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Total kidney volume (TKV) is the main imaging biomarker used to monitor disease progression and to classify patients affected by autosomal dominant polycystic kidney disease (ADPKD) for clinical trials. However, patients with similar TKVs may have drastically different cystic presentations and phenotypes. In an effort to quantify these cystic differences, we developed the first 3D semantic instance cyst segmentation algorithm for kidneys in MR images. We have reformulated both the object detection/localization task and the instance-based segmentation task into a semantic segmentation task. This allowed us to solve this unique imaging problem efficiently, even for patients with thousands of cysts. To do this, a convolutional neural network (CNN) was trained to learn cyst edges and cyst cores. Images were converted from instance cyst segmentations to semantic edge-core segmentations by applying a 3D erosion morphology operator to up-sampled versions of the images. The reduced cysts were labeled as core; the eroded areas were dilated in 2D and labeled as edge. The network was trained on 30 MR images and validated on 10 MR images using a fourfold cross-validation procedure. The final ensemble model was tested on 20 MR images not seen during the initial training/validation. The results from the test set were compared to segmentations from two readers. The presented model achieved an averaged R 2 value of 0.94 for cyst count, 1.00 for total cyst volume, 0.94 for cystic index, and an averaged Dice coefficient of 0.85. These results demonstrate the feasibility of performing cyst segmentations automatically in ADPKD patients., (© 2021. The Author(s).)

Purpose: For patients affected by autosomal-dominant polycystic kidney disease (ADPKD), successful differentiation of cysts is useful for automatic classification of patient phenotypes, clinical decision-making, and disease progression. The objective was to develop and evaluate a fully automated semantic segmentation method to differentiate and analyze renal cysts in patients with ADPKD., Methods: An automated deep learning approach using a convolutional neural network was trained, validated, and tested on a set of 60 MR T2-weighted images. A three-fold cross-validation approach was used to train three models on distinct training and validation sets (n = 40). An ensemble model was then built and tested on the hold out cases (n = 20), with each of the cases compared to manual segmentations performed by two readers. Segmentation agreement between readers and the automated method was assessed., Results: The automated approach was found to perform at the level of interobserver variability. The automated approach had a Dice coefficient (mean ± standard deviation) of 0.86 ± 0.10 vs Reader-1 and 0.84 ± 0.11 vs. Reader-2. Interobserver Dice was 0.86 ± 0.08. In terms of total cyst volume (TCV), the automated approach had a percent difference of 3.9 ± 19.1% vs Reader-1 and 8.0 ± 24.1% vs Reader-2, whereas interobserver variability was - 2.0 ± 16.4%., Conclusion: This study developed and validated a fully automated approach for performing semantic segmentation of kidney cysts in MR images of patients affected by ADPKD. This approach will be useful for exploring additional imaging biomarkers of ADPKD and automatically classifying phenotypes.

Background: Polycystic liver disease can cause severe symptomatic hepatomegaly. Combined partial hepatectomy and cyst fenestration can be performed to reduce liver volume and symptom burden. We aimed to assess change in symptom relief and quality of life 6 months after partial hepatectomy and cyst fenestration in polycystic liver disease patients., Method: We established a prospective cohort between 2014 and 2018 at a referral center in the United States. Patients who underwent partial hepatectomy and cyst fenestration for volume-related symptoms were included. Primary outcome was change in polycystic liver disease-related symptoms, measured with Polycystic Liver Disease Questionnaire. Secondary outcomes were change in liver volume (computed tomography/ magnetic resonance imaging) and change in quality of life, measured with the 12-Item Short Form Survey and the EuroQoL Visual Analogue Scale. Questionnaire scores range from 0 to 100 and were assessed before and 6 months after partial hepatectomy and cyst fenestration. Surgical complications were scored according to Clavien-Dindo (grade 1 to 5)., Results: We included 18 patients (mean age 52 years, 82% female). Partial hepatectomy and cyst fenestration reduced median liver volume (4,917 to 2,120 mL). Symptoms, measured with Polycystic Liver Disease Questionnaire, decreased (76.9 to 34.8 points; P < .001) 6 months after surgery; 15/16 symptoms declined after treatment, with the most impact seen on early satiety and dyspnea. Quality of life also improved after surgery: median physical and mental component scales of the 12-Item Short Form Survey and EuroQoL Visual Analog Scale increased (24.9 to 45.7, P = .004; 40.5 to 55.4, P = .02; and 40.0 to 72.5, P = .003). Major complications (grade 4) occurred in 2 patients. There was no procedure-related mortality., Conclusion: Partial hepatectomy and cyst fenestration substantially improves symptom burden and quality of life in highly symptomatic polycystic liver disease patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Unlabelled: Treatment of polycystic liver disease (PLD) focuses on symptom improvement. Generic questionnaires lack sensitivity to capture PLD-related symptoms, a prerequisite to determine effectiveness of therapy. We developed and validated a disease-specific questionnaire that assesses symptoms in PLD (PLD-Q). We identified 16 PLD-related symptoms (total score 0-100 points) by literature review and interviews with patients and clinicians. The developed PLD-Q was validated in Dutch (n = 200) and United States (US; n = 203) PLD patients. We assessed the correlation of PLD-Q total score with European Organization for Research and Treatment of Cancer (EORTC) symptom scale, global health visual analogue scale (VAS) of EQ-5D, and liver volume. To test discriminative validity, we compared PLD-Q total scores of patients with different PLD severity stages (Gigot classification) and PLD-Q total scores of PLD patients with general controls and polycystic kidney disease patients without PLD. Reproducibility was tested by comparing original test scores with 2-week retest scores. In total, 167 Dutch and 124 US patients returned the questionnaire. Correlation between PLD-Q total score and EORTC symptom scale (The Netherlands [NL], r = 0.788; US, r = 0.811) and global health VAS (NL, r = -0.517; US, r = -0.593) was good. There was no correlation of PLD-Q total score with liver volume (NL, r = 0.138; P = 0.236; US, r = 0.254; P = 0.052). Gigot type III individuals scored numerically higher than type II patients (NL, 46 vs. 40; P = 0.089; US, 48 vs. 36; P = 0.055). PLD patients scored higher on the PLD-Q total score than general controls (NL, 42 vs. 17; US, 40 vs. 13 points) and polycystic kidney disease patients without PLD (22 points). Reproducibility of PLD-Q was excellent (NL, r = 0.94; US, 0.96)., Conclusion: PLD-Q is a valid, reproducible, and sensitive disease-specific questionnaire that can be used to assess PLD-related symptoms in clinical care and future research. (Hepatology 2016;64:151-160)., (© 2016 by the American Association for the Study of Liver Diseases.)

Background: Partial hepatectomy and cyst fenestration (PHCF) selectively provides clinical benefit in highly symptomatic patients with polycystic liver disease (PLD). This study aims to ascertain whether the reduction in liver volume (LV) achieved by PHCF is sustained long term., Study Design: Clinical data were retrieved from the electronic records of all patients with PLD who underwent PHCF between 1985 and 2014. Preoperative LVs (LV1), postoperative LVs (LV2), and late follow-up LVs (LV3) were measured from magnetic resonance or CT images., Results: Among 186 patients who underwent PHCF, 91% were Caucasian women with autosomal dominant polycystic kidney disease with a mean age of 49 years. Major perioperative complications (Clavien III/IV) occurred in 21% of the patients. Operative mortality (<90 days) was 2.7%. Eleven patients had liver failure develop, received liver transplants, or had liver-related deaths. Overall survival was 95.7%, 93.3%, 85.6%, and 77.7% at 1, 5, 10, and 15 years respectively. Imaging records for volumetry were unavailable in 32 patients. Of the remaining 154 patients, 34 had imaging for 1 LV, 64 for 2 LVs, and 55 for all 3 LVs. Median LV was 6,781 mL (interquartile range 4,903 to 8,341 mL) preoperatively and 2,502 mL (interquartile range 2,089 to 3,136 mL) after PHCF, leading to a median postoperative LV reduction of 61%. At follow-up (mean 8 years), median LV was 2,519 mL (interquartile range 2,083 to 3,752 mL). Interestingly, 33 of 62 patients with available LV2 and LV3 showed additional regression in LV at follow-up (median -14.1%), and the rest showed mild growth of 9.9%. Overall volumetric comparison of preoperative with follow-up liver imaging showed sustained LV reduction (median 61%)., Conclusions: Sustained long-term reductions in LV after PHCF can be achieved in selected patients with severe, highly symptomatic PLD. In our experience, liver-related death and subsequent liver transplantation are infrequent after PHCF., (Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Autosomal-dominant polycystic kidney disease (ADPKD) is a common, progressive, adult-onset disease that is an important cause of end-stage renal disease (ESRD), which requires transplantation or dialysis. Mutations in PKD1 or PKD2 (∼85% and ∼15% of resolved cases, respectively) are the known causes of ADPKD. Extrarenal manifestations include an increased level of intracranial aneurysms and polycystic liver disease (PLD), which can be severe and associated with significant morbidity. Autosomal-dominant PLD (ADPLD) with no or very few renal cysts is a separate disorder caused by PRKCSH, SEC63, or LRP5 mutations. After screening, 7%-10% of ADPKD-affected and ∼50% of ADPLD-affected families were genetically unresolved (GUR), suggesting further genetic heterogeneity of both disorders. Whole-exome sequencing of six GUR ADPKD-affected families identified one with a missense mutation in GANAB, encoding glucosidase II subunit α (GIIα). Because PRKCSH encodes GIIβ, GANAB is a strong ADPKD and ADPLD candidate gene. Sanger screening of 321 additional GUR families identified eight further likely mutations (six truncating), and a total of 20 affected individuals were identified in seven ADPKD- and two ADPLD-affected families. The phenotype was mild PKD and variable, including severe, PLD. Analysis of GANAB-null cells showed an absolute requirement of GIIα for maturation and surface and ciliary localization of the ADPKD proteins (PC1 and PC2), and reduced mature PC1 was seen in GANAB(+/-) cells. PC1 surface localization in GANAB(-/-) cells was rescued by wild-type, but not mutant, GIIα. Overall, we show that GANAB mutations cause ADPKD and ADPLD and that the cystogenesis is most likely driven by defects in PC1 maturation., (Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)