Transient myeloproliferative disorder (TMD), an acute leukemia-like disorder in neonates with Down's syndrome, is characterized by spontaneous regression of abnormal blast growth. Because proliferating blasts frequently express phenotypes of megakaryocytic lineage and, as a result, this disorder resembles acute megakaryoblastic leukemia (AMKL), it would be of interest to determine whether myelofibrosis, a common complication of AMKL, is also present in TMD. Pathologic observations of four autopsy cases of TMD showed that myelofibrosis was not present in any of them, whereas intralobular diffuse liver fibrosis was present in all of them. Laboratory data of four additional cases showed hepatic dysfunction in all of them, suggesting a close association between hepatic lesions and TMD. From these results, we propose a hypothesis that the abnormal blasts with megakaryocytic properties in TMD originate from the fetal liver and cause liver fibrosis, as AMKL cells are thought to cause myelofibrosis by producing collagen-stimulating cytokines in the bone marrow. This hypothesis also seems to explain some other unique aspects of TMD.

Vascular invasion and intrahepatic metastasis by hepatocellular carcinoma are important factors predisposing to tumor recurrence. Recurrences of this malignancy occur frequently in residual liver, and its prevention is one of the most important factors in obtaining better surgical survival. Fifty patients who underwent hepatectomy for invasive hepatocellular carcinoma with vascular invasion and/or intrahepatic metastases were studied to evaluate the effect of adjuvant bolus hepatic arterial infusion of iodized poppyseed oil (Lipiodol) containing anticancer drugs in preventing recurrence and in prolonging survival. Patients were assigned to two treatment groups. Twenty-three of the fifty patients received adjuvant bolus infusion of Lipiodol containing doxorubicin and mitomycin C, whereas 27 patients received no therapy. The disease-free survival rate for the patients who received adjuvant therapy was significantly better (p < 0.05) than that for those who did not when measured at 172, 516, 688 and 860 days after hepatectomy, and the disease-free survival curve for patients with adjuvant therapy was significantly (p = 0.0237) better than that without adjuvant therapy. The cumulative survival rates and curves were not significantly different between the two groups. While adjuvant hepatic arterial infusion of Lipiodol containing anticancer drugs was effective in improving disease-free survival, the effect was not satisfactory. Further trials of adjuvant chemotherapy are required to improve the surgical survival of hepatocellular carcinoma patients.

FK506 is a powerful immunosuppressive drug currently in use that inhibits the activation of several transcription factors (nuclear factor (NF)-AT and NF-B) critical for T cell activation. We show here that, contrary to the situation in T cells, FK506 activates transcription factor NF-B in nonlymphoid cells such as fibroblasts and renal mesangial cells. We further show that FK506 induces NF-B-regulated IL-6 production in vitro and in vivo, in particular in kidney. IL-6 has been shown previously to produce renal abnormalities in vivo, such as mesangioproliferative glomerulonephritis. Similar renal abnormalities were also observed in FK506-treated animals. These results thus suggest a causal relationship between FK506-induced NF-B activation/IL-6 production and some of FK506-induced renal abnormalities. (

Eighty cases (82 tumors) of hepatic angiomyolipoma (AML) from the world literature were reviewed, including our 8 cases. The tumors occurred predominantly in females (female:male ratio, 56:24). Only six patients (7.5 %) had associated tuberous sclerosis. The majority of the tumors (95%) occurred in non-cirrhotic, almost normal liver. The tumors usually presented as a hyperechoic mass on ultrasound (US) examination, a hypodense mass on computed tomography (CT) scan, and hyperintense mass on both T1-and T2-weighted magnetic resonance (MR) imagings. However, the imaging features of the tumor were occasionally variable according to the content of fat tissue component, and the tumors could not be clearly differentiated from other hepatic tumors, particularly hepatocellular carcinoma (HCC), based on the imaging features alone. Tumor location was recorded in 81 tumors; 44 were located in the right lobe, 30 in the left, 5 in the caudate, and 2 in both lobes of the liver. The tumor diameter ranged from 0.3 to 36 cm (mean, 8.0 + 7.0cm). Macroscopically, the tumors usually had no fibrous capsule. The cut surface was yellow to dark brown depending on the amount of fat tissue or blood vessels. The histologic features were quite variable and occasionally included atypical and/or pleomorphic cells, which could lead to the erroneous diagnosis of a variety of benign and malignant tumors, including lipoma, leiomyoma, HCC, hepatoblastoma, leiomyosarcoma, and malignant fibrous histiocytoma. Extramedullary hematopoiesis was found in 33% of the tumors. Reactivity of the tumor cells of the liver with HMB-45, a melanoma-specific antibody, can accurately establish the diagnosis of AML.

Both untreated and treated primary neuroblastomas from 52 patients were analyzed to determine the correlation between the amplification of N-myc oncogene and various prognostic factors. Amplification of N-myc was observed in eight of 28 untreated cases and in 12 of 24 treated cases. As a whole, 12 of 18 tumors (67%) in Stage IV had N-myc amplification, but there were fewer cases in the unadvanced disease stage, as reported previously by others. Furthermore, the authors detected N-myc amplification in three of nine tumors in Stage IV-S, although the amplification was less than 50 copies. Analysis of progression-free survival at 24 months revealed that amplification of N-myc was associated with the worst prognosis (P less than 0.001). In the untreated group, no amplification of N-myc was detected in any of two ganglioneuromas and four ganglioneuroblastomas, whereas amplification of N-myc was observed in all two round-cell and six of 20 rosette fibrillary neuroblastomas. On the other hand, the authors detected amplification of N-myc in three of eight less differentiated ganglioneuroblastomas in the treated group and observed the worst prognosis in these three patients. The total percentage of the cases from both untreated and treated groups suggest that amplification of N-myc may occur more frequently in undifferentiated types of neuroblastomas than in less malignant types. In conclusion, the amplification of N-myc in neuroblastomas was closely associated with the worst prognosis, which was suggested by both disease stage and histologic characteristics.