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Metastatic colorectal neuroendocrine carcinoma (NEC) is often treated using a chemotherapy protocol for small-cell lung cancer; however, the prognosis is extremely poor. A 55-year-old woman with BRAF V600E-mutated transverse colon NEC and liver metastases underwent colectomy followed by FOLFOXIRI plus bevacizumab. Consequently, the liver metastases markedly shrank. Owing to later worsening of the liver metastases, she received encorafenib and binimetinib plus cetuximab. Despite discontinuing binimetinib due to myalgia, she had a long-term response with a progression-free survival of 14 months and an overall survival of more than 27 months. A chemotherapy protocol for BRAF-mutated metastatic colorectal cancer may be a treatment option for BRAF V600E-mutated colorectal NEC.
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Sampling of bile juice during endoscopic retrograde cholangiopancreatography (ERCP) has potential benefit of being amenable to the identification of novel biomarkers in liquid biopsy. This study reports the results of a global investigation of exosomal microRNAs (miRNAs) in bile to identify potential biomarkers for biliary tract cancers (BTCs). Eighty-eight bile samples collected during ERCP (45 BTC and 43 noncancer control samples) were enrolled in this study. Eleven BTC samples and nine control samples were assigned as the discovery set. Exosomes in bile and serum samples were collected using a glass membrane column with size-controlled macroporous glass (MPG), and exosomal miRNA expression profiles were evaluated using comprehensive miRNA microarray analysis (3D-Gene). For validation, exosomal miRNA in the bile samples of 34 BTCs and 34 controls were comprehensively evaluated using 3D-Gene. In the discovery set, eight exosomal miRNAs in bile were identified as significant aberrant expression markers, while no miRNA with aberrant expression in serum was identified. In a comparison of the discovery and validation sets, miR-451a and miR-3619-3p were identified as reproducible upregulated markers, and the combination of the two bile miRNAs showed an excellent area under the curve (0.819) value for diagnosing BTCs. In addition, high miR-3619-3p expression in bile reflects poorer prognosis of BTCs (hazard ratio = 2.89). The MPG-extracted exosomal miRNAs in bile aspirated during ERCP provide a convenient new approach for diagnosing biliary diseases. Bile-derived miRNA analysis with miR-451a and miR-3619-3p represents a potentially valuable diagnostic strategy for identifying BTCs as well as a predictive indicator of BTC prognosis.
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Neoplasias do Sistema Biliar , Exossomos , MicroRNAs , Humanos , MicroRNAs/metabolismo , Prognóstico , Bile/metabolismo , Perfilação da Expressão Gênica/métodos , Biomarcadores Tumorais/genética , Neoplasias do Sistema Biliar/diagnóstico , Neoplasias do Sistema Biliar/genética , Biomarcadores , Exossomos/genética , Exossomos/metabolismoRESUMO
AIM: Minocycline hydrochloride (MINO) aspiration sclerotherapy (AS) has been widely used for treating hepatic cysts (HC). However, cyst recurrence remains problematic. Information on monoethanolamine oleate (EO) AS, another effective HC treatment, is currently limited. We investigated the efficacy of EO on ineffective MINO treatments, and the relationship between MINO AS and cyst fluid pH. METHODS: A total of 22 cases with symptomatic HC underwent AS with 500 mg of MINO from January 2016 to June 2021. Cyst fluid pH was measured before and after MINO injection. Cyst volume ratio (CVR, %) after 2 weeks was calculated as follows:cyst volume 2 weeks after MINO injection / pre-treatment cyst volume × 100. Treatment was completed if CVR after 2 weeks was ≤35% (MINO-group). For patients with CVR >35%, 2 g of EO was added (MINO/EO-group). Cyst volume ratio was measured every 12 months thereafter. RESULTS: There were no recurrence symptoms in any of the patients during follow-up. Of the 22 cases, 21 had CVR ≤20% after 12 months. The MINO/EO-group (n = 8) tended to have smaller CVRs after 12 months than the MINO-group (n = 14). Cyst volume ratio after 2 weeks was correlated to pH change (p = 0.012) and was larger in patients whose pH decreased by <1.5 (p = 0.015). All adverse events were mild, including in elderly patients. CONCLUSION: Adding EO is an effective and safe treatment for symptomatic HC when MINO AS alone is insufficient. Patients with pH decreases of <1.5 should be considered for additional EO treatment.
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OBJECTIVES: Nab -paclitaxel and gemcitabine (GnP) or FOLFIRINOX (a combination of leucovorin, fluorouracil, irinotecan, and oxaliplatin [FFX]) is currently recognized as the standard first-line regimen for unresectable pancreatic ductal adenocarcinoma (PDAC). Class III ß-tubulin (TUBB3) has the potential to predict resistance to taxane in various tumors; therefore, this study aimed to clarify whether TUBB3 is a predictive marker for GnP response. METHODS: We retrospectively reviewed 113 patients with PDAC who received GnP or FFX as first-line chemotherapy and examined immunohistochemically the TUBB3 expression in specimens obtained by endoscopic ultrasound-guided fine-needle aspiration. RESULTS: High TUBB3 expression was associated with a significantly lower disease control rate ( P = 0.017) and shorter progression-free survival (PFS) ( P = 0.019), and multivariate analysis revealed that TUBB3 expression was an independent variable for PFS in the GnP first-line group ( P = 0.045). In addition, in the FFX first-line group, TUBB3 expression was not correlated with PFS or overall survival (OS). In all 113 patients, TUBB3 expression was not also associated with OS. CONCLUSIONS: Class III ß-tubulin might be a predictive factor for the response of GnP, but not a prognostic factor for OS, helping the selection of an optimized first-line chemotherapy regimen for unresectable PDAC.
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Adenocarcinoma , Albuminas/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Flavonoides , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Tubulina (Proteína)/metabolismo , Gencitabina , Neoplasias PancreáticasRESUMO
The Japanese guidelines for the treatment of gastric cancer recommend nivolumab as third-line chemotherapy for metastatic gastric cancer. We report a case of gastric cancer exhibiting a durable response after the discontinuation of nivolumab due to the early onset of immune-related adverse event (irAE). A 64-year-old man with advanced HER2-positive gastric cancer and distant lymph node metastasis received nivolumab as fourth-line therapy. After two courses of nivolumab, the lymph nodes showed progression. However, the treatment was discontinued because of interstitial pneumonia as an irAE. Disease regression was sustained for approximately 11 months without the readministration of nivolumab.
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Doenças Pulmonares Intersticiais , Neoplasias Gástricas , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Linfonodos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Neoplasias Gástricas/tratamento farmacológicoRESUMO
PURPOSE: The standard first-line treatment for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer (AGC) is trastuzumab in combination with cisplatin and fluoropyrimidines. We evaluated the efficacy and safety of S-1 and oxaliplatin (100 mg/m2) (SOX100) combined with trastuzumab, a monoclonal antibody against HER2 for HER2-positive AGC. METHODS: In this single-arm, multicenter phase II study, patients with HER2-positive AGC received S-1 (80-120 mg per day) orally on days 1-14, oxaliplatin (100 mg/m2) intravenously on day 1, and trastuzumab (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) intravenously. The primary end point was 1-year survival rate. The secondary end points included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety. RESULTS: A total of 25 patients from six centers were enrolled from December 2015 to March 2020. In the 25 patients evaluable for analysis, the 1-year survival rate was 70.8% [90% confidence interval (CI) = 55.5-86.1%], whereas the median OS, PFS, and ORR were 17.8 (95% CI 10.5-22.9) months, 7.6 (95% CI 5.0-10.9) months, and 75.0% (95% CI 53.3-90.2), respectively. Major grade 3/4 adverse events included anorexia (20%), anemia (16%), peripheral sensory neuropathy (16%), and diarrhea (15%). CONCLUSION: SOX100 combined with trastuzumab was effective with a favorable safety profile in patients with HER2-positive AGC.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Gástricas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Oxaliplatina , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/uso terapêuticoRESUMO
BACKGROUND AND AIM: Two methods of transpapillary covered self-expandable metal stent (SEMS) placement are used for distal malignant biliary obstruction (MBO): after initial drainage by plastic stent (two-step method) and without previous drainage (one-step method). METHODS: In total, 90 patients with unresectable pancreatic cancer and distal MBO were enrolled in this prospective multicenter randomized study and allocated to one-step (n = 45) and two-step (n = 45) groups. The main outcome was the time to recurrent biliary obstruction (TRBO). Secondary outcomes were the rates of early and late adverse events, survival time, the time required for bilirubin level reduction, and cost-effectiveness. RESULTS: The median TRBO did not differ significantly between the one-step and two-step groups (not available vs 314 days, P = 0.134). SEMS migration occurred significantly more frequently in the two-step group (14.3% vs 0%, P = 0.026). No significant difference was observed between groups in early (7.3% vs 14.3%, P = 0.483) or late (12.2% and 11.9%, P = 1) adverse events other than RBO, survival time (P = 0.104), or the median number of days required to reach a bilirubin level considered to be acceptable for chemotherapy administration (<3 mg/dL; P = 0.881). The total costs of stent placement and reintervention were significantly lower in the one-step SEMS group (3347 vs 5465 US dollars, P < 0.001). CONCLUSIONS: The superiority of TRBO with two-step SEMS placement was not demonstrated. One-step SEMS placement might be a promising method from the viewpoints of cost-effectiveness and less invasiveness (UMIN-CTR clinical trial registration number: UMIN000016010).
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Colestase , Recidiva Local de Neoplasia , Bilirrubina , Colestase/etiologia , Colestase/terapia , Humanos , Estudos Prospectivos , Stents/efeitos adversosRESUMO
PURPOSE: Self-expandable metallic stents (SEMSs) may be used to effectively palliate malignant gastric outlet obstructions (GOOs), but their utility and efficacy in patients under best supportive care (BSC) have not been explored. METHOD: In this multicenter retrospective study, we reviewed data on patients under BSC who underwent endoscopic SEMS placement to treat malignant GOO without chemotherapy. We evaluated the safety and efficacy of the procedure. RESULTS: We enrolled a total of 208 patients. SEMS placement was technically successful in 207 (99.5%) and clinically successful in 164 (78.8%). The mean procedure time was 25.6 ± 2.8 min. Stent dysfunction later developed in 30 (14.4%) patients, of whom 90% (27/30) underwent reintervention. The procedure-related mortality rate was 1.44%; all deaths were due to pneumonia. Subgroup analysis by Karnofsky performance status (KPS) revealed that neither technical success, stent dysfunction, reintervention rate, procedure-related pneumonia or death, nor death within 14 days differed between patients with good and poor KPS. However, the clinical success rate and the median survival time were significantly lower and shorter, respectively, in those with poor KPS (p < 0.001). CONCLUSIONS: Duodenal SEMS placement is an effective palliative treatment for malignant GOO in BSC patients. Although the GOO score did not dramatically improve in patients with poor KPS, the procedure was safe and palliatively feasible. Procedure-related pneumonia was fatal; thus, it is essential to proceed with great caution. TRIAL REGISTRATION: Clinical trial registration number: UMIN000028367.
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Obstrução da Saída Gástrica/etiologia , Obstrução da Saída Gástrica/terapia , Cuidados Paliativos/métodos , Stents Metálicos Autoexpansíveis , Neoplasias Gástricas/complicações , Neoplasias Gástricas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/normas , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Stents Metálicos Autoexpansíveis/efeitos adversos , Stents Metálicos Autoexpansíveis/estatística & dados numéricos , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: Endoscopic biliary and duodenal stenting (DS; double stenting) is widely accepted as a palliation therapy for malignant bilioduodenal obstruction. The aim of the current study was to investigate the patency and adverse events of duodenal and biliary stents in patients with DS. METHODS: Patients who underwent DS from April 2004 to March 2017 were analyzed retrospectively with regard to clinical outcomes and predictive factors of recurrent biliary and duodenal obstruction (recurrent biliary obstruction [RBO] and recurrent duodenal obstruction [RDO]). RESULTS: A total of 109 consecutive patients was enrolled. Technical success of DS was achieved in 108 patients (99.1%). Symptoms due to biliary and duodenal obstruction were improved in 89 patients (81.7%). RBO occurred in 25 patients (22.9%) and RDO in 13 (11.9%). The median times to RBO and RDO from DS were 87 and 76 days, respectively. Placement of a duodenal uncovered self-expandable metal stent (U-SEMS) was significantly associated with RBO in the multivariable analysis (P = 0.007). Time to RBO was significantly longer in the duodenal covered self-expandable metal stent group than in the U-SEMS group (P = 0.003). No predictive factors of RDO were detected, and duodenal stent type was not associated with the time to RDO (P = 0.724). CONCLUSIONS: Double stenting was safe and effective for malignant bilioduodenal obstruction. Duodenal U-SEMS is a risk factor for RBO. The covered self-expandable metal stent is the preferred type of duodenal SEMS in patients with DS (Clinical trial registration number: UMIN000027606).
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Colestase/cirurgia , Obstrução Duodenal/cirurgia , Endoscopia do Sistema Digestório/métodos , Stents Metálicos Autoexpansíveis , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Stents Metálicos Autoexpansíveis/efeitos adversos , Resultado do TratamentoRESUMO
There have been few reports on 2 tumor necrosis factor alpha inhibitors, infliximab and adalimumab, with respect to patient preference and efficacy in ulcerative colitis (UC).We used questionnaires to evaluate the preference and reasons for drug choice between infliximab and adalimumab in UC patients naive to antitumor necrosis factor alpha therapy. We also analyzed the efficacy of infliximab and adalimumab prospectively and endoscopically before treatment and at 14 and 54 weeks.Of the 25 UC patients, infliximab and adalimumab were chosen by 10 (40%) and 15 (60%), respectively. Patients who favored infliximab considered "fear of syringes" (7/10, 70%) as the most important influencing factor, whereas patients who favored adalimumab considered "ease of administration" (10/15, 66.7%) and "time required for therapy" (10/15, 66.7%) as the most important factors. There were no statistical differences in remission induction and maintenance between the infliximab and adalimumab groups with regard to response, remission, mucosal healing, steroid-free, and steroid-free remission rates at weeks 14 and 54.The efficacy of adalimumab in remission induction and maintenance was equivalent to that of infliximab in UC patients naive to antitumor necrosis factor alpha therapy in this prospective study, but more patients preferred adalimumab.
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Adalimumab/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Preferência do Paciente/psicologia , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Vias de Administração de Medicamentos , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Humanos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Seringas , Fatores de TempoRESUMO
This article was retracted on 25/08/2017.
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BACKGROUND: Endoscopic metallic stenting is widely accepted as a palliation therapy for malignant gastric outlet obstruction (GOO). However, the predictors of stent dysfunction have not been clarified. We aimed to evaluate the predictors, especially tumor ingrowth in uncovered self-expandable metallic stents (U-SEMS) and migration of covered self-expandable metallic stents (C-SEMS), which are the main causes related to the stent characteristics. METHODS: In this multicenter retrospective study, we compared patients with U-SEMS and C-SEMS in terms of clinical outcomes, and predictors of stent dysfunction. RESULTS: In total, 252 patients (126 with U-SEMS and 126 with C-SEMS) were enrolled. There were no significant differences in technical success, clinical success, GOO score, or time to stent dysfunction. Tumor ingrowth was significantly more frequent in U-SEMS (U-SEMS, 11.90% vs. C-SEMS, 0.79%; p = 0.002), and stent migration was significantly more frequent for C-SEMS (C-SEMS, 8.73% vs. U-SEMS, 0.79%; p = 0.005). Karnofsky performance status (p = 0.04), no presence of ascites (p = 0.02), and insufficient (<30%) stent expansion (p = 0.003) were significantly associated with tumor ingrowth in U-SEMS. Meanwhile, a shorter stent length (p = 0.05) and chemotherapy (p = 0.03) were predictors of C-SEMS migration. CONCLUSIONS: Both U-SEMS and C-SEMS are effective with comparable patencies. Tumor ingrowth and stent migration are the main causes of stent dysfunction for U-SEMS and C-SEMS, respectively. With regard to stent dysfunction, U-SEMS might be a good option for patients receiving chemotherapy, while C-SEMS with longer stents for patients in good condition. (Clinical trial registration number: UMIN000024059).
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Neoplasias do Sistema Biliar/cirurgia , Obstrução da Saída Gástrica/cirurgia , Neoplasias Pancreáticas/cirurgia , Falha de Prótese , Stents Metálicos Autoexpansíveis , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/complicações , Neoplasias do Sistema Biliar/patologia , Feminino , Obstrução da Saída Gástrica/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Cuidados Paliativos , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Fatores de Risco , Stents/efeitos adversos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Uncovered self-expandable metal stents (U-SEMSs) and covered self-expandable metal stents (C-SEMSs) are available for palliative therapy for malignant gastric outlet obstruction (GOO). However, clinical differences and indications between the 2 types of SEMSs have not been elucidated. METHODS: We retrospectively compared 126 patients with U-SEMS and 126 patients with C-SEMSs with regard to clinical outcome and factors predictive of clinical improvement after SEMSs placement. RESULTS: No significant difference was observed between the U-SEMS and C-SEMS groups with respect to technical success, clinical success, GOO score, or time to stent dysfunction. Stent migration was significantly more frequent in patients with C-SEMSs (U-SEMSs, .79%; C-SEMSs, 8.73%; P = .005). Karnofsky performance status, chemotherapy, peritoneal dissemination, and stent expansion ≤ 30% were associated significantly with poor GOO score improvement in multivariable analyses, but stent type was not (P = .213). In subgroup analyses, insufficient (≤30%) stent expansion was an independent factor in patients with U-SEMSs (P = .041) but not C-SEMSs. In the insufficient stent expansion subgroup, C-SEMSs was associated significantly with superior clinical improvement compared with U-SEMSs (P = .01). Insufficient stent expansion was observed more frequently in patients with GI obstruction because of anastomotic sites or metastatic cancer (44.8% [13/29], P = .001). CONCLUSIONS: No clinical difference, apart from stent migration, was observed between patients with U-SEMSs and C-SEMSs. GI obstruction because of an anastomotic site or metastatic cancer may be an indication for C-SEMS use to improve oral intake after SEMSs placement.
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Antineoplásicos/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Obstrução da Saída Gástrica/cirurgia , Neoplasias Pancreáticas/tratamento farmacológico , Stents Metálicos Autoexpansíveis , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/complicações , Feminino , Obstrução da Saída Gástrica/etiologia , Gastroscopia , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/complicações , Neoplasias Peritoneais/secundário , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/complicações , Resultado do TratamentoRESUMO
Some patients with gastroesophageal reflux disease experience persistent reflux symptoms despite proton pump inhibitor therapy. These symptoms reduce their health-related quality of life. Our aims were to evaluate the relationship between proton pump inhibitor efficacy and health-related quality of life and to evaluate predictive factors affecting treatment response in Japanese patients. Using the gastroesophageal reflux disease questionnaire, 145 gastroesophageal reflux disease patients undergoing proton pump inhibitor therapy were evaluated and classified as responders or partial-responders. Their health-related quality of life was then evaluated using the 8-item Short Form Health Survey, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale questionnaires. Sixty-nine patients (47.6%) were partial responders. These patients had significantly lower scores than responders in 5/8 subscales and in the mental health component summary of the 8-item Short Form Health Survey. Partial responders had significantly higher Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale scores, including anxiety and depression scores, than those of responders. Non-erosive reflux disease and double proton pump inhibitor doses were predictive factors of partial responders. Persistent reflux symptoms, despite proton pump inhibitor therapy, caused mental health disorders, sleep disorders, and psychological distress in Japanese gastroesophageal reflux disease patients.
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BACKGROUND: We evaluated the efficacy and safety of 5-weekly S-1 and cisplatin combined with trastuzumab, a monoclonal antibody against human epidermal growth factor receptor type 2 (HER2) for HER2-positive advanced gastric cancer (AGC). METHODS: This phase II study treatment consisted of S-1 (80-120 mg per day) orally on day 1-21, cisplatin (60 mg/m(2)) intravenously on day 8, and trastuzumab (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) intravenously. The primary end point was 1-year survival rate. The secondary end points included overall survival, progression-free survival (PFS), response rate (RR), and safety. RESULTS: A total 22 patients from seven centers were enrolled. In the 20 patients evaluable for analysis, the 1-year survival rate was 70 % (95 % confidence interval (CI) 49.9-90.1 %), and median survival time, PFS, and RR were 15.3, 7.5 months and 41.2 %, respectively. Major grade 3/4 adverse events were neutropenia (30 %), anorexia (30 %), leukopenia (25 %), fatigue (20 %), and anemia (15 %). CONCLUSIONS: Five-weekly S-1 and cisplatin combined with trastuzumab showed effective with favorable safety profile in patients with HER2-positive AGC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Ácido Oxônico/uso terapêutico , Receptor ErbB-2/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Trastuzumab/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Critérios de Avaliação de Resposta em Tumores Sólidos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversosRESUMO
It has been shown that adipose-derived mesenchymal stem cells (AMSCs) can differentiate into adipocytes, chondrocytes and osteoblasts. Several clinical trials have shown the ability of AMSCs to regenerate these differentiated cell types. Age-associated dysregulation of the gastrointestinal (GI) immune system has been well documented. Our previous studies showed that impaired mucosal immunity in the GI tract occurs earlier during agingthan is seen in the systemic compartment. In this study, we examined the potential of AMSCs to restore the GI mucosal immune system in aged mice. Aged (>18 mo old) mice were adoptively transferred with AMSCs. Two weeks later, mice were orally immunized with ovalbumin (OVA) plus cholera toxin (CT) three times at weekly intervals. Seven days after the final immunization, when fecal extract samples and plasma were subjected to OVA- and CT-B-specific ELISA, elevated levels of mucosal secretory IgA (SIgA) and plasma IgG antibody (Ab) responses were noted in aged mouse recipients. Similar results were also seen aged mice which received AMSCs at one year of age. When cytokine production was examined, OVA-stimulated Peyer's patch CD4+ T cells produced increased levels of IL-4. Further, CD4+ T cells from the lamina propria revealed elevated levels of IL-4 and IFN-γ production. In contrast, aged mice without AMSC transfer showed essentially no OVA- or CT-B-specific mucosal SIgA or plasma IgG Ab or cytokine responses. Of importance, fecal extracts from AMSC transferred aged mice showed neutralization activity to CT intoxication. These results suggest that AMSCs can restore impaired mucosal immunity in the GI tract of aged mice.
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Tecido Adiposo/imunologia , Envelhecimento/imunologia , Linfócitos T CD4-Positivos/imunologia , Imunidade nas Mucosas , Células-Tronco Mesenquimais/imunologia , Nódulos Linfáticos Agregados/imunologia , Aloenxertos , Animais , Toxina da Cólera/toxicidade , Feminino , Imunoglobulina A Secretora/imunologia , Interferon gama/imunologia , Interleucina-4/imunologia , Masculino , Transplante de Células-Tronco Mesenquimais , CamundongosRESUMO
BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is frequently performed for the diagnosis and treatment of type 1 autoimmune pancreatitis (AIP). However, the prevalence of ERCP-related adverse events in patients with type 1 AIP has not been evaluated. We aimed to clarify the feasibility of ERCP in patients with type 1 AIP. METHODS: We retrospectively reviewed 82 consecutive ERCP procedures performed in patients with type 1 AIP from 2004 to 2014 in one university hospital and three tertiary-care referral centers. One hundred four ERCP procedures in chronic pancreatitis and 1123 in non-AIP cohort were enrolled as control groups. We compared the incidence of post-ERCP pancreatitis (PEP) between type 1 AIP and control groups. We evaluated the incidence of ERCP-related adverse events and various predictive factors for hyperamylasemia after ERCP. RESULTS: Pancreatography and cholangiography by ERCP were obtained in 78 (95.1%) and 76 (92.7%) patients, respectively. The incidence of PEP, cholangitis, and bleeding was 1.2% (1/82), 0%, and 1.2%, respectively. PEP occurred in type 1 AIP patient with diffuse parenchymal imaging, and the severity was mild. The incidences of PEP were 2.9% (3/104) and 5.4% (61/1123) in chronic pancreatitis and normal cohort, respectively. The incidence of PEP was slightly lower in type 1 AIP than non-AIP cohort (1.2% vs 5.8%, p = 0.119). There were no significant predictive factors for hyperamylasemia after ERCP in type 1 AIP. CONCLUSIONS: The incidence of ERCP-related adverse events is low in patients with type 1 AIP. ERCP-related procedures are feasible in the diagnosis and treatment of AIP.
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Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Pancreatite/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/classificação , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: We aimed to clarify the clinical benefits of using 8-mm versus 10-mm diameter self-expandable metallic stent (SEMS) in bilateral endoscopic stent-in-stent (SIS) deployment for malignant hilar biliary obstruction (MHBO). METHODS: A total of 72 consecutive patients with MHBO treated by endoscopic bilateral SIS deployment were enrolled. The 8-mm and 10-mm diameter SEMSs were used in 37 patients (8-mm group) and 35 patients (10-mm group), respectively. We retrospectively compared technical success, functional success, complications, successful re-intervention, time to recurrent biliary obstruction (RBO) and survival time between two groups. RESULTS: There were no significant inter-group differences in terms of technical success (8-mm vs. 10-mm group, both 100%), functional success (96% vs. 100%), early (5% vs. 9%) and late (19% vs. 14%) complications other than RBO, and successful endoscopic re-intervention (94% vs. 100%), respectively. Time to RBO (median: 198 days vs. 222 days; log-rank, P = 0.440) and survival time (median: 186 days vs. 235 days; log-rank, P = 0.883) did not differ significantly between the two groups. However, the success rate of endoscopic bilateral revisionary stent insertion for RBO was significantly higher in the 10-mm compared to the 8-mm group (68% vs. 31%; P = 0.044). CONCLUSIONS: The 10-mm diameter SEMS is more suitable with regard to endoscopic re-intervention.
Assuntos
Neoplasias dos Ductos Biliares/complicações , Ductos Biliares Intra-Hepáticos , Colestase/etiologia , Colestase/terapia , Stents Metálicos Autoexpansíveis , Idoso , Idoso de 80 Anos ou mais , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retratamento , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIM: We aimed to elucidate the relationship between the contrast enhancement effect of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) on magnetic resonance imaging (MRI) of hepatocellular carcinomas (HCC) and the expressions of hepatocyte transporters (i.e. organic anion-transporting polypeptide [OATP]1B3, multidrug-resistant protein [MRP]2 and MRP3) and to clarify the characteristics of HCC with an MRI high-contrast enhancement effect. METHODS: We retrospectively examined the relationship between the relative enhancement ratio (RER) of HCC, absolute and relative immunohistochemical staining scores of hepatocyte transporters, and histological differentiation of 22 HCC from 21 patients who had undergone preoperative Gd-EOB-DTPA-enhanced MRI. RESULTS: RER had a significant correlation with OATP1B3 expression according to the absolute and relative scores (P = 0.016 vs 0.0006). The RER of HCC with high OATP1B3 and MRP2 expression levels was higher than that of HCC with low OATP1B3 or MRP2 expression levels (P = 0.0003). The RER of HCC with higher OATP1B3 rates was greater than that of HCC with lower OATP1B3 rates (P = 0.0005). HCC histological differentiation showed a significant correlation with OATP1B3 expression and RER (P = 0.023 vs 0.0095). CONCLUSION: We found that coexpression of OATP1B3 and MRP2 influenced the high contrast enhancement of HCC on MRI.