Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Diseases and Abnormalities at or Before Birth

Digestive System Diseases

Neoplasms

Symptoms and General Pathology

Rare Diseases

Behaviors and Mental Disorders

Kidney Diseases

Polycystic Kidney Diseases

Polycystic Kidney, Autosomal Dominant

Liver Diseases

Cysts

Gastrointestinal Diseases

Pathological Conditions, Anatomical

Autosomal Dominant Multiple Pterygium Syndrome

Quality of Life

Polycystic Liver Disease

Hematinics

All Drugs and Chemicals

Liver Extracts

will receive PLD-Q, EORTC QLQ-30 symptoms subscale, EQ5D-VAS score and SF36

PLD-Q

Marie C Hogan, MD, PhD

Marie C Hogan

Tom Gevers

Patrick Kamath

Jeff Sloan

Joost Drenth

This Pilot study will enable development \& assessment of a Polycystic Liver Disease-specific patient reported outcomes questionnaire (PLD-Q). Polycystic liver disease (PLD) is characterized by the formation of numerous cysts in the liver, and can lead to severe symptomatic hepatomegaly. It is common in patients with autosomal dominant polycystic liver disease (ADPLD) and autosomal dominant polycystic kidney disease (ADPKD).

As liver function is preserved, quality of life is the main outcome in PLD. Patient reported outcomes are increasingly utilized to assess treatment efficacy \& can include any endpoint derived from patient reports \& are usually assessed by questionnaire. Several existing generic questionnaires assess gastrointestinal symptoms, but include irrelevant items for polycystic liver disease (PLD) \& do not examine relevant extra-abdominal symptoms. Also, a questionnaire that assesses the full range of PLD related problems is more likely to be responsive to changes after treatment initiation. Therefore, a tool that accurately detects changes in PLD symptoms is required.

The development and first steps of validation of this questionnaire are already completed in Netherlands. We will further develop this questionnaire for English speaking patients and validate it in Mayo Clinic cohorts.

The study contains three phases. Phase 1: pilot testing of the directly translated questionnaire (from dutch into english) in a small group of polycystic liver disease (PLD) patients. We will include both symptomatic \& asymptomatic patients (i.e. from mild to severe PLD). Phase 2: further refinement of the questionnaire using the results of the pilot test and input of Mayo patient and clinician focus groups. Phase 3: Further validation in a large cohort of 200 PLD patients with (1) comparison with 200 controls without PLD, (2) cross-sectional correlation with total liver (TLV) \& kidney volumes (TKV), (3) comparing ADPKD patients with \& without PLD (5) against other validated questionnaires (e.g. SF36) \& (5) development of a custom "Worry Questionnaire" examining disease-related worries \& concerns. Finally, longitudinal analyses will be performed to assess PLD-Q sensitivity to change in symptoms. Statistical \& psychometric analyses will be provided by Mayo Clinic quality of life Research group, \& developed in accordance with Food and Drug Administration (FDA) guidance on patient-reported outcome measures in consultation with their Study Endpoints \& Labeling Development Division.

Development and Assessment of The Polycystic Liver Disease Questionnaire (PLD-Q).

Development and Assessment of the Psychometric Properties of a Polycystic Liver Disease-specific Patient Reported Outcomes Questionnaire (PLD-Q).

measured in patients with autosomal dominant polycystic kidney disease (ADPKD)

Mayo Clinic

Musculoskeletal Diseases

Nervous System Diseases

Arthrogryposis

Joint Diseases

Muscular Diseases

Congenital Abnormalities

Musculoskeletal Abnormalities

Kidney Diseases, Cystic

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Abnormalities, Multiple

Ciliopathies

Genetic Diseases, Inborn

Arthrogryposis Multiplex Congenita

Anti-Infective Agents

Central Nervous System Depressants

Pharmaceutical Solutions

Ethanol

Minocycline

Sclerosing Solutions

Aspiration sclerotherapy is a percutaneous procedure that evacuates fluid from the liver cyst and subsequently exposes cyst lining to a sclerosing agent (e.g. ethanol, minocycline) for a limited period of time.

Laparoscopic fenestration exposes the liver through laparoscopic surgery. During this procedure the cyst is punctured and drained followed by resection of the extra-hepatic cyst wall

aspiration sclerotherapy versus laparoscopic fenestration

Joost P.H. Drenth

Thijs Barten

Radboudumc University M Center

Patients with large hepatic cysts (\> 5cm) may develop symptoms. These can be captured with the polycystic liver disease questionnaire (PLD-Q). Treatment of large hepatic cysts consists of aspiration sclerotherapy or laparoscopic fenestration.

The safety and efficacy of both procedures has been explored in two recent systematic reviews yet no evident conclusion regarding superiority of either procedure could be drawn.

The main objective of the ATLAS trial is to compare laparoscopic fenestration and aspiration sclerotherapy in patients with large symptomatic hepatic cysts on patient-reported outcomes.

Rationale: Patients with large hepatic cysts(\>5cm) may develop symptoms due to distention of Glisson's capsule and/or compression on other abdominal organs. Frequently reported symptoms include abdominal pain, early satiety, nausea, and dyspnea. These symptoms can be captured in the disease-specific Polycystic Liver Disease Questionnaire (PLD-Q), a validated instrument. The treatment of symptomatic liver cysts is aimed to improve symptoms and quality of life by reducing cyst volume. There are two procedures available to treat symptomatic liver cysts: percutaneous aspiration sclerotherapy and laparoscopic fenestration.

In aspiration sclerotherapy, fluid is evacuated from the liver cyst and subsequently the cyst lining is exposed to a sclerosing agent for a limited period of time. Sclerotherapy causes temporary recurrence of cyst fluid after drainage, but subsequently results in a steady decrease of cyst volume in the majority of patients.

In laparoscopic fenestration the liver is exposed through laparoscopic surgery. In this procedure the cyst is punctured and drained followed by resection of extra-hepatic cyst wall.

The safety and efficacy of aspiration sclerotherapy and laparoscopic fenestration have been explored in two recent systematic reviews. No evident conclusion could be drawn because of the retrospective study design in the vast majority of the studies and the heterogeneity among these. A randomized controlled trial is warranted to identify the possible differences in safety and efficacy in aspiration sclerotherapy and laparoscopic fenestration.

Hypothesis: The investigators expect patients treated with laparoscopic fenestration to have better clinical outcome; i.e. a lower PLD-Q score, compared to aspiration sclerotherapy, when measured 4 weeks after the procedure. The investigators expect this difference to become smaller over time (after 6 and 12 months), with loss of statistical significance.

Objective: The main objective is to compare laparoscopic fenestration and aspiration sclerotherapy in patients with large symptomatic hepatic cysts on patient-reported outcomes. This information can be used to assess cost-effectiveness in both treatments.

Study design: A prospective, randomized clinical superiority trial in which patients will be randomized 1:1 to one of the treatment arms. Patients will be followed for 1 year.

Study population: All patients ≥18 years who are diagnosed with a dominant, simple hepatic cyst (\>5 cm in diameter), that are symptomatic (PLD-Q score ≥20) and have an indication for treatment (both aspiration sclerotherapy and laparoscopic fenestration) are suitable for inclusion in this study. Only patients that are eligible for both treatments can be included in this study. In particular, patients with multiple cysts (\>20 cysts of \>1.5 cm) will be excluded as surgery leads to more complications in these patients.

Intervention: Patients will be randomly allocated to either aspiration sclerotherapy or laparoscopic fenestration. Both procedures are performed according to the standard Radboudumc protocols. Aspiration sclerotherapy consists of ultrasound-guided, percutaneous drainage of the cyst with subsequent sclerosation with ethanol. Laparoscopic fenestration consists of standard abdominal laparoscopy in which the large cyst(s) are drained and deroofed.

Main study parameters: The main study parameter is the PLD-Q score at 4 weeks after treatment. Secondary parameters are among others: PLD-Q score at baseline, 6 months and 12 months; liver volume (CT) at baseline and 4 weeks; cyst volume (ultrasound) at baseline, 4 weeks, 6 months and 12 months; complications according to Clavien-Dindo; admission duration, recurrence and re-intervention rates.

Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts

Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts (ATLAS): a Randomized Clinical Trial.

Individual participant data are available to other researchers for clinical research purposes upon reasonable request to the principal investigator

Comparison of PLD-Q scores 4 weeks after the procedure, adjusted for baseline PLD-Q score.

PLD-Q score at 1, 6 and 12 months after intervention, adjusted for baseline

PLD-Q individual symptom scores at 1, 6 and 12 months after intervention, compared to baseline

SF-36 Mental Component Score at 1, 6 and 12 months after intervention, adjusted to baseline

SF-36 Physical Component Score at 1, 6 and 12 months after intervention, adjusted to baseline

EQ-5D-5L score at 1, 6 and 12 months after intervention, adjusted to baseline

Liver and cyst volume with CT before and 12 months after the intervention

Liver and cyst volume in cases of recurrence of symptoms

Cyst volume with ultrasound, at baseline and 1, 6 and 12 months after intervention.

Adverse events (according to Clavien-Dindo)

Re-intervention rates during 12 months follow-up.

Cost-effectiveness of both procedures iPCQ 1, 6 and 12 months after intervention, adjusted for baseline

Cost-effectiveness of both procedures iMCQ 1, 6 and 12 months after intervention, adjusted for baseline

Radboud University Medical Center

Cassie Howe, CRC

Marie C. Hogan, M.D., Ph.D.

Marie Hogan, MD, PhD

An observational prospective study to determine the impact of foam sclerotherapy of large, dominant kidney/liver cysts on quality of life outcomes and kidney/liver cyst volumes at up to 12 months of follow-up in patients with autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD).

Cyst burden is an important determinant of outcomes in both autosomal dominant polycystic kidney disease (ADPKD) (1, 2) and autosomal dominant polycystic liver disease (ADPLD) (3, 4). Furthermore, mass symptoms (from liver and kidney volume) greatly impact upon quality of life in patients with severe disease. Cyst volume increases exponentially with age and results in the development of end-stage renal disease and hypertension, compromised quality of life due to compressive symptoms, and predisposes patients to cyst complications such as infection, hemorrhage, rupture, and torsion. Existing percutaneous treatments for cyst burden in ADPKD and ADPLD include cyst aspiration with or without sclerotherapy. Although frequently effective in the short-term, recurrence rates and the need for repeat procedures are high after these procedures (5, 6). Extrarenal disease (primarily liver disease) is the most important aspect of disease burden to ADPKD patients (7), and there are few effective treatments.

Foam sclerotherapy (FS) with 3% Sodium Tetradecyl Sulfate (STS) a sclerosing agent. (Sotradecol®; Mylan, Galway, Ireland) is approved by the FDA for the management of varicose veins. While increasing cyst burden significantly compromises quality of life, the impact of FS on patient-reported outcomes has not been evaluated. In collaboration with the Center for Science of Healthcare delivery, we have developed a patient-reported outcome tool for polycystic liver disease capable of detecting symptom burden in individuals with polycystic liver disease that has been approved by the FDA as a patient-reported outcomes tool in research. Furthermore measurement of liver and kidney volumes can be performed in the Polycystic Kidney Disease Imaging Research Core that monitors organ volumes before and after interventions. At this time, patients are interested in procedures that will alleviate and palliate their mass symptoms but desire preliminary information on the procedural efficacy. We aim to report our experience with a new therapeutic advance - FS for the treatment of liver and kidney cysts at Mayo Clinic - and to determine the impact of this procedure on patient-reported quality of life measures and changes in organ volumes.

A Prospective Observational Study of Foam Sclerotherapy .

A Prospective Observational Study of Foam Sclerotherapy for the Treatment of Symptomatic Kidney or Liver Cysts in Patients With Autosomal Dominant Polycystic Kidney and Liver Disease.

Measured using self assessed brief pain inventory (short form) questionnaire, using a scale of 0 is no pain and 10 is pain as bad as you can imagine

Measured using the linear analogue self assessed questionnaire, using a scale of 0 is as bad as it can be and 10 is as good as it can be

Measured using the self assessed Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), using a scale that ranges from yes and no or all of the time to none of the time

Measured using the self assessed Polycystic Liver Disease Questionnaire, using a scale that ranges from never/not at all to always/a lot

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Development and Assessment of The Polycystic Liver Disease Questionnaire (PLD-Q).	NCT02173080	Polycystic Live...	PLD-Q	18 Years -	Mayo Clinic
Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts	NCT05500157	Liver Cyst Polycystic Live... Autosomal Domin... Autosomal Domin...	aspiration scle...	18 Years - 75 Years	Radboud University Medical Center
A Prospective Observational Study of Foam Sclerotherapy .	NCT04111692	Autosomal Domin... Renal Cyst Autosomal Domin... Hepatic Cyst		18 Years - 100 Years	Mayo Clinic
Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts	NCT05500157	Liver Cyst Polycystic Live... Autosomal Domin... Autosomal Domin...	aspiration scle...	18 Years - 75 Years	Radboud University Medical Center
Development and Assessment of The Polycystic Liver Disease Questionnaire (PLD-Q).	NCT02173080	Polycystic Live...	PLD-Q	18 Years -	Mayo Clinic
A Prospective Observational Study of Foam Sclerotherapy .	NCT04111692	Autosomal Domin... Renal Cyst Autosomal Domin... Hepatic Cyst		18 Years - 100 Years	Mayo Clinic

Spots Global Cancer Trial Database for autosomal dominant polycystic liver disease