Large Hepatic Adenomas and Hepatic Adenomatosis: A Multicenter Study of Risk Factors, Interventions, and Complications.

INTRODUCTION: Beyond oral contraceptives (OCs), metabolic factors have been suggested to increase the risk of hepatocellular adenoma (HCA). The impact of risks remains poorly defined, particularly among men and those with adenomatosis. Thus, we aimed to examine HCA clinical and outcome characteristics through a large multicenter cohort. METHODS: HCA diagnosis was made based on a combination of clinical, radiologic, and histologic criteria. Patient and clinical data including follow-up imaging, complications, and interventions were collected between 2004 and 2018 from 3 large academic centers. RESULTS: Among 187 patients (163 female and 24 male) with HCA, 75 had solitary HCA, 58 had multiple HCAs, and 54 had adenomatosis. Over a median follow-up of 3.3 years (quartile 1: 1.2, quartile 3: 8.8), 34 patients (18%) had radiologic interventions, 41 (21%) had surgical resections, 10 (5%) developed tumoral hemorrhage, and 1 had malignant transformation. OC and corticosteroid use were present in 70% and 16%, respectively. Obesity (51%), type 2 diabetes (24%), hypertension (42%), and hypertriglyceridemia (21%) were also common. Metabolic comorbidities were more common in patients with large HCAs and adenomatosis. Compared with women, men had less hepatic steatosis (4% vs 27%), smaller HCAs (2.3 cm vs 4.4 cm), and more corticosteroid use (38% vs 11%) ( P < 0.05 for all). With OC cessation, 69% had a decrease in size of HCA, but 25% eventually required advanced interventions. DISCUSSION: In this large HCA cohort, obesity and metabolic comorbidities were important risk factors associated with large HCAs and adenomatosis. Long-term adverse outcomes were infrequent, 5% had tumor hemorrhage, and 1 patient exhibited malignant transformation.

Risk factors for bleeding hepatocellular adenoma in a United States cohort.

BACKGROUND & AIMS: Known risk factors for hepatocellular adenoma (HCA) bleeding are size >5 cm, growth rate, visible vascularity, exophytic lesions, ß-catenin and Sonic Hedgehog activated HCAs. Most studies are based on European cohorts. The objective of this study is to identify additional risk factors for HCA bleeding in a US cohort. METHODS: Retrospective chart review was performed on patients diagnosed with HCA on magnetic resonance imaging (n = 184) at an academic tertiary institution. Clinical, pathological, and imaging data were collected. Primary outcomes measured were HCA bleeding and malignancy. Statistical analysis was performed with SAS 9.4 using Chi-Square, Fisher's exact test, sample t test, non-parametric Wilcoxon test, and logistic regression. RESULTS: After excluding patients whose pathology showed focal nodular hyperplasia and non-adenoma lesions, follow-up data were available for 167 patients. 16% experienced microscopic or macroscopic bleeding and 1.2% had malignancy. HCA size predicted bleeding (P < .0001) and no patients with lesion size <1.8 cm bled. In unadjusted analysis, hepatic adenomatosis (≥10 lesions) trended towards 2.8-fold increased risk of bleeding. Of patients with a single lesion that bled, 77% bled from a lesion >5 cm. In patients with multiple HCAs that bled, 50% bled from lesions <5 cm. In patients with multiple adenomas, size (P = .001) independently predicted bleeding and hepatic steatosis trended towards increased risk of bleeding (P = .05). CONCLUSIONS: In a large US cohort, size predicted increased risk of HCA bleeding while hepatic adenomatosis trended towards increased risk of bleeding. In patients with multiple HCAs, size predicted bleeding and hepatic steatosis trended toward increased risk of bleeding.

A Multicenter, 10-Year Experience With Hepatocellular Adenoma: Risk Factors and Disease Course.

BACKGROUND: Management of hepatocellular adenoma (HA) is marked by a paucity of recent studies. Long-term follow-up data from an equal access health care system may facilitate our understanding of the natural disease course of HA and identify modifiable risk factors. METHODS: A multi-institutional, retrospective review of patients with HA from 2008-2017 was performed. Patient demographics, disease characteristics, and clinical outcomes were analyzed. RESULTS: Of 124 patients identified, 94% were women with a mean age at diagnosis of 39.5 years (range 20-82). Median follow-up was 22.5 months (range 0-114) with thirty-four (27.4%) patients eventually undergoing hepatectomy. Mean BMI of the study population was 30.5 kg/m2 (range 16-72). Stratified by size, average BMI for adenomas ≥5 cm was 34 kg/m2 compared to 28 kg/m2 for those <5 cm (P < .05). The predominant symptom at presentation was abdominal pain (41.1%), while just 4% presented with acute rupture. Overall incidence of the malignancy was 2.5%. Among all patients, oral contraceptive use was documented in 74 (59.7%) patients, of whom 36 (29.0%) discontinued OC for at least six months. Regression after OC cessation occurred in seven patients (19.4%) while the majority (77.8%) remained stable. DISCUSSION: This decade-long review analyzing the impact of modifiable risk factors identifies a direct correlation between BMI and hepatocellular adenoma size. Rupture and malignant transformation are rare entities. Cessation of OC appears to be an effective strategy in the management of hepatic adenoma. Further investigations are warranted to determine if addressing modifiable risk factors such as BMI might induce further HA regression.

Perfil dos pacientes operados por adenoma hepático em serviço de cirurgia hepatobiliar do Rio Grande do Sul / Profile of patients who underwent operation for liver adenoma in an hepatobiliary surgery service in Rio Grande do Sul

Introdução: O trabalho objetiva avaliar o perfil epidemiológico dos pacientes operados por adenoma hepático e os fatores de influência nas diferentes apresentações clínicas. Métodos: Estudo transversal descritivo com 21 pacientes operados por adenoma hepático. Dados de prontuário e laudos anatomopatológicos foram revisados a fim de estudar a relação entre perfil dos pacientes, apresentação clínica e características do tumor. Resultados: Sexo feminino foi predominante na amostra. A idade média dos pacientes foi de 32 anos e o IMC médio 25,9. Uso de anticoncepcional oral foi relatado em 93% dos casos, sendo 13 anos o tempo médio de uso. A presença de comorbidades teve associação com adenomas de maior tamanho, e diabetes mellitus foi doença mais frequente associada a este tumor. Houve associação clínica entre tamanho do adenoma e sintomatologia: pacientes com sinais e sintomas mais pronunciados apresentaram lesões de tamanho médio superior em comparação aos pacientes com sintomas inespecíficos ou ausentes. Conclusão: Os fatores já conhecidos associados ao Adenoma Hepático envolvem o sexo feminino, uso de contraceptivo oral de longa data, doenças do armazenamento do glicogênio, uso de anabolizantes e, menos comumente, gestação e diabetes mellitus. Neste trabalho evidenciamos o diabetes mellitus como a comorbidade mais frequente entre os pacientes com diagnóstico de Adenoma Hepático, relacionando-se a adenomas de maior tamanho na amostra deste estudo, o que sugere possível associação do diabetes mellitus na gênese dos adenomas hepáticos e também no prognóstico, visto que lesões maiores representam risco aumentado de complicações.

Introduction: This work aims to evaluate the epidemiological profile of patients who underwent surgery for liver adenoma and the factors that could influence different clinical presentations. Methods: Descriptive cross-sectional study with 21 patients with liver adenoma who underwent surgery. Medical records and pathological reports were reviewed to study the connection between patients' profile, clinical presentation, and features of the tumor. Results: Female sex predominated in the sample. The mean age of patients was 32 years and the mean BMI was 25.9. The use of oral contraceptives was reported in 93% of the cases, with an average usage time of 13 years. The presence of comorbidities was associated with larger adenomas, and diabetes mellitus was the most frequent comorbidity co-existing with this tumor. Clinical association between the size of adenomas and symptoms was identified: patients with more pronounced signs and symptoms had larger lesions compared with patients with nonspecific or absent symptoms. Conclusion: The known factors associated with Hepatic Adenoma involve female sex, long-term use of oral contraceptives, glycogen storage diseases, use of anabolic steroids, and, less commonly, pregnancy and diabetes mellitus. In this study, we highlight diabetes mellitus as the most frequent comorbidity among patients diagnosed with Hepatic Adenoma, relating to larger adenomas in this study sample, which suggests a possible association of diabetes mellitus in the genesis of liver adenomas and in the prognosis, since larger lesions represent an increased risk of complications.

Hepatocellular adenoma in the paediatric population: Molecular classification and clinical associations.

Hepatocellular adenomas (HCAs) represent rare, benign liver tumours occurring predominantly in females taking oral contraceptives. In children, HCAs comprise less than 5% of hepatic tumours and demonstrate association with various conditions. The contemporary classification of HCAs, based on their distinctive genotypes and clinical phenotypes, includes hepatocyte nuclear factor 1 homeobox alpha-inactivated HCAs, beta-catenin-mutated HCAs, inflammatory HCAs, combined beta-catenin-mutated and inflammatory HCAs, sonic hedgehog-activated HCAs, and unclassified HCAs. In children, there is a lack of literature on the characteristics and distribution of HCA subtypes. In this review, we summarized different HCA subtypes and the clinicopathologic spectrum of HCAs in the paediatric population.

A systematic review on the complications and management of hepatic adenomas: a call for a new approach.

Hepatic adenomas are benign hepatic lesions with heterogeneous characteristics. Awareness of complications, including haemorrhage and malignant transformation, has improved alongside a concurrent rise in their detection. Monitoring and management guidelines, however, remain inconsistent. This systematic review analyses the natural history of hepatic adenomas, and existing and novel risk factors associated with haemorrhage and malignant transformation. Results of this systematic review commonly identified male sex, and the beta-catenin histopathological hepatic adenoma subtype, as risk factors for malignant transformation, whilst those associated with haemorrhage included lesion size and number, exophytic nature, and recent hormone use. Overall, females demonstrated higher rates of haemorrhage, whilst males exhibited a higher risk of hepatocellular carcinoma development. This systematic review highlights that tumour size and subtype may not be as characteristically linked with complications as previously thought. We have additionally reported novel risk factors contributing to development of hepatic adenoma-related complications. We conclude by highlighting the risk of taking a conservative approach to seemingly low-risk lesions and suggest revised practice guidelines.

New insights in the management of Hepatocellular Adenoma.

Hepatocellular adenoma (HCA) are benign liver tumours that may be complicated by haemorrhage or malignant transformation to hepatocellular carcinoma. Epidemiological data are fairly outdated, but it is likely to assume that the incidence has increased over the past decades as HCA are more often incidentally found due to the more widespread use of imaging techniques and the increased incidence of obesity. Various molecular subgroups have been described. Each of these molecular subgroups are defined by specific gene mutations and pathway activations. Additionally, they are all related to specific risk factors and show a various biological behaviour. These molecular subgroups may be identified using immunohistochemistry and molecular characterization. Contrast-enhanced MRI is the recommended imaging modality to analyse patients with suspected hepatocellular adenoma allowing to determine the subtype in up to 80%. Surgical resection remains to be the golden standard in treating HCA, although resection is deemed unnecessary in a large number of cases, as studies have shown that the majority of HCA will regress over time without complications such as haemorrhage or malignant transformation occurring. It is preferable to treat patients with suspected HCA in high volume centres with combined expertise of liver surgeons, hepatologists, radiologists and (molecular) pathologists.

Growth of hepatocellular adenoma during pregnancy: A prospective study.

BACKGROUND & AIMS: The presence of hepatocellular adenoma (HCA) in pregnant women requires special consideration, as it has been reported to carry the risk of growth and clinically significant haemorrhage. In this prospective study we assessed aspects of growth of HCA <5 cm during pregnancy. METHODS: This was a multicentre prospective cohort study in pregnant women with suspected HCA <5 cm on imaging. Definitive HCA diagnosis was established by MRI with hepatobiliary contrast agents (LCE-MRI), preferably before pregnancy. If at study inclusion a definitive diagnosis was lacking, LCE-MRI was performed after giving birth. Growth of the adenoma (defined as an increase of >20%) was closely monitored with ultrasound examinations throughout pregnancy. RESULTS: Of the 66 women included, 18 were excluded from analysis because postpartum LCE-MRI did not confirm the diagnosis of HCA and showed the lesion to be focal nodular hyperplasia. The remaining 48 women, with an HCA confirmed by LCE-MRI, were followed during 51 pregnancies. Median age was 30 years (IQR 27-33) and median body mass index 31.9 kg/m2 (IQR 26.3-36.6). Growth of HCA was seen in 13 of the pregnancies (25.5%); the median increase was 14 mm (IQR 8-19). One woman whose HCA grew to >70 mm successfully underwent transarterial embolization at week 26 of pregnancy to prevent further growth. The other 50 pregnancies proceeded without complications. CONCLUSION: This study suggests that an HCA <5 cm confers minimal risk to a pregnant woman and none to her child. HCA increased in size during a quarter of pregnancies, so we recommend close monitoring with ultrasound examinations, enabling intervention if needed. In light of the large proportion of misdiagnosed HCA, LCE-MRI should be performed to prevent unnecessary anxiety in women with a benign liver lesion. LAY SUMMARY: The presence of hepatocellular adenoma in pregnant women requires special consideration, as it carries the risk of growth and haemorrhage. In this study we followed 48 patients with hepatocellular adenoma <5 cm during 51 pregnancies and found that a hepatocellular adenoma during pregnancy confers minimal risk to the pregnant woman and none to her child.

Hepatocellular adenoma in Taiwan: Distinct ensemble of male predominance, overweight/obesity, and inflammatory subtype.

BACKGROUND AND AIM: The clinicopathologic features of hepatocellular adenoma in Asian populations have been poorly defined. The study aimed to characterize this rare entity in a single institution in Taiwan. METHODS: In total, 45 hepatocellular adenomas from 1995 to 2018 were included and sent for pathologic review and molecular subtyping. RESULTS: The numbers of patients with hepatocellular adenoma has doubled in the recent decade. Surprisingly, men outnumbered women in our cohort (n = 26, 58% vs N = 19, 42%). A collection of clinical information revealed that overweight/obesity accounts for most of the associated conditions of hepatocellular adenoma. Only three women took oral contraceptives. There were 34 inflammatory (75%), three LFABP-negative (7%), four ß-catenin activated (9%), and four unclassified (9%) hepatocellular adenomas. Ten inflammatory hepatocellular adenomas demonstrated strong and homogeneous glutamine synthetase staining and were thus also ß-catenin activated. Notably, overweight and obesity were significantly associated with inflammatory hepatocellular adenoma than other subtypes (P = .029 and .056, respectively) and were strongly correlated with steatosis in background liver (P = .028 and.007, respectively). Malignant transformation (four borderline tumors and two hepatocellular carcinomas) was identified in six adenomas (two women and four men). All six hepatocellular adenomas with malignancy were ß-catenin activated; ß-catenin activation could serve as a biomarker for malignant progression. CONCLUSIONS: The clinicopathologic features of hepatocellular adenoma in Taiwan are distinct from those reported in Western countries. Rare oral contraceptive usage and an emerging epidemic of overweight/obesity in Taiwan provides new insights into the pathogenesis of hepatocellular adenoma.

Natural history of liver adenomatosis: A long-term observational study.

BACKGROUND & AIMS: Liver adenomatosis (LA) is characterized by the presence of at least 10 hepatocellular adenomas (HCAs), but the natural history of this rare liver disorder remains unclear. Thus, we aimed to reappraise the natural history and the risk of complications in a cohort of patients with at least 10 HCAs. METHODS: We analyzed the natural history of 40 patients with LA, excluding glycogen storage disorders, in a monocentric cohort. Pathological examination was performed, with immunostaining and molecular biology carried out on surgical specimens or liver biopsies. RESULTS: Forty patients (36 female) were included with a median follow-up of 10.6 (1.9-26.1) years. Six (15%) patients had familial LA, all with germline HNF1A mutations. Median age at diagnosis was 39 (9-55) years. Thirty-three (94%) women had a history of oral contraception, and 29 (81%) women had a pregnancy before LA diagnosis. Overall, thirty-seven (93%) patients underwent surgery at diagnosis. Classification of HCAs showed 46% of patients with HNF1A-mutated HCA, 31% with inflammatory HCA, 3% with sonic hedgehog HCA, 8% with unclassified HCA. Only 15% of the patients demonstrated a "mixed LA" with different HCA subtypes. Hepatic complications were identified in 7 patients: 1 patient (3%) died from recurrent hepatocellular carcinoma after liver transplantation; 6 (15%) had hemorrhages, of which 5 occurred at diagnosis, with 1 fatal case during pregnancy, and 2 occurred in male patients with familial LA. Four patients (10%) had repeated liver resections. Finally, 4 (10%) patients developed extrahepatic malignancies during follow-up. CONCLUSIONS: The diversity in HCA subtypes, as well as the occurrence of bleeding and malignant transformation during long-term follow-up, underline the heterogeneous nature of LA, justifying close and specific management. In patients with germline HNF1A mutation, familial LA occurred equally frequently in males and females, with a higher rate of bleeding in male patients. LAY SUMMARY: Liver adenomatosis is a rare disease characterized by the presence of 10 or more hepatocellular adenomas that may rarely be of genetic origin. Patients with liver adenomatosis have multiple adenomas of different subtypes, with a risk of bleeding and malignant transformation that justify a specific management and follow-up.

Contrast-enhanced ultrasound patterns of hepatocellular adenoma: an Italian multicenter experience.

PURPOSE: Hepatocellular adenoma (HCA) is a rare benign monoclonal neoplasm, recently categorized on genetic and histopathological basis into four subtypes with different biological behaviors. Since contrast-enhanced ultrasonography (CEUS) is nowadays a well-established technique for liver nodule characterization, the aim of our study was to assess CEUS features of HCAs to identify criteria that correlate with different HCA subtypes as compared to histopathologic examination and other imaging modalities. METHODS: We retrospectively analyzed data of patients with histology-proven HCA who underwent CEUS, computed tomography or magnetic resonance imaging (MRI) in seven different Italian ultrasound units. RESULTS: The study enrolled 19 patients (16 females; 69% with concomitant/prior use of oral contraceptives): the mean size of all HCAs was 4.2 cm (range 1.6-7.1 cm); 14/19 had inflammatory HCAs (I-HCA), 1/19 ß-catenin-activated HCA, and the others unclassified HCAs. On CEUS, during the arterial phase, all but one HCA displayed a rapid enhancement, with 89% of these showing centripetal and 11% centrifugal filling pattern, whereas during the portal and late venous phase 58% of HCA showed washout and the remaining 42% displayed persistent enhancement. In particular, among I-HCAs 7/14 showed no washout, 3/14 and 4/14 showed washout in the portal or late phase, respectively. CONCLUSIONS: This dataset represents one of the few published experiences on HCAs and CEUS in Italy and shows that HCAs are hypervascularized in the arterial phase usually with a centripetal flow pattern and have a heterogeneous behavior in portal and late phase. In particular, occurrence of delayed washout on CEUS but not on MRI is frequently observed in the subtype of I-HCA.

Inflammatory and multiple hepatocellular adenoma are associated with a higher BMI.

AIM: To identify patient and lesion characteristics associated with the occurrence of single or multiple hepatocellular adenoma (HCA). PATIENTS AND METHODS: Using a tertiary centre database, we retrospectively collected information on patient and lesion characteristics, management and follow-up of all patients with HCA included between 2001 and 2016. Patients were classified into three groups; patients with a single HCA, 2-9 HCA and at least 10 HCA. RESULTS: A total of 458 patients were diagnosed with HCA, including 121 (26.4%) with single HCA, 235 (51.3%) with 2-9 HCA and 102 (22.3%) with at least 10 HCA. Significant differences in the mean BMI were found, with the highest BMI in patients with more than 10 HCA (P<0.05). The mean BMI was significantly higher in patients with inflammatory HCA compared with steatotic HCA (31 vs. 26, respectively, P<0.05). Steatotic HCA were more often single lesions (22/55, 40%), whereas patients with inflammatory HCA were often diagnosed with multiple lesions (122/166, 73%). CONCLUSION: Our series show a significantly higher BMI and frequency of inflammatory HCA in patients with multiple HCA compared with single HCA.

Men with biopsy-confirmed hepatocellular adenoma have a high risk of progression to hepatocellular carcinoma: A nationwide population-based study.

BACKGROUND & AIMS: Hepatocellular adenoma is a benign liver tumour that may transform to hepatocellular carcinoma (HCC). We used data from Danish nationwide healthcare registries to investigate the incidence and prognosis of hepatocellular adenoma. METHODS: We included all patients with a hospital discharge diagnosis for benign liver tumour (ICD-10: D13.4) in 1997-2012 and a liver biopsy confirming the hepatocellular adenoma diagnosis. Follow-up began 1 year after adenoma diagnosis, to minimise the possibility that the tumour was a misdiagnosed HCC. All patients were age- and gender-matched with 50 random controls from the Danish population. We followed patients and controls with respect to HCC development, adenoma resection, and death without HCC (ie, death without having been diagnosed with HCC) through 2013. HCC diagnoses were identified in the Danish Cancer Registry. RESULTS: We included 67 patients with hepatocellular adenoma, and 58 (87%) were women. The overall incidence rate of histologically verified hepatocellular adenoma in the Danish general population was 0.07 (95% CI: 0.06-0.09) per 100 000 population per year. Fifteen patients had their adenoma resected before follow-up began, leaving 52 patients for follow-up. Men with biopsy-confirmed hepatocellular adenoma had a 10-year cumulative HCC risk as high as 60.0% (95% CI: 15.3%-87.0%). All men who developed HCC were older than 50 years at adenoma diagnosis. By contrast, none of the 44 women in the follow-up analysis developed HCC. CONCLUSION: Histologically verified hepatocellular adenoma is rare in Denmark. It is a minor concern for women, but men have a very high risk of progression to HCC.

European experience of 573 liver resections for hepatocellular adenoma: a cross-sectional study by the AFC-HCA-2013 study group.

BACKGROUND: Hepatocellular adenoma (HCA) is a benign hepatic lesion that may be complicated by bleeding and malignant transformation. The aim of the present study is to report on large series of liver resections for HCA and assess the incidence of hemorrhage and malignant transformation. METHODS: A retrospective cross-sectional study, from 27 European high-volume HPB units. RESULTS: 573 patients were analyzed. The female: male gender ratio was 8:2, mean age: 37 ± 10 years. Of the 84 (14%) patients whose initial presentation was hemorrhagic shock (Hemorrhagic HCAs), hemostatic intervention was urgently required in 25 (30%) patients. No patients died after intervention. Tumor size was >5 cm in 74% in hemorrhagic HCAs and 64% in non-hemorrhagic HCAs (p < 0.001). In non-hemorrhagic HCAs (n = 489), 5% presented with malignant transformation. Male status and tumor size >10 cm were the two predictive factors. Liver resections included major hepatectomy in 25% and a laparoscopic approach in 37% of the patients. In non-hemorrhagic HCAs, there was no mortality and major complications occurred in 9% of patients. DISCUSSION: Liver resection for HCA is safe. Presentation with hemorrhage was associated with larger tumor size. In males with a HCA >10 cm, a HCC should be suspected. In such situation, a preoperative biopsy is preferable and an oncological liver resection should be considered.

Diffuse glutamine synthetase overexpression restricted to areas of peliosis in a ß-catenin-activated hepatocellular adenoma: a potential pitfall in glutamine synthetase interpretation.

Hepatocellular adenomas have recently been classified into four subtypes based on molecular findings: hepatocyte nuclear factor 1α (HNF1α) inactivated, inflammatory/telangiectatic, ß-catenin activated, and unclassifiable. ß-catenin-activated adenomas have the potential for malignant transformation and are thus important to recognize. Diffuse glutamine synthetase immunohistochemical positivity has been shown to be a reliable surrogate marker for ß-catenin activation, though variations in staining patterns may be difficult to interpret. We report a case of a peliotic adenoma that was morphologically consistent with a ß-catenin wild-type hepatocellular adenoma but harbored a ß-catenin mutation by molecular analysis. The tumor lacked nuclear ß-catenin positivity and demonstrated a hitherto undescribed pattern of glutamine synthetase overexpression restricted to areas of peliosis with mostly negative staining in non-peliotic areas. This pattern was initially interpreted as physiologic and may represent a potential pitfall in glutamine synthetase interpretation.

Estudio multicéntrico sobre adenomas hepáticos / Multicentre study on hepatic adenomas

INTRODUCCIÓN: El adenoma hepático (AH) es un tumor benigno que puede presentar graves complicaciones por lo que, clásicamente, todos eran resecados. Actualmente se ha demostrado que los menores de 3 cm, y si no expresan Beta -catenina, solo se complican excepcionalmente, lo que ha cambiado la estrategia terapéutica. MATERIAL Y MÉTODOS: Estudio retrospectivo en 14 unidades HPB. Criterio de inclusión: pacientes con AH resecado y confirmado histológicamente. Periodo de estudio: 1995-2011. RESULTADOS: Fueron intervenidos 81 pacientes. Edad: 39,5 años (rango: 14-75). Sexo: mujeres (75%). Consumo de estrógenos en mujeres: 33%. Tamaño: 8,8 cm (rango: 1-20 cm). Solo 6 AH (7,4%) eran menores de 3 cm. La mediana de AH fue 1 (rango: 1-12). Nueve pacientes presentaban adenomatosis (> 10 AH). El 51% de los pacientes presentaban síntomas; el más frecuente (77%) era dolor abdominal. Ocho pacientes (10%) comenzaron con abdomen agudo por rotura o hemorragia. El 67% de los diagnósticos preoperatorios fueron correctos. La cirugía fue programada en el 90% de los pacientes. Las técnicas fueron: hepatectomías mayores (22%), menores (77%) y un trasplante hepático. Un 20% fueron realizadas por laparoscopia. La morbilidad fue 28%. No hubo mortalidad. Tres pacientes presentaron malignización (3,7%). El seguimiento fue 43 meses (rango: 1-192). Se detectaron 2 recidivas que fueron resecadas. DISCUSIÓN: Los pacientes con AH resecados son habitualmente mujeres con lesiones grandes, con un consumo de estrógenos inferior al esperado. Su diagnóstico preoperatorio correcto es aceptable (70%). La tasa de hepatectomías mayores es 25% y la de laparoscopia, 20%. Hemos obtenido una baja morbilidad y nula mortalidad

INTRODUCTION: Hepatic adenomas (HA) are benign tumours which can present serious complications, and as such, in the past all were resected. It has now been shown that those smaller than 3 cm not expressing Beta-catenin only result in complications in exceptional cases and therefore the therapeutic strategy has been changed. MATERIAL AND METHOD: Retrospective study in 14 HPB units. Inclusion criteria: patients with resected and histologically confirmed HA. Study period: 1995-2011. RESULTS: 81 patients underwent surgery. Age: 39.5 years (range: 14-75). Sex: female (75%). Consumption of oestrogen in women: 33%. Size: 8.8 cm (range, 1-20 cm). Only 6 HA (7.4%) were smaller than 3 cm. The HA median was 1 (range: 1-12). Nine patients had adenomatosis (> 10HA). A total of 51% of patients displayed symptoms, the most frequent (77%) being abdominal pain. Eight patients (10%) began with acute abdomen due to rupture and/or haemorrhage. A total of 67% of the preoperative diagnoses were correct. Surgery was scheduled for 90% of patients. The techniques employed were: major hepatectomy (22%), minor hepatectomy (77%) and one liver transplantation. A total of 20% were performed laparoscopically. The morbidity rate was 28%. There were no cases of mortality. Three patients had malignisation (3.7%). The follow-up period was 43 months (range 1-192). Two recurrences were detected and resected. DISCUSSION: Patients with resected HA are normally women with large lesions and oestrogen consumption was lower than expected. Its correct preoperative diagnosis is acceptable (70%). The major hepatectomy rate is 25% and the laparoscopy rate is 20%. There was a low morbidity rate and no mortality

Molecular characterization of hepatocellular adenomas developed in patients with glycogen storage disease type I.

BACKGROUND & AIMS: Hepatocellular adenomas (HCA) are benign liver tumors mainly related to oral contraception and classified into 4 molecular subgroups: inflammatory (IHCA), HNF1A-inactivated (H-HCA), ß-catenin-activated (bHCA) or unclassified (UHCA). Glycogen storage disease type I (GSD) is a rare hereditary metabolic disease that predisposes to HCA development. The aim of our study was to characterize the molecular profile of GSD-associated HCA. METHODS: We characterized a series of 25 HCAs developed in 15 patients with GSD by gene expression and DNA sequence of HNF1A, CTNNB1, IL6ST, GNAS, and STAT3 genes. Moreover, we searched for glycolysis, gluconeogenesis, and fatty acid synthesis alterations in GSD non-tumor livers and compared our results to those observed in a series of sporadic H-HCA and various non-GSD liver samples. RESULTS: GSD adenomas were classified as IHCA (52%) mutated for IL6ST or GNAS, bHCA (28%) or UHCA (20%). In contrast, no HNF1A inactivation was observed, showing a different molecular subtype distribution in GSD-associated HCA from that observed in sporadic HCA (p = 0.0008). In non-tumor GSD liver samples, we identified glycolysis and fatty acid synthesis activation with gluconeogenesis repression. Interestingly, this gene expression profile was similar to that observed in sporadic H-HCA. CONCLUSIONS: Our study showed a particular molecular profile in GSD-related HCA characterized by a lack of HNF1A inactivation. This exclusion could be explained by similar metabolic defects observed with HNF1A inactivation and glucose-6-phosphatase deficiency. Inversely, the high frequency of ß-catenin mutations could be related to the increased frequency of malignant transformation in hepatocellular carcinoma.