Jin Okazaki

l-Arginine inhibits smooth muscle cell proliferation of vein graft intimal thickness in hypercholesterolemic rabbits

OBJECTIVEnThe effect of the chronic administration of L-arginine on intimal thickness and the kinetics of smooth muscle cell proliferation in autovein grafts in hypercholesterolemic rabbits were examined.nnnMETHODSnMale rabbits were fed a 1% cholesterol diet (control group) and a 1% cholesterol diet supplemented by 2.25% L-arginine HCl in drinking water (arginine group). Each group underwent reversed autologous vein bypass grafting of the left common carotid artery using the left external jugular vein. At 2 or 4 weeks after operation, intimal cell proliferation was determined by 5-bromo-2-deoxyuridine (BrdU) incorporation and intimal thickness of the graft was measured with an ocular cytometer. At 4 weeks after operation, endothelium-dependent responses were examined by isometric tension recording.nnnRESULTSnAt 4 weeks after operation, the level of plasma arginine and citrulline are significantly higher in the arginine group (n = 7), compared with the control (n = 7). Intimal thickness in the arginine group (n = 7) was significantly reduced, compared with that of the control (n = 7). At 2 weeks after operation, the BrdU labeling index of the control (n = 5) was significantly higher than that of the arginine group (n = 5). At 4 weeks after operation, ACh caused endothelium-dependent relaxation in the arginine group (n = 4), while in the control (n = 4), ACh did not relax.nnnCONCLUSIONSnThese results suggest that smooth muscle cell proliferation of the rabbit jugular vein grafts during hypercholesterolemia occurs at an early stage after graft implantation, prior to the development of intimal thickness. Intimal thickness of vein graft during hypercholesterolemia was reduced by chronic administration of dietary L-arginine, by inhibiting smooth muscle cell proliferation. The enhancement of NO production in the blood vessel wall may therefore be useful for preventing late graft failure.

Outcome of repeat hepatectomy in patients with hepatocellular carcinoma aged 75 years and older.

BACKGROUNDnWe sought to evaluate the influence of age on the outcome of repeat hepatectomies in patients > or = 75 years with recurrent hepatocellular carcinoma (HCC).nnnMETHODSnWe studied 121 curative repeat hepatectomies retrospectively. Among the 121 patients, 100, 20, and 1 received second, third, and fourth hepatectomies, respectively. The short-term surgical results of a younger group (<75 years; n = 88) and those of an elderly group (> or = 75 years; n = 33) were compared. The long-term prognosis of the patients who underwent second hepatectomies was also compared between a younger group (<75 years; n = 77) and an elderly group (> or = 75 years; n = 23).nnnRESULTSnThe patients in the elderly group displayed more comorbid conditions pre-operatively, including hypertension and cardiovascular diseases, than the younger group (P < .05); however, there was no significant difference in the incidence of postoperative complications or the duration of postoperative hospital stay. The long-term prognosis in the elderly group was almost identical to that in the younger group. The 3-year overall survival rates for the younger group and the elderly group were 83 vs 73% (P = .51). Disease-free, 3-year survival rates for the younger group and the elderly group were 35% vs 38% (P = .88).nnnCONCLUSIONnOur findings suggest that advanced age by itself does not have an adverse effect on operative outcomes, including postoperative complications and long-term prognosis. Repeat hepatectomy may, therefore, be justified for recurrent HCC in selected elderly patients.

DVC1-0101 to Treat Peripheral Arterial Disease: A Phase I/IIa Open-label Dose-escalation Clinical Trial

We here report the results of a Phase I/IIa open-label four dose-escalation clinical study assessing the safety, tolerability, and possible therapeutic efficacy of a single intramuscular administration of DVC1-0101, a new gene transfer vector based on a nontransmissible recombinant Sendai virus (rSeV) expressing the human fibroblast growth factor-2 (FGF-2) gene (rSeV/dF-hFGF2), in patients with peripheral arterial disease (PAD). Gene transfer was done in 12 limbs of 12 patients with rest pain, and three of them had ischemic ulcer(s). No cardiovascular or other serious adverse events (SAEs) caused by gene transfer were detected in the patients over a 6-month follow-up. No infectious viral particles, as assessed by hemagglutination activity, were detected in any patient during the study. No representative elevation of proinflammatory cytokines or plasma FGF-2 was seen. Significant and continuous improvements in Rutherford category, absolute claudication distance (ACD), and rest pain were observed (P < 0.05 to 0.01). To the best of our knowledge, this is the first clinical trial of the use of a gene transfer vector based on rSeV. The single intramuscular administration of DVC1-0101 to PAD patients was safe and well tolerated, and resulted in significant improvements of limb function. Larger pivotal studies are warranted as a next step.

Outcome of hepatectomy in hepatocellular carcinoma patients aged 80 years and older

BACKGROUND/AIMSnThe aim of this retrospective study was to determine the effect of age on the outcome of hepatic resection in octogenarian patients with hepatocellular carcinoma (HCC).nnnMETHODOLOGYnData of 408 consecutive primary HCC patients who underwent curative hepatectomy were studied. The surgical results of the younger group (<80 years of age) and the elderly group (≥80 years of age) were compared.nnnRESULTSnPreoperative parameters, such as comorbid conditions and liver function tests, of the younger group (n=385) were comparable with those of the elderly group (n=23). Surgical data and the prevalence of postoperative complications did not differ significantly between the two groups. The long-term prognosis of the elderly group patients was almost identical to that of the younger group patients. Overall 3-year survival rates for the elderly group and the younger group were 95.7% vs. 84.8%, respectively (p=0.56). Disease-free three-year survival rates for the elderly group and the younger group were 47.2% vs. 47.7%, respectively (p=0.65).nnnCONCLUSIONSnHepatectomy is a viable treatment alternative with satisfactory surgical outcome for HCC even in patients aged 80 years or older.

Surgical strategy of abdominal aortic aneurysm with preoperative renal failure

OBJECTIVESnTo determine the effect of preoperative renal failure on the outcome of patients suffering from infrarenal abdominal aortic aneurysm (AAA).nnnMETHODnDuring the period from January 1979 to August 1995, 364 patients with AAA were admitted to our hospital and 323 underwent elective repair. The patients were retrospectively analysed in three groups. Group I was composed of 273 patients with a normal renal function who underwent an aneurysm repair. Group II was composed of 50 patients who demonstrated a preoperative renal dysfunction (creatinine above 2.0 mg/dl or creatinine clearance below 40 ml/min) and underwent an operation, including three patients maintained on chronic haemodialysis. Group III was composed of 18 patients with a renal dysfunction who did not undergo repair, including one patients maintained on chronic haemodialysis.nnnRESULTSnThe operative mortality rate of groups I and II were 0.4% and 2.0%, respectively, although no significant difference was observed. The incidence of postoperative cardiac and pulmonary complications were also comparable in two groups. No patients required acute haemodialysis. The 5-year survival rate of group II (44%) was significantly higher than that of group III (20%), and seven of the 18 patients (39%) in group III ultimately died of a rupture of the AAA.nnnCONCLUSIONSnPatients with chronic renal failure can undergo an abdominal aortic aneurysm repair based on the same indications as those without renal failure.

The effect of probucol on intimal thickening of autologous vein grafts in hyperlipidemic rabbit

Probucol is used to treat hypercholesterolemia and also has an anti-atherogenic effect. The effects of probucol on intimal thickening of autologous vein graft in hyperlipidemic rabbits with poor distal run-off were investigated. A poor distal run-off model was prepared in the right hindlimb of 18 rabbits allocated to four groups depending on diet: normolipidemic commercial diet, (NL group, n = 5); hyperlipidemic diet (HL group, n = 5); commercial diet with 1% probucol (NP group, n = 4); and hyperlipidemic diet with 1% probucol (HP group, n = 4). After 4 weeks the femoral vein grafts were implanted into normal (n = 18) or poor (n = 18) runoff limbs. Vein grafts were harvested 4 weeks after implantation. Intimal thickening of the graft was measured and macrophages therein examined immunohistochemically. The serum cholesterol level was not reduced by probucol treatment. The mean flow rate of the graft was significantly reduced in the poor run-off limb. On histological examination intimal thickening in the poor run-off limb was significantly greater than that of controls, while intimal thickening in the HL and HP groups was enhanced compared with that in the NL and NP groups, respectively. Mean intimal thickening in each limb in HP group rabbits was significantly lower than that in HL rabbits (microm): control (HL/HP): 99.4(7.4)/58.8(0.7) (P < 0.05); poor run-off (HL/HP): 155.3(9.6)/130.3(7.3) (P < 0.O5). There was no difference between NL and NP (microm): control (NL/NP): 44.6(24.7)/31.5(12.8); poor run-off (HL/HP): 115.3(13.8)/97.5(34.0). In addition, enhanced intimal thickening due to poor distal run-off was not suppressed. Immunohistochemical staining showed intimal macrophage infiltration in the HL and HP groups; however, macrophage infiltration in grafts in the HP group was less than in the HL group. In conclusion, under hyperlipidemic conditions, probucol decreased intimal thickening enhancement of the vein graft, and suppressed intimal macrophage infiltration. These findings were similar to the anti-atherogenic effect of probucol in the native artery. Hence, probucol administration after vascular reconstruction with vein grafts in patients with hyperlipidemia may be beneficial.

Midterm outcomes of endovascular repair for abdominal aortic aneurysms with the on-label use compared with the off-label use of an endoprosthesis

PurposeEndovascular repair of an abdominal aortic aneurysm (EVAR) is sometimes not performed in accordance with the instructions for use (IFU) of the endoprosthesis (“off-label use”). We investigated whether the off-label use of the endograft affected the outcomes of EVAR.MethodsDemographic, anatomical, intraoperative and follow-up data on 100 patients in whom the endograft was used on-label in EVAR were compared retrospectively with the corresponding data of 50 patients with off-label endograft use.ResultsThe endograft IFU were most often not followed in patients with challenging aortic neck anatomy or iliac access or fixation, steep neck angulation or bilateral hypogastric artery embolization. Compared with patients in whom the device was used on-label, patients with off-label use had significantly higher rates of intraoperative type I or III endoleaks and proximal aortic cuff placement or other adjunctive procedures. However, there were no midterm differences between the two groups in the rates of type 1b or II endoleaks, sac enlargement, device–limb occlusion or patient survival.ConclusionsMost midterm outcomes of EVAR in which the endografts were used off-label were similar to those associated with on-label use of the devices. Off-label use of EVAR endoprostheses is feasible, but requires the use of special techniques in patients with challenging anatomical features.

Fibromuscular Dysplasia of the Lower Extremities

Fibromuscular dysplasia (FMD) is a nonatherosclerotic, non-inflammatory vascular disease that mainly affects the renal and internal carotid arteries. Involvement of other sites, including arteries of the extremities, is uncommon, and only a few histologically confirmed cases have been reported. FMD of the arteries of the extremities can result in ischemia requiring surgical or endovascular reconstruction. In the present report, two cases of FMD are described: one case of femoropopliteal artery occlusive disease, and one case of nonsymptomatic progression of external iliac artery dissection, both with histological confirmation of FMD. Clinical presentation, treatment, outcome and histological findings of previously reported cases are reviewed. FMD should be considered as a cause of occlusion, stenosis, dissection or aneurysm of the peripheral arteries: although rare, it can lead to limb-threatening ischemia or life-threatening aneurysm rupture.

Laparoscopy-assisted resection for Mesenteric Castleman's disease: Report of a case.

A 65-year-old female patient was diagnosed with breast cancer in 1995. An abdominal mass was detected by computed tomography and the patient was preoperatively diagnosed with a gastrointestinal stromal tumor. Laparoscopy-assisted surgical resection revealed a mesenteric Castleman’s tumor of the hyaline vascular type. Mesenteric Castleman’s disease is rare, and there have been only 42 cases reported in the English literature. We herein discuss the clinical findings of these cases.

High Dorsal Resection for Recurrent Hepatocellular Carcinoma Originating in the Caudate Lobe

Standards that enable surgeons to balance radical operative procedures with functional preservation for recurrent hepatocellular carcinoma (HCC) in the caudate lobe have not yet been established. A 54-year-old man with recurrent HCC originating in the caudate lobe was readmitted to our hospital. The combined resection of the adjacent hepatic parenchyma may have carried a risk of postoperative liver failure. The anterior transhepatic approach may have caused massive bleeding due to the presence of scarring from the previous hepatectomy. Therefore, we performed an isolated total caudate lobectomy, i.e., a “high dorsal resection” as a second hepatectomy. The postoperative course of the patient was uneventful, and there has been no local recurrence 1 year after the repeat hepatectomy. Indeed a “high dorsal resection“ is rarely required, but it is still ingenious, and this surgical modality can balance the curability with the hepatic functional reserve even for recurrent caudate HCC in patients with liver cirrhosis.