Surgery for hepatic neuroendocrine tumors: a single institutional experience in Japan

BACKGROUND: Surgical resection has been advocated as an effective treatment for hepatic neuroendocrine tumors (HNETs) in Western countries, but few data are available to define its indications. We evaluated the results of Japanese patients to determine the prognostic factors and the feasibility of our aggressive surgical approach. METHODS: The records of all consecutive patients who underwent surgical resection for HNETs at our institution were retrospectively reviewed. Patients were selected for surgery if all tumors were deemed resectable, regardless of their extent. RESULTS: A total of 21 patients were identified. Bilobar disease was present in 13 patients (62%). Eleven patients (52%) underwent major hepatectomy, which included right trisectionectomy, extended right or left hepatectomy and right hepatectomy. No in-hospital death occurred. The overall 1-, 3- and 5-year survival rates were 95, 68 and 41%, respectively, with a median follow-up of 34 months. Metastatic HNETs from bronchopulmonary primaries exhibited significantly poor outcome compared with other primary sites (P = 0.04). Patients who underwent curative resection had an improved overall 5-year survival rate of 73% compared with palliative resection (0%, P = 0.01). The longest survival in the latter group was 57 months. Complete symptom resolution rate was 92%. CONCLUSIONS: This is the first study from Asia demonstrating the safety of aggressive hepatic resection for HNETs. Significant symptom relief and long-term survival were achieved irrespective of the extent of disease or the magnitude of operation. Metastatic HNETs from bronchopulmonary primaries may represent a more lethal subset of tumors.     

Establishment and characterization of the new splenic marginal zone lymphoma-derived cell line UCH1 carrying a complex rearrangement involving t(8;14) and chromosome 3

A new cell line, designated UCH1, was established from a patient with splenic marginal zone lymphoma (SMZL). UCH1 cells feature a mature B-cell phenotype, characterized by surface IgM +, kappa+, CD5-, CD10-, CD19+ and CD20+. The BCL2 and BCL6 genes retained their germ-line configurations and overexpression of cyclin D1 was not detected. UCH1 cells carry numerical and structural aberrations in chromosome 3, but these were too complex to be analyzed with the conventional G-banding method. Spectral karyotyping (SKY) and fluorescence in situ hybridization analysis clearly demonstrated the presence of a balanced translocation between chromosomes 8 and 14 [t(8;14)(q24;q32)] in the complex aberrations involving chromosome 3. The results of Southern blot analysis supported this finding by showing rearrangement of the c-myc gene in UCH1 cells. SKY analysis also identified a translocation involving chromosome band 18q21, to which BCL2 and MALT1 genes were assigned, suggesting their implication in the development or progression of SMZL.     

Characterization of skin blister fluids from children with Epstein–Barr virus‐associated lymphoproliferative disease

Epstein–Barr virus (EBV)‐associated T‐ or natural killer (NK)‐cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV‐infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)‐like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV‐infected lymphocytes. However, blister fluids have not been fully assessed in patients with this disease. Blister fluids were collected from three patients with EBV‐associated LPD: two with HMB and one with HV. Immunophenotyping of blister lymphocytes and measurement of tumor necrosis factor (TNF)‐α in blister fluids were performed. The patients with HMB and HV exhibited markedly increased percentages of NK and γδ T cells, respectively, in both peripheral blood and blister fluids. These NK and γδ T cells strongly expressed the activation marker human leukocyte antigen‐DR and were considered to be cellular targets of EBV infections. TNF‐α was highly elevated in all blister fluids. Severe local skin reactions of EBV‐associated LPD may be associated with infiltrating EBV‐infected lymphocytes and a high TNF‐α concentration in blister fluids.     

A case of accessory hepatic duct entering cystic duct successfully treated by laparoscopic cholecystectomy for cholecystolithiasis

Although laparoscopic cholecystectomy is a well-established surgical procedure, an accessory hepatic duct (AcHD) entering the cystic duct is poorly understood. A 77-year-old woman with symptomatic cholecystlithiasis was referred to our hospital. Abdominal ultrasonography indicated several small stones in the gall bladder. Magnetic resonance cholangiopancreatography (MRCP) did not reveal an anomalous cystic duct. Dissecting the gall bladder bed at operation, AcHD entering the cystic duct was suspected. Intraoperative cholangiography revealed that B5 branch entered the cystic duct. We ligated the AcHD, and divided it. Laparoscopic cholecystectomy was completed, and the patient was discharged without any complication. A week after the operation, MRCP showed that ventral branch of B5 was dilated. The patient showed no symptom for more than a year. The present case exhibited extremely rare AcHD entering the cystic duct, which was hardly recognized before surgery. It is possible to recognize such anomalous variants with standard laparoscopic approach based on 2018 Tokyo Guidelines and with attention to the possibilities of AcHD entering the cystic duct.     

Methamphetamine-Induced Modification of Dopamine Metabolism in Cultured Striatal Astrocytes

Abstract: The role of striatal astrocytes in the metabolic processing (by deamination) of methamphetamine-released dopamine is not known. To investigate the relationship between methamphetamine and dopamine metabolism, we measured 6-hydroxydopamine, dopamine and 3, 4-dihydroxyphenylacetic acid (DOPAC) concentrations following methamphetamine treatment of cultured striatal astrocytes prepared from 1-2 day-old rats. Addition of low concentrations of dopamine (5×10^–5 to 5×10^–4 M) to cultured astrocytes increased DOPAC levels in a dose-dependent fashion while higher concentrations (5×10^–3 to 10^–2 M) inhibited its metabolism and induced formation of 6-hydroxydopamine. Under the same experimental conditions, 10^–4 M dopamine in combination with methamphetamine (10^–5 to 10^–3 M) inhibited DOPAC formation and increased dopamine levels in a dose-dependent fashion, but the formation of intracellular 6-hydroxydopamine was not evident. Deprenyl (10^–5 or 10^–4 M), an inhibitor of monoamine oxidase B, and pargyline (10^–5 or 10^?4 M), a non-selective monoamine oxidase inhibitor, completely inhibited DOPAC formation and increased dopamine levels, while clorgyline (10^?5 or 10^–4 M), an inhibitor of monoamine oxidase-A, only partially inhibited DOPAC formation (42 or 45% of control, respectively). These results support the hypothesis that methamphetamine inhibits monoamine oxidase and causes increases in dopamine levels in cultured striatal astrocytes.