Treatment strategy changes for inflammatory bowel diseases in biologic era: results from a multicenter cohort in Japan, Far East 1000.

Many molecular targeted agents, including biologics, have emerged for inflammatory bowel diseases (IBD), but their high prices have prevented their widespread use. This study aimed to reveal the changes in patient characteristics and the therapeutic strategies of IBD before and after the implementation of biologics in Japan, where the unique health insurance system allows patients with IBD and physicians to select drugs with minimum patient expenses. The analysis was performed using a prospective cohort, including IBD expert and nonexpert hospitals in Japan. In this study, patients were classified into two groups according to the year of diagnosis based on infliximab implementation as the prebiologic and biologic era groups. The characteristics of therapeutic strategies in both groups were evaluated using association analysis. This study analyzed 542 ulcerative colitis (UC) and 186 Crohn's disease (CD). The biologic era included 53.3% of patients with UC and 76.2% with CD, respectively. The age of UC (33.9 years vs. 38.8 years, P < 0.001) or CD diagnosis (24.3 years vs. 31.9 years, P < 0.001) was significantly higher in the biologic era group. The association analysis of patients with multiple drug usage histories revealed that patients in the prebiologic era group selected anti-tumor necrosis factor (TNF)-α agents, whereas those in the biologic era group preferred biologic agents with different mechanisms other than anti-TNF-α. In conclusion, this study demonstrated that both patient characteristics and treatment preferences in IBD have changed before and after biologic implementation.

Efficacy of early clip-with-line method for colorectal endoscopic submucosal dissection.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) remains demanding due to technical difficulties and high risk of perforation. Most of the reported traction methods are initiated after creating a mucosal flap, which is time consuming. To obtain a good visualization at the mucosal incision stage, we developed the early clip-with-line (ECL) method. This method was started immediately after injection of sodium hyaluronate solution into the submucosal layer. In this study, we evaluated the efficacy and the safety of the ECL method for colorectal ESD. METHODS: We retrospectively analyzed all cases of colorectal ESDs (41 cases in total) performed from January 2017 to February 2019 in our institution. From January 2017 to August 2018, 27 of these cases were performed using conventional (non-ECL) ESDs, while from September 2018 onwards, the remaining 14 cases were performed using the ECL method. Retrospective comparison between the ECL group and the non-ECL group was conducted in terms of clinical characteristics, treatment outcomes, and adverse events. RESULTS: There were no significant differences in clinical characteristics between two groups. Procedure time (median [range]) was significantly shorter in the ECL group than in the non-ECL group (66 [29-131] min vs 90 [30-410] min; P = 0.03). As for adverse events, no case of perforation occurred in the ECL group, whereas perforation was observed in 7.4% (2/27) cases in the non-ECL group (no significant difference). CONCLUSION: Early clip-with-line method for colorectal endoscopic submucosal dissection reduced procedure time.

The neural correlates of biomechanical constraints in hand laterality judgment task performed from other person's perspective: A near-infrared spectroscopy study.

Previous studies, mainly using a first-person perspective (1PP), have shown that the judgments of the hand laterality judgment (HLJ) task are dependent on biomechanical constraints (BC). Specifically, differing reaction times (RT) for hand pictures rotated medially or laterally around the mid sagittal plane are attributed to the BC effect on motor imagery. In contrast, we investigated whether the HLJ task is also subject to BC when performed from a third-person perspective (3PP) as well as 1PP using near-infrared spectroscopy (NIRS) to measure the brain activity of prefrontal cortex (PFC) in right-handed participants assigned to 1PP or 3PP groups. The 1PP group judged whether a presented hand was their own left or right hand, and the 3PP group whether it was the other's left or right hand. Using their HLJ task error rates, the 1PP and 3PP groups were subdivided into an Error Group (EG) and No Error Group (NEG). For the 1PP group, both EG and NEG showed a significant Hand Laterality × Orientation interaction for RT, indicating the BC effect on motor imagery. For the 3PP group, however, neither EG nor NEG showed the interaction, even though EG showed a significantly longer RT than NEG. These results suggest that the 3PP EG appropriately followed the 3PP task instruction, while the NEG might have taken 1PP. However, the 3PP EG NIRS profile of left PFC showed a significant Hand Laterality × Orientation interaction, while the 1PP EG did not. More noteworthy is that the left PFC activation of EG showed an interaction between the 1PP and 3PP groups when the left hand was presented. Furthermore, in the NEG, the PFC activation was not influenced by the BC in either the 1PP or 3PP condition. These results indicate that BC interferes with the HLJ task performed from the 1PP and 3PP.

Inter-brain network underlying turn-based cooperation and competition: A hyperscanning study using near-infrared spectroscopy.

The present study examined neural substrates underlying turn-based cooperation and competition in a real two-person situation. We simultaneously measured pairs of participants' activations in their bilateral frontal, temporal, and parietal regions using a 96-channel near-infrared spectroscopy (NIRS) system, when participants played a turn-taking disk-game on a computer. NIRS data demonstrated significant inter-brain neural synchronization (INS) across participant pairs' right posterior superior temporal sulcus (pSTS) in both the cooperation and competition conditions, and the competition condition also involved significant INS in the right inferior parietal lobule (IPL). In addition, competitive dyads' INS in the bilateral inferior frontal gyrus (IFG) may play as a role of mediation in relationship between their empathy score and disk-manipulation latency, but cooperative dyads' INS did not. These results suggest that first the right pSTS may be commonly involved in both cooperation and competition due to task demands of joint attention and intention understanding, while the right IPL may be more important for competition due to additional requirements of mentalizing resources in competing contexts. Second, participants' empathy may promote INS in the bilateral IFG across competitors, and in turn affect their competitive performance.

[A Case Report of Long-Term Survival after Excision for Needle Tract Implantation of Biopsy and Hepatectomy for Cholangiocarcinoma with Gall Bladder Hemorrhage].

A 77-year-old men with abdominal pain suffered from gall bladder hemorrhage and liver abcess was admitted for intensive care of severe acute cholangitis. He had hemobilia which was treated by the endoscopic retrograde bile duct drainage. After 2 months treatment with rest for purulent myelitis, he had neoplastic change of liver abcess diagnosed as intrahepatic bile duct cancer by percutaneous core needle biopsy. He underwent surgery as central bisegmentectomy and left the hospital at home 3 months later after rehabilitation for surgical site infection. He noticed growing mass on right chest 6 months later after hepatectomy and was diagnosed as needle tract implantation in chest wall by CT examination. Pathological exam revealed cholangiocarcinoma by radical excision. He have disease free for 5 years after second operation. Although percutaneous biopsy for hepatic tumor increases risks of needle tract implantation and dissemination, there is an advantage of radical resection for tract implantaion.

Enhanced detection of lymphovascular invasion in small rectal neuroendocrine tumors using D2-40 and Elastica van Gieson immunohistochemical analysis.

Rectal neuroendocrine tumor (RNET) lymphovascular invasion (LVI) is regarded as an important predictor of nodal metastasis after endoscopic resection (ER). However, little is known about the frequency of immunohistochemical detection of LVI in RNETs. This study was performed to establish the actual detection of LVI rate in RNETs ≤10 mm and to evaluate associated clinical outcomes. We retrospectively reviewed the records for 98 consecutive patients treated by ER with a total of 102 RNETs ≤10 mm. Tissue sections were labeled with hematoxylin-eosin (HE) stain, the D2-40 monoclonal antibody to evaluate lymphatic invasion, and Elastica van Gieson (EVG) stain to detect venous invasion. LVI detection rate by HE versus immunohistochemical analysis was compared. Follow-up findings and clinical outcomes were also evaluated for 91 patients who were followed for ≥12 months. Lymphatic and venous invasion were detected using HE staining alone in 6.9% and 3.9% of patients, respectively, whereas they were detected using D2-40 and EVG staining in 20.6% and 47.1% of the patients, respectively. Thus, the LVI detection frequency using D2-40 and EVG staining (56.9%) was significantly higher than with HE (8.8%). Two out of seven patients who required additional surgery had regional lymph node metastases. However, among the 84 patients who were followed up without surgery, no distant metastases or recurrences were detected. Compared with HE staining, immunohistochemical analysis significantly increased the frequency of LVI detection in RNETs ≤10 mm. However, the clinical impact of LVIs detected using immunohistochemical analysis remains unclear. Clarification of the actual role of LVI using immunohistochemical analysis requires a patient long-term follow-up and outcomes.

Understand after like, viewer's delight? A fNIRS study of order-effect in combined hedonic and cognitive appraisal of art.

We investigate neural and behavioral aspects of the interrelation between 'liking' and 'understanding' when both appraisals are made within one judgment task. Our goal was to explore questions regarding how these appraisals combine, and specifically whether there is an order-effect when both are employed in sequence. To this end, we tested a hypothesis derived from new models in neuroaesthetics, and concerning processing of art, which suggest that perception may involve a natural sequence from first processing for hedonic quality (i.e., liking) followed by processing for understanding. Thus, due to the initial liking assessment's capacity to prime deepened cognitive involvement, a Liking-Understanding order may show key differences in final assessments or brain activation when compared to an Understanding-Liking sequence. Thirty-two participants evaluated a range of paintings, balanced for visual appeal and understandability, in a two-part task in which half evaluated for understanding followed by liking and the other half had question order reversed. Brain activity was recorded via functional Near Infrared Spectroscopy (fNIRS). Results showed no assessment interrelation or order effect in artwork evaluations. However, participants who began with evaluation for liking, and who came to incongruent combinations (i.e., "I like, but I don't understand" or "I don't like, but I understand"), showed significantly higher activation in left medial prefrontal cortex. This area is functionally associated with attention and integration of hedonic/informational elements. Findings provide tentative support for a liking-driven order-effect, as well as for physiological connection between appraisals, which may not appear in behavioral evidence, and suggest need for further consideration of this topic in appraisal research.

The neural mechanism of biomechanical constraints in the hand laterality judgment task: A near-infrared spectroscopy study.

The mental rotation (MR) task is defined as a discrimination task between mirror-reversed images involving discrepancy in angular orientation. Various studies have shown that the MR task likely causes mental imagery, that is, visual and/or motor imagery, depending on stimulus types. When figures of rotated hands are presented to be identified as a left or right hand, reaction times (RTs) usually show an effect of biomechanical constraints (BC): a hand in a position difficult to reach with a real movement results in longer RTs. The BC effect as a marker of motor imagery has been investigated by brain function measures (fMRI, PET, EEG and MEG) as well as by RTs. Unlike other neuroimaging techniques, NIRS (near-infrared spectroscopy) imposes few physical constraints on participants and is relatively unaffected by motion artifact, which permits serial assessments of tasks in relaxed and natural environment. Focusing on these advantages, a NIRS study on motor imagery in HLJ was carried out in which we measured the brain activation during the HLJ task and a single character judgment task. In the HLJ task, both the RTs and the activity of the left superior parietal lobe (SPL) showed an interaction between Hand (left, right) and Orientation (135°, 225°) i.e., the BC effect, but not in the character judgment task. More specifically, in the analysis of BC-related activity of SPL, although the Hand×Orientation interaction was significant, the left SPL for the left hand significantly increased from 135° to 225°, but the reversed increase (from 225° to 135°) was not found for the right hand. These results suggest that left SPL is involved in the BC effect and NIRS differentiates left hand awkwardness of right-hander in the HLJ task.

Obstruction increases activation in the right inferior frontal gyrus.

The right inferior frontal gyrus (IFG) is involved in intention understanding during interpersonal interactions. To examine how prior experience of cooperation and competition affects one's right IFG activation in the subsequent interaction, using near-infrared spectroscopy (NIRS) we simultaneously measured paired participants' bilateral IFG activations during a turn-taking game. Participant pairs were assigned to either one of two roles: a Builder taking the initial move to copy a target disk-pattern on monitor and the Partner taking the second move to aid in (cooperation) or to obstruct (competition) the Builder. The experiment consisted of two sessions. One participant (B-P) played as a Builder (B-) in session 1 and changed the role to the Partner (-P) in session 2, and vice versa for the paired participant (P-B). NIRS data in competition demonstrated that the Builder (B-) being obstructed in session 1 showed higher right IFG activation when (s)he took a role of obstructor (-P) in session 2 (the obstructed effect), whereas "the cooperated effect" was not revealed in cooperation. These results suggest that prior experience of being obstructed may facilitate understanding of the Builder and/or the obstructor's tactical move, thereby increasing his/her right IFG activation when one is meant to obstruct in subsequent competitions.

Role of the right inferior frontal gyrus in turn-based cooperation and competition: A near-infrared spectroscopy study.

Interpersonal interaction can be classified into two types: concurrent and turn-based interaction, requiring synchronized body-movement and complementary behaviors across persons, respectively. To examine the neural mechanism of turn-based interaction, we simultaneously measured paired participants activations in their bilateral inferior frontal gyrus (IFG) and the bilateral inferior parietal lobule (IPL) in a turn-taking game using near-infrared spectroscopy (NIRS). Pairs of participants were assigned to either one of two roles (game builder and the partner) in the game. The builder's task was to make a copy of a target disk-pattern by placing disks on a monitor, while the partner's task was to aid the builder in his/her goal (cooperation condition) or to obstruct it (competition condition). The builder always took the initial move and the partner followed. The NIRS data demonstrated an interaction of role (builder vs. partner) by task-type (cooperation vs. competition) in the right IFG. The builder in the cooperation condition showed higher activation than the cooperator, but the same builder in the competition condition showed lower activation than in the cooperation condition. The activations in the competitor-builder pairs showed positive correlation between their right IFG, but the activations in the cooperator-builder pairs did not. These results suggest that the builder's activation in the right IFG is reduced/increased in the context of interacting with a cooperative/competitive partner. Also, the competitor may actively trace the builder's disk manipulation, leading to deeper mind-set synchronization in the competition condition, while the cooperator may passively follow the builder's move, leading to shallower mind-set synchronization in the cooperation condition.

Co-speech gesture production in an animation-narration task by bilinguals: a near-infrared spectroscopy study.

To examine the neural mechanism of co-speech gesture production, we measured brain activity of bilinguals during an animation-narration task using near-infrared spectroscopy. The task of the participants was to watch two stories via an animated cartoon, and then narrate the contents in their first language (Ll) and second language (L2), respectively. The participants showed significantly more gestures in L2 than in L1. The number of gestures lowered at the ending part of the narration in L1, but not in L2. Analyses of concentration changes of oxygenated hemoglobin revealed that activation of the left inferior frontal gyrus (IFG) significantly increased during gesture production, while activation of the left posterior superior temporal sulcus (pSTS) significantly decreased in line with an increase in the left IFG. These brain activation patterns suggest that the left IFG is involved in the gesture production, and the left pSTS is modulated by the speech load.

[A case of recurrent transverse colon cancer invading the pancreas and duodenum successfully treated with biliary and duodenal stenting].

We report a case of recurrent transverse colon cancer invading the pancreas and duodenum that was successfully treated with biliary and duodenal stenting. A 46-year-old man underwent ascending colostomy for the treatment of obstructive transverse colon cancer with hepatic metastasis. Chemotherapy achieved a partial response, but the levels of tumor markers later began to rise again. He then underwent right hemicolectomy and partial hepatectomy. Post-operative chemotherapy was administered, but the recurrent tumor caused obstructive jaundice and duodenal obstruction. These were successfully treated with biliary and duodenal stenting, and the patient was able to remain at home and maintain his quality of life.

Aneurysm of the internal mammary artery with cystic medial degeneration.

We herein report the histopathology of a rare case of an idiopathic internal mammary artery aneurysm in a 61-year-old asymptomatic woman. Chest radiography during an annual medical check-up incidentally revealed the aneurysm, which was initially mistaken for a mediastinal tumor. Given that a rupture of the aneurysm could have been life-threatening, it was removed surgically, and found to possess a paper-thin arterial wall with cystic medial degeneration.

Appraisal of a copresent observer as supportive activates the left inferior parietal lobule: a near-infrared spectroscopy study using a driving video game.

The role of the presence of others in a social context has been debated widely. Although the importance of mutual cognitive functions between performer and observer is generally accepted, little is known about the neural correlates of paired performers and observers themselves. In this near-infrared spectroscopy (NIRS) study we measured the activation in the bilateral inferior parietal lobule (IPL) when driver-observer pairs of participants performed a driving video game task. The performer's task was to drive from start to goal using a default route map, while their partner observed the performance. According to the performer's subjective appraisal of the copresent observer obtained after the driving task, the pairs were divided into three groups: supportive, nonsupportive, and neutral. The driving time, error, and tension score did not show significant differences between the three groups. However, NIRS data of performers in the supportive group showed significantly higher activation in the left IPL than those in the nonsupportive group, but not in the right IPL. NIRS data of observers in the concerned two groups did not show significant differences bilaterally in IPL. These results suggest that the left IPL distinctively responds according to a performer's cognitive appraisal of a copresent observer.

Distinctive activation patterns under intrinsically versus extrinsically driven cognitive loads in prefrontal cortex: a near-infrared spectroscopy study using a driving video game.

To investigate the neural bases of intrinsically and extrinsically driven cognitive loads in daily life, we measured repetitively prefrontal activation in three (one control and two experimental) groups during a driving video game using near-infrared spectroscopy. The control group drove to goal four times with distinct route-maps illustrating default turning points. In contrast, the memory group drove the memorized default route without a route-map, and the emergency group drove with a route-map, but was instructed to change the default route by an extrinsically given verbal command (turn left or right) as an envisioned emergency. The predictability of a turning point in the route in each group was relatively different: due to extrinsic dictate of others in the emergency group, intrinsic memory in the memory group, and route-map aid in the control group. We analyzed concentration changes of oxygenated hemoglobin (CoxyHb) in the three critical periods (pre-turning, actual-turning, and post-turning). The emergency group showed a significantly increasing pattern of CoxyHb throughout the three periods, and a significant reduction in CoxyHb throughout the repetitive trials, but the memory group did not, even though both experimental groups showed higher activation than the control group in the pre-turning period. These results suggest that the prefrontal cortex differentiates the intrinsically (memory) and the extrinsically (dictate of others) driven cognitive loads according to the predictability of turning behavior, although the two types of cognitive loads commonly show increasing activation in the pre-turning period as the preparation effect.

Factors involved in resistance to early treatment of acute cholangitis patients.

BACKGROUND/AIMS: Severity-based treatment is not homogenously effective for acute cholangitis patients and some are resistant to early treatment. We performed a retrospective cohort study involving acute cholangitis patients and analyzed factors strongly associated with resistance to early treatment. METHODOLOGY: The subjects were 94 patients admitted to the Department of Gastroenterology, Showa University Hospital and diagnosed with acute cholangitis. The endpoint was set as the presence or absence of resistance to early treatment. Background and blood test results of the patients immediately after admission were surveyed and significant factors independently contributing to resistance to early treatment were extracted from the surveyed factors employing a logistic regression model. RESULTS: The mean age of the patients was 73.2 ± 11.6 years and 58 were male (61.7%). Jaundice, fever and abdominal pain were observed in 46 (48.9%), 66 (70.2%) and 85 patients (90.4%), respectively. Twenty-eight patients (29.8%) were resistant to early treatment. On multivariate analysis, 3 factors (fever, serum amylase level and systolic blood pressure (below 100 mm Hg)) were extracted as significant factors independently contributing to resistance to early treatment (p<0.05). CONCLUSIONS: If such resistance can be predicted before treatment, appropriate treatment may be selected to shorten the persistence of symptoms, improving the patient's QOL.

Semantic judgment of Chinese-Japanese bilinguals: a near-infrared spectroscopy study.

We used functional near-infrared spectroscopy to investigate the role of the dorsolateral prefrontal cortex of bilinguals in semantic processing. Chinese-Japanese bilinguals and Japanese monolinguals judged if visually presented pairings of a word and a definition were Japanese. The four types of pairs appeared in Japanese and/or Chinese dictionaries: both, Japanese-specific, Chinese-specific, and neither. The bilinguals showed greater oxy-hemoglobin concentrations in their left dorsolateral prefrontal cortex for the Chinese-specific pair, while those in its right homologue were greater for the Japanese-specific, the Chinese-specific, and the neither pairs. These results imply that in the bilinguals, the left dorsolateral prefrontal cortex is related to reducing activation of semantic information in the nontarget language, while its right homologue focuses attention on the target language.

In vivo evaluation of bonding ability and biocompatibility of a novel biodegradable glue consisting of tartaric acid derivative and human serum albumin.

We recently developed a novel biological glue from tartaric acid derivative (TAD) with two active ester groups and human serum albumin (HSA), named TAD-A. In this study, in vivo experiments were performed to investigate clinical applicability of TAD-A. TAD was prepared by reacting carboxyl groups of tartaric acid with N-hydroxysuccinimide in the presence of carbodiimide. Bonding strength was evaluated by using mouse skin closed with TAD-A of different TAD concentrations from 0.1 to 0.5 mmol in 0.8 mg of 44 w/w % HSA solution. Commercially available glues such as fibrin and aldehyde-based glue were used for comparison. We found that TAD-A's bonding strength increased significantly with TAD-A concentration. The bonding strength of 0.5 mmol of TAD-A in 0.8 mg of 44 w/w % HSA solution was significantly higher than that of fibrin or aldehyde-based glue (p < 0.01), and that of 0.3 mmol of TAD-A was significantly higher than of fibrin glue (p < 0.05). To determine toxicity, we implanted disks made from TAD-A of different TAD concentrations from 0.1 to 0.5 mmol in 0.8 mg of 44 w/w % HSA solution subcutaneously in mice. The inflammatory reaction in surrounding tissue increased with increasing TAD concentration, and then the disks were absorbed. In conclusion, TAD-A has sufficient bonding strength and comparatively low toxicity in clinical use of 0.3 mmol or less of TAD and 0.8 mL of 44 w/w % HSA solution.