Randomized controlled Phase III study comparing hepatic arterial infusion with systemic chemotherapy after curative resection for liver metastasis of colorectal carcinoma: JFMC 29-0003.

BACKGROUND: The feasibility and efficacy of adjuvant hepatic arterial infusion (HAI) in preventing the development of liver metastases in patients with advanced colon carcinoma have not been validated. The aim of this randomized controlled study was to compare the feasibility of HAI and the protective effect against liver metastasis after curative resection to those of systemic chemotherapy. METHODS: Between July 2000 and June 2003, 91 patients were enrolled. Patients were randomly assigned to receive 5-fluorouracil (5-FU) via continuous venous infusion (CVI) or intra-hepatic arterial weekly high-dose 5-FU (WHF). The primary endpoint was overall survival (OS). RESULTS: In the WHF group, the cumulative failure rate of hepatic arterial catheterization was 16.7% at 6 months. The occurrence of grade 3 adverse events was comparable between the groups. The 5-year OS rates were 59.0% in the CVI group and 34.9% in the WHF group (P = 0.164). CVI tended to show a protective effect against liver metastasis regarding the 5-year liver-specific cumulative recurrence rate: CVI, 45.0% vs. WHF, 68.3%; P = 0.037). CONCLUSION: HAI therapy has a certain protective effect against liver metastasis after curative resection in patients with colorectal cancer. However, this therapy did not contribute to any marked improvement in their overall survival.

Questionnaire-Based Development of an Educational Program of Traditional Japanese Kampo Medicine.

Traditional Japanese Kampo medicine has been widely used in clinical practice in Japan. Though it is a compulsory subject in Japanese medical schools, a standard educational program in Kampo medicine does not exist. Tohoku University has incorporated Kampo medicine into clinical education via didactic lectures since 2003; however, student evaluations have been lower for Kampo than for all other clinical specialties. We administered a questionnaire about a Kampo medicine course for fifth-year students from 2009 to 2012 and developed an educational program based on feedback obtained. The questionnaire consisted of nine questions (a clear training plan; opportunities for learning, practice, and patient contact; acquisition of medical knowledge and physical examination; learning professionalism; understanding the specialty; overall assessment) that were rated on a 5-point Likert scale along with open-ended questions about the course's strengths and weaknesses. The students responded to the questionnaire after clinical practice in Kampo medicine and other clinical specialty courses. Scores for Kampo medicine and the average of other clinical specialties were compared. All 389 students who participated in Kampo clinical practice answered the questionnaire. In 2009, scores for Kampo medicine for nine questions were lower than for the average of the other clinical specialties. After curriculum reformation involving hands-on training in 2012, all scores except "opportunities to learn about clinical cases" and "opportunities to practice involvement" were higher than the average of all other clinical specialties. In conclusion, we have successfully developed a Kampo medicine educational program for our university through this survey study.

The Pilot Study of Evaluating Fluctuation in the Blood Flow Volume of the Radial Artery, a Site for Traditional Pulse Diagnosis.

BACKGROUND: Radial artery (RA) pulse diagnosis has been used in traditional Asian medicine. Blood pressure (BP) and pulse rate related to heart rate variability (HRV) can be monitored via the RA. The fluctuation in these parameters has been assessed using fast Fourier transform (FFT) analytical methods that calculate power spectra. METHODS: We measured blood flow volume (Volume) in the RA and evaluated its fluctuations. Normal participants (n = 34) were enrolled. We measured the hemodynamics of the right RA for approximately 50 s using ultrasonography. RESULTS: The parameters showed the center frequency (CF) of the power spectrum at low frequency (LF) and high frequency (HF). More than one spectral component indicated that there were fluctuations. The CF at LF for Volume was significantly different from that for vessel diameter (VD); however, it was significantly correlated with blood flow velocity (Velocity). On the other hand, the CF at HF for Volume was significantly different from that for Velocity; however, it was significantly correlated with VD. CONCLUSION: It is suggested that fluctuation in the Volume at LF of RA is influenced by the fluctuation in Velocity; on the other hand, fluctuation in the Volume at HF is influenced by the fluctuation in VD.

Heart rate variability and hemodynamic change in the superior mesenteric artery by acupuncture stimulation of lower limb points: a randomized crossover trial.

Objective. We investigated the relationship between superior mesenteric artery blood flow volume (SMA BFV) and autonomic nerve activity in acupuncture stimulation of lower limb points through heart rate variability (HRV) evaluations. Methods. Twenty-six healthy volunteers underwent crossover applications of bilateral manual acupuncture stimulation at ST36 or LR3 or no stimulation. Heart rate, blood pressure, cardiac index, systemic vascular resistance index, SMA BFV, and HRV at rest and 30 min after the intervention were analyzed. Results. SMA BFV showed a significant increase after ST36 stimulation (0% to 14.1% ± 23.4%, P = 0.007); very low frequency (VLF), high frequency (HF), low frequency (LF), and LF/HF were significantly greater than those at rest (0% to 479.4% ± 1185.6%, P = 0.045; 0% to 78.9% ± 197.6%, P = 0.048; 0% to 123.9% ± 217.1%, P = 0.006; 0% to 71.5% ± 171.1%, P = 0.039). Changes in HF and LF also differed significantly from those resulting from LR3 stimulation (HF: 78.9% ± 197.6% versus -18.2% ± 35.8%, P = 0.015; LF: 123.9% ± 217.1% versus 10.6% ± 70.6%, P = 0.013). Conclusion. Increased vagus nerve activity after ST36 stimulation resulted in increased SMA BFV. This partly explains the mechanism of acupuncture-induced BFV changes.

Brief effect of acupoint stimulation using focused ultrasound.

BACKGROUND: Acupuncture is used worldwide in medical treatment. However, needle insertion damages the skin and patients sometimes feel pain. To avoid such drawbacks, an acupoint stimulation device using focused ultrasound has been developed. Ultrasound stimulation does not damage the skin like acupuncture does because ultrasound can deliver vibration energy to soft tissues noninvasively. OBJECTIVES: The aim of this study was to clarify the effect of acupoint stimulation using focused ultrasound. SUBJECTS: Fifty (50) healthy volunteers (40 males and 10 females) were included in this experiment. DESIGN: Subjects were randomly assigned to two groups. LR-3 was stimulated bilaterally for 36 seconds by focused ultrasound and conventional acupuncture. Brachial artery blood flow volume was monitored by an ultrasound with an echo-tracking system. The hemodynamic parameters were measured before, during, and 30, 60, 180 seconds after stimulation. RESULTS: During stimulation, the blood flow volume of the acupuncture stimulation group decreased significantly (p<0.05) compared with resting value, but that of the focused ultrasound stimulation group did not decrease. Blood flow volume of both groups increased gradually and showed significant increase at 180 seconds after stimulation (p<0.05). CONCLUSIONS: Blood flow volume was increased significantly by both focused ultrasound stimulation and conventional acupuncture. Although a significant decrease of blood flow volume during acupuncture stimulation was observed, no such decrease was observed during ultrasound stimulation. Findings of the present study show that noninvasive stimulation of acupoints by focused ultrasound is as effective as conventional acupuncture in blood flow volume of the brachial artery.

Evaluation of the effects of acupuncture on blood flow in humans with ultrasound color Doppler imaging.

Color Doppler imaging (CDI) can be used to noninvasively create images of human blood vessels and quantitatively evaluate blood flow in real-time. The purpose of this study was to assess the effects of acupuncture on the blood flow of the peripheral, mesenteric, and retrobulbar arteries by CDI. Statistical significance was defined as P values less than 0.05. Blood flow in the radial and brachial arteries was significantly lower during needle stimulation on LR3 than before in healthy volunteers, but was significantly higher after needle stimulation than before. LR3 stimulation also resulted in a significant decrease in the vascular resistance of the short posterior ciliary artery and no significant change of blood flow through the superior mesenteric artery (SMA) during acupuncture. In contrast, ST36 stimulation resulted in a significant increase in blood flow through the SMA and no significant change in the vascular resistance of the retrobulbar arteries. Additionally, acupuncture at previously determined acupoints in patients with open-angle glaucoma led to a significant reduction in the vascular resistance of the central retinal artery and short posterior ciliary artery. Our results suggest that acupuncture can affect blood flow of the peripheral, mesenteric, and retrobulbar arteries, and CDI can be useful to evaluate hemodynamic changes by acupuncture.

Development and clinical application of a precise temperature-control device as an alternate for conventional moxibustion therapy.

Moxibustion therapy has been used in East Asian medicine for more than a thousand years. However, there are some problems associated with this therapy in clinical practice. These problems include lack of control over the treatment temperature, emission of smoke, and uneven temperature distribution over the treatment region. In order to resolve these problems, we developed a precise temperature-control device for use as an alternate for conventional moxibustion therapy. In this paper, we describe the treatment of a single patient with paralytic ileus that was treated with moxibustion. We also describe an evaluation of temperature distribution on the skin surface after moxibustion therapy, the development of a heat-transfer control device (HTCD), an evaluation of the HTCD, and the clinical effects of treatment using the HTCD. The HTCD we developed can heat the skin of the treatment region uniformly, and its effect may be equivalent to conventional moxibustion, without the emission of smoke and smell. This device can be used to treat ileus, abdominal pain, and coldness of abdomen in place of conventional moxibustion in modern hospitals.

Haemodynamic changes in the superior mesenteric artery induced by acupuncture stimulation on the lower limbs.

Acupuncture is commonly performed on acupoints. A comparison of quantitative physiological alterations induced by stimulation on different acupoints has never been performed in the superior mesenteric artery (SMA) in humans. Therefore, we investigated changes in blood flow volume (BFV) in the SMA as an indicator of physiological effects induced by stimulation on 3 points. Thirty healthy participants aged 29 ± 10 years (mean ± SD) were enrolled. All participants underwent stimulations on 3 points located in the lower legs: ST36, LR3, and a non-acupoint. Control pertains to a condition with no-stimulation. Stimulation was performed bilaterally with manual rotation of the needles. BFV was measured by ultrasonography before insertion and 10, 20, 30, and 60 minutes after stimulation. Following acupuncture on ST36, BFV increased significantly 20 and 30 minutes after stimulation, compared to BFV before insertion (P < 0.05). Following stimulation on LR3 and the non-acupoint, no significant differences in BFV could be found. Relative to the no-stimulation group, stimulation on LR3, and the non-acupoint, stimulation on ST36 elicited a significant increase in BFV (P < 0.05). The results suggest that stimulation on the different points causes distinct physiological effects in BFV in the SMA.

Development of a questionnaire for the diagnosis of Qi stagnation.

The objective of this study was to develop a questionnaire for the diagnosis of Qi stagnation. At first, we made the preliminary version of the questionnaire from 30 symptoms most frequently mentioned about Qi stagnation in classic books of Oriental Medicine. Two hundred and seven participants completed the preliminary version of the questionnaire rating the severity of 30 symptoms. Those participants were assessed for Qi stagnation by 2 physicians. Logistic regression analysis was performed between the physicians' assessment of Qi stagnation and the severity of symptoms in the preliminary questionnaire. The final version of the questionnaire was developed with 23 symptoms that had significant odds ratios. The Cronbach's α coefficient was 0.83. The area under the curve was 0.90 and cut-off value for diagnosis of Qi stagnation was 28.5 in receiver operating characteristic (ROC) analysis. Sensitivity and specificity were 0.83 and 0.80, respectively. The Spearman's correlation coefficient was 0.72 in the test-retest. This questionnaire would enable standardization and objective verification of the diagnosis of Qi stagnation.

Report on disaster medical operations with acupuncture/massage therapy after the great East Japan earthquake.

The Great East Japan Earthquake inflicted immense damage over a wide area of eastern Japan with the consequent tsunami. Department of Traditional Asian Medicine, Tohoku University, started providing medical assistance to the disaster-stricken regions mainly employing traditional Asian therapies.We visited seven evacuation centers in Miyagi and Fukushima Prefecture and provided acupuncture/massage therapy. While massage therapy was performed manually, filiform needles and press tack needles were used to administer acupuncture. In total, 553 people were treated (mean age, 54.0 years; 206 men, 347 women). Assessment by interview showed that the most common complaint was shoulder/back stiffness. The rate of therapy satisfaction was 92.3%. Many people answered that they experienced not only physical but also psychological relief.At the time of the disaster, acupuncture/massage therapy, which has both mental and physical soothing effects, may be a therapeutic approach that can be effectively used in combination with Western medical practices.

Hemodynamic changes in the brachial artery induced by acupuncture stimulation on the lower limbs: a single-blind randomized controlled trial.

Acupuncture is commonly performed at acupoints. No comparisons of quantitative physiological alterations in the brachial artery (BA) induced by the stimulation of different acupoints in the lower limbs have been performed in humans. Therefore, we investigated changes in blood flow volume (BFV) in the BA as an indicator of the physiological effects induced by stimulation at 3 points. Seventy-five healthy participants aged 33 ± 9 years (mean ± SD) were enrolled and randomly assigned to 3 groups; they received stimulation at 3 different points located on the lower limbs: ST36, LR3, and a non-acupoint. Stimulation was performed bilaterally with manual rotation of the needles. Using ultrasonography, BFV was measured continuously from rest to 180 seconds after stimulation. LR3 stimulation significantly increased BFV compared to that before needle insertion. Meanwhile, stimulation at ST36 and the non-acupoint significantly decreased BFV compared to that before needle insertion. Stimulation at LR3 elicited a significant increase in BFV compared to that at ST36 and the non-acupoint. The results suggest that the stimulation of different points on the lower limbs causes distinct physiological effects on BFV in the BA.

Short-term effects of acupuncture on open-angle glaucoma in retrobulbar circulation: additional therapy to standard medication.

Background. The relation between glaucoma and retrobulbar circulation in the prognosis has been indicated. Purpose. To investigate the effects of acupuncture on retrobulbar circulation in open-angle glaucoma (OAG) patients. Methods. Eleven OAG patients (20 eyes with OAG) who were treated by topical antiglaucoma medications for at least 3 months were enrolled. Acupuncture was performed once at acupoints BL2, M-HN9, ST2, ST36, SP6, KI3, LR3, GB20, BL18, and BL23 bilaterally. Retrobulbar circulation was measured with color Doppler imaging, and intraocular pressure (IOP) was also measured at rest and one hour after rest or before and after acupuncture. Results. The Δ value of the resistive index in the short posterior ciliary artery (P < .01) and the Δ value of IOP (P < .01) were decreased significantly by acupuncture compared with no acupuncture treatment. Conclusions. Acupuncture can improve the retrobulbar circulation and IOP, which may indicate the efficacy of acupuncture for OAG.

Changes of blood flow volume in the superior mesenteric artery and brachial artery with abdominal thermal stimulation.

In traditional Chinese medicine, moxibustion is a local thermal therapy that is used for several conditions. Quantifying the effects of moxibustion therapy has been difficult because the treatment temperature depends on the physician's experience, and the temperature distribution in the target area is not uniform. This prospective observational study aims to quantify the effect of local thermal stimulation to the abdomen. We developed a heat transfer control device (HTCD) for local thermal stimulation. Twenty-four healthy subjects were enrolled and they underwent abdominal thermal stimulation to the para-umbilical region with the device for 20 min. Blood flow volume in the superior mesenteric artery (SMA) and brachial artery (BA), the heart rate and the blood pressure were measured at rest, 15 min after starting thermal stimulation and 10, 20, 30 and 40 min after completing thermal stimulation. Blood flow parameters were measured by high-resolution ultrasound. In the SMA, blood flow volume was significantly increased during thermal stimulation (P < .01), as well as at 10 min (P < .01) and 20 min (P < .05) after stimulation. In the BA, blood flow volume decreased at 40 min after stimulation (P < .01). In conclusion we could quantify the effect of local thermal stimulation with an HTCD and high-resolution ultrasound. Thermal stimulation of the para-umbilical region increased blood flow in the SMA 20 min after stimulation in healthy subjects.

The effect of warming of the abdomen and of herbal medicine on superior mesenteric artery blood flow - a pilot study.

BACKGROUND: In traditional Japanese and Chinese medicine, warming the abdomen with moxibustion or herbal medicines has been used for various diseases. However, the effects of these therapies on hemodynamics have not been clear. We clarify the physiological effects of these therapies on the superior mesenteric artery (SMA) blood flow. PARTICIPANTS AND METHODS: 28 healthy male volunteers were randomly assigned to groups A and B. Group A (n = 14) underwent local thermal stimulation of the paraumbilical region for 20 min at a temperature of 40 °C; this simulated the heat and mechanical pressure effects of moxibustion. Group B (n = 14) took the herbal medicine Daikenchuto (TJ-100; 5.0 g) with distilled water. As a control, group C (n = 14) took distilled water alone. Blood flow volume in the SMA was measured by ultrasound from rest to 50 min after the start of each intervention. RESULTS: The SMA blood flow volume increased significantly between 10 to 40 min after the start of thermal stimulation (p < 0.05), and it also increased significantly between 10 to 50 min after administration of TJ-100 (p < 0.01) as compared to the resting volume. However, SMA blood flow volume did not change significantly after administration of water alone. There was no significant difference in SMA blood flow changes between groups A and B. CONCLUSIONS: The results suggest that one of the physiological effects of warming the abdomen according to a traditional concept in thermal stimulation and herbal medicine is an increase of SMA blood flow volume.

Brief effect of acupuncture on the peripheral arterial system of the upper limb and systemic hemodynamics in humans.

BACKGROUND: Pulse diagnosis of the peripheral artery is an important technique in Traditional Chinese Medicine, where, in acupuncture therapy, the treatment is adjusted according to the observed changes of the pulse. We investigated the change of blood flow in the peripheral artery and the cardiac index during acupuncture treatment. OBJECTIVES: The aim of this study is to explore the effect of acupuncture on radial and brachial artery blood flow volume and the cardiac index in healthy subjects. METHODS: Eighteen (18) healthy volunteers were enrolled. Acupuncture was performed bilaterally on LR-3 with manual rotation of the needles. The blood pressure and heart rate were measured at rest and 180 seconds after acupuncture. Radial and brachial artery blood flow volume was monitored continuously by an ultrasound with an echo-tracking system. Cardiac index was measured by impedance cardiography. The hemodynamic parameters were measured before, during, and 30, 60, 180 seconds after acupuncture. RESULTS: The peripheral artery blood flow volume decreased significantly during acupuncture (radial; p < 0.01, brachial; p < 0.05) but increased at 180 seconds after acupuncture (radial; p < 0.05, brachial; p < 0.05) compared with before acupuncture. The cardiac index did not change significantly after acupuncture, but systemic vascular resistance index significantly decreased (p < 0.05). CONCLUSIONS: The present study showed that radial and brachial artery blood flow volume decreased immediately during acupuncture on LR-3 acupoint, but increased at 180 seconds after acupuncture. This reaction is attributed to the change in peripheral vascular resistance.

The herbal medicine Daikenchuto increases blood flow in the superior mesenteric artery.

Daikenchuto is a traditional herbal medicine that is used for the treatment of cold feeling in the abdomen, while Orengedokuto, also a traditional herbal medicine, is used for treating inflammatory and ulcerative diseases affecting internal organs. However, the effects of these herbal medicines on cardiac output (CO) and intestinal blood flow have never been investigated. This examiner-blinded randomized crossover study intended to clarify the influence of Daikenchuto and Orengedokuto on CO and blood flow volume in the superior mesenteric artery (SMA). Fourteen healthy men (35 +/- 7 years old) were randomly assigned to two groups: group A and group B. Initially, all subjects were given 50 ml of water orally. After 7 days, subjects in group A were given 5.0 g of Daikenchuto, and 7 days later they were given 2.5 g of Orengedokuto. These herbal medicines were given to group B subjects in the reverse order. CO and SMA blood flow volume were measured from rest to 90 min after the administration of water or each medicine. There was a significant increase in SMA blood flow volume after the administration of Daikenchuto, compared to water alone (p < 0.05) and Orengedokuto (p < 0.05). SMA blood flow volume was significantly increased between 5 and 90 min after administration of Daikenchuto (p < 0.01) compared to the resting state. However, there was no significant change in CO after the administration of either agent. The present study indicates that Daikenchuto increases SMA blood flow volume without increasing CO.

Influence of soil properties on the biodegradation of 1,3,6,8-tetrachlorodibenzo-p-dioxin and fungal treatment of contaminated paddy soil by white rot fungus Phlebia brevispora.

To examine the bioremediation potential of Phlebia brevispora in dioxin-contaminated soil, the fungus was inoculated into autoclaved soil that was contaminated with 2,7-dichlorodibenzo-p-dioxin (2,7-DCDD) or 1,3,6,8-tetrachlorodibenzo-p-dioxin (1,3,6,8-TCDD). Three types of soils, organic-rich soil (Andosol), organic-poor soil (Granitic Regosols), and paddy soil, were used for the construction of artificially contaminated soil to understand the influence of the soil property on fungal growth and dioxin degradation ability. Under a solid-state condition, although the growth of the fungus improved in organic-rich soil, the degradation of 2,7-DCDD was inhibited. Although the degradation of 1,3,6,8-TCDD under a solid-state condition was inhibited severely, 1,3,6,8-TCDD degradation was observed under a slurry-state condition in organic-poor soil. In the case of organic-rich soil, an increase in water content improved the 1,3,6,8-TCDD degradation efficiency. When the historically contaminated paddy soil was treated with P. brevispora under a slurry-state condition, 1,3,6,8-TCDD as the main contaminant degraded 50% after 90d incubation.

[Case report of a liver metastasis from rectal cancer achieving complete response (CR) by a combination of intra-hepatic arterial infusion of irinotecan (CPT-11) with degradable starch microspheres (DSM) and weekly high-dose intra-hepatic arterial chemotherapy with 5-FU].

A 67-year-old woman, who was diagnosed with rectal cancer and liver metastasis, underwent a low anterior resection of the rectum in May 2004. Two months later, the level of tumor markers increased and a CT scan revealed a 45 x 35 mm liver metastasis in the S(8) segment. She was referred to our hospital for treatment of the liver tumor. Intra-hepatic arterial infusion of irinotecan (CPT-11) and mitomycin C (MMC) with degradable starch microspheres (DSM) was given in July 2004. Following this, a 34-week course of weekly high-dose intra-hepatic arterial 5-FU infusion (5-FU 1,000 mg/m(2)) was performed. In April 2005, the size of the liver metastasis decreased, and the level of serum tumor marker normalized. A CT and echo scan revealed a calcified tumor, and therefore all chemotherapy was stopped. She was followed in the outpatient clinic, with no evidence of recurrence for 12 months. This case suggests that the use of intra-hepatic arterial infusion of CPT-11 and MMC with DSM is useful for the treatment of liver metastases in colorectal cancer.