://dx.doi.org/10.1002/jum.14862DOI Listing
July 2019

Successful Integration of Contrast-enhanced US into Routine Abdominal Imaging.

Radiographics 2018 Sep-Oct;38(5):1454-1477. Epub 2018 Jul 30.

From the Department of Medical Imaging, University of Toronto, University Health Network, Toronto General Hospital, 585 University Ave, Toronto, ON, Canada M5G 2N2.

Contrast material-enhanced US is recognized increasingly as a useful tool in a wide variety of hepatic and nonhepatic applications. The modality recently was approved for limited use for liver indications in adult and pediatric patients in the United States. Contrast-enhanced US uses microbubbles of gas injected intravenously as a contrast agent to demonstrate blood flow and tissue perfusion. The growing worldwide application of contrast-enhanced US in multiple organ systems is due largely to its advantages, including high contrast resolution (sensitivity to the contrast agent), real-time imaging, lack of nephrotoxicity, the purely intravascular property of microbubble contrast agents that allows the use of disruption-replenishment techniques, and repeatability during the same examination. Through illustrative cases, common useful clinical scenarios are discussed, including characterization of liver and renal masses, especially indeterminate lesions at CT or MRI; differentiation of neoplastic cysts from nonneoplastic cysts in various organs; differentiation of tumor thrombus from bland thrombus; and assessment after a renal transplant or local ablative therapy. Common applications in the biliary system, pancreas, spleen, and vasculature also are introduced. Successful routine use of contrast-enhanced US requires an efficient setup and workflow and a thorough understanding of appropriate clinical indications and its advantages that provide added value after CT and MRI. This article familiarizes radiologists with common abdominal applications of contrast-enhanced US and guides them to implement contrast-enhanced US successfully in their clinical practice. Online supplemental material is available for this article. RSNA, 2018.
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http://dx.doi.org/10.1148/rg.2018170152DOI Listing
December 2018

Negative Predictive Value of Contrast-Enhanced Ultrasound in Differentiating Avascular Solid-Appearing From Vascularized Masses: A Retrospective Consecutive Study.

J Ultrasound Med 2018 Dec 15;37(12):2935-2942. Epub 2018 May 15.

Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada.

Objectives: To determine the negative predictive value (NPV) of contrast-enhanced ultrasound (CEUS) to establish the lack of vascularity in a mass.

Methods: This work was an Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study. Acquisition of consent was waived. We included all CEUS examinations performed for tissue characterization between 2004 and 2014 that reported showing no vascularity in a mass. Contrast-enhanced ultrasound findings were considered true-negative when there was stability on imaging for at least 1 year or no evidence of a solid mass, if biopsied, and false-negative if there was lesion growth on imaging within 12 months or an indication of a solid mass on the pathologic examination, if biopsied. One author reviewed all of the reports and follow-up examinations. We conducted a consensus review of all false-negative findings mixed with an equal number of true-negative findings by 2 reviewers, who were blinded to the final results.

Results: The study population consisted of 97 CEUS examinations in 97 patients, including 48 women and 49 men (mean age ± SD, 65 ± 14 years). Examinations were performed for lesion characterization in the liver (n = 23), pancreas (n = 17), kidney (n = 54), 1 gallbladder, 1 adnexa, and 1 peritoneal lesion. The overall false-negative rate on the official prospective review was 2% (2 of 97). Two false-negative findings were correctly identified on the consensus review. The NPV of CEUS was 97.9% (95 of 97; 95% confidence interval, 93%- 99%) on the official review.

Conclusions: Contrast-enhanced ultrasound has a very high NPV to exclude the presence of flow in a mass, and it can be used to exclude the presence of a solid mass.
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http://dx.doi.org/10.1002/jum.14659DOI Listing
December 2018

Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease.

Am J Hum Genet 2018 05 26;102(5):832-844. Epub 2018 Apr 26.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA. Electronic address:

Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney cysts, often resulting in end-stage renal disease (ESRD). This disorder is genetically heterogeneous with ∼7% of families genetically unresolved. We performed whole-exome sequencing (WES) in two multiplex ADPKD-like pedigrees, and we analyzed a further 591 genetically unresolved, phenotypically similar families by targeted next-generation sequencing of 65 candidate genes. WES identified a DNAJB11 missense variant (p.Pro54Arg) in two family members presenting with non-enlarged polycystic kidneys and a frameshifting change (c.166_167insTT) in a second family with small renal and liver cysts. DNAJB11 is a co-factor of BiP, a key chaperone in the endoplasmic reticulum controlling folding, trafficking, and degradation of secreted and membrane proteins. Five additional multigenerational families carrying DNAJB11 mutations were identified by the targeted analysis. The clinical phenotype was consistent in the 23 affected members, with non-enlarged cystic kidneys that often evolved to kidney atrophy; 7 subjects reached ESRD from 59 to 89 years. The lack of kidney enlargement, histologically evident interstitial fibrosis in non-cystic parenchyma, and recurring episodes of gout (one family) suggested partial phenotypic overlap with autosomal-dominant tubulointerstitial diseases (ADTKD). Characterization of DNAJB11-null cells and kidney samples from affected individuals revealed a pathogenesis associated with maturation and trafficking defects involving the ADPKD protein, PC1, and ADTKD proteins, such as UMOD. DNAJB11-associated disease is a phenotypic hybrid of ADPKD and ADTKD, characterized by normal-sized cystic kidneys and progressive interstitial fibrosis resulting in late-onset ESRD.
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http://dx.doi.org/10.1016/j.ajhg.2018.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986722PMC
May 2018

Abdominal imaging findings in adult patients with Fontan circulation.

Insights Imaging 2018 Jun 5;9(3):357-367. Epub 2018 Apr 5.

Department of Medical Imaging, Toronto General Hospital, 585 University Avenue, Toronto, ON, M5G 2N2, Canada.

The Fontan procedures, designed to treat paediatric patients with functional single ventricles, have markedly improved the patient's survival into adulthood. The physiology of the Fontan circuit inevitably increases systemic venous pressure, which may lead to multi-system organ failure in the long-term follow-up. Fontan-associated liver disease (FALD) can progress to liver cirrhosis with signs of portal hypertension. Focal nodular hyperplasia-like nodules commonly develop in FALD. Imaging surveillance is often performed to monitor the progression of FALD and to detect hepatocellular carcinoma, which infrequently develops in FALD. Other abdominal abnormalities in post-Fontan patients include protein losing enteropathy and pheochromocytoma/paraganglioma. Given that these abdominal abnormalities are critical for patient management, it is important for radiologists to become familiar with the abdominal abnormalities that are common in post-Fontan patients on cross-sectional imaging.

Teaching Points: • Fontan procedure for functional single ventricle has improved patient survival into adulthood. • Radiologists should be familiar with unique imaging findings of Fontan-associated liver disease. • Focal nodular hyperplasia-like nodules commonly develop in Fontan-associated liver disease. • Hepatocellular carcinoma, protein-losing enteropathy, pheochromocytoma/paraganglioma may develop.
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http://dx.doi.org/10.1007/s13244-018-0609-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991003PMC
June 2018

Shrinking Hepatic Hemangiomas in a Patient Treated for Metastatic Germ Cell Tumor.

Clin Genitourin Cancer 2017 Aug 31. Epub 2017 Aug 31.

Department of Medicine, University of Toronto, Toronto, ON, Canada; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.clgc.2017.08.008DOI Listing
August 2017

Toronto HCC risk index: A validated scoring system to predict 10-year risk of HCC in patients with cirrhosis.

J Hepatol 2017 Aug 24. Epub 2017 Aug 24.

Toronto Centre for Liver Disease, University Health Network, University of Toronto, Canada. Electronic address:

Background & Aims: Current guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in all patients with cirrhosis, regardless of etiology. However, HCC incidence is not well established for many causes of cirrhosis. We aimed to assess the disease-specific incidence of HCC in a large cohort of patients with cirrhosis and to develop a scoring system to predict HCC risk.

Methods: A derivation cohort of patients with cirrhosis diagnosed by biopsy or non-invasive measures was identified through retrospective chart review. The disease-specific incidence of HCC was calculated according to etiology of cirrhosis. Factors associated with HCC were identified through multivariable Cox regression and used to develop a scoring system to predict HCC risk. The scoring system was evaluated in an external cohort for validation.

Results: Of 2,079 patients with cirrhosis and ≥6months follow-up, 226 (10.8%) developed HCC. The 10-year cumulative incidence of HCC varied by etiologic category from 22% in patients with viral hepatitis, to 16% in those with steatohepatitis and 5% in those with autoimmune liver disease (p<0.001). By multivariable Cox regression, age, sex, etiology and platelets were associated with HCC. Points were assigned in proportion to each hazard ratio to create the Toronto HCC Risk Index (THRI). The 10-year cumulative HCC incidence was 3%, 10% and 32% in the low-risk (<120points), medium-risk (120-240) and high-risk (>240) groups respectively, values that remained consistent after internal validation. External validation was performed on a cohort of patients with primary biliary cirrhosis, hepatitis B viral and hepatitis C viral cirrhosis (n=1,144), with similar predictive ability (Harrell's c statistic 0.77) in the validation and derivation cohorts.

Conclusion: HCC incidence varies markedly by etiology of cirrhosis. The THRI, using readily available clinical and laboratory parameters, has good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis.

Lay Summary: HCC incidence varies markedly depending on the underlying cause of cirrhosis. Herein, using readily available clinical and laboratory parameters we describe a risk score, THRI, which has a good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis.
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http://dx.doi.org/10.1016/j.jhep.2017.07.033DOI Listing
August 2017

Wait Time for Curative Intent Radio Frequency Ablation is Associated with Increased Mortality in Patients with Early Stage Hepatocellular Carcinoma.

Ann Hepatol 2017 Sep-Oct;16(5):765-771

University of Toronto, Toronto, ON, Canada Department of Medicine, Division of Gastroenterology.

Introduction: Radiofrequency ablation (RFA) is a recommended curative intent treatment option for patients with early stage hepatocellular carcinoma (HCC). We investigated if wait times for RFA were associated with residual tumor, tumor recurrence, need for liver transplantation, or death.

Material And Methods: We conducted a retrospective study of patients diagnosed with HCC between January 2010 and December 2013 presenting to University Health Network (UHN) in Toronto, Canada. All patients receiving curative intent RFA for HCC were included. Multivariable Cox regression was used to determine if wait times were associated with clinical outcomes.

Results: 219 patients were included in the study. 72.6% were male and the median age was 62.7 years (IQR 55.6-71). Median tumor size at diagnosis was 21.5 mm (IQR 17-26); median MELD was 8.7 (IQR 7.2-11.4) and 57.1% were Barcelona stage 0. The cause of liver disease was viral hepatitis in 73.5% (Hepatitis B and C). The median time from HCC diagnosis to RFA treatment was 96 days (IQR 75-139). In multivariate analysis, wait time was not associated with requiring liver transplant or tumor recurrence, however, each incremental 30-day wait time was associated with an increased risk of residual tumor (HR = 1.09; 95% CI 1.01-1.19; p = 0.033) as well as death (HR = 1.23; 95% CI 1.11-1.36; p ≤ 0.001).

Conclusion: Incremental 30-day wait times are associated with a 9% increased risk of residual tumor and a 23% increased risk of death. We have identified system gaps where quality improvement measures can be implemented to reduce wait times and allocate resources for future RFA treatment, which may improve both quality and efficiency of HCC care.
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http://dx.doi.org/10.5604/01.3001.0010.2776DOI Listing
May 2018

Polycystic Kidney Disease without an Apparent Family History.

J Am Soc Nephrol 2017 Sep 18;28(9):2768-2776. Epub 2017 May 18.

Division of Nephrology and

The absence of a positive family history (PFH) in 10%-25% of patients poses a diagnostic challenge for autosomal dominant polycystic kidney disease (ADPKD). In the Toronto Genetic Epidemiology Study of Polycystic Kidney Disease, 210 affected probands underwent renal function testing, abdominal imaging, and comprehensive and mutation screening. From this cohort, we reviewed all patients with and without an apparent family history, examined their parental medical records, and performed renal imaging in all available parents of unknown disease status. Subsequent reclassification of 209 analyzed patients revealed 72.2% (151 of 209) with a PFH, 15.3% (32 of 209) with disease, 10.5% (22 of 209) with an indeterminate family history, and 1.9% (four of 209) with PFH in retrospect. Among the patients with cases, we found two families with germline mosaicism and one family with somatic mosaicism. Additionally, analysis of renal imaging revealed that 16.3% (34 of 209) of patients displayed atypical PKD, most of which followed one of three patterns: asymmetric or focal PKD with PFH and an identified or mutation (15 of 34), asymmetric and PKD with proven or suspected somatic mosaicism (seven of 34), or focal PKD without any identifiable or mutation (eight of 34). In conclusion, PKD without an apparent family history may be due to disease, missing parental medical records, germline or somatic mosaicism, or mild disease from hypomorphic and mutations. Furthermore, mutations of a newly identified gene for ADPKD, , and somatic mosaicism need to be considered in the mutation-negative patients with focal disease.
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http://dx.doi.org/10.1681/ASN.2016090938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576926PMC
September 2017

Editorial: Not All Nodules Are Created Equal: A Personalized Approach to Indeterminate (<2 cm) Nodules Identified on HCC Surveillance.

Am J Gastroenterol 2017 03;112(3):471-472

Department of Radiology, University of Toronto, Toronto, Ontario, Canada.

Indeterminate small (<2 cm) nodules are often discovered in cirrhotics who undergo contrast enhanced imaging for further characterization of lesions detected on ultrasound surveillance for hepatocellular carcinoma (HCC). These are either arterially enhancing (without venous washout or capsule) or are non-enhancing (with washout). Differentials include small HCCs (14-23%), atypical arterio-portal shunts, regenerative, and dysplastic nodules. A risk score that combines imaging features (arterial enhancement and nodule size) with clinical (age, prior h/o HCC) and laboratory features (albumin, AFP, hepatitis B 'e' antigen) appear to be superior to radiological features alone in the risk stratification of these nodules.
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http://dx.doi.org/10.1038/ajg.2016.603DOI Listing
March 2017
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