Evaluation of vascular anatomy for colon cancer located in the splenic flexure using the preoperative three-dimensional computed tomography angiography with colonography.

PURPOSE: The aim of this study is to reveal the vascular branching variation in SFC (splenic flexure cancer) patients using the preoperative three-dimensional computed tomography angiography with colonography (3D-CTAC). METHODS: We retrospectively analyzed patients with SFC who underwent preoperative 3D-CTAC between January 2014 and December 2019. RESULTS: Among 1256 colorectal cancer (CRC) patients, 96 (7.6%) manifested SFC. The arterial branching from the superior mesenteric artery (SMA) was classified into five patterns, as follows: (type 1A) the left branch of middle colic artery (LMCA) diverged from middle colic artery (MCA) (N = 47, 49.0%); (2A) the LMCA diverged from the MCA and the accessory middle colic artery (AMCA) (N = 26, 27.1%); (3A) the LMCA independently diverged from the SMA (N = 16, 16.7%); (4A) the LMCA independently diverged from the SMA and AMCA (N = 3, 3.1%); (5A) only the AMCA and the LMCA was absent (N = 4, 4.1%). Venous drainage was classified into four patterns, as follows: (type 1V) the SFV flows into the inferior mesenteric vein (IMV) then back to the splenic vein (N = 50, 52.1%); (2V) the SFV flows into the IMV then back to the superior mesenteric vein (SMV) (N = 19, 19.8%); (type 3V) the SFV independently flows into the splenic vein (N = 3, 3.1%); (type 4V) the SFV is absent (N = 24, 25.0%). CONCLUSION: 3D-CTAC could reveal accurate preoperative tumor localization and vascular branching. These classifications should be helpful in performing accurate complete mesocolic excision and central vessel ligation for SFC.

Multiple optical stimulation to neuron using Si opto-neural probe with multiple optical waveguides and metal-cover for optogenetics.

We have developed a Si opt-neural probe with multiple waveguides and metal cover for highly accurate optical stimulation. This neural probe had 16 recording sites, three optical waveguides, and metal cover for suppressing light leakage. We evaluated electrochemical properties of the recording sites, and confirmed that the neural probe had suitable characteristics for neural recording. We also demonstrated the optical stimulation to the neurons expressing ChR2 using our probe. As a result, we succeeded multisite optical stimulation, and observed that no light leakage from the optical waveguides because of the metal cover. From in vivo experiments, we successfully recorded optically modulated local field potential using the fabricated Si neural probe with optical waveguides. Moreover, we applied current source density analysis to the recorded LFPs. As a result, we confirmed that light induced membrane current sink in locally stimulated area. Our Si opto-neural probe with multiple optical waveguides and metal-cover is one of the most versatile tools for optogenetics.

Cancer gene therapy using a novel secretable trimeric TRAIL.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF family, is a type II transmembrane cytokine molecule. Soluble TRAIL has been shown to induce apoptosis in a wide variety of cancer cells in vitro and to suppress tumor growth specifically without damaging normal cells and tissues in vivo. In our previous report, we have demonstrated that an artificial gene encoding the polypeptide composed of the three functional elements (a secretion signal, a trimerization domain and an apoptosis-inducing moiety of TRAIL gene sequence) expresses and secretes highly apoptotic trimeric TRAIL into the culture supernatant. Here, as an approach to TRAIL-based cancer gene therapy, we developed an adenoviral vector delivering the gene that encodes our secretable trimeric TRAIL (stTRAIL). This adenovirus (Ad-stTRAIL) potently induced apoptosis in vitro in cancer cell lines such as HeLa, MDA-MB-231, A549, HCT116 and U-87MG. In an animal xenograft tumor model bearing a human glioma cell line U-87MG, intratumoral delivery of Ad-stTRAIL dramatically suppressed tumor growth without showing detectable adverse side effects. Histological analysis revealed that Ad-stTRAIL suppresses tumor growth by inducing apoptotic cell death. Contrary to the known rapid clearance of systemically delivered TRAIL protein from the blood circulation, stTRAIL expressed by Ad-stTRAIL in tumor tissues persisted for more than 4 days. In a comparison of tumor suppressor activity between Ad-stTRAIL and Ad-flTRAIL (delivering the full-length TRAIL gene) after mixing infected cells with uninfected cells and implanting these mixed cells in nude mice, Ad-stTRAIL showed higher tumor suppressor activity than that of Ad-flTRAIL. Our data reveal that a gene therapy using Ad-stTRAIL has a promising potential to treat human cancers including gliomas.

Visually based path-planning by Japanese monkeys.

To construct an animal model of strategy formation, we designed a maze path-finding task. First, we asked monkeys to capture a goal in the maze by moving a cursor on the screen. Cursor movement was linked to movements of each wrist. When the animals learned the association between cursor movement and wrist movement, we established a start and a goal in the maze, and asked them to find a path between them. We found that the animals took the shortest pathway, rather than approaching the goal randomly. We further found that the animals adopted a strategy of selecting a fixed intermediate point in the visually presented maze to select one of the shortest pathways, suggesting a visually based path planning. To examine their capacity to use that strategy flexibly, we transformed the task by blocking pathways in the maze, providing a problem to solve. The animals then developed a strategy of solving the problem by planning a novel shortest path from the start to the goal and rerouting the path to bypass the obstacle.

Rostrocaudal distinction of the dorsal premotor area based on oculomotor involvement.

To investigate functional differences between the rostral and caudal parts of the dorsal premotor cortex (PMd), we first examined the effects of intracortical microstimulation (ICMS) while monkeys were performing oculomotor and limb motor tasks or while they were at rest. We found that saccades were evoked from the rostral part (PMdr) whereas ICMS in the caudal part (PMdc) predominantly produced forelimb or body movements. Subsequently, we examined neuronal activity in relation to the performance of visually cued and memorized saccades while monkeys reached an arm toward a visual target. We found that roughly equal numbers of PMdr neurons were active during performance of the oculomotor and limb motor tasks. In contrast, the majority of PMdc neurons were related preferentially to arm movements and not to saccades. In the subsequent analysis, we found that the oculomotor effects evoked in the PMdr differ from the effects evoked in either the frontal eye field (FEF) or supplementary eye field (SEF). These findings suggest that the PMdr is involved in oculomotor as well as limb motor behavior. However, the oculomotor involvement of the PMdr seems to have a functional aspect different from that operating in the FEF and SEF.

Microstimulation of the lateral wall of the intraparietal sulcus compared with the frontal eye field during oculomotor tasks.

We compared the effects of intracortical microstimulation (ICMS) of the lateral wall of the intraparietal sulcus (LIP) with those of ICMS of the frontal eye field (FEF) on monkeys performing oculomotor tasks. When ICMS was applied during a task that involved fixation, contraversive saccades evoked in the LIP and FEF appeared similar. When ICMS was applied to the FEF at the onset of voluntary saccades, the evoked saccades collided with the ongoing voluntary saccade so that the trajectory of voluntary saccade was compensated by the stimulus. Thus the resultant saccade was redirected and came close to the endpoint of saccades evoked from the fixation point before the start of voluntary saccade. In contrast, when ICMS was applied to the LIP at the onset of voluntary saccades, the resultant saccade followed a trajectory that was different from that evoked from the FEF. In that case, the colliding saccades were redirected toward an endpoint that was close to the endpoint of saccades evoked when animals were already fixating at the target of the voluntary saccade. This finding suggests that the colliding saccade was directed toward an endpoint calculated with reference to the target of the voluntary saccade. We hypothesize that, shortly before initiation of voluntary saccades, a dynamic process occurs in the LIP so that the reference point for calculating the saccade target shifts from the fixation point to the target of a voluntary saccade. Such predictive updating of reference points seems useful for immediate reprogramming of upcoming saccades that can occur in rapid succession.

[A case of video-assisted thoracic surgery for congenital esophago-bronchial fistula].

A 42-year-old male was admitted to our hospital because barium esophagograpm showed an esophago-bronchial fistula with an esophageal deverticulum. He has had frequent episodes of cough at drinking water since childhood. A chest CT scan showed mild inflammatory change and bronchiectasis in the right S6. Division of the fistula by video-assisted thoracoscopic surgery (VATS) was performed. There was no evidence of inflammation and adherent lymph nodes around the fistula. This case was diagnosed as a congenital esophago-bronchial fistula by operative findings and clinical course. The fistula was dissected easily and divided by an auto-suturing instrument. The affected lung could be preserved. The patient was discharged on the 10th postoperative day. VATS is an effective treatment for the patients of congenital esophago-bronchial fistula (Braimbrige type I and II), if they are not accompanied with pulmonary abscess or pleural empyema.

An oculomotor representation area within the ventral premotor cortex.

We explored the ventral part of the premotor cortex (PMV) with intracortical microstimulation (ICMS) while monkeys performed a visual fixation task, to see whether the PMV is involved in oculomotor control. ICMS evoked saccades from a small-restricted region in the PMV, without evoking movements in the limbs, neck, or body. We found the saccade-evoking site in the PMV in a total of three hemispheres in two monkeys. Quantitative analysis of the effects of eye position on saccades evoked by microstimulation of the PMV characterized the evoked saccades as goal directed. The nature of the saccades evoked in the PMV contrasted with the fixed vector nature of saccades evoked by ICMS of the frontal eye field. We also found that neurons in this restricted area of the PMV were active while the animals were performing a saccade task that required them to make saccades toward targets without arm movements. These data provide evidence for the presence of an oculomotor-specific subregion within the PMV. This subregion and the surrounding skeletomotor-representing regions of the PMV seem to coordinate oculomotor and skeletomotor control in performing goal-directed motor tasks.

Intracortical microstimulation of bilateral frontal eye field.

We trained two monkeys to perform a fixation task. Intracortical microstimulation (ICMS) was applied to the monkey frontal eye field (FEF) while monkeys were fixating on one of five fixation LEDs. The ICMS was applied in two different manners. Under the single stimulation condition, ICMS was delivered to either right or left FEF. Under the paired stimulation condition, bilateral FEF were successively stimulated with an interval of 30-250 ms. The single stimulation elicited contraversive saccades. As reported previously, these saccades were not much affected by initial eye positions, maintaining the same vector. In contrast, the paired stimulation elicited double-step saccades. The first of the paired stimulation elicited constant vector saccades, but the second of the paired stimulation evoked saccades whose vector varied greatly depending on the eye position at the start of individual saccades. The second saccades, starting from various initial positions, were directed to the endpoint of saccades that were elicited from the same FEF site under the single stimulation condition. Endpoints of second saccades varied little despite variations of intervals of the stimulation pairs, ranging from 60 to 150 ms. On the basis of these observations, we propose a novel view that the FEF is involved in directing saccades to an internally referenced visual target.

Neuronal activity in the ventral part of premotor cortex during target-reach movement is modulated by direction of gaze.

We recorded 200 neurons from the ventral part of the premotor cortex (PMv) and 110 neurons from the primary motor cortex (MI) of a monkey performing a visually cued arm-reaching task with a delay. We compared neuronal activity in the premovement period while the monkey reached the target with the eyes fixating on either a left or right fixation target. Our data demonstrate that about half of the movement-related activity in the PMv was modulated by the direction of gaze. In contrast, a vast majority of the activity of MI neurons and about half of PMv neurons were not influenced by the direction of gaze. We further analyzed the movement-related activity during the reaching movement to targets at the top, bottom, left, and right of each fixation point. The magnitude of activity of neurons showing the gaze-direction selectivity was primarily determined by the position of the reaching target relative to the eye-fixation target, and not by the position of the target relative to the animal's body. These data suggest that a part of the coordinate transformation of the motor command signals concerning the direction of reaching from the retinotopic to body-centered frame of reference may occur at the level of premotor cortex but not in MI.

Role for cells in the presupplementary motor area in updating motor plans.

Two motor areas are known to exist in the medial frontal lobe of the cerebral cortex of primates, the supplementary motor area (SMA) and the presupplementary motor area (pre-SMA). We report here on an aspect of cellular activity that characterizes the pre-SMA. Monkeys were trained to perform three different movements sequentially in a temporal order. The correct order was planned on the basis of visual information before its execution. A group of pre-SMA cells (n = 64, 25%) were active during a process when monkeys were required to discard a current motor plan and develop a plan appropriate for the next orderly movements. Such activity was not common in the SMA and not found in the primary motor cortex. Our data suggest a role of pre-SMA cells in updating motor plans for subsequent temporally ordered movements.

Visually guided saccade versus eye-hand reach: contrasting neuronal activity in the cortical supplementary and frontal eye fields.

1. We studied neuronal activity in the supplementary eye field (SEF) and frontal eye field (FEF) of a monkey during performance of a conditional motor task that required capturing of a target either with a saccadic eye movement (the saccade-only condition) or with an eye-hand reach (the saccade-and-reach condition), according to visual instructions. 2. Among 106 SEF neurons that showed presaccadic activity, more than one-half of them (54%) were active preferentially under the saccade-only condition (n = 12) or under the saccade-and-reach condition (n = 45), while the remaining 49 neurons were equally active in both conditions. 3. By contrast, most (97%) of the 109 neurons in the FEF exhibited approximately equal activity in relation to saccades under the two conditions. 4. The present results suggest the possibility that SEF neurons, at least in part, are involved in signaling whether the motor task is oculomotor or combined eye-arm movements, whereas FEF neurons are mostly related to oculomotor control.

Comparison of neuronal activity in the supplementary motor area and primary motor cortex.

Neuronal activity in the supplementary motor area (SMA) and primary motor cortex (MI) have been compared in many experiments during performance of many different motor tasks. On one hand, the activity in both areas may appear similar, especially when the motor task is simple. On the other hand, if the motor tasks are more demanding, neuronal activity in the SMA exhibits a variety of complex relationship to many different aspects of motor behavior, while the activity in MI is mostly related to execution of motor task itself. Of particular interest is the neuronal activity in the SMA during preparation and execution of motor tasks when no external cues for the retrieval of appropriate motor act is available. Temporal sequencing of multiple movements is a typical example of the kind of motor task that requires profound activity in the SMA.

Pallidal neuron activity during sequential arm movements.

1. We examined the activity of neurons in the globus pallidus (GP) while monkeys (n = 2) performed sequential pointing movements under two task conditions: visually guided (TRACK task) and remembered (REM task). 2. Almost two-thirds of the task-related neurons in GP (155/236) were considered task dependent because they displayed exclusive or enhanced (greater than +/- 50%) changes in activity for one of the two task conditions. 3. More than 65% of the task-dependent neurons were termed REM neurons because they either displayed changes in activity that occurred only during the REM task or displayed changes that were more pronounced (greater than +/- 50%) during the REM task than during the TRACK task. 4. Nearly half of the REM neurons in GP displayed changes in activity that were limited to a single phase of the REM task (i.e., phase specific). Phase-specific neurons varied in the extent to which their activity depended on the particular sequence of movements performed. Some displayed a change in activity for all of the eight different movement sequences. Others displayed a change in activity during only one of the eight different sequences (i.e., phase and sequence specific). 5. We speculate that an ensemble of GP neurons with phase-specific responses could be used to encode the detailed spatio-temporal characteristics of a sequential movement. In this way, GP neurons would provide part of the neural substrate that solves the "serial order of motor behavior problem".

Microstimulation of the supplementary eye field during saccade preparation.

Electrical stimulation of the supplementary eye field (SEF) of monkeys has been reported to evoke saccades with low threshold currents. In previous reports, the evoked saccades have appeared either as 'converging', 'goal directed', or at times 'constant vector'. In the present study, a new aspect of intracortical microstimulation (ICMS) was found when the stimulus was applied at the time when an animal was prepared to initiate its own voluntary saccades. A cue signal was given to the animal that indicated targets of impending saccades. After a variable delay period, a 'go' signal told the monkey to initiate the saccade toward the target. ICMS was applied shortly (50-100 ms) before the go signal. The stimulus-evoked saccades were directed toward and captured the cued target, provided that the target direction was contralateral to the cortical stimulus site. Saccades with that property were evoked only from a limited portion of the cortical field that corresponded to the SEF, characterizing this particular oculomotor area.

[Evaluation of new drug delivery system for primary lung cancer: intermittent intra-arterial injection therapy with implantable port system (reservoir)--II. Evaluation of technical methods for cannulation of feeding arteries of lung cancer with implantation of implantable port system].

As mentioned in the first of the present series of reports, lung cancers were fed by various arteries such as bronchial arteries, internal mammary arteries, inter-costal arteries and branches of subclavian arteries such as thyro-cervical truncus or thoraco-dorsal arteries, according to the size and stages of tumors and the processes of therapy. On the basis of these anatomical findings of the feeders of lung cancers, we tried several effective and reasonable ways of cannulation of catheters, which were connected with an implantable port system.