RESUMO
Calcineurin inhibitors (CNIs), used as immunosuppressants, have revolutionized transplantation medicine with their strong suppressive activity on alloreactive T lymphocytes; however, they may also cause various adverse effects, including an increased risk for infection and nephrotoxicity. Regulatory T (Treg) cells can complement the deleterious side effects of CNIs with their effective Ag-specific suppressive activities. However, several studies have shown that CNIs suppress Treg cell differentiation. Therefore, an understanding of the mechanisms by which CNIs suppress Treg cell differentiation, as well as an approach for promoting the differentiation of Treg cells in the presence of CNIs, has significant clinical value. In this article, we report that the nuclear orphan receptor Nr4a1 plays a pivotal role in Treg cell differentiation in the presence of CNIs. Unlike that of its family members, Nr4a2 and Nr4a3, the expression of Nr4a1 was not suppressed by CNI treatment, thereby mediating Treg cell differentiation in the presence of CNIs. In a mouse allogeneic graft-versus-host disease model, Nr4a1 mediated tolerance by promoting Treg cell differentiation in mice administered cyclosporine A, prolonging the survival of recipients. Furthermore, activation of Nr4a1 via its agonist partially restored Treg cell differentiation, which was suppressed by cyclosporine A treatment. Finally, we found that the rs2701129 single-nucleotide polymorphism, which was shown to downregulate NR4A1 expression, showed a trend toward a higher incidence of chronic graft-versus-host disease in patients undergoing hematopoietic stem cell transplantation. Therefore, our study will be of clinical significance because we demonstrated the role of Nr4a1 in Treg cell differentiation in the presence of CNIs.
Assuntos
Doença Enxerto-Hospedeiro , Imunossupressores , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares , Linfócitos T Reguladores , Animais , Diferenciação Celular , Ciclosporina/farmacologia , Humanos , Imunossupressores/farmacologia , Camundongos , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Fatores de TranscriçãoRESUMO
The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35-74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study uses an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants, and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability and functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.
Assuntos
Metabolômica , Humanos , Pessoa de Meia-Idade , Adulto , Japão/epidemiologia , Feminino , Masculino , Idoso , Estudos de Coortes , BiomarcadoresRESUMO
Obesity and aging are major risk factors for several life-threatening diseases. Accumulating evidence from both rodents and humans suggests that the levels of nicotinamide adenine dinucleotide (NAD+), a regulator of many biological processes, declines in multiple organs and tissues with aging and obesity. Administration of an NAD+ intermediate, nicotinamide mononucleotide (NMN), replenishes intracellular NAD+ levels and mitigates aging- and obesity-associated derangements in animal models. In this human clinical study, we aimed to investigate the safety and effects of 8-week oral administration of NMN on biochemical, metabolic, ophthalmologic, and sleep quality parameters as well as on chronological alterations in NAD+ content in peripheral tissues. An 8-week, single-center, single-arm, open-label clinical trial was conducted. Eleven healthy, middle-aged Japanese men received two 125-mg NMN capsules once daily before breakfast. The 8-week NMN supplementation regimen was well-tolerated; NAD+ levels in peripheral blood mononuclear cells increased over the course of NMN administration. In participants with insulin oversecretion after oral glucose loading, NMN modestly attenuated postprandial hyperinsulinemia, a risk factor for coronary artery disease (n = 3). In conclusion, NMN overall safely and effectively boosted NAD+ biosynthesis in healthy, middle-aged Japanese men, showing its potential for alleviating postprandial hyperinsulinemia.
Assuntos
Hiperinsulinismo , NAD , Masculino , Pessoa de Meia-Idade , Animais , Humanos , NAD/metabolismo , Mononucleotídeo de Nicotinamida/metabolismo , Leucócitos Mononucleares/metabolismo , Japão , Obesidade , Sono , Suplementos NutricionaisRESUMO
AIM: Live two-way video, easily accessible from home via smartphones and other devices, is becoming a new way of providing psychiatric treatment. However, lack of evidence for real-world clinical setting effectiveness hampers its approval by medical insurance in some countries. Here, we conducted the first large-scale pragmatic, randomized controlled trial to determine the effectiveness of long-term treatment for multiple psychiatric disorders via two-way video using smartphones and other devices, which are currently the primary means of telecommunication. METHODS: This randomized controlled trial compared two-way video versus face-to-face treatment for depressive disorder, anxiety disorder, and obsessive-compulsive disorder in the subacute/maintenance phase during a 24-week period. Adult patients with the above-mentioned disorders were allocated to either a two-way video group (≥50% video sessions) or a face-to-face group (100% in-person sessions) and received standard treatment covered by public medical insurance. The primary outcome was the 36-Item Short-Form Health Survey Mental Component Summary (SF-36 MCS) score. Secondary outcomes included all-cause discontinuation, working alliance, adverse events, and the severity rating scales for each disorder. RESULTS: A total of 199 patients participated in this study. After 24 weeks of treatment, two-way video treatment was found to be noninferior to face-to-face treatment regarding SF-36 MCS score (48.50 vs 46.68, respectively; p < 0.001). There were no significant differences between the groups regarding most secondary end points, including all-cause discontinuation, treatment efficacy, and satisfaction. CONCLUSION: Two-way video treatment using smartphones and other devices, was noninferior to face-to-face treatment in real-world clinical settings. Modern telemedicine, easily accessible from home, can be used as a form of health care.
Assuntos
Depressão , Transtorno Obsessivo-Compulsivo , Adulto , Humanos , Transtornos de Ansiedade/terapia , Transtornos de Ansiedade/psicologia , Transtorno Obsessivo-Compulsivo/terapia , Transtorno Obsessivo-Compulsivo/psicologia , Ansiedade , Psicoterapia , Resultado do TratamentoRESUMO
BACKGROUND: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have greatly changed migraine treatment options. In Japan, although CGRPmAb guidelines (≥ 4 monthly migraine days (MMDs) and ≥ 1 previous preventive failure) are well-acknowledged, the actual use of CGRPmAbs and the circumstances of the related headache care are unknown. METHODS: We conducted an online survey of Japanese Headache Society members, inquiring about the physicians' experience with CGRPmAbs and how they make decisions related to their use. RESULTS: Of the 397 respondents, 320 had prescribed CGRPmAbs. The threshold number of previous preventive failures for recommending a CGRPmAb was two for the majority of the respondents (n = 170, 54.5%), followed by one (n = 64, 20.5%). The MMD threshold was ≥ 4 for 71 respondents (22.8%), ≥ 6 for 68 (21.8%), ≥ 8 for 76 (24.4%), and ≥ 10 for 81 (26.0%). The respondents tended to assess treatment efficacy after 3 months (episodic migraine: n = 217, 69.6%, chronic migraine: n = 188, 60.3%). The cost of CGRPmAbs was described by many respondents in two questions: (i) any request for a CGRPmAb (27.7%), and (ii) the most frequently reported reason for responders to discontinue CGRPmAbs (24.4%). CONCLUSIONS: Most of the respondents recommended CGRPmAbs to patients with ≥ 2 preventive failures, followed by ≥ 1. The MMD threshold ranged mostly from ≥ 4 to ≥ 10. The concern for costs was raised as a major limiting factor for prescribing CGRPmAbs.
Assuntos
Anticorpos Monoclonais , Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Humanos , Anticorpos Monoclonais/uso terapêutico , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Cefaleia/tratamento farmacológico , Japão , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Médicos , Sociedades CientíficasRESUMO
BACKGROUND: Minimal data was reported regarding the characteristics, risks of lymph node metastasis, and prognostic factors in esophageal cancer patients who achieved remarkable response in the primary lesion to neoadjuvant treatment (NAT). METHODS: This study evaluated the nationwide data of esophageal squamous cell carcinoma (ESCC) patients who underwent surgery following NAT in Japan. Of 4484 patients, 300 (6.7%) had ypT0 following NAT and curative esophagectomy. Factors associated with lymph node metastasis and prognosis were analyzed. RESULTS: Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) were administered in 260 (86.2%) and 40 (13.8%) patients, respectively. Pathologically, 72 (24.0%) had lymph node metastasis (residual nodal disease; RND), and pretherapeutic lymph node metastasis was the independent risk factor for RND (odd ratio [OR]: 3.21; 95% confidence interval [CI]: 1.44-8.20; P = 0.008). The 5-year overall and relapse-free survivals were significantly longer in patients with pathological complete response (pCR) than in those with RND (both P < 0.001). Pretherapeutic cT3 or T4a tumors (hazard ratio [HR]: 1.71; 95% CI: 1.02-2.88; P = 0.043), RND (HR: 3.30; 95% CI: 1.98-5.50; P < 0.001), and operative blood loss (Liter, HR: 1.53; 95% CI: 1.07-2.19; P = 0.021) were independent risk factors affecting relapse-free survival in multivariable analysis. CONCLUSIONS: Of patients with ypT0 after NAT, 24.0% had RND, and pretherapeutic lymph node metastasis was the risk factor. In addition, pretherapeutic cT3, or T4a tumors, RND, and operative blood loss were the poor prognosticators in patients with ypT0 after NAT.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/patologia , Japão , Estudos de Coortes , Carcinoma de Células Escamosas/patologia , Terapia Neoadjuvante , Metástase Linfática , Perda Sanguínea Cirúrgica , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Resposta Patológica CompletaRESUMO
OBJECTIVE: This study aimed to validate the prognostic significance of stratification using pathological stage and response to neoadjuvant chemotherapy with a nationwide database from an authorized institute by the Japan Esophageal Society. BACKGROUND: We proposed the combined criteria using pStage and pathological response. Conducting a validation study using an expanded cohort in the clinical setting would be valuable since it was developed using retrospective data collection. METHODS: Patients with esophageal squamous cell carcinoma who underwent subtotal esophagectomy at 85 authorized institutes were retrospectively reviewed for esophageal cancer between 2010 and 2015. The prognostic value of the pathological response was evaluated within the same pStage. Moreover, risk stratification was developed to predict cancer-specific survival (CSS). RESULTS: The pathological response showed significant stratification of CSS in 3761 patients included in this analysis. We classified the patients into 7 groups as survival was significantly different between responders and nonresponders under the stratification with pStage, excluding pStage I comprising pStage 0-I/II responder/II nonresponder/III responder/III nonresponder/IV responder/IV nonresponder with the 5-year CSS of 83.7%/75.8%/68.9%/59.8%/44.4%/40.7%/23.1%, respectively. Furthermore, the area under the curve was significantly higher under the new classification than in the pStage alone ( P <0.001). CONCLUSIONS: The prognostic value of classification using pStage and the pathological response was successfully validated using real-world data in Japan. This result would guide appropriate treatment for patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy followed by esophagectomy.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Prognóstico , Neoplasias Esofágicas/tratamento farmacológico , Estudos Retrospectivos , Carcinoma de Células Escamosas/tratamento farmacológico , Terapia Neoadjuvante , Resultado do Tratamento , Estadiamento de Neoplasias , Esofagectomia/efeitos adversosRESUMO
OBJECTIVE: We aimed to evaluate the efficacy of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy over cisplatin and 5-fluorouracil (CF) in patients with surgically resectable advanced esophageal squamous cell carcinoma (ESCC), using real-world data from 85 esophageal centers. BACKGROUND: JCOG1109 trial, which assessed the superiority of DCF over CF, and the superiority of chemoradiotherapy with CF over CF alone demonstrated the significant survival advantage of neoadjuvant DCF in overall survival (OS) over CF for ESCC. METHODS: The ESCC patients who received neoadjuvant CF or DCF at 85 Japanese esophageal centers certified by the Japan Esophageal Society were retrospectively reviewed. After propensity score (PS) matching, the OS and recurrence-free survival were compared between CF and DCF. RESULTS: We initially enrolled 4781 patients. After data cleaning and PS matching using pretreatment variables, 1074 patients for each group were selected for subsequent analysis. There was no significant difference in the incidence of postoperative pneumonia and anastomotic leakage. In the survival analysis, OS was significantly longer in DCF group than CF group (hazard ratio, 0.868; 95% confidence interval, 0.770-0.978; P =0.02), as well as recurrence-free survival (hazard ratio, 0.850; 95% confidence interval, 0.761-0.949; P =0.004). The survival advantage of DCF was not observed in patients with 76 years old or older. CONCLUSIONS: Neoadjuvant DCF therapy showed a remarkable survival advantage in surgically resectable ESCC patients, especially in patients who were 75 years old or younger. The current real-world evidence will encourage recommendations for DCF as a standard regimen in neoadjuvant chemotherapy-based treatment strategy for ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Idoso , Carcinoma de Células Escamosas do Esôfago/cirurgia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/tratamento farmacológico , Cisplatino/uso terapêutico , Docetaxel/uso terapêutico , Terapia Neoadjuvante , Fluoruracila/efeitos adversos , Pontuação de Propensão , Japão/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Taxoides , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS. METHODS: We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected. RESULTS: 44 patients (median (interquartile range) age 39 (29-57)â years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 versus 40â mmHg; p<0.001) and pulmonary vascular resistance (760 versus 514â dyn·s·cm-5; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively. CONCLUSIONS: In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.
Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Estenose de Artéria Pulmonar , Adulto , Feminino , Humanos , Criança , Estenose de Artéria Pulmonar/diagnóstico por imagem , Estenose de Artéria Pulmonar/terapia , Hipertensão Pulmonar/terapia , Constrição Patológica , Artéria Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar Primária Familiar/tratamento farmacológicoRESUMO
BACKGROUND: Neoadjuvant treatment has become the standard of care for patients with advanced esophageal cancer. However, few studies have elucidated the clinical factors that predict response to neoadjuvant therapy in a large multicenter cohort. We aimed to develop a predictive model of therapeutic effect in patients with esophageal squamous cell carcinoma (SCC) who received neoadjuvant treatment. METHODS: This nationwide study included 4078 patients from 85 institutions. Patients who received neoadjuvant treatment followed by surgery for esophageal SCC were eligible. We developed a logistic regression model to predict good pathological therapeutic effects, and a predictive nomogram was generated by applying the logistic regression formula. RESULTS: Among neoadjuvant regimens, cisplatin plus 5-fluorouracil (CF) was the most frequently used (60.2%), followed by docetaxel plus CF (DCF, 27.4%), CF with radiotherapy (CF-RT, 4.5%), adriamycin plus CF (3.6%), nedaplatin plus 5-fluorouracil (0.9%), and DCF-RT (0.5%). Multivariable analysis revealed that male sex, advanced cT category, and increased pretherapeutic SCC antigen level were independently associated with not achieving a good therapeutic effect. Moreover, intensified neoadjuvant regimens were independently associated with favorable therapeutic effects; DCF-RT elicited the best therapeutic effect, followed by CF-RT and DCF. A predictive model including nine commonly measured preoperative variables was generated, and the area under the curve was 0.679 (95% confidence interval: 0.658-0.700). This nomogram was also adequately validated internally. CONCLUSIONS: The model developed in this study was validated and predicts the therapeutic effect in patients with esophageal SCC who received neoadjuvant treatment. This model might contribute to individualized treatment strategies.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Masculino , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Neoplasias Esofágicas/patologia , Terapia Neoadjuvante , Estudos Retrospectivos , Japão , Taxoides , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino , Docetaxel , FluoruracilaRESUMO
BACKGROUND: Although neoadjuvant treatment has become the standard of care for patients with locally advanced esophageal cancer, previous studies comparing neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) have demonstrated inconclusive results. METHODS: Our study cohort included 3978 patients from 85 institutions. Those who underwent NAC or NACRT followed by surgery for esophageal squamous cell carcinoma (ESCC) were eligible for inclusion. We used the inverse probability of treatment weighting (IPTW) method to compare the outcomes between NAC and NACRT. RESULTS: Among the 3978 patients, 3777 (94.9%) received NAC and 201 (5.1%) received NACRT. After IPTW adjustment, the NACRT group had more patients with pathologically downstaged diseases and significantly better pathological response compared with the NAC group (p < 0.001); however, 5-year overall survival (OS), recurrence-free survival (RFS), and regional recurrence-specific survival (RRSS) were comparable between the groups. Subgroup analysis stratifying patients according to cT category showed that among cT1-2 patients, those in the NACRT group had significantly longer 5-year OS, RFS, and RRSS than those in the NAC group (P = 0.024, < 0.001, and 0.020, respectively). In contrast, no significant differences were observed among cT3-4a patients. The competing risks regression model showed comparable subdistribution hazard ratios for 10-year cancerous and noncancerous deaths between the NAC and NACRT groups. CONCLUSIONS: Compared with NAC, NACRT for ESCC did not promote better survival despite better therapeutic effects and did not increase noncancerous deaths.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Terapia Neoadjuvante , Neoplasias Esofágicas/patologia , População do Leste Asiático , Quimiorradioterapia , Estudos RetrospectivosRESUMO
BACKGROUND: There have been very few real-world studies reported in the literature solely focusing on fremanezumab in Asia. This study aimed to evaluate the efficacy and safety of fremanezumab in a real-world setting in Japan. METHOD: This single-centered, observational, retrospective study examined patients with migraines who received four doses of fremanezumab between December 2021 and August 2022 at Keio University Hospital. We assessed the changes in monthly migraine days, responder rates, and migraine-associated symptoms, as well as injection site reactions and adverse events. RESULT: Twenty-nine patients were enrolled, wherein 79.3% were women. Compared with those at baseline, the monthly migraine days decreased by 5.9 days at 4 months. The 50% responder rate was 55.2% at 4 months. A total of 57.9%, 47.8%, and 65.0% of patients showed improvement in the severity of photophobia, phonophobia, and nausea/vomiting, respectively. Moreover, injection site reactions were the most common adverse events (55.2%). CONCLUSION: Fremanezumab is effective and safe for migraine prevention in Japan. Fremanezumab also improved migraine-associated symptoms in half of the patients.
Assuntos
Reação no Local da Injeção , Transtornos de Enxaqueca , Humanos , Feminino , Masculino , Estudos Retrospectivos , Japão/epidemiologia , Resultado do Tratamento , Método Duplo-Cego , Transtornos de Enxaqueca/diagnósticoRESUMO
BACKGROUND: Intestinal microinflammation with immune dysfunction due to severe acute respiratory syndrome coronavirus 2 reportedly precipitates post-infectious irritable bowel syndrome. This study aimed to elucidate potential risk factors for subsequent development of irritable bowel syndrome, hypothesizing that it is associated with specific symptoms or patient backgrounds. METHODS: This single-center retrospective observational study (2020-2021) included adults with confirmed coronavirus disease requiring hospital admission and was conducted using real-world data retrieved from a hospital information system. Patient characteristics and detailed gastrointestinal symptoms were obtained and compared between patients with and without coronavirus disease-induced irritable bowel syndrome. Multivariate logistic models were used to validate the risk of developing irritable bowel syndrome. Moreover, daily gastrointestinal symptoms during hospitalization were examined in patients with irritable bowel syndrome. RESULTS: Among the 571 eligible patients, 12 (2.1%) were diagnosed with irritable bowel syndrome following coronavirus disease. While nausea and diarrhea during hospitalization, elevated white blood cell count on admission, and intensive care unit admission were associated with the development of irritable bowel syndrome, nausea and diarrhea were identified as risk factors for its development following coronavirus disease, as revealed by the adjusted analyses (odds ratio, 4.00 [1.01-15.84] and 5.64 [1.21-26.31], respectively). Half of the patients with irritable bowel syndrome had both diarrhea and constipation until discharge, and constipation was frequently followed by diarrhea. CONCLUSIONS: While irritable bowel syndrome was rarely diagnosed following coronavirus disease, nausea and diarrhea during hospitalization precede the early signs of irritable bowel syndrome following coronavirus disease.
Assuntos
COVID-19 , Gastroenteropatias , Síndrome do Intestino Irritável , Adulto , Humanos , Síndrome do Intestino Irritável/complicações , COVID-19/complicações , Gastroenteropatias/complicações , Constipação Intestinal/diagnóstico , Diarreia/etiologia , NáuseaRESUMO
Esophagectomy is a highly invasive surgical procedure; however, anastomotic leakage is one of the major surgical complications that should be prevented. Institutions have their own inherited or specialized anastomosis methods. The superior anastomosis procedure remains unknown despite the many studies to determine the optimal method. The present study enrolled 341 patients who underwent esophagectomy at Keio University Hospital, Tokyo, Japan, between January 2009 and January 2019. The anastomosis method was changed from circular stapled anastomosis to hand-sewn anastomosis in February 2014 to reduce the risk of anastomotic leakage. We retrospectively compared short-term results (anastomotic leakage and stricture) between hand-sewn and circular stapled anastomoses. Analysis of heterogeneity after propensity score matching between the 107 patients in the hand-sewn anastomosis group and 107 patients in the circular stapled anastomosis group revealed almost equal distributions. The incidence rate of anastomotic leakage was significantly lower in the hand-sewn anastomosis group than in the circular stapled anastomosis group (9 vs. 20%, hazard ratio: 2.521; 95% confidence interval: 1.112-5.716; P = 0.027). No significant difference was found in the incidence of anastomotic stricture (16 vs. 18%, P = 0.844). Furthermore, no significant difference was found in the incidence of anastomotic leakage in any of the tumor locations between the two anastomosis procedures. For esophagogastric anastomosis in the neck after esophagectomy, hand-sewn anastomosis is superior to circular stapled anastomosis with regard to reducing the risk of anastomotic leakage.
Assuntos
Neoplasias Esofágicas , Neoplasias Torácicas , Humanos , Esofagectomia/efeitos adversos , Fístula Anastomótica/etiologia , Constrição Patológica/etiologia , Estudos Retrospectivos , Pontuação de Propensão , Resultado do Tratamento , Neoplasias Esofágicas/cirurgia , Anastomose Cirúrgica/efeitos adversos , Grampeamento Cirúrgico , Neoplasias Torácicas/cirurgia , Complicações Pós-Operatórias/epidemiologiaRESUMO
BACKGROUND: We have reported the possible benefits of radical esophagectomy with thoracic duct (TD) resection in elective esophageal cancer surgery. However, the effect of TD resection on the long-term nutrition status remains unclear. METHODS: Patients who underwent esophagectomy at Keio University between January 2006 and December 2018 were included, and those who had no recurrence for more than three years were evaluated. Changes in each body composition (muscle mass and body fat) were comparatively assessed between those who underwent TD resection or not, before and at, one, three and five years after surgery. Computed tomography images were analyzed on postoperative year 1, 3 and 5. RESULTS: This study included 217 patients categorized in the TD-resected (TD-R) (156 patients) and TD-preserved (TD-P) (61 patients) groups. The loss of muscle mass was comparable between the groups. On the other hand, the loss of adipose tissues was significantly greater in the TD-R group than in the TD-P group at one and three years after surgery, while there was no statistical difference five years after surgery. Additionally, among patients with cT1N0M0 disease in whom survival advantage of TD resection has been reported previously, the loss of muscle mass did not differ between each group. CONCLUSIONS: The change of muscle mass between the two groups was comparable. Although body fat mass was reduced by TD resection, it eventually recovered in the long term. In patients with esophageal cancer, TD resection may be acceptable without significant impact on body composition in the long term.
Assuntos
Neoplasias Esofágicas , Ducto Torácico , Humanos , Ducto Torácico/cirurgia , Esofagectomia/métodos , Estudos Retrospectivos , Neoplasias Esofágicas/cirurgia , Composição CorporalRESUMO
PURPOSE: Recent reports suggest that postoperative cerebral infarction following lung cancer surgery is caused by thrombus formation at the stump of the pulmonary vein and that the risk is highest after left upper lobectomy (LUL). Thrombosis at the stump of the pulmonary vein and the incidence of cerebral infarction was investigated prospectively in patients who underwent lobectomy for lung cancer. METHODS: Lung cancer patients undergoing planned pulmonary lobectomy were enrolled. The endpoint was to confirm if there is a higher incidence of thrombus formation (primary) and a higher incidence of cerebral infarction (secondary) in patients undergoing LUL. We planned to accrue 600 patients. An interim analysis was scheduled for just after the data center received the final clinical review form of the 300th patient. RESULTS: The interim analysis revealed a significant difference in the primary endpoint. In the final analysis, thrombus was identified in 16 of 88 LUL patients (20.5%), and in 4 of 247 patients who underwent other types of lobectomy (1.6%) (p < 0.05). Cerebral infarction was identified in 1 of the LUL patients (1.3%) and in 9 of the other patients (3.6%) (p = 0.318). CONCLUSIONS: Thrombus frequently forms at the stump of the left superior pulmonary vein after LUL. However, our study did not identify a relationship between thrombosis and cerebral infarction.
Assuntos
Neoplasias Pulmonares , Veias Pulmonares , Trombose , Trombose Venosa , Humanos , Veias Pulmonares/cirurgia , Estudos Prospectivos , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Pneumonectomia/efeitos adversos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/efeitos adversos , Trombose/epidemiologia , Trombose/etiologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/complicações , Infarto Cerebral/epidemiologia , Infarto Cerebral/etiologiaRESUMO
BACKGROUND: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are a favourable option for patients with migraine who experience distressful headache disability and fail to respond to traditional preventive treatment options. However, since CGRPmAb has been available for only 2 years in Japan, the difference between good and poor responders remains unknown. We aimed to investigate the clinical characteristics of patients with migraine in Japan who responded well to CGRPmAb based on real-world data. METHODS: We analysed patients who visited Keio University Hospital, Tokyo, Japan, between the 12th of August 2021 and 31st of August 2022, and were prescribed one of three CGRPmAbs (erenumab, galcanezumab, and fremanezumab) for more than 3 months. We recorded the patients' basic migraine characteristics, such as pain quality, monthly migraine days (MMD)/monthly headache days (MHD), and the number of prior treatment failures. We defined good responders as patients whose MMDs decreased by more than 50% after 3 months of treatment and other patients as poor responders. We compared the baseline migraine characteristics between the two groups and performed logistic regression analysis based on the items that showed statistically significant differences. RESULTS: In total, 101 patients were considered eligible for the responder analysis (galcanezumab: 57 (56%), fremanezumab: 31 (31%), and erenumab: 13 (13%)). After 3 months of treatment, 55 (54%) patients achieved ≥ 50% reduction in MMDs. Comparisons between ≥ 50% responders and non-responders revealed that age was significantly higher (p = 0.003), and MHD and total prior treatment failures were significantly lower (p = 0.027, 0.040, respectively), in responders than in non-responders. Age was a positive predictive factor, and the total number of prior treatment failures and past medical history of immuno-rheumatologic diseases were negative predictive factors of CGRPmAb responsiveness in Japanese patients with migraine. CONCLUSIONS: Patients with migraine who are older, with fewer prior treatment failures and no past history of immuno-rheumatologic disease, may respond well to CGRPmAbs.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Humanos , Peptídeo Relacionado com Gene de Calcitonina/uso terapêutico , Japão , Resultado do Tratamento , Método Duplo-Cego , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Cefaleia/tratamento farmacológicoRESUMO
BACKGROUND: The prognostic impact of docetaxel, cisplatin, and 5-FU (DCF) reported in JCOG1109 was successfully validated using real-world data in patients < 75 years old. However, DCF was not reported to be beneficial in elderly patients with a relatively higher postoperative complication incidence. This study aimed to clarify the impact of postoperative complications on the prognosis of ESCC and the difference in the magnitude of the impact by age and regimen. METHODS: Patients with esophageal squamous cell carcinoma (ESCC) who underwent subtotal esophagectomy at 85 authorized institutes were retrospectively reviewed from 2010 to 2015. The prognostic impact of postoperative anastomotic leakage (AL) and pneumonia on survival was evaluated. The prognostic value of the postoperative complications was assessed by stratifying patients according to age and neoadjuvant chemotherapy regimen. RESULTS: Patients with AL, pneumonia, and infectious complications (ICs: a combination of pneumonia and AL) showed significantly worse overall survival (OS). IC served as a negative prognostic factor of OS and recurrence-free survival, and its negative prognostic impact was more evident in patients aged > 75 years. When the patients were further stratified by chemotherapeutic regimens, using the CF/IC(-) group as a reference, the DCF/IC (+) group showed significantly shorter OS in patients aged > 75 years with a hazard ratio (HR) of 2.551. The HR of the CF/IC (+) group was 1.503. CONCLUSIONS: The negative impact of postoperative complications on survival was confirmed in this nationwide study. Furthermore, its magnitude was higher in elderly patients who received triplet chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Pneumonia , Idoso , Humanos , Fístula Anastomótica/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/uso terapêutico , Docetaxel/efeitos adversos , População do Leste Asiático , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Fluoruracila/uso terapêutico , Terapia Neoadjuvante/efeitos adversos , Pneumonia/epidemiologia , Pneumonia/etiologia , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: We previously reported that postoperative recurrence in responders occurred in the regional field mostly as a solitary lesion without distant failure. However, further validation is necessary due to the low percentage of pathological responders, especially those with pCR. This study aimed to validate the prognostic impact of pathological response and the distribution of residual tumors in pathological responders using a nationwide database from 85 Japanese esophageal centers. METHODS: We retrospectively reviewed patients with esophageal squamous cell carcinoma (ESCC) who underwent subtotal esophagectomy at 85 authorized institutes for esophageal cancer between 2010 and 2015. The recurrence free survival (RFS), overall survival (OS), and recurrent tumor patterns were compared among the pathological responses. RESULTS: Of 4781 patients initially enrolled, 3840 were selected for subsequent analysis, including 237 patients with pathological complete response (pCR, 6%). The RFS and OS were significantly correlated with pathological response. When the recurrence pattern was classified into regional or distant recurrence, the incidence of distant failure was significantly lower in patients with pCR in cT1/2. Three percent of all patients with pCR in cT1/2 encountered postoperative recurrence in distant organs. CONCLUSION: The prognostic impact of pathological response was reproduced in the nationwide data. pCR in ESCC patients with cT1/2 provides a favorable prognosis with less incidence of distant failure. This finding may contribute to selecting appropriate candidates for an organ preservation approach based on the response to induction therapy.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Prognóstico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Terapia Neoadjuvante , Estudos Retrospectivos , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologiaRESUMO
BACKGROUND: Diabetes is known to be associated with anastomotic leakage (AL) after esophagectomy. However, it is unknown whether well-controlled diabetes is also associated with AL. METHODS: We conducted a two-center retrospective cohort database study of patients who underwent oncological esophagectomy (2011-2019). Patients were divided into four groups: normoglycemia, pre-diabetes, well-controlled diabetes (hemoglobin A1c [HbA1c] < 7.0%), and poorly controlled diabetes (HbA1c ≥ 7.0%). The occurrence of AL and length of stay were compared between groups using multivariable analyses. The relationship between categorical HbA1c levels and AL was also investigated in patients stratified by diabetes medication before admission. RESULTS: Among 1901 patients, 1114 (58.6%) had normoglycemia, 480 (25.2%) had pre-diabetes, 180 (9.5%) had well-controlled diabetes, and 127 (6.7%) had poorly controlled diabetes. AL occurred in 279 (14.7%) patients. Compared with normoglycemia, AL was significantly associated with both well-controlled diabetes (odds ratio 1.83, 95% confidence interval [CI] 1.22-2.74) and poorly controlled diabetes (odds ratio 1.95, 95% CI 1.23-3.09), but not with pre-diabetes. Preoperative HbA1c levels showed a J-shaped association with AL in patients without diabetes medication, but no association in patients with diabetes medication. Compared with normoglycemia, only poorly controlled diabetes was significantly associated with longer hospital stay after surgery, especially in patients with operative morbidity (unstandardized coefficient 14.9 days, 95% CI 5.6-24.1). CONCLUSIONS: Diabetes was associated with AL after esophagectomy even in well-controlled patients, but pre-diabetes was not associated with AL. Operative morbidity, including AL, in poorly controlled diabetes resulted in prolonged hospital stays compared with normoglycemia.