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OBJECTIVES: This study investigated the incidence of lymph node metastasis and long-term outcomes in patients with T1 colorectal cancer where endoscopic submucosal dissection (ESD) resulted in noncurative treatment. It is focused on those with deep submucosal invasion, a factor considered a weak predictor of lymph node metastasis in the absence of other risk factors. METHODS: This nationwide, multicenter, prospective study conducted a post-hoc analysis of 141 patients with T1 colorectal cancer ≥20 mm where ESD of the lesion resulted in noncurative outcomes, characterized by poor differentiation, deep submucosal invasion (≥1000 µm), lymphovascular invasion, high-grade tumor budding, or positive vertical margins. Clinicopathologic features and patient prognoses focusing on lesion sites and additional surgery requirements were evaluated. Lymph node metastasis incidence in the low-risk T1 group, identified by deep submucosal invasion as the sole high-risk histological feature, was assessed. RESULTS: Lymph node metastasis occurred in 14% of patients undergoing additional surgery post-noncurative endoscopic submucosal dissection for T1 colorectal cancer. In the low-risk T1 group, in the absence of other risk factors, the frequency was 9.7%. The lymph node metastasis rates in patients with T1 colon and rectal cancers did not differ significantly (14% vs. 16%). Distant recurrence was observed in one patient (2.3%) in the ESD only group and in one (1.0%) in the additional surgery group, both of whom had had rectal cancer removed. CONCLUSION: The risk of lymph node metastasis or distant occurrence was not negligible, even in the low-risk T1 group. The findings suggest the need for considering additional surgery, particularly for rectal lesions (Clinical Trial Registration: UMIN000010136).
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This study examined the utility of the combined use of transabdominal ultrasonography (TUS) and fecal immunochemical testing (FIT) to detect mucosal inflammation, vis-a-vis the Mayo endoscopic subscore (MES), in ulcerative colitis (UC). Sixty-three UC patients who underwent TUS and FIT were retrospectively enrolled. For TUS, the colon was divided into five segments, and the bowel wall thickness was measured and evaluated. The accuracy of FIT (> 100 ng/ml) in detecting mucosal inflammation (MES>0) was 0.93, whereas that of TUS (BWT>2 mm) in each segment was 0.84-0.97. The combined use of TUS and FIT may be helpful in noninvasive treatment strategies.
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Colitis Ulcerosa , Humanos , Colitis Ulcerosa/diagnóstico por imagen , Colonoscopía , Estudios Retrospectivos , Mucosa Intestinal/química , Mucosa Intestinal/diagnóstico por imagen , Ultrasonografía , Índice de Severidad de la Enfermedad , Inflamación , BiomarcadoresRESUMEN
BACKGROUND: People with schizophrenia have a lower colorectal screening rate than the general population. A previous study reported an intervention using case management to encourage colorectal cancer screening for patients with schizophrenia in psychiatric outpatient settings. In this feasibility study, we developed provider-level implementation strategies and evaluated the feasibility of conducting a definitive trial in terms of the penetration of the intervention assessed at the patient level. Additionally, we examined the fidelity of strategies to implement the intervention at the provider level in a routine clinical psychiatric setting. METHODS: This was a multicenter, single-arm feasibility study with medical staff at psychiatric hospitals in Japan. The provider-level implementation strategies developed in this study included three key elements (organizing an implementation team appointed by the facility director, interactive assistance using a clear guide that outlines who in the hospital should do what, and developing accessible educational materials) to overcome major barriers to implementation of the intervention and four additional elements (progress monitoring, joint meetings and information sharing among participating sites, adaptation of encouragement methods to specific contexts, and education of on-site staff), with reference to the elements identified in the Expert Recommendations for Implementing Change (ERIC). The feasibility of the strategies was evaluated by the proportion of patients who were eligible for encouragement (patients with schizophrenia aged 40, 50, or 60) who received encouragement. We set the goal of providing encouragement to at least 40% of eligible patients at each site. RESULTS: Two public and four private psychiatric hospitals in Okayama and Shimane prefectures participated in this study. Regarding fidelity, all elements of the strategies were conducted as planned. Following the procedures in the guide, each team prepared and provided encouragement according to their own facility and region. Penetration, defined as the proportion of eligible patients who received encouragement, ranged from 33.3 to 100%; five of the six facilities achieved the target proportion. CONCLUSIONS: The provider-level implementation strategies to implement encouragement were feasible in terms of penetration of the intervention assessed at the patient level. The results support the feasibility of proceeding with a future definitive trial of these strategies. TRIAL REGISTRATION: jRCT, jRCT1060220026 . Registered on 06/04/2022.
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BACKGROUND & AIMS: Reported rates of delayed bleeding (DB) after endoscopic resection using direct oral anticoagulants (DOACs) are high and heterogeneous. This large-scale multicenter study analyzed cases of DB after colorectal endoscopic submucosal dissection related to various types of DOACs in Japan (the ABCD-J study) with those associated with warfarin. METHODS: We retrospectively reviewed 1019 lesions in patients treated with DOACs and 459 lesions in patients treated with warfarin among 34,455 endoscopic submucosal dissection cases from 47 Japanese institutions between 2012 and 2021. The DB rate (DBR) with each DOAC was compared with that with warfarin. Risk factors for DB in patients treated with DOACs or warfarin were also investigated. RESULTS: The mean tumor sizes in the DOAC and warfarin groups were 29.6 ± 14.0 and 30.3 ± 16.4 mm, respectively. In the DOAC group, the DBR with dabigatran (18.26%) was significantly higher than that with apixaban (10.08%, P = .029), edoxaban (7.73%, P = .001), and rivaroxaban (7.21%, P < .001). Only rivaroxaban showed a significantly lower DBR than warfarin (11.76%, P = .033). In the multivariate analysis, heparin bridging therapy (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.27-3.73, P = .005), rectal location (2.01, 1.28-3.16, P = .002), and procedure time ≥55 minutes (2.43, 1.49-3.95, P < .001) were significant risk factors for DB in the DOAC group. The DB risk in the DOAC group (OR, (95% CI)) was 2.13 (1.30-3.50) and 4.53 (2.52-8.15) for 1 and 2 significant risk factors, respectively. CONCLUSIONS: Dabigatran was associated with a higher DBR than other DOACs, and only rivaroxaban was associated with a significantly lower DBR than warfarin.
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Fibrilación Atrial , Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Humanos , Warfarina , Rivaroxabán/efectos adversos , Dabigatrán/efectos adversos , Japón , Resección Endoscópica de la Mucosa/efectos adversos , Estudios Retrospectivos , Hemorragia/inducido químicamente , Anticoagulantes , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/complicaciones , Administración Oral , Fibrilación Atrial/complicacionesRESUMEN
OBJECTIVES: We previously demonstrated that a favorable long-term prognosis indicated that endoscopic submucosal dissection (ESD) could be the standard treatment for large colorectal epithelial neoplasms, but the usefulness of ESD for local residual or recurrent tumors with submucosal fibrosis has not been fully demonstrated. The aim of the present study was to assess the usefulness of ESD for local residual or recurrent colorectal tumors. METHODS: We conducted a nationwide multicenter prospective study to evaluate the outcomes of ESD for colorectal tumors. In this post hoc analysis, a total of 54 local residual or recurrent colorectal tumors in 54 patients were included, and we analyzed the short-term and long-term outcomes of ESD for these lesions. RESULTS: The median size of the lesions was 16.0 (interquartile range [IQR] 11-25) mm. ESD was completed in 53 cases (98.1%) with a median procedure time of 65.0 min, but it was discontinued in one case because of submucosal cancer invasion. En bloc resection was achieved in 52 cases (96.3%), whereas R0 resection was achieved in 45 cases (83.3%). Intraoperative perforation was observed in four cases (7.4%) and delayed perforation in one (1.9%), but all cases could be managed conservatively. Delayed bleeding was not observed. There were no significant differences in short-term outcomes between the rectal and colonic lesions. There was no recurrence of the tumor during the median follow-up period of 60 (IQR 50-64) months. CONCLUSION: An analysis of our multicenter prospective study suggests that ESD is an effective salvage management for local residual or recurrent colorectal lesions.
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OBJECTIVES: The incidence of colorectal neuroendocrine tumors (NETs) has increased with colorectal cancer screening programs and increased colonoscopies. The management of colorectal NETs has recently shifted from radical surgery to endoscopic resection. We aimed to evaluate the short-term outcomes of various methods of endoscopic resection for colorectal NETs. METHODS: Among those registered in the C-NET STUDY, patients with colorectal NETs who underwent endoscopic treatment as the initial therapy were included. Short-term outcomes, such as the en bloc resection rate and R0 resection (en bloc resection with tumor-free margin) rate, were analyzed based on treatment modalities. RESULTS: A total of 472 patients with 477 colorectal NETs received endoscopic treatment. Of these, 418 patients with 421 lesions who met the eligibility criteria were included in the analysis. The median age of the patients was 55 years, and 56.9% of them were men. The lower rectum was the most commonly affected site (88.6%), and lesions <10 mm accounted for 87% of the cases. Endoscopic submucosal resection with a ligation device (ESMR-L, 56.5%) was the most common method, followed by endoscopic submucosal dissection (ESD, 31.4%) and endoscopic mucosal resection using a cap (EMR-C, 8.5%). R0 resection rates <10 mm were 95.5%, 94.8%, and 94.3% for ESMR-L, ESD, and EMR-C, respectively. All 16 (3.8%) patients who developed treatment-related complications could be treated conservatively. Overall, 23 (5.5%) patients had incomplete resection without independent clinicopathological risk factors. CONCLUSION: ESMR-L, ESD, and EMR-C were equally effective and safe for colorectal NETs with a diameter <10 mm.
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Although the clinical usefulness of colonoscopy has been established, the procedure remains painful for many patients. This study was designed to clarify the factors predicting colonoscopy-related pain. We evaluated 283 consecutive patients who completed a first-ever, total colonoscopy without sedatives or analgesics. The severity of pain symptoms was evaluated by a numeric rating scale (NRS) in a questionnaire immediately after the colonoscopy. Patient backgrounds and endoscopic findings were analyzed to evaluate their association with pain. Out of 283 patients, 53 scored their pain 0-1 on the NRS while 48 scored it 6-10. We defined the colonoscopies of the former and latter patients as painless and painful, respectively, and compared the two. Multivariate analyses revealed that low body weight (OR 4.95, 95%CI 1.89-12.99) and longer intubation time (OR 3.63, 95%CI 1.46-9.03) were significant risk factors for painful colonoscopy. To identify factors contributing to the increased intubation time, we divided subjects into short- and long-intubation-time groups based on a median insertion time of 7 min. Older age (OR 2.28, 95%CI 1.31-3.98), previous abdominal surgery (OR 1.93, 95%CI 1.13-3.32) and findings of invasive cancer (OR 10.90, 95%CI 1.34-88.90) were significant factors for longer intubation time.
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Colonoscopía , Dolor , Humanos , Dimensión del Dolor/efectos adversos , Dolor/etiología , Colonoscopía/efectos adversos , Hipnóticos y Sedantes , Intubación Intratraqueal/efectos adversosRESUMEN
Adrenal medullary chromaffin (AMC) and sympathetic ganglion cells are derived from the neural crest and show a similar developmental path. Thus, these two cell types have many common properties in membrane excitability and signaling. However, AMC cells function as endocrine cells while sympathetic ganglion cells are neurons. In rat sympathetic ganglion cells, muscarinic M1 and M4 receptors mediate excitation and inhibition via suppression of M-type K+ channels and suppression of voltage-dependent Ca2+ channels, respectively. On the other hand, M1 receptor stimulation in rat AMC cells also produces excitation by suppressing TWIK-related acid sensitive K+ (TASK) channels. However, whether M4 receptors are coupled with voltage-dependent Ca2+ channel suppression is unclear. We explore this issue electrophysiologically and biochemically. Electrical stimulation of nerve fibers in rat adrenal glands trans-synaptically increased the Ca2+ signal in AMC cells. This electrically evoked increased Ca2+ signal was not altered during muscarine-induced increase in Ca2+ signal, whereas it decreased significantly during a GABA-induced increase, due to a shunt effect of increased Cl- conductance. The whole-cell current recordings revealed that voltage-dependent Ca2+ currents in AMC cells were suppressed by adenosine triphosphate, but not by muscarinic agonists. The fractionation analysis and immunocytochemistry indicated that CaV1.2 Ca2+ channels and M4 receptors are located in the raft and non-raft membrane domains, respectively. We concluded that muscarinic stimulation in rat AMC cells does not produce voltage-dependent Ca2+ channel inhibition. This lack of muscarinic inhibition is at least partly due to physical separation of voltage-dependent Ca2+ channels and M4 receptors in the plasma membrane.
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One of the mechanisms for hypertension is an increase in blood catecholamines due to increased secretion from sympathetic nerve terminals and adrenal medullary chromaffin (AMC) cells. Spontaneously hypertensive rats (SHRs) are used as an animal model of hypertension. Catecholamine secretion in AMC cells occurs in response to humoral factors and neuronal inputs from the sympathetic nerve fibres. Acetylcholine (ACh) released from the nerve terminals activates nicotinic as well as muscarinic ACh receptors. The present experiment aimed to elucidate whether muscarinic receptor-mediated excitation is altered in SHR AMC cells and, if it is, how. Compared with normotensive rat AMC cells, muscarinic stimulation induced greater catecholamine secretion and larger depolarising inward currents in SHR AMC cells. In contrast to normotensive rat AMC cells, the muscarine-induced current consisted of quinine-sensitive and quinine-insensitive components. The former and the latter are possibly ascribed to nonselective cation channel activation and TWIK-related acid-sensitive K+ (TASK) channel inhibition, as noted in guinea pig AMC cells. In fact, immunoreactive material for TASK1 and several isoforms of transient receptor potential canonical (TRPC) channels was detected in SHR AMC cells. Stromal interaction molecule 1 (STIM1), which plays an essential role for heteromeric TRPC1-TRPC4 channel formation and is not expressed in normotensive rat AMC cells, was detected in the cytoplasm and co-localised with TRPC1. The expression of muscarinic M1 receptors was enhanced in SHR AMC cells compared with normotensive rats. The results indicate that muscarinic excitation is enhanced in SHR AMC cells, probably through facilitation of TRPC channel signalling.
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Médula Suprarrenal , Células Cromafines , Hipertensión , Ratas , Animales , Cobayas , Ratas Endogámicas SHR , Quinina/metabolismo , Células Cromafines/metabolismo , Médula Suprarrenal/metabolismo , Receptores Muscarínicos/metabolismo , Colinérgicos/metabolismo , Hipertensión/metabolismo , Catecolaminas/metabolismoRESUMEN
Adrenal medullary chromaffin (AMC) cells in the perinatal period and carotid body glomus cells after birth respond to hypoxia with catecholamine secretion. The hypoxia detection mechanism in such O2-sensitive cells is still not well defined. One hypothesis is that a decrease in cellular ATP may be involved in the hypoxia detection. This idea is based on ATP dependence of TASK channel activity that regulates the resting membrane potential and is suppressed by hypoxia in glomus cells. Mitochondrial ATPase inhibitor factor-1 (IF1), a physiological regulator of ATP synthase, helps prevent ATP hydrolysis under hypoxic conditions. In cells where IF1 expression is high, exposure to hypoxia is expected to have no effect on TASK channel activity. This possibility was electrophysiologically and immunocytochemically explored. Single channel recordings revealed that 36-pS TASK3-like channels contribute to the resting membrane potential in young rat adrenal cortical (AC) cells. TASK3-like channel activity in a cell-attached patch was not affected by bath application of mitochondrial inhibitors. Consistent with this finding, IF1-like immunoreactive material was well expressed in rat AC cells. In further support of our hypothesis, IF1-like immunoreactive material was well expressed in adult rat AMC cells that are known to be hypoxia-insensitive and minimally expressed in newborn AMC cells that are hypoxia-sensitive. These results provide evidence for the functional relevance of IF1 expression in excitability in O2-sensitive cells in response to mitochondrial inhibition.
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Células Cromafines , Embarazo , Femenino , Ratas , Animales , Hipoxia de la Célula , Células Cromafines/metabolismo , Mitocondrias/metabolismo , Hipoxia/metabolismo , Adenosina Trifosfato/metabolismoRESUMEN
OBJECTIVES: Double balloon enteroscopy (DBE) with retrograde contrast is useful as a monitoring tool for small intestinal lesions in Crohn's disease (CD), but these are burdensome for patients. Intestinal ultrasound (IUS) can be used with ease in daily clinical practice, but there is less evidence regarding the accuracy of detection of small intestinal stenosis in CD. This study aimed to examine the diagnostic power of IUS for small intestinal stenosis in patients with CD. METHODS: The findings of DBE and IUS in 86 patients with CD with small intestinal lesions were evaluated. Using DBE as the reference standard, we examined the detection rate of IUS for small intestinal stenosis. We evaluated three parameters: luminal narrowing, prestenotic dilation, and to-and-fro movement for determining stenosis using IUS. In addition, we compared the characteristics between the stenosis-detectable and stenosis-undetectable groups by IUS. RESULTS: Of the 86 patients, 30 had small intestinal stenosis. In IUS findings, when lesions that met two or more of the three parameters were judged as stenosis, the detection rate was 70.0% for sensitivity, 98.2% for specificity, and 88.4% for accuracy. Moreover, there were patients with a younger age at diagnosis (P < 0.05) and more ileocolonic disease location (P < 0.05) in the stenosis-detectable group by IUS. The stenoses detected by IUS were significantly longer than those undetected by IUS (14.1 mm versus 5.2 mm, P < 0.05). CONCLUSIONS: IUS delivered reliable results for clinically important small intestinal stenosis of CD with high diagnostic accuracy.
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Enfermedad de Crohn , Humanos , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico por imagen , Constricción Patológica/diagnóstico por imagen , Intestinos/diagnóstico por imagen , Intestinos/patología , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/patología , Ultrasonografía/métodosRESUMEN
Immunocytochemistry enables the detection and localization of proteins in cells that are acutely dissociated or in culture. There are advantages and disadvantages to the use of cultured cells for immunocytochemistry. One of the advantages is that cultured cells can be used for one or more weeks after the dissociation of cells, whereas one of the disadvantages is that the properties of cells in culture might change under artificial conditions. On the other hand, acutely dissociated cells are expected to have the original properties of cells because almost all procedures before fixation, except for enzymatic digestion, are carried out at low temperatures. Here, we describe how adrenal medullary cells of small animals are acutely dissociated for immunostaining.
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Médula Suprarrenal , Células Cromafines , Células Endocrinas , Animales , Células Cultivadas , InmunohistoquímicaRESUMEN
Chronic intermittent hypoxia (CIH) has been used as a model to mimic nocturnal apnea, which is associated with hypertension. One of the mechanisms for hypertension in patients with nocturnal apnea is an enhancement of the plasma membrane response to acute hypoxia in carotid body glomus cells. Hypoxia is known to induce depolarization via inhibiting TWIK-related acid-sensitive K+ (TASK) channels, one type of leak K+ channels, in glomus cells. The present experiment was undertaken to immunocytochemically investigate the effects of CIH on the expression and intracellular localization of TASK1 channels and p11 that critically affect the trafficking of TASK1 to the cell surface. The expression levels of TASK1 proteins and p11 and their intracellular localization in rat carotid body glomus cells were not noticeably affected by CIH, suggesting that the enhanced membrane response to acute hypoxia is not due to an increase in surface TASK channels.
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Cuerpo Carotídeo , Hipertensión , Animales , Apnea/metabolismo , Cuerpo Carotídeo/metabolismo , Hipoxia/metabolismo , RatasRESUMEN
BACKGROUND & AIMS: To determine the long-term outcomes after colorectal endoscopic submucosal dissection (ESD), we conducted a large, multicenter, prospective cohort trial with a 5-year observation period. METHODS: Between February 2013 and January 2015, we consecutively enrolled 1740 patients with 1814 colorectal epithelial neoplasms ≥20 mm who underwent ESD. Patients with noncurative resection (non-CR) lesions underwent additional radical surgery, as needed. After the initial treatment, intensive 5-year follow-up with planned multiple colonoscopies was conducted to identify metastatic and/or local recurrences. Primary outcomes were overall survival, disease-specific survival, and intestinal preservation rates. The rates of local recurrence and metachronous invasive cancer were evaluated as the secondary outcomes. RESULTS: The 5-year overall survival, disease-specific survival, and intestinal preservation rates were 93.6%, 99.6%, and 88.6%, respectively. Patients with CR lesions had no metastatic occurrence, and patients with non-CR lesions had 4 metastatic occurrences. Kaplan-Meier curves revealed that overall survival and disease-specific survival rates were significantly higher in patients with CR lesions than in those with non-CR lesions (P > .001 and P = .009, respectively). Local recurrence occurred in only 8 lesions (0.5%), which were successfully resected by subsequent endoscopic treatment. Multiple logistic regression analyses revealed that piecemeal resection (hazard ratio, 8.19; 95% CI, 1.47-45.7; P = .02) and margin-positive resection (hazard ratio, 8.06; 95% CI, 1.76-37.0; P = .007) were significant independent predictors of local recurrence after colorectal ESD. Fifteen metachronous invasive cancers (1.0%) were identified during surveillance colonoscopy, most of which required surgical resection. CONCLUSIONS: A favorable long-term prognosis indicates that ESD can be the standard treatment for large colorectal epithelial neoplasms. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000010136.
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Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Neoplasias Glandulares y Epiteliales , Humanos , Resección Endoscópica de la Mucosa/efectos adversos , Japón/epidemiología , Estudios Prospectivos , Recurrencia Local de Neoplasia/epidemiología , Colonoscopía , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Resultado del Tratamiento , Estudios Retrospectivos , Mucosa Intestinal/diagnóstico por imagen , Mucosa Intestinal/cirugía , Mucosa Intestinal/patologíaRESUMEN
OBJECTIVES: We examined the efficacy of case management (CM) interventions to encourage participation in colorectal cancer screening for patients with schizophrenia. This study aimed to clarify patients' acceptability of the intervention and the helpful components of the intervention. Simultaneously, the study aimed to determine the acceptability, appropriateness and feasibility of the intervention from the perspective of psychiatric care providers. STUDY DESIGN AND SETTING: This study was a secondary qualitative analysis of a mixed-method randomised controlled trial that evaluated the efficacy of the CM approach to encourage participation in cancer screening for people with schizophrenia. The intervention comprised education and patient navigation for colorectal cancer screening. Interviews were conducted with patients who received the intervention and staff from two psychiatric hospitals in Japan who delivered the intervention. PARTICIPANTS: Of the 172 patients with schizophrenia who participated in the trial, 153 were included. In addition, three out of six providers were included. DATA COLLECTION AND ANALYSIS: Using a structured interview, the case manager asked participants about patient acceptability and the helpful components of the intervention. Content analysis was conducted for the responses obtained, and the number of responses was tabulated by two researchers. For the interviews with the providers, opinions obtained from verbatim transcripts were extracted and summarised. RESULTS: Forty-three of the 56 patients perceived that the intervention was acceptable. For the intervention component, inperson counselling with an explanation of the screening process by psychiatric care providers was most frequently reported by the patients as helpful (48 of the 68 respondents). Psychiatric care providers evaluated the intervention as acceptable, appropriate and easy to understand and administer. However, providing the intervention to all patients simultaneously was considered difficult with the current human resources. CONCLUSIONS: This study showed that the CM intervention was perceived as acceptable by patients and acceptable and appropriate by psychiatric care providers. TRIAL REGISTRATION NUMBER: UMIN000036017.
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Neoplasias Colorrectales , Esquizofrenia , Manejo de Caso , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer , Estudios de Factibilidad , Humanos , Esquizofrenia/complicaciones , Esquizofrenia/diagnóstico , Esquizofrenia/terapiaRESUMEN
TWIK-related acid-sensitive K+ (TASK) channels are thought to contribute to the resting membrane potential in adrenal cortical (AC) cells. However, the molecular identity of TASK channels in AC cells have not yet been elucidated. Thus, immunocytochemical and molecular biological approaches were employed to investigate the expression and intracellular distribution of TASK1 and TASK3 in mouse AC cells and H295R cells derived from human adrenocortical carcinoma. Immunocytochemical study revealed that immunoreactive materials were mainly located in the cytoplasm for TASK1 and at the cell periphery for TASK3 in mouse AC cells. A similar pattern of localization was observed when GFP-TASK1 and GFP-TASK3 were exogenously expressed in H295R cells. In addition, p11 that is known to suppress the endoplasmic reticulum exit of TASK1 was localized in the cytoplasm in mouse AC and H295R cells, but not in adrenal medullary cells. Proximity ligation assay (PLA) suggested formation of heteromeric TASK1-3 channels that were found predominantly in the cytoplasm and weakly at the cell periphery. A similar distribution was observed following exogenous expression of tandem TASK1-3 channels in H295R cells. When stimulated by angiotensin II, however, tandem TASK1-3 channels were present mainly in the cytoplasm in all H295R cells. In contrast to that in H295R cells, tandem channels were exclusively located at the cell periphery in all non-stimulated and exclusively in the cytoplasm in stimulated PC12 cells, respectively. From these results, we conclude that TASK1 proteins are present mainly in the cytoplasm and minimally at the cell periphery as a heteromeric channel with TASK3, whereas the majority of TASK3 is at the cell periphery as homomeric and heteromeric channels.
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Células Endocrinas , Proteínas del Tejido Nervioso/metabolismo , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Angiotensina II/metabolismo , Animales , Células Endocrinas/metabolismo , Humanos , Ratones , Células PC12 , Canales de Potasio/metabolismo , RatasRESUMEN
BACKGROUND: This is the first report from a multicenter prospective cohort study of colorectal neuroendocrine tumor (NET), the C-NET STUDY, conducted to assess the long-term outcomes of the enrolled patients. This report aimed to elucidate the clinicopathological features of the enrolled patients and lesions. METHODS: Colorectal NET patients aged 20-74 years were consecutively enrolled and followed up at 50 institutions. The baseline characteristics and clinicopathological findings at enrollment and treatment were assessed. RESULTS: A total of 495 patients with 500 colorectal NETs were included. The median patient age was 54 years, and 85.3% were asymptomatic. The most frequent lesion location was the lower rectum (88.0%); 99.4% of the lesions were clinically diagnosed to be devoid of metastatic findings, and 95.4% were treated with endoscopic resection. Lesions < 10 mm comprised 87.0% of the total, 96.6% had not invaded the muscularis propria, and 92.6% were classified as WHO NET grade 1. Positive lymphovascular involvement was found in 29.2% of the lesions. Its prevalence was high even in small NETs with immunohistochemical/special staining for pathological assessment (26.4% and 40.9% in lesions sized < 5 mm and 5-9 mm, respectively). Among 70 patients who underwent radical surgery primarily or secondarily, 18 showed positive lymph node metastasis. CONCLUSIONS: The characteristics of real-world colorectal NET patients and lesions are elucidated. The high positivity of lymphovascular involvement in small NETs highlights the necessity of assessing the clinical significance of positive lymphovascular involvement based on long-term outcomes, which will be examined in later stages of the C-NET STUDY. TRIAL REGISTRATION NUMBER: UMIN000025215.
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Neoplasias Colorrectales , Tumores Neuroendocrinos , Neoplasias del Recto , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Humanos , Neoplasias Intestinales , Japón/epidemiología , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/cirugía , Neoplasias Pancreáticas , Estudios Prospectivos , Neoplasias del Recto/patología , Estudios Retrospectivos , Neoplasias GástricasRESUMEN
To prevent falls, it is important to devise a safe balance training program that can be easily performed. This study investigated whether tilting an image in virtual reality (VR) can generate a center-of-gravity sway. Five men and five women were asked to rest standing upright (control condition) and to rest standing upright with a head-mounted display showing a tilted virtual image (VR condition), and changes in their standing balance were observed. Standing balance was assessed by measuring the distance traveled by the center of pressure (COP) of each of the participants' legs. In order to investigate the effects of different tilt speeds and angles on COP, four different images were displayed in VR: an image tilting to 10° moving at a rate of 1°/s; an image tilting to 20° moving 1°/s; an image tilting to 10° moving 10°/s; an image tilting to 20° moving 10°/s. Change in COP was significantly greater in the VR than in the control condition (p < 0.01), and a tilt of 10° moving 1°/s showed the greatest change in COP (p < 0.01). Tilting an image in VR while in a resting standing position can change an individual's COP; thus, VR may be applied to balance training.
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Objectives: Transient fever and electrocoagulation syndrome after colorectal endoscopic submucosal dissection (ESD) remain a challenge. The aim of this study was to assess the risk factors of post-ESD fever and post-ESD coagulation syndrome (PECS), focusing on the involvement of immunosuppressive drugs and steroids (IM). Methods: This retrospective analysis included 510 patients who underwent colorectal ESD at Okayama University Hospital from 2015 to 2020. The incidence rate, clinical outcome, and factors associated with post-ESD fever and PECS were investigated. Results: Post-ESD fever and PECS occurred in 63 patients (12.4%) and 43 patients (8.4%), respectively. In multivariate analysis, the American Society of Anesthesiologists Physical Status ≥3, the use of immunosuppressants or prednisolone ≥5mg (IM group), and injury to muscle layer/perforation were significantly associated with post-ESD fever. In PECS, IM group, tumors located on the right side, treatment time ≥60 min, injury to the muscle layer, and multiple lesions were independent risk factors. Both post-ESD fever and PECS improved conservatively in the IM group, and no serious complication was observed. Conclusions: The use of IM was a risk factor for both post-ESD fever and PECS. However, there were no serious complications in colorectal ESD for patients taking IM.
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Objective Transabdominal ultrasonography (TUS) is a non-invasive procedure that is reportedly useful for managing ulcerative colitis (UC) and assessing bowel wall thickness (BWT), the most common measure of mucosal inflammation. However, the exact range of BWT that reflects disease activity remains undetermined. The present study clarified the BWT due to disease activity by comparing the use of TUS in each segment of the colon versus using colonoscopy (CS) and determined the usefulness of TUS in patients with UC. Methods We divided the colon into five segments and measured the BWT using TUS. The results were then compared to the Mayo endoscopic subscore (MES) classification to determine the accuracy of BWT measurement. Patients Eighty patients with UC who underwent TUS within 14 days of CS were retrospectively registered. Results We evaluated a total of 268 images depicting each segment among 80 patients with UC. The BWT was positively correlated with endoscopic activity (0.69, p<0.0001). In each segment, the relationship between a BWT>2 mm and an MES>0 had the highest sensitivity, specificity, and accuracy (0.85-1.00, 0.67-0.92, and 0.81-0.97, respectively). Conclusion This study concluded that TUS was a useful method of detecting an MES>0, which indicates the presence of inflammation and its location among UC patients. MES>0 was found to be highly accurate when a BWT>2 mm was considered positive. This non-invasive method may help control disease activity in patients with UC.