Magnetic anchor-guided endoscopic submucosal dissection for gastric lesions (with video).

BACKGROUND AND AIMS: The feasibility of magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD) using a neodymium magnet for gastric lesions has not been clarified. The aim of study was to evaluate the feasibility of MAG-ESD using neodymium magnets while treating gastric lesions. METHODS: This prospective trial was conducted at the Yamashita Hospital. MAG-ESD was performed for 50 gastric lesions using an insulated-tip knife. The magnetic anchor consisted of an internal neodymium magnet attached to a hemoclip with 3-0 silk. The external and internal magnets were made from the neodymium magnet. The feasibility of traction using MAG-ESD, en bloc resection rate, complete en bloc resection rate, time required for preparation and attaching the magnetic anchor, procedure time, rate of retrieval of the magnetic anchors, and adverse events were evaluated. RESULTS: Fifty patients (median lesion size, 20 mm [range, 5-100]) were enrolled. MAG-ESDs were successfully performed for all 50 gastric lesions. Adequate counter-traction was obtained using the external magnet. En bloc resections were achieved and complete en bloc resections confirmed in all cases without adverse events. Attaching the magnetic anchor required a median of 6 minutes (range, 2-14). The median procedure time was 49 minutes (range, 15-301), and the magnetic anchors could be retrieved in all cases. CONCLUSIONS: This study clearly demonstrated the feasibility of this MAG-ESD in the stomach. We hope this procedure will facilitate the resection of difficult lesions. (Clinical trial registration number: UMIN000024100.).

Synchronous rectal and esophageal cancer treated with chemotherapy followed by two-stage resection.

We report a case of 61-year-old male who had synchronous advanced rectal cancer involving the urinary bladder massively associated with multiple liver metastases, and esophageal cancer successfully treated by neoadjuvant chemotherapy followed by two-stage resection. Although complete resection of each of the lesions was considered possible by performing anterior pelvic exenteration, liver resection, and esophagectomy, it might be impossible for the patient to endure the stress of all of these operative procedures at once. Therefore, we planned to perform staged treatment with prioritizing consideration. First, we instituted chemotherapy with the FOLFOX (oxaliplatin + fluorouracil + leucovorin) plus cetuximab regimen, which could adequately control both rectal and esophageal cancer. After 6 cycles of chemotherapy, high anterior resection combined with cystoprostatectomy and lateral segmentectomy plus partial hepatectomy was performed followed by staged esophagectomy with three-field lymph node dissection. It was possible to use oxaliplatin and cetuximab safely as neoadjuvant therapy not only for advanced rectal cancer but for esophageal cancer, and it was effective.

A randomized, prospective, double-blind, placebo-controlled trial of the effect of diltiazem gel on pain after hemorrhoidectomy.

BACKGROUND: Spasm of the internal anal sphincter is considered to be one of the causes of pain in anal diseases. We have evaluated the effects of topical diltiazem on postoperative pain after hemorrhoidectomy. METHODS: Sixty-two patients were randomly assigned to receive a 2 % diltiazem gel (n = 32) or a placebo gel (n = 30) after hemorrhoidectomy. Patients applied the gel to the anal region three times per day for 14 days. Pain both in the resting state and on defecation ranged from 0 to 10 on a numerical rating scale, and the number of prescribed loxoprofen tablets (Loxonin) were recorded and confirmed daily by telephone. Any morbidity during the follow-up period was recorded. RESULTS: Both pain scores during defecation and the number of analgesic tablets consumed tended to be lower in the diltiazem group, although they did not reach statistical significance (P = 0.09, P = 0.12, respectively). Total number of complications was significantly higher in the diltiazem group, but each incidence of complications, including itching sensation, headache, and dizziness was not statistically different. CONCLUSIONS: Perianal application of 2 % diltiazem gel after hemorrhoidectomy has the potential to reduce postoperative pain during defecation.

Quality of life in patients with chronic anal fissure after topical treatment with diltiazem.

AIM: To assess the physical and mental health of fissure patients before and after topical treatment with diltiazem. METHODS: Consecutive patients were enrolled prospectively into the study. Quality of life was measured with the short-forum 36 health survey (SF-36) before and after 6-wk treatment with diltiazem. Patients scored symptoms of pain, bleeding, and irritation using numeral rating scales at the initial and follow-up visits. Fissure healing was assessed and side effects were noted. RESULTS: Fissures healed in 21 of 30 (70%) patients. There were significant reductions in the scores of pain, bleeding, and irritation after 1 wk of treatment, respectively. Four patients experienced perianal itching and one patient reported headache. When measured at baseline, pain and irritation showed a negative impact on two of the eight subscales on the SF-36, respectively (bodily pain and social functioning for pain; vitality and mental health for irritation). Repeating the SF-36 showed an improvement in bodily pain (P = 0.001). Patients whose fissures healed reported an improvement in bodily pain, health-perception, vitality, and mental health (P < 0.05). CONCLUSION: Successful treatment of chronic anal fissure with topical diltiazem leads to improvement in health-related quality of life.

A screening for essential cell growth-related genes involved in arsenite toxicity in Saccharomyces cerevisiae.

Genes that are essential for growth in yeast were screened to identify those involved in arsenite sensitivity. We found that the knockdown of YPT1, ERG8, or RKI1 enhanced arsenite sensitivity in yeast.

[A case of intractable hepatic encephalopathy successfully treated by oral administration of vancomycin hydrochloride, with subsequent improvement of hepatic function reserve enabling transcatheter arterial chemoembolization against hepatocellular carcinoma].

We report a case of an 80-year-old male who suffered from intractable hepatic encephalopathy and hepatocellular carcinoma( HCC), associated with hepatitis type C-related liver cirrhosis. He was unable to receive HCC treatment due to the deterioration of his liver. His hepatic encephalopathy was resistant to oral administration of laxatives, lactulose, and kanamycin sulfate, etc. His blood ammonia concentration averaged about 130 mg/dL, and often exceeded 200 mg/dL(normal range: <80 mg/dL). Later, an oral administration of vancomycin hydrochloride, 0. 5 g once every 3 days, was initiated. Soon after ward, his blood ammonia concentration declined to the normal range(about 50 mg/dL), and the clinical symptoms of hepatic encephalopathy showed a remarkable improvement. By the continuation of vancomycin administration, the normalization of his state of consciousness was achieved, improving his quality of life, and his activities of daily living. Three months after beginning treatment, he was able to receive transcatheter arterial chemoembolization for the treatment of HCC, because his liver function reserve improved(Child-Pugh score decreased from 10 to 7).

[A case of metastatic pancreatic cancer with a remarkable response to combination therapy of gemcitabine and adoptive immune cell therapy].

A 52-year-old woman with a chief complaint of epigastric distress was diagnosed as having pancreatic cancer with multiple liver metastases. After insertion of a metallic stent for biliary stenosis, combination therapy of gemcitabine (GEM) and adoptive immune cell therapy (AICT) was initiated. GEM 1,000 mg/m2 was administered on day 1, 8 and 15 every 4 weeks, while AICT using MUC1 peptide-pulsed dendritic cells (DC) and anti-CD3-activated T lymphocytes (CAT) was given biweekly. After 6 courses of GEM and 9 courses of DC-CAT, the patient was considered to have a complete response (CR) on CT and MRI examination. CR has still been maintained by the continuous administration of GEM and CAT. The combination therapy of GEM and AICT was suggested to be effective against advanced pancreatic cancer.

Dysfunctional nascent polypeptide-associated complex (NAC) activity in ribosomes enhances adriamycin toxicity in budding yeast.

To elucidate the role of ribosomes in the manifestation of adriamycin toxicity, ribosome-binding proteins involved in adriamycin sensitivity were identified using budding yeast as a eukaryotic model. This revealed that adriamycin toxicity was enhanced byloss of the Egd1 or Egd2 subunits of the nascent polypeptide-associated complex(NAC). NAC is a heterodimer consisting of alpha (Egd2) and beta (Egd1 or Btt1)subunits, and is known to be involved in the translocation of nascent polypeptides into mitochondria or endoplasmic reticulum and in transcriptional activation in the nucleus. Because the loss of the Btt1 subunit had no effect on adriamycin sensitivity, the NAC conformation responsible for resistance to adriamycin appears to be the Egd1/Egd2 complex. We propose that functional NACin the ribosome is involved in resistance to adriamycin toxicity.

[A case of hepatitis B-related multiple hepatocellular carcinomas, most of which lead to necrosis possibly due to the implantation of an arterial infusion catheter].

The patient was a 59-year-old male with chronic hepatitis type B. He was diagnosed as having multiple hepatocellular carcinomas (HCCs), most of which showed hypervascular features on contrast-enhanced CT scan. He underwent the implantation of a 5-french catheter by" GDA coil method" for hepatic arterial infusion of chemotherapy. After the implantation, he suffered from high fever with a sharp elevation in transaminase levels. Since his liver function gradually deteriorated, he was not able to receive hepatic arterial infusion of chemotherapy. However, three weeks after catheter implantation, most of the tumors were no longer enhanced on dynamic CT scan, suggesting a loss of tumor vascularity, ie, induction of tumor necrosis. It was speculated that necrosis of the tumors was caused by the reduction of hepatic arterial blood flow due to the catheter placement.

Important parameters in the detection of left main trunk disease using stress myocardial perfusion imaging.

OBJECTIVES: We sought noninvasively to diagnose left main trunk (LMT) disease using myocardial perfusion imaging (MPI). METHODS: Five hundred and eight patients with suspected coronary artery disease (CAD) underwent both stress MPI and coronary angiography. The extent and severity of perfusion abnormalities were assessed using a 20-segment model. In addition, perfusion defects in both left anterior descending and left circumflex arterial territories were defined as a left main (LM) pattern defect, and those in 3-coronary arterial territories as a 3-vessel pattern defect. RESULTS: In 42 patients with LMT disease, a summed stress score (19.4 ± 10.0 vs. 13.5 ± 10.0; p < 0.0001) and a summed rest score (12.1 ± 9.7 vs. 7.0 ± 7.8; p = 0.002) were greater than in 466 patients without LMT disease, while a summed difference score was similar (7.3 ± 7.7 vs. 6.5 ± 6.1; p = NS). The prevalence of an LM-pattern defect was low in both groups (12% vs. 8%; p = NS). However, a 3-vessel pattern defect (33% vs. 7%; p < 0.0001), lung uptake of radiotracers (38% vs. 11%; p < 0.0001), and transient ischemic dilation (31% vs. 13%; p = 0.003) were more frequently observed in patients with LMT disease than in those without. Logistic regression analysis showed that a 3-vessel pattern defect (OR=3.5, 95% CI = 1.4-8.8; p = 0.007), lung uptake of radiotracers (OR = 2.5, 95% CI = 1.1-5.7; p = 0.03), and previous myocardial infarction (MI) (OR = 2.4, 95% CI = 1.0-5.7; p = 0.05) were the most important parameters to detect LMT disease. After excluding 163 patients with previous MI, a repeat analysis revealed that lung uptake of radiotracers (OR = 8.2, 95% CI = 2.3-29.2; p = 0.001) and an LM-pattern defect (OR = 6.3, 95% CI = 1.4-27.2; p < 0.02) were independent predictors for LMT disease. CONCLUSION: In the identification of LMT disease, lung uptake of radiotracers was a single best parameter, which was independent of the presence or absence of previous MI.

The diagnostic utility of the Heston index in gated SPECT to detect multi-vessel coronary artery disease.

OBJECTIVES: Although the Heston index, derived left ventricular (LV) volumetric analysis, is reported to best represent transient LV dilation on non-gated single-photon emission computed tomography (SPECT), its diagnostic performance has not been proven to identify extensive coronary artery disease (CAD) as assessed by coronary angiogram. Accordingly, we sought to evaluate the diagnostic utility of Heston index to detect multi-vessel CAD. METHODS: Post-stress and resting electrocardiogram-gated 99mTc-sestamibi SPECT was performed in 223 patients with suspected or known CAD. All of the patients underwent coronary angiography within 3 months of gated SPECT. The summed stress, summed rest, and summed difference scores were calculated using a 20-segment model. The left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were calculated automatically with the QGS program. In addition, stress-to-rest ratios of EDV, ESV, and (ESVx5+EDV) were calculated; the latter was defined as Heston index. RESULTS: In the 104 patients with multi-vessel CAD, the summed stress score (17.5+/-10.0 vs. 11.7+/-9.2, p<0.001), the summed difference score (9.1+/-6.3 vs. 4.3+/-4.2, p<0.0001), the Heston index (1.17+/-0.15 vs. 1.02+/-0.13, p<0.0001), the stress-to-rest ratio of EDV (1.05+/-0.10 vs. 0.99+/-0.09; p<0.0001), and that of ESV (1.23+/-0.21 vs. 1.04+/-0.17; p<0.0001, respectively) were greater than in the 119 patients with one-vessel CAD or insignificant lesion. The best cut-off value was determined as 1.09 for Heston index, giving a sensitivity of 76%, specificity of 77% for detection of multi-vessel CAD. Multiple stepwise logistic regression analysis showed that Heston index >or =1.09, summed stress score > or =14, and summed difference score > or =9 were the independent predictors of detecting multi-vessel CAD, yielding a sensitivity of 76% and specificity of 77% (global chi 2, 88.8). CONCLUSIONS: The Heston index is simple and achieves higher diagnostic value in the detection of multi-vessel CAD, compared with conventional analysis alone.

Hemodynamic and neurohumoral responses to the restriction of femoral blood flow by KAATSU in healthy subjects.

The application of an orthostatic stress such as lower body negative pressure (LBNP) has been proposed to minimize the effects of weightlessness on the cardiovascular system and subsequently to reduce the cardiovascular deconditioning. The KAATSU training is a novel method to induce muscle strength and hypertrophy with blood pooling in capacitance vessels by restricting venous return. Here, we studied the hemodynamic, autonomic nervous and hormonal responses to the restriction of femoral blood flow by KAATSU in healthy male subjects, using the ultrasonography and impedance cardiography. The pressurization on both thighs induced pooling of blood into the legs with pressure-dependent reduction of femoral arterial blood flow. The application of 200 mmHg KAATSU significantly decreased left ventricular diastolic dimension (LVDd), cardiac output (CO) and diameter of inferior vena cava (IVC). Similarly, 200 mmHg KAATSU also decreased stroke volume (SV), which was almost equal to the value in standing. Heart rate (HR) and total peripheral resistance (TPR) increased in a similar manner to standing with slight change of mean blood pressure (mBP). High-frequency power (HF(RR)) decreased during both 200 mmHg KAATSU and standing, while low-frequency/high-frequency power (LF(RR)/HF(RR)) increased significantly. During KAATSU and standing, the concentration of noradrenaline (NA) and vasopressin (ADH) and plasma renin activity (PRA) increased. These results indicate that KAATSU in supine subjects reproduces the effects of standing on HR, SV, TPR, etc., thus stimulating an orthostatic stimulus. And, KAATSU training appears to be a useful method for potential countermeasure like LBNP against orthostatic intolerance after spaceflight.

Hemodynamic and hormonal responses to a short-term low-intensity resistance exercise with the reduction of muscle blood flow.

We investigated the hemodynamic and hormonal responses to a short-term low-intensity resistance exercise (STLIRE) with the reduction of muscle blood flow. Eleven untrained men performed bilateral leg extension exercise under the reduction of muscle blood flow of the proximal end of both legs pressure-applied by a specially designed belt (a banding pressure of 1.3 times higher than resting systolic blood pressure, 160-180 mmHg), named as Kaatsu. The intensity of STLIRE was 20% of one repetition maximum. The subjects performed 30 repetitions, and after a 20-seconds rest, they performed three sets again until exhaustion. The superficial femoral arterial blood flow and hemodynamic parameters were measured by using the ultrasound and impedance cardiography. Serum concentrations of growth hormone (GH), vascular endothelial growth factor (VEGF), noradrenaline (NE), insulin-like growth factor (IGF)-1, ghrelin, and lactate were also measured. Under the conditions with Kaatsu, the arterial flow was reduced to about 30% of the control. STLIRE with Kaatsu significantly increased GH (0.11+/-0.03 to 8.6+/-1.1 ng/ml, P < 0.01), IGF-1 (210+/-40 to 236+/-56 ng/ml, P < 0.01), and VEGF (41+/-13 to 103+/-38 pg/ml, P < 0.05). The increase in GH was related to neither NE nor lactate, but the increase in VEGF was related to that in lactate (r = 0.57, P < 0.05). Ghrelin did not change during the exercise. The maximal heart rate (HR) and blood pressure (BP) in STLIRE with Kaatsu were higher than that without Kaatsu. Stroke volume (SV) was lower due to the decrease of the venous return by Kaatsu, but, total peripheral resistance (TPR) did not change significantly. These results suggest that STLIRE with Kaatsu significantly stimulates the exercise-induced GH, IGF, and VEGF responses with the reduction of cardiac preload during exercise, which may become a unique method for rehabilitation in patients with cardiovascular diseases.

Do eicosapentaenoic acid supplements attenuate age-related increases in arterial stiffness in patients with dyslipidemia?: A preliminary study.

The present study was conducted to examine the effect of eicosapentaenoic acid supplements on pulse wave velocity (PWV) in patients with dyslipidemia as a prospective open-labeled study. Eicosapentaenoic acid supplements (1,800 mg/day) were prescribed to 40 patients, and diet therapy in consultation with a nutritionist was conducted in 44 patients as a control group. These interventions were continued for 12 months, and PWV and blood examinations were performed at the start and end of these interventions. PWV increased in the control group but not in the eicosapentaenoic acid group. After adjustment for age, gender, the initial PWV, and the changes in mean blood pressure during the study period, a general linear model univariate analysis post hoc comparison demonstrated that the change in PWV during the period of study was significantly larger in the control group (42 +/- 20 cm/s) than in the eicosapentaenoic acid group (-9 +/- 19 cm/s) (p<0.05). Thus, this preliminary study suggested that eicosapentaenoic acid supplements attenuate age-related increases in arterial stiffness in patients with dyslipidemia. A further study with a larger number of subjects is proposed to confirm this beneficial effect of eicosapentaenoic acid supplements on arterial stiffness.

Amlodipine increases nitric oxide production in exhaled air during exercise in patients with essential hypertension.

BACKGROUND: Endothelial production of nitric oxide (NO) is attenuated in patients with essential hypertension. We investigated whether treatment with amlodipine increased exhaled NO output (VNO) at rest and during exercise in patients with essential hypertension. METHODS: We studied the effect of amlodipine in seven untreated hypertensive patients. Cardiopulmonary exercise testing and NO measurement of exhaled air were performed on these patients before and after 2 months of amlodipine treatment. RESULTS: Amlodipine decreased blood pressure (BP) both at rest and during exercise (at rest: 147.1 +/- 6.4 [SEM]/89.9 +/- 4.4 v 133.6 +/- 5.4/82.7 +/- 3.9 mm Hg, P <.05; at peak exercise: 224.9 +/- 8.0/113.1 +/- 5.3 v 207.0 +/- 6.0/100.7 +/- 5.0 mm Hg, P <.05) without affecting heart rate (at rest: 67.6 +/- 3.9 v 70.4 +/- 4.5 beats/min, P =.33; peak exercise: 146.4 +/- 7.4 v 144.0 +/- 7.2 beats/min, P =.49). Amlodipine did not affect minute ventilation (VE) at rest or during exercise. It did not alter anaerobic threshold, peak oxygen uptake (peak VO(2)), or peak workload. However, after amlodipine treatment, VNO was significantly greater both at rest (130.8 +/- 19.4 v 180.4 +/- 24.8 nL/min, P <.05) and at peak exercise (380.0 +/- 47.5 v 582.6 +/- 74.3 nL/min, P <.05). CONCLUSIONS: Amlodipine increased NO production, at least in the pulmonary circulation, in patients with essential hypertension. In addition to its antihypertensive effect, the enhancement of NO production by amlodipine in the vasculature of other organs may contribute to its beneficial effects on the cardiovascular system.

[Effects of acute administration of beraprost sodium on parameters related to atherosclerotic vascular damage in coronary artery disease].

OBJECTIVES: The present study was conducted to examine the effects of acute administration of prostacyclin derivatives on plasma levels of adhesion molecules, endothelial function, and pulse wave velocity in patients with coronary heart disease. METHODS: In 20 patients with coronary heart disease, plasma levels of vascular cell adhesion molecule-1, P-selectin, and beta-thromboglobulin, endothelial function, and pulse wave velocity were assessed before and after the cold pressor test. These assessments were performed again 2 hr after the oral administration of prostacyclin derivatives (beraprost sodium 40 micrograms) or placebo. Endothelial function was assessed by changes in forearm blood flow before and after reactive hyperemia. Pulse wave velocity was determined by the volume rendering method. RESULTS: Prostacyclin derivatives significantly improved endothelial function and decreased plasma beta-thromboglobulin level, but did not affect blood pressure and pulse wave velocity. Prostacyclin derivatives did not prevent the elevations of blood pressure and pulse wave velocity induced by the cold pressor test, but did prevent the elevations of P-selectin and beta-thromboglobulin induced by the cold pressor test. CONCLUSIONS: Prostacyclin derivatives improved endothelial function and prevented platelet activation induced by the cold pressor test. Prostacyclin apparently has an anti-atherogenic effect.

AT-1015, a novel serotonin2A receptor antagonist, improves resaturation of exercised ischemic muscle in hypercholesterolemic rabbits.

OBJECTIVE: The effect of AT-1015, a serotonin(2A) receptor antagonist, on the resaturation of ischemic muscle in a hypercholesterolemic rabbit model was examined with near-infrared spectroscopy. METHODS: New Zealand White male rabbits were fed normal chow or cholesterol-rich chow. Ischemia was induced in the right hindlimb by ligation of the femoral artery, accompanied by balloon injury of the iliac artery. At 3 days after induction of ischemia, the bilateral gastrocnemius muscles were subjected to passive contraction for 2 minutes. The oxygen resaturation time of the gastrocnemius muscle after exercise was measured by near-infrared spectroscopy. AT-1015 was orally administered for 3 days after induction of ischemia. Assay of serotonin level in platelet-poor plasma and histologic examination of muscle and artery were performed in another set of rabbits. RESULTS: Oxygen resaturation time of the ischemic gastrocnemius was significantly prolonged in hypercholesterolemic rabbits compared with in normal rabbits without AT-1015, whereas there was no difference between both groups of rabbits that were administered AT-1015. Plasma level of serotonin in hypercholesterolemic rabbits was significantly increased compared with that in normal rabbits. No histologic differences were found in both muscle and artery among all groups. CONCLUSIONS: A serotonin(2A) receptor antagonist improved the oxygen resaturation of ischemic calf muscle after exercise in hypercholesterolemia. The interaction between plasma free serotonin and the serotonin(2A) receptor may play an important role in muscle oxygenation in ischemic limbs.