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1.
Biochem Biophys Res Commun ; 708: 149819, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38531221

RESUMEN

Metastasis, which is the spread of cancer cells into distant organs, is a critical determinant of prognosis in patients with cancer, and blood vessels are the major route for cancer cells to spread systemically. Extravasation is a critical process for the hematogenous metastasis; however, its underlying molecular mechanisms remain poorly understood. Here, we identified that senescent ECs highly express C-type lectin domain family 1 member B (CLEC-1b), and that endothelial CLEC-1b inhibits the hematogenous metastasis of a certain type of cancer. CLEC-1b expression was enhanced in ECs isolated from aged mice, senescent cultured human ECs, and ECs of aged human. CLEC-1b overexpression in ECs prevented the disruption of endothelial integrity, and inhibited the transendothelial migration of cancer cells expressing podoplanin (PDPN), a ligand for CLEC-1b. Notably, target activation of CLEC-1b in ECs decreased the hematogenous metastasis in the lungs by cancer cells expressing PDPN in mice. Our data reveal the protective role of endothelial CLEC-1b against cancer hematogenous metastasis. Considering the high CLEC-1b expression in senescent ECs, EC senescence may play a beneficial role with respect to the cancer hematogenous metastasis.


Asunto(s)
Lectinas Tipo C , Neoplasias , Anciano , Animales , Humanos , Ratones , Plaquetas/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Neoplasias/metabolismo , Factores de Transcripción/metabolismo , Migración Transendotelial y Transepitelial
2.
Surg Today ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38740574

RESUMEN

The sigmoid colon simulator was designed to accurately reproduce the anatomical layer structure and the arrangement of characteristic organs in each layer, and to have conductivity so that energy devices can be used. Dry polyester fibers were used to reproduce the layered structures, which included characteristic blood vessels, nerve sheaths, and intestinal tracts. The adhesive strength of the layers was controlled to allow realistic peeling techniques. The features of the Sigmaster are illustrated through a comparison of simulated sigmoidectomy using Sigmaster and actual surgery. We developed a laparoscopic sigmoidectomy simulator called Sigmaster. Sigmaster is a training device that closely reproduces the membrane structures of the human body and allows surgeons to experience the entire laparoscopic sigmoidectomy process.

3.
Glia ; 71(2): 467-479, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36286494

RESUMEN

In the brain, neurons, glial cells, vascular endothelial cells (ECs), and mural cells form a functional structure referred to as the neurovascular unit (NVU). The functions of the NVU become impaired with aging. To gain insight into the mechanism underlying the aging-related changes in the NVU, we characterized in the present study the gliovascular interface in transgenic mice expressing a dominant-negative form of the telomeric repeat-binding factor 2 (TERF2) specifically in ECs using the Tie2 promoter. In these transgenic mice, senescence occurred in the cerebral ECs and was accompanied by upregulation of the mRNAs of proinflammatory cell adhesion molecules and cytokines. It is noteworthy that in the deep layers of the cerebral cortex, astrocytes exhibited an increase in the signals for S100ß as well as a decrease in the polarization of the water channel aquaporin-4 (AQP4) to the perivascular endfeet of the astrocytes. Mechanistically, the perivascular localization of dystroglycan and its ligand, laminin α2, was decreased, and their localization correlated well with the perivascular localization of AQP4, which supports the notion that their interaction regulates the perivascular localization of AQP4. The diminished perivascular localization of laminin α2 may be attributed to its proteolytic degradation by the matrix metalloproteinase-2 released by senescent ECs. Pericyte coverage was increased and negatively correlated with the decrease in the perivascular localization of AQP4. We propose that aging-related changes in ECs induce a mild morphological alteration of astrocytes and affect the localization of AQP4 at the gliovascular interface.


Asunto(s)
Senescencia Celular , Células Endoteliales , Laminina , Metaloproteinasa 2 de la Matriz , Neuroglía , Animales , Ratones , Acuaporina 4/genética , Acuaporina 4/metabolismo , Astrocitos/metabolismo , Células Endoteliales/metabolismo , Laminina/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones Transgénicos , Neuroglía/metabolismo
4.
Br J Surg ; 110(12): 1834-1839, 2023 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-37695301

RESUMEN

BACKGROUND: The Endoscopic Surgical Skill Qualification System (ESSQS) in Japan evaluates the surgical skills required for laparoscopic surgery as an operator as well as a supervisor. This study aimed to demonstrate the benefits of an ESSQS-certified surgeon's participation in laparoscopic rectal resections as a supervisor (assistant or advisor). METHODS: We retrospectively reviewed laparoscopic resection results for cStage II and III rectal cancer performed at 56 Japanese hospitals between 2014 and 2016. We used propensity score matching to generate paired cohorts with or without an ESSQS-certified supervisor at a one-to-one ratio. The impact of ESSQS-certified supervisors' participation on short-term outcomes was assessed. In the matched cohort, multivariable logistic regression analysis and multivariable regression analysis of postoperative complication rate and intraoperative blood loss were performed to further mitigate the impact of pathological factors. RESULTS: Two groups (n = 399 each) with or without an ESSQS-certified supervisor were well matched by clinical factors. The group with an ESSQS-certified supervisor had lower blood loss (68 mL vs. 98 mL, P = 0.036) and a lower incidence of severe morbidities of Clavien-Dindo grade ≥IIIa (8.0% vs. 13.3%, P = 0.016). Multivariable logistic regression analysis and multivariable regression analysis confirmed that the attendance of ESSQS-certified supervisors reduced postoperative complication occurrence (adjusted odds ratio: 2.28, 95% confidence interval: 1.38 - 3.80, P = 0.001) and intraoperative blood loss (estimated difference: -15.7 mL, P = 0.016). CONCLUSION: This study demonstrated the educational benefits of ESSQS-certified supervisors, including assistants and advisors, evidenced by their superior short-term outcomes.


Asunto(s)
Laparoscopía , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Puntaje de Propensión , Laparoscopía/métodos , Neoplasias del Recto/cirugía , Estudios de Cohortes , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Resultado del Tratamiento
5.
Surg Endosc ; 37(7): 5256-5264, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36973567

RESUMEN

BACKGROUND: An optimal surgical approach to lateral lymph node dissection (LLND) remains controversial. With the recent popularity of transanal total mesorectal excision, a two-team procedure combining the transabdominal and transanal approaches was established as a novel approach to LLND. This study aimed to clarify the safety and feasibility of two-team LLND (2team-LLND) and compare its short-term outcomes with those of conventional transabdominal LLND (Conv-LLND). METHODS: Between April 2013 and March 2020, 463 patients diagnosed with primary locally advanced rectal cancer underwent a transanal total mesorectal excision; among them, 93 patients who underwent bilateral prophylactic LLND were included in this single-center, retrospective study. Among these patients, 50 and 43 patients underwent Conv-LLND (the Conv-LLND group) and 2team-LLND (the 2team-LLND group), respectively. The short-term outcomes, including the operation time, blood loss volume, number of complications, and number of harvested lymph nodes, were compared between the two groups. RESULTS: The intraoperative and postoperative complications in the 2team-LLND group were equivalent to those in the Conv-LLND group; furthermore, the incidence of postoperative urinary retention in the 2team-LLND group was acceptably low (9%). Compared with the Conv-LLND group, the 2team-LLND group had a significantly shorter operation time (P = 0.003), lower median blood loss (P = 0.02), and higher number of harvested lateral lymph nodes (P = 0.0005). CONCLUSION: The intraoperative and postoperative complications of 2team-LLND were comparable with those of Conv-LLND. Thus, 2team-LLND was safe and feasible for advanced lower rectal cancer. Moreover, it was superior to Conv-LLND in terms of the operation time, blood loss volume, and number of harvested lateral lymph nodes. Therefore, it can be a promising LLND approach.


Asunto(s)
Escisión del Ganglio Linfático , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Recurrencia Local de Neoplasia/cirugía
6.
Surg Endosc ; 37(6): 4698-4706, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36890411

RESUMEN

BACKGROUND: Transanal total mesorectal excision is a promising surgical treatment for rectal cancer. However, evidence regarding the differences in outcomes between the transanal and laparoscopic total mesorectal excisions is scarce. We compared the short-term outcomes of transanal and laparoscopic total mesorectal excisions for low and middle rectal cancers. METHODS: This retrospective study included patients who underwent low anterior or intersphincteric resection for middle (5-10 cm) or low (< 5 cm) rectal cancer at the National Cancer Center Hospital East, Japan, from May 2013 to March 2020. Primary rectal adenocarcinoma was confirmed histologically. Circumferential resection margins (CRMs) of resected specimens were measured; margins ≤ 1 mm were considered positive. The operative time, blood loss, hospitalization length, postoperative readmission rate, and short-term treatment results were compared. RESULTS: Four hundred twenty-nine patients were divided into two mesorectal excision groups: transanal (n = 295) and laparoscopic (n = 134). Operative times were significantly shorter in the transanal group than in the laparoscopic group (p < 0.001). The pathological T stage and N status were not significantly different. The transanal group had significantly lower positive CRM rates (p = 0.04), and significantly lower incidence of the Clavien-Dindo grade III (p = 0.02) and IV (p = 0.03) complications. Both groups had distal margin positivity rates of 0%. CONCLUSIONS: Compared to laparoscopic, transanal total mesorectal excision for low and middle rectal cancers has lower incident postoperative complication and CRM-positivity rates, demonstrating the safety and usefulness of local curability for middle and low rectal cancers.


Asunto(s)
Laparoscopía , Neoplasias del Recto , Cirugía Endoscópica Transanal , Humanos , Estudios Retrospectivos , Países en Desarrollo , Cirugía Endoscópica Transanal/métodos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Laparoscopía/métodos , Recto/cirugía , Recto/patología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Resultado del Tratamiento
7.
Surg Today ; 53(4): 490-498, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36255499

RESUMEN

PURPOSE: In abdominoperineal excision (APE), the advantages of the "down-to-up" approach are expected to be more obvious when performed as a two-team approach, including transperineal minimally invasive surgery (TpMIS). We investigated the efficacy of TpMIS with laparoscopic APE for lower rectal cancer. METHODS: Patients who underwent laparoscopic APE with (n = 20) or without (n = 30) TpMIS between December 2013 and April 2020 were retrospectively reviewed. Patient and tumor characteristics, intraoperative outcome, short-term outcome, and pathological findings were compared. Additional subgroup analyses were performed in technically challenging cases, including male patients, obese patients, and patients with tumors located at the anterior wall. RESULTS: There was no marked difference in the patient or tumor characteristics or short-term outcomes, including morbidity and mortality between the two groups. Pathological results were comparable, and the circumferential resection margin (CRM) positive rate was 10% in both groups. TpMIS achieved a significant reduction in operative time (p = 0.02). In a subgroup analysis, the amount of blood loss was also smaller in males (p = 0.02) and patients with a high BMI (> 25) (p = 0.005) than in others. CONCLUSION: Simultaneously performing TpMIS and laparoscopic APE is feasible owing to the favorable complication and CRM-positive rates. In terms of operative time and blood loss, TpMIS is expected to be advantageous in both easy and challenging cases.


Asunto(s)
Hominidae , Laparoscopía , Proctectomía , Neoplasias del Recto , Humanos , Masculino , Animales , Estudios Retrospectivos , Resultado del Tratamiento , Laparoscopía/métodos , Neoplasias del Recto/patología , Proctectomía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos , Márgenes de Escisión
8.
BMC Oral Health ; 23(1): 695, 2023 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-37759198

RESUMEN

BACKGROUND: This study aimed to evaluate the efficacy and safety of dentin hypersensitivity (DH) treatment using a newly developed device based on a powder jet deposition (PJD) technique that creates a hydroxyapatite (HAP) layer on the dentin surface, thereby alleviating the hypersensitivity. The effect of the PJD treatment was compared with that of conventional treatment using Teethmate Desensitizer (TMD; calcium-phosphate containing material with TTCP (Ca4(PO4)2O) and DCPA (CaHPO4)), which has been used clinically in Japan with well-confirmed effectiveness. MATERIALS AND METHODS: A randomized controlled trial was conducted including 35 patients who had symptoms of DH in two or more quadrants. Two test teeth were selected per patient (70 teeth in total) and randomly assigned to PJD or TMD treatment. The efficacy was evaluated using the improvement rate for air and scratch pain according to the scores obtained via visual analog scale 12 weeks after treatment. The safety assessment was performed focusing on gingival index (GI) and spontaneous pain. The t-test was used to analyze the non-inferiority of PJD treatment compared to TMD treatment. RESULTS: The improvement rate of air pain was 69.0% for PJD and 69.7% for TMD. The improvement rate of scratch pain was 80.8% for PJD and 81.7% for TMD. Non-inferiority with a margin of 10% was not observed for both air and scratch pain. No change was observed in GI from baseline and the improvement rate of spontaneous pain for PJD was higher than that for TMD. CONCLUSION: Non-inferiority of PJD to TMD treatment was not observed in this study; however, it was not statistically demonstrated, and the results were thus interpreted as inconclusive. PJD did improve the DH symptoms, as did TMD. PJD's therapeutic effect was most likely attributable to the deposition of a HAP layer on the tooth surface, which would alleviate hypersensitivity for at least 12 weeks without causing severe adverse events. TRIAL REGISTRATION: UMIN-CTR. ID: UMIN000025022. date: 02/12/2016.


Asunto(s)
Sensibilidad de la Dentina , Polvos , Humanos , Sensibilidad de la Dentina/terapia , Durapatita/uso terapéutico , Japón , Dolor , Polvos/uso terapéutico
9.
J Phys Ther Sci ; 35(6): 471-478, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37266364

RESUMEN

[Purpose] This study aimed to extract knowledge for the development of a training program for creating a social model of disability for physical therapists, focusing on the experiential learning of those physical therapists who did not use acceptance of disability according to their subjective judgment. [Participants and Methods] The study included 11 physical therapists who were interviewed about their use of acceptance of disability and the circumstances leading to its non-use. [Results] The study identified the past and current use of acceptance of disability, as well as cases and reasons for its discontinuation, along with changes in clinical content. [Conclusion] The study extracted knowledge for the development of training programs in line with the components of the experiential learning model.

10.
J Biol Chem ; 297(5): 101232, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34582891

RESUMEN

Obesity is a global health problem that is often related to cardiovascular and metabolic diseases. Chronic low-grade inflammation in white adipose tissue (WAT) is a hallmark of obesity. Previously, during a search for differentially expressed genes in WAT of obese mice, we identified glycoprotein nonmetastatic melanoma protein B (GPNMB), of which expression was robustly induced in pathologically expanded WAT. Here, we investigated the role of GPNMB in obesity-related metabolic disorders utilizing GPNMB-deficient mice. When fed a high-fat diet (HFD), GPNMB-deficient mice showed body weight and adiposity similar to those of wild-type (WT) mice. Nonetheless, insulin and glucose tolerance tests revealed significant obesity-related metabolic disorders in GPNMB-KO mice compared with WT mice fed with HFD. Chronic WAT inflammation was remarkably worsened in HFD-fed GPNMB-KO mice, accompanied by a striking increase in crown-like structures, typical hallmarks for diseased WAT. Macrophages isolated from GPNMB-KO mice were observed to produce more inflammatory cytokines than those of WT mice, a difference abolished by supplementation with recombinant soluble GPNMB extracellular domain. We demonstrated that GPNMB reduced the inflammatory capacity of macrophages by inhibiting NF-κB signaling largely through binding to CD44. Finally, we showed that macrophage depletion by addition of clodronate liposomes abolished the worsened WAT inflammation and abrogated the exacerbation of metabolic disorders in GPNMB-deficient mice fed on HFD. Our data reveal that GPNMB negatively regulates macrophage inflammatory capacities and ameliorates the WAT inflammation in obesity; therefore we conclude that GPNMB is a promising therapeutic target for the treatment of metabolic disorders associated with obesity.


Asunto(s)
Tejido Adiposo Blanco/metabolismo , Proteínas del Ojo/metabolismo , Macrófagos/metabolismo , Glicoproteínas de Membrana/metabolismo , Enfermedades Metabólicas/prevención & control , Obesidad/metabolismo , Células 3T3-L1 , Tejido Adiposo Blanco/patología , Animales , Dieta Alta en Grasa/efectos adversos , Proteínas del Ojo/genética , Macrófagos/patología , Glicoproteínas de Membrana/genética , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/genética , Enfermedades Metabólicas/metabolismo , Ratones , Ratones Noqueados , Ratones Obesos , Obesidad/complicaciones , Obesidad/genética , Obesidad/patología
11.
Dis Colon Rectum ; 65(2): 246-253, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-34657080

RESUMEN

BACKGROUND: The International Transanal Total Mesorectal Excision Registry group showed that transanal total mesorectal excision included clinical issues regarding anastomosis-related complications. OBJECTIVE: This study evaluated anastomotic complications in patients whose anastomoses were created with the stapler plus reinforced sutures procedure after transanal total mesorectal excision for low rectal cancer. DESIGN: This was a retrospective single-center study. SETTING: The study was conducted at the National Cancer Center Hospital East, Japan. PATIENTS: Between June 2016 and December 2019, 150 patients underwent transanal total mesorectal excision for low rectal cancer. Stapled anastomosis was performed for 55 patients, and coloanal handsewn anastomosis was performed for 95 patients. Blood perfusion of the colon was routinely evaluated with intraoperative indocyanine green fluorescence angiography. All patients who underwent stapled anastomosis received additional handsewn sutures on all rounds of the stapled line. Patients who underwent intersphincteric resection were excluded. MAIN OUTCOME MEASURES: The anastomosis-related complications were compared between the groups. RESULTS: Early anastomotic leakage was found in one (1.8%) and eight (8.4%) patients in the stapled group and handsewn group. Overall anastomosis-related complications, pelvic abscess, and anastomotic stenosis were significantly less frequent in the stapled group (p < 0.001, p < 0.048, and p < 0.032). Incomplete donuts after the stapled anastomosis were observed in 9 patients (16.4%); however, we reinforced all around the stapled line in these patients, and this reduced the subsequent occurrence of anastomotic leakage. LIMITATIONS: First, this was a retrospective single-center study that was not randomized or controlled. Second, there were chronological differences regarding the anastomotic method between the two groups. Third, our study included a relatively small number of patients who received preoperative chemoradiotherapy. CONCLUSIONS: Stapled anastomosis with reinforced handsewn sutures resulted in fewer anastomosis-related complications than did coloanal handsewn anastomosis after transanal total mesorectal excision for low rectal cancer; thus, the former may be superior and should be the preferred method, when technically possible. See Video Abstract at http://links.lww.com/DCR/B749.COMPLICACIONES RELACIONADAS CON LAS ANASTOMOSIS ENGRAMPADAS Y REFORZADAS CON SUTURAS EN LA EXCISIÓN TOTAL DEL MESORRECTO POR VÍA TRANSANAL EN CASOS DE CÁNCER DE RECTO BAJO: ESTUDIO RETROSPECTIVO UNICÉNTRICO. ANTECEDENTES: El grupo del Registro Internacional de Excisión Total del Mesorrecto por vía Transanal mostró que la excisión total mesorrectal transanal incluía problemas clínicos relacionados a las complicaciones involucradas con la anastomosis. OBJETIVO: Se evaluaron las complicaciones anastomóticas en pacientes cuyas anastomosis se realizaron con engrampadora reforzada de suturas después de la excisión total de l mesorrecto por vía transanal en casos de cáncer de recto bajo. DISEO: Estudio retrospectivo unicéntrico. AJUSTE: El Hospital del Centro Nacional del Cáncer del Este, Japón. PACIENTES: Entre junio de 2016 y diciembre de 2019, 150 pacientes se sometieron a excisión total del mesorrecto por vía transanal en casos de cáncer de recto bajo. Se realizó anastomosis con engrampadora en 55 y anastomosis coloanal suturada a mano en 95 pacientes. La perfusión tisular sanguínea del colon operado se evaluó de forma rutinaria con angiografía de fluorescencia con verde de indocianina intraoperatoria. Todos los pacientes que se sometieron a anastomosis con grapas recibieron suturas realizadas a mano adicionales sobre la totalidad de la línea de grapas. Se excluyeron los pacientes sometidos a resección interesfintérica. PRINCIPALES MEDIDAS DE RESULTADO: Las complicaciones relacionadas con la anastomosis se compararon entre los grupos. RESULTADOS: Se encontró fuga anastomótica temprana en 1 (1.8%) y 8 (8.4%) pacientes en el grupo de engrampado y en el grupo suturado a mano, respectivamente. En general, las complicaciones relacionadas con la anastomosis, el absceso pélvico y la estenosis anastomótica fueron significativamente menos frecuentes en el grupo con grapas (p < 0.001, p < 0.048, p < 0.032, respectivamente). Se observaron donas incompletas después de la anastomosis grapada en 9 pacientes (16,4%); sin embargo, reforzamos todo alrededor de la línea de grapas en estos pacientes, y esto redujo la aparición posterior de fugas anastomóticas. LIMITACIONES: Inicialmente, este fue un estudio retrospectivo de un solo centro que no fue aleatorizado ni controlado. En segundo lugar, hubo diferencias cronológicas con respecto al método anastomótico entre los dos grupos. En tercer lugar, nuestro estudio incluyó un número relativamente pequeño de pacientes que recibieron quimiorradioterapia preoperatoria. CONCLUSIONES: La anastomosis engrapada reforzada con suturas realizadas a mano dio como resultado menos complicaciones relacionadas con la anastomosis que la anastomosis coloanal suturada a mano después de la excisión total del mesorrecto por vía transanal en casos de cáncer de recto bajo; por tanto, el primero puede ser superior y debería ser el método preferido, cuando sea técnicamente posible. Consulte Video Resumen en http://links.lww.com/DCR/B749. (Traducción-Dr. Xavier Delgadillo).


Asunto(s)
Anastomosis Quirúrgica/efectos adversos , Complicaciones Posoperatorias/epidemiología , Proctectomía/efectos adversos , Neoplasias del Recto/cirugía , Grapado Quirúrgico/efectos adversos , Suturas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/instrumentación , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Neoplasias del Recto/patología , Estudios Retrospectivos , Grapado Quirúrgico/instrumentación
12.
Arterioscler Thromb Vasc Biol ; 41(3): 1076-1091, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33504177

RESUMEN

OBJECTIVE: Chondroitin sulfate proteoglycans are the primary constituents of the macrophage glycosaminoglycan and extracellular microenvironment. To examine their potential role in atherogenesis, we investigated the biological importance of one of the chondroitin sulfate glycosaminoglycan biosynthesis gene, ChGn-2 (chondroitin sulfate N-acetylgalactosaminyltransferase-2), in macrophage foam cell formation. Approach and Results: ChGn-2-deficient mice showed decreased and shortened glycosaminoglycans. ChGn-2-/-/LDLr-/- (low-density lipoprotein receptor) mice generated less atherosclerotic plaque after being fed with Western diet despite exhibiting a metabolic phenotype similar to that of the ChGn-2+/+/LDLr-/- littermates. We demonstrated that in macrophages, ChGn-2 expression was upregulated in the presence of oxLDL (oxidized LDL), and glycosaminoglycan was substantially increased. Foam cell formation was significantly altered by ChGn-2 in both mouse peritoneal macrophages and the RAW264.7 macrophage cell line. Mechanistically, ChGn-2 enhanced oxLDL binding on the cell surface, and as a consequence, CD36-an important macrophage membrane scavenger receptor-was differentially regulated. CONCLUSIONS: ChGn-2 alteration on macrophages conceivably influences LDL accumulation and subsequently accelerates plaque formation. These results collectively suggest that ChGn-2 is a novel therapeutic target amenable to clinical translation in the future. Graphic Abstract: A graphic abstract is available for this article.


Asunto(s)
Aterosclerosis/metabolismo , Células Espumosas/metabolismo , Glicosaminoglicanos/metabolismo , N-Acetilgalactosaminiltransferasas/metabolismo , Animales , Aterosclerosis/etiología , Aterosclerosis/patología , Modelos Animales de Enfermedad , Femenino , Células Espumosas/patología , Glicosaminoglicanos/química , Lipoproteínas LDL/metabolismo , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , N-Acetilgalactosaminiltransferasas/deficiencia , N-Acetilgalactosaminiltransferasas/genética , Placa Aterosclerótica/etiología , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Células RAW 264.7 , Regulación hacia Arriba
13.
Int J Colorectal Dis ; 37(9): 1975-1982, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35943579

RESUMEN

PURPOSE: Rectal gastrointestinal stromal tumors (GISTs) surgery is often challenging owing to the anatomical constraints of the narrow pelvis and tumor hugeness. Despite the increasing number of patients undergoing trans-anal total mesorectal excision (taTME) globally, the feasibility of trans-anal surgery with the taTME technique for rectal GISTs remains unclear. We aimed to evaluate the feasibility of trans-anal surgery with the taTME technique for rectal GISTs. METHODS: Using a prospectively collected database, we retrospectively analyzed the clinical findings, surgical outcomes, pathological outcomes, urinary and anal functions, and prognoses of patients who underwent trans-anal surgery with the taTME technique for primary rectal GISTs at the National Cancer Center Hospital East from September 2014 to March 2020. RESULTS: Twenty-one patients with primary rectal GISTs were included in this study. The median distance from the anal verge to the lower edge of the tumor was 40 mm (range, 15-60 mm), and the median tumor size was 59 mm (range, 11-175 mm). Moreover, seven and 14 patients underwent one-team and two-team surgeries, respectively, with curative intent. Nineteen patients (90.5%) underwent anus-preserving surgery, and the urinary tracts were preserved in all cases. Two-team surgery showed a significantly lower blood loss volume and shorter operation time than one-team surgery (58 vs. 222 mL, P = 0.017; 184 vs 356 min, P = 0.041, respectively). The pathological negative-margin resection rate was 100%. During the follow-up period, no patient developed local GIST recurrence and one (4.8%) developed distant metastasis. CONCLUSION: Trans-anal surgery with the taTME technique is feasible for rectal GISTs, and two-team surgery may be more advantageous than one-team surgery in terms of operation time and blood loss.


Asunto(s)
Tumores del Estroma Gastrointestinal , Laparoscopía , Neoplasias del Recto , Canal Anal/cirugía , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Laparoscopía/métodos , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Recto/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
14.
BMC Surg ; 22(1): 12, 2022 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-34998376

RESUMEN

BACKGROUND: Mastery of technical skills is one of the fundamental goals of surgical training for novices. Meanwhile, performing laparoscopic procedures requires exceptional surgical skills compared to open surgery. However, it is often difficult for trainees to learn through observation and practice only. Virtual reality (VR)-based surgical simulation is expanding and rapidly advancing. A major obstacle for laparoscopic trainees is the difficulty of well-performed dissection. Therefore, we developed a new VR simulation system, Lap-PASS LP-100, which focuses on training to create proper tension on the tissue in laparoscopic sigmoid colectomy dissection. This study aimed to validate this new VR simulation system. METHODS: A total of 50 participants were asked to perform medial dissection of the meso-sigmoid colon on the VR simulator. Forty-four surgeons and six non-medical professionals working in the National Cancer Center Hospital East, Japan, were enrolled in this study. The surgeons were: laparoscopic surgery experts with > 100 laparoscopic surgeries (LS), 21 were novices with experience < 100 LS, and five without previous experience in LS. The participants' surgical performance was evaluated by three blinded raters using Global Operative Assessment of Laparoscopic Skills (GOALS). RESULTS: There were significant differences (P-values < 0.044) in all GOALS items between the non-medical professionals and surgeons. The experts were significantly superior to the novices in one item of GOALS: efficiency ([4(4-5) vs. 4(3-4)], with a 95% confidence interval, p = 0.042). However, both bimanual dexterity and total score in the experts were not statistically different but tended to be higher than in the novices. CONCLUSIONS: Our study demonstrated a full validation of our new system. This could detect the surgeons' ability to perform surgical dissection and suggest that this VR simulator could be an effective training tool. This surgical VR simulator might have tremendous potential to enhance training for surgeons.


Asunto(s)
Laparoscopía , Entrenamiento Simulado , Realidad Virtual , Competencia Clínica , Colectomía , Colon Sigmoide , Simulación por Computador , Disección , Humanos , Interfaz Usuario-Computador
15.
J Phys Ther Sci ; 34(4): 262-268, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35400828

RESUMEN

[Purpose] This study aimed to elucidate the content of work beliefs related to proficiency among physical therapists in Japan. [Participants and Methods] Participants included 50 therapists who met the definition of proficiency to participate in a questionnaire survey conducted between October 2017 and March 2019. Participants were asked to freely describe their daily work beliefs, including their thoughts, values, and ideals. This content was coded and categorized using open coding; a hierarchical cluster analysis (Ward's method) was conducted of the proficient therapists with the individuals and belief categories as the variables. All belief categories were classified into three groups. [Results] Three work beliefs were identified as follows: 1) practices that emphasize building relationships in the field, 2) broad practices with physical therapist pride (responsibility and enthusiasm), and 3) practices with awareness of treatment outcomes and social benefits. [Conclusion] A better understanding of the three aforementioned work beliefs would facilitate good support for and development of physical therapists. We recommend continuing to elucidate the three work beliefs identified among proficient therapists and verify their educational effects.

16.
BMC Cancer ; 21(1): 302, 2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33757462

RESUMEN

BACKGROUND: Transmembrane protein 180 (TMEM180) is a newly identified colorectal cancer (CRC)-specific molecule that is expressed very rarely in normal tissue and up-regulated under hypoxic conditions. We developed a monoclonal antibody (mAb) against TMEM180 and decided to examine the medical significance using the mAb. METHODS: A total of 157 patients (86 men and 71 women; median age 63.0 years) with stage III CRC who underwent curative surgery were analyzed for TMEM180 expression as a retrospective cohort design. Immunohistochemistry with anti-TMEM180 mAb was conducted on frozen sections, and the data were evaluated for any correlation with clinicopathological indices or prognosis. SW480 CRC cells were examined to investigate the relationship between the expression of TMEM180 and tumourigenesis of xenografts. RESULTS: In total, 92 cases had low TMEM expression and 65 had high TMEM180 expression. For disease-free survival, hazard ratio in high-TMEM180 cases was 1.449 (95% confidential interval = 0.802-2.619) higher than in low-TMEM180 cases, but the difference was not significant (p = 0.219). For cancer specific survival, hazard ratio in high-TMEM180 cases was 3.302 (95% confidential interval = 1.088-10.020), significantly higher than in low-TMEM180 cases (p = 0.035). In an assay examining in vitro colony-forming activity in soft agar, SW480-WT cells clearly formed colonies, but neither KD1 nor KD2 cells did. The in vivo tumour-initiating activity of SW480 cell lines was positively correlated with the level of TMEM180 expression. CONCLUSION: These results indicate that TMEM180 is a useful marker for clinical prognosis in patients with CRC. We believe that these fundamental data warrant further basic and translational studies of TMEM180, and its mAb, for development of therapeutics against CRC.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Colorrectales/mortalidad , Proteínas de la Membrana/análisis , Anciano , Línea Celular Tumoral , Neoplasias Colorrectales/química , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos
17.
Dis Colon Rectum ; 64(12): 1479-1487, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34657076

RESUMEN

BACKGROUND: Identifying preoperative risk factors of local recurrence and patterns of treatment failure resulting after rectal cancer management is important for planning treatment strategies and improving the results of multidisciplinary care. OBJECTIVE: The purpose of this study was to analyze the associations between the preoperative factors and local recurrence and to investigate the local recurrence areas in patients with locally advanced lower rectal cancer who underwent lateral pelvic lymph node dissection. DESIGN: The study used a retrospective cohort design. SETTINGS: It was conducted at a single institution. PATIENTS: Overall 469 patients with locally advanced lower rectal adenocarcinoma located below the peritoneal reflex who received curative resection with lateral pelvic lymph node dissection during 2010 to 2018 were included. MAIN OUTCOME MEASURES: Independent risk factors for local recurrence were assessed using multivariate Cox regression. Local recurrence was classified into 3 areas using follow-up images. RESULTS: A total of 286 patients underwent upfront surgery, 132 patients received neoadjuvant chemotherapy followed by surgery, and 51 patients received preoperative chemoradiotherapy followed by surgery. Eighty-six patients (18.3%) were extramural venous invasion positive, and 113 patients (24.1%) were circumferential resection margin positive. The median follow-up period was 46 months. Local recurrence showed significant association with extramural venous invasion positive (HR = 2.596 (95% CI, 1.321-5.102); p = 0.006) or circumferential resection margin positive (HR = 2.298 (95% CI, 1.158-4.560); p = 0.017). The incidence of local recurrence was observed in 51 patients (10.8%), with the pelvic plexus and internal iliac area being the most frequent (6.6%), followed by the central pelvis area (3.8%), and was markedly low in the obturator area (0.4%). LIMITATIONS: This was a retrospective, single-institution design. CONCLUSIONS: Extramural venous invasion status and circumferential resection margin status were associated with a high local recurrence rate in patients who underwent lateral pelvic lymph node dissection. In addition, local recurrence in the obturator area was low compared with that in other areas. See Video Abstract at http://links.lww.com/DCR/B683. FACTORES RADIOLGICOS Y REAS DE RECURRENCIA LOCAL EN EL CNCER DE RECTO INFERIOR LOCALMENTE AVANZADO DESPUS DE LA DISECCIN GANGLIONAR PLVICA LATERAL: ANTECEDENTES:El identificar los factores de riesgo preoperatorios para recurrencia local y los patrones de fracaso del tratamiento que resultan del manejo del cáncer de recto es importante para planificar las estrategias de tratamiento y mejorar los resultados de la atención multidisciplinaria.OBJETIVO:Analizar las asociaciones entre los factores preoperatorios y la recidiva local, e investigar las áreas de recidiva local en pacientes con cáncer de recto inferior localmente avanzado que se sometieron a disección de ganglios linfáticos pélvicos laterales.DISEÑO:Un diseño de cohorte retrospectivo.ENTORNO CLÍNICO:Una sola institución.PACIENTES:Un total de 469 pacientes con adenocarcinoma rectal inferior localmente avanzado ubicado debajo del reflejo peritoneal que recibieron resección curativa con disección de ganglios linfáticos pélvicos laterales durante 2010-2018.PRINCIPALES MEDIDAS DE RESULTADO:Los factores de riesgo independientes de recurrencia local se evaluaron mediante regresión de Cox multivariante. La recurrencia local se clasificó en 3 áreas utilizando imágenes de seguimiento.RESULTADOS:Doscientos ochenta y seis pacientes se sometieron a cirugía inicial, 132 pacientes recibieron quimioterapia neoadyuvante seguida de cirugía y 51 pacientes recibieron quimiorradioterapia preoperatoria seguida de cirugía. Ochenta y seis pacientes (18,3%) fueron positivos para invasión venosa extramural y 113 pacientes (24,1%) fueron positivos para el margen de resección circunferencial. La mediana del período de seguimiento fue de 46 meses. La recidiva local mostró una asociación significativa con la invasión venosa extramural positiva (cociente de riesgo: 2,596; intervalo de confianza del 95%: 1,321-5,102; p = 0,006) o el margen de resección circunferencial positivo (cociente de riesgo: 2,298; intervalo de confianza del 95%: 1,158-4,560; p = 0,017). La incidencia de recidiva local se observó en 51 pacientes (10,8%), siendo el plexo pélvico y el área ilíaca interna los más frecuentes (6,6%), seguidos del área pélvica central (3,8%), y fue marcadamente baja en el área del obtudador (0.4%).LIMITACIONES:Un diseño retrospectivo de una sola institución.CONCLUSIONES:El estado de invasión venosa extramural o el estado del margen de resección circunferencial se asociaron con una alta tasa de recurrencia local en pacientes que se sometieron a disección de ganglios linfáticos pélvicos laterales. Además, la recurrencia local en el área del obturador fue baja en comparación con la de otras áreas. Consulte Video Resumen en http://links.lww.com/DCR/B683.


Asunto(s)
Adenocarcinoma/cirugía , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/cirugía , Recurrencia Local de Neoplasia/diagnóstico por imagen , Pelvis/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Ganglios Linfáticos/patología , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias/métodos , Periodo Preoperatorio , Neoplasias del Recto/patología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad
18.
Circ J ; 85(12): 2137-2145, 2021 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-33952835

RESUMEN

BACKGROUND: The effect of treatment with paclitaxel-containing devices (PTXD) on mortality in patients with peripheral artery disease remains controversial.Methods and Results:An independent patient-level meta-analysis of 12 clinical trials (1,389 PTXD patients and 1,192 non-PTXD patients) was conducted. This study included 7 pivotal trials and 5 post-marketing surveillance studies on endovascular treatment for femoropopliteal artery by 6 companies. The primary endpoint was all-cause death, and 5-year cumulative mortality was estimated by a Kaplan-Meier curve. Cox proportional hazard model was used to calculate the hazard ratio (HR) and confidential interval (CI). During the median follow up of 3.0 years, 459 patients died. The cumulative 5-year mortality for the entire cohort was significantly lower in the PTXD than in the non-PTXD group (24.4% vs. 27.4%, respectively; HR, 0.81; 95% CI, 0.67-0.97; P=0.023), but this difference was no longer significant after adjustment for relevant covariates (HR, 1.01; 95% CI, 0.39-2.58; P=0.987). The Cox proportional hazard model revealed that sex, hyperlipidemia, Type 2 diabetes, hemodialysis, Rutherford category, and age above 75 years were significantly associated with 5-year mortality, but treatment with PTXD was not. CONCLUSIONS: This large individual meta-analysis of patients with femoropopliteal artery disease found that the use of PTXD does not have a negative effect on 5-year mortality.


Asunto(s)
Angioplastia de Balón , Diabetes Mellitus Tipo 2 , Enfermedad Arterial Periférica , Anciano , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Arteria Femoral , Humanos , Japón/epidemiología , Paclitaxel , Enfermedad Arterial Periférica/terapia , Arteria Poplítea , Resultado del Tratamiento , Grado de Desobstrucción Vascular
19.
Colorectal Dis ; 23(2): 405-414, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33124126

RESUMEN

AIM: Transanal total mesorectal excision (TaTME) is expected to improve the quality of total mesorectal excision as well as preserve urinary function. We aimed to study the frequency and risk factors of urinary dysfunction in rectal cancer patients after TaTME. Moreover, we analysed the association between urinary function and resected pattern of the autonomic nerve system (ANS) in TaTME. METHOD: We retrospectively analysed 231 patients who underwent TaTME at our hospital from 2013 to 2018. Independent risk factors for urinary dysfunction were assessed by multivariate analysis. Urinary dysfunction was defined as a condition that requires urethral catheterisation. We intraoperatively judged and classified the preserved or resected pattern of ANS into four categories. RESULTS: The rate of urinary dysfunction after TaTME was 12.1% at discharge. Multivariate analysis revealed that beyond TME and ANS resection were the two major independent risk factors for urinary dysfunction. Total ANS preservation had reduced rates of urinary dysfunction, and all patients were free from catheterisation 6 months post-surgery. There was a higher rate of urinary dysfunction in total ANS resection than in partial ANS resection at 6 months post-surgery. CONCLUSION: This study showed that urinary function after TaTME was associated with resection of the ANS. Furthermore, the rate of urinary dysfunction and recovery time were closely related to the pattern of ANS resection.


Asunto(s)
Laparoscopía , Neoplasias del Recto , Cirugía Endoscópica Transanal , Vías Autónomas/cirugía , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Neoplasias del Recto/cirugía , Recto/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
20.
BMC Musculoskelet Disord ; 22(1): 754, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34479525

RESUMEN

BACKGROUND: Patients' perceptions and beliefs of disease could be influenced by their lifestyle and culture. Although it is important to understand their perceptions and beliefs toward disease to prevent and manage osteoarthritis (OA) through conservative care, this topic has not been investigated in Japanese people with knee OA. Therefore, this qualitative study aims to clarify how Japanese patients with knee OA experience and perceive their symptoms and disabilities, and how they face them during conservative care. METHODS: Participants were recruited by purposive sampling. Face-to-face, semi-structured interviews were conducted with nine patients (2 men and 7 women; mean age, 74.3 ± 5.5 years) with knee OA until data saturation was reached. Interview data comprised participants' accounts of particular personal experiences of living with knee OA, including their perceptions and attitudes toward knee OA-related symptoms and disabilities. Two physiotherapists (one with extensive experience conducting qualitative studies) and four physiotherapy students conducted the interviews. Recorded interview data were transcribed verbatim in Japanese. Data analysis, including developing a coding scheme, was conducted based on a grounded theory approach. RESULTS: Two core categories were extracted from the data: 'Negative experiences' and 'Coping with difficulties'. 'Negative experiences' included three main categories: 'Self-analysis on the cause of knee OA', 'Difficulties in daily life due to knee symptoms', and 'Psychological barrier'. 'Coping with difficulties' included three main categories: 'How to deal with knee pain and difficulty in moving', 'Information considered useful to cope with knee OA' and 'Importance of connecting with others'. Japanese patients with knee OA desired evidence-based information and to connect with other people in the same situation to solve problems related to their condition. CONCLUSIONS: To address patients' concerns, medical professionals should conduct careful interviews and obtain information regarding patients' past experiences, and understand their experiences related to knee OA. Symptoms and difficulties experienced by patients with knee OA should be managed by evidence-based information integrating their perceptions and beliefs toward knee OA.


Asunto(s)
Osteoartritis de la Rodilla , Anciano , Femenino , Humanos , Japón/epidemiología , Masculino , Osteoartritis de la Rodilla/diagnóstico , Osteoartritis de la Rodilla/terapia , Percepción , Modalidades de Fisioterapia , Investigación Cualitativa
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