Living donor liver transplantation in a patient with giant hepatic hemangioma complicated by Kasabach-Merritt syndrome: Report of a case

We herein present a case of unresectable giant hepatic hemangiomas with Kasabach-Merritt syndrome which was successfully treated by living donor liver transplantation using a left lobe graft. The patient was a 45-year-old woman who complained of abdominal distension. Two sessions of transarterial embolization were performed, but failed to reduce the size of the tumor. The hepatic tumors were thus judged untreatable and the only option for a cure was to offer living donor liver transplantation, because of the tumor size, its location, and the association with Kasabach-Merritt syndrome. A left lobe graft with the middle hepatic vein donated by her 47-year-old brother was transplanted under venovenous bypass. The postoperative course of the recipient was complicated by small-for-size graft syndrome, which developed after episodes of acute cellular rejection on postoperative day 8 and sepsis on day 31. The patient successfully recovered from the complications and was discharged on day 72, and she remains well at 10 months after transplantation. In conclusion, living donor liver transplantation was found to be an effective option for the treatment of a patient with unresectable giant hepatic hemangiomas complicated by Kasabach-Merritt syndrome.     

A case of intrahepatic cholangiocarcinoma successfully treated by hepatic arterial infusion chemotherapy

The patient was a 67-year-old man who had been operated for eshophageal cancer 4 years ago. He was diagnosed as intrahepatic cholangiocarcinoma by CT after 2 years of the operation. After admission to our hospital, he was treated by hepatic arterial infusion chemotherapy with CDDP, levofolinate calcium (L-LV) and 5-FU with chronomodulation. After a few more months of the treatment, abdominal CT revealed that the size of hepatic tumor decreased remarkably. There were no side effects without bone marrow suppression (grade 1). It seemed that hepatic arterial infusion chemotherapy with chronomodulation may be an effective strategy against intrahepatic cholangiocarcinoma in high risk case.     

Antitumor activity of histone deacetylase inhibitors in non-small cell lung cancer cells: development of a molecular predictive model

To ascertain the potential for histone deacetylase (HDAC) inhibitor-based treatment in non-small cell lung cancer (NSCLC), we analyzed the antitumor effects of trichostatin A (TSA) and suberoylanilide hydroxamic acid (vorinostat) in a panel of 16 NSCLC cell lines via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSA and vorinostat both displayed strong antitumor activities in 50% of NSCLC cell lines, suggesting the need for the use of predictive markers to select patients receiving this treatment. There was a strong correlation between the responsiveness to TSA and vorinostat (P < 0.0001). To identify a molecular model of sensitivity to HDAC inhibitor treatment in NSCLC, we conducted a gene expression profiling study using cDNA arrays on the same set of cell lines and related the cytotoxic activity of TSA to corresponding gene expression pattern using a modified National Cancer Institute program. In addition, pathway analysis was done with Pathway Architect software. We used nine genes, which were identified by gene-drug sensitivity correlation and pathway analysis, to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. The prediction performance of the support vector machine model was validated by an additional nine cell lines, resulting in a prediction value of 100% with respect to determining response to TSA and vorinostat. Our results suggested that (a) HDAC inhibitors may be promising anticancer drugs to NSCLC and (b) the nine-gene classifier is useful in predicting drug sensitivity to HDAC inhibitors and may contribute to achieving individualized therapy for NSCLC patients.     

Regulatory polymorphisms of multidrug resistance 1 (MDR1) gene are associated with the development of childhood acute lymphoblastic leukemia

The aim of this study is to determine whether the polymorphisms of the MDR1 gene are associated with the development of childhood acute lymphoblastic leukemia (ALL).

The MDR1 gene polymorphisms, −2352 G > A, −934A > G, −692T > C (5′ regulatory region) and 3435C > T (exon 26), were examined in 157 ALL patients and 96 healthy children. The amounts of MDR1 mRNA were quantified in 54 healthy individuals using normal peripheral blood mononuclear cells to evaluate the effect of each polymorphism on the gene expression.

The frequency of the G/G genotype of the −2352 G > A was significantly higher in ALL than in controls (74/109 versus 52/96, p = 0.04). The frequency of the T/T genotype of the 3435C > T was also significantly higher in ALL (29/118 versus 10/96, p = 0.006). In a haplotype analysis using the 5′ regulatory sites, the frequency of a certain haplotype was higher in ALL than in controls (59/90 versus 42/88, p = 0.048). When the −2352G > A was examined in different age groups, patients aged six or older were found to have the G/G genotype more frequently than the controls (42/51 versus 52/96, p = 0.0014), while no difference was observed in the younger age group. The amounts of MDR1 mRNA were significantly higher in either G/G or G/A genotype of the −2352 G > A than in A/A genotype (p = 0.04).

The present study suggests that the genetic background of MDR1 may be associated with the development of childhood ALL, possibly due to a quantitative change in the MDR1 gene resulting from genetic polymorphisms.     

Effect of lafutidine, a novel histamine H2-receptor antagonist, on monochloramine-induced gastric lesions in rats: Role of capsaicin-sensitive sensory neurons

BACKGROUND: Lafutidine ((+/-)-2-(furfurylsulfinyl)-N-(4-(4-(piperidinomethyl)-2-pyr idyl)oxy-(Z)-2-butenyl)acetamide) is a novel histamine H2-receptor antagonist and has been shown to exhibit a potent gastroprotective activity in addition to its antisecretory action. In the present study, we examined the effects of lafutidine on the mucosal ulcerogenic and potential difference (PD) responses induced by monochloramine (NH2Cl) in rat stomachs. METHODS: Oral administration of NH2Cl at 120 mmol/L produced haemorrhagic lesions in the stomach in unanaesthetized rats. RESULTS: Lafutidine (3-30mg/kg), given p.o., showed a dose-dependent and significant inhibition against damage caused by NH2Cl: the effect was significant at 10 mg/kg or greater but disappeared almost totally in the sensory deafferented animals following capsaicin pretreatment. Likewise, capsaicin (10 mg/kg, p.o.), but not cimetidine (100 mg/kg, p.o.) exhibited a potent protection against NH2Cl-induced gastric lesions. Topical application of NH2Cl (10 mmol/L) reduced transmucosal PD in ex-vivo stomachs of anaesthetized rats, but this PD response was also prevented by pre-exposure to lafutidine, in a dose-dependent and sensory neuron-sensitive manner. Mucosal exposure to NH4OH (60 mmol/L) also caused PD reduction in ex-vivo stomachs made ischaemic by bleeding from the carotid artery (1 mL/100 g bodyweight), resulting in severe gastric lesions. These ulcerogenic and PD responses caused by NH4OH plus ischaemia were attenuated by prior application of lafutidine as well as taurine, a scavenger of NH2Cl. The former effect was, again, dependent on the sensory neurons. Intraluminal capsaicin but not cimetidine was also effective in preventing a PD response to NH2Cl. CONCLUSIONS: These results suggest that lafutidine, but not cimetidine, protects the stomach against NH2Cl, whether occurring endogenously or administered exogenously and that this action may be mediated by capsaicin-sensitive sensory neurons.