Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease.

The gut-liver axis plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which is the third leading cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study was to explore what features of the gut microbiota are associated with HCC in patients with cirrhosis and NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1, 21 patients), NAFLD-related cirrhosis without HCC (group 2, 20 patients), and healthy controls (group 3, 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status, and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, while intestinal permeability was similar to patients with cirrhosis but without HCC. Plasma levels of interleukin 8 (IL8), IL13, chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5 were higher in the HCC group and associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of patients with cirrhosis showed higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides. Conclusion: Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis.

A resected case of hepatoblastoma originating in the caudate lobe.

A very rare case of hepatoblastoma originating in the caudate lobe in an 18-month-old female infant is reported. Three years after surgical resection of the tumor, she is alive without signs of a recurrence.

[Familial hepatocellular carcinoma in B or non-A non-B cirrhosis. Report of 4 families]. / Carcinomes hépato-cellulaires familiaux sur cirrhose B ou non A non B. A propos de 4 familles.

We report the cases of four families in whom 2 or 3 cases of hepatocellular carcinoma were observed. In the first family, the mother and 2 daughters had hepatocellular carcinoma. In 2 other families, 2 brothers had hepatocellular carcinoma. In the first three families, all patients with hepatocellular carcinoma, as well as other members of these three families, were chronic HBsAg carriers. In the fourth family, hepatocellular carcinoma developed in 2 brothers with HBsAg negative Mediterranean cirrhosis. Because of the high risk of hepatocellular carcinoma in chronic HBsAg carriers, it is conceivable that the occurrence of familial cases of hepatocellular carcinoma could be fortuitous. However, we cannot exclude the possibility of the familial predisposition to hepatocellular carcinoma. Therefore, it seems wise, when hepatocellular carcinoma develops in one patient in a family, to carefully monitor other members of this family, whether HBsAg positive or with non A non B chronic hepatitis, for the development of hepatocellular carcinoma.

Congenital hepatoblastoma and Beckwith-Wiedemann syndrome: a case study including DNA ploidy profiles of tumor and adrenal cytomegaly.

A case of fatal congenital hepatoblastoma is described in which the autopsy provided the first evidence of Beckwith-Wiedemann syndrome. Aneuploid quantitative DNA patterns were found by image analysis of the tumor and the cytomegalic adrenal gland.

Multicystic kidney in association with hepatoblastoma--a case report.

In the absence of functional renal tissue on the right side, differentiating between a liver tumor and a renal tumor, both clinically and on routine imaging, is difficult. This clinical dilemma is highlighted here in a case report of a 2 year old girl with hepatoblastoma occurring in association with multicystic kidney. To our knowledge no other such case has been reported so far.

Fetal hepatoblastoma presenting as nonimmune hydrops.

The list of conditions associated with nonimmune hydrops fetalis has been steadily increasing. We describe a liveborn neonate with fetal hepatoblastoma presenting as nonimmune hydrops. The hepatic tumor was diagnosed on prenatal ultrasound. The infant survived for 2 days. The pathophysiology of nonimmune hydrops in this case is also described.

[Hepatoblastoma: a catamnestic study and proposal of a therapy concept]. / Das Hepatoblastom: Eine katamnestische Untersuchung und Vorschlag eines Therapiekonzeptes.

Since 1977, 28 infants and children with hepatoblastomas were seen in the Department of Paediatric Surgery, Hanover Medical School. Five tumours could only be biopsied. One 11-months-old infant had a successful liver transplantation done at the Dept. of Transplantation Surgery (Professor R. Pichlmayr). Following a biopsy for unresectable tumour, chemotherapy was instituted in 5 cases: three of these could be resected in a second look operation 10 to 26 weeks later. Altogether, 22 tumours (= 81%) were resected: 14 had an extended resection (trisegmentectomy), and 8 had a lobectomy. Operative mortality was 14%. Out of 27 patients which were operated upon (resection or biopsy) longer than one year ago, 11 are alive and free from disease (= 40%). Early metastatic disease was diagnosed 3 weeks to 5 months postoperatively in 5 cases: only one of these children survived, following an intensive course of chemotherapy. In another two patients lung metastases were found 14 resp. 20 months after operation: both of these are alive and free from disease following chemotherapy and thoracotomy. One patient died of brain metastases 3 years postoperatively. Results of therapy are correlated to primary findings, type of operation, chemotherapy and histological subtype of the tumour. In comparison with published data a possible advantage of more aggressive operative strategies is discussed, and the benefit of a preoperative chemotherapy is evaluated. As a result of these considerations a treatment protocol for hepatoblastomas is proposed, designed as a national multicentre prospective study conducted by the German Society of Paediatric Oncology (GPO).(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatocellular carcinoma associated with congenital macronodular cirrhosis in a neonate.

Hepatocellular carcinoma is rare in infancy. This report describes the first documented case of congenital hepatocellular carcinoma associated with macronodular cirrhosis.

A rare case of Aicardi syndrome with severe brain malformation and hepatoblastoma.

A 2-month-old Japanese girl exhibited tonic seizure, agenesis of the corpus callosum, lacunar chorioretinopathy, vertebral anomalies, electroencephalographic abnormalities and a malignant tumor. Autopsy revealed a hepatoblastoma and severe brain malformations consisting of callosal agenesis, arhinencephaly, marked polymicrogyria and optic nerve anomalies. It was thought that the pathogenic factor in this case may exert its effect during the fourth or fifth week of intrauterine life, and then may continue until the beginning of neuronal migration (about 3 months). This is the first reported case of Aicardi syndrome associated with hepatoblastoma, and may provide a link between teratogenicity and oncogenicity.

Neonatal hepatic malignant tumor. A correlative imaging approach.

We report the hepatobiliary study of a neonate with hepatomegaly. Biliary atresia was ruled out. Fortuitous demonstration of massive parenchymal lesions redirected the clinical management of the child. Other imaging modalities were employed to define further the nature of the lesions. Pediatric reports of non-biliary lesions demonstrated by hepatobiliary scintigraphy are uncommon. To our knowledge, the present case of multiple hepatoblastomas discovered by hepatobiliary imaging is the first report in the literature.

[Congenital hepatoblastoma of mixed type. Light and electron microscopy studies]. / Konnatales Hepatoblastom vom Mischtyp. Licht- und elektronenmikroskopische Untersuchungen.

Malignant liver tumors of infancy are uncommon. In this report the histological and ultrastructural features of a congenital mixed hepatoblastoma in a female infant are described. The tumor was obtained by radical surgery at the eighth day of life. Histologically the mass was characterized by a mixture of variously differentiated hepatic tissue and mesenchymal tissue. The epithelial component is represented by liver cells of the embryonic and fetal type. Electron microscopical investigation revealed a changing organelle composition of the epithelial tumor cells showing a decreased number of cytoplasmic organelles in the cells of the embryonic type. At cellular junctions, however, these cells are connected by desmosome-like structures without lumina as well as empty canaliculi-developing structures of cholangiolar microvilli. At light microscopical level the former corresponded to pseudorosettes , the latter to so-called rosettes. Furthermore, in places sinus-like structures are encountered but in the absence of true sinusoidal channels with Disse's spaces. Some areas consisted of undifferentiated cells lacking cytoplasmic organelles and resembled a multipotential blastema. The ultrastructural findings suggest that hepatoblastoma may arise from an undifferentiated progenitor cell capable of various forms of differentiation.

[Congenital hepatoblastoma with a rhabdomyoblastic component]. / Vrozhdennaia gepatoblastoma s rabdomioblasticheskim komponentom.

An observation of congenital hepatoblastoma of a mixed type in a baby dying on the 50th day of life is described. The boy was born with a metastasis of the tumour into the left superciliary area. The process of hepatoblastoma metastasising had begun in the intrauterine period. The main and metastatic nodes of the tumour consisted of epithelial and mesenchymal components. The multicomponent structure of the tumour attests to its origin from a pluripotent blastoma like Wilms tumour. In addition to the hepatoblastoma with disseminated metastases the boy had malformations in the liver and kidneys. The combination of hepatoblastoma with congenital malformations appears to be due to the effect on the fetus of some harmful factors in the first trimester of pregnancy (toxicosis, influenza).