Symptom relief and not cyst reduction determines treatment success in aspiration sclerotherapy of hepatic cysts.

OBJECTIVE: To assess whether quantitative assessment of symptom reduction is a better outcome parameter than cyst volume reduction for treatment success in patients treated by aspiration sclerotherapy. METHODS: We included patients with symptomatic, large (> 5 cm), hepatic cysts from a randomized controlled trial (NCT02048319). At baseline and 6 months after treatment, symptoms were assessed with the polycystic liver disease questionnaire (PLD-Q) and we measured cyst volume using ultrasonography. Patient-reported change in health was assessed on a 5-point Likert scale (much worse to much better) after 6 months. We tested whether PLD-Q scores and cyst volumes changed after aspiration sclerotherapy (responsiveness). Changes in PLD-Q scores and cyst volume were compared with change in health as a measure of treatment success (discriminative ability). As secondary analysis, we compared baseline characteristics between responders (improved) and non-responders (not improved). RESULTS: We included 32 patients. Six months after treatment, 23 patients (72%) improved. Both PLD-Q score and cyst volume significantly decreased (median 38 to 18 points, p < 0.001, and 479 to 68 mL, p < 0.001). Larger improvement in PLD-Q score was associated with a positive change in health (p = 0.001), while larger proportional reduction in cyst volume was not significantly associated with health improvement after treatment (p = 0.136). Responders had larger baseline cyst volumes compared to non-responders (median 624 mL [IQR 343-1023] vs. 322 mL [IQR 157-423] p = 0.008). CONCLUSION: Cyst diameter reduction does not reflect treatment success in aspiration sclerotherapy from patients' perspective, while symptoms measured with the PLD-Q can be used as a reliable outcome measure. KEY POINTS: • Cyst diameter reduction poorly reflects treatment success in aspiration sclerotherapy. • Symptoms measured by the polycystic liver disease questionnaire (PLD-Q) is a better outcome measure than cyst volume reduction for treatment success after aspiration sclerotherapy. • Particularly patients with larger cysts (≥ 529 mL) benefit from aspiration sclerotherapy.

Pasireotide does not improve efficacy of aspiration sclerotherapy in patients with large hepatic cysts, a randomized controlled trial.

OBJECTIVES: We tested whether complementary use of the somatostatin analogue pasireotide would augment efficacy of aspiration sclerotherapy of hepatic cysts. METHODS: We conducted a double-blind, placebo-controlled trial in patients who underwent aspiration sclerotherapy of a large (>5 cm) symptomatic hepatic cyst. Patients were randomized to either intramuscular injections of pasireotide 60 mg long-acting release (n = 17) or placebo (sodium chloride 0.9 %, n = 17). Injections were administered 2 weeks before and 2 weeks after aspiration sclerotherapy. The primary endpoint was proportional cyst diameter reduction (%) from baseline to 6 weeks. Secondary outcomes included long-term cyst reduction at 26 weeks, patient-reported outcomes including the polycystic liver disease-questionnaire (PLD-Q) and safety. RESULTS: Thirty-four patients (32 females; 53.6 ± 7.8 years) were randomized between pasireotide or placebo. Pasireotide did not improve efficacy of aspiration sclerotherapy at 6 weeks compared to controls (23.6 % [IQR 12.6-30.0] vs. 21.8 % [9.6-31.8]; p = 0.96). Long-term cyst diameter reduction was similar in both groups (49.1 % [27.0-73.6] and 45.6 % [29.6-59.6]; p = 0.90). Mean PLD-Q scores improved significantly in both groups (p < 0.01) without differences between arms (p = 0.92). CONCLUSIONS: In patients with large symptomatic hepatic cysts, complementary pasireotide to aspiration sclerotherapy did not improve cyst reduction or clinical response. KEY POINTS: • Complementary pasireotide treatment does not improve efficacy of aspiration sclerotherapy. • Cyst fluid reaccumulation after aspiration sclerotherapy is a transient phenomenon. • Aspiration sclerotherapy strongly reduces symptoms and normalizes quality of life.

Development and Validation of a Disease-Specific Questionnaire to Assess Patient-Reported Symptoms in Polycystic Liver Disease.

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).

Predictors of treatment response following aspiration sclerotherapy of hepatic cysts: an international pooled analysis of individual patient data.

OBJECTIVES: To identify predictive variables of treatment response following aspiration sclerotherapy of large symptomatic hepatic cysts. METHODS: We collected individual patient data from two tertiary referral centres and included all patients treated with aspiration sclerotherapy of a large (>5 cm), symptomatic hepatic cyst. At six months, clinical response was defined as complete or incomplete. Secondary, suboptimal technical response was defined as lower quartile of cyst reduction. Predictive variables of clinical and technical response were analyzed by logistic regression analysis. RESULTS: We included 86 patients (58 ± 10 years; female 90 %). Complete clinical response rate was 55 %. Median cyst diameter and volume reduction were 71 % (IQR 50-87 %) and 98 % (IRQ 88-100 %), respectively. Patients with complete clinical response had a significantly higher cyst reduction compared to incomplete responders (OR 1.02, 95 % CI 1.00-1.04). Aspiration of haemorrhagic cyst fluid (OR 4.39, 95 % CI 1.34-14.39) or a lower cyst reduction at one month (OR 1.06, 95 % CI 1.02-1.10) was associated with a suboptimal technical response at six months. CONCLUSION: Complete clinical response is associated with effective cyst reduction. Aspiration of haemorrhagic cyst fluid or a restricted diameter reduction at one month predicts a suboptimal technical treatment response, however, these variables did not predict symptom disappearance. KEY POINTS: • Aspiration sclerotherapy of hepatic cysts shows excellent clinical and technical efficacy. • Optimal clinical responders have a markedly higher cyst reduction. • Haemorrhagic aspirate and a strong fluid reaccumulation predict suboptimal cyst reduction.

Efficacy and Safety of Aspiration Sclerotherapy of Simple Hepatic Cysts: A Systematic Review.

OBJECTIVE: Aspiration sclerotherapy is a percutaneous procedure indicated for treatment of symptomatic simple hepatic cysts. The efficacy and safety of this procedure have been sources of debate and disagreement for years. The purpose of this study was to assess the long-term efficacy and safety of aspiration sclerotherapy in a systematic review of the literature. MATERIALS AND METHODS: A systematic search was conducted of the electronic databases PubMed MEDLINE, Embase, Web of Science, and the Cochrane Library (until August 2015). Studies of proportional volume or diameter reduction after aspiration sclerotherapy of simple hepatic cysts were included for full-text evaluation. Case reports and case series were excluded. Risk of bias was assessed by use of the Newcastle-Ottawa scale. RESULTS: From 9357 citations, 100 were selected for full-text assessment. We included 16 studies, which included 526 patients with a total of 588 treated cysts. Overall, risk of bias was high, with 12 of 16 studies having a score of poor. Proportional cyst volume reduction ranged between 76% and 100% after a median follow-up period of 1-54 months. Change in symptoms was evaluated in 10 studies: 72-100% of patients reported symptom reduction, and 56-100% reported disappearance. Postprocedural pain occurred most frequently, at a rate of 5-90% among studies. Ethanol intoxication occurred in up to 93% of cases and was reported more frequently in studies with either high ethanol volumes (133.7-138.3 mL) or long sclerotherapy duration (120-180 minutes). CONCLUSION: We found excellent results with respect to long-term efficacy and safety after aspiration sclerotherapy of hepatic cysts. Nevertheless, because of the high risk of bias in the included studies, definite conclusions regarding efficacy cannot be drawn.

Evaluating health-related quality of life in patients with polycystic liver disease and determining the impact of symptoms and liver volume.

BACKGROUND & AIMS: Polycystic liver disease (PLD) follows a progressive course ultimately leading to severe hepatomegaly and mechanical complaints in a subset of patients. It is still unknown to what extent this compromises health-related quality of life (HRQL). Our aim was to determine HRQL in PLD patients and investigate its association with concurrent abdominal symptoms and liver volume. METHODS: Pooled data of 92 severe PLD patients from two randomized clinical trials were used for our cross-sectional analysis. HRQL was assessed using the generic short-form health survey (SF-36) resulting in eight scale scores and the summarizing physical (PCS) and mental component score (MCS). Subsequently, these were compared with the general population. Abdominal symptoms were measured with a standardized, 7-point scale questionnaire in 54 patients. We dichotomized symptoms for absence or presence and compared them with the component scores. Finally, a possible correlation between liver volume and HRQL was explored. RESULTS: Demographics showed severe polycystic livers (mean 4906 ± 2315 ml). PCS was significantly lower compared with the general population (P < 0.001), in contrast with a similar MCS (P = 0.82). PLD patients had statistically significant (P < 0.05) diminished physical functioning, role physical, general health, vitality and social functioning scores. Upper- and lower abdominal pain and dyspnoea were significantly associated with a reduced PCS (P < 0.01). No correlation was found between liver volume and HRQL. CONCLUSION: Polycystic liver disease patients had significantly lower HRQL in the physical dimension compared with the general population. Abdominal pain and dyspnoea had a significant impact on this physical dimension of HRQL.

Aspiration sclerotherapy combined with pasireotide to improve reduction of large symptomatic hepatic cysts (SCLEROCYST): study protocol for a randomized controlled trial.

BACKGROUND: Aspiration sclerotherapy is an effective therapeutic option for large symptomatic hepatic cysts. However, incomplete cyst reduction following aspiration sclerotherapy is frequently reported. Strong post-procedural cyst fluid secretion by cholangiocytes, which line the epithelium of the hepatic cyst, seems to be associated with lower reduction rates. Previous studies showed that somatostatin analogues curtail hepatic cyst fluid production. This trial will evaluate the effect of aspiration sclerotherapy combined with the somatostatin analogue pasireotide on cyst reduction. By combining treatment modalities we aim to improve cyst reduction leading to greater symptomatic relief and reduced rates of cyst recurrence. METHODS/DESIGN: This single center, randomized, double-blind, placebo-controlled clinical trial evaluates the additional effect of pasireotide when combined with aspiration sclerotherapy in patients with a large (>5 cm) symptomatic hepatic cyst. A total of 34 participants will be randomized in a 1:1 ratio. In the active arm, patients will receive pasireotide (long-acting release, 60 mg injection) two weeks prior to and two weeks following aspiration sclerotherapy. Patients in the control arm will receive placebo injections at corresponding intervals. The primary outcome is proportional cyst diameter reduction four weeks after aspiration sclerotherapy compared to baseline measurements, obtained by ultrasonography. As secondary outcomes, proportional volume reduction, recurrence, symptomatic relief and improvement of health-related quality of life will be assessed. Furthermore, safety and tolerability of the combination of pasireotide and aspiration sclerotherapy will be evaluated. DISCUSSION: This trial aims to improve efficacy of aspiration sclerotherapy by a combined approach of two treatment modalities. We hypothesize that pasireotide will decrease fluid re-accumulation after aspiration sclerotherapy, leading to effective hepatic cyst reduction and symptomatic relief. TRIALS REGISTRATION: This trial is registered with ClinicalTrials.gov (identifier: NCT02048319 ; registered on 6 January 2014) and EudraCT (identifier: 2013-003168-29; registered on 16 August 2013).

Hepatic cyst infection following aspiration sclerotherapy: a case series.

Mass-related symptoms caused by hepatic cysts are effectively treated by aspiration sclerotherapy (AS). This minimal-invasive intervention is regarded as a safe procedure. Hence, occurrence of complications is low. Transient fever is commonly reported as a side effect. However, documentation on a post-procedural hepatic cyst infection as a complication of AS is limited. We present five cases in which a tentative diagnosis of post-procedural hepatic cyst infection was made. Patients typically presented with abdominal pain and fever, had to be admitted to our hospital, and were treated with long term antibiotics. Ultimately, the cyst infection successfully resolved with ciprofloxacin in all cases.