The Efficacy of the Transdermal Isosorbide Dinitrate Patch in Patients With Chronic Limb-Threatening Ischemia.

Recently, the number of patients with peripheral artery disease (PAD), including those with chronic limb-threatening ischemia (CLTI), has increased because of the increasing number of diabetic or dialysis patients worldwide. Revascularization is an important therapy for patients with CLTI. However, we sometimes experience refractory cases with insufficient peripheral circulation or microcirculation after revascularization. In this situation, additional therapy can be administered, such as low-density lipoprotein apheresis, high-pressure oxygen therapy, and spinal cord stimulation. However, they are not effective in some cases. Some reports have also indicated that transdermal isosorbide dinitrate patch (ISDN-P) is a useful therapy for PAD. As the efficacy of ISDN-P for patients with CLTI is not well-known, we examined it in this study. We assessed the skin perfusion pressure (SPP) after affixing an ISDN-P on the foot, because SPP measurement has proved useful in the assessment of PAD and is a good indicator of wound healing potential. The SPP (dorsal and plantar aspects) after ISDN-P application on the foot of healthy volunteers increased (n = 8; mean ± SD, 12.6 ± 7.9 [P = .12], and 21.2 ± 7.7 mm Hg [P < .05], respectively), as did SPP of patients with CLTI (n = 10; mean ± SD, 19.8 ± 2.5 [P < .01], and 14.1 ± 5.9 mm Hg [P < .05], respectively). All the patients who received an ISDN-P on the foot had no major complication, and no significant change in blood pressure. In conclusion, the ISDN-P is one of the effective and safe therapies for patients with CLTI.

Giant Hepatic Cyst: A Possible Cause of Inferior Vena Cava Syndrome.

An 80-year-old man was transferred to our institution with lower limb edema and worsening dyspnea following the administration of diuretic medication. Transthoracic echocardiography and computed tomography revealed a giant hepatic cyst (176×190 mm) compressing his right atrium and inferior vena cava (IVC). Laparoscopic cyst deroofing combined with omental packing and subsequent tube drainage immediately alleviated all his symptoms. The procedure was uneventful, and he was discharged without any complications on postoperative day 9; he had no recurrent symptoms or hepatic cysts at the postoperative 2-month follow-up. Therefore, a giant hepatic cyst can cause IVC syndrome, and laparoscopic deroofing is a beneficial approach for the treatment of accessible cysts.

Pseudo-aneurysm caused by stent fracture in the "sub-acute" phase after endovascular therapy for in-stent restenosis lesions.

Despite the reported favorable patency of stents in the treatment of femoropopliteal lesions, concern regarding stent fracture is increasing. Development of pseudo-aneurysm by stent fracture is rare and has been reported to occur in the chronic phase owing to mechanical fatigue. Here, we present the first report of a pseudo-aneurysm caused by stent fracture in the "sub-acute" phase after endovascular therapy for in-stent restenosis lesion. A 79-year-old man underwent endovascular therapy for an in-stent restenosis lesion of the right superficial femoral artery. Echography 48 days after the treatment showed a saccular pseudo-aneurysm at the proximal stent site, suggestive of stent fracture. Angiography confirmed the pseudo-aneurysm caused by stent fracture. A self-expandable endoluminal stent graft was deployed, which showed complete resolution of the pseudo-aneurysm. A pseudo-aneurysm caused by stent fracture can occur in the "sub-acute" phase after endovascular therapy for in-stent restenosis lesions. .

Combined Use of Excimer Laser and High-Speed Rotational Atherectomy to Overcome a Severely Calcified Lesion in Endovascular Therapy.

Although endovascular therapy (EVT) is commonly used in treatment of peripheral artery disease (PAD), severely calcified lesions pose a challenge, in spite of the technical advancement. In this report, we discuss the case of a 74-year-old male with coronary artery disease and end-stage renal disease who presented at our institution with bilateral intermittent claudication. Angiography showed chronic total occlusion (CTO) of the right superficial femoral arteries (SFA). Because the bilateral external iliac arteries demonstrated moderate stenosis, we performed endovascular therapy on the right SFA-CTO using a contralateral approach. With the antegrade wire progressing into the subintimal space, direct distal-SFA puncture was performed and wire externalization was established. However, no devices (minimal balloon, microcatheter, or Crosser system) were able to pass the lesion in antegrade or retrograde manner, even though the child catheter support or needle cracking technique from outside/inside was applied. Therefore, we used a combination of an excimer laser and high-speed rotational atherectomy to overcome the severely calcified lesion. First, the excimer laser catheter (Turbo Elite 0.9 mm) ablated the entry to the CTO; however, it did not pass through completely. Thereafter, the thin microcatheter (Caravel) succeeded in crossing the CTO in an antegrade manner using the BAlloon Deployment using FORcible Manner (BADFORM) technique. After wire-exchange to the Rota-wire, rotational atherectomy (RotaLink Plus 1.5 mm) passed through the CTO. Subsequently, we could dilate the CTO lesion with a conventional balloon followed by bare metal stent deployment. The right ankle-brachial index of the patient improved from being unmeasurable to 0.79, and the intermittent claudication disappeared. This combination therapy, described as the "RASER" technique in coronary section, is accepted for reimbursement. However, these devices in EVT section are considered off-label use in Japan. Therefore, we have to refrain from frequent use of this strategy; however, this method provides an option for severely calcified lesions.

Optimal blood pressure in patients with peripheral artery disease following endovascular therapy.

This study examined the associations between blood pressure (BP) and event incidence to define optimal BP after endovascular therapy (EVT) in patients who underwent EVT. BP was monitored every 6 months for 5 years, and the patients were divided into two groups by average BP: ≥ 140/90 mmHg and < 140/90 mmHg. The association of BP with several events was examined. Although no significant differences in total mortality were observed between the groups, restenosis rates were significantly higher among patients who did not achieve target BP (36.2%) than among those who did (18.2%) (p < 0.01). The percentage of patients with glycosylated haemoglobin > 7.0% was significantly higher among those who did not achieve target BP in the restenosis group (42.9%) than in the other group (10.8%) (p < 0.01). In the restenosis group, there was a significantly higher percentage of patients taking metformin (p < 0.01) than in the other group. Metformin seemed to be administered to patients with more severe diabetes mellitus. In conclusion, it is important to manage hypertension and diabetes to prevent restenosis after EVT.

Prognosis of medically treated patients at least 80 years old with severe sclerotic aortic stenosis.

BACKGROUND: The prevalence of severe sclerotic aortic stenosis (ScAS) in those at least ≧80 years old has been increasing in Japan; however, the prognosis of these Japanese patients without surgical treatment has not been reported. METHODS AND RESULTS: Ninety consecutive patients with medically treated severe ScAS were prospectively studied. To assess further event-free survival rate (EFSR) from either cardiac (heart failure or cardiac death) events or noncardiac deaths, they were divided into three groups based on aortic valve area (AVA) at the initial diagnosis (group A: AVA≦0.6cm(2), group B: 0.6cm(2)

PAX4 has the potential to function as a tumor suppressor in human melanoma.

We hypothesize that dysregulated expression levels of the developmental regulatory genes in the adult body result in tumor development and malignant progression. PAX genes discovered as human orthologous genes of Drosophila 'paired' encode transcription factors, which control the expression of target genes to go on along the program of development. In this study, we first quantified expression of 9 PAX genes in human nevus pigmentosus tissues, melanoma tissues and melanoma cell lines by the real-time reverse transcription-PCR method. As a result, we found that the expression levels of PAX4 and PAX9 were extremely low in melanoma tissues and cell lines compared to nevus pigmentosus tissues. We then established melanoma cells overexpressing PAX4 and examined roles of PAX4 in cell growth. PAX4-overexpression reduced in vitro cell growth of human melanoma C8161 and MeWo cells. BrdU-uptake assay and cell cycle analysis by flow cytometry indicated that the retardation of cell proliferation by PAX4-overexpression was due to decreased DNA synthesis and cell cycle arrest at the G0/G1 phase. Furthermore, treatment of C8161 and MeWo cells with 5-azacytidine, a DNA demethylating agent, induced the expression of PAX4, suggesting that DNA methylation repressed the PAX4 gene expression in human melanoma. These results suggest that PAX4 functions as a potent tumor suppressor.

Evaluation of the sclerotherapeutic efficacy of ethanol, polidocanol, and OK-432 using an in vitro model.

BACKGROUND: Sclerosants are used to treat vascular malformations. Owing to variations in the flow, the injected concentrations and the duration of exposure of these sclerosants are altered. Therefore, the clinical effectiveness of sclerotherapy is variable. OBJECTIVE: The objective was to evaluate the differences in clinical response, usually observed among ethanol, polidocanol, and OK-432, using an in vitro sclerotherapy model. METHODS: Endothelial cells were cultured and exposed to different concentrations of the sclerosants for 5 seconds and the remaining viable cells were counted using a MTT assay kit. Dyes were used to visualize the morphologic changes. Precipitant formation in blood was also evaluated. Finally, the degree of ICAM-1 expression, after exposure to lower concentrations of these sclerosants, was studied using immunocytochemistry. RESULTS: Only ethanol causes precipitant formation and kills almost all cells from 30% concentration. Polidocanol begins to disrupt the cell membrane from 0.0125% onward. Only OK-432 induces ICAM-1 expression. CONCLUSION: Ethanol's strong precipitant-forming effect may induce thromboembolism, thus enhancing sclerosis. Polidocanol's endothelial cell-lysing effect was clearly documented. OK-432 may mediate its effect by inducing inflammatory response of the endothelium via ICAM-1 expression. This in vitro model may be useful in evaluating other sclerosants as well.

Dysregulated expression of HOX and ParaHOX genes in human esophageal squamous cell carcinoma.

Homeobox genes function as master regulators in embryonic morphogenesis. We hypothesized that homeobox genes are essential to maintain tissue- or organ-specificity even in adult body and that the dysregulated expression of homeobox genes results in tumor development and progression. To better understand the roles of homeobox genes in development and progression of esophageal cancer, we analyzed the expression patterns of 39 HOX genes and 4 ParaHOX (CDX1, CDX2, CDX4 and PDX1) genes in esophageal squamous cell carcinoma (ESCC) and normal esophageal mucosa tissues. A total of 48 primary ESCC tissues and 7 normal esophageal mucosa tissues were resected from patients who underwent radical surgery without any preoperative chemotherapy or radiotherapy. The expression of HOX and ParaHOX genes were analyzed by a quantitative real-time RT-PCR method and immunohistochemistry. The expression levels of 24 HOX genes, CDX1, CDX2 and PDX1 were significantly higher in ESCC compared to normal mucosa (p<0.01, Mann-Whitney U test). The Immunohistochemical study revealed that HOXA5 and D9 proteins were more cytoplasmic in ESCC than normal mucosa cells. Our data indicate that the disordered expression of HOX and ParaHOX genes are involved in the development of ESCC or its malignancy.

Prediction of metastases in melanoma patients with positive sentinel node: histological and molecular approach.

It is now established that sentinel node (SN) biopsy is a minimally-invasive procedure that accurately indicates the regional nodal status. In our institute, 14 consecutive patients had only one node micrometastases after elective lymph node dissection or positive SN for primary cutaneous melanoma. These 14 patients could be clearly divided into two groups: (i) patients who developed distant metastases or in-transit metastases (metastasized group); and (ii) and patients who remains free from metastases (non-metastasized group). The purpose of this study was to identify the histological and molecular factors that might predict the further dissemination beyond the SN. We assessed the maximum depth from the capsule to the deepest melanoma cells and the maximum diameter of melanoma nests in the lymph nodes as histological parameters and also evaluated the quantitative expression of tyrosinase mRNA as a molecular approach. The mean maximum depth and the maximum diameter were significantly smaller in the metastasized group than those in the non-metastasized group. Tyrosinase mRNA expression was strongly correlated with the histological tumor burden. Tyrosinase mRNA expression was higher in the former group than that in the latter group but there were no significant differences between them. Melanoma patients with small micrometastases (<0.5 mm deep, <1 mm in diameter) and a low level of tyrosinase mRNA had less chances for hematogenous metastases via lymph nodes.