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1.
Int J Mol Sci ; 22(18)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34575921

RESUMO

To treat malignant glioma, standard fractionated radiotherapy (RT; 60 Gy/30 fractions over 6 weeks) was performed post-surgery in combination with temozolomide to improve overall survival. Malignant glioblastoma recurrence rate is extremely high, and most recurrent tumors originate from the excision cavity in the high-dose irradiation region. In our previous study, protoporphyrin IX physicochemically enhanced reactive oxygen species generation by ionizing radiation and combined treatment with 5-aminolevulinic acid (5-ALA) and ionizing radiation, while radiodynamic therapy (RDT) improved tumor growth suppression in vivo in a melanoma mouse model. We examined the effect of 5-ALA RDT on the standard fractionated RT protocol using U251MG- or U87MG-bearing mice. 5-ALA was orally administered at 60 or 120 mg/kg, 4 h prior to irradiation. In both models, combined treatment with 5-ALA slowed tumor progression and promoted regression compared to treatment with ionizing radiation alone. The standard fractionated RT protocol of 60 Gy in 30 fractions with oral administration of 120 and 240 mg/kg 5-ALA, the human equivalent dose of photodynamic diagnosis, revealed no significant increase in toxicity to normal skin or brain tissue compared to ionizing radiation alone. Thus, RDT is expected to enhance RT treatment of glioblastoma without severe toxicity under clinically feasible conditions.

2.
Anticancer Res ; 41(9): 4489-4495, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475074

RESUMO

BACKGROUND/AIM: The chemokine receptors C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 7 (CCR7) play an important role in the invasion and metastasis of cancer. This study investigated the relationship between relative expression of CXCR4 and CCR7 mRNA, clinicopathological factors, and outcomes in patients with colorectal cancer (CRC). PATIENTS AND METHODS: We studied 202 patients who underwent surgery for CRC. The expression levels of CXCR4 and CCR7 mRNA in cancerous tissue were measured using quantitative real-time reverse-transcriptase polymerase chain reaction. RESULTS: High CCR7 mRNA expression levels in CRC tissues were positively associated with tumour size and were more frequently associated with cancer of the rectum than of the colon. Moreover, outcomes were significantly poorer in patients with high CCR7 mRNA expression than in those with low expression. On multivariate Cox regression analysis, a higher CCR7 mRNA expression level was a significant independent predictor of poorer overall survival in patients with CRC. CONCLUSION: Overexpression of CCR7 mRNA may be a useful independent prognostic factor in patients with CRC.


Assuntos
Neoplasias Colorretais/cirurgia , Perfilação da Expressão Gênica/métodos , Receptores CCR7/genética , Receptores CXCR4/genética , Regulação para Cima , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral
3.
In Vivo ; 35(5): 2771-2777, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410967

RESUMO

BACKGROUND/AIM: Cancer stem cells (CSCs) are reported to associated with cancer metastasis, relapse, and chemoresistance. This study examined the clinical significance of the expression of two CSC markers, the transporter associated with antigen processing 1 (TAP1) and the Delta-like 4 (DLL4) protein, in patients with locally advanced GC. PATIENTS AND METHODS: This study was performed using samples obtained from 413 pathological stage II/III GC patients after curative gastrectomy. We examined TAP1 and DLL4 expression using immunohistochemical analysis with tissue microarray and examined the association between TAP1 or DLL4 expression, clinicopathological factors and survival. RESULTS: High TAP1 expression was associated with better overall survival compared to low TAP1 expression (p=0.004). Furthermore, in multivariate analysis, high TAP1 expression was defined as a predictive factor for good survival. There was no significant difference between DLL4 expression and clinicopathological features and overall survival. CONCLUSION: TAP1 expression may be a useful prognostic marker in patients with locally advanced GC.


Assuntos
Neoplasias Gástricas , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Proteínas Adaptadoras de Transdução de Sinal , Apresentação do Antígeno , Proteínas de Ligação ao Cálcio , Gastrectomia , Humanos , Recidiva Local de Neoplasia , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia
4.
In Vivo ; 35(4): 2369-2377, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182520

RESUMO

BACKGROUND/AIM: The changes of dietary intake (DI) after gastrectomy have not been objectively reported. It has not been clear how much DI loss is experienced after total gastrectomy (TG) in comparison to after distal gastrectomy (DG). This study quantified the changes of DI after gastrectomy, and clarified how much DI loss is experienced after TG. PATIENTS AND METHODS: This was a prospective observational study. Patients who underwent gastrectomy for gastric cancer were enrolled. The DI loss was evaluated at 1 and 3 months postoperatively. RESULTS: Thirty-three patients underwent TG, and 117 patients underwent DG. The median %DI loss of the overall study population at 1 and 3 months after surgery was -9.3% and -3.6%. The median %DI loss at 1 and 3 months postoperatively was -15.6% and -5.3% in TG group, -8.9% and -3.3% in DG group (p=0.10 and 0.49, respectively). CONCLUSION: The patients experienced DI loss of approximately 10% at 1 month after gastrectomy. Patients who received TG tended to show a greater %DI loss at 1 month postoperatively.


Assuntos
Neoplasias Gástricas , Ingestão de Alimentos , Gastrectomia/efeitos adversos , Gastroenterostomia , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Gástricas/cirurgia
5.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808722

RESUMO

Chemo-radiotherapy, which combines chemotherapy with radiotherapy, has been clinically practiced since the 1970s, and various anticancer drugs have been shown to have a synergistic effect when used in combination with radiotherapy. In particular, cisplatin (CDDP), which is often the cornerstone of multi-drug combination cancer therapies, is highly versatile and frequently used in combination with radiotherapy for the treatment of many cancers. Therefore, the mechanisms underlying the synergistic effect of CDDP and radiotherapy have been widely investigated, although no definitive conclusions have been reached. We present a review of the combined use of CDDP and radiotherapy, including the latest findings, and propose a mechanism that could explain their synergistic effects. Our hypothesis involves the concepts of overlap and complementation. "Overlap" refers to the overlapping reactions of CDDP and radiation-induced excessive oxidative loading, which lead to accumulating damage to cell components, mostly within the cytoplasm. "Complementation" refers to the complementary functions of CDDP and radiation that lead to DNA damage, primarily in the nucleus. In fact, the two concepts are inseparable, but conceptualizing them separately will help us understand the mechanism underlying the synergism between radiation therapy and other anticancer drugs, and help us to design future radiosensitizers.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias/terapia , Radiossensibilizantes/uso terapêutico , Radioterapia Adjuvante , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Estudos Clínicos como Assunto , Ensaios Clínicos como Assunto , Terapia Combinada , Avaliação Pré-Clínica de Medicamentos , Humanos , Neoplasias/diagnóstico , Neoplasias/etiologia , Neoplasias/mortalidade , Radiossensibilizantes/administração & dosagem , Radiossensibilizantes/efeitos adversos , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Resultado do Tratamento
6.
In Vivo ; 35(2): 707-712, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622863

RESUMO

Gastrectomy with D2 lymph node dissection and perioperative adjuvant treatment is the standard treatment for locally advanced gastric cancer. However, the morality rate is reported to be 20%-40% after gastrectomy for gastric cancer. Perioperative sarcopenia and obesity are strongly related to postoperative surgical complications after gastrectomy. Furthermore, recent studies have shown that postoperative surgical complications are related to long-term oncological outcomes. If we can prevent or improve perioperative sarcopenia or obesity in gastric cancer patients, the rate of postoperative surgical complications in these patients might be reduced, thereby improving the long-term oncological outcomes. Given this hypothesis, recent studies have focused on enacting perioperative exercise programs for gastric cancer patients with sarcopenia and overweight/obesity. Such exercise programs have proven promising and demonstrated some clinical benefits for gastric cancer patients with sarcopenia and overweight/obesity. However, whether or not perioperative exercise programs have clinical benefits with regard to long-term oncological outcomes in gastric cancer patients is unclear. To optimize these perioperative exercise programs for gastric cancer patients, it is necessary to clarify the benefits with regard to the long-term oncological outcomes in these patients and establish an optimal perioperative exercise program.


Assuntos
Sarcopenia , Neoplasias Gástricas , Terapia por Exercício , Gastrectomia/efeitos adversos , Humanos , Excisão de Linfonodo , Obesidade/complicações , Sobrepeso , Complicações Pós-Operatórias , Sarcopenia/etiologia , Sarcopenia/terapia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
7.
Int J Mol Sci ; 21(23)2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33297519

RESUMO

Recently, modern therapies involving immune checkpoint inhibitors, cytokines, and oncolytic virus have been developed. Because of the limited treatment effect of modern therapy alone, the immunostimulatory effect of radiotherapy attracted increasing attention. The combined use of radiotherapy and modern therapy has been examined clinically and non-clinically, and its effectiveness has been confirmed recently. Because melanomas have high immunogenicity, better therapeutic outcomes are desired when using immunotherapy. However, sufficient therapeutic effects have not yet been achieved. Thus far, radiotherapy has been used only for local control of tumors. Although extremely rare, radiotherapy has also been reported for systemic control, i.e., abscopal effect. This is thought to be due to an antitumor immune response. Therefore, we herein summarize past information on not only the mechanism of immune effects on radiotherapy but also biomarkers reported in case reports on abscopal effects. We also reviewed the animal model suitable for evaluating abscopal effects. These results pave the way for further basic research or clinical studies on new treatment methods for melanoma. Currently, palliative radiation is administered to patients with metastatic melanoma for local control. If it is feasible to provide both systemic and local control, the treatment benefit for the patients is very large.


Assuntos
Imunoterapia/métodos , Melanoma/terapia , Radioterapia/métodos , Animais , Biomarcadores Tumorais/sangue , Terapia Combinada/métodos , Humanos , Melanoma/sangue , Melanoma/imunologia , Radioterapia/efeitos adversos
8.
In Vivo ; 34(5): 2769-2774, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32871813

RESUMO

BACKGROUND/AIM: Radiotherapy is widely accepted as the treatment of choice for early glottic squamous cell carcinoma (EGSCC), although it varies greatly with respect to dose, dose per fraction, and treatment techniques. The study aim was to evaluate the use of accelerated fractionation strategy (AFS) for EGSCC in standard clinical practice. PATIENTS AND METHODS: Patients treated with definitive radiotherapy for EGSCC between 2008 and 2019 were retrospectively identified and received either conventional fractionation, hypofractionation, or hyperfractionation. RESULTS: One hundred six patients were analyzed, and 19, 71, and 16 patients underwent conventional fractionation, hypofractionation, and hyperfractionation, respectively. The median follow-up was 56 months. The 5-year local control and overall survival rates were 79% and 83%; 78% and 79%; and 87% and 77%, respectively, and no significant difference was observed between the fractionation schedules. CONCLUSION: Our findings confirmed the utility of AFS in standard clinical practice and support its use for patients with EGSCC.


Assuntos
Carcinoma de Células Escamosas , Glote , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas/radioterapia , Fracionamento da Dose de Radiação , Glote/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Dosagem Radioterapêutica , Estudos Retrospectivos
9.
BMC Surg ; 20(1): 95, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32380979

RESUMO

BACKGROUND: Cancer cells are often found postoperatively at surgical resection margins (RM) in patients with gastric cancer because of submucosal infiltration or hesitation to secure adequate RM. This study was designed to evaluate risk factors for microscopic positive RM and to clarify which patients should undergo intraoperative frozen section diagnosis (IFSD). METHODS: Patients who underwent R0/1 gastrectomy for gastric adenocarcinoma between 2000 and 2018 in a single cancer center in Japan were studied. We divided the patients into a positive RM group and negative RM group according to the results of definitive histopathological examinations. We performed multivariate analysis to analyze risk factors for positive RM by and used the identified risk factors to risk stratify the patients. RESULTS: A total of 2757 patients were studied, including 49 (1.8%) in the positive RM group. The risk factors significantly associated with positive RM were remnant gastric cancer (odds ratio [OR] 4.7), esophageal invasion (OR 6.3), tumor size ≥80 mm (OR 3.9), and a histopathological diagnosis of undifferentiated type (OR 3.6), macroscopic type 4 (OR 3.7), or pT4 disease (OR 4.6). On risk stratification analysis, the incidence of positive RM was 0.1% without any risk factors, increasing to 0.4% with one risk factor, 3.1% with two risk factors, 5.3% with three risk factors, 21.3% with four risk factors, and 85.7% with five risk factors. CONCLUSIONS: The risk of macroscopically positive RM increased in patients who have risk factors. IFSD should be performed in patients who have four or more risk factors.


Assuntos
Adenocarcinoma/cirurgia , Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Idoso , Estudos de Coortes , Feminino , Coto Gástrico/patologia , Humanos , Japão , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
10.
Int J Mol Sci ; 21(7)2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32225109

RESUMO

Recent reports have suggested that 5-aminolevulinic acid (5-ALA), which is a precursor to protoporphyrin IX (PpIX), leads to selective accumulation of PpIX in tumor cells and acts as a radiation sensitizer in vitro and in vivo in mouse models of melanoma, glioma, and colon cancer. In this study, we investigated the effect of PpIX under X-ray irradiation through ROS generation and DNA damage. ROS generation by the interaction between PpIX and X-ray was evaluated by two kinds of probes, 3'-(p-aminophenyl) fluorescein (APF) for hydroxyl radical (•OH) detection and dihydroethidium (DHE) for superoxide (O2•-). •OH showed an increase, regardless of the dissolved oxygen. Meanwhile, the increase in O2•- was proportional to the dissolved oxygen. Strand breaks (SBs) of DNA molecule were evaluated by gel electrophoresis, and the enhancement of SBs was observed by PpIX treatment. We also studied the effect of PpIX for DNA damage in cells by X-ray irradiation using a B16 melanoma culture. X-ray irradiation induced γH2AX, DNA double-strand breaks (DSBs) in the context of chromatin, and affected cell survival. Since PpIX can enhance ROS generation even in a hypoxic state and induce DNA damage, combined radiotherapy treatment with 5-ALA is expected to improve therapeutic efficacy for radioresistant tumors.


Assuntos
Quebras de DNA de Cadeia Dupla , Melanoma/metabolismo , Protoporfirinas/metabolismo , Radiossensibilizantes/metabolismo , Ácido Aminolevulínico/metabolismo , Animais , Linhagem Celular Tumoral , Melanoma/genética , Melanoma/radioterapia , Camundongos , Protoporfirinas/efeitos da radiação , Radiossensibilizantes/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Terapia por Raios X/métodos , Raios X
11.
Anticancer Res ; 40(3): 1503-1512, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132050

RESUMO

AIM: We examined whether the perioperative systemic inflammation score (SIS), which describes systemic inflammation and/or malnutrition, affected the tumor recurrence and survival in advanced gastric cancer patients. PATIENTS AND METHODS: The study retrospectively analyzed 160 patients with stage II/III gastric cancer who underwent curative resection at the Kanagawa Cancer Center. The SIS was evaluated before surgery, one week after surgery and one month after surgery, as determined by the serum albumin level (cut-off value=4.0 g/dl) and lymphocyte-to-monocyte ratio (cut-off value=4.44). RESULTS: A high SIS at one month after surgery was identified as an independent predictor for overall survival [hazard ratio (HR)=2.143, p=0.020] and showed a marginal significance for the relapse-free survival (HR=1.814, p=0.053) in multivariate analyses. CONCLUSION: The SIS at one month after surgery is a useful biomarker for predicting the long-term outcome in patients with advanced gastric cancer.


Assuntos
Inflamação/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Quimioterapia Adjuvante , Humanos , Inflamação/sangue , Linfócitos/patologia , Pessoa de Meia-Idade , Monócitos/patologia , Estadiamento de Neoplasias , Oxaloacetatos/administração & dosagem , Período Perioperatório , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Análise de Sobrevida , Adulto Jovem
12.
World J Surg ; 44(4): 1209-1215, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31953612

RESUMO

BACKGROUND: Surgery for gastric cancer should be performed as soon as possible after diagnosis. However, sometimes the waiting time for surgery tends to be longer. The relation between the waiting time for surgery and survival in patients with gastric cancer remains to be fully investigated. METHODS: This retrospective, single-center cohort study evaluated patients with gastric cancer who underwent curative surgery from 2006 through 2012 at Kanagawa Cancer Center in Japan. Patients who received neoadjuvant chemotherapy were excluded. The waiting time for surgery was defined as the time between the first visit and surgery. We investigated whether the waiting time for surgery has a linear negative impact on outcomes by using a Cox regression model with clinical prognostic factors. RESULTS: In total, 801 patients were eligible. The median waiting time was 45 days (range 10-269 days). The restricted cubic spline regression curve showed that the adjusted time-specific hazard ratios of waiting times did not indicate a linear negative trend on survival between 20 and 100 days (p = 0.759). In the Cox model with a quartile of waiting times, waiting times in the 32-44-day group, 43-62-day group, and ≥63 day groups were not associated with poorer overall survival as compared with the ≤31 day group (HR: 1.01, 95% CI 0.63-1.60, p = 0.984, HR: 1.17, 95% CI 0.70-1.94, p = 0.550, HR: 1.06, 95% CI 0.60-1.88, p = 0.831, respectively). CONCLUSIONS: There was no negative relation between the waiting time for surgery (within 100 days) and survival in patients with gastric cancer.


Assuntos
Neoplasias Gástricas/cirurgia , Adenocarcinoma/cirurgia , Idoso , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Fatores de Tempo , Listas de Espera
13.
Surg Endosc ; 34(1): 429-435, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30969360

RESUMO

BACKGROUND: Laparoscopic gastrectomy is becoming more commonly performed, but acquisition of its technique remains challenging. We investigated whether laparoscopy-assisted distal gastrectomy (LDG) performed by trainees (TR) supervised by a technically qualified experienced surgeon (QS) is feasible and safe. METHODS: The short-term outcomes of LDG were assessed in patients with gastric cancer between 2008 and 2018. We compared patients who underwent LDG performed by qualified experienced surgeons (QS group) with patients who underwent LDG performed by the trainees (TR group). RESULTS: The operation time was longer in the TR group than in the QS group (median time: 270 min vs. 239 min, p < 0.001). The median duration of the postoperative hospital stay was 9 days in the QS group and 8 days in the TR group (p = 0.003). The incidence of postoperative complications did not differ significantly between the two groups. Grade 2 or higher postoperative complications occurred in 18 patients (12.9%) in the QS group and 47 patients (11.7%) in the TR group (p = 0.763). Grade 3 or higher postoperative complications occurred in 9 patients (6.4%) in the QS group and 17 patients (4.2%) in the TR group (p = 0.357). Multivariate analysis showed that the American Society of Anesthesiologist Physical Status was an independent predictor of grade 2 or higher postoperative complications and that gender was an independent predictor of grade 3 or higher postoperative complications. The main operator (TR/QS) was not an independent predictor of complications. CONCLUSIONS: Laparoscopy-assisted distal gastrectomy performed by trainees supervised by an experienced surgeon is a feasible and safe procedure similar to that performed by experienced surgeons.


Assuntos
Competência Clínica , Gastrectomia/métodos , Laparoscopia , Cirurgiões , Adulto , Idoso , Estudos de Viabilidade , Feminino , Gastrectomia/educação , Humanos , Japão , Laparoscopia/educação , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores Sexuais , Neoplasias Gástricas/cirurgia
14.
Asian J Endosc Surg ; 13(2): 238-241, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31297969

RESUMO

INTRODUCTION: We propose a novel technique to close Petersen's defect using barbed sutures and evaluate the safety and usefulness of this technique by assessing postoperative complications and measuring the time required to close Petersen's defect. MATERIALS AND SURGICAL TECHNIQUE: Petersen's defect was closed laparoscopically with running non-absorbable barbed sutures (V-loc®) after a nodal dissection and reconstruction procedure. First, the transverse colon was elevated cranially, making the dorsal side of the transverse mesocolon a flattened surface. The intersection of the transverse mesocolon and Roux limb mesentery was then identified, and closure was started from this point. We continued to sew the transverse mesocolon and Roux limb mesentery toward the transverse colon with a running suture. At the end of suturing, we placed one or two stitches in the fatty appendices of the transverse colon and cut the free tail of thread as short as possible. DISCUSSION: We investigated postoperative complications and measured the time required to close Petersen's defect in 64 patients who underwent this technique. The results showed that this closure technique could be performed promptly and safely regardless of the patient, surgical procedure, and the experience of the operator.


Assuntos
Gastrectomia/efeitos adversos , Hérnia Interna/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Neoplasias Gástricas/cirurgia , Técnicas de Sutura , Suturas , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose em-Y de Roux , Feminino , Humanos , Hérnia Interna/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Neoplasias Gástricas/patologia
15.
Int J Clin Oncol ; 25(4): 584-594, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31865480

RESUMO

INTRODUCTION: We retrospectively evaluated the blood coagulation activity using the D-dimer level in the early period after gastrectomy and investigated whether postoperative hypercoagulation affects tumor recurrence and long-term survival in gastric cancer patients. METHODS: The study involved 650 patients who underwent curative resection for gastric cancer at Kanagawa Cancer Center between July 2009 and July 2013. They were divided into a low-D-dimer group (LD group) and high-D-dimer group (HD group) according to the median D-dimer level on postoperative day (POD) 7. The risk factors for overall survival (OS) and relapse-free survival (RFS) were identified. RESULTS: Of the 448 enrolled patients, 218 were classified into the LD group and 230 into the HD group. The 5-year OS rates after surgery were 90.8% and 81.3% in the LD and HD groups, respectively (p < 0.001). The 5-year RFS rates after surgery were 89.9% and 76.1% in the LD and HD groups, respectively (p < 0.001). A high D-dimer level on POD 7 (≥ 4.9 µg/ml) was identified as an independent predictive factor for both the OS (hazard ratio [HR] 1.955, 95% confidence interval [CI] 1.158-3.303, p = 0.012) and RFS (HR 2.182, 95% CI 1.327-3.589, p = 0.002). Furthermore, hematological recurrence was significantly more frequent in the HD group than in the LD group (p = 0.014). CONCLUSION: A high D-dimer level on POD 7 may predict tumor recurrence and the long-term survival in patients who undergo gastrectomy for locally advanced gastric cancer. Patients with an elevated postoperative D-dimer level need careful observation and diagnostic imaging to timely detect tumor recurrence.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Gastrectomia/métodos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Período Pós-Operatório , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Taxa de Sobrevida
16.
Int J Mol Sci ; 20(20)2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31627442

RESUMO

Melanoma is a highly aggressive cancer with a propensity for brain metastases. These can be treated by radiotherapy, but the radiation-resistant nature of melanoma makes the prognosis for melanoma patients with brain metastases poor. Previously, we demonstrated that treatment of mice with subcutaneous melanoma with 5-aminolevurinic acid (5-ALA) and X-rays in combination, ("radiodynamic therapy (RDT)"), instead of with 5-ALA and laser beams ("photodynamic therapy"), improved tumor suppression in vivo. Here, using the B16-Luc melanoma brain metastasis model, we demonstrate that 5-ALA RDT effectively treats brain metastasis. We also studied how 5-ALA RDT damages cells in vitro using a B16 melanoma culture. Cell culture preincubated with 5-ALA alone increased intracellular photosensitizer protoporphyrin IX. On X-ray irradiation, the cells enhanced their ∙OH radical generation, which subsequently induced γH2AX, a marker of DNA double-strand breaks in their nuclei, but decreased mitochondrial membrane potential. After two days, the cell cycle was arrested. When 5-ALA RDT was applied to the brain melanoma metastasis model in vivo, suppression of tumor growth was indicated. Therapeutic efficacy in melanoma treatment has recently been improved by molecular targeted drugs and immune checkpoint inhibitors. Treatment with these drugs is now expected to be combined with 5-ALA RDT to further improve therapeutic efficacy.


Assuntos
Ácido Aminolevulínico/uso terapêutico , Neoplasias Encefálicas/secundário , Melanoma Experimental/patologia , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/radioterapia , Camundongos
17.
Gan To Kagaku Ryoho ; 46(13): 2264-2266, 2019 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-32156899

RESUMO

A 72-year-old man presented with right lower abdominal pain. Abdominal enhanced CT showed a large tumor in the ascending colon. Colonoscopyrevealed a type 2 tumor infiltrating three-quarters of the ascending colon. The biopsyspecimen showed a malignant lymphoma. Thus, the patient underwent ileocecal resection with D3 lymph node dissection. The histopathological diagnosis was primarydiffuse large B-cell lymphoma of the ascending colon. Post-operative PET-CT showed disseminated extra-nodal involvement, Stage Ⅳ(Lugano staging system). He was administered 2 courses of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy. However, the patient was diagnosed with progressive disease. He received several chemotherapies and finallydied 8 months after surgery. We report our present case and literature review.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colo Ascendente , Neoplasias do Colo , Linfoma Difuso de Grandes Células B , Idoso , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/tratamento farmacológico , Ciclofosfamida , Doxorrubicina , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prednisona , Rituximab , Vincristina
18.
Gan To Kagaku Ryoho ; 45(13): 2018-2020, 2018 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-30692430

RESUMO

We report a rare case of liver recurrence of gastric cancer 14 years and 3 months after curative gastrectomy. An 81-yearold man underwent total gastrectomy, D2 lymphadenectomy, Roux-en-Y reconstruction, and cholecystectomy for advanced gastric cancer in November 2002. H e was diagnosed pathologically with M, Type 5, 53×42 mm, tub2>tub1, pT4a, ly2, v2, pN1, pPM0, pDM0, M0, pStage ⅢA(JGCA 15th). Postoperative adjuvant therapy was not administered. He was followed up for 5 years after surgery without adjuvant therapy, and he did not exhibit recurrence. In February 2017, he experienced difficulties in swallowing and visited our hospital. Abdominal contrast-enhanced CT showed an 8×5 cm liver tumor in the lateral segment. Part of the tumor protruded to outside of the liver, and the tumor invaded and pushed the jejunum in the Roux limb. We performed liver biopsy and diagnosed him with liver metastasis of recurrent gastric cancer. Late relapse after gastrectomy, especially after 10 years or more, is very rare.


Assuntos
Neoplasias Hepáticas , Neoplasias Gástricas , Idoso de 80 Anos ou mais , Anastomose em-Y de Roux , Gastrectomia , Humanos , Neoplasias Hepáticas/secundário , Masculino , Recidiva Local de Neoplasia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Fatores de Tempo
19.
Gan To Kagaku Ryoho ; 45(13): 2297-2299, 2018 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-30692443

RESUMO

We report a case of mediastinal lymph node recurrence of esophageal cancer after endoscopic submucosal dissection (ESD). We first administered chemotherapy and then performed esophagectomy. A 78-year-old man underwent ESD for early esophageal cancer at a different hospital in January 2015. H e was diagnosed pathologically with scc, pSM1, pHM1, pVM0, ly0, v0. Additional treatment was not administered because of his age. In June 2017, chest enhanced CT showed swollen mediastinal lymph nodes. This was diagnosed as a recurrence of esophageal cancer, and he presented at our hospital. We first performed chemotherapy for that lesion, because the swollen lymph node was large and may have invaded the surrounding organs. We then performed esophagectomy.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Metástase Linfática , Idoso , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Excisão de Linfonodo , Linfonodos , Masculino , Recidiva Local de Neoplasia
20.
Gan To Kagaku Ryoho ; 45(13): 2291-2293, 2018 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-30692441

RESUMO

An 81-year-old man with esophageal cancer had undergone subtotal thoracic esophagectomy and retrosternal reconstruction using a gastric tube. He developed anemia. Gastrointestinal endoscopy was performed, which revealed a tumor in the posterior wall of the lower part of the gastric tube. Biopsy revealed well-differentiated adenocarcinoma. There was no lymph node metastasis and no distal metastasis on CT. We performed partial resection of the stomach tube because of his age and physical condition. We identified the position of the tumor by upper gastrointestinal series CT and gastrointestinal endoscopy. The tumor was located on the posterior wall of the lower part of the gastric tube and the back of the sternum lower border. Marking was performed by gastrointestinal endoscopy before operation. We simulated the operation and decided to perform laparostomy without sternotomy incision. We cut the anterior wall of the gastric tube in front of the tumor using the endoscope. We could then confirm the diagnosis of cancer, and clipped and removed the tumor from the posterior wall. The resected site was sutured with 4-0 absorbable thread. The pathological diagnosis was T1a(M)N0M0, ly0, v0, PM0, DM0, pStage ⅠA.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Adenocarcinoma/cirurgia , Idoso de 80 Anos ou mais , Endoscópios Gastrointestinais , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Masculino , Neoplasias Gástricas/cirurgia
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