Domino liver transplantation from a living related donor

BACKGROUND: Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery lie in the small size of the graft volume and the short length of the vascular cuffs in the graft. METHODS: The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient. At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A). RESULTS: The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence. CONCLUSION: A domino OLT from the living related donor can therefore be done safely when careful attention is paid to the graft volume and the length of the vascular cuffs for anastomosis.     

Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery.

PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. PATIENTS AND METHODS: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. RESULTS: Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001). CONCLUSION: Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone.     

Modulation of platelet aggregation after percutaneous transluminal angioplasty of the iliac artery for atherosclerosis obliterans

BACKGROUND: Platelet aggregation is modulated by blood flow. We investigated whether platelet function is altered during percutaneous transluminal balloon angioplasty in patients with atherosclerosis obliterans. METHODS: Blood samples were obtained from the iliac artery in 9 lower limbs of 7 patients undergoing percutaneous balloon angioplasty of the iliac artery. An agonists-induced platelet aggregation test was performed with an aggregometer. Femoral blood flow was measured with a Doppler velocimeter before and after the procedure. RESULTS: Before dilatation, the maximum platelet aggregation rates (+/- SEM) induced by adenosine phosphate, epinephrine, and arachidonic acid were 54.7% +/- 5.8%, 64.8% +/- 4.3%, and 60.5% +/- 6.1%, respectively. After angioplasty, these values reduced to 36.7% +/- 4.1%, 36.1% +/- 8.6%, and 40.1% +/- 5.0%, respectively (P < .05). The pre-procedural ankle-brachial pressure index, mean flow rate, mean velocity, and shear stress variation were 0.63 +/- 0.1, 218.1 +/- 32.1 mL/min, 9.4 +/- 1.1 cm/sec, and 60.6 +/- 17.7 dyne/cm2, respectively. The mean velocity at the stenotic lesion was 215.1 +/- 83.9 cm/sec, which was significantly greater than those of the distal artery or after angioplasty (P < .01). Both ankle-brachial pressure index and shear stress variation increased after angioplasty to 0.99 +/- 0.07 (P < .05) and 139.8 +/- 17.0 (P < .05) dyne/cm2, but the mean flow rate and the mean velocity (198.3 +/- 24.5 mL/min and 8.8 +/- 1.2 cm/sec after angioplasty) did not change significantly. CONCLUSIONS: These results indicate that activated platelet function at a stenosed artery was decreased after angioplasty, possibly because of normalized blood flow with reduction of stenotic lesion.     

The expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase associates with angiogenesis in epithelial ovarian cancer

Background The object of this study is to clarify the association of an angiogenic factor, PD-ECGF (platelet-derived endothelial cell growth factor/thymidine phosphorylase), with clinicopathologic factors, in this case tumor angiogenesis, in epithelial ovarian cancers. Methods Tumor specimens were obtained at the time of surgery from the primary lesion in 60 patients with epithelial ovarian cancer. Histologic cell types were assigned to tumors according to the World Health Organization classification: 26 were classified as serous adenocarcinoma, 15 as endometrioid adenocarcinoma, 9 as mucinous adenocarcinoma, 9 as clear cell carcinoma, and 1 as undifferentiated carcinoma. Surgical staging was based on the international Federation of Gynecology and Obstetrics (FIGO) staging system: 16 were stage I, 6 were stage II, 34 were stage III, and 4 were stage IV. Expression of PD-ECGF was evaluated by immunohistochemical staining. Microvessel density was assessed by immunostaining for factor VIII-related antigen in the most neovascularized area. Results Stroma cells stained more strongly than cancer cells (80% vs. 33%). The immunopositivity of PD-ECGF in stroma cells was higher in cases of advanced cancer. Expression of PD-ECGF in mucinous adenocarcinomas was significantly higher than that in serous adenocarcinomas, while PD-ECGF expression in clear cell carcinomas was significantly lower. The microvessel density in the cases with marked PD-ECGF-positive stroma cells was significantly higher than that in the cases with absent/minimal PD-ECGF-positive stroma cells (P<0.05). Conclusion The expression of PD-ECGF may play a crucial role in the promotion of angiogenesis in epithelial ovarian cancers.     

Multivariate analysis of long-term results after an axillobifemoral and aortobifemoral bypass in patients with aortoiliac occlusive disease

BACKGROUND: Controversy still remains regarding the long-term results and indications for axillofemoral bypass (AxFB). A comparison of axillobifemoral bypass (AxBFB) and aortobifemoral bypass (ABFB) was thus conducted to determine whether AxFB is an acceptable alternative vascular procedure to anatomic bypass for high-risk patients. METHODS: Sixty-three patients who underwent a total of 25 AxBFBs and 38 ABFBs for aortoiliac occlusive disease were reviewed retrospectively, and both univariate and multivarate analyses were perfomed. RESULTS: The overall survival was 82.8% at five years. A univariate analysis revealed significantly lower survival rates for patients with limb-threatening ischemia, coronary disease, and cerebrovascular disease. A multivariate analysis disclosed no significant factors influencing survival rates. The overall primary patency was 79.8% at five years. The primary patency rates for AxBFB (67.7% at five years) were significantly lower than for ABFB (88.5% at five years) based on a univariate analysis (p=0.0045). In addition, the secondary patency rates for AxBFB (80.3% at five years) were significantly lower than for ABFB (96.5% at five years, p=0.0025). A multivariate analysis disclosed significantly lower primary patency rates for grafts with a higher angiographic outflow score and simultaneous infrainguinal reconstructive procedures, but the differences between AxBFB and ABFB were not significant. CONCLUSIONS: The survival and primary patency for the AxBFB group were both inferior to the ABFB group, however a multivarate analysis disclosed no significant differences between the two groups. Poor femoral run-off and the presence of synchronous infrainguinal reconstructive procedures significantly affected graft patency, and these factors modulated the patency of AxBFB. AxFB for aortoiliac occlusive disease is therefore considered to be an acceptable procedure in appropriately selected patients.     

Local epinephrine release in the rabbit myocardial interstitium in vivo

Although several investigations have suggested cardiac epinephrine (Epi) release, local Epi release in the myocardial interstitium in vivo has not been measured. Using cardiac microdialysis in the rabbit, we measured dialysate Epi and norepinephrine (NE) concentrations as indices of myocardial interstitial Epi and NE levels, respectively. Exocytotic release induced by local administration of KCl (100 mM) through the dialysis probe increased Epi to 24.2 +/- 13.2 pg/ml from a control value of 3.2 +/- 3.6 pg/ml (P < 0.01, n = 6). Non-exocytotic release induced by the local administration of tyramine (10 microg/ml) also increased Epi to 34.6 +/- 15.3 pg/ml (p < 0.05 from control, n = 6). We conclude that Epi can be released via both exocytotic and non-exocytotic release mechanisms from the heart.     

Experimental study of the effects of deletion variant of hepatocyte growth factor on hepatic ischaemia-reperfusion injury

BACKGROUND: Hepatic ischaemia-reperfusion (IR) injury is still a serious complication following liver surgery. The effect of the deletion variant of hepatocyte growth factor (dHGF) on hepatic IR injury was examined in rats. METHODS: Male Wistar rats were divided into two groups after 90 min of partial liver ischaemia: the dHGF group which was given dHGF 0.5 mg/kg intravenously immediately after reperfusion, followed by 0.5 mg/kg every 12 h, and the control group, which received vehicle buffer only. Serum chemistry, histopathological findings and liver weights were compared between the groups. RESULTS: In the dHGF group, the increase in serum alanine transaminase and hyaluronic acid levels was significantly reduced, and the serum albumin level increased after reperfusion. The extent of hepatic necrosis 24 h after reperfusion was decreased in the dHGF group. Moreover, the proportion of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labelling-positive hepatocytes 6 h after reperfusion was reduced in the dHGF group. The non-ischaemic-, ischaemic- and whole-liver weight : body-weight ratio significantly increased in the dHGF group after reperfusion. The proportion of proliferating cell nuclear antigen-positive hepatocytes in the dHGF group markedly increased after 6 h after reperfusion in the non-ischaemic lobes, while in the ischaemic lobes it increased 24 h after reperfusion. CONCLUSION: These data suggest that dHGF not only improves recovery from IR injury, but also accelerates recovery from these injuries. dHGF may be an effective pharmacological agent for prevention and treatment of hepatic IR injury.     

Role of the endothelial-to-mesenchymal transition in renal fibrosis of chronic kidney disease

All types of progressive chronic kidney disease (CKD) inevitably induce renal fibrosis, the hallmark of which is the activation and accumulation of a large number of matrix-producing fibroblasts or myofibroblasts. The activated fibroblasts or myofibroblasts are derived from diverse origins, such as residential fibroblasts, vascular pericytes, epithelial-to-mesenchymal transition (EMT), and bone marrow (circulating fibrocytes). Recently, endothelial-to-mesenchymal transition (EndMT) or endothelial-to-myofibroblast transition has also been suggested to promote fibrosis and is recognized as a novel mechanism for the generation of myofibroblasts. Similar to EMT, during EndMT, endothelial cells lose their adhesion and apical–basal polarity to form highly invasive, migratory, spindle-shaped, elongated mesenchymal cells. More importantly, biochemical changes accompany these distinct changes in cell polarity and morphology, including the decreased expression of endothelial markers and the acquisition of mesenchymal markers. This review highlights evidence supporting the important role of EndMT in the development of renal fibrosis in CKD and its underlying mechanisms, including novel biological significance of microRNA regulation.