Bleeding hepatocellular adenoma: historical series and outcomes.

INTRODUCTION: hepatocellular adenoma - AHC - is a rare benign neoplasm of the liver more prevalent in women at reproductive age and its main complication is hemorrhage. In the literature, case series addressing this complication are limited. METHODS: between 2010 and 2022, 12 cases of bleeding AHC were attended in a high-complexity university hospital in southern Brazil, whose medical records were retrospectively evaluated. RESULTS: all patients were female, with a mean age of 32 years and a BMI of 33kg/m2. The use of oral contraceptives was identified in half of the sample and also half of the patients had a single lesion. The mean diameter of the largest lesion was 9.60cm and the largest lesion was responsible for bleeding in all cases. The presence of hemoperitoneum was documented in 33% of the patients and their age was significantly higher than the patients who did not have hemoperitoneum - 38 vs 30 years, respectively. Surgical resection of the bleeding lesion was performed in 50% of the patients and the median number of days between bleeding and resection was 27 days. In only one case, embolization was used. The relation between ingrowth of the lesions and the time, in months, was not obtained in this study. CONCLUSION: it is concluded that the bleeding AHC of the present series shows epidemiological agreement with the literature and may suggest that older patients trend to have hemoperitoneum more frequently, a fact that should be investigated in further studies.

Vitamin D3 supplementation alleviates chemically-induced cirrhosis-associated hepatocarcinogenesis.

Vitamin D3 (VD3) deficiency has been associated with increased risk for cirrhosis and hepatocellular carcinoma, a highly incident malignant neoplasia worldwide. On the other hand, VD3 supplementation has shown some beneficial effects in clinical studies and rodent models of chronic liver disease. However, preventive effects of dietary VD3 supplementation in cirrhosis-associated hepatocarcinogenesis is still unknow. To investigate this purpose, male Wistar rats submitted to a combined diethylnitrosamine- and thioacetamide-induced model were concomitantly supplemented with VD3 (5,000 and 10,000 IU/kg diet) for 25 weeks. Liver samples were collected for histological, biochemical and molecular analysis. Serum samples were used to measure 25-hydroxyvitamin D [25(OH)D] and alanine aminotransferase levels. Both VD3 interventions decreased hepatic collagen deposition and pro-inflammatory p65 protein levels, while increased hepatic antioxidant catalase and glutathione peroxidase activities and serum 25(OH)D, without a clear dose-response effect. Nonetheless, only the highest concentration of VD3 increased hepatic protein levels of VD receptor, while decreased the number of large preneoplastic glutathione-S-transferase- (>0.5 mm²) and keratin 8/18-positive lesions, as well the multiplicity of hepatocellular adenomas. Moreover, this intervention increased hepatic antioxidant Nrf2 protein levels and glutathione-S-transferase activity. In summary, dietary VD3 supplementation - in special the highest intervention - showed antifibrotic and antineoplastic properties in chemically-induced cirrhosis-associated hepatocarcinogenesis. The positive modulation of Nrf2 antioxidant axis may be mechanistically involved with these beneficial effects, and may guide future clinical studies.

Pigmented hepatocellular adenoma with ß-catenin activation: case report and literature review.

 Hepatocellular adenomas (HCAs) are benign liver tumors recently characterized into 4 different types according to genetic, pathological and clinical features. The prognosis is not well established yet and malignant transformation has been recently associated with ß-catenin activation. We aimed to describe a case of a pigmented HCA with ß-catenin nuclear expression and inflammatory features and to review the cases of pigmented HCAs in the literature. We report a case of a young female patient without contraceptive use, with a liver tumor diagnosis. Liver biopsy revealed diffuse expression of ß-catenin and a partial hepatic resection was performed. The histologic analysis revealed a hepatocellular tumor composed of uniform trabeculae of hepatocytes and solid areas, the later with a significant amount of black pigment highlighted by Masson-Fontana stain. Immunohistochemistry showed co-expression of C-reactive protein and serum amyloid A in the tumor. Literature review revealed that pigmented HCAs, previously reported as dark adenomas, are rare tumors. In HCAs, the presence of ß-catenin activation should be searched for due to the higher risk of malignant transformation in hepatocarcinoma. We describe a pigmented HCA with ß-catenin nuclear expression and inflammatory features being the fifth case reported so far.

Giant hepatocellular adenoma in a previously obese thirteen-year-old boy.

Hepatocellular adenoma is an uncommon neoplasm, especially in the childhood age group. We describe a previously obese 13-year-old male with a giant hepatocellular adenoma requiring an extensive hepatic resection. The related pediatric tumor literature, diagnosis and clinical management is discussed.

Hepatocellular carcinoma arising in a telangiectatic hepatocellular adenoma.

Telangiectatic hepatocellular adenoma is a rare, recently recognized subtype of benign liver tumor that may very rarely undergo transformation into hepatocellular carcinoma. We report an unusual case of a 75-year-old woman with no history of oral contraceptive use that underwent malignant transformation of a telangiectactic hepatocellular adenoma. No risk factors for adenoma development were identified in this otherwise healthy woman. Radiological characteristics, gross features and histopathology are herein described. In conclusion, telangiectatic hepatocellular adenoma can undergo malignant transformation. Further studies are needed to better clarify the factors associated with malignant progression.

Lesiones focales hepáticas en niños / Focal liver lesions in children

Las lesiones focales del hígado comprenden un grupo heterogéneo de entidades como tumores benignos y malignos, sólidos o quistes, vasculares, masas inflamatorias y metástasis, entre otras. Reportar lesiones focales hepáticas en niños, características clínicas, estudios por imágenes y conducta terapéutica. Estudio descriptivo, retrospectivo, basado en la revisión de 16 historias clínicas de niños con lesiones focales hepáticas en el periodo comprendido entre enero 2007 a enero 2012. Se excluyeron los abscesos hepáticos. El 68,75%11 eran del sexo masculino y 31,25%5 del sexo femenino; con edad promedio de 9,5 años (rango: 10 días - 14 años). Las lesiones focales benignas fueron: hemangioma 4/16 (25%), hematoma hepático 4/16 (25%), quiste hepático 3/16 (18,75%), hiperplasia nodular focal 1/16 (6,25%) adenoma 1/16 (6,25%) y las malignas: hepatocarcinoma 2/16 (12,50%) y hepatoblastoma 1/16 (6,25%). La mayoría de los pacientes (56,25%) se encontraban asintomáticos, 3/16 (18,75%) presentaron dolor abdominal, 3/16 (18,75%) masa palpable y 2/16 (12,5%) ictericia. La lesión fue identificada por ultrasonido abdominal en todos los pacientes y sólo el 56,25% (9/16) ameritaron tomografía con contraste. Al 43,75% (7/16) se les realizó marcadores tumorales y de estos el 42,85% (3/7) reportaron neoplasias. El funcionalismo hepático reportó normal en el 75% de los casos. El ultrasonido abdominal es el método de elección para el diagnóstico y seguimiento de las lesiones focales hepáticas, mientras el origen de las mismas, guía la conducta terapéutica

Focal liver lesions comprise a heterogeneous group of entities such as benign and malignant, solid or cysts, vascular, inflammatory masses and metastasis among others. To report focal liver lesions in children, clinical features, imaging and therapeutic behavior. A descriptive, retrospective study based on a review of 16 case histories of children with focal liver lesions in the period from January 2007 to January 2012. Liver abscesses were excluded. 68.75%11 were male and 31.25%5 females, mean age 9.5 years (range: 10 days - 14 years). Focal lesions were benign: Hemangioma 4/16 (25%), liver hematoma 4/16 (25%), hepatic cyst 3/16 (18.75%), nodular focal hyperplasia 1/16 (6.25%) and adenomas 1/16 (6.25%) and malignant: Hepatocellular carcinoma 2/16 (12.50%) and hepatoblastoma 1/16 (6.25%). Most patients (56.25%) were asymptomatic, 3/16 (18.75%) had abdominal pain, 3/16 (18.75%) and palpable mass 2/16 (12.5%) jaundice. The lesion was identified by abdominal ultrasound in all patients and only 56.25% (9/16) needed tomography with contrast. To 43.75% (7/16) underwent tumor markers and of these 42.85% (3/7) reported neoplasm. Normal hepatic function reported in 75% of cases. An abdominal ultrasound is the method of choice for the diagnosis and management of focal liver lesions, while the origin of them, guide therapeutic conduct

Nódulos hepáticos en adolescente con glucogenosis tipo Ia / Liver nodules in an adolescent with glycogenosis type Ia

La glucogenosis tipo I o Enfermedad de Gierke, es una enfermedad metabólica, hereditaria, por deficiencia de la Glucosa6-Fosfatasa, que ocasiona acumulo anormal de glucógeno en hígado, riñón y mucosa intestinal. Las manifestaciones clínicas: hipoglucemia, hepatomegalia, hiperlactacidemia, hiperlipidemia. Las complicaciones a largo plazo: gota, insuficiencia renal progresiva y adenoma hepático en la segunda o tercera década de la vida. Caso clínico: adolescente masculino de 12 años, en control desde su diagnóstico de Glucogenosis Ia a los 7 meses, con tratamiento nutricional y manejo multidisciplinario. El paciente presenta mal control metabólico con hipoglicemias recurrentes y hospitalizaciones secundarias a transgresión dietética. Examen físico: palidez cutánea mucosa moderada, obesidad troncal, cara de muñeca, abdomen prominente, hepatoesplenomegalia y postura lordótica. En control ecográfico, se reporta: nefromegalia bilateral y hepatoesplenomegalia difusa con lesiones de aspecto nodular, múltiples, intrahepáticas, sugestivas de Adenoma hepático. La biopsia de las lesiones: daño hepatocelular difuso, glucogenosis tipo I. TAC abdominal: hepatomegalia con 4 lesiones nodulares (adenomas) y lesión de ocupación de espacio hipercaptante en segmento hepático IV. En su seguimiento anual, se solicita ecografía abdominal, alfa-fetoproteína y otros marcadores, por tratarse de una lesión premaligna, de presentación precoz. En caso de deterioro clínico, el paciente es candidato a trasplante hepático, en caso de deterioro.

The type I glycogenosis Gierke's Disease is a metabolic disease, hereditary deficiency of glucose-6-phosphatase, which causes abnormal accumulation of glycogen in liver, kidney and intestinal mucosa. Clinical manifestations: hypoglycemia, hepatomegaly, hyperlactataemia, hyperlipidemia. The long-term complications: gout, progressive renal failure and hepatic adenoma in the second or third decade of life. Case report: A male adolescent of 12 years in control after diagnosis of glycogenosis Ia at 7 months, nutritional treatment and multidisciplinary management. The patient has poor metabolic control with recurrent hypoglycemia, and hospitalizations secondary to dietary transgression. Physical exam: moderate mucosal pallor, truncal obesity, doll face, protruding abdomen, hepatosplenomegaly and lordosis. In ultrasound guidance, it is reported: nephromegaly bilateral and diffuse hepatosplenomegaly with nodular lesions, multiple, intrahepatic, suggesting hepatic adenoma. The biopsy of the lesions: diffuse hepatocellular damage, glycogen storage disease type I. Abdominal CT: 4 hepatomegaly with nodular lesions (adenomas) and space-occupying lesion uptake in liver segment IV. In its annual monitoring is required abdominal ultrasound, alpha-fetoprotein and other markers, because it is a premalignant lesion, which occurred early. In case of clinical deterioration, the patient is a candidate for liver transplantation, in case of damage.

Hepatocellular adenoma: an excellent indication for laparoscopic liver resection.

OBJECTIVES: Laparoscopic resection for benign liver disease has gained wide acceptance in recent years and hepatocellular adenoma (HA) seems to be an appropriate indication. This study aimed to discuss diagnosis and treatment strategies, and to assess the feasibility, safety and outcomes of pure laparoscopic liver resection (LLR) in a large series of patients with HA. METHODS: Of 88 patients who underwent pure LLR, 31 were identified as having HA. Diagnosis was based on radiological evaluation and resections were performed for lesions measuring >5.0 cm. RESULTS: The sample included 29 female and two male patients. Their mean age was 33.2 years. A total of 27 patients had a single lesion, one patient had two and one had four lesions. The two remaining patients had liver adenomatosis. Mean tumour size was 7.5 cm. Three right hepatectomies, 17 left lateral sectionectomies and 11 wedge resections or segmentectomies were performed. There was no need for blood transfusion or conversion to open surgery. Postoperative complications occurred in two patients. Mean hospital stay was 3.8 days. CONCLUSIONS: Hepatocellular adenoma should be regarded as an excellent indication for pure LLR. Pure LLR is safe and feasible and should be considered the standard of care for the treatment of HA when performed by surgeons with experience in liver and laparoscopic surgery.

[Transformation of hepatic adenoma into hepatocellular carcinoma in patients with prolonged use of oral contraceptives]. / Transformação de adenoma hepático em carcinoma hepatocelular em pacientes com uso prolongado de contraceptivo oral.

Liver cell adenomas were relatively rare until the use of oral contraceptives. Most of these tumors have occurred in otherwise healthy young women who have been exposed to oral contraceptives. The treatment of this condition remained controversial for a long time. However, bleeding is still a frequent complication and can lead to a significant mortality rate. The better surgical results in hepatic resection, due to technological advances, has contributed to the indication of surgical management as therapeutic option in hepatic cell adenoma. Some authors believe that liver cell adenomas were potentially premalignant and could degenerate into hepatocellular carcinoma but there is very few well documented reports of this transformation. We report our experience in the management of liver cell adenoma.

PIP: Two cases of hepatic cell adenoma associated with hepatocellular carcinoma in long-term oral contraceptive (OC) users are described. Hepatic cell adenomas are rare benign tumors whose incidence has increased with the use of OCs. They generally occur in women over age 30 who have used OCs for five years or longer. The preferred treatment is currently hepatic resection, which reduces the risk of intraperitoneal hemorrhage leading to death. A 30-year-old woman with a history of 15 years of OC use and a 37-year-old woman with a history of 20 years of OC use underwent diagnostic procedures followed by laparotomy and resection of hepatic cell adenomas. Histologic examination in both cases revealed hepatic cell adenoma with areas of hepatocellular carcinoma in a liver with otherwise normal parenchyma. Although the causal relationship between OC use and hepatic cell adenoma is well accepted, a similar etiologic relationship between OCs and hepatocellular carcinoma has not been definitively established despite anecdotal evidence and some suggestive epidemiological data. Relatively few well documented cases of malignant transformation of hepatic cell adenoma have been published. Many authors believe that hepatic cell adenomas induced by OC use are potentially premalignant, but the mechanism through which the transformation might occur has not been explained. It is likely that nonspecific pharmacological actions as well as actions mediated by hormonal receptors are involved.

Hepatocellular adenoma and focal nodular hyperplasia of the liver: differential diagnosis in dogs / Adenoma hepatocelular e hiperplasia nodular focal do fígado: diagnóstico diferencial em cäes

Dentre as alteraçöes hepáticas encontradas na rotina de necrópsias em medicina veterinária, as lesöes nodulares säo as menos caracterizadas. Estas incluem processos reacionais ou hiperplásicos, neoplásicos e hamartomas. Este estudo foi realizado com a finalidade de diferenciar os adenomas hepatocelulares (AH) das hiperplasias nodulares focais (HNF) do fígado em cäes. Dez casos de lesöes nodulares hepáticas em cäes foram levantados dos arquivos do Departamento de Patologia da Faculdade de Medicina Veterinária e Zootecnia da Universidade de Säo Paulo. Métodos histoquímicos e imunohistoquímicos foram aplicados a cada caso, com a finalidade de caracterizar as lesöes, de acordo com critérios histológicos definidos para as mesmas lesöes no homem. Dos resultados descritos foi possível diagnosticar oito casos de HNF e dois casos de AH. Conclui-se que estas técnicas podem ser facilmente utilizadas e que säo adequadas para os objetivos propostos