Recurrence of hepatocellular carcinoma 102 months after successful eradication and removal of membranous obstruction of the inferior vena cava

We report a 54-year-old Japanese woman who developed liver tumors 102 months after hepatic resection for hepatocellular carcinoma (HCC) and percutaneous transluminal angioplasty (PTA) for membranous obstruction of the inferior vena cava (MOVC), which is one form of Budd-Chiari syndrome. In the present admission workup showed no evidence of co-infection with hepatitis B and C viruses. Dynamic computed tomography (CT) and magnetic resonance imaging showed an enhanced lesion, 1.5cm in diameter, in segment 3 of the liver, and no obstruction of the inferior vena cava after PTA. CT during both arterial portography and hepatic arteriography revealed another lesion, showing different hemodynamics, in segment 2. The patient therefore underwent hepatic resection, and the tumors were diagnosed histologically as HCC. The two tumors differed in their morphological features, one containing abundant fibrous stroma, whereas the other did not. The nontumorous liver tissue showed central zonal fibrosis, i.e., reversed lobulation, and partial expansion of nodule-like formations, indicating lack of progression since the situation seen at the initial hepatectomy. The presence of nontumorous liver tissue showing the above features suggests that, even after successful treatment for relief of congestion, patients who have had MOVC should be followed closely for as long as possible because of the risk of HCC recurrence. This is the first reported case of HCC recurrence after successful treatment of MOVC.     

Establishment of a leukaemic cell line from a patient with acquisition of chromosomal abnormalities during disease progression in myelodysplastic syndrome

Summary. A cell line designated SKM-1 was newly established from leukaemic cells of a 76-year-old Japanese male patient with monoblastic leukaemia following myelodysplastic syndrome (MDS). The cells were obtained from peripheral blood of the patient when he lost multiple point mutations of ras genes with acquisition of chromosomal abnormalities during disease progression in MDS. The cells grew as a single floating cell, and have been continuously growing with the morphological characteristics of immature monoblasts by serial passages during the past 42 months with a doubling time of about 48 h. By cytochemical analysis. the cloned cells were positive for butyrate esterase, but negative for the Epstein-Barr virus associated nuclear antigen. Phenotypic analysis revealed the expression of myelomonocyte specific antigens such as CD4, CD13, CD33 and HLA-DR. Cells from the primary peripheral blood and those from SO passages of the SKM-1 cell line both possessed no activated ras genes but showed karyotype abnormalities with 46.XY, del(9)(q13;q22), der(17) t(17:?)(p13:?). The SKM-1 cells have two mutations in p53 gene and overexpress the pS3 products. This cell line may contribute to a better understanding of molecular mechanisms in the progression from MDS to myelogenous leukaemia.     

Glucocorticoids induce G1 cell cycle arrest in human neoplastic thymic epithelial cells

Purpose Glucocorticoids exert anti-proliferative effects in various cell types and have long been known to induce apoptosis in thymocytes. Although a few reports have described the regression of human thymoma with glucocorticoid therapy, its effects on neoplastic thymic epithelial cells (TECs) have not been reported. In the present study, we investigated glucocorticoid receptor (GR) expression on neoplastic TECs and the effects of glucocorticoids in vitro on the cell cycle progression of tumor cells.Patients and methods Thymoma specimens were obtained during surgery from 21 patients. Three of the specimens with glucocorticoid therapy were examined using the TdT-mediated dUTP-biotin nick-end labeling method. Primary tumor specimens from ten untreated thymomas were examined for GR expression by immunohistochemistry. Isolated neoplastic TECs from the remaining eight untreated thymomas were examined using immunohistochemistry, flow cytometric and cell cycle analysis.Results GR are expressed on neoplastic TECs as well as on non-neoplastic thymocytes in thymomas, regardless of WHO histological classification. Glucocorticoids caused an accumulation of TEC in G0/G1 phase in all cases examined (n=6), and also induced apoptosis in the three with the lowest levels of Bcl-2 expression.Conclusions Our results indicate that neoplastic TECs express GR and that glucocorticoids directly suppress their in vitro proliferation.     

Separation Methods of T Cells,Natural Killer,and Dendritic Cells from Peripheral Blood of Cancer Patients using Interleukin-2 and Functional Analysis of Natural Killer Cells after Separation

We aimed to induce three different immune cell subsets from a single blood sample from cancer patients to target different biological characters of cancer cells. In the presence of 6000 IU/ml IL-2, natural killer (NK) cells adhere to plastic. By using this ability, we could separate dendritic cells, T cells, and NK cells from peripheral blood mononuclear cells. The cultured NK cells demonstrated higher nonspecific cytotoxicity against tumor cell lines than did the T cells. Furthermore, adherent NK cells demonstrated higher cytotoxicity than nonadherent NK cells, although there was no difference between adherent and nonadherent NK cells in natural cytotoxicity receptors (NKp30, NKp44, NKp46) and NKG2D expression. With these results, we confirmed that we could induce dendritic cell, T cell, and higher cytotoxic NK cells from a single blood draw, and this methodology facilitates to the use of these cells for clinical grade conditions.     

Percutaneous transhepatic gallbladder stenting for recurrent acute acalculous cholecystitis after failed endoscopic attempt

Endoscopic gallbladder stenting is useful palliative therapy for acute cholecystitis in high‐risk patients. Although the success rate of endoscopic gallbladder stenting is 79%–100%, an alternative method has not been reported. We succeeded in employing a method for percutaneous gallbladder stenting (PTGS) and herein describe this new method. A patient with acute acalculous cholecystitis related to ischemic atherosclerotic vascular disease, cholangitis due to Lemmel syndrome, and severe congestive heart failure underwent PTGS through the cystic duct from the gallbladder to the duodenal papilla, because an endoscopic method failed in the treatment of Lemmel syndrome. Because we were unable to place endoscopic transpapillary gallbladder drainage, percutaneous transhepatic gallbladder drainage (PTGBD) was performed and both the cholecystitis and cholangitis ceased. PTGS was performed as an alternative to endoscopic gallbladder stenting. Access to the cystic duct and gallbladder was obtained by the PTGBD route, using a guidewire (0.035‐inch diameter) and seeking catheter (6.5 Fr) under fluoroscopic control. A 7‐Fr 12‐cm double‐pigtail biliary polyethylene stent was placed. The patient remained asymptomatic for 3 months after the PTGS until he died, of an acute recurrent myocardial infarction. This new PTGS placement is an alternative treatment for symptomatic gallbladder disease in patients with increased operative risk when the endoscopic method is unsuccessful.     

Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use?

Background Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects.Methods A total of 22 healthy male, Helicobacter pylori-negative volunteers participated in this randomized, two-way crossover study. They were randomly assigned to receive a single oral dose of 10mg lafutidine or 20mg rabeprazole after fasting overnight (12 subjects, fasting study) or after eating a test meal (noodles, 364kcal; protein, 10.1g; fat, 16g; carbohydrates, 44.9g; NaCl, 1.1g; 10 subjects, postprandial study). Intragastric pH was monitored continuously for 6h after treatment. The other drug was given after a washout period of at least 7 days, and intragastric pH was similarly monitored.Results In the fasting study, lafutidine sustained pH at >3 and >4 during the second, third, fourth, fifth, and sixth hours of the study for significantly longer than rabeprazole. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In the postprandial study, lafutidine sustained pH >3 and >4 for longer periods than rabeprazole during the third, fourth, fifth, and sixth hours of the study. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole.Conclusions Lafutidine 10mg produces a prompter rise in intragastric pH than rabeprazole 20mg in fasting and postprandial Helicobacter pylori-negative male subjects.