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1.
JAMA ; 329(15): 1271-1282, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37071094

RESUMO

Importance: For patients with RAS wild-type metastatic colorectal cancer, adding anti-epidermal growth factor receptor (anti-EGFR) or anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined. Objective: To evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) vs bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic colorectal cancer. Design, Setting, and Participants: Randomized, open-label, phase 3 clinical trial at 197 sites in Japan in May 2015-January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic colorectal cancer (final follow-up, January 14, 2022). Interventions: Panitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days. Main Outcomes and Measures: The primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resection rate. Results: In the as-treated population (n = 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had left-sided tumors. Median follow-up was 61 months. Median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio [HR] for death, 0.82; 95.798% CI, 0.68-0.99; P = .03) and 36.2 vs 31.3 months, respectively, in the overall population (HR, 0.84; 95% CI, 0.72-0.98; P = .03). Median progression-free survival for panitumumab vs bevacizumab was 13.1 vs 11.9 months, respectively, for those with left-sided tumors (HR, 1.00; 95% CI, 0.83-1.20) and 12.2 vs 11.4 months overall (HR, 1.05; 95% CI, 0.90-1.24). Response rates with panitumumab vs bevacizumab were 80.2% vs 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI, 4.4%-17.9%) and 74.9% vs 67.3% overall (difference, 7.7%; 95% CI, 1.5%-13.8%). Median duration of response with panitumumab vs bevacizumab was 13.1 vs 11.2 months for left-sided tumors (HR, 0.86; 95% CI, 0.70-1.10) and 11.9 vs 10.7 months overall (HR, 0.89; 95% CI, 0.74-1.06). Curative resection rates with panitumumab vs bevacizumab were 18.3% vs 11.6% for left-sided tumors; (difference, 6.6%; 95% CI, 1.0%-12.3%) and 16.5% vs 10.9% overall (difference, 5.6%; 95% CI, 1.0%-10.3%). Common treatment-emergent adverse events were acneiform rash (panitumumab: 74.8%; bevacizumab: 3.2%), peripheral sensory neuropathy (panitumumab: 70.8%; bevacizumab: 73.7%), and stomatitis (panitumumab: 61.6%; bevacizumab: 40.5%). Conclusions and Relevance: Among patients with RAS wild-type metastatic colorectal cancer, adding panitumumab, compared with bevacizumab, to standard first-line chemotherapy significantly improved overall survival in those with left-sided tumors and in the overall population. Trial Registration: ClinicalTrials.gov Identifier: NCT02394795.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Neoplasias Colorretais , Panitumumabe , Idoso , Feminino , Humanos , Masculino , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Bevacizumab/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila/administração & dosagem , Leucovorina/administração & dosagem , Panitumumabe/administração & dosagem , Panitumumabe/efeitos adversos , Panitumumabe/uso terapêutico , Oxaliplatina/administração & dosagem , Receptores ErbB/antagonistas & inibidores , Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
2.
Gastric Cancer ; 24(3): 701-709, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33179192

RESUMO

BACKGROUND: Gastric cancer (GC) patients with peritoneal metastasis are defined as stage IV in the Japanese classification of GC. For patients with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) and/or localized peritoneal metastasis (P1a), gastrectomy followed by S1 monotherapy is one of the most widely accepted therapeutic strategy in Japan. This study investigated the efficacy of preoperative chemotherapy as initial treatment in GC patients with CY1 and/or P1a. METHODS: We retrospectively reviewed GC patients diagnosed with CY1 and/or P1a at 34 institutions in Japan between 2008 and 2012. Selection criteria were: adenocarcinoma, no distant metastasis except CY1 or P1a, and no prior treatment. The subjects were divided into an Initial-Chemotherapy group and an Initial-Surgery group, according to the initial treatment. RESULTS: A total of 824 patients were collected and 713 eligible patients were identified for this study. As the initial treatment, 150 patients received chemotherapy (Initial-Cx), and 563 patients underwent surgery (Initial-Sx). Initial-Cx regimens were cisplatin plus S1/docetaxel plus cisplatin plus S1/others (n = 90/37/23). Both overall survival (OS) and progression-free survival (PFS) were similar between the Initial-Cx and Initial-Sx groups (median OS 24.8 and 24.0 months, HR 1.07, 95% CI 0.87-1.3; median PFS 14.9 and 13.9 months, HR 1.04, 95% CI 0.85-1.27). The 5-year OS rates were 22.3% in the Initial-Cx group and 21.5% in the Initial-Sx group. CONCLUSIONS: Although, the preoperative chemotherapy did not show a survival benefit for GC patients with CY1 and/or P1a, initial-Cx showed favorable survival in patients who converted to P0 and CY0.


Assuntos
Recidiva Local de Neoplasia/terapia , Neoplasias Peritoneais/terapia , Neoplasias Gástricas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrectomia , Humanos , Japão , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Metástase Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Lavagem Peritoneal , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
3.
Int J Clin Oncol ; 26(2): 399-408, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33097971

RESUMO

PURPOSE: FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes. METHODS: Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR). RESULTS: Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8-77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively. CONCLUSIONS: FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Resultado do Tratamento
4.
Esophagus ; 17(3): 264-269, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31776810

RESUMO

BACKGROUND: Anastomotic leakage (AL) is a serious complication after esophagectomy. The retrosternal (RS) route has been selected majorly to reduce reflux and related pneumonia and considering mediastinal recurrences. AL has been developed more in RS than posterior mediastinal (PM) route reconstruction. Therefore, we suspected the sterno-tracheal distance (STD) might be related to AL and started the selection according to the STD from 2009. METHODS: A total of 221 patients who underwent a subtotal esophagectomy with gastric tube reconstruction during January 2004-April 2017 were investigated. The patients were classified into the 'after STD selection' (A; n = 144) group and the 'before STD selection' (B, n = 77) group. The incidences of and the risk factors for AL between the two groups were compared. RESULTS: The incidence of AL was high in the B group (18.2%), and 78.6% of the patients who developed AL were treated with RS route reconstruction. The median STDs of the patients with AL and no AL were 10.3 mm and 14.5 mm, respectively (p = 0.001). These results demonstrated that the STD was a risk factor for AL in the RS route. Based on these results, 13 mm was set as the cutoff value. After STD selection, the median STD increased from 14.0 to 17.3 mm (p = 0.001), and the incidence of AL decreased significantly from 26.2 to 11.1% in the RS route (p = 0.037). CONCLUSION: The STD was the independent risk factor for AL in the RS route. RS route reconstruction should be avoided for the patients with STD < 13 mm.


Assuntos
Fístula Anastomótica/etiologia , Nutrição Enteral/efeitos adversos , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Esterno/diagnóstico por imagem , Traqueia/diagnóstico por imagem , Idoso , Fístula Anastomótica/epidemiologia , Estudos de Casos e Controles , Nutrição Enteral/métodos , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Mediastino/cirurgia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/normas , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos
5.
Gan To Kagaku Ryoho ; 46(6): 1057-1059, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31273175

RESUMO

According to the REGARD and RAINBOW trials, ramucirumab(RAM)was introduced as second-line therapy for advanced or metastatic gastric cancer. Endoscopic metallic stent placement and angiogenesis inhibitor administration carry the risk of gastrointestinal perforation. The outcomes of patients who undergo endoscopic placement of metallic stents during RAM treatment have not yet been fully assessed. A 60's man was diagnosed with advanced esophagogastric junction cancer(por) with Virchow's lymph node metastases. His tumor was classified as cT4a(SE), N1(#1), M1, stage Ⅳ. He received chemotherapy, but the size of the primary tumor and metastases increased. After stenting for gastric outlet obstruction, he received a paclitaxel(PTX)plus RAM regimen as third-line treatment. Because of CTCAE Grade 2 peripheral neuropathy, PTX was discontinued after 10 courses. For 11 months, tumor control without adverse events was maintained. The patient was then switched to CPT-11 as fourth-line treatment.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Gástricas , Anticorpos Monoclonais Humanizados , Junção Esofagogástrica , Humanos , Masculino , Stents , Neoplasias Gástricas/terapia , Ramucirumab
6.
Gastric Cancer ; 21(3): 421-427, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28936560

RESUMO

BACKGROUND: S-1 plus cisplatin is a standard regimen for advanced gastric cancer (AGC) in Asia. The ToGA trial established a fluoropyrimidine plus cisplatin and trastuzumab as a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive AGC. In the HERBIS-1 trial, trastuzumab combined with S-1 plus cisplatin showed promising antitumor activity in patients with HER2-positive AGC. However, cisplatin has several important drawbacks, including vomiting and renal toxicity. These disadvantages of cisplatin are prominent in elderly patients. Therefore, we conducted a prospective phase II study of trastuzumab plus S-1 without cisplatin in elderly patients with HER2-positive AGC. METHODS: Patients 65 years or older who had HER2-positive AGC received S-1 orally on days 1-28 of a 42-day cycle and trastuzumab intravenously on day 1 of a 21-day cycle. RESULTS: A total of 51 patients were enrolled. Two patients were ineligible. The full analysis set thus comprised 49 patients. The median age was 71 years (range 65-85). The confirmed response rate was 40.8% (95% CI 27.1-54.6%), and the null hypothesis was rejected. The median follow-up period was 10.6 months. Median overall survival was 15.8 months. Median progression-free survival was 5.1 months, and time to treatment failure was 4.0 months. Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%), and anorexia (12.0%). There was one treatment-related death. CONCLUSIONS: Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects as well as promising survival results in elderly patients with HER2-positive AGC. CLINICAL TRIALS REGISTRATION: UMIN000007368.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Masculino , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Estudos Prospectivos , Receptor ErbB-2/biossíntese , Neoplasias Gástricas/mortalidade , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos
8.
Esophagus ; 15(2): 75-82, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29892933

RESUMO

BACKGROUND: Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. METHODS: Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. RESULTS: We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. CONCLUSIONS: TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.


Assuntos
Neoplasias Esofágicas/cirurgia , Trato Gastrointestinal/fisiopatologia , Estado Nutricional/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Adrenomedulina/sangue , Idoso , Proteína C-Reativa/metabolismo , Defecação/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Esofagectomia/efeitos adversos , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Panax , Extratos Vegetais/uso terapêutico , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Albumina Sérica/metabolismo , Redução de Peso/efeitos dos fármacos , Zanthoxylum , Zingiberaceae
9.
Ann Surg Oncol ; 24(3): 832-840, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26577115

RESUMO

BACKGROUND: Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The chemokine CXCL12 and its receptors CXCR4 and CXCR7 were suggested to be involved in cancer invasion and metastasis. The aim of this retrospective study was to evaluate the prognostic impact of the expressions of CXCL12, CXCR4 and CXCR7 in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We used immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate the expressions of CXCL12, CXCR4, and CXCR7 in ESCC patients' tumor biopsy specimens obtained during preoperative endoscopy or surgery. These results were compared with the patients' clinicopathological parameters and survival. RESULTS: IHC was conducted for 172 patients. High expression of CXCR4 in the cytoplasm and nuclei and that of CXCR7 were associated with poor cause-specific survival (CSS) (P= .002 and .010, respectively). The specimens from 52 of the 172 patients were examined by RT-PCR and quantitative real-time PCR. The expression levels of messenger RNA (mRNA) of CXCR4 and CXCR7 were significantly increased in the tumors compared with normal esophageal mucosae (P < .0001). The expression level of mRNA of CXCR4 was associated with poor recurrence-free survival and CSS (P = .012 and .038, respectively). CONCLUSIONS: CXCR4 expression is associated with poor prognosis in patients with ESCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Quimiocina CXCL12/metabolismo , Neoplasias Esofágicas/metabolismo , RNA Mensageiro/metabolismo , Receptores CXCR4/metabolismo , Receptores CXCR/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Quimiocina CXCL12/genética , Intervalo Livre de Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Esofagectomia , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Receptores CXCR/genética , Receptores CXCR4/genética , Estudos Retrospectivos , Taxa de Sobrevida
10.
J Strength Cond Res ; 30(12): 3405-3411, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27870698

RESUMO

Iguchi, J, Watanabe, Y, Kimura, M, Fujisawa, Y, Hojo, T, Yuasa, Y, Higashi, S, and Kuzuhara, K. Risk factors for injury among Japanese collegiate players of American football based on performance test results. J Strength Cond Res 30(12): 3405-3411, 2016-The purpose of this study was to identify how risk factors for injury during American football are related to players' physical strength as determined using typical performance tests. One hundred 53 Japanese collegiate players of American football were recruited for this study. Eight potential risk factors were evaluated: position (skill vs. lineman), body mass index, back squat one-repetition maximum, vertical jump height, power, height, body weight, and previous injury. Using multivariate Cox regression, we examined how these factors were associated with knee sprain, ankle sprain, and hamstring strain. We recorded 63 injuries (17 knee sprains, 23 ankle sprains, and 23 hamstring strains). Players with higher power were at significantly greater risk for knee sprains (p = 0.04), those with low power had a significantly higher incidence of ankle sprain (p = 0.01), and vertical jump height was a significant predictor of hamstring strain (p = 0.02). We identified several independent predictors of injuries associated with American football. Our findings may contribute to the development of effective screening tests and prevention exercises.


Assuntos
Traumatismos do Tornozelo/etiologia , Traumatismos em Atletas/etiologia , Desempenho Atlético/fisiologia , Futebol Americano/lesões , Traumatismos do Joelho/etiologia , Traumatismos do Tornozelo/epidemiologia , Povo Asiático , Traumatismos em Atletas/epidemiologia , Estudos de Coortes , Músculos Isquiossurais/lesões , Humanos , Incidência , Traumatismos do Joelho/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Universidades , Adulto Jovem
11.
Gan To Kagaku Ryoho ; 42(11): 1431-4, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26602406

RESUMO

A 61-year-old man with advanced sigmoid colon cancer was admitted to our hospital. Abdominal computed tomography (CT) revealed locally advanced sigmoid colon cancer, with suspected invasion of the bladder and small intestine. The clinical stage of the disease was T4b, N1, M0, and Stage III a, with wild-type KRAS expression. A transverse colostomy was performed because of the presence of a bowel obstruction. The patient received 4 courses of Leucovorin, 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI). The size of the tumor and lymph nodes decreased noticeably after chemotherapy and laparoscopic high anterior resection with lymph node dissection. During this phase, the pathological stage of the disease was ypT0, N0, and Stage 0(no viable carcinoma cells, Grade 3). This result suggested that preoperative FOLFOXIRI chemotherapy is a useful regimen for the treatment of locally advanced colon cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo Sigmoide/tratamento farmacológico , Biópsia , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias do Colo Sigmoide/patologia , Neoplasias do Colo Sigmoide/cirurgia , Tomografia Computadorizada por Raios X
12.
Gan To Kagaku Ryoho ; 42(5): 637-40, 2015 May.
Artigo em Japonês | MEDLINE | ID: mdl-25981663

RESUMO

In our hospital, a clinical trial on the effects of preoperative 2-week S-1 administration for advanced gastric cancer is being conducted. A7 5-year-old man presented to our hospital with a type 2 tumor(poorly differentiated adenocarcinoma)in the pyloric antrum. Subpyloric lymph node enlargement and a c-T2(MP), N1, M0, Stage II A tumor (according to the gastric cancer handling agreement, 14th edition)were diagnosed, and S-1(100mg/day)was subsequently administered for 14 days. On day 15, we performed laparoscopy-assisted distal gastrectomy, with D2 dissection. Analysis of the resected specimen, ie the primary tumor and metastatic lymph nodes, confirmed the effect of the treatment as Grade 2, and revealed a type 2 gastric cancer of 30×20mm in size; this tumor was downstaged to yp-T1b(SM), N1, Stage I B. No adverse events associated with perioperative S-1 were observed, and the postoperative course was good. At the latest follow-up(6 years after treatment), no recurrence was observed.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Adenocarcinoma/cirurgia , Idoso , Combinação de Medicamentos , Gastrectomia , Humanos , Excisão de Linfonodo , Masculino , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
13.
J Med Invest ; 71(1.2): 141-147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38735710

RESUMO

CapeOX is a regimen used as postoperative adjuvant chemotherapy for the treatment of advanced recurrent colorectal cancer. If early adverse events occur, treatment may not progress as planned and further dose reduction may be necessary. In this study, we investigated whether pre-treatment medical records could be used to predict adverse events in order to prevent adverse events caused by CapeOX treatment. The 178 patients were classified into two groups (97 in the adverse event positive group and 81 in the adverse event-negative group) based on withdrawal or postponement of four or fewer courses. In univariate analysis, age, height, weight, body surface area (BSA), creatinine clearance, muscle mass, and lean body mass were associated with early adverse events (P<0.05). The area under the receiver operating characteristic curve obtained by Stepwise logistic regression analysis using the Akaike information criterion method was 0.832. For nested k-fold cross validation, the accuracy rates of the support vector machine, random forest, and logistic regression algorithms were 0.71, 0.70, and 0.75, respectively. The results of the present study suggest that a logistic regression prediction model may be useful in predicting early adverse events caused by CapeOX therapy in patients with colorectal cancer. J. Med. Invest. 71 : 141-147, February, 2024.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/tratamento farmacológico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Capecitabina/efeitos adversos , Capecitabina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Idoso de 80 Anos ou mais , Adulto , Estudos Retrospectivos
14.
Nat Med ; 30(3): 730-739, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38347302

RESUMO

Certain genetic alterations and right-sided primary tumor location are associated with resistance to anti-epidermal growth factor (EGFR) treatment in metastatic colorectal cancer (mCRC). The phase 3 PARADIGM trial (n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. This prespecified exploratory biomarker analysis of PARADIGM (n = 733) evaluated the association between circulating tumor DNA (ctDNA) gene alterations and efficacy outcomes, focusing on a broad panel of gene alterations associated with resistance to EGFR inhibition, including KRAS, NRAS, PTEN and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK, RET and NTRK1 fusions. Overall survival was prolonged with panitumumab plus modified FOLFOX6 versus bevacizumab plus modified FOLFOX6 in patients with ctDNA that lacked gene alterations in the panel (that is, negative hyperselected; median in the overall population: 40.7 versus 34.4 months; hazard ratio, 0.76; 95% confidence interval, 0.62-0.92) but was similar or inferior with panitumumab in patients with ctDNA that contained any gene alteration in the panel (19.2 versus 22.2 months; hazard ratio, 1.13; 95% confidence interval, 0.83-1.53), regardless of tumor sidedness. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795 .


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Panitumumabe/uso terapêutico , Bevacizumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Biomarcadores , Receptores ErbB/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)
15.
Ann Surg Oncol ; 20(1): 209-17, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22847125

RESUMO

BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) and CD44 act as important biomarkers in several solid tumors. However, few studies have examined the relationships between ALDH1 expression and the prognosis and clinical characteristics of esophageal squamous cell carcinoma (ESCC). METHODS: This study was a retrospective case-control study and included 152 patients with ESCC. A total of 56 patients underwent surgery (OP group), 40 patients received neoadjuvant chemotherapy involving weekly docetaxel plus 5-fluorouracil and low-dose cisplatin (DFP therapy) prior to undergoing surgery (NAC group), and 56 patients received initial systemic DFP therapy (CT group). The ALDH1 and CD44 immunohistochemical expression levels of each tumor were evaluated and compared with the prognosis and clinical characteristics of the ESCC patients. RESULTS: In the OP and NAC groups, multivariate analysis found that ALDH1 was independently associated with postoperative recurrence and prognosis (OP group, P=0.004 and 0.016, respectively; NAC group, P=0.026 and 0.014, respectively). In addition, CD44 was found to be associated with postoperative recurrence in the OP group and prognosis in the NAC group (P=0.024 and 0.047, respectively). Among the ALDH1-negative clinical stage II/III patients, the OP and NAC groups displayed better prognoses than the CT group (P<0.001). However, among the ALDH1-positive clinical stage II/III patients, the OP and NAC groups displayed poorer prognoses than the CT group (P=0.049). CONCLUSIONS: ALDH1 was found to be a predictor of postoperative recurrence and prognosis in ESCC, and CD44 might be a predictor of recurrence and prognosis. ALDH1 expression might affect the treatment strategy for ESCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Receptores de Hialuronatos/metabolismo , Isoenzimas/metabolismo , Recidiva Local de Neoplasia/metabolismo , Retinal Desidrogenase/metabolismo , Idoso , Família Aldeído Desidrogenase 1 , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Esofagectomia , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxoides/administração & dosagem
16.
Ann Surg Oncol ; 19(2): 486-93, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21792510

RESUMO

BACKGROUND: The sentinel lymph node (SLN) concept has been gaining attention for gastrointestinal neoplasms but remains controversial for esophageal cancer. This study evaluated the feasibility of SLN identification using intraoperative indocyanine green (ICG) fluorescence imaging (IGFI) navigated by preoperative computed tomographic lymphography (CTLG) to treat superficial esophageal cancer. METHODS: Subjects comprised 20 patients clinically diagnosed with superficial esophageal cancer. Five minutes after endoscopic submucosal injection of iopamidol around the primary lesion using a four-quadrant injection pattern with a 23-gauge endoscopic injection sclerotherapy needle, three-dimensional multidetector computed tomography was performed to identify SLNs and lymphatic routes. ICG solution was injected intraoperatively around the tumor. Fluorescence imaging was obtained by infrared ray electronic endoscopy. Thoracoscope-assisted standard radical esophagectomy with lymphadenectomy was performed to confirm fluorescent lymph nodes detected by CTLG. RESULTS: Lymphatic vessels and SLNs were identified preoperatively using CTLG in all cases. Intraoperative detection rates were 100% using CTLG and 95% using IGFI. Lymph node metastases were found in four cases, including one false-negative case with SLNs occupied by bulky metastatic tumor that were not enhanced with both methods. The other 19 cases, including three cases of metastatic lymph nodes, were accurately identified by both procedures. CONCLUSIONS: Preoperative CTLG visualized the correct number and site of SLNs in surrounding anatomy during routine computed tomography to evaluate distant metastases. Referring to CTLG, SLNs were identified using IGFI, resulting in successful SLN navigation and saving time and cost. This method appears clinically applicable as a less-invasive method for treating superficial esophageal cancer.


Assuntos
Corantes , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Verde de Indocianina , Linfografia , Biópsia de Linfonodo Sentinela , Idoso , Estudos de Viabilidade , Fluorescência , Seguimentos , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
17.
Int J Surg Case Rep ; 94: 107147, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35658309

RESUMO

INTRODUCTION AND IMPORTANCE: Secondary aortoduodenal fistula (sADF) is a complication of prosthetic graft replacement of the abdominal aorta which often follows a fatal course. This report details our experience with a case of lymphatic fistula that developed after sADF repair. The fistula was refractory to conservative treatment but ultimately responded to lipiodol lymphangiography. CASE PRESENTATION: A 75-year-old man had undergone prosthetic graft replacement to treat an abdominal aortic aneurysm in 2012 and a thoracic aortic aneurysm in 2015. Upper gastrointestinal endoscopy was performed in 2020, and examination for worsening anemia revealed that the abdominal aortic graft had eroded into the horizontal duodenum. The patient was treated with prosthetic graft replacement and duodenectomy. A refractory lymphatic fistula was noted after surgery, which made ascites accumulation difficult to control, but the patient's condition rapidly improved following therapeutic lymphangiography. CLINICAL DISCUSSION: Surgery is the first-line therapy for sADF, but clinicians must stay vigilant for infection recurrence and aortoenteric fistulae after a repair, and this requires patient-specific postoperative management. Our modifications, intended to minimize contamination of the operative field in the present case, also facilitated our ability to subsequently treat a refractory lymphatic fistula, which is a rare postoperative complication of the procedure. CONCLUSION: Procedural modifications to sADF repair aimed at minimizing perioperative contamination are crucial for preventing infection recurrence. Given the extent of invasion, the surgery can cause various postoperative complications, requiring individualized strategies for management and treatment. Therapeutic lymphangiography is one such approach, which holds promise as a first-line treatment for refractory lymphatic fistula.

18.
J Strength Cond Res ; 25(12): 3368-77, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22076091

RESUMO

Iguchi, J, Yamada, Y, Ando, S, Fujisawa, Y, Hojo, T, Nishimura, K, Kuzuhara, K, Yuasa, Y, and Ichihashi, N. Physical and performance characteristics of Japanese division 1 collegiate football players. J Strength Cond Res 25(12): 3368-3377, 2011-This study aimed to establish the physical and performance characteristics of football players in the Japanese Division 1 collegiate football program and perform a comparison of these characteristics between Japanese (n = 208) and US Division 1 football players (n = 797). The following comparisons were made: (a) between a higher-ranked university team vs. a lower-ranked university team in Japan, (b) between different playing positions in Japan, (c) between starters and nonstarters in Japan, and (d) between playing positions in Japan vs. those in the United States. The results of this study suggest that players in the higher-ranked university team were heavier, stronger in back squat, jumped higher, and had greater power than those on the lower-ranked team. Furthermore, linemen were generally characterized by larger size, greater strength, and more fat as compared with backs. On the other hand, backs tended to be faster, smaller in physical size, have higher vertical jump height, and show greater relative strength than linemen did. Starters were taller, heavier, stronger, had more powerful, and more fat-free mass than nonstarters. Finally, our results revealed that players in the United States were superior to players in Japan in all body status comparisons (p < 0.01). This study revealed that performance and superior body composition are essential for the success of a football player. Power and strength seem to be key factors in defining good football performance.


Assuntos
Desempenho Atlético , Tamanho Corporal , Futebol Americano/fisiologia , Força Muscular , Músculo Esquelético/fisiologia , Adiposidade , Adolescente , Adulto , Análise de Variância , Humanos , Japão , Masculino , Corrida/fisiologia , Estados Unidos , Adulto Jovem
19.
Int J Surg Case Rep ; 71: 163-167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454453

RESUMO

INTRODUCTION: In case of gastrointestinal diverticula, the duodenal type is quite frequent; duodenum is the second most common site for diverticula following the colon (Glener et al., 2016). However, duodenal diverticular perforation is rare, so the appropriate surgical treatment for this condition is yet unclear (Simoes et al., 2014). This literature has been written in line with the SCARE criteria (Agha et al., 2018). PRESENTATION OF CASE: A 94-year-old woman emergently presented to our department with diffuse abdominal tenderness and guarding, indicating pan-peritonitis. Computed tomography revealed pneumoretroperitoneum; Therefore, gastrointestinal perforation was suspected. Emergency surgery was performed; we detected the perforated diverticulum located at the posterior wall of the duodenum with accompanying inflammation. Considering the location, postoperative leakage, and the patient's advanced age, we placed trans-section on duodenal wall against the lesion and resected the diverticulum, The lumen was then manually sutured from within. The anterior wall was closed using linear staplers. The patient recovered uneventfully and was discharged 24 days after surgery. DISCUSSSIONS: As perforated duodenal diverticulum is rare, the ideal management is unclear. Several studies mention various surgical procedures. However, actual treatment varies based on the patient's situation and surgeon's assessment. Almost all cases that require surgery present emergently; therefore, simpler and more effective treatment methods are required (Simoes et al., 2014; Philip et al., 2019; Fujisaki et al., 2014). CONCLUSION: We used a unique surgical technique; intraduodenal suture for perforated diverticulum. This technique can be a feasible alternative for managing this condition.

20.
Int J Surg Case Rep ; 76: 240-246, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33053481

RESUMO

INTRODUCTION: Pancreatoduodenectomy (PD) after gastrectomy requires more attention during surgery than ordinary PD due to anatomical variation with different types of gastrointestinal anastomoses, the complication of anatomical dissection, and the extent of adhesions present. Herein, we describe the PD strategies we used in three patients who strategy for three patients who had previously undergone distal gastrectomy for gastric cancer treatment. DISCUSSION: Generally, reconstruction following PD in patients who have undergone a prior Billroth I reconstruction is simple, as there is no previous afferent loop. By comparison, reconstruction after a Billroth II or R-Y reconstruction requires special consideration of the point of circulation and length of the remnant intestine used for pancreaticojejunostomy, choledochojejunostomy or gastrojejunostomy. CONCLUSION: There is no consensus regarding the best method for performing PD and reconstruction in patients with a prior history of gastrectomy. The appropriateness of using the existing afferent loop for reconstruction depends on whether the jejunum is of sufficient length for bile duct and pancreatic anastomosis. Regardless of the approach used, it is necessary to avoid excessive tension during reconstruction. Based on our experience and previous studies published in the English literature, we propose that reconstruction needs to be considered on a case-by-case basis.

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