Yasuharu Ohno

Persistent hepatitis associated with chronic active Epstein-Barr virus infection.

A previously healthy boy developed persistent hepatitis without fever or lymphoproliferative disorder. Although serologic tests were not indicative, Epstein-Barr virus (EBV) genome and transcripts were detected from the liver tissue, and real time PCR detected extremely high levels of EBV viremia. EBV infection should be included in the differential diagnoses of hepatitis of unknown etiology, even with unremarkable serologic data.

Annular pancreas causing localized recurrent pancreatitis in a child: report of a case.

Annular pancreas is a rare congenital anomaly. We report a case of relapsing acute pancreatitis localized in the annulus of an annular pancreas in a young child. A 6-year-old boy complained of abdominal pain and we made a diagnosis of acute pancreatitis based on blood biochemistry results. Over the subsequent 12 months, he experienced two more pancreatitis-like attacks. Endoscopy revealed a duodenal stenosis in the second portion of the duodenum. Ultrasound, computed tomography, and magnetic resonance imaging depicted a ring of pancreatic tissue encircling the duodenum with a duct in the tissue, manifesting dilatation with a characteristic circular pattern around the duodenum. No dilatation of the dorsal pancreatic duct or pancreatic divisum was found. Based on these findings, we diagnosed acute pancreatitis localized in an annulus in an annular pancreas. This case report suggests that an annular pancreas may predispose to localized relapsing acute pancreatitis even in a child.

Changes in liver regenerative factors in a case of living-related liver transplantation

Liver regeneration in a patient with fulminant hepatic failure (FHF) who underwent living‐related partial liver transplantation (LRLT) was investigated regarding hepatic growth factors. The patient was a 16‐yr‐old Japanese male who developed severe subacute FHF. LRLT was performed using an extended left lobe of the ABO matched patients mother. In the recipient, the pre‐transplant levels of both plasma hepatocyte growth factor (HGF) and transforming growth factor (TGF)‐β were extremely high and rapidly decreased following the liver replacement. The liver volume evaluated using a CAT scan increased 195% after 2 wk in graft liver and 110% after 2 wk in the hepatectomized donor. The explanted liver (FHF liver), the liver from donor (normal liver), and the graft liver [the 3rd post‐transplant day (POD 3)] were all investigated immunohistochemically. FHF liver: No liver regeneration was observed [proliferative cell nuclear antigen (PCNA) labeling index (L.I.): 0%]. In the liver, both HGF in the hepatocytes and c‐met on the membrane of the hepatocytes were positive. TGF‐β was positive in the hepatocytes and no apoptosis was detected by the TUNEL method. Donor liver (POD 0): Few PCNA stained hepatocytes were detected. No HGF was detected but c‐met was clearly detected on the cell membrane of the hepatocytes. Neither TGF‐β nor apoptosis was detected. Graft liver (POD 3): The PCNA L.I. was conspicuous at 40%. HGF was positive in non‐parenchymal cells and c‐met was positive in the cytoplasm of the hepatocytes. TGF‐β was negative while apoptosis was positive in the zone 3 hepatocytes. In conclusion, these findings suggested that the liver of the patient with FHF did not respond to liver regenerative stimulus, in part, through involvement of inhibitor TGF‐β. On POD 3, the transplanted graft was in a vigorous regenerative status in comparison to that in the hepatectomized donor. The HGF/c‐met system is thought to be involved in the mechanism of regeneration. Intrahepatic apoptosis was detected in the graft on the 3rd post‐transplant day probably due to transient ischemia in the liver, which was not related to the Fas/Fas‐ligand system.

Situs ambiguous with gastric cancer: report of a case.

Situs ambiguous is an unpredictable anomaly characterized by disorder of the organ arrangement in the chest and abdomen. We report a case of situs ambiguous found incidentally in a 73-year-old man with gastric cancer. Preoperative imaging showed polysplenia, a bridging liver, a midline gall bladder, and pancreatic divisum. The vessels around the stomach were clearly shown by computed tomography with multiplanar reconstruction (MPR). Computed tomography with MPR proved a good diagnostic tool for identifying both the abdominal vessels and the location of the organs. Based on a precise evaluation of this unusual anatomy, we performed distal gastrectomy with dissection of the regional lymph nodes.

Early development of cavernomatous vasculatures in portal venous thrombosis: morphometric kinetics in rabbit model.

We tried to establish an animal model of portal venous thrombosis in order to analyze the ensuing pathological changes of the liver. An emulsion with Escherichia coli endotoxin and Lipiodol-Ultra-Fluide was injected into the portal vein of the left anterior lobe of the rabbit liver. The target lobe and portal vein were time-sequentially examined. In the experimental groups, it was found that fibrin thrombi were formed in the portal vein within 48 h after the injection and thrombi persisted for over 7 days. In an association with thrombus formation, numerous tortuously dilated vasculatures developed in the portal tract (cavernomatous vasculature) within 48 h. Both the number and the total area of the cavernomatous vasculatures increased from 2- to 3-fold more than in the control group at 72 h. The majority of proliferated vasculatures were positive for alpha-smooth muscle actin, thus suggesting that they derived from the portal venous branches. In conclusion, portal endotoxemia may be one of the pathogenetic factors of portal venous thrombosis and, in this model, the cavernomatous vasculatures rapidly developed from the portal venous branches.

Possible protection of sinusoidal endothelial cells by endothelin B receptor during hepatic warm ischemia-reperfusion.

PurposeEndothelins (ETs) are important regulators of the hepatic microcirculation. We investigated the pure biological roles of endothelin B receptors (ETB-Rs) on hepatic warm ischemia–reperfusion (I/R) injury using ETB-R deficient spotting lethal (sl) rats.MethodsHomozygous (sl/sl) and wild-type (+/+) rats were exposed to 60 min of 92% partial hepatic ischemia and then were killed at 2, 6, and 24 h, and 3 and 7 days after reperfusion. We measured the serum alanine aminotransferase (ALT) levels to assess hepatocyte injury, and the serum hyaluronic acid (HA) levels and factor VIII-related antigen (FVIIIRAg) staining to assess sinusoidal endothelial cell (SEC) injury. We also measured the concentrations of ET-1 and nitrite (NO2−) and nitrate (NO3−) of liver tissue samples.ResultsAlthough no significant difference was observed in the ALT levels, the HA levels were significantly elevated at an early stage after reperfusion in the sl/sl rats. Regarding FVIIIRAg staining, positive SECs were enhanced in the sl/sl rats. The ET-1 levels were also significantly elevated at an early stage after reperfusion in the sl/sl rats. Regarding the NO2− and NO3− levels, no significant difference was observed.ConclusionEndothelin B receptor was shown to have a protective effect on SECs through the inhibition of ET-1 during hepatic warm I/R injury.

Two infantile cases of congenital myotonic dystrophy with cholelithiasis/cholestasis

Myotonic dystrophy (MyD) is an autosomal dominant disorder characterized by myotonia, muscle dystrophy, cataract and EEG changes. MyD is classified into two types, DM1 1 and DM2. 2,3 DM1, a classical type of MyD, is caused by expansion of unstable trinucleotide (CTG) repeats at the 3 ′ untranslated region of a gene on chromosome 19q13.3 encoding myotonin protein kinase (DMPK). 1 Severity of this disease is related to the length of the triplet repeats. Severe type of MyD, known as congenital myotonic dystrophy (CMyD), may have thousands of repeats in the DMPK gene. 4,5 Clinical features of CMyD in the newborn period include polyhydramniosis, respiratory distress and abdominal distention. 6 If CMyD patients can survive beyond the infant period, the above symptoms are gradually improved. However, other symptoms such as facial weakness, mental retardation, arrhythmia, and cataract gradually progress. Cholelithiasis has been occasionally associated with adolescent to adult patients with MyD; however, this complication is very rare in the infantile period. 5 We report two Japanese infants with CMyD who had cholelithiasis/ cholestasis.

Congenital occurrence of solitary infantile myofibromatosis of the spleen.

Infantile myofibromatosis (IM) is a rare soft tissue tumor of infancy and childhood. We report the case of a newborn girl with an abdominal tumor discovered at 32 weeks of gestation by fetal ultrasound. She underwent a laparotomy for an unexplained abdominal mass 20 days after birth. The tumor originated from the spleen and was removed by splenectomy. There were no other abnormal findings on diagnostic modalities. Based on the histological examinations, the tumor was diagnosed as an IM. Although extremely rare during the neonatal period, solitary type IM should be considered as a differential diagnosis of the splenic tumor.

Hyperbaric oxygen therapy for intestinal obstruction in children: An exceptional experience in a compromised child

Intestinal obstruction in a 2-year-old girl with a histologically proven diagnosis of retroperitoneal yolk sac carcinoma developed after the second course of anticancer chemotherapy. Nonoperative treatment was not effective. Because the patient had fallen into a state of chemotherapy-induced myelosuppression, surgery was ruled out. Thus, hyperbaric oxygen therapy was the next treatment of choice. It was performed twice under hyperbaric oxygen conditions at 2.8 atmospheric pressure for 111 minutes. After the procedure, her general status recovered well. The air-fluid level disappeared on the radiograph, and no adverse effects were observed. Later, a surgical removal of the primary tumor was performed successfully, but an intestinal resection was not required. This is the first instance in which we performed hyperbaric oxygen therapy on a child in the management of an intestinal obstruction. Based on the successful outcome in this case, hyperbaric oxygen therapy is suggested to be a useful adjunct to nonoperative therapy for intestinal obstruction when a patients overall state does not allow operative intervention.

Probable Noonan syndrome in a boy without PTPN11 mutation, manifesting unusual complications

© 2009 Japan Pediatric Society Noonan syndrome (NS; MIM No.163950) is autosomal dominant disorder characterized by short stature, cardiovascular defects, and dysmorphological features, including hypertelorism, a webbed neck, a pectus excavatum and cuvitus valgus. Mental retardation and hearing diffi culty are often observed in affected individuals. Approximately 40% of NS patients have protein-tyrosine phosphatase, non-receptor type 11 ( PTPN11 ) mutations. 1 The genotype – phenotype correlation and phenotypical heterogeneity between the two genotypes have been reported. 1 Pulmonary valve stenosis is more frequent in PTPN11 mutation-positive patients than mutation-negative patients, 1 whereas hypertrophic cardiomyopathy is more frequent in PTPN11 mutation-negative patients than mutation-positive patients. Gastrointestinal complications are very few among NS patients. Double outlet right ventricle (DORV) and congenital rectal atresia have never been associated with the PTPN11 mutation-negative NS patients. We here report a Japanese boy with DORV and rectal atresia. He fulfi lled clinical criteria for NS and had no PTPN11 gene mutation.