Pre-Operative Four Dimensional Flow Sensitive Magnetic Resonance Imaging Assessment of Aortic Side Branches as a Method to Predict Risk of Type II Endoleak Resulting in Sac Enlargement After EVAR.

OBJECTIVE: To predict sac enlargement with type II endoleak (ELII) before endovascular aneurysm repair (EVAR) using four dimensional flow sensitive magnetic resonance imaging (4D flow MRI). METHODS: A single centre retrospective analysis of prospectively collected data was conducted. Patients with an abdominal aortic aneurysm (AAA) who underwent EVAR between 2013 and 2019 were included. Aortic branches occluded pre-EVAR, and patients with endoleaks other than ELII were excluded. The aortic branch diameter, peak flow velocity (PFVe), and amplitude of the dynamics of flow volume (AFV) were measured in each aortic branch pre-EVAR. Total flow volume per minute (TFV/min), defined as the sum of AFV/min, was calculated in each case. According to computed tomography findings one year post-EVAR, the aortic branches and patients were divided into patent vessel and occluded vessel groups and sac expanding and non-expanding groups. PFVe, AFV/min, and TFV/min were analysed via receiver operating characteristic curve analysis. RESULTS: The patent aortic branches pre-EVAR (69 inferior mesenteric arteries [IMAs]; 249 lumbar arteries [LAs]) of 100 patients were included. Patent IMAs (n = 14) and occluded IMAs (n = 55), patent LAs (n = 23) and occluded LAs (n = 226), and expanding (n = 9) and non-expanding (n = 91) groups were compared, respectively. No statistically significant difference was observed in branch diameters (IMA; patent, 2.5 ± 0.8 mm, occluded, 2.5 ± 0.8 mm, p < .78 and LA; patent, 1.5 ± 0.3 mm, occluded, 1.5 ± 0.4 mm, p < .35). PFVe (IMA; patent, 262.6 mm2/sec, occluded, 183.4 mm2/sec and LA; patent, 142.6 mm2/sec, occluded, 47.7 mm2/sec) and AFV/min (IMA; patent, 8.4 mL, occluded, 5.2 mL and LA; patent, 4.2 mL, occluded, 1.4 mL) were higher in the patent vessel group (p < .050). TFV/min was statistically significantly higher in the expanding group (24.1 mL/min) than in the non-expanding group (7.0 mL/min) (p < .010). CONCLUSION: Pre-EVAR haemodynamic analyses using 4D flow MRI were useful to detect aortic branches responsible for ELII and to predict AAA cases with sac enlargement. This analysis suggests a new strategy for pre-EVAR aortic branch embolisation.

Usefulness of a finger-mounted tissue oximeter with near-infrared spectroscopy for evaluating the intestinal oxygenation and viability in rats.

PURPOSE: To investigate the utility of the device for evaluating intestinal oxygenation and viability using an animal model. METHODS: Sprague-Dawley rats underwent laparotomy under general anesthesia, and the blood vessels in the terminal ileum were clamped to create ischemia. We measured the regional tissue oxygenation saturation (rSO2) using an oximeter after 1, 3, and 6 h of vessel clamping. Ischemic tissue damage was assessed using a histological score. The intestine was reperfused after each clamping period, and intestinal rSO2 and survival rate were evaluated. RESULTS: When reperfusion was performed at 1 and 3 h after ischemia, rSO2 increased after 10 min, and it improved to the same level as for normal intestine after 1 h; all rats survived for 1 week. In contrast, after 6 h of ischemia, rSO2 did not increase after reperfusion, and all animals died within 2 days. The histological scores increased after 1 h of reperfusion, with longer clamping periods. CONCLUSION: A finger-mounted tissue oximeter could evaluate intestinal ischemia and the viability, which is thus considered to be a promising result for future clinical application.

Tissue Oximeter with Selectable Measurement Depth Using Spatially Resolved Near-Infrared Spectroscopy.

Tissue oxygenation sensing at a few millimeters deep is useful for surgical and postoperative management. However, the measurement sensitivity at each depth and the proper sensor combination have not been clarified. Here, the measurement characteristics of oximetry by spatially resolved near-infrared spectroscopy were analyzed using Monte Carlo simulation and phantom experiment. From summing the sensitivities of each depth, it was quantitatively found that the measurement sensitivity curve had a peak, and the measurement depth can be adjusted by combining the two distances between the light source and the detector. Furthermore, the gastric tissue was 10-20% smaller in terms of measurement depth than the skin-subcutaneous tissue. A miniaturized oximeter was prototyped so that it could be used in combination with an endoscope or laparoscope. The optical probes consisted of light emitting diodes with wavelengths of 770 nm and 830 nm and photodetectors located 3 to 30 mm from the light source. Phantom experiments using the probes demonstrated the tendency of theoretical analysis. These results suggest the possibility of measuring tissue oxygen saturation with a selectable measurement depth. This selectable method will be useful for obtaining oxygenation information at a depth of 2-5 mm, which is difficult to measure using only laparoscopic surface imaging.

Potential role of transforming growth factor-beta 1/Smad signaling in secondary lymphedema after cancer surgery.

Secondary lymphedema often develops after cancer surgery, and over 250 million patients suffer from this complication. A major symptom of secondary lymphedema is swelling with fibrosis, which lowers the patient's quality of life, even if cancer does not recur. Nonetheless, the pathophysiology of secondary lymphedema remains unclear, with therapeutic approaches limited to physical or surgical therapy. There is no effective pharmacological therapy for secondary lymphedema. Notably, the lack of animal models that accurately mimic human secondary lymphedema has hindered pathophysiological investigations of the disease. Here, we developed a novel rat hindlimb model of secondary lymphedema and showed that our rat model mimics human secondary lymphedema from early to late stages in terms of cell proliferation, lymphatic fluid accumulation, and skin fibrosis. Using our animal model, we investigated the disease progression and found that transforming growth factor-beta 1 (TGFB1) was produced by macrophages in the acute phase and by fibroblasts in the chronic phase of the disease. TGFB1 promoted the transition of fibroblasts into myofibroblasts and accelerated collagen synthesis, resulting in fibrosis, which further indicates that myofibroblasts and TGFB1/Smad signaling play key roles in fibrotic diseases. Furthermore, the presence of myofibroblasts in skin samples from lymphedema patients after cancer surgery emphasizes the role of these cells in promoting fibrosis. Suppression of myofibroblast-dependent TGFB1 production may therefore represent an effective pharmacological treatment for inhibiting skin fibrosis in human secondary lymphedema after cancer surgery.

The Role of Animal Models in Elucidating the Etiology and Pathology of Abdominal Aortic Aneurysms: Development of a Novel Rupture Mechanism Model.

Existing animal models do not replicate all aspects of abdominal aortic aneurysms (AAAs), including the rupture mechanisms. From histopathological analyses conducted in humans, it has been found that the vasa vasorum of the AAA wall is the starting point of circulatory failure and that bulging and dilatation of the abdominal aorta occurs through inflammation and tissue degeneration. We created a new animal model (the hypoperfusion-induced model) of AAAs. In this study, we describe the current animal models of AAAs and present the utility of our new model of AAAs.

Flow dynamics of type II endoleaks can determine sac expansion after endovascular aneurysm repair using four-dimensional flow-sensitive magnetic resonance imaging analysis.

OBJECTIVE: The objective of this study was to investigate the hemodynamic parameters of type II endoleaks (T2ELs) to predict sac expansion using four-dimensional flow-sensitive magnetic resonance imaging (4D-flow MRI) analysis. METHODS: Patients who underwent endovascular aneurysm repair (EVAR) and were diagnosed with a T2EL were included in the study. Using 4D-flow MRI at 7 days, the peak flow velocity and amplitude of dynamics of blood flow per minute were measured in each T2EL vessel. The peak flow velocity was defined as the maximum of the absolute value of the blood flow velocity. The amplitude of dynamics of blood flow in the tributary arteries was defined as the sum of the absolute values of the inflow and outflow volume in each vessel. The amplitude of dynamics of blood flow in the tributary arteries per sac was calculated in each sac. The aneurysm sac diameter was measured by computed tomography (CT) at 1 year. The patients were divided into two groups according to the presence or absence of sac expansion. RESULTS: Of 155 patients who underwent EVAR, both CT angiography and 4D-flow MRI were performed in 107 patients at 7 days after EVAR. Among them, 39 (36.4%) were found to have a T2EL, of whom 28 were re-evaluated with CT angiography and 4D-flow at 1 year; 7 patients had expanding sacs (expanding group), whereas 21 had nonexpanding sacs (not-expanding group). At 7 days, 28 patients had 80 T2EL vessels detected by 4D-flow MRI, of which 39 vessels (48.8%) had stopped flowing at 1 year (transient vessels); 41 vessels (51.3%) had sustained flow (persistent vessels). The persistent vessels had significantly larger peak flow velocity and amplitude of dynamics of blood flow. The comprehensive analysis of T2EL vessels per sac identified that the amplitude of dynamics of blood flow in the tributary arteries per sac was significantly higher in the expanding group than in the not-expanding group. A receiver operating characteristic curve analysis revealed that the sensitivity and specificity of sac enlargement at a cutoff value of 3750 mm3/min were 85.7% and 76.2%, respectively. CONCLUSIONS: The fate of aneurysm sacs with T2ELs after EVAR has remained difficult to predict. A comprehensive analysis of concurrent multiple T2EL vessels using 4D-flow MRI analysis may enable prediction of the sac expansion after EVAR.

The Effect of a High-Fat Diet on the Development of Abdominal Aortic Aneurysm in a Vascular Hypoperfusion-Induced Animal Model.

Abdominal aortic aneurysm (AAA) is a vascular disease characterized by chronic inflammation in the infrarenal aorta. Most cases of AAA remain asymptomatic until rupture, and the mortality rate of patients with AAA rupture is very high. Currently, the relation between dietary habits and AAA development remains unknown. In this study, we evaluated the effects of a high-fat diet on the development of AAA in a vascular hypoperfusion-induced animal model. The risk of AAA rupture and AAA diameter in the high-fat group significantly increased compared with those in the control group. The number and size of adipocytes in the vascular wall in the high-fat group significantly increased as compared with those in the control group. Additionally, the collagen-positive sections in the areas with adipocytes significantly decreased as compared with those without adipocytes. The protein levels of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-12, and macrophage-positive areas in the parts with adipocytes also significantly increased as compared with those without adipocytes. These data suggested that AAA rupture risk increased through accelerating chronic inflammation due to the accumulation of adipocytes in the vascular wall in the high-fat group.

Lysophosphatidylcholine Acyltransferase-3 Expression Is Associated with Atherosclerosis Progression.

Free arachidonic acid (AA) is an important precursor of lipid mediators such as leukotrienes and prostaglandins that induces inflammation and is associated with atherosclerosis progression. Recent studies have shown that lysophosphatidylcholine acyltransferase-3 (LPCAT3) converts lysophosphatidylcholine (LPC) and free AA into phosphatidylcholine (PC)-containing AA (arachidonyl-PC) and thereby can regulate intracellular free-AA levels. However, the association between LPCAT3 and atherosclerosis remains to be established. In this study, we analyzed human and mouse atherosclerotic tissues to gain insight into the arachidonyl-PC metabolism involving LPCAT3 using imaging mass spectrometry. The data revealed a complementary distribution of arachidonyl-PC and LPC in human atherosclerotic tissues with arachidonyl-PC decreasing and LPC increasing as atherosclerosis progressed. Furthermore, we found a homologous distribution of LPCAT3 expression and arachidonyl-PC based on atherosclerotic progression. In contrast, in ApoE-deficient mice, atherosclerosis increased both arachidonyl-PC accumulation and LPCAT3 expression. Taken together, these findings suggest that the regulation of LPCAT3 expression might be associated with atherosclerotic progression in humans.

Multi-center rater-blinded study of early intervention with the Hand Incubator for breast cancer-related lymphedema (the BEAT-EDEMA trial): Proposal of a research protocol.

Postoperative lymphedema is considered irreversible once it has developed, and significantly lowers the patient's quality of life. However, lymphatic function has recently been clarified, and it is possible that lymphedema can be cured if early treatment is started. This two-arm randomized clinical trial (UMIN000026124) will prospectively evaluate 24 patients with early-stage breast cancer-related lymphedema at the Nagoya University Hospital and Aichi Cancer Center Hospital. The eligibility criteria will be patients who are diagnosed with stage 0-1 breast cancer-related lymphedema, as defined by the International Society of Lymphology, within 12 weeks after breast cancer surgery. The diagnosis of lymphedema will be confirmed using a bioimpedance spectroscopy device (L-Dex®). Participants will be randomized 1:1 into the intervention and control groups. The physicians and patients will be aware of their group assignment, although treatment efficacy will be evaluated by raters who are blinded to the group assignments. The intervention group will complete grasping exercises in the Hand Incubator device for 4 weeks. The primary outcome will be the change in the affected upper limb's volume after the intervention, as measured using the water displacement method. This study may help establish a standard treatment for postoperative lymphedema.

Hemodynamic Analysis of Endoleaks After Endovascular Abdominal Aortic Aneurysm Repair by Using 4-Dimensional Flow-Sensitive Magnetic Resonance Imaging.

BACKGROUND: An endoleak is a common complication of endovascular abdominal aortic aneurysm repair (EVAR), and it can be associated with aneurysmal growth. This pilot study used 4-dimensional flow-sensitive magnetic resonance imaging (4D-flow) to assess the hemodynamics of different types of endoleaks (I-IV). METHODS AND RESULTS: Magnetic resonance angiography, 4D-flow, and computed tomography angiography (CTA) were performed in 31 patients after nitinol-based stent-graft deployment. With 4D-flow, the 3D streamlines of endoleaks appear as integrated traces along the instantaneous velocity vector field that are color-coded according to the local velocity magnitude of the leak. The 4D-flow analysis identified endoleaks in 18 patients (58.1%), whereas CTA identified endoleaks in 13 patients (41.9%). The 4D-flow analysis created a characteristic image of each type of endoleak. Among patients with endoleaks, 4D-flow identified concomitant multiple endoleaks in 7 (39%) patients, and it further differentiated type II endoleaks from type IIa endoleaks (to-and-fro biphasic flow pattern from a branch vessel) and from type IIb endoleaks (monophasic flow pattern with a connection between the inflow and outflow branches). CONCLUSIONS: The 4D-flow analysis was more sensitive than CTA for detecting an endoleak, and it could subclassify type II endoleaks. In addition, 4D-flow differentiated between concomitant endoleak types in a single patient. (Circ J 2016; 80: 1715-1725).

The preventive effect of fish oil on abdominal aortic aneurysm development.

Abdominal aortic aneurysm (AAA) is a vascular disease involving gradual dilation of the abdominal aorta and high rupture-related mortality rates. AAA is histologically characterized by oxidative stress, chronic inflammation, and extracellular matrix degradation in the vascular wall. We previously demonstrated that aortic hypoperfusion could cause the vascular inflammation and AAA formation. However, the preventive method for hypoperfusion-induced AAA remains unknown. In this study, we evaluated the effect of fish oil on AAA development using a hypoperfusion-induced AAA animal model. Dilation of the abdominal aorta in the fish oil administration group was smaller than in the control group. Collagen destruction and oxidative stress were suppressed in the fish oil administration group than in the control group. These results suggested that fish oil could prevent the development of AAA induced by hypoperfusion.

Imaging Mass Spectrometry Reveals a Unique Distribution of Triglycerides in the Abdominal Aortic Aneurysmal Wall.

The pathophysiology underlying abdominal aortic aneurysms (AAAs) remains unknown. In this study, we applied imaging mass spectrometry (IMS) to analyze the pathophysiology of the aneurysmal wall. Comparisons were performed between the tissue samples from the neck and the sac of the AAA, at a single time point, in 30 patients who underwent elective surgery of their AAAs. The localization of each lipid molecule in the aortic wall was assessed by IMS. Histopathological examination and IMS revealed a characteristic distribution of triglycerides (TGs) specifically in the aneurismal adventitia of the sac. This characteristic TG distribution was derived from an ectopic appearance of adipocytes in the adventitia. Furthermore, ectopic adipocyte accumulation in the aortic wall leads to the loss of the collagen fiber network subsequent to the wall rupture. The underlying mechanism of adipocyte accumulation involves the presence of adipose-derived stem cells (ADSCs) in the aneurismal adventitia and the expression of peroxisome proliferator-activated receptor gamma 2, a master regulator of adipocyte differentiation by some ADSCs. This study reveals new, previously overlooked aspects of AAA pathology.

Quantitative assessment of the free jejunal graft perfusion.

BACKGROUND: Reconstruction with free jejunal graft (FJG) is often performed for patients with hypopharyngeal or cervical esophageal cancer. During reconstruction with an FJG after pharyngoesophagectomy, it is critical to intraoperatively detect venous anastomotic failure and subsequent venous malperfusion to avoid postoperative FJG necrosis. This study introduces a novel method for assessing blood perfusion in FJGs by using indocyanine green (ICG) fluorescence angiography. METHODS: We used ICG fluorescence angiography to quantitatively assess FJG blood perfusion in archived fluorescence video files from 26 patients who had undergone FJG transfer. A software program "ROIs", was used to create a time-fluorescence intensity curve. We retrospectively measured the maximum fluorescence intensity at the terminal ileum and the duration (T1/2max) between when the intensity began rising and when it reached half of the maximum. RESULTS: Among the 26 patients, 5 patients suffered venous anastomotic failure. In three of these cases, anastomosis was corrected intraoperatively; the other two patients underwent a second FJG transfer. Retrospective assessment showed that the mean T1/2max at the FJG serosae was significantly longer in these five patients than that in FJGs with good blood perfusion. Our analysis revealed that a T1/2max >9.6 s may be a good indicator of FJG venous malperfusion. CONCLUSIONS: Quantitative analysis of ICG fluorescence angiography proved useful for detecting venous anastomotic failure of FJG, and may help to reduce vascular problems in FJG reconstruction.

Early outcomes of iliac branch grafts in the endovascular repair of abdominal aortic aneurysms with concomitant bilateral common iliac artery aneurysms at a Japanese institution.

PURPOSE: Endovascular aneurysm repair (EVAR) is used to treat abdominal aortic aneurysms (AAAs) with bilateral common iliac artery aneurysms (CIAAs), and an interruption of the bilateral internal iliac arteries (IIAs) is often needed, which may cause postoperative ischemic complications. An iliac branch device (IBD) has thus been introduced as an endovascular technique to preserve the IIA flow. This study aimed to evaluate the technical feasibility and short-term results of using an IBD when treating AAA with bilateral CIAAs in a Japanese institution, where IBD use has still not been approved by the government. METHODS: EVAR was performed using an IBD in six patients at high risk for open repair of an AAA with bilateral CIAAs. RESULTS: Advanta V12 stent grafts were successfully placed in the IIA, bridging between the IIA and the IBD side branch from the contralateral iliac artery. Subsequently, EVAR was performed as usual. The technical success rate was 100 %. At the most recent follow-up (mean follow-up period, 14.2 months), all IBDs were patent. No patients complained of buttock claudication or ischemic colitis. CONCLUSIONS: The implantation of an IBD during EVAR is technically feasible in Japanese AAA patients with bilateral CIAAs, and may be a viable method to avoid pelvic ischemic complications, such as intractable buttock claudication.

Current venous thromboembolism management and outcomes in Japan.

BACKGROUND: Epidemiology and clinical management of acute venous thromboembolism (VTE) are not readily available in Japan. METHODS AND RESULTS: The Japan VTE Treatment Registry (JAVA) is a multicenter cohort study of consecutive patients with an objectively confirmed, symptomatic acute pulmonary embolism (PE), symptomatic acute deep vein thrombosis (DVT), or asymptomatic acute proximal DVT. Of the 1,076 patients enrolled with acute VTE, 68.7% presented with an isolated DVT; 17.0% had PE alone; and 14.4% had both. VTE management was characterized by a high rate of inferior vena cava filter insertion (40.6%), frequent thrombolysis (21.1%), and sub-therapeutic unfractionated heparin-based anticoagulation, followed by warfarin prescription, mostly targeting an international normalized ratio of 2.0 (range, 1.5-2.5). During a mean observation period of 252.5 days, 29 recurrent cases of VTE were documented, yielding an incidence rate of 3.9 per 100 patient-years. A total of 123 patients died during the study period, corresponding to a rate of 16.6 deaths per 100 patient-years. The incidence of major bleeding was 3.2% per patient-year, including 2 fatal hemorrhages and 7 intracranial hemorrhages. CONCLUSIONS: VTE management in Japan is characterized by a highly aggressive strategy in the acute phase, in contrast to protocols that use low-level anticoagulation. The VTE recurrence rates in Japan and Western countries are similar, but mortality is higher in Japan, with significant variability depending on patient and management characteristics.

Intraoperative lymph mapping with preoperative vein mapping to prevent postoperative lymphorrhea following paramalleolar bypass surgery in patients with critical limb ischemia.

PURPOSE: Paramalleolar bypass surgery requires a long incision to harvest the great saphenous vein (GSV), which is often associated with intractable postoperative lymphorrhea. To prevent this complication, we developed a novel method of intraoperative lymph imaging and preoperative vein mapping for vein harvesting. METHODS: Thirteen consecutive patients with critical limb ischemia (CLI) underwent both preoperative vein mapping and intraoperative lymph mapping (Group A). Duplex vein mapping was performed to mark the GSV. Lymph mapping was performed with indocyanine green fluorescence lymphography. Paramalleolar bypasses were performed using reversed GSV grafts, with careful ligation of the subcutaneous lymph collector vessels above the GSV. The development of intractable postoperative lymphorrhea and the length of the postoperative hospital stay were compared with those in the previous ten consecutive CLI patients without lymph mapping who underwent paramalleolar bypass (Group B). RESULTS: The occurrence of intractable wound lymphorrhea by the 30th postoperative day was 3/10 (30 %) in Group B, while it was 0/13 (0 %) in Group A (p < 0.05). The length of the postoperative hospital stay was 31.7 ± 8.8 and 57.5 ± 39.5 days (Group A and Group B, respectively, p < 0.05). CONCLUSIONS: Intraoperative lymph mapping and preoperative vein mapping are technically feasible and can positively contribute to the prevention of postoperative lymphorrhea after GSV harvesting.

Cilostazol inhibits accumulation of triglycerides in a rat model of carotid artery ligation.

OBJECTIVE: Triglyceride (TG) accumulation in arterial tissue is associated with the development of cardiovascular disease; however, the underlying mechanism remains unclear. Cilostazol (CLZ), a selective inhibitor of phosphodiesterase 3, has antiplatelet and vasodilating effects and may decrease serum TG levels. We examined the effect of CLZ on TG accumulation in the arterial tissue of a rat model of carotid artery ligation. METHODS: Rats were fed normal chow with 0.1% CLZ (CLZ group) or without CLZ (control group) for 4 weeks after unilateral carotid artery ligation near the carotid bifurcation. RESULTS: At the end of this period, the control group showed 3.3-fold higher TG levels in the ligated carotid artery than in the contralateral artery; however, compared with the contralateral artery, the ligated artery in the CLZ group showed significantly lower levels of TG accumulation but similar serum levels of TG, total cholesterol, and high-density lipoprotein cholesterol. Furthermore, matrix-assisted laser desorption/ionization imaging mass spectrometry revealed that the ligated carotid artery in both groups had ubiquitous accumulation of TG in the intima, media, and adventitia, along with decreased heme B signals, which was indicative of ischemia. However, heme B signals were less reduced in the CLZ group than in the control group. CONCLUSIONS: Our results indicate that CLZ can inhibit the ubiquitous accumulation of TG in arterial tissues, possibly by ameliorating tissue ischemia. CLZ may be useful in improving arterial tissue hemodynamics and lipid metabolism.

Detection of hepatocellular carcinomas with near-infrared fluorescence imaging using indocyanine green: its usefulness and limitation.

BACKGROUND: Indocyanine green (ICG), an agent for measuring liver function, becomes fluorescent under near-infrared (NIR) light after binding to serum proteins. Hepatocellular carcinoma (HCC) with a deposit of preoperatively administered ICG becomes clearly detectable under ICG fluorography; however, it remains unclear whether this detection method is always reliable. This case series study was designed to clarify the reliability of this method. METHODS: ICG (0.5 mg/kg) was injected from the 3rd to 28th preoperative day to evaluate hepatic function in 58 patients with HCCs. Preoperative imaging modalities identified 76 HCC foci. The operative fields and resected specimens were observed with an NIR camera system. Preoperatively detected lesions and lesions newly detected by the ICG fluorography were histologically investigated. RESULTS: ICG fluorography identified 73 of 76 preoperatively diagnosed HCC lesions. Intraoperative ICG fluorography visualized 47 lesions in 40 patients. The other 26 lesions showing emission were found in the sectioned specimens under NIR observation. Other than preoperatively diagnosed foci, ICG fluorography visualized 35 new lesions, including 6 HCCs, 2 dysplastic nodules and 27 non-neoplastic lesions, such as bile plugs and cysts. The sensitivity of ICG fluorography for HCCs was 96% and its positive predictive value was 71.5%. CONCLUSIONS: Indocyanine green fluorography is useful to detect HCCs; however, attention should be paid to the fact that HCCs may be occasionally overlooked by this imaging method and that lesions detected by this method are not always neoplastic lesions.

Effects of inhaled ß­caryophyllene on vascular stiffness in smokers: A randomized, double­blind, placebo­controlled trial.

Approximately 1.14 billion smokers worldwide are at risk of developing tumors, cardiovascular diseases and respiratory diseases. Smoking cessation is the first choice of health care; however, the disease should be attenuated in individuals who never stop smoking, which escalates medical costs. Therefore, alternative options are needed to manage the social burden. The present study proposed an alternative method to prevent such diseases by inhalation of ß-caryophyllene (BCP). A placebo-targeted, dose-searching, double-blind, parallel-group comparative study was conducted on 19 subjects. The BCP intervention was performed using a flavor capsule inserted in a cigarette filter. The primary endpoint was the reducibility of brachial-ankle pulse wave velocity (baPWV). The secondary endpoints were confirmation of the bioavailability of BCP inhalation with cigarette smoke, confirmation of the effect of BCP inhalation on respiratory function, and association between respiratory function and blood concentration and baPWV reduction. The BCP concentration in the blood reached 4 ng/ml in the BCP 15% group 10 min after inhalation. The baPWV decreased in BCP-inhaling subjects whose initial baPWV was >1,300 cm/sec. The correlation analyses revealed that the higher the forced expiratory volume in 1 sec, the better the transition of baPWV. Inhaled BCP with cigarette smoke could reduce the baPWV and the risk of cardiovascular diseases in smokers. These findings indicated that with the introduction of BCP capsule-cigarettes in the future, smokers will be able to take care of their health, which may help reduce national medical costs. BCP microcapsules placed in cigarette wrapping paper may possibly reduce the risk of sidestream smoke and contribute to improved public health. This clinical research was retrospectively registered in the University Hospital Medical Information Network (UMIN)-Clinical Trials Registry with the following identifications: UMIN000048510 and UMIN000048512 on August 15, 2022.

The Usefulness of a Three-Microneedle Device for Indocyanine Green Fluorescence Lymphography.

Background: Indocyanine green (ICG) fluorescence lymphography is widely used to diagnose lymphedema. There is little consensus on the appropriate injection method for ICG fluorescence lymphangiography. We used a three-microneedle device (TMD) for skin injection of ICG solution and investigated its usefulness. Methods and Results: Thirty healthy volunteers were injected with ICG solution using a 27-gauge (27G) needle in one foot and a TMD in the other foot. Injection-related pain was evaluated using the Numerical Rating Scale (NRS) and Face Rating Scale (FRS). The skin depth of the injected ICG solution was evaluated by injecting the solution into the skin of amputated lower limbs using a 27G needle or TMD using ICG fluorescence microscopy. The median and interquartile range of the NRS scores was 3 (3-4) and 2 (2-4) in the 27G needle and TMD groups, respectively; that of the FRS scores was 2 (2-3) and 2 (1-2) in the 27G needle and TMD groups, respectively. Injection-related pain was significantly lower with the TMD than with the 27G needle. The lymphatic vessels were similarly visible using both needles. The depth of the ICG solution varied for each injection with a 27G needle (400-1200 µm) and was consistent at ∼300-700 µm below the skin surface using the TMD. Injection depth was significantly different between the 27G needle and the TMD. Conclusions: Injection-related pain decreased using the TMD, and ICG solution depth was consistent on fluorescence lymphography. A TMD may be useful for ICG fluorescence lymphography. Clinical Trials Registry (UMIN-CTR; ID: UMIN000033425).