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1.
Dis Esophagus ; 34(10)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33884407

RESUMO

The 11th edition of the "Japanese Classification of Esophageal Cancer" by the Japan Esophageal Society (JES) and the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) "Cancer Staging Manual" are two separate classification systems both widely used for the clinical and pathological staging of esophageal cancer. Furthermore, the lymph node stations from these classification systems are combined for research purposes in the multinational TIGER study, which investigates the distribution pattern of lymph node metastases. The existing classification systems greatly differ with regard to number, location and anatomical boundaries of locoregional lymph node stations. The differences in these classifications cause significant heterogeneity in studies on lymph node metastases in esophageal cancer. This makes data interpretation difficult and comparison of studies challenging. In this article, we propose a match for these two commonly used classification systems and additionally for the TIGER study classification, in order to be able to compare results of studies and exchange knowledge and to make steps towards one global uniform classification system for all patients with esophageal cancer.


Assuntos
Neoplasias Esofágicas , Humanos , Linfonodos , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico
2.
Br J Surg ; 107(12): 1640-1647, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32430907

RESUMO

BACKGROUND: Omentectomy is performed widely for locally advanced gastric cancer to prevent disease recurrence. However, its clinical benefit is unknown. METHODS: This retrospective cohort study compared the outcome of gastrectomy with preservation of the omentum (GPO) and gastrectomy with resection of the omentum (GRO) among patients with cT3-T4 gastric cancer who underwent gastrectomy between 2006 and 2012 in one of five participating institutions. A consensus conference identified 28 variables potentially associated with outcome after gastrectomy for the estimation of propensity scores, and propensity score matching (PSM) was undertaken to control for possible confounders. Postoperative surgical outcomes, overall survival and disease recurrence were compared between GPO and GRO. RESULTS: A total of 1758 patients were identified, of whom 526 remained after PSM, 263 in each group. Median follow-up was 4·9 (i.q.r. 3·1-5·9) years in the GRO group and 5·0 (2·5-6·8) years in the GPO group. The incidence of postoperative complications of Clavien-Dindo grade III or more was significantly higher in the GRO group (17·5 versus 10·3 per cent; P = 0·016). Five-year overall survival rates were 77·1 per cent in the GRO group and 79·4 per cent in the GPO group (P = 0·749). There were no significant differences in recurrence rate or pattern of recurrence between the groups. CONCLUSION: Overall survival and disease recurrence were comparable in patients with cT3-4 gastric cancer who underwent GPO or GRO.


ANTECEDENTES: La omentectomía se realiza ampliamente en el cáncer gástrico localmente avanzado para prevenir la recidiva de la enfermedad. Sin embargo, se desconoce su beneficio clínico. MÉTODOS: Este estudio retrospectivo comparó el resultado de la gastrectomía con preservación del omento (gastrectomy with preservation of the omentum, GPO) con la gastrectomía con resección del omento (gastrectomy with resection of the omentum, GRO) para el cáncer gástrico con estadio clínico T3/T4. Se incluyeron pacientes sometidos a gastrectomía por cáncer gástrico clínico T3/T4 (2006-2012) y se recogieron datos relevantes de 5 hospitales participantes. A través de una conferencia de consenso se identificaron 28 variables potencialmente asociadas con el resultado tras la gastrectomía, mediante las cuales se estimaron las puntuaciones de propensión, utilizándose el emparejamiento por puntuación de propensión (propensity score matching, PSM) para el control de posibles factores de confusión. Los resultados quirúrgicos postoperatorios, la supervivencia global y la recidiva de la enfermedad se compararon entre las gastrectomías con GPO y GRO. RESULTADOS: En total, se identificaron 1.758 pacientes, seleccionándose 526 (263 GRO y 263 GPO) tras el PSM. La mediana (rango intercuartílico) de seguimiento fue de 4,9 años (3,1-5,9) en el grupo GRO y de 5,0 años (2,5-6,8) en el grupo GPO. La incidencia de complicaciones postoperatorias de Clavien-Dindo grado III o más alto fue significativamente más elevada en el grupo GRO que en el grupo GPO (17,1% versus 9,1%; P = 0,010). La supervivencia global a los 5 años fue del 77,1% para el grupo GRO y del 79,4% para el grupo GPO (P = 0,749). No hubo diferencias estadísticamente significativas en la tasa de recidiva o patrón de recidiva entre ambos grupos. CONCLUSIÓN: La supervivencia global y la recidiva de la enfermedad son comparables en pacientes con cáncer gástrico estadio clínico T3-4 sometidos a GPO o GRO.


Assuntos
Gastrectomia/métodos , Omento/cirurgia , Neoplasias Gástricas/cirurgia , Idoso , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Resultado do Tratamento
3.
Br J Surg ; 107(6): 705-711, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32077101

RESUMO

BACKGROUND: Oesophageal squamous cell carcinoma is an aggressive disease owing to early and widespread lymph node metastases. Multimodal therapy and radical surgery may improve prognosis. Few studies have investigated the efficacy of radical lymph node and thoracic duct resection. METHODS: Patients with oesophageal squamous cell carcinoma who underwent transthoracic minimally invasive oesophagectomy (TMIE) for cancer at Keio University Hospital between January 2004 and December 2016 were selected. Between 2004 and 2008, TMIE was performed in the lateral decubitus position without thoracic duct resection (standard TMIE). From 2009 onwards, TMIE with extended lymph node and thoracic duct resection was introduced (extended TMIE). Demographics, co-morbidity, number of retrieved lymph nodes, pathology, postoperative complications and recurrence-free survival (RFS) were compared between groups. RESULTS: Forty-four patients underwent standard TMIE and 191 extended TMIE. There were no significant differences in clinical and pathological tumour stage or postoperative complications. The extended-TMIE group had more lymph nodes removed at nodal stations 106recL and 112. Among patients with cT1 N0 disease, RFS was better in the extended-TMIE group (P < 0·001), whereas there was no difference in RFS between groups in patients with advanced disease. CONCLUSION: Extended TMIE including thoracic duct resection increased the number of lymph nodes retrieved and was associated with improved survival in patients with cT1 N0 oesophageal squamous cell carcinoma.


Assuntos
Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Excisão de Linfonodo/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Ducto Torácico/cirurgia , Adulto , Idoso , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Ducto Torácico/patologia , Resultado do Tratamento
4.
Dis Esophagus ; 31(6)2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29701761

RESUMO

Recurrent laryngeal nerve paralysis (RLNP) is a frequent and serious complication following esophageal cancer surgery. Therefore, this study aims to evaluate the correlation between recurrent laryngeal nerve (RLN) size and RLNP. This was a retrospective study of esophageal cancer patients who underwent thoracoscopic esophagectomy from January 2012 to December 2014. Eighty-four patients were included in the primary analysis. Diameter of the RLN was measured using the digital video recording of surgical procedures by the ratio between scissor and RLN. For evaluation of vocal cord paralysis or paresis, indirect laryngoscopy was performed. Because RLNP more frequently occurs on the left side than the right, we evaluated the correlation between size of the left RLN and left RLNP. The median size of the left RLN was 1.51 mm. We found that the incidence of postoperative left RLNP (Clavien-Dindo classification ≥1) was significantly higher (71% vs. 24%; P < 0.001) in thin RLNs (≤1.5 mm) than in thick RLNs (>1.5 mm). Thin RLN (P < 0.001), female sex (P = 0.025), and being overweight (P = 0.034) were identified as significant independent risk factors for postoperative RLNP. RLNP more easily occurred when the RLN was thin. It is difficult to confirm occurrence of postoperative RLNP before and at extubation. Therefore, it is helpful to know its risk factors including size of RLN.


Assuntos
Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Nervo Laríngeo Recorrente/patologia , Paralisia das Pregas Vocais/etiologia , Idoso , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
5.
Dis Esophagus ; 27(7): 654-61, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23980622

RESUMO

Among multidisciplinary therapies developed for advanced esophageal cancer, neoadjuvant chemotherapy and chemoradiotherapy have been established as standard treatments. To deliver cautious follow up and intense treatment for high-risk patients, a simple and instructive biomarker for the postoperative recurrence needs to be identified. Fibrinogen, a common component of hemostasis, has been suggested to not only play an important role in cancer metastasis, but also correlate with tumor recurrence. We aim to clarify the validity of plasma fibrinogen as a marker for predicting the postoperative recurrence of esophageal squamous cell carcinoma patients who received neoadjuvant treatment. We reviewed 72 consecutive patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy or chemoradiotherapy, followed by esophagectomy at the Keio University Hospital from 2001 to 2010. Of them, we retrospectively examined 68 patients who underwent plasma fibrinogen examination before and after neoadjuvant treatment and underwent transthoracic radical esophagectomy. We investigated patient characteristics, clinicopathological factors, neoadjuvant treatment effects, postoperative course, and plasma fibrinogen levels. We investigated pretreatment and preoperative (postneoadjuvant treatment) plasma fibrinogen levels, as well as changes in fibrinogen levels before and after neoadjuvant treatment. Patients with preoperative hyperfibrinogenemia (>350 mg/dL) and patients with increased plasma fibrinogen levels during neoadjuvant treatment showed significantly shorter postoperative disease-free survival (DFS) (P = 0.002 and P = 0.037, respectively). Moreover, we classified these patients into three classes on the basis of their preoperative fibrinogen levels and changes in fibrinogen levels during neoadjuvant treatment. Patients who had both high preoperative plasma fibrinogen and increased fibrinogen levels showed significantly shorter DFS than others. In contrast, patients who had normal preoperative plasma fibrinogen and decreased fibrinogen levels showed significantly longer DFS. Based on this fibrinogen classification, we could differentiate between significantly favorable and poor prognosis patients group. Overall, this classification (hazard ratio = 1.812, P = 0.013) and the response to neoadjuvant treatment (hazard ratio = 0.350, P = 0.007) were found to be significant determining factors for postoperative DFS. With the validity of preoperative plasma fibrinogen levels and changes in fibrinogen levels during neoadjuvant treatment, the plasma fibrinogen level was found to be a possible biomarker for postoperative recurrence in advanced esophageal cancer patients who received neoadjuvant treatment. Moreover, plasma fibrinogen classification could be a simple and valuable predictive marker for postoperative follow up.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , Esofagectomia , Fibrinogênio/metabolismo , Recidiva Local de Neoplasia/sangue , Idoso , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Estudos de Coortes , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos
6.
Dis Esophagus ; 26(6): 616-22, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23237474

RESUMO

An identification of bronchial arteries (BAs) is critical in esophageal cancer surgery to avoid tracheobronchial ischemia and unexpected massive bleeding during surgical procedure particularly in thoracoscopic video-assisted esophagectomy. We describe the efficacy of three-dimensional computed tomographic angiography (3D-CTA) of BAs for preoperative evaluation in esophageal cancer surgery. Sixty-four patients with esophageal cancer who preoperatively underwent multidetector computed tomography examination were included in this study. We evaluated the number, origin, and intraoperative preservation rate of BAs, and we compared the number of thoracic paratracheal lymph nodes harvested between two groups comprising patients who either underwent preoperative 3D-CTA of BAs (3D-CTA group) or did not (non-3D-CTA group). The right and left BAs were preoperatively identified in 62 patients (97%) and 55 patients (86%), respectively, using 3D-CTA. In 34 patients (53%), the right BA originated as a common trunk with the right intercostal artery. In 48 patients (75%), the left BA originated from the descending aorta as a single or double branch. Some anomalies such as the right BA originated from the left subclavian artery were observed. In all patients, either the right or the left BA was preserved. The number of harvested lymph nodes in left side of paratrachea was significantly increased in 3D-CTA group, than those in non-3D-CTA group. 3D-CTA clearly revealed BA anatomy, contributing to BA preservation and safe and precise lymphadenectomy in esophageal cancer surgery. 3D-CTA of BAs is useful for preoperative evaluation in esophageal cancer surgery.


Assuntos
Angiografia/métodos , Artérias Brônquicas/diagnóstico por imagem , Neoplasias Esofágicas/cirurgia , Imageamento Tridimensional/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/diagnóstico por imagem , Perda Sanguínea Cirúrgica/prevenção & controle , Brônquios/irrigação sanguínea , Artérias Brônquicas/lesões , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/diagnóstico por imagem , Esofagectomia/métodos , Feminino , Humanos , Complicações Intraoperatórias/prevenção & controle , Isquemia/prevenção & controle , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios , Respiração Artificial , Costelas/irrigação sanguínea , Artéria Subclávia/diagnóstico por imagem , Traqueia/irrigação sanguínea , Cirurgia Vídeoassistida/métodos
7.
J Hosp Infect ; 131: 156-163, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36370963

RESUMO

BACKGROUND: Long-term placement of prophylactic drains may result in retrograde infections. AIM: To investigate the association between the timing of drain removal and clinical outcomes. METHODS: This retrospective, single-centre cohort study evaluated 110 patients who underwent elective gastrointestinal or hepatopancreatobiliary surgery and developed subsequent organ/space surgical site infection (SSI) between 2016 and 2020. The difference between the culture-positive species of prophylactic drains and direct aspiration was evaluated; whether the prophylactic drains functioned effectively at the time of SSI diagnosis; and whether the empirical antibiotics administered before drainage were effective against all the detected bacteria. Finally, clinical outcomes were compared between early (i.e. cases wherein the prophylactic drain had already been removed or replaced at the time of SSI diagnosis) and late (removal after diagnosis) drain removal. FINDINGS: The prophylactic drains functioned effectively in only 27 (25%) patients at the time of SSI diagnosis. Due to the results of direct aspiration cultures, 43% of patients required antibiotic escalation. The median time to drain removal or first replacement was seven postoperative days. The early removal group included 43 patients (39%). Compared with early removal, late removal resulted in a higher frequency of vancomycin use (7.0% vs 22.4%; P = 0.037). CONCLUSION: Prolonged prophylactic drain placement is associated with complicated infections requiring vancomycin; therefore, the drains should be removed as soon as possible. Additionally, obtaining the cultures of direct aspiration should be actively considered, as escalation of antimicrobial therapy is often performed based on culture results.


Assuntos
Drenagem , Infecção da Ferida Cirúrgica , Humanos , Antibacterianos/uso terapêutico , Estudos de Coortes , Drenagem/efeitos adversos , Drenagem/métodos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/etiologia , Vancomicina/uso terapêutico
10.
Hernia ; 26(6): 1669-1678, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35536371

RESUMO

BACKGROUND: Because of the complexity of the intra-abdominal anatomy in the posterior approach, a longer learning curve has been observed in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair. Consequently, automatic tools using artificial intelligence (AI) to monitor TAPP procedures and assess learning curves are required. The primary objective of this study was to establish a deep learning-based automated surgical phase recognition system for TAPP. A secondary objective was to investigate the relationship between surgical skills and phase duration. METHODS: This study enrolled 119 patients who underwent the TAPP procedure. The surgical videos were annotated (delineated in time) and split into seven surgical phases (preparation, peritoneal flap incision, peritoneal flap dissection, hernia dissection, mesh deployment, mesh fixation, peritoneal flap closure, and additional closure). An AI model was trained to automatically recognize surgical phases from videos. The relationship between phase duration and surgical skills were also evaluated. RESULTS: A fourfold cross-validation was used to assess the performance of the AI model. The accuracy was 88.81 and 85.82%, in unilateral and bilateral cases, respectively. In unilateral hernia cases, the duration of peritoneal incision (p = 0.003) and hernia dissection (p = 0.014) detected via AI were significantly shorter for experts than for trainees. CONCLUSION: An automated surgical phase recognition system was established for TAPP using deep learning with a high accuracy. Our AI-based system can be useful for the automatic monitoring of surgery progress, improving OR efficiency, evaluating surgical skills and video-based surgical education. Specific phase durations detected via the AI model were significantly associated with the surgeons' learning curve.


Assuntos
Hérnia Inguinal , Laparoscopia , Humanos , Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Telas Cirúrgicas , Inteligência Artificial , Laparoscopia/métodos
11.
BJS Open ; 2(5): 276-284, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30263978

RESUMO

BACKGROUND: Oesophagectomy has a high risk of postoperative morbidity. The impact of postoperative complications on overall survival of oesophageal cancer remains unclear. This meta-analysis addressed the impact of complications on long-term survival following oesophagectomy. METHODS: A search of PubMed and Cochrane Library databases was undertaken for systematic review of papers published between January 1995 and August 2016 that analysed the relation between postoperative complications and long-term survival. In the meta-analysis, data were pooled. The main outcome was overall survival (OS). Secondary endpoints included disease-free (DFS) and cancer-specific (CSS) survival. RESULTS: A total of 357 citations was reviewed; 21 studies comprising 11 368 patients were included in the analyses. Overall, postoperative complications were associated with significantly decreased 5-year OS (hazard ratio (HR) 1·16, 95 per cent c.i. 1·06 to 1·26; P = 0·001) and 5-year CSS (HR 1·27, 1·09 to 1·47; P = 0·002). Pulmonary complications were associated with decreased 5-year OS (HR 1·37, 1·16 to 1·62; P < 0·001), CSS (HR 1·60, 1·35 to 1·89; P < 0·001) and 5-year DFS (HR 1·16, 1·00 to 1·33; P = 0·05). Patients with anastomotic leakage had significantly decreased 5-year OS (HR 1·20, 1·10 to 1·30; P < 0·001), 5-year CSS (HR 1·81, 1·11 to 2·95; P = 0·02) and 5-year DFS (HR 1·13, 1·02 to 1·25; P = 0·01). CONCLUSION: Postoperative complications after oesophagectomy, including pulmonary complications and anastomotic leakage, decreased long-term survival.

12.
Oncol Rep ; 14(6): 1453-9, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16273238

RESUMO

Many molecular alterations occur in esophageal carcinogenesis; however, little is known about the molecular genetic events responsible for the development of carcinoma. We investigated the expression of ki67, p53, cyclin D1 and pRB in 105 biopsy specimens using immunohistochemistry from iodine unstained lesions as indicators of carcinogenesis of the esophagus. Also, the genetic alternation of esophageal dysplasia from patients with accompanying esophageal squamous cell carcinoma (ESCC) was examined to study the evidence for field carcinogenesis in the esophagus. The expression of p53, cyclin D1 and pRB was detected in 31, 0 and 51.7% respectively of mild dysplasia; 40, 0 and 70% of moderate dysplasia; 40, 20 and 70% of severe dysplasia; and 48, 32 and 80% of carcinoma specimens. p53 expression was significantly increased in mild dysplasia, whereas cyclin D1 and pRB expression were significantly increased in carcinoma as compared to both normal epithelium and esophagitis. The ki67 LI and the rate of p53 expression were significantly higher in dysplasia with ESCC than in dysplasia without ESCC. Ki67, p53, cyclin D1 and pRB expression may be useful biomarkers for assessing the risk of developing esophageal cancer. Dysplasia observed at screening for secondary lesions has a highly malignant potential and careful follow-up studies are required.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Esôfago/patologia , Proteínas de Neoplasias/biossíntese , Carcinoma de Células Escamosas/metabolismo , Ciclina D1/biossíntese , Neoplasias Esofágicas/metabolismo , Esofagite/metabolismo , Esofagite/patologia , Esôfago/química , Humanos , Imuno-Histoquímica , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Proteína do Retinoblastoma/biossíntese , Proteína Supressora de Tumor p53/biossíntese
13.
Curr Cancer Drug Targets ; 4(2): 165-82, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15032667

RESUMO

The Transforming Growth Factor-beta (TGFbeta) superfamily of cytokines is comprised of a number of structurally-related, secreted polypeptides that regulate a multitude of cellular processes including proliferation, differentiation and neoplastic transformation. These growth regulatory molecules induce ligand-mediated hetero-oligomerization of distinct type II and type I serine/threonine kinase receptors that transmit signals predominantly through receptor-activated Smad proteins but also induce Smad-independent pathways. Ligands, receptors and intracellular mediators of signaling initiated by members of the TGFbeta family are expressed in the mammary gland and disruption of these pathways may contribute to the development and progression of human breast cancer. Since many facets of TGFbeta and breast cancer have been recently reviewed in several articles, except for discussion of recent developments on some aspects of TGFbeta, the major focus of this review will be on the role of activins, inhibins, BMPs, nodal and MIS-signaling in breast cancer with emphasis on their utility as potential diagnostic, prognostic and therapeutic targets.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta/fisiologia , Ativinas/fisiologia , Animais , Hormônio Antimülleriano , Biomarcadores Tumorais , Proteínas Morfogenéticas Ósseas/fisiologia , Feminino , Glicoproteínas/fisiologia , Humanos , Inibinas/fisiologia , Proteína Nodal , Transdução de Sinais/efeitos dos fármacos , Hormônios Testiculares/fisiologia , Fator de Crescimento Transformador beta/genética
14.
J Med Chem ; 33(11): 3110-6, 1990 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1977911

RESUMO

[1]Benzothieno[2,3-c]pyridines (10a-c, 11, 12a-t, and 13a,b) and 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines (3a-c, 7, 8a-c, and 9) were synthesized. The compounds are bioisosteres of beta-carbolines and 1,2,3,4-tetrahydro-beta-carbolines where the indole nitrogen is replaced by sulfur. Their pharmacological activity was evaluated in a water lick conflict test in rats and a passive avoidance test in mice. In the 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridine series, the presence of ethyl ester (3b) or cyclohexyl carboxamide (7) groups at C-3 conferred good anticonflict activity and lessening of memory impairment, while N-acylation of 3b abolished activity. In the [1]benzothieno(2,3-c]pyridine series, the aminoethyl carboxamide (12a) group at C-3 also conferred activity, but other amides studied were not active. The most potent compounds (3b, 7, and 12a) were also administered orally and had potent anticonflict and antiscopolamine amnesia-reversal activity. These compounds did not bind to the BZP receptor in spite of having structures similar to those of beta-carbolines. Compound 7 bound strongly to 5-HT1A receptors and would be expected to be a novel anxiolytic.


Assuntos
Ansiolíticos/farmacologia , Conflito Psicológico , Memória/efeitos dos fármacos , Piridinas/farmacologia , Sulfetos/farmacologia , Animais , Ansiolíticos/síntese química , Ansiolíticos/química , Aprendizagem da Esquiva/efeitos dos fármacos , Fenômenos Químicos , Química , Masculino , Camundongos , Estrutura Molecular , Piridinas/síntese química , Piridinas/química , Ratos , Ratos Endogâmicos , Receptores de GABA-A/metabolismo , Receptores de Serotonina/metabolismo , Relação Estrutura-Atividade , Sulfetos/síntese química , Sulfetos/química , Tienopiridinas
15.
J Med Chem ; 36(23): 3526-32, 1993 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-7902439

RESUMO

(R)-1,2,3,4-Tetrahydro[1]benzothieno[2,3-c]pyridine derivatives (60-114) were synthesized. The (R)-isomers have affinity for the 5-HT1A receptor while the (S)-isomers have no such ability. The affinity of the (R)-isomers was discussed on the basis of structure-activity relationships between the affinity and hydrophobicity of the (R)-isomers. Compounds 71 and 107, which are representative derivative compounds, have anticonflict activity and lessening of memory impairment. In particular, compound 107 cannot bind to receptors other than the 5-HT1A receptor, demonstrating that it is a unique compound with a different mechanism of action from that of conventional anxiolytics.


Assuntos
Amnésia/tratamento farmacológico , Ansiolíticos/síntese química , Piridinas/síntese química , Receptores de Serotonina/metabolismo , Tiofenos/síntese química , 8-Hidroxi-2-(di-n-propilamino)tetralina/metabolismo , Amnésia/induzido quimicamente , Animais , Ansiolíticos/metabolismo , Ansiolíticos/farmacologia , Aprendizagem da Esquiva , Conflito Psicológico , Masculino , Camundongos , Estrutura Molecular , Piridinas/metabolismo , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Escopolamina , Estereoisomerismo , Relação Estrutura-Atividade , Tienopiridinas , Tiofenos/metabolismo , Tiofenos/farmacologia
16.
Jpn J Physiol ; 50(4): 463-7, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11082546

RESUMO

NMR micro-images of the kidney and liver were measured at 9.4 T in intact mouse, schistosoma Mansoni-infected mouse, and lupus nephritis in an MRL/lpr mouse. High-field NMR imaging has the advantages of sensitivity, spatial resolution, and tissue contrasts based on longitudinal and transverse relaxations, magnetic susceptibility differences and blood flow.


Assuntos
Rim/parasitologia , Fígado/parasitologia , Espectroscopia de Ressonância Magnética , Schistosoma mansoni , Esquistossomose mansoni/diagnóstico , Animais , Modelos Animais de Doenças , Rim/irrigação sanguínea , Fígado/irrigação sanguínea , Circulação Hepática , Nefrite Lúpica/diagnóstico , Camundongos , Camundongos Endogâmicos BALB C , Circulação Renal , Sensibilidade e Especificidade
17.
Adv Exp Med Biol ; 247B: 249-53, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2610068

RESUMO

The assay method based on the principle of kallikrein-kinin cascade was established for evaluating the inhibitory effects of various substances on the production of plasma kallikrein. In this in vitro assay, it was found that indomethacin, ketoprofen, ibuprofen and an extract obtained from inflamed rabbit skin inoculated with vaccinia virus (NSP) had the inhibitory effect on the production of plasma kallikrein. Kinins generated in the reaction mixture were measured by RIA. It was shown that the generation of kinins was also inhibited by these substances. From these results, it is hoped that this assay method may be useful for screening the substances which inhibited the production of kinin.


Assuntos
Calicreínas/sangue , Pré-Calicreína/fisiologia , Aminopirina/farmacologia , Aspirina/farmacologia , Humanos , Ibuprofeno/farmacologia , Indometacina/farmacologia , Cetoprofeno/farmacologia , Cinética , Cininas/isolamento & purificação , Morfina/farmacologia , Pentazocina/farmacologia
18.
Nihon Jinzo Gakkai Shi ; 32(3): 319-26, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1693990

RESUMO

It has been reported that Neurotropin can markedly improve pruritus in patients undergoing hemodialysis (HD). In order to elucidate the probable causes of pruritus and the antipruritic effect of Neurotropin, various biochemical parameters in the plasma of patients before and during HD were investigated. Forty-three patients undergoing HD were divided into three groups. Eighteen patients had suffered no episode of pruritus (group A), 17 patients had on-going pruritus (group B) and the remaining 8 patients had experienced improvement of pruritus following Neurotropin treatment (group C). The mean concentration of substance P was in only B group significantly increased with HD only in B group, indicating that substance P could be one of the causes of pruritus in patients undergoing HD. Neurotropin appears to exert its antipruritic effect by lowering the level of substance P. The change in parathyroid hormone (PTH) level during HD was not significant in any of the groups, but the mean concentration of PTH in group B was higher than that of group A, indicating that PTH may also be one of the causes of pruritus.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Polissacarídeos/uso terapêutico , Prurido/prevenção & controle , Diálise Renal , Feminino , Histamina/sangue , Humanos , Imunoglobulina E/análise , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Prurido/etiologia , Somatostatina/sangue , Substância P/sangue
19.
Nihon Jinzo Gakkai Shi ; 31(10): 1061-7, 1989 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2615018

RESUMO

The causes of pruritus in patients undergoing hemodialysis and the mechanism of the antipruritic effect of Neurotropin, an extract isolated from the inflamed dermis of rabbits inoculated with vaccinia virus and clinically used in Japan as an analgesic and antiallergic drug, were investigated by measuring the levels of C3a, C5a, bradykinin and lipid peroxides in venous blood collected before dialysis, and at 15 min and 4 hr after starting hemodialysis. C3a increased considerably in pruritic patients compared to non-pruritic patients at 15 min after starting hemodialysis. Neurotropin significantly suppressed the C3a level and improved the condition of pruritic patients. There was no significant difference in the level of bradykinin between pruritic patients and non-pruritic patients. Therefore, bradykinin was not thought to be related to the incidence of pruritus in such patients. A tendency towards lowering of the levels of lipid peroxides in the patients' plasma by Neurotropin was also observed. It seems possible that elevation of C3a may be one of the underlying causes for the appearance of pruritus, and that Neurotropin may exert its antipruritic effect through suppression of the activation of C3 in patients undergoing hemodialysis.


Assuntos
Bradicinina/sangue , Proteínas do Sistema Complemento/análise , Polissacarídeos/uso terapêutico , Prurido/tratamento farmacológico , Diálise Renal/efeitos adversos , Complemento C5a/análise , Feminino , Humanos , Peróxidos Lipídicos/sangue , Masculino , Pessoa de Meia-Idade , Prurido/sangue
20.
Gan To Kagaku Ryoho ; 26(3): 315-20, 1999 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-10065094

RESUMO

The prognostic influence of post-operative adjuvant chemotherapy on stage I b or II gastric cancer was studied retrospectively. The immunohistochemical expressions of p53 protein and thymidine phosphorylase (TP) were also examined; the relations between these protein expressions and clinicopathological features along with the effect of adjuvant chemotherapy were also investigated. The 5-year survival rate of the patients who received adjuvant chemotherapy was 95.5%, which was better than that (89.8%) of those who did not, although the difference did not reach significance (p = 0.09). The venous invasion of tumor was slight frequently observed in p53 or TP positive cases than negative cases, respectively (p < 0.1), but no significant associations were found between the t-, n- or ly-factor, and p53 or TP expression. Moreover p53 and TP expression had no significant influence on post-operative survival. But, among the patients with p53- or TP-positive tumor, adjuvant chemotherapy conferred survival benefits, although the difference did not reach significance. The 5-year survival rate was 100% with adjuvant chemotherapy, 84.3% without chemotherapy in p53-positive patients (p = 0.137), 97.0% with adjuvant chemotherapy, and 90.8% without chemotherapy in TP-positive tumors (p = 0.326).


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Fluoruracila/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Administração Oral , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Feminino , Gastrectomia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Tegafur/administração & dosagem , Timidina Fosforilase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Uracila/administração & dosagem
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