A Feasibility Study of Moxibustion for Treating Anorexia and Improving Quality of Life in Patients With Metastatic Cancer: A Randomized Sham-Controlled Trial.

OBJECTIVE: The aim of this study was to determine the feasibility, acceptability, and safety of using moxibustion for treating anorexia and improving quality of life in patients with metastatic cancer. METHODS: We conducted a randomized sham-controlled trial of moxibustion. Sixteen patients with metastatic cancer were recruited from Daejeon, South Korea. The patients were randomly placed into a true or a sham moxibustion group and received 10 true or sham moxibustion treatments administered to the abdomen (CV12, CV8, CV4) and legs (ST36) over a 2-week period. Outcome measures included interest in participating in the trial, identification of successful recruitment strategies, the appropriateness of eligibility criteria, and compliance with the treatment plan (ie, attendance at treatment sessions). Clinical outcomes included results of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT), answers on the European Organization for Research and Treatment of Cancer 30-item core quality of life (EORTC QLQ-C30) questionnaires, scores on the visual analogue scale (VAS), and the results from blood tests and a safety evaluation. RESULTS: Moxibustion was an acceptable intervention in patients with metastatic cancer. Compliance with the treatment protocol was high, with 11 patients completing all 10 treatments. No serious adverse events related to moxibustion occurred, but 4 patients in the true moxibustion group reported mild rubefaction, which disappeared in a few hours. CONCLUSION: This study suggests that moxibustion may be safely used to treat anorexia and improve quality of life in patients with metastatic cancer. However, further research is needed to confirm this result.

Anti-Fatigue Effects of Enzyme-Modified Ginseng Extract: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: Ginseng saponin is known to have biological activities in maintaining homeostasis and enhancing vital energy. Enzyme-modified ginseng extract (EMGE) was designed to increase the content of its active constituents and to intensify biological activity. The present study investigated the anti-fatigue effects of EMGE in healthy adults in a randomized, double-blind, placebo-controlled trial. DESIGN: Fifty-two healthy subjects met the diagnostic criteria and were randomly allocated into one of two groups: EMGE (2,000 mg/day) or placebo. EMGE or placebo were administered to each group for 4 weeks. Fatigue scores using the Visual Analogue Fatigue Scale (VAFS) and Revised Piper Fatigue Scale (RPFS) were considered as the primary outcome measure. Life-quality scores were investigated using the Short-Form Health Survey (SF-36). The safety and adverse effects of EMGE were also assessed. RESULTS: A repeated-measures analysis of variance showed that there was a significant difference in the VAFS scores VAFS between the treatment and placebo groups after 4 weeks. The treatment group's score decreased more than that of the placebo group. There was no difference in the RPFS and SF-36 scores between the two groups. There were no fatal adverse effects. CONCLUSION: EMGE treatment for 4 weeks decreased fatigue severity in a healthy population. Adverse effects were rare, and EMGE was generally well tolerated. Randomized, placebo-controlled trials of EMGE are justified in order to elucidate the underlying mechanism of EMGE in combating fatigue.

Impacts of rapid recanalization and collateral circulation on clinical outcome after intraarterial thrombolysis.

BACKGROUND AND PURPOSE: Rapid recanalization might improve clinical outcomes after intraarterial thrombolysis (IAT) for acute ischemic stroke patients with collateral circulation. We determined whether rapid recanalization and collateral circulation affect clinical outcomes after IAT. METHODS: We retrospectively evaluated the clinical and radiological data of 134 consecutive patients who underwent IAT for intracranial artery occlusion. The interval from symptom onset to recanalization after IAT (onset-to-recanalization time) as an estimate of the probability of good clinical outcome (modified Rankin scale 0-2) was calculated in patients with collateral circulation in the ischemic hemisphere, which was rated poor (0/1 American Society of Interventional and Therapeutic Neuroradiology criteria) or good (2-4). Changes in National Institute of Health Stroke Scale (NHISS) score before and after IAT and modified Rankins scale scores 3 months after discharge were compared with respect to onset-to-recanalization time. RESULTS: In patients with good collateral circulation, the estimated onset-to-recanalization time for a 0.5 probability of a good clinical outcome was 347 minutes; with poor collateral circulation, it was 172 minutes for a 0.2 probability of good clinical outcome. Outcome analyses according to onset-to-recanalization time showed patients recanalized <6 hours had lower NHISS scores (<4.5, 4.5-6, >6 hours of onset-to-recanalization time, and non-recanalization: 5.1, 6.9, 11.9, and 19.8, respectively) at discharge and higher percentages of good clinical outcome (69%, 66.7%, 21.9%, and 0%, respectively) 3 months after IAT. CONCLUSIONS: The time window to expect a high probability of a good clinical outcome after IAT is highly dependent on the collateral circulation.

Effect of acupuncture for radioactive-iodine-induced anorexia in thyroid cancer patients: a randomized, double-blinded, sham-controlled pilot study.

OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of acupuncture for radioactive iodine (RAI)-induced anorexia in thyroid cancer patients. METHODS: Fourteen thyroid cancer patients with RAI-induced anorexia were randomized to a true acupuncture or sham acupuncture group. Both groups were given 6 true or sham acupuncture treatments in 2 weeks. Outcome measures included the change of the Functional Assessment of Anorexia and Cachexia Treatment (FAACT; Anorexia/Cachexia Subscale [ACS], Functional Assessment of Cancer Therapy-General [FACT-G]), Visual Analogue Scale (VAS), weight, body mass index (BMI), ACTH, and cortisol levels. RESULTS: The mean FAACT ACS scores of the true and sham acupuncture groups increased from baseline to exit in intention-to-treat (ITT) and per protocol (PP) analyses; the true acupuncture group showed higher increase but with no statistical significance. Between groups, from baseline to the last treatment, statistically significant differences were found in ITT analysis of the Table of Index (TOI) score (P = .034) and in PP analysis of the TOI (P = .016), FACT-G (P = .045), FAACT (P = .037) scores. There was no significant difference in VAS, weight, BMI, ACTH, and cortisol level changes between groups. CONCLUSION: Although the current study is based on a small sample of participants, our findings support the safety and potential use of acupuncture for RAI-induced anorexia and quality of life in thyroid cancer patients.

Predictive factors for early clinical improvement after intra-arterial thrombolytic therapy in acute ischemic stroke.

BACKGROUND: In acute ischemic stroke, the speed of improvement after intra-arterial thrombolytic therapy (IAT)-mediated recanalization varies. This study aimed to identify clinical and radiological variables that are predictive of early improvement (EI) after IAT in acute ischemic stroke. METHODS: This single-center retrospective cohort study included 141 consecutive patients who underwent IAT for terminal internal carotid and/or middle cerebral artery (MCA) occlusions. EI was defined as a National Institutes of Health Stroke Scale (NIHSS) score less than 3 or NIHSS score improvement of 8 points or more within 72 hours of IAT. The EI and non-EI groups were compared in terms of clinical and radiological findings before and after IAT. RESULTS: Forty-nine patients showed EI (34.8%). Multivariate analysis revealed that atrial fibrillation (odds ratio [OR] .35, 95% confidence interval [CI] .14-.89, P = .028) and hyperdense MCA sign (OR .39, CI .15-.97, P = .042) were related with lack of EI. The independent EI predictors were less extensive parenchymal lesion on baseline computed tomography (OR 4.92, CI 1.74-13.9, P = .003), intermediate to good collaterals (OR 3.28, CI 1.16-9.31, P = .026), and recanalization within 6 hours of symptom onset (OR 5.2, CI 1.81-14.94, P = .002). EI associated with favorable outcomes (modified Rankin scale score 0-2) at discharge (88% versus 7%; P < .001) and 3 months after discharge (92% versus 18%; P < .001). CONCLUSIONS: The clinical and radiological variables maybe useful for predicting EI and favorable long-term outcomes after IAT.

Intracranial hemodynamic stabilization patterns after stenting of severe stenosis in the proximal internal carotid artery.

PURPOSE: To evaluate intracranial hemodynamic stabilization patterns after carotid artery stenting (CAS) in patients having variable collateral developments before CAS. METHODS: The hemodynamic and angiographic data of 62 patients (58 men; mean age 68.0±8.4 years) who underwent CAS for unilateral proximal internal carotid artery stenosis were analyzed. The patients had transcranial Doppler examinations before and at 1 and 90 days after CAS. Patients were classified according to pre-CAS mean blood flow velocity (MBFV) of the ipsilateral middle cerebral artery (MCA): low (<30 cm/s; n=17), normal (30 to 48 cm/s; n=26), or high (>48 cm/s; n=19). The collaterals from contralateral anterior and/or posterior circulations prior to CAS, the stabilization pattern of MBFV, and the pulsatility index (PI) after CAS were compared across the 3 groups. RESULTS: The presence of collaterals was lowest in the low MBFV group (17.6% of patients) than in the normal (38.5%) or high (68.4%) MBFV groups (p=0.008). The low MBFV group exhibited an increase in MBFV and PI in the ipsilateral MCA at 1 and 90 days after CAS (p<0.05). By contrast, the high MBFV group exhibited a decrease in MBFV and no change in PI in the ipsilateral MCA up to 90 days after CAS (p<0.05). The normal MBFV group showed an increase in MBFV at post-CAS day 1 but a subsequent decrease at 90 days and an increase in PI in the ipsilateral MCA at 1 and 90 days post-CAS (p<0.05). CONCLUSION: The pattern of post-CAS intracranial hemodynamic stabilization differs according to the pre-CAS MBFV in the ipsilateral MCA.

A comparison of stent-assisted mechanical thrombectomy and conventional intra-arterial thrombolysis for acute cerebral infarction.

BACKGROUND AND PURPOSE: We evaluated whether stent-assisted thrombectomy (SAT) is safer or more clinically beneficial than aggressive mechanical clot disruption (AMCD) for patients with acute intracranial artery occlusion. METHODS: We retrospectively analyzed the clinical data of 72 patients (33 with SAT and 39 with AMCD) who underwent intra-arterial thrombolysis for acute intracranial artery occlusions. Procedure parameters, clinical outcomes, and incidence of complications were compared between the SAT and AMCD groups. RESULTS: The time interval to recanalization was shorter in SAT patients (69.2±39.6 minutes, mean±standard deviation) than in AMCD patients (94.4±48.0 minutes, p<0.05). Recanalization was achieved in more SAT patients (91%) than AMCD patients (80%), but with no statistically significance. Urokinase was used less frequently in SAT patients (21%) than in AMCD patients (92%, p<0.05), and the incidence of symptomatic hemorrhages was lower in SAT patients (3%) than in AMCD patients (18%, p<0.05). Device-related complications in SAT patients comprised two cases of stent fracture and one case of distal migration of a captured thrombus. The proportion of patients with good outcomes, defined as scores from 0 to 3 on the modified Rankin Scale, was similar in the two groups at discharge (SAT, 46%; AMCD, 39%), but significantly higher in the SAT group than in the AMCD group at 3 months (64% vs. 40%, p<0.05) and 6 months (67% vs. 42%, p<0.05) after discharge. CONCLUSIONS: The outcomes and clinical parameters were better for SAT during thrombolytic procedures for acute intracranial artery occlusions than for AMCD for up to 6 months. However, some device-related complications occurred during stent interventions.

Promoter methylation status of VEGF receptor genes: a possible epigenetic biomarker to anticipate the efficacy of intracellular-acting VEGF-targeted drugs in cancer cells.

We evaluated whether the inhibitory effects of vascular endothelial growth factor (VEGF)-targeted drugs on the proliferation of cancer cells differed according to VEGF receptor (VEGFR) genes, Flt1 and KDR, promoter methylation status. Five hyper-VEGFR-methylation and six no-VEGFR-methylation cancer cells were used for the present study, together with human umbilical endothelial cells (HUVECs) as a control. No-VEGFR-methylation cancer cells showed higher expression of Flt1 and KDR than hyper-VEGFR-methylation cancer cells. Hyper-VEGFR-methylation cancer cells only showed increased expression and protein levels of Flt1 and KDR after treatment with the demethylase 5-aza-2'-deoxycytidine. Two drugs (a VEGF-specific-antibody, bevacizumab, and a KDR-specific-antibody) targeting extracellular VEGF-VEGFR signaling and two VEGF-specific-tyrosine kinase inhibitors (PTK/ZK and sunitinib) targeting intracellular VEGFR signaling were used in the cell proliferation assay. HUVECs showed dose- and time-dependent proliferation decrease with all tested drugs over a 72 h incubation period. No- or hyper-VEGFR-methylation cancer cells showed no significant proliferation differences after treatment with VEGF-specific-antibody or VEGFR2-specific-antibody. After PTK/ZK or sunitinib treatment, no-VEGFR-methylation cancer cells showed dose- or time-dependent decreases in proliferation. Hyper-VEGFR-methylation cancer cells also showed proliferation inhibition by VEGF-specific-tyrosine kinase inhibitors after demethylation of Flt1 and KDR. Proliferation inhibition synergistically increased after combination of demethylation with PTK/ZK in hyper-VEGF-methylation cancer cells. We observed that intracellular targeting of VEGF-VEGFR signaling could be more effective than extracellular targeting of the pathway in the suppression of proliferation of some cancer cells. In particular, the efficacy of intracellular targeting of VEGF-specific-tyrosine kinase inhibitors might be influenced by the epigenetic alteration of VEGFRs.

Treatment of an acute mycotic aneurysm of the common carotid artery with a covered stent-graft.

We report herein a case successful endovascular treatment with a stent-graft of a rare case of rapidly growing mycotic aneurysm of the left common carotid artery due to acute bacterial endocarditis after eradication of the infection. Infected mycotic aneurysms of the peripheral vasculature have been considered as a contraindication for stent-graft implantation because of the possibility of microorganism spreading to the stent-graft; however, if there is evidence of complete eradication of microorganism and surgery is not an option, stent-graft implantation can be an effective and safe treatment modality for exclusion of the mycotic aneurysm.

Rapidly aggravated dissecting flap by angiography during percutaneous stent placement for acute isolated superior mesenteric artery dissection.

Acutely aggravated dissecting flap and consequent occlusion of the superior mesenteric artery (SMA) by simple contrast passage during initial angiography for percutaneous stent placement is a uncommon event, which usually is not reported. After analysis of many factors that underlie development of such complications, we present herein one case of successful treatment of isolated SMA dissection and its complications with favorable outcomes during 25 months follow-up after percutaneous stent placement.

Successful recanalization of acute superior mesenteric artery thrombotic occlusion with primary aspiration thrombectomy.

Prompt revascularization of the superior mesenteric artery (SMA) thrombotic occlusion can prevent intestinal infarction and decrease necrosis of the bowel segment. Herein, we describe two cases who underwent successful endovascular recanalization for acute SMA thrombosis using a primary aspiration thrombectomy because of possible consequent laparotomy for survey of bowel viability. The two patients had dramatic pain relief immediately after the procedure and remained symptom-free during the follow-up period.

Pretreatment with nafamostat mesilate, a kallikrein inhibitor, to decrease withdrawal response associated with rocuronium.

PURPOSE: This randomized, double-blind, placebo-controlled study was conducted to examine the preventive effect of nafamostat mesilate, a kallikrein inhibitor, on the withdrawal response associated with rocuronium injection. METHODS: Ninety American Society of Anesthesiology (ASA) physical status I or II patients, aged 18-65 years, were randomly divided into two groups that received either a 1.5-ml solution containing 1.5 mg nafamostat mesilate diluted in a 5% glucose solution or a 1.5-ml 5% glucose solution. Anesthesia was induced by 5 mg/kg 2.5% thiopental. After confirming loss of consciousness, a tourniquet was applied to the mid forearm and tightened to block venous flow. The test solution was then administered, 1 min after which the tourniquet was removed and 0.6 mg/kg rocuronium was administered. Each patient's response to rocuronium injection was graded on a four-point scale in a double-blind manner. Activated coagulation time and plasma potassium concentration were measured before and 5 and 10 min after nafamostat administration. RESULTS: The incidence of withdrawal response was 68.9% in the control group and 24.4% in the nafamostat group (P < 0.001). The number of patients showing generalized movement (response 4) with the rocuronium injection was significantly lower in nafamostat group [1 (2.2%)] than the control group [15 (33.3%)], P < 0.001. Five and 10 min after nafamostat administration, measured potassium and activated coagulation time were similar to baseline values. CONCLUSION: Pretreatment with 1.5 mg nafamostat mesilate decreased withdrawal response associated with rocuronium injection.

The expression of VEGF receptor genes is concurrently influenced by epigenetic gene silencing of the genes and VEGF activation.

Vascular endothelial growth factor (VEGF) activates the VEGF-VEGF receptor (VEGFR) signaling pathway in angiogenesis. Some cancer cell lines show decreased expression of the two VEGFRs, Flt-1 and KDR, even though VEGF is uniformly expressed in cancer cell lines. Promoter methylation is a well-known cause of epigenetic gene silencing in cancer cells. Although VEGF, Flt-1 and KDR have typical CpG islands in their promoter regions, the epigenetic transcriptional alterations of these genes have not yet been described. The present study evaluated the epigenetic gene silencing of VEGF and VEGFR genes in cancer tissues. We also analyzed whether the epigenetic alterations of VEGFR genes influence VEGFR expression concurrently with VEGF activation in cancer tissues. All cancer tissues we tested showed no methylation of VEGF, and variable promoter hypermethylation of Flt-1 and KDR. The promoter hypermethylation of Flt-1 and KDR was correlated with decreasing expression of the respective genes. In contrast, an increase in VEGF expression was positively correlated with Flt-1 and KDR expression in primary cancer tissues. The opposing influences of promoter methylation of VEGFR and increased VEGF expression concurrently influence Flt-1 and KDR expression in stomach cancer, colon cancer and hepatocellular carcinoma. The findings we observed showed that the epigenetic alteration developing in VEGFR genes might be an important factor to concurrently modulate expressions of the genes in addition to VEGF stimulation in cancer tissues. The epigenetic silencing of VEGFR genes should be considered in the activation of VEGF-VEGFR signaling pathway in the cancer cells.

The expression of VEGF receptor genes is concurrently influenced by epigenetic gene silencing of the genes and VEGF activation.

Vascular endothelial growth factor (VEGF) activates the VEGF-VEGF receptor (VEGFR) signaling pathway in angiogenesis. Some cancer cell lines show decreased expression of the two VEGFRs, Flt-1 and KDR, even though VEGF is uniformly expressed in cancer cell lines. Promoter methylation is a well-known cause of epigenetic gene silencing in cancer cells. Although VEGF, Flt-1 and KDR have typical CpG islands in their promoter regions, the epigenetic transcriptional alterations of these genes have not yet been described. The present study evaluated the epigenetic gene silencing of VEGF and VEGFR genes in cancer tissues. We also analyzed whether the epigenetic alterations of VEGFR genes influence VEGFR expression concurrently with VEGF activation in cancer tissues. All cancer tissues we tested showed no methylation of VEGF, and variable promoter hypermethylation of Flt-1 and KDR. The promoter hypermethylation of Flt-1 and KDR was correlated with decreasing expression of the respective genes. In contrast, an increase in VEGF expression was positively correlated with Flt-1 and KDR expression in primary cancer tissues. The opposing influences of promoter methylation of VEGFR and increased VEGF expression concurrently influence Flt-1 and KDR expression in stomach cancer, colon cancer and hepatocellular carcinoma. The findings we observed showed that the epigenetic alteration developing in VEGFR genes might be an important factor to concurrently modulate expressions of the genes in addition to VEGF stimulation in cancer tissues. The epigenetic silencing of VEGFR genes should be considered in the activation of VEGF-VEGFR signaling pathway in the cancer cells.

Intracranial hemodynamic changes during adult moyamoya disease progression.

BACKGROUND AND PURPOSE: This study evaluated the changes in blood flow velocity in the anterior and posterior intracranial circulations according to the progression of moyamoya disease in adult patients. METHODS: We evaluated Suzuki's angiographic stage and mean blood flow velocity (MBFV) changes in intracranial vessels from both sides in 19 adult moyamoya patients. We then analyzed the linearity of MBFV changes from early to late moyamoya stages in each intracranial vessel using piecewise linear regression models. RESULTS: The MBFV in the middle cerebral artery, terminal internal carotid artery, and anterior cerebral artery increased non linearly until stage III, and then decreased progressively up to stage VI. The ophthalmic artery also showed nonlinear velocity changes, with an increase in MBFV up to stage IV, followed by a decrease in MBFV up to stage VI. The MBFV of the basilar artery increased linearly from a normal velocity at an early moyamoya stage to a stenotic velocity at a late stage. There was no statistically significant regression model for the relationship between the MBFV in the posterior cerebral artery and moyamoya stage. CONCLUSIONS: The nonlinear and/or linear MBFV changes associated with variable intracranial vessels might be useful in initial and follow-up evaluations of different stages of moyamoya disease.