Variation in the management of benign liver tumors: A European survey and case vignette study.

BACKGROUND: Management of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA), is multidisciplinary and subject to practice variation. We aimed to evaluate variation in clinical management of FNH and HCA in Europe. METHODS: We distributed an online survey (November 2021-March 2022) among 294 European experts. The survey included questions on local practice and included eight clinical vignettes. The clinical vignettes focused on FNH or HCA management in the setting of sex, lifestyle modification, and pregnancy. RESULTS: The response rate was 32% and respondents included surgeons (38%), gastroenterologists/hepatologists (25%), radiologists (32%), and pathologists (1.6%) from ten European countries. We observed practice variation with regard to lifestyle modification and imaging follow-up in patients with FNH, and with regard to the management of HCA >5 cm before and during pregnancy. Finally, the management of HCA >5 cm after lifestyle modification deviated from EASL guideline recommendations. CONCLUSION: Our survey illustrates variability in FNH and HCA management in Europe. Several areas were identified for future research and guideline recommendations, including FNH follow-up and the management of HCA >5 cm. We propose the organization of Delphi consensus meetings to prioritize areas of research and update current guidelines to optimize management for all patients with benign liver tumors.

A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation.

BACKGROUND & AIMS: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. METHODS: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. RESULTS: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). CONCLUSIONS: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. IMPACT AND IMPLICATIONS: This randomized controlled phase III trial is the first to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation. Compared to conventional cold storage, HOPE did not have a significant effect on the number of patients with at least one Clavien ≥III complication. However, we believe that HOPE may have a beneficial effect on the quantity of complications per patient, based on its application leading to fewer severe liver graft-related complications, and to a lower risk of liver-related graft loss. The HOPE approach can be applied easily after organ transport during recipient hepatectomy. This appears fundamental for wide acceptance since concurring perfusion technologies need either perfusion at donor sites or continuous perfusion during organ transport, which are much costlier and more laborious. We conclude therefore that the post hoc findings of this trial should be further validated in future studies.

A nationwide assessment of hepatocellular adenoma resection: Indications and pathological discordance.

Hepatocellular adenomas (HCAs) are benign liver tumors associated with bleeding or malignant transformation. Data on the indication for surgery are scarce. We analyzed indications and outcome of patients operated for HCAs < 50 mm compared to HCAs ≥ 50 mm. Changes in final postoperative diagnosis were assessed. We performed a retrospective study that included patients who underwent resection for (suspected) HCAs in the Netherlands from 2014 to 2019. Indication for resection was analyzed and stratified for small (<50 mm) and large (≥50 mm) tumors. Logistic regression analysis was performed on factors influencing change in tumor diagnosis. Out of 222 patients who underwent surgery, 44 (20%) patients had a tumor <50 mm. Median age was 46 (interquartile range [IQR], 33-56) years in patients with small tumors and 37 (IQR, 31-46) years in patients with large tumors ( p  = 0.016). Patients with small tumors were more frequently men (21% vs. 5%, p  = 0.002). Main indications for resection in patients with small tumors were suspicion of (pre)malignancy (55%), (previous) bleeding (14%), and male sex (11%). Patients with large tumors received operations because of tumor size >50 mm (52%), suspicion of (pre)malignancy (28%), and (previous) bleeding (5.1%). No difference was observed in HCA-subtype distribution between small and large tumors. Ninety-six (43%) patients had a postoperative change in diagnosis. Independent risk factors for change in diagnosis were tumor size <50 mm (adjusted odds ratio [aOR], 3.4; p  < 0.01), male sex (aOR, 3.7; p  = 0.03), and lack of hepatobiliary contrast-enhanced magnetic resonance imaging (CE-MRI) (aOR, 1.8; p  = 0.04). Resection for small (suspected) HCAs was mainly indicated by suspicion of (pre)malignancy, whereas for large (suspected) HCAs, tumor size was the most prevalent indication. Male sex, tumor size <50 mm, and lack of hepatobiliary CE-MRI were independent risk factors for postoperative change in tumor diagnosis.

Development of a set of patient reported outcome measures for patients with benign liver tumours and cysts: patient focus groups and systematic review.

BACKGROUND: Patient reported outcome measures (PROMs) may be useful for patients with benign liver tumours and cysts (BLTC) to evaluate the impact of treatment and/or guide shared decision making. Yet, a set of PROMs relevant to patients with BLTC is currently unavailable. In this study, we selected a PROMs set for patients with BLTC. METHODS: Potentially relevant patient reported outcomes (PROs) were selected by psychologist-researchers based on keywords used or suggested by participants of two virtual focus groups meetings consisting of thirteen female BLTC patients with a median age of 50 years. Subsequently, patients were asked to report their most relevant PROs. PROMs identified by systematic literature review and computerized adaptive tests (CATs) in the Patient-Reported Outcomes Measurement Information System (PROMIS) were considered in selecting the final PROMs set to assess relevant outcomes. RESULTS: The most important PROs were: insecurity/anxiety (11/12 patients), pain (9/12 patients), fatigue (8/12 patients), and limitations in daily life (5/12 patients). The literature review included 23 studies, which used various generic and disease-specific PROMs, often not measuring (all) relevant PROs. The final selected PROMs set included numerical rating scales for pain, two questions on overall health and quality of life and four PROMIS CATs. CONCLUSIONS: A PROMs set generically and efficiently measuring outcomes relevant for patients with BLTC was developed and may be used in future research and clinical practice.

High childhood serum triglyceride concentrations associate with hepatocellular adenoma development in patients with glycogen storage disease type Ia.

Background & Aims: Glycogen storage disease type Ia (GSDIa) is an inborn error of carbohydrate metabolism caused by pathogenic variants in the glucose-6-phosphatase catalytic subunit 1 (G6PC1) gene and is associated with hepatocellular adenoma (HCA) formation. Data on risk factors for HCA occurrence in GSDIa are scarce. We investigated HCA development in relation to sex, G6PC1 genotype, and serum triglyceride concentration (TG). Methods: An observational study of patients with genetically confirmed GSDIa ≥12 years was performed. Patients were categorised for sex; presence of 2, 1, or 0 predicted severe G6PC1 variant (PSV); and median TG during childhood (<12 years; stratified for above/below 5.65 mmol/L, i.e. 500 mg/dl). Results: Fifty-three patients (23 females) were included, of which 26 patients developed HCA at a median (IQR) age of 21 (17-25) years. At the age of 25 years, 48% of females and 30% of males had developed HCA (log-rank p = 0.045). Two-thirds of patients with GSDIa carried 2 PSVs, 20% carried 1, and 13% carried none. Neither the number of PSVs nor any specific G6PC1 variants were associated with HCA occurrence. Childhood TG was 3.4 (3.0-4.2) mmol/L in males vs. 5.6 (4.0-7.9) mmol/L in females (p = 0.026). Childhood TG >5.65 mmol/L was associated with HCA development at younger age, compared with patients with childhood TG <5.65 mmol/L (18 vs. 33 years; log-rank p = 0.001). Cox regression analysis including TG, sex, and TG-sex interaction correction revealed childhood TG >5.65 mmol/L as an independent risk factor for HCA development (hazard ratio [HR] 6.0; 95% CI 1.2-29.8; p = 0.028). Conclusions: In patients with GSDIa, high childhood TG was associated with an increased risk of HCA, and earlier onset of HCA development, independent of sex-associated hypertriglyceridaemia, and G6PC1 genotype. Lay summary: Glycogen storage disease type Ia (GSDIa) is a rare, inherited metabolic disease that can be complicated by liver tumours (hepatocellular adenomas), which in turn may cause bleeding or progress to liver cancer. Risk factors associated with hepatocellular adenoma formation in patients with GSDIa are largely unknown. In our study, we found that high serum triglyceride concentrations during childhood, but not specific genetic variants, were associated with increased risk of hepatocellular adenoma diagnosis later in life.

Sequential hypothermic and normothermic machine perfusion enables safe transplantation of high-risk donor livers.

Ex situ normothermic machine perfusion (NMP) is increasingly used for viability assessment of high-risk donor livers, whereas dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia-reperfusion injury. We aimed to resuscitate and test the viability of initially-discarded, high-risk donor livers using sequential DHOPE and NMP with two different oxygen carriers: an artificial hemoglobin-based oxygen carrier (HBOC) or red blood cells (RBC). In a prospective observational cohort study of 54 livers that underwent DHOPE-NMP, the first 18 procedures were performed with a HBOC-based perfusion solution and the subsequent 36 procedures were performed with an RBC-based perfusion solution for the NMP phase. All but one livers were derived from extended criteria donation after circulatory death donors, with a median donor risk index of 2.84 (IQR 2.52-3.11). After functional assessment during NMP, 34 livers (63% utilization), met the viability criteria and were transplanted. One-year graft and patient survival were 94% and 100%, respectively. Post-transplant cholangiopathy occurred in 1 patient (3%). There were no significant differences in utilization rate and post-transplant outcomes between the HBOC and RBC group. Ex situ machine perfusion using sequential DHOPE-NMP for resuscitation and viability assessment of high-risk donor livers results in excellent transplant outcomes, irrespective of the oxygen carrier used.

Study protocol for a multicentre nationwide prospective cohort study to investigate the natural course and clinical outcome in benign liver tumours and cysts in the Netherlands: the BELIVER study.

INTRODUCTION: Benign liver tumours and cysts (BLTCs) comprise a heterogeneous group of cystic and solid lesions, including hepatic haemangioma, focal nodular hyperplasia and hepatocellular adenoma. Some BLTCs, for example, (large) hepatocellular adenoma, are at risk of complications. Incidence of malignant degeneration or haemorrhage is low in most other BLTCs. Nevertheless, the diagnosis BLTC may carry a substantial burden and patients may be symptomatic, necessitating treatment. The indications for interventions remain matter of debate. The primary study aim is to investigate patient-reported outcomes (PROs) of patients with BLTCs, with special regards to the influence of invasive treatment as compared with the natural course of the disease. METHODS AND ANALYSIS: A nationwide observational cohort study of patients with BLTC will be performed between October 2021 and October 2026, the minimal follow-up will be 2 years. During surveillance, a questionnaire regarding symptoms and their impact will be sent to participants on a biannual basis and more often in case of invasive intervention. The questionnaire was previously developed based on PROs considered relevant to patients with BLTCs and their caregivers. Most questionnaires will be administered by computerised adaptive testing through the Patient-Reported Outcomes Measurement Information System. Data, such as treatment outcomes, will be extracted from electronic patient files. Multivariable analysis will be performed to identify patient and tumour characteristics associated with significant improvement in PROs or a complicated postoperative course. ETHICS AND DISSEMINATION: The study was assessed by the Medical Ethics Committee of the University Medical Center Groningen and the Amsterdam UMC. Local consultants will provide information and informed consent will be asked of all patients. Results will be published in a peer-reviewed journal. STUDY REGISTRATION: NL8231-10 December 2019; Netherlands Trial Register.

Scoping review of clinical practice guidelines on the management of benign liver tumours.

OBJECTIVE: Benign liver tumours (BLT) are increasingly diagnosed as incidentalomas. Clinical implications and management vary across and within the different types of BLT. High-quality clinical practice guidelines are needed, because of the many nuances in tumour types, diagnostic modalities, and conservative and invasive management strategies. Yet, available observational evidence is subject to interpretation which may lead to practice variation. Therefore, we aimed to systematically search for available clinical practice guidelines on BLT, to critically appraise them, and to compare management recommendations. DESIGN: A scoping review was performed within MEDLINE, EMBASE, and Web of Science. All BLT guidelines published in peer-reviewed, and English language journals were eligible for inclusion. Clinical practice guidelines on BLT were analysed, compared, and critically appraised using the Appraisal of Guidelines, Research and Evaluation (AGREE II) checklist regarding hepatic haemangioma, focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA). Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations (PRISMA) for scoping reviews were adhered to. RESULTS: The literature search yielded unique 367 papers, 348 were excluded after screening of title/abstract, and 16 after full-text screening. Three guidelines were included: the American College of Gastroenterology (ACG; 2014), Brazilian Society of Hepatology (SBH; 2015), and European Association for the Study of the Liver (EASL; 2016). There was no uniformity in the assessment methods for grading and gravity of recommendations between guidelines. Among observed differences were: (1) indications for biopsy in all three tumours; (2) advices on contraceptive pills and follow-up in FNH and HCA; (3) use of an individualised approach to HCA; (4) absence of recommendations for treatment of HCA in men; and (5) approaches to HCA subtype identification on magnetic resonance imaging. CONCLUSION: Recognising differences in recommendations can assist in harmonisation of practice standards and identify unmet needs in research. This may ultimately contribute to improved global patient care.

Hepatocellular adenoma in men: A nationwide assessment of pathology and correlation with clinical course.

BACKGROUND & AIMS: Hepatocellular adenomas (HCA) rarely occur in males, and if so, are frequently associated with malignant transformation. Guidelines are based on small numbers of patients and advise resection of HCA in male patients, irrespective of size or subtype. This nationwide retrospective cohort study is the largest series of HCA in men correlating (immuno)histopathological and molecular findings with the clinical course. METHODS: Dutch male patients with available histological slides with a (differential) diagnosis of HCA between 2000 and 2017 were identified through the Dutch Pathology Registry (PALGA). Histopathology and immunohistochemistry according to international guidelines were revised by two expert hepatopathologists. Next generation sequencing (NGS) was performed to confirm hepatocellular carcinoma (HCC) and/or subtype HCA. Final pathological diagnosis was correlated with recurrence, metastasis and death. RESULTS: A total of 66 patients from 26 centres fulfilling the inclusion criteria with a mean (±SD) age of 45.0 ± 21.6 years were included. The diagnosis was changed after expert revision and NGS in 33 of the 66 patients (50%). After a median follow-up of 9.6 years, tumour-related mortality of patients with accessible clinical data was 1/18 (5.6%) in HCA, 5/14 (35.7%) in uncertain HCA/HCC and 4/9 (44.4%) in the HCC groups (P = .031). Four B-catenin mutated HCA were identified using NGS, which were not yet identified by immunohistochemistry and expert revision. CONCLUSIONS: Expert revision with relevant immunohistochemistry may help the challenging but prognostically relevant distinction between HCA and well-differentiated HCC in male patients. NGS may be more important to subtype HCA than indicated in present guidelines.

Behavior and complications of hepatocellular adenoma during pregnancy and puerperium: a retrospective study and systematic review.

BACKGROUND: Hepatocellular adenomas (HCA) are benign liver tumors at risk of hemorrhage. The influence of pregnancy on HCA growth and potential bleeding remains unclear. This study investigates HCA-associated behavior and bleeding complications during or shortly after pregnancy. METHODS: (I) Single center retrospective cohort study of HCA during and after pregnancy (II) Systematic literature review. RESULTS: The retrospective study included 11 patients, of which 4 with HCA ≥5 cm. In only two patients HCA showed growth during pregnancy. In this local cohort, no HCA-related hemorrhages occurred during median follow-up of 34 months (interquartile range 19-58 months). The systematic review yielded 33 studies, totaling 90 patients with 99 pregnancies. Of 73 pregnancies without prior HCA-related intervention, 39 HCA remained stable (53.4%), 11 regressed (15.1%), and 23 (31.5%) progressed. Fifteen HCA-related hemorrhages occurred in HCA measuring 6.5-17.0 cm. Eight patients experienced bleeding during pregnancy, two during labor and five postpartum. CONCLUSION: Although hemorrhage of HCA during or shortly after pregnancy is rare and only reported in HCA ≥6.5 cm, it can be fatal. Pregnancy in women with HCA, regardless of size, warrant a close surveillance strategy. Observational studies on behavior and management of HCA ≥5 cm during and immediately after pregnancy are needed.

[Viability testing of discarded donor livers; More livers fit for transplantation because of machine perfusion]. / Testen van de vitaliteit van afgekeurde donorlevers.

In the Netherlands, the average quality of donor organs continues to decrease as a result of the increasing life expectancy, as well as higher incidence of obesity, diabetes mellitus, and other comorbidities in the general population. Storing donor organs on ice, the current standard practice, appears to be inadequate for preserving these high-risk donor livers. Consequently, an increasing number of donor organs is discarded for transplantation. Over the past years, a novel dynamic preservation technique using a machine perfusion device has been developed. Preservation by machine perfusion enables optimisation and viability testing of high-risk donor livers prior to liver transplantation. A large proportion of initially declined donor livers appeared to be suitable for transplantation after evaluation during machine perfusion. Testing of donor livers has led to a significant increase in the number of liver transplantations performed in the Netherlands. This technique has the potential for use in other organs, such as kidney allografts.

[Elevated CA19-9 levels; not always cancer]. / Verhoogde CA19-9-concentratie.

BACKGROUND: The levels of carbohydrate antigen 19-9 (CA19-9) are often tested to stage pancreatobiliary tumours or to monitor the effects of treatment of such tumours. Benign diseases can also be associated with elevated CA 19-9 levels, but extreme elevation is rare in such cases. CASE DESCRIPTION: An 84-year-old man was diagnosed with cholecystitis at the emergency department and received conservative treatment with antibiotics for this. After 5 weeks, the patient came to the outpatient clinic with unexplained icterus. Additional imaging revealed indications of malignancy and the CA19-9 concentration was 4240 kU/l. We suspected pancreatobiliary malignancy. However, ERCP revealed obstructive choledocholithiasis and we subsequently performed laparoscopic cholecystectomy. Based on histopathology examination of the gallbladder, a diagnosis of xanthogranulomatous cholecystitis was made. After surgery, CA19-9 levels decreased and the patient swiftly recovered. CONCLUSION: Significantly elevated CA19-9 levels are not proof of pancreatobiliary malignancy. Our case underscores that CA19-9 is not an ideal tumour marker and that the results of CA19-9 tests should therefore be interpreted with some caution.

Surgical outcomes of laparoscopic and open resection of benign liver tumours in the Netherlands: a nationwide analysis.

BACKGROUND: Data on surgical outcomes of laparoscopic liver resection (LLR) versus open liver resection (OLR) of benign liver tumour (BLT) are scarce. This study aimed to provide a nationwide overview of postoperative outcomes after LLR and OLR of BLT. METHODS: This was a nationwide retrospective study including all patients who underwent liver resection for hepatocellular adenoma, haemangioma and focal nodular hyperplasia in the Netherlands from 2014 to 2019. Propensity score matching (PSM) was applied to compare 30-day overall and major morbidity and 30-day mortality after OLR and LLR. RESULTS: In total, 415 patients underwent BLT resection of whom 230 (55.4%) underwent LLR. PSM for OLR and LLR resulted in 250 matched patients. Median (IQR) length of stay was shorter after LLR than OLR (4 versus 6 days, 5.0-8.0, p < 0.001). Postoperative 30-day overall morbidity was lower after LLR than OLR (12.0% vs. 22.4%, p = 0.043). LLR was associated with reduced 30-day overall morbidity in multivariable analysis (aOR:0.46, CI:0.22-0.95, p = 0.043). Both 30-day major morbidity and 30-day mortality were not different. CONCLUSIONS: LLR for BLT is associated with shorter hospital stay and reduced overall morbidity and is preferred if technically feasible.

Are all voices heard in the COVID-19 debate?

The COVID-19 pandemic has vast global consequences. Yet, effective mitigation strategies and economic and medical outfall differ extensively across the globe. It is currently unclear how well researchers from all continents are represented in the unsolicited and solicited publications. A literature review was performed in SCOPUS on COVID-19 oriented publications in the four most impactful medical journals. These included the British Medical Journal, Journal of the American Medical Association, the New England Journal of Medicine and The Lancet. We identified 809 eligible publications out of identified 924 records. The vast majority of publications on COVID-19, in the four can be considered European (47.7%) or North-American (37.3%) research. Chinese reports were relatively common (8.8%); however, reports from other Asian countries (3.2%) were minimal. Research from the African (1.0%) and South-American continents (0.6%) was rarely published in these journals. These observations are not surprising, as they reflect global academic publishing. However, involving all continents into COVID-19 research is important as COVID-19 management strategies and societal and economic consequences differ extensively across the globe. We see an important role for medical journals in encouraging global voices through solicited articles, to ensure a weighted research and humanitarian response.

Systematic review on percutaneous aspiration and sclerotherapy versus surgery in symptomatic simple hepatic cysts.

BACKGROUND: Simple hepatic cysts (SHC) may cause pain and bloating and thus impair quality of life. Whereas current guidelines recommend laparoscopic cyst deroofing, percutaneous aspiration and sclerotherapy (PAS) may be used as a less invasive alternative. This review aimed to assess the efficacy of PAS and surgical management in patients with symptomatic SHC. METHODS: A systematic search in PubMed and Embase was performed according to PRISMA-guidelines. Studies reporting symptoms were included. Methodological quality was assessed by the MINORS-tool. Primary outcomes were symptom relief, symptomatic recurrence and quality of life, for which a meta-analysis of proportions was performed. RESULTS: In total, 736 patients from 34 studies were included of whom 265 (36%) underwent PAS, 348 (47%) laparoscopic cyst deroofing, and 123 (17%) open surgical management. During weighted mean follow-up of 26.1, 38.2 and 21.3 months, symptoms persisted in 3.5%, 2.1%, 4.2%, for PAS, laparoscopic and open surgical management, respectively. Major complication rates were 0.8%, 1.7%, and 2.4% and cyst recurrence rates were 0.0%, 5.6%, and 7.7%, respectively. CONCLUSION: Outcomes of PAS for symptomatic SHC appear to be excellent. Studies including a step-up approach which reserves laparoscopic cyst deroofing for symptomatic recurrence after one or two PAS procedures are needed.

A multicentre retrospective analysis on growth of residual hepatocellular adenoma after resection.

BACKGROUND & AIMS: Hepatocellular adenoma (HCA) is a benign liver tumour that may require resection in select cases. The aim of this study was to the assess growth of residual HCA in the remnant liver and to advise on an evidence-based management strategy. METHOD: This multicentre retrospective cohort study included all patients with HCA who underwent surgery of HCA and had residual HCA in the remnant liver. Growth was defined as an increase of >20% in transverse diameter (RECIST criteria). Data on patient and HCA characteristics, diagnostic work-up, treatment and follow-up were documented and analysed. RESULTS: A total of 134 patients were included, one male. At diagnosis, median age was 38yrs (IQR 30.0-44.0) and median BMI was 29.9 kg/m2 (IQR 24.6-33.3). After resection, median number of residual sites of HCA was 3 (IQR 2-6). Follow-up of residual HCA showed regression in 24.6%, stable HCA in 61.9% and growth of at least one lesion in 11.2%. Three patients (2.2%) developed new HCA that were not visible on imaging prior to surgery. Four patients (3%, one male) underwent an intervention as growth was progressive. No statistically significant differences in clinical characteristics were found between patients with growing residual or new HCA versus those with stable or regressing residual HCA. CONCLUSION: In patients with multiple HCA who undergo resection, growth of residual HCA is not uncommon but interventions are rarely needed as most lesions stabilize and do not show progressive growth. Surveillance is indicated when residual HCA show growth after resection, enabling intervention in case of progressive growth.

Surgical treatment for non-parasitic liver cysts improves quality of life.

BACKGROUND&PURPOSE: Liver cysts occur frequently. Most are harmless, however some carry a significant patient burden. Optimizing treatment strategy is complicated as needs differ between patients. The current study assesses the effect of surgery on quality of life (QoL) of patients with non-parasitic liver cysts. METHODS: A retrospective cohort study of all patients who underwent surgery for non-parasitic liver cysts in three major Dutch medical centers from 1993 to 2017. Patient characteristics and surgery related variables were collected from the electronic patient file. QoL was measured before and after surgery using the EORTC QLQ-C30. Summary scores (SumSc) were calculated and compared to reference values of the general population. Multivariate analysis using logistic regression was performed for identifying outcome related factors. Increase of ≥ 10% in SumSc was defined as clinically relevant. MAIN FINDINGS: Eighty-eight of 132 eligible patients (67%) completed two QoL assessments. Respondents demonstrated significant improvement in the global health status, on all 5 functional scales (all p ≤ 0.005), on all 9 symptom scales after surgery (all p < 0.05), and on SumSc (p < 0.001) to levels similar or better than the general population. Patients with complications demonstrated a significant QoL gain (p < 0.05), and reported a similar postoperative status compared to patients without complications (p = 0.74). QoL gain for patients who underwent open and laparoscopic cyst fenestration were similar (p = 0.08). Multivariate analysis of SumSc found mechanical complaints as significant factor for ≥ 10% SumSc increase (OR 0.11, 95% CI (0.02-0.55). CONCLUSIONS: Surgery is a safe and effective strategy to significantly improve QoL in patients with symptomatic liver cysts.

Diagnosis of hepatocellular adenoma in men before onset of diabetes in HNF1A-MODY: Watch out for winkers.

Hepatocyte nuclear factor 1A (HNF1A) maturity-onset diabetes of the young (MODY) is a monogenetic, autosomal dominantly inherited form of diabetes. HNF1A-MODY is associated with HNF1A-inactivated hepatocellular adenoma (H-HCA) formation. Hepatocellular adenoma (HCA) are benign liver tumours and related complications are rare but serious: hepatic haemorrhage and malignant transformation. Guidelines recommend resection of all HCA in men and do not take any co-occurring metabolic disorders into account. We report a family with HCA preceding diabetes mellitus. Male index patient presented with numerous, irresectable HCA. After initial diagnostic and aetiologic uncertainty HNF1A germline mutation c.815G>A (p.Arg272His) was confirmed 8 years later. No HCA-related complications occurred. His diabetic mother was diagnosed with HCA after severe hepatic haemorrhage years before. HNF1A-MODY should be considered in (non-)diabetic (male) patients with H-HCA. We advocate liver biopsy and, if necessary, genetic analysis to precede any intervention for HCA in males and screening for HCA in HNF1A-MODY patients.