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

A female patient with liver failure and pseudocirrhosis

AchtergrondAcuut-op-chronisch leverfalen wordt gekenmerkt door acute, ernstige verslechtering van de leverfunctie bij patiënten met pre-existente cirrose, gerelateerd aan een uitlokkende factor. Dat klinische beeld kan soms het gevolg zijn van een andere aandoening die niet primair de lever treft.CasusEen 65-jarige vrouw, bekend met cirrose, werd overgeplaatst naar ons transplantatiecentrum vanwege het beeld van acuut-op-chronisch leverfalen. Vanwege haar voorgeschiedenis van mammacarcinoom, onverwacht afwijkende laboratoriumuitslagen en een fenotype dat niet geheel bij de diagnose paste, verrichtten we een leverbiopsie. Het biopt toonde diffuse metastasering van mammacarcinoom. Eerder beeldvormend onderzoek had kenmerken van cirrose laten zien, zonder aanwijzingen voor maligniteit; dit misleidende beeld wordt pseudocirrose genoemd.ConclusieEen diffuus hepatogeen gemetastaseerde maligniteit kan lijken op gedecompenseerde cirrose en acuut-op-chronisch leverfalen, zowel in presentatie als bij beeldvormend onderzoek. Levertransplantatie is bij acuut-op-chronisch leverfalen soms de enige levensreddende behandeling, maar is gecontra-indiceerd bij maligniteit. Om een gegronde indicatie voor levertransplantatie te verkrijgen moet een leverbiopsie worden overwogen, ook in spoedsituaties.BACKGROUND: Acute-on-chronic liver failure encompasses an acute deterioration of liver function in patients with pre-existent cirrhosis. Sometimes the clinical picture of acute-on-chronic liver failure is misleading and may not be secondary to primary liver disease, as described in our case.CASE DESCRIPTION: A 65-year-old woman with cirrhosis was transferred to our transplantation centre because of suspected acute-on-chronic liver failure. Given her medical history of breastcancer and suspicious laboratory results, we performed a liver biopsy. This showed diffuse metastases of mammary carcinoma. Earlier CT-scans showed features of cirrhosis without signs of malignancy: a misleading phenomenon called pseudocirrhosis.CONCLUSION: Diffuse malignant hepatic infiltration can resemble cirrhosis and acute-on-chronic liver failure, both in clinical presentation as in imaging. Liver transplantation is contraindicated in malignant liver failure. To assure a solid indication for transplantation, a liver biopsy has to be considered, even in emergency situations.</p

Malignant Transformation of an HNF1a-Inactivated Hepatocellular Adenoma to Hepatocellular Carcinoma

Hepatocellular adenomas (HCA) are rare benign tumors of the liver, occurring predominantly in females using oral contraceptives. Our case describes a 66-year-old woman presenting with a palpable mass in her upper abdomen. Contrast-enhanced computed tomography and magnetic resonance imaging showed a large exophytic mass protruding from the caudal border of liver segments IV and V, without visible metastases. Laparoscopic resection of the tumor and gallbladder was performed. Histopathological examination showed a hepatocellular carcinoma with areas of HNF1a-HCA (H-HCA). This case shows that malignant transformation is possible in H-HCA. We present our preoperative decision-making process, as well as the role of imaging techniques in this rare case

Surgery for Ampullary Cancer in a Patient with Pancreatic Lipomatosis Caused by Cystic Fibrosis

A patient with cystic fibrosis (CF) with pancreatic insufficiency presented with jaundice due to an ampullary tumour. CF is known for a higher incidence of gastrointestinal malignancies. The patient suffered from pancreatic insufficiency. At computed tomography (CT), pancreatic lipomatosis with absence of the pancreatic duct was seen. This is uncommon, also in patients with CF. During surgery, a total pancreatectomy was performed, because there was no possibility to construct a duct to mucosa anastomosis due to the absence of the pancreatic duct and more importantly the pancreas was already afunctional. The presence of lipomatosis increases the risk of leakage at the pancreaticojejunal anastomosis. Therefore, it is important to take this phenomenon, in this case already visible on the preoperative CT scan, into account during the workup for surgery

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

Biobanking of patient and patient-derived xenograft ovarian tumour tissue:efficient preservation with low and high fetal calf serum based methods

Using patient-derived xenografts (PDXs) for preclinical cancer research demands proper storage of tumour material to facilitate logistics and to reduce the number of animals needed. We successfully established 45 subcutaneous ovarian cancer PDXs, reflecting all histological subtypes, with an overall take rate of 68%. Corresponding cells from mouse replaced human tumour stromal and endothelial cells in second generation PDXs as demonstrated with mouse-specific vimentin and CD31 immunohistochemical staining. For biobanking purposes two cryopreservation methods, a fetal calf serum (FCS)-based (95% v/v) "FCS/DMSO" protocol and a low serum-based (10% v/v) "vitrification" protocol were tested. After primary cryopreservation, tumour take rates were 38% and 67% using either the vitrification or FCS/DMSO-based cryopreservation protocol, respectively. Cryopreserved tumour tissue of established PDXs achieved take rates of 67% and 94%, respectively compared to 91% using fresh PDX tumour tissue. Genotyping analysis showed that no changes in copy number alterations were introduced by any of the biobanking methods. Our results indicate that both protocols can be used for biobanking of ovarian tumour and PDX tissues. However, FCS/DMSO-based cryopreservation is more successful. Moreover, primary engraftment of fresh patient-derived tumours in mice followed by freezing tissue of successfully established PDXs is the preferred way of efficient ovarian cancer PDX biobanking

Indeterminate pediatric acute liver failure:Clinical characteristics of a temporal cluster of five children in the Netherlands in the spring of 2022

There is increasing global concern of severe acute hepatitis of unknown etiology in young children. In early 2022, our center for liver transplantation in the Netherlands treated five children who presented in short succession with indeterminate acute liver failure. Four children underwent liver transplantation, one spontaneously recovered. Here we delineate the clinical course and comprehensive diagnostic workup of these patients. Three of five patients showed a gradual decline of liver synthetic function and had mild neurological symptoms. Their clinical and histological findings were consistent with hepatitis. These three patients all had a past SARS-CoV-2 infection and two of them were positive for adenovirus DNA. The other two patients presented with advanced liver failure and encephalopathy and underwent dialysis as a bridge to transplantation. One of these children spontaneously recovered. We discuss this cluster of patients in the context of the currently elevated incidence of severe acute hepatitis in children

Een patiënte met leverfalen en pseudocirrose

Achtergrond Acuut-op-chronisch leverfalen wordt gekenmerkt door acute, ernstige verslechtering van de leverfunctie bij patiënten met pre-existente cirrose, gerelateerd aan een uitlokkende factor. Dat klinische beeld kan soms het gevolg zijn van een andere aandoening die niet primair de lever treft. Casus Een 65-jarige vrouw, bekend met cirrose, werd overgeplaatst naar ons transplantatiecentrum vanwege het beeld van acuut-op-chronisch leverfalen. Vanwege haar voorgeschiedenis van mammacarcinoom, onverwacht afwijkende laboratoriumuitslagen en een fenotype dat niet geheel bij de diagnose paste, verrichtten we een leverbiopsie. Het biopt toonde diffuse metastasering van mammacarcinoom. Eerder beeldvormend onderzoek had kenmerken van cirrose laten zien, zonder aanwijzingen voor maligniteit; dit misleidende beeld wordt pseudocirrose genoemd. Conclusie Een diffuus hepatogeen gemetastaseerde maligniteit kan lijken op gedecompenseerde cirrose en acuut-op-chronisch leverfalen, zowel in presentatie als bij beeldvormend onderzoek. Levertransplantatie is bij acuut-op-chronisch leverfalen soms de enige levensreddende behandeling, maar is gecontra-indiceerd bij maligniteit. Om een gegronde indicatie voor levertransplantatie te verkrijgen moet een leverbiopsie worden overwogen, ook in spoedsituaties