Early Enhancement with Contrast-Enhanced Ultrasonography Relates to the Number of Small-Diameter Neovessels in the Carotid Plaque.

BACKGROUND AND PURPOSE: Intraplaque neovessels (INVs) have been recognized as a major cause of intraplaque hemorrhage and subsequent vulnerability of the carotid plaque. However, the exact mechanisms by which INVs cause intraplaque hemorrhage remain unclear. Various sizes of INVs coexist in carotid plaques pathologically, and we hypothesized that the size of INVs would be associated with carotid plaque histology, particularly in terms of intraplaque hemorrhage. Detection method of INV is important when determining whether carotid plaques are vulnerable, and contrast-enhanced ultrasonography (CEUS) is one of the most useful methods to detect them. The purpose of this study was to examine the relationship between findings from CEUS and vascular pathology obtained by carotid endarterectomy (CEA). We focused on associations between small and large INVs evaluated by CEUS and histologically defined intraplaque hemorrhage. METHODS: Participants comprised 115 patients (mean age, 73.0 ± 7.2 years; 96 men) who underwent preoperative CEUS and underwent CEA. CEUS findings were evaluated as vascular grade at 0 min (Vas-G0) and 10 min (Vas-G10) after contrast injection. Plaques were histologically evaluated quantitatively for the total area of intraplaque hemorrhage, cholesterol, and calcification and the thinnest fibrous cap. Immunohistochemical studies were conducted using anti-CD-34 antibody as a marker for endothelial cells. INVs were divided into two groups depending on diameter: small INVs, <50 µm; and large INVs, ≥50 µm. The numbers of small and large blood vessels in the plaque were quantified histologically. Associations of small and large INVs with CEUS, plaque histology, and clinical findings were assessed by uni- and multivariable analyses. RESULTS: Multivariable analyses indicated that CEUS Vas-G0 was associated with the 4th quartile of the number of small INVs compared with other quartiles, and Vas-G10 was associated with the 4th quartile of the number of large INVs. Histologically, the presence and area of intraplaque hemorrhage were associated with the number of small INVs, while the increased number of large INVs was associated with infrequent plaque disruption and thicker fibrous cap. CONCLUSIONS: Our study showed that early phase enhancement in the CEUS can help identify plaque vulnerability by predicting a larger number of small INVs. This information can also help determine treatment strategies for carotid plaque.

Patient-Derived Training Simulator for Image-Guided Adaptive Brachytherapy of Locally Advanced Cervical Cancers: Development and Initial Use.

Image-guided adaptive brachytherapy (IGABT) using intracavitary and interstitial (IC/IS) techniques plays a pivotal role in definitive radiotherapy for locally advanced cervical cancers. However, the training opportunities for interstitial needle application are limited, preventing this technique from becoming widespread. This study aimed to develop a training simulator for IC/IS brachytherapy. The simulator consists of a soft silicone tumor phantom and acrylic tube mimicking the vagina; it has high visibility because of translucent materials and is compatible with computed tomography (CT) and magnetic resonance imaging (MRI). A patient harboring a typical bulky and irregular-shaped cervical tumor was selected from 495 in-house IGABT-treated candidates, and a tumor phantom (68 × 49 × 45 mm) modeled on this patient was produced from three-dimensional real-scale measurements of the MRI-based high-risk clinical target volume at first brachytherapy. In trial use by two physicians with different levels of IGABT skills, a Fletcher-Suit Asian Pacific applicator, and a Venezia applicator with interstitial needles were nicely applied to the simulator, facilitating successful creation of CT-based treatment plans consistent with clinical practice. Thus, the training simulator can be useful for the training of IC/IS brachytherapy, and warrants further research employing a greater number of phantoms and practitioners to verify its educational value.

Single-cell genotyping of phytoplankton from ocean water by gel-based cell manipulation.

A comprehensive understanding of phytoplankton diversity is valuable for assessing an environment of interest as phytoplankton are primary producers in various aquatic food webs. Microscopic analyses are useful for diversity assessment based on characteristic cell morphologies. However, phylogenetic classification based solely on morphology requires an extremely high level of expertise. The genetic approach is another option for evaluating phytoplankton diversity; however, it cannot reveal morphological information. To integrate these two approaches, an original technology was developed, that is referred to as microcavity array (MCA)/gel-based cell manipulation (GCM). The model experiments using monocultures of various phytoplankton indicated that the efficiencies of cell recovery and isolation of single-cell plankton were dependent on cell size and shape. Cells with widths larger than the cavity width showed high level of recovery and isolation efficiency. Subsequent whole-genome amplification (WGA) of isolated single-cell plankton provided a sufficient amount (≈30 µg) of WGA products for genetic analyses. Furthermore, it is showed that MCA/GCM could directly analyze phytoplankton in ocean water obtained from Suruga Bay, Japan, without any cumbersome pretreatment. These results indicate that MCA/GCM technology is a powerful tool for elucidating the phytoplankton diversity in marine environment.

Implementation of a rapid response system at an isolated radiotherapy facility through simulation training.

A rapid response system is required in a radiotherapy department for patients experiencing a critical event when access to an emergency department is poor due to geographic location and the patient is immobilised with a fixation device. We, therefore, rebuilt the response system and tested it through onsite simulations. A multidisciplinary core group was created and onsite simulations were conducted using a Plan-Do-Study-Act cycle. We identified the important characteristics of our facility, including its distance from the emergency department; the presence of many staff with little direct contact with patients; the treatment room environment and patient fixation with radiotherapy equipment. We also examined processes in each phase of the emergency response: detecting an emergency, calling the medical emergency team (MET), MET transportation to the site and on-site response and patient transportation to the emergency department. The protocol was modified, and equipment was updated. On-site simulations were held with and without explanation of the protocol and training scenario in advance. The time for the MET to arrive at the site during a 2017 simulation prior to the present project was 7 min, whereas the time to arrive after the first simulation session was shortened to 5 min and was then shortened further to 4 min in the second session, despite no prior explanation of the situation. A multidisciplinary project for emergency response with on-site simulations was conducted at an isolated radiation facility. A carefully planned emergency response is important not only in heavy ion therapy facilities but also in other departments and facilities that do not have easy access to hospital emergency departments.

Relationship between oral mucositis and the oral bacterial count in patients with head and neck cancer undergoing carbon ion radiotherapy: A prospective study.

BACKGROUND AND PURPOSE: Acute adverse events, such as oral mucositis, can affect treatment success in patients undergoing head and neck radiotherapy. In this study, we aimed to identify the relationship between oral mucositis and oral bacterial counts during carbon ion radiotherapy (C-ion RT) in patients with head and neck cancer. MATERIALS AND METHODS: This prospective study included patients with head and neck tumors treated with C-ion RT between 2017 and 2019. C-ion RT consisted of treatment at 57.6, 64.0, or 70.4 Gy (relative biological effectiveness) in 16 fractions. Bacterial counts in the saliva and the back of the tongue were measured using a rapid oral bacteria quantification system. The relationship between the oral bacterial count and oral mucositis was subsequently analyzed. RESULTS: In total, 46 patients were included in the analysis. The bacterial count in the saliva gradually increased from the commencement of C-ion RT and peaked at 16 fractions. Bacterial counts at the back of the tongue were already high at the beginning of C-ion RT; however, they decreased with continued treatment, peaked at 16 fractions, and subsequently decreased again. Patients with bacterial counts exceeding the mean before C-ion RT (high-count group) did not experience more severe mucositis than those with counts below the mean (low-count group). However, patients in the high-count group tended to experience faster-onset mucositis and slower healing than those in the low-count group. CONCLUSION: Bacterial counts may aid in the development of clinical strategies for C-ion RT-induced oral mucositis.

Evaluation of Threshold Dose of Damaged Hepatic Tissue After Carbon-Ion Radiation Therapy Using Gd-EOB-DTPA-Enhanced Magnetic Resonance Imaging.

PURPOSE: To evaluate the threshold dose and associated factors using signal-intensity changes in the irradiated area after carbon-ion radiation therapy (C-ion RT) for patients with liver cancer. METHODS AND MATERIALS: Patients treated for the first time with C-ion RT for malignant liver tumors and followed up with 3-Tesla gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) 3 months after treatment completion were retrospectively enrolled. The volume of focal liver reaction (FLR), a low-intensity area in the hepatobiliary phase of Gd-EOB-DTPA after treatment, was measured. Corrected FLR (cFLR) volume, defined as FLR corrected for changes in tumor volume from before to after treatment, was calculated, and the threshold dose was determined by applying the cFLR volume in the dose-volume histogram. To evaluate potential mismatch in fusion images of planning computed tomography and follow-up MRI, the concordance coefficient (CC) was measured, and patients with a CC < 0.7 were excluded. Sixty patients were included. Multiple regression analysis was performed with the threshold dose as the objective variable and the age, dose, number of fractionations, Child-Pugh score, pretreatment liver volume, and pretreatment tumor volume as explanatory variables. The Student t test or Mann-Whitney U test was used as required. RESULTS: The median threshold doses for each number of dose fractionations (4 fractions, 12 fractions, and overall) were 51.6, 51.9, and 51.8 Gy (relative biological effectiveness [RBE]), respectively, in patients categorized as Child-Pugh class A and 27.0, 28.8, and 27.0 Gy (RBE), respectively, in patients categorized as Child-Pugh class B. In the multiple-regression analysis, only the Child-Pugh score was significant (P < .001). The number of dose fractionations was not statistically significant. CONCLUSIONS: Although few patients in the study had decreased liver function, baseline liver function was the only factor significantly associated with the median threshold dose. These findings facilitate appropriate patient selection to receive C-ion RT for malignant hepatic tumors.

Clinical features and dosimetric evaluation of carbon ion radiation-induced osteoradionecrosis of mandible in head and neck tumors.

BACKGROUND AND PURPOSE: Osteoradionecrosis (ORN) affects the patient's quality of life by making eating and maintaining oral hygiene painful. This study aimed to analyze carbon ion radiotherapy (C-ion RT)-induced ORN of the mandible. MATERIALS AND METHODS: A retrospective study of 199 patients with head and neck tumors treated with C-ion RT was performed from 2010 to 2019. Only 11 patients with tumors located in the oropharynx and floor of the mouth were analyzed. C-ion RT consisted of 57.6 Gy or 64.0 Gy (relative biological effectiveness) in 16 fractions. The mandible was analyzed for magnetic resonance imaging (MRI) changes and bone exposure. The relationship between the radiation dose and ORN of the mandible was analyzed. RESULTS: Five patients (45.5%) had ORN of the mandible. The median follow-up time was 68 months. The median onset times based on MRI changes and bone exposure were 9 and 15 months, respectively. Doses of 30 Gy (relative biological effectiveness) to the mandible and teeth showed the most significant effect, causing ORN at 29.5 ± 6.7 cc and 3.9 ± 1.8 cc, respectively, with cut-off values at 16.5 cc (p = 0.002) and 1.8 cc (p = 0.0059), respectively. CONCLUSION: This is the first study reporting the incidence, onset time, and risk-predictive dosimetry parameters of C-ion RT-induced ORN of the mandible. Our study will be useful for establishing clinical strategies for C-ion RT to the head and neck near the mandible.

Rectovaginal fistula in a cervical cancer patient treated with sequential radiotherapy and bevacizumab: A dose-volume analysis.

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor that exerts antitumor effect by preventing tumor angiogenesis. Gastrointestinal fistula is a common side effect of bevacizumab in combination with radiotherapy. This case of rectovaginal fistula indicates that the side effect may be unpredictable by the conventional dose-volume parameters for the rectum.

Association of carotid ultrasonography with perioperative stroke after thoracic aortic aneurysm treatment: a retrospective study.

PURPOSE: The purpose of this study was to verify whether carotid ultrasonography (CUS) findings could be associated with the occurrence of perioperative stroke after thoracic aortic aneurysm (TAA) treatment. METHODS: Patients with TAAs who were treated by either total arch replacement or thoracic endovascular aortic repair (TEVAR) were retrospectively enrolled. Left subclavian artery (LSA) embolization and bypass surgery of the left common carotid artery (CCA) to the LSA before TEVAR were additionally performed for some patients. CUS was performed before TAA treatment to evaluate carotid atherosclerosis and flow velocities of bilateral cervical arteries. After dividing patients into those with and without perioperative stroke, their background, atherosclerotic risk factors, history of stroke, TAA location and size, treatment procedures, and CUS parameters were compared between the two groups. RESULTS: Of the 60 patients (18 women, 42 men; mean age 73.5 ± 10.2 years) with TAA, four (7.5%) developed perioperative stroke. There were no significant differences in the patients' characteristics and their TAAs between those with and without perioperative stroke. For the CUS parameters, end-diastolic velocity (EDV) of bilateral CCAs was significantly decreased in perioperative stroke patients (with vs without stroke; right: 9.2 ± 1.8 vs. 14.5 ± 4.6 cm/s, P = 0.025, left: 9.1 ± 0.3 vs. 15.0 ± 4.5 cm/s, P = 0.012), whereas the resistance index (RI) of bilateral CCAs was significantly elevated (right: 0.76 vs. 0.87, P = 0.008, left: 0.76 vs. 0.87, P < 0.001). CONCLUSIONS: Lower EDV and higher RI of bilateral CCAs were significantly associated with perioperative stroke after TAA treatment. Thus, CUS findings may help predict the occurrence of perioperative stroke.

Quantification of Carotid Plaque Histology Using iPlaque Software.

The iPlaque software package can use integrated backscatter (IB) values of carotid plaque to extract information on tissue composition. The aim of this study was to evaluate the association between the plaque histologic classification and IB values evaluated by iPlaque. In 49 patients undergoing carotid endarterectomy, IB values of whole carotid plaque were measured using iPlaque from the long-axis ultrasonographic image. Histologic findings of resected plaques were defined using the classification of the American Heart Association. The average IB values were statistically compared with the classification. Plaque samples from 49 patients were categorized into V, VI and VII, (13, 32 and 4 cases, respectively). Both the average and standard deviation of the IB values in each plaque sample significantly differed among the three classifications (p = 0.001). The IB of carotid plaque obtained by iPlaque analysis was associated with its histologic characteristics.

Detection and Differentiation of Dural Arteriovenous Fistulas in the Transverse Sinus/Sigmoid Sinus and Cavernous Sinus Using Carotid Ultrasound: Importance of Evaluation of the Occipital Artery.

OBJECTIVES: Dural arteriovenous fistula (DAVFs) in the transverse sinus (TS)/sigmoid sinus (SS) and cavernous sinus (CS) are observed frequently in the clinic. This study aimed to detect DAVFs with ultrasound and compare carotid ultrasound findings between these conditions. METHODS: We retrospectively reviewed 26 patients with either a TS/SS DAVF or a CS DAVF who were admitted to our hospital for evaluation of DAVFs from 2014 to 2018. The shunt site decision was made by neuroendovascular experts, whereas carotid ultrasound examinations were performed by ultrasound specialists. The flow velocity of the ipsilateral external carotid artery was reviewed in all 26 patients, whereas that of the occipital artery (OA) was examined in 20 patients. Blood flow velocities were compared between the TS/SS DAVF and CS DAVF groups. RESULTS: The study included 18 patients with a TS/SS DAVF (11 women and 7 men; mean age ± SD, 65.3 ± 18.6 years) and 8 patients with a CS DAVF (7 women and 1 man; mean age, 70.4 ± 9.3 years). Evaluations of feeder arteries on cerebral angiography showed that all patients had dural branches from the internal carotid and middle meningeal arteries as feeders of CS DAVFs, whereas the OA was the major feeder source of all TS/SS DAVF cases. The end-diastolic velocity (EDV) of the external carotid artery was significantly higher in patients with a TS/SS DAVF compared with those with a CS DAVF (P = .004). The EDV of the OA was significantly elevated in TS/SS DAVF cases compared with CS DAVF cases (P < .001). CONCLUSIONS: Duplex ultrasound parameters are significantly different between patients with TS/SS and CS DAVFs. An increased EDV of the OA can predict the presence of a TS/SS DAVF.

Evaluation of Carbon Ion Radiation-Induced Trismus in Head and Neck Tumors Using Dose-Volume Histograms.

Carbon ion radiotherapy (C-ion RT) provides a highly localized deposition of energy that can increase radiation doses to tumors while minimizing irradiation of adjacent normal tissues. For tumors located near the temporomandibular joint, C-ion RT-induced trismus may occur. However, the relationship between the carbon ion dose and the onset of trismus is unclear. In this prospective observational study, we assessed the trismus/carbon ion dose relationship using dose-volume histograms in 35 patients who received C-ion RT in their head and neck regions between 2010 and 2014. Trismus was evaluated in patients according to the Common Terminology Criteria for Adverse Events, version 4.0. All patients were treated with 57.6 or 64.0 Gy (relative biological effectiveness (RBE)) in 16 fractions, and the median follow-up time was 57 months. Grade 2 trismus was observed in six patients. The median onset time was 12 months. At maximum radiation doses, all masticatory muscles and coronoid processes, particularly the masseter muscle, were significantly different (p = 0.003). The contouring of the masseter muscle and coronoid process requires different treatment planning. The maximum radiation doses of the coronoid process can be proposed as a guideline for treatment planning, considering the ease of contouring in C-ion RT.

MRI response of obturator internus muscle to carbon-ion dose in prostate cancer treatment.

It is important to confirm the dose distribution and its biophysiological response in patients subjected to carbon-ion radiotherapy (CIRT) by using medical imaging methods. In this study, the correlation between the signal intensity changes of muscles observed in magnetic resonance imaging (MRI) after CIRT and planned dose distribution was evaluated. Seven patients were arbitrarily selected from among localized prostate cancer patients on whom CIRT was performed in our facilities in 2010. All subjects received the same dose of CIRT, namely, 57.6 Gy relative biological effectiveness (RBE) in 16 fractions. The following two types of images were acquired for each subject: planning computed tomography (CT) images overlaying the dose distribution of CIRT and MRI T2-weighted images (T2WI) taken 1 year after CIRT. The fusion image of the planning CT and MRI images was registered by using a treatment-planning system, and the CIRT dose distribution was compared with changes observed in the MRI of the obturator internus muscles located near the prostate. The signal changes in the axial image passing through the isocenter of the planning target volume were digitized, and a scatter diagram was created showing the relationship between the radiation dose and digitized signal changes. A strong correlation between the radiation dose and the MRI signal intensity changes was observed, and a quadratic function was found to have the best fit. However, estimating the dose distribution from the normalized MRI signal intensity is difficult at this point, owing to the wide variation. Therefore, further investigation is required.

Utility of intraoperative monitoring with motor-evoked potential during the surgical enucleation of peripheral nerve schwannoma.

Although it is thought that the surgical enucleation of schwannomas can be easily performed, certain patients present with postoperative neurological symptoms. The present study examined the utility of intraoperative motor-evoked potential (MEP) in predicting neurological deficits following the surgical enucleation of peripheral nerve schwannoma. The current study included 23 patients and MEP was performed using transcranial electrical stimulation. In three cases, the MEP decreased to <50% of the preoperative value; however, in two cases that involved the peroneal nerve and tibial nerve, results appeared to be false positives induced by a tourniquet during surgery. In another case, the MEP was completely lost following enucleation of the tumor from the sciatic nerve, which recovered to 61% of the original MEP within 10 min. This patient presented with common peroneal palsy postoperatively. By contrast, another case involving the lumbar nerve root and in which there was reversible postoperative motor loss, the MEP did not change intraoperatively. Postoperative neurological deficit occurred in 22% of patients in the present study, which is similar to that of previous reports. The present study also demonstrated that even if a nerve is not transected or injured, traction or compression of a peripheral nerve may induce ischemia, which can be monitored using MEP. Although MEP alone was not able to predict postoperative transient sensory or motor deficits, the combination of MEP with other methods of neurological monitoring may improve accuracy and should be investigated in future studies.

Clinical course of the bony lesion of single-system single-site Langerhans cell histiocytosis - Is appropriate follow-up sufficient treatment?

BACKGROUND: Langerhans cell histiocytosis (LCH) is categorized into three types, which include single-system single-site (SS-s), single-system multiple-site (SS-m) and multisystem (MS). The most commonly affected site in LCH is bone, and the bony lesion of SS-s LCH has a good prognosis. The bony lesion of SS-s LCH has been thought to regress spontaneously. Although treatments such as curettage, direct injection of corticosteroids, and chemotherapy have been performed, regular follow-up is the first line of treatment for the bony lesion of SS-s LCH. For preventing orthopedic sequelae, strict and appropriate follow-up should be performed, but the appropriate period and method of follow-up has not yet been established. METHODS: In the present study, we retrospectively analyzed a series of 7 cases of patients with SS-s LCH with a bony lesion treated in the Department of Orthopedic Surgery at Kagoshima University Hospital (Kagoshima, Japan) from 2006 to 2015. RESULTS: The bony lesion regressed spontaneously in all patients. Factors such as location, size, preoperative C-reactive protein (CRP) value, standardized uptake (SUV) value of positron emission tomography (PET), age, sex and direct steroid injection were not related to the clinical course. Temporary expansion of the lesion occurred in 3 patients and a temporary worsening of pain occurred in 1 patient during the follow-up period. These events occurred within 6 weeks after biopsy. CONCLUSION: Careful follow-up and the use of an appropriate orthosis can lead to a good clinical course for the bony lesion of SS-s LCH. Future research should seek to determine the appropriate follow-up period.

Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis.

The disease model of familial amyloidotic polyneuropathy-7.2-hMet30 mice-manifests amyloid deposition that consists of a human amyloidogenic mutant transthyretin (TTR) (TTR V30M). Our previous study found amyloid deposits in 14 of 27 7.2-hMet30 mice at 21-24 months of age. In addition, non-fibrillar TTR deposits were found in amyloid-negative 7.2hMet30 mice. These results suggested that TTR amyloidogenesis required not only mutant TTR but also an additional factor (or factors) as an etiologic molecule. To determine the differences in serum proteome in amyloid-positive and amyloid-negative mice in the 7.2-hMet30 model, we used proteomic analyses and studied serum samples obtained from these mice. Hemopexin (HPX) and transferrin (Tf) were detected in the serum samples from amyloid-positive mice and were also found in amyloid deposits via immunohistochemistry, but serum samples from amyloid-negative mice did not contain HPX and Tf. These two proteins were also not detected in non-fibrillar TTR deposits. In addition, in silico analyses suggested that HPX and Tf facilitate destabilization of TTR secondary structures and misfolding of TTR. These results suggest that HPX and Tf may be associated with TTR amyloidogenesis after fibrillogenesis in vivo.

Evaluation of the Time-Dependent Changes and the Vulnerability of Carotid Plaques Using Contrast-Enhanced Carotid Ultrasonography.

BACKGROUND: The association of carotid plaque enhancement on contrast-enhanced carotid ultrasound (CEUS) and plaque vulnerability evaluated by magnetic resonance imaging (MRI) was to be determined. MATERIALS AND METHODS: The 103 patients underwent CEUS from May 2013 until June 2016. CEUS images of the carotid plaque were obtained offline. Plaque images obtained at 1, 3, 5, and 10 minutes were compared with the reference image, defined as the image obtained at 0 minute. Plaque brightness was assessed using the gray-scale median during contrast enhancement (GSM-C). Plaque vulnerability was evaluated using T1- and T2-weighted MRI and Volume ISotropic TSE Acquisition (VISTA), with a VISTA cutoff value for the plaque muscle ratio (PMR) of 1.5. Time-dependent changes in the GSM-C were evaluated, and those between 0 and 1 minute were compared with the PMR values determined on MRI. FINDINGS: GSM-C decreased significantly over time, from 32.0 at 0 minute to 28.0 at 1 minute, 25.0 at 3 minutes, and 19.0 at 10 minutes. The greater the increase in the changes in the GSM-C from 0 to 1 minute, the more significant the association with a PMR higher than the median on T1 (GSM-C: 0 minute: 29.0, 1 minute: 24.0, P = .015), a PMR less than or equal to the median on T2 (0 min: 35.0, 1 min: 28.0, P = .003), and a PMR more than 1.5 determined on VISTA (GSM-C: 0 minute: 29.0, 1 minute: 24.0, P = .005). CONCLUSIONS: Early changes in the GSM-C evaluated with CEUS indicate significant plaque vulnerability on MRI.

Intra-Plaque Vessels on Contrast-Enhanced Ultrasound Sonography Predict Carotid Plaque Histology.

BACKGROUND AND PURPOSE: Although the echogenicity of carotid plaques on carotid enhanced ultrasound (CEUS) was reported to correlate with the historological density of intra-plaque neovessels, it is unclear whether the intra-plaque vessel size is associated with carotid plaque vulnerability. We evaluated the relationship of size of intra-plaque vessels on CEUS with carotid plaque histology. METHODS: We prospectively registered patients with carotid stenosis who were hospitalized to receive carotid endarterectomy between 2012 and 2016. CEUS was performed by ultrasound specialists using a 7-MHz linear transducer (GE LOGIQ7; GE Healthcare, Milwaukee, WN, USA). Sonazoid® was used for conducting CEUS. The sizes of microbubbles inside the plaques were scored at 0, 1, 3, and 5 min after the injection of contrast agent, and were categorized according to our defined vascular score (Vas-S; 0: the effect of contrast was not recognized; 1: the microbubbles were visible, but so blurred and vague that their shape could not be recognized; 2: dot or string-like microbubbles with movement, localized in part or the whole site of the plaque). At histological examination, we simplified the modified American Heart Association classification and defined as an atherosclerotic category (Ath-cat; 1: unruptured plaque; 2: ruptured plaque; 3: healed plaque). We then assessed the correlation of Vas-S with Ath-cat, which describes the process of rupture and restoration of carotid plaques. RESULTS: A total of 97 patients were included in this study. A higher Ath-cat was significantly associated with higher Vas-S at any time. Spearman signed-rank test indicated that Vas-S at 1 min was most strongly correlated with Ath-cat (ρ = 0.43, p = 0.001). Receiver operating curve analysis indicated that a Vas-S of 0 at 1 min was significantly associated with an unruptured plaque (area under curve [AUC] 0.72, p = 0.006), while a Vas-S of 2 at 1 min was significantly associated with a healed plaque (AUC 0.72, p = 0.001). CONCLUSION: Vas-S values of 0 and 2 at 1 min indicated unruptured and healed plaques respectively. Thus, a Vas-S of 1 at 1 min is an indicator of a ruptured plaque. The intra-plaque vessel size on CEUS was significantly associated with carotid plaque histology, and may predict the process of plaque rupture and restoration.

Prognostic factors in patients with skeletal-related events at non-small-cell lung cancer diagnosis.

The aim of the present study was to detect prognostic factors in patients with skeletal-related events (SREs) and bone metastasis at the time of non-small-cell lung cancer (NSCLC) diagnosis. A total of 85 NSCLC patients were retrospectively enrolled, 47 (55.2%) of whom presented with SREs at the time of NSCLC diagnosis. Multivariate logistic regression analysis identified squamous cell carcinoma as a risk factor for SRE. Kaplan-Meier analysis demonstrated that there was no difference in the overall survival between the SRE and no SRE groups. Cox hazard model revealed that a higher Eastern Cooperative Oncology Group (ECOG) performance status (PS) score was a risk factor for poor prognosis, while surgery for bone metastasis and molecular-targeted therapy were factors for better prognosis in patients with SREs at the time of NSCLC diagnosis. Multivariate analysis revealed that a higher ECOG PS score and metastasis to the adrenal gland were risk factors for poor prognosis, while surgery for bone metastasis and molecular-targeted therapy were factors for better prognosis. Thus, while surgical treatment and molecular-targeted therapy appear to improve the prognosis of patients with bone metastasis at the time of NSCLC diagnosis, those with a higher ECOG PS score and adrenal metastasis may benefit more from radiotherapy or supportive care.

Acceleration of blood flow as an indicator of improved hemodynamics after indirect bypass surgery in Moyamoya disease.

OBJECTIVE: The ultrasonography findings in the superficial temporal artery (STA) in Moyamoya disease patients treated with indirect bypass remain unclear. We evaluated the time-related changes in ultrasonography findings of the STA main trunk and branches in patients with Moyamoya disease who underwent encephalo-duro-arterio-synangiosis (EDAS). PATIENTS AND METHODS: Patients (n=21, 30 sides) with Moyamoya disease who underwent EDAS at Fukuoka University Hospital were prospectively registered between 2008 and 2015. EDAS using the frontal and parietal branches of the STA was adopted in an indirect bypass procedure. Mean velocity (MV) and resistance index (RI) were used as ultrasonography markers, and their changes over time in the STA main trunk and branches were assessed. RESULTS: There was a significant increase in MV in both the STA main trunk (p=0.001) and branches (frontal: p=0.005, parietal: p=0.003) at 3 months after EDAS, whereas there was a decrease in RI at 14days after EDAS (main trunk: p <0.001, frontal: p <0.001, parietal: p=0.014). In subgroup analysis of patients divided by EDAS outcome, compared with before EDAS, there were significant differences at 3 months after EDAS in MV (responders: main trunk: p=0.002, frontal: p=0.001, parietal: p=0.001; non-responders: main trunk: p=0.093, frontal: p=0.24, parietal: p=0.96) and RI (responders: main trunk: p<0.001, frontal: p<0.001, parietal: p=0.006; non-responders: main trunk: p=0.17, frontal: p=0.12, parietal: p=0.17). CONCLUSIONS: Measurement of MV may be useful for predicting outcome at 3 months after EDAS.