Focal nodular hyperplasia-like nodules arising in the setting of hepatic vascular disorders with portosystemic shunting show ß-catenin activation.

Hepatocellular nodules can develop in the setting of chronic hepatic vascular disorders including those characterized by portosystemic shunts such as Abernethy malformation and post-Fontan procedure. The nodules can range from benign lesions such as regenerative nodules, focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA) to malignant neoplasms such as hepatocellular carcinoma (HCC). In many instances, these nodules are difficult to place into well-defined categories based on radiologic or histologic features. Nodular lesions that resemble FNH are common in this context and have been described as FNH-like nodules, the nature of which is not well-established. This study examines 6 liver resections from patients with vascular disease characterized by portosystemic shunts. A wide range of nodules were present in these cases, including regenerative nodules (n = 2), FNH and FNH-like (n = 30), HCA (n = 10), HCA-like (n = 13), and HCC (n = 2). Six nodules from 3 patients were categorized as FNH-like due to one or more features such as nodular architecture, fibrous septa, and ductular reaction, but lack of typical map-like glutamine synthetase (GS) staining. Further characterization of these 6 FNH-like nodules showed diffuse GS staining in all nodules (3 diffuse homogeneous, 3 diffuse heterogeneous). Targeted next-generation sequencing identified CTNNB1 alterations in all tested FNH-like nodules (n = 4). These results indicate that FNH-like nodules in the setting of chronic hepatic vascular disorders can be neoplastic. Since the presence of ß-catenin activation portends a potential risk for malignant progression, GS and ß-catenin immunohistochemistry should be obtained in all cases showing FNH-like morphology, with molecular analysis performed in cases with indeterminate staining pattern.

Surgical indications for solid hepatic benign tumors: An updated literature review.

Hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma are the most common benign solid liver tumors. However, their surgical indications have been the subject of debate. Minimally invasive liver resection reduces the cost of surgery and may lead to overtreatment of benign liver tumors. Recently, there has been a growing understanding of the etiology, pathogenesis, and natural history of these tumors. Great progress has also been made in imaging. The use of MRI and contrast agents has improved the accuracy of non-invasive diagnosis of these tumors, and especially in the identification of specific molecular subtypes of liver adenoma. These factors have resulted in alterations of surgical indications for these tumors. This article examines recent literature and it discusses the surgical indications for hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma while summarizing modifications in clinical management.

Large focal nodular hyperplasia of the liver treated with transcatheter arterial embolization and laparoscopic resection: A case report.

Focal nodular hyperplasia (FNH) is a rare benign hepatic tumor which is frequently observed in women of reproductive age, and therapeutic intervention needs to be considered in cases wherein the tumor has a risk of rupture. The laparoscopic approach is beneficial, especially for young women, but is often challenging because the tumor is large and hemorrhagic. Herein, we report a case of large FNH in a 22-year-old woman. The patient was asymptomatic; however, the tumor was approximately 15 cm in diameter and protruded from the liver. Given the risk of rupture, we decided to perform surgical resection. Preoperative transcatheter arterial embolization led to rapid shrinkage of the tumor and control of intraoperative bleeding, which enabled us to safely perform laparoscopic liver resection. The combination of surgical resection with intravascular embolization may be a promising therapeutic option for hypervascular tumors such as FNH.

Laparoscopic resection of focal nodular hyperplasia in the hepatic caudate lobe.

OBJECTIVE: To investigate the safety and feasibility of laparoscopic resection of focal nodular hyperplasia (FNH) in the hepatic caudate lobe. METHODS: The clinical data of eight patients who underwent laparoscopic hepatic caudate lobe FNH resection at the Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of Army Medical University, were retrospectively analyzed. RESULTS: The laparoscopic procedures were successful in all eight patients, and no patients required conversion to open surgery. Five patients underwent partial caudate lobe resection, one patient underwent caudate lobe resection, and two patients underwent combined left hemihepatectomy with caudate lobe resection. Tumor resection was performed using the left approach in five cases, the right approach in one case, the middle hepatic fissure approach in one case, and the left and right combined approach in one case. The operation time ranged from 120 to 360 min, with a mean of 225 min. The intraoperative blood loss ranged from 50 to 600 ml, with a mean of 235 ml. No postoperative bleeding, bile leakage or abdominal infection occurred. CONCLUSIONS: Laparoscopic resection of hepatic caudate lobe FNH was safe and feasible in appropriate patients. Skilled laparoscopic hepatectomy techniques, adequate preoperative evaluation, appropriate choice of surgical approach and the control of intraoperative bleeding are critical to perform this surgery.

Fk506 Inhibit Liver Regeneration in HOC Model Rat.

BACKGROUND: Studies have shown that lymphocytes support hepatic oval cell (HOC)-dependent liver regeneration and FK506（Tacrolimus） is known as an immunosuppressor. Therefore, we studied the role of FK506 in HOC activation and/or proliferation to guide the clinical use of FK506. METHODS: Thirty male Lewis rats were randomly divided into 4 groups: (A) intervene in activation (n = 8), (B) intervene in proliferation (n = 8), (C) control HOC model (n = 8), and (D) pure partial hepatectomy (PH) (n = 6). The HOC model was established by 2AAF(2-acetylaminofluorene)/PH in groups A to C. FK506 (at a dose of 1 mg/kg/d) was given subcutaneously in group A except on operation day, and not until day 8 post-operation (PO) in group B. Half of the animals were euthanized on days 10 and 14 PO, respectively. The remnant liver was weighed and stained by hematoxylin and eosin and immunohistochemical staining of proliferating cell nuclear antigen and epithelial cell adhesion molecule enabled HOC proliferation analysis. RESULTS: FK506 intervention exacerbated liver damage and hindered the recovery of the HOC model rat. Weight gain was severely retarded or even negative. Liver weight and the liver body weight ratio were lower than control group. HE and immunohistochemistry showed pooer proliferation of hepatocytes and fewer HOC numbers in group A. CONCLUSION: FK506 inhibited HOC activation by affecting T and NK cells, ultimately blocking liver regeneration. Poor liver regeneration after auxiliary liver transplantation might be associated with the inhibition of HOC activation and proliferation caused by FK506 treatment.

Rare benign liver tumors that require differentiation from hepatocellular carcinoma: focus on diagnosis and treatment.

BACKGROUND/AIM: Recently, an increase in the number of asymptomatic rare benign liver tumors (BLTs) has been reported during health check-ups. It is difficult to determine the nature of partial rare BLTs and not easy to distinguish from malignant liver tumors. This study aimed to analysis clinical features, diagnosis and treatment of rare BLTs to reduce misdiagnosis and provide reference for clinical practice. METHODS: From January 2012 to January 2021, we treated 112 rare BLTs by hepatectomy, including 54 focal nodular hyperplasias, 14 hepatocellular adenomas, 28 hepatic angiomyolipomas, 3 hepatic granulomas, 2 inflammatory pseudotumors of the liver, 2 nodular regenerative hyperplasia, 2 hepatic lipomas, 1 solitary fibrous tumor of the liver, 1 hepatic schwannoma and 1 hepatic myelolipoma. RESULTS: The majority of patients were middle-aged female and asymptomatic. Single tumors were dominant. The diagnostic accuracies of computed tomography (CT) and magnetic resonance imaging (MRI) were 32.5% and 44.2%, respectively. The majority of tumors were likely to be misdiagnosed as hepatocellular carcinoma (HCC) or difficult to distinguish from HCC. All patients underwent surgical treatment. Postoperative pathological and immunohistochemical examination can confirm the diagnosis. No patients without tumor recurrence or metastasis during follow-up period. CONCLUSION: Altogether, the clinical symptoms of rare BLTs lack specificity, and their preoperative diagnosis largely depends on imaging examination, with a low diagnostic accuracy rate and high chances of misdiagnosis as HCC. Diagnosis is confirmed by pathological and immunohistochemical examination. Surgical resection for rare BLT is safe and effective, regular postoperative follow-up is necessary.

A case of focal nodular hyperplasia with hepatic failure treated with liver transplantation.

Focal nodular hyperplasia (FNH) is a benign nodular lesion, but because of its feature of portal tract vessel abnormality, it may induce portal hypertension. A 27-year-old woman was admitted with a fever. A large nodule with satellite lesions was found in the liver and cotton wool-like feature of arteries were detected on angiography. Technetium galactosyl serum albumin scintigraphy and diagnostic laparoscopy showed that the tumor site was functional, while the surrounding area was a non-functional fibrotic area. A biopsy specimen indicated that the nodular lesion was an FNH-like lesion. She experienced several instances of variceal rupture and suffered liver failure, receiving liver transplantation. The excised liver showed a centrally scarred area in the nodule, indicating that the diagnosis was FNH. We herein report this case as a rare case of FNH that progressed to liver failure.

Focal nodular hyperplasia mimicking hepatocellular adenoma and carcinoma in two cases.

Focal nodular hyperplasia (FNH) is a solid benign tumor of the liver, predominantly in young women. A correct diagnosis of FNH is essential for making appropriate clinical decisions and avoiding unnecessary liver resection. Herein, we reported that two male cases with FNH, who initially presented with persistent abdominal discomfort, were misdiagnosed with hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) on contrast-enhanced magnetic resonance imaging and computed tomography scans, respectively. After surgery, a histological diagnosis of FNH was finally established. In this paper, we also reviewed the knowledge regarding diagnosis and differential diagnosis of FNH on imaging examinations, which are helpful for avoiding misdiagnoses and guiding clinical interventions.

Liver Transplantation Using Right Lobe Graft With Focal Nodular Hyperplasia: Report of 2 Cases.

We described 2 cases of adult-to-adult liver transplantation using right lobe grafts donated by 2 patients suffering from focal nodular hyperplasia, the volumes of which were 360 cm3 and 220 cm3. This study was performed in compliance with the Declaration of the Helsinki. For preparation of the graft, back-table hepatic venous outflow reconstruction, including replacement of the retrohepatic inferior vena cava and bridging of hepatic segment V5/V8, was performed by using prosthetic vessel grafts. The liver grafts after subtracting the weight of focal nodular hyperplasia functioned well without serious small-for-size syndrome or graft dysfunction in spite of graft-to-recipient weight ratio less than 0.8%. This suggested the functioning of hepatocyte within focal nodular hyperplasia, which avoided graft deficiency. These 2 recipients were given not only conventional immunosuppressants (tacrolimus and mycophenolate sodium) but also anticoagulants (low molecular weight heparin and warfarin). Thrombosis of the prosthetic inferior vena cava 1 month after transplant in recipient 1 was treated by placement of intravascular stent. Biliary duct anastomotic stricture 2 weeks after transplant in recipient 2 was treated by placement of biliary stent. These 2 recipients remain well at more than 2 years post-transplant. These successful explorative cases highlight the safe use of a graft containing focal nodular hyperplasia. The partial liver resection grafts with focal nodular hyperplasia could be applied to the patients on the waiting list for liver transplantation.

Focal nodular hyperplasia of the liver in children: A report of 2 cases.

Focal nodular hyperplasia (FNH) is a benign non-neoplastic lesion of the liver usually found in adults. It is uncommon in children, comprising 2-10% of all pediatric liver tumours. In children, it can occur at all ages, with increased frequency between 6-10 years. We present two cases of FNH in childhood- the first being that of a 5-month-old infant, and the second in a 6-year-old boy. The possibility of congenital FNH had been excluded in the first case. The second case posed diagnostic difficulty initially and was wrongly treated for hepatoblastoma by neoadjuvant chemotherapy, but later correctly diagnosed to be FNH. Both the children are doing well on follow-up. Paediatric FNH though rare, should be kept in mind while dealing with a hepatic mass. Radiological features can be variable and needle sampling may not be sufficient to reach to a diagnosis. Histological examination with glutamine synthetase immunostaining should be performed in doubtful cases to differentiate FNH from other paediatric liver masses, as management differs.

Should Focal Nodular Hyperplasia Still be Operated Upon? Analysis of a Case Series.

BACKGROUND: Focal nodular hyperplasia (FNH) is a frequent benign liver lesion. Its course is considered benign, and there is no recommendation for its treatment. Nevertheless, the literature presents a high incidence of surgery. AIM: To evaluate the results of conservative treatment in a series of patients with presumed FNH. METHODS: The study included patients diagnosed with FNH from May 2007 to July 2017 based on conventional imaging or magnetic resonance imaging with liver-specific contrast (MRI-LSC) or lesion biopsy (histology/immunohistochemical analysis). Patients were followed clinically and using imaging exams. RESULTS: In a total of 54 patients, the diagnosis was obtained by typical findings on computed tomography scan and gadolinium MRI in 48.1% of the patients, by MRI-LSC in 31.5%, and by histological examination in 20.4% of cases. The mean follow-up time was 35.5 months. The initially asymptomatic patients remained symptom-free, and none of those with HNF-related pain had to worsen of the initial symptom. Conservative treatment was effective in 94.4% of the cases. In only 3 cases, there was a need for some therapeutic approach (5.5%); 2 cases for pain and 1 case for lesion growth during follow-up. CONCLUSION: The present study suggests that it is safe to conservatively manage patients with FNH presumed by highly accurate imaging tests. Similar to hepatic hemangiomas, surgery for FNH should be an exception.

Regenerative nodular hyperplasia, portal vein thrombosis and primary myelofibrosis: an unusual triple association.

We report a case of a regenerative nodular hyperplasia with a portal vein cavernomatosis with a subsequent progression to symptomatic, occlusive thrombosis of the superior mesenteric vein. A thorough investigation resulted in a final diagnosis of primary myelofibrosis associated with the V617F mutation in the JAK2 gene.

Growth of Focal Nodular Hyperplasia is Not a Reason for Surgical Intervention, but Patients Should be Referred to a Tertiary Referral Centre.

BACKGROUND: When a liver lesion diagnosed as focal nodular hyperplasia (FNH) increases in size, it may cause doubt about the initial diagnosis. In many cases, additional investigations will follow to exclude hepatocellular adenoma or malignancy. This retrospective cohort study addresses the implications of growth of FNH for clinical management. METHODS: We included patients diagnosed with FNH based on ≥2 imaging modalities between 2002 and 2015. Characteristics of patients with growing FNH with sequential imaging in a 6-month interval were compared to non-growing FNH. RESULTS: Growth was reported in 19/162 (12%) patients, ranging from 21 to 200%. Resection was performed in 4/19 growing FNHs; histological examination confirmed FNH in all patients. In all 15 conservatively treated patients, additional imaging confirmed FNH diagnosis. No adverse outcomes were reported. No differences were found in characteristics and presentation of patients with growing or non-growing FNH. CONCLUSION: This study confirms that FNH may grow significantly without causing symptoms. A significant increase in size should not have any implications on clinical management if confident diagnosis by imaging has been established by a tertiary benign liver multidisciplinary team. Liver biopsy is only indicated in case of doubt after state-of-the-art imaging. Resection is deemed unnecessary if the diagnosis is confirmed by multiple imaging modalities in a tertiary referral centre.

Managing Focal Nodular Hyperplasia of the Liver: Surgery or Minimally-invasive Approaches? A Review of the Preferable Treatment Options.

BACKGROUND/AIM: Focal nodular hyperplasia (FNH) is the second most common benign tumor of the liver. As of 2017, many clinical, radiological and surgical features have been largely documented. On the other hand, little is still known about the correlation of FNH with hepatocellular carcinoma, nor the preferable modality of treatment. Our aim was to elucidate the latter topic. MATERIALS AND METHODS: We investigated the pertinent literature available as of 2017 through four popular search engines (PubMed, Science Direct, Scopus and Google Scholar). Four main approaches were selected: conservative treatment, surgery, radiofrequency ablation (RFA) and transarterial embolization (TAE). RESULTS: We found most works to be on conservative and surgical approaches. On the contrary, only one article has been published for RFA to date. Seventeen articles dealt with TAE. CONCLUSION: TAE currently represents the most cogent and successful alternative to surgery.

Papel de la embolización selectiva intraarterial en los tumores hepáticos benignos / Role of selective intra-arterial embolization in benign liver tumors

Objetivo. Presentar los casos de tumores hepáticos benignos sintomáticos diagnosticados y tratados con embolización intraarterial previa a la cirugía. Describimos la técnica y analizamos los resultados obtenidos. Material y métodos. Presentamos 7 pacientes diagnosticadas de tumores benignos sintomáticos que requirieron tratamiento: 1 hiperplasia nodular focal, 2 hemangiomas cavernosos gigantes, 1 adenomatosis hepática y 3 adenomas hepáticos. Una vez identificadas las arterias nutricias de cada tumor se embolizaron con partículas de PVA de 500 a 700 micras y posteriormente se cerró la arteria nutricia con coils si presentaban pedículo arterial para asegurar la exclusión vascular total del tumor. La intervención quirúrgica se realizó de 4 a 7 días después de la embolización. Resultados. Los 7 casos eran mujeres con un rango de edad de 23 a 74 años. En 6 pacientes se realizó la embolización intraarterial prequirúrgica. En 1 caso, de adenomatosis, la embolización fue para control de una hemorragia intraparenquimatosa hepática. En las 6 pacientes intervenidas se realizó una exéresis tumoral completa y no tuvieron eventos hemorrágicos intraoperatorios ni ulteriores complicaciones. Conclusiones. La embolización de los tumores hepáticos benignos gigantes y/o sintomáticos es una opción terapéutica útil para el manejo perioperatorio, siempre consensuado en un comité multidisciplinar (AU)

Objective. To present cases of symptomatic benign liver tumors diagnosed and treated with intra-arterial embolization before surgery. Material and methods. We present the cases of 7 patients diagnosed with symptomatic benign liver tumors that required treatment: 1 focal nodular hyperplasia, 2 giant cavernous hemangiomas, 1 hepatic adenomatosis, and 3 hepatic adenomas. Once the feeding arteries were identified, tumors were embolized with polyvinyl alcohol particles (500μm–700μm) and then the feeding artery was plugged with coils if there was an arterial pedicle to ensure the total vascular exclusion of the tumor. The surgical intervention took place 4 to 7 days after embolization. Results. All 7 patients were women (age range, 23-74 years); presurgical intra-arterial embolization was done in 6. In 1 patient with adenomatosis, embolization was done to control intraparenchymal hepatic hemorrhage. In the 6 patients who underwent surgery, the tumor was completely excised and no intraoperative bleeding events or postoperative complications occurred. Conclusions. Provided there is a consensus among the multidisciplinary team, embolization is a useful option in the perioperative management of giant and/or symptomatic benign liver tumors (AU)

Resection of benign liver tumours: an analysis of 62 consecutive cases treated in an academic referral centre.

BACKGROUND: Benign tumours of the liver are increasingly diagnosed and constitute a substantial proportion of all hepatic tumours evaluated and resected at tertiary referral centres. This study assessed the safety and outcome after resection of benign liver tumours at a major referral centre. METHOD: All patients with symptomatic benign liver tumours who underwent resection were identified from a prospective departmental database of a total of 474 liver resections (LRs). Demographic data, operative management and morbidity and mortality using the Accordion classification were analysed. RESULTS: Sixty-two patients (56 women, 6 men, median age 45 years, range 17-82) underwent resection of symptomatic haemangiomata n=23 (37.1%), focal nodular hyperplasia n=19 (30.6%), biliary cystadenoma n=16 (25.8%) and hepatic adenomas n=4 (6.5%). A major resection was required in 25 patients, 14 patients had 4 segments resected, 11 had 3 segments and 37 patients had 2 or fewer segments resected. Median operating time was 169 minutes (range 80-410). Median blood loss was 300 ml (range 50-4500 ml) and an intra-operative blood transfusion was required in 6 patients. Median length of post-operative hospital stay was 7 days (range 4-32). Complications occurred in 11 patients (Accordion grades 1 n=1, 2 n=4, 3 n=1, 4 n=4, 6 n=1). Four patients required re-operation (bleeding n=2, bile leak n=1, small bowel obstruction n=1). An elderly patient died in hospital on day 16 following a postoperative cerebrovascular accident. CONCLUSION: Clinically relevant symptomatic benign liver tumours comprise a substantial proportion of LRs. Our data suggest that resections can be performed safely with minimal blood loss and transfusion requirements. We advocate selective resection according to established indications. Despite the low postoperative mortality rate, the risk of postoperative complications emphasizes the need for careful selection of patients for resection.