Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 472
Filtrar
2.
J Gynecol Oncol ; 30(6): e103, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31576694

RESUMO

OBJECTIVE: We conducted a retrospective, multi-institutional, collaborative study to accumulate cases of neuroendocrine carcinoma of the endometrium, to clarify its clinicopathologic features, treatment, prognosis and prognostic factors to collate findings to establish future individualized treatment regimens. To our knowledge, this is the largest case study and the first study to statistically analyze the prognosis of this disease. METHODS: At medical institutions participating in the Kansai Clinical Oncology Group/Intergroup, cases diagnosed at a central pathologic review as neuroendocrine carcinoma of the endometrium between 1995 and 2014 were enrolled. We retrospectively analyzed the clinicopathologic features, treatment, prognosis and prognostic factors of this disease. RESULTS: A total of 65 cases were registered from 18 medical institutions in Japan. Of these, 42 (64.6%) cases were diagnosed as neuroendocrine carcinoma of the endometrium based on the central pathological review and thus included in the study. Advanced International Federation of Gynecology and Obstetrics stages (stage III and IV) and pure type small cell neuroendocrine carcinoma cases had a significantly worse prognosis. Upon multivariate analysis, only histologic subtypes and surgery were significant prognostic factors. Pure type cases had a significantly worse prognosis compared to mixed type cases and complete surgery cases had a significantly better prognosis compared to cases with no or incomplete surgery. CONCLUSION: Our findings suggest that complete surgery improves the prognosis of neuroendocrine carcinoma of the endometrium. Even among cases with advanced disease stages, if complete surgery is expected to be achieved, clinicians should consider curative surgery to improve the prognosis of neuroendocrine carcinoma of the endometrium.

3.
Gan To Kagaku Ryoho ; 46(9): 1367-1371, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31530772

RESUMO

Recent advances in cancer immunotherapies, such as immune checkpoint inhibitors(ICIs), have shown some durable clinical responses in patients with various types of advanced cancers. The development of the next-generation sequencing technologies can result in a comprehensive characterization of the human cancer genomes. Personalized immunotherapy and precision cancer medicine might enable the next generation of rational cancer immunotherapy. Conventional cancer vaccines are designed to target tumor-associated antigens(TAAs), which are overexpressed in cancers. However, since TAAs are also expressed in normal tissues, cancer vaccine against TAAs can potentially initiate central and peripheral tolerance responses, which results in low vaccination efficiency. Cancer neoantigens derived from somatic mutations in tumor tissue represent highly immunogenic and can escape from central thymic tolerance. They are suggested to provide tumor specific targets for personalized cancer vaccines. Therefore, neoantigen-based cancer vaccine, which can induce tumor-specific cytotoxic T lymphocytes( CTLs), should be developed. The efficacy of current immunotherapies also remains limited due to the immunosuppressive tumor microenvironment, which leads to CTLs exhaustion or anergy and the escape of tumor cells from immune attack. The combination of neoantigen-based cancer vaccine and ICIs should be a potential therapeutic approach. In this paper, we provide a brief overview of the recent advances in the development of neoantigen-based cancer vaccines.


Assuntos
Vacinas Anticâncer , Neoplasias , Antígenos de Neoplasias , Humanos , Imunoterapia , Medicina de Precisão , Microambiente Tumoral
4.
Br J Cancer ; 121(8): 659-665, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31488881

RESUMO

BACKGROUND: CD3 + and CD8 + T-cell infiltration were reported as positive predictive markers of survival in colorectal cancer (CRC) patients. Here, we demonstrate the prognostic significance of CD4 + and FOXP3 + T-cell densities in CRC. METHODS: We quantified the intratumoural densities of CD3 + , CD8 + , CD4 + and FOXP3 + T cells by immunohistochemistry and digital pathology in 342 CRC patients who underwent curative resection. Microsatellite instability was also assessed in 322 specimens. Patient demographics, clinicopathological features and survival rates were analysed. RESULTS: High CD3 + , CD4 + and FOXP3 + T-cell densities were associated with improved relapse-free survival (RFS); high CD8 + , CD4 + and FOXP3 + T-cell densities were associated with improved disease-specific survival (DSS). Patients with low CD4 + and low FOXP3 + T-cell densities exhibited extremely poor prognoses. T stage, vascular/lymphatic invasion and CD4 + T-cell density were independent prognostic indicators for DSS. The distributions of CD4 + and FOXP3 + T-cell densities were not significantly different between the high microsatellite instability group and other groups, in contrast to those of CD3 + and CD8 + T-cell densities. CONCLUSIONS: Intratumoural CD4 + T-cell density and combined CD4 + and FOXP3 + T-cell densities were stronger prognostic indicators than other clinicopathological features. These results may facilitate the establishment of novel prognostic factors and therapeutic strategies for CRC.

5.
Ann Surg Oncol ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31440928

RESUMO

BACKGROUND: Neoadjuvant therapy reportedly shows only marginal clinical benefit in pancreatic ductal adenocarcinoma (PDAC), especially in resectable cases. However, with more effective regimens, neoadjuvant therapy may become a standard of care for resectable cases. A prospective, open-label, multicenter phases 1 and 2 trial of neoadjuvant therapy was conducted using full-dose gemcitabine and S-1 concurrently with 50.4 Gy of radiation therapy (GSRT) for resectable PDAC. This report describes the phase 2 results. METHODS: The phase 2 part of this study enrolled 57 patients with cytologically or histologically proven PDAC deemed resectable based on imaging before neoadjuvant therapy. These patients received GSRT. After reevaluation by computed tomography scan, surgical exploration was performed, followed by adjuvant therapy. According to the prescribed protocol of the clinical trial, statistical analyses included 57 phase 2 patients and 6 phase 1 patients who received the same dosage as in phase 2. RESULTS: This trial enrolled 63 patients (42 men and 21 women) with a median age of 70 years. Leukopenia or neutropenia of grade 3 or higher occurred for 79% of the patients, but no other severe adverse events were observed. Among the 63 patients, 54 underwent surgical resection. Intention-to-treat analysis of the 63 patients showed an excellent median survival time lasting as long as 55.3 months. The patients who completed neoadjuvant therapy, surgery, and adjuvant therapy had a 5-year survival rate of 56.6%. CONCLUSIONS: This regimen showed outstanding clinical efficacy with acceptable tolerability for patients with resectable PDAC.

6.
J Immunother ; 42(7): 244-250, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31398179

RESUMO

We previously found that heat-shock protein 70 (HSP70) is expressed on hepatocellular carcinoma cells and developed an HSP70 mRNA-transfected dendritic cell therapy for treating unresectable or recurrent hepatocellular carcinoma. The phase I trial was completed successfully. The purpose of this study is to identify a promiscuous epitope peptide derived from HSP70 for the purpose of developing a novel cancer peptide vaccine. Using a computational algorithm to analyze the specificity of previously reported major histocompatibility complex class I-binding peptides, we selected candidates that bound to >2 of the 3 HLA types. Twenty-nine HSP70-derived peptides (9-mers) that bound to HLA-class I was selected. The peptides were prioritized based on the results of peptide binding experiments. Using dendritic cells stimulated with the candidate peptide described previously as stimulators and CD8 T cells as effectors, an ELISPOT assay was performed. Cytotoxicity of CD8 lymphocytes stimulated with the candidate peptides toward HSP70-expressing cancer cells was analyzed using an xCELLigence System. Peptides were administered to HLA-A 24 transgenic mice as vaccines, and peptide-specific T-cell induction was measured in vivo. We identified a multi-HLA-class I-binding epitope peptide that bound to HLA-A*02:01, *02:06, and *24:02 in vitro using an interferon-γ ELISPOT immune response induction assay. Cytotoxicity was confirmed in vitro, and safety and immune response induction were confirmed in vivo using HLA-A 24 transgenic mice. Our study demonstrated that the promiscuous HSP70-derived peptide is applicable to cancer immunotherapy in patients with HLA-A*24:02-positive, *02:01-positive, and *02:06-positive HSP70-expressing cancers.

7.
Cancer Sci ; 110(10): 3079-3088, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432594

RESUMO

Chimeric antigen receptor-engineered T (CAR-T)-cell therapy holds significant promise for the treatment of hematological malignancies, especially for B-cell leukemia and lymphoma. However, its efficacy against non-hematological malignancies has been limited as a result of several biological problems characteristic of the tumor microenvironment of solid tumors. One of the main hurdles is the heterogeneous nature of tumor-associated antigens (TAA) expressed in solid tumors. Another hurdle is the inefficient activation and limited persistence of CAR-T cells, mainly as a result of T-cell exhaustion caused by immunosuppressive factors in the tumor microenvironment. In the present study, to address these problems, we engineered CAR-T cells to produce antagonistic anti-programmed cell death protein 1 (PD-1) single-chain variable fragment (scFv), by which PD-1-dependent inhibitory signals in CAR-T cells and adjacent tumor-specific non-CAR-T cells are attenuated. In mouse solid tumor models, PD-1 scFv-producing CAR-T cells induced potent therapeutic effects superior to those of conventional CAR-T cells, along with a significant reduction of apoptotic cell death not only in CAR-T cells themselves but also in TAA-specific T cells in the tumor tissue. In addition, the treatment with anti-PD-1 scFv-producing CAR-T cells resulted in an increased concentration of PD-1 scFv in tumor tissue but not in sera, suggesting an induction of less severe systemic immune-related adverse events. Hence, the present study developed anti-PD-1 scFv-producing CAR-T cell technology and explored its cellular mechanisms underlying potent antitumor efficacy.


Assuntos
Imunoterapia Adotiva/métodos , Neoplasias/terapia , Receptor de Morte Celular Programada 1/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Anticorpos de Cadeia Única/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Técnicas de Cocultura , Masculino , Camundongos , Neoplasias/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Hepatol Res ; 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31336394

RESUMO

The fourth version of Clinical Practice Guidelines for Hepatocellular Carcinoma was revised by the Japan Society of Hepatology, according to the methodology of evidence-based medicine and partly to the Grading of Recommendations Assessment, Development, and Evaluation system, which was published in October 2017 in Japanese. New or revised recommendations were described, herein, with a special reference to the surveillance, diagnostic, and treatment algorithms.

9.
Cancer Sci ; 110(9): 2973-2981, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31293054

RESUMO

Every year, approximately 1.2 million cases of colorectal carcinoma (CRC) are newly diagnosed worldwide. Although metastases to distant organs are often fatal complications of CRC, little information is known as to how such metastatic lesions are formed. To reveal the genetic profiles for CRC metastasis, we conducted whole-exome RNA sequencing on CRC tumors with liver metastasis (LM) (group A, n = 12) and clinical stage-matched larger tumors without LM (group B, n = 16). While the somatic mutation profiles were similar among the primary tumors and LM lesions in group A and the tumors in group B, the A-to-C nucleotide change in the context of "AAG" was only enriched in the LM regions in group A, suggesting the presence of a DNA damage process specific to metastasis. Genes already known to be associated with CRC were mutated in all groups at a similar frequency, but we detected somatic nonsynonymous mutations in a total of 707 genes in the LM regions, but not in the tumors without LM. Signaling pathways linked to such "LM-associated" genes were overrepresented for extracellular matrix-receptor interaction or focal adhesion. Further, fusions of the ADAP1 (ArfGAP with dual PH domain 1) were newly identified in our cohort (3 out of 28 patients), which activated ARF6, an ADAP1-substrate. Infrequently, mutated genes may play an important role in metastasis formation of CRC. Additionally, recurrent ADAP1 fusion genes were unexpectedly discovered. As these fusions activate small GTPase, further experiments are warranted to examine their contribution to CRC carcinogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais/genética , Fusão Gênica , Neoplasias Hepáticas/genética , Proteínas do Tecido Nervoso/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/genética , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , Feminino , Perfilação da Expressão Gênica , Células HEK293 , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Sequenciamento Completo do Exoma
10.
Gan To Kagaku Ryoho ; 46(4): 760-762, 2019 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-31164527

RESUMO

We have performed a combination therapy of hepatic arterial infusion chemotherapy(HAIC), radiation therapy(RT), and surgical resection for the treatment of hepatocellular carcinoma(HCC)with portal vein tumor thrombosis(PVTT)since 2013. We retrospectively analyzed 36 patients with HCC with PVTT who underwent hepatectomy between 1995 and 2016 to evaluate the clinical outcomes. Ten patients received preoperative HAIC, 7 underwent RT, and 14 received postoperative HAIC. The median survival time(MST)was 19.3 months, and the MST was significantly longer in the patients who underwent curative resection than those in patients who did not. In the non-curative resection group, postoperative HAIC prolonged the survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Veia Porta , Estudos Retrospectivos , Trombose , Resultado do Tratamento
11.
Gan To Kagaku Ryoho ; 46(4): 808-810, 2019 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-31164543

RESUMO

A questionnaire survey was conducted on the administration of secondary chemotherapy for unresectable or recurrent gastric cancer by 43 doctors involved in gastric cancer treatment in the Yamaguchi prefecture. Seventy-one percent of doctors replied that the secondary chemotherapy transfer rate was more than 60%, and 29% of doctors replied that the secondary chemotherapy transfer rate was less than 60%. The reasons why patients could not be transferred to secondary chemotherapy included inferior performance status, poor general condition, and elderly age, among others. Weekly paclitaxel plus ramucirumab therapy was used as the major regimen of secondary chemotherapy by 95% of doctors. In addition, 93% of doctors indicated that weekly nab-paclitaxel would be an option for gastric cancer secondary chemotherapy. Secondary chemotherapy for gastric cancer in the Yamaguchi prefecture has a standard regimen selection according to guidelines.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Recidiva Local de Neoplasia , Paclitaxel/uso terapêutico , Padrões de Prática Médica , Neoplasias Gástricas/tratamento farmacológico , Inquéritos e Questionários
12.
J Vasc Surg Venous Lymphat Disord ; 7(4): 562-569, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31203860

RESUMO

OBJECTIVE: This study aimed to clarify the variations in indices derived from noninvasive assessments for the early detection of postmastectomy lymphedema (LE) from 1 month preoperatively until 2 years postoperatively. METHODS: In total, 120 patients who underwent surgery for breast cancer in our institution were prospectively followed up with a questionnaire for arm swelling as well as with tape measurements, bioimpedance analysis (BIA), and skin and subcutaneous tissue ultrasound at 1 month before and 3, 6, 12, 18, and 24 months after surgery. RESULTS: Ninety-seven patients completed the study. Among 93 patients who did not present with LE, 9% complained of arm swelling even before surgery, and the incidence peaked at 17% at 6 months after surgery. There were no differences in the circumferences of the upper arm, forearm, and hand between sides throughout the study period. However, the postoperative circumference values of the upper arm only on the operation side were slightly increased compared with the preoperative values. The mean excess fluid in the arm on the operation side compared with the contralateral side, as assessed by BIA, was nearly zero throughout the study period. There were no differences in subcutaneous echogenicity or skin and subcutaneous thicknesses between the sides throughout the study period. However, time-dependent increases in subcutaneous thicknesses were noticed on both sides. Four patients (4.1%) developed LE. In three of these patients, abnormality in the BIA was recorded 6 to 12 months before presentation. Immediately after presentation, the common findings included BIA abnormality and increased subcutaneous echogenicity and skin thickness in the medial forearm. CONCLUSIONS: In this study, a complaint of arm swelling was not sensitive enough for detection of the early onset of LE because a certain number of patients constantly complained of this symptom. Measurements of circumference might help in the diagnosis of LE onset, but this method is not specific enough because these measurements are also affected by various factors. However, BIA and skin and subcutaneous ultrasound were identified as potential tools for the early detection of LE.

13.
Dig Surg ; : 1-6, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185468

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is one of the critical complications that can occur after surgery. A positive association between cancer and VTE risk is well established; however, the safety and efficacy of VTE prophylaxis have not been established in hepatobiliary-pancreatic surgery, especially in surgery for malignancies. METHODS: A prospective, multi-center Phase I study to determine the safety of enoxaparin was performed. Subcutaneous injection of enoxaparin was initiated 48-72 h after surgery and repeated for 8 days. The primary endpoint was the incidence of bleeding events. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000007761). RESULTS: A total of 154 patients was registered and 133 patients including 74 hepatectomies and 35 pancreaticoduodenectomies were analyzed. Three patients (2.3%) exhibited major bleeding events postoperatively, while 7 (5.2%) had minor bleeding. No Symptomatic VTE was observed. CONCLUSIONS: Our study indicated that enoxaparin was well tolerated and safe for patients who received hepatobiliary-pancreatic surgery for malignancies.

14.
PLoS One ; 14(6): e0218780, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31237900

RESUMO

BACKGROUND: The clinical component of medical education for students and resident doctors in Japan occurs almost entirely in the hospital setting. Because of this inpatient focus, graduate medical education clinical training often fails to expose physicians-in-training to the challenges that patients may face in the outpatient or home setting. This is a descriptive study in which we explore what participating students and resident doctors learned through our brief home-based teaching experience. METHODS: From June 2016 to December 2017, attending physicians on the internal medicine service had medical students and resident doctors accompany them on home care visits. Participants were selected by convenience sampling based on their rotation availability. After the home visit and the interactive discussion, the participants were expected to prepare a reflective journal on their experience and learning. Thematic analysis was applied, and key themes were developed based on Kolb's ELT (Experiential learning theory). Three months after completion of the experience, semi-structured interviews were individually conducted assessing participants' self-perceived changes. RESULTS: Thirty-two medical students(10) or residents(22)participated in a home visit. Thirty of these learners were able to complete a reflective journal. Using thematic analysis, we identified 2 domains and 6 key themes from the participants' perceptions. Participants recognized the importance of patient-centered care, inter-professional collaboration of the home care team, and reconceptualized the meaning of medical practice and their professional identity as a doctor. Three month post-experience interviews were completed on 12 of the original 30 participants who completed the reflective journal. 2 domains and 6 key themes from the residents' experiences and perceptions were generated. The participants reported an increased attention to the daily lives and social situations of their hospitalized patients, and an extension of their focus beyond the clinical medical treatment of the patient. CONCLUSION: The experience of a brief visit to a patient's home is a novel educational approach that may potentially provide medical students and resident doctors with opportunities to learn about out-of-hospital, patient-centered, home-based medical care.

15.
Int J Clin Oncol ; 24(10): 1223-1230, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31144145

RESUMO

BACKGROUND: Triweekly capecitabine plus irinotecan (CAPIRI) was not a replacement for fluorouracil, leucovorin, and irinotecan (FOLFIRI) in the treatment of metastatic colorectal cancer (mCRC) because of the potential for greater toxicity. Recently, it has reported that mCAPIRI is well tolerated and non-inferior to FOLFIRI. In this study, we conducted a multicenter phase II trial to assess the efficacy and safety of biweekly CAPIRI plus bevacizumab as second-line chemotherapy for mCRC with reduced toxicity and preserved efficacy. METHODS: Patients with mCRC who had received prior chemotherapy, including oxaliplatin-based regimens, were eligible for this study. The treatment protocol administered capecitabine at 1000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan at 150 mg/m2 on day 1, and bevacizumab at 10 mg/kg on day 1 every 2 weeks. Primary endpoints for this study were progression-free survival (PFS) and safety. Secondary endpoints were overall survival (OS), time to treatment failure, response rate (RR), and disease control rate (DCR). RESULTS: Fifty-one patients were enrolled in this study. Median PFS was 5.5 months [95% confidence interval (CI) 4.23-7.40 months], and median OS was 13.5 months (95% CI 11.57-20.23 months). The RR was 14.6% (95% CI 6.5-28.4%), and the DCR was 66.7% (95% CI 51.5-79.2%). Hypertension was the most common Grade 3 adverse event (27.5%), followed by neutropenia (17.6%). Only two patients suffered from grade 3 hand-foot syndrome. CONCLUSIONS: In mCRC patients, biweekly CAPIRI + bevacizumab appears effective and feasible as a second-line chemotherapy with relatively low toxicities, and has potential as a useful substitute for FOLFIRI + bevacizumab.

16.
Clin Transplant ; 33(6): e13584, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31074181

RESUMO

AIMS: This study examined the long-term quality of life (QOL) of living liver donors (LLDs) in Japan using both generic and LLD-specific instruments. METHODS: The sample comprised 374 LLDs from five university hospitals in Japan who underwent surgery more than a year previously. QOL was evaluated using the Short Form-36 health survey (SF-36) and LLD-QOL scale. RESULTS: SF-36 results indicated that the overall long-term QOL of LLDs was significantly better than the Japanese standard. When comparing by donor factors, LLDs whose recipients were children scored higher for "satisfaction" than those whose recipients were adults on the LLD-QOL scale. LLDs with complications had lower QOL for "scars" and "burden" on the LLD-QOL scale but no differences in SF-36 scores. LLDs with longer hospital stay had lower physical QOL on SF-36 and lower QOL for "scars" and "after-effects" on the LLD-QOL scale. LLDs whose recipients have died showed lower mental QOL on SF-36 and lower "satisfaction" and greater "lack of understanding of donor health" on the LLD-QOL scale. CONCLUSIONS: Our multicenter study clarified the long-term QOL of LLDs and suggested that donors' QOL was related to the donors' and recipients' ages, donor's complications and hospital stay length, and recipient's prognosis.

17.
Trials ; 20(1): 242, 2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31029154

RESUMO

BACKGROUND: Pancreatic cancer is a refractory malignancy, and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms' tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy. METHODS: This is an investigator-initiated, double-blind, comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines. DISCUSSION: Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety, as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000027179 . Registered on 9 April 2017.

18.
Gan To Kagaku Ryoho ; 46(2): 324-326, 2019 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-30914548

RESUMO

Case 1: A 64-year-old man with a chiefcomplaint ofbloody stools was seen in our hospital. He underwent an extended right lobe resection for hilar cholangiocarcinoma 3 years ago and was in the middle of chemotherapy for multiple metastases. Case 2: A 69-year-old man with a chiefcomplaint ofbloody emesis and stools was seen. He underwent left hepatic trisegmentectomy for hilar cholangiocarcinoma and ligation of the right portal vein for postoperative portal venous thrombus 6 months ago. After careful examination, the patients in both cases were diagnosed with bleeding of the jejunal varices formed at the site ofhepaticojejunostomy. The patient in Case 1 underwent percutaneous transhepatic obliteration ofvarices and the patient in Case 2 underwent transileocolic vein obliteration ofvarices. After hepatobiliary pancreatic surgery with biliary tract reconstruction, we should be aware of ectopic varices during differential diagnosis of gastrointestinal bleeding.


Assuntos
Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma , Tumor de Klatskin , Varizes , Idoso , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/complicações , Colangiocarcinoma/cirurgia , Humanos , Tumor de Klatskin/complicações , Tumor de Klatskin/cirurgia , Masculino , Pessoa de Meia-Idade , Ruptura/etiologia , Varizes/patologia
19.
Gan To Kagaku Ryoho ; 46(3): 526-528, 2019 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-30914603

RESUMO

A 65-year-old woman with cecum cancer underwent laparoscopic right colectomy.After 3 years, she was diagnosed with a local recurrence with small bowel invasion and underwent tumor resection.One year later, she had a re-recurrent lesion involving her right iliac bone.After one year of chemotherapy, a PET-CT showed no other abdominal lesions suggestive of malignancy.She underwent resection of the re-recurrent tumor involving the right iliac bone and R0 resection was achieved. She was able to ambulate postoperatively and returned home.In selected cases, extended surgery including bone resection can be an option for the local recurrence of advanced colon cancer.


Assuntos
Neoplasias do Colo , Ílio , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Colectomia , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Ílio/patologia , Recidiva Local de Neoplasia
20.
Gan To Kagaku Ryoho ; 46(3): 543-545, 2019 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-30914608

RESUMO

A 77-year-old man underwent a follow-up examination after distal gastrectomy. Contrast-enhanced computed tomography revealed a tumor of the pancreatic body and tail that contacted the common hepatic artery/celiac artery. Subsequently, the tumor was diagnosed as a borderline resectable pancreatic cancer. After chemoradiation therapy, the tumor was considered resectable. Preoperative angiography with intraoperative contrast-enhanced ultrasonography and indocyanine green fluorescence imaging confirmed blood flow in the residual stomach. Postoperatively, ischemic necrosis of the residual stomach was not observed. After distal gastrectomy, distal pancreatectomy with en bloc celiac axis resection was performed to safely and curatively address the cancer of the pancreatic body and tail.


Assuntos
Artéria Celíaca , Gastrectomia , Pancreatectomia , Neoplasias Pancreáticas , Idoso , Quimiorradioterapia , Artéria Hepática , Humanos , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA