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1.
Medicine (Baltimore) ; 99(9): e19275, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118738

RESUMO

The advent of imatinib mesylate (IM) has dramatically revolutionized the prognosis of advanced and metastatic/recurrent gastrointestinal stromal tumors (GISTs). The objective of this retrospective study is to investigate the safety and efficacy of combination of surgery following IM treatment in the management of advanced and metastatic/recurrent GISTs. We further explore the long-term clinical outcomes in these who underwent therapy of preoperative IM.Eligible patients with GISTs before the onset of the IM therapy and were periodically followed up in the outpatient clinic were included in this study. Detailed clinical and pathologic characteristics were obtained from the medical records of our institution. Univariate and multivariate regression analyses were performed to use for the evaluation of potential prognostic factors.A total of 51 patients were included in the study, of these patients, 36 patients underwent surgery and median duration of preoperative IM is 8.2months (range 3.5-85 months). Significant median tumor shrinkage rate was 29.27% (95% confidence interval 21.00%-34.00%) observed in these patients who responded to IM, and partial response and stable disease were achieved in 24 patients (47.06%) and 23 patients (45.10%), respectively, in light of the RECIST guideline (version 1.1). After the median follow-up of 43.70 months (range 14.2-131.1 months), 1- and 3-year overall survival (OS) were estimated to be 96.1% and 94.0%, respectively, and there was a significant improvement in OS for patients who received surgical intervention versus those who did not.Our study consolidates that patients were received preoperative IM therapy could shrink the size of tumors and facilitate organ-function preservation. The long-term analysis on this study supports that surgical intervention following IM therapy benefits for patients with primary advanced and recurrent or metastatic GISTs on long-term prognosis.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Gastrointestinais/terapia , Tumores do Estroma Gastrointestinal/terapia , Mesilato de Imatinib/uso terapêutico , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , China , Feminino , Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/administração & dosagem , Masculino , Registros Médicos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
2.
Anticancer Res ; 39(11): 6413-6416, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704875

RESUMO

BACKGROUND/AIM: The aim of this study was to present the clinical characteristics, natural history and survival outcomes of primary gastrointestinal non-Hodgkin lymphomas (PGINHL) in the pediatric population. PATIENTS AND METHODS: Surveillance, Epidemiology, and End Results (SEER) database was queried for patients aged 0 to 19 years with PGINHL between 1973 and 2014. RESULTS: A total of 452 cases were identified [mean age 11.0 (±5.1)] years, whites 84.1%, males (76.5%). The majority of tumors were noted in the small bowel (SB) (47.6%), followed by large bowel (LB) (28.5%) and the stomach (10.0%). Overall, the most common histological subtype was Burkitt lymphoma (51.8%), followed by diffuse large B-cell lymphoma (DLBCL) (26.1%). Mean overall survival (OS) of the entire cohort was 33,33 years with a 5-yr, 10-yr and 30-yr survival rate of 86%, 86% and 79%, respectively. Large bowel tumors had the best long-term survival rates whereas; gastric tumors had the worst with 30-yr survival rate 84% and 74%, respectively. Overall, 328 (72.6%) patients received surgery. No significant survival difference was noted between patients who underwent surgery and those who did not. CONCLUSION: This study presents the largest dataset of pediatric PGINHL and describes the clinical features and outcomes of these patients in addition to summarizing the literature.


Assuntos
Neoplasias Gastrointestinais , Linfoma não Hodgkin , Adolescente , Linfoma de Burkitt/mortalidade , Linfoma de Burkitt/patologia , Linfoma de Burkitt/cirurgia , Neoplasias do Ceco/mortalidade , Neoplasias do Ceco/patologia , Neoplasias do Ceco/cirurgia , Criança , Pré-Escolar , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Humanos , Neoplasias do Íleo/mortalidade , Neoplasias do Íleo/patologia , Neoplasias do Íleo/cirurgia , Lactente , Recém-Nascido , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/cirurgia , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/cirurgia , Masculino , Programa de SEER , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Adulto Jovem
3.
World J Gastroenterol ; 25(38): 5732-5772, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31636470

RESUMO

In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer cell. The functions of ion channels in the gastrointestinal (GI) tract influence a variety of cellular processes, many of which overlap with these hallmarks of cancer. In this review we focus on the roles of the calcium (Ca2+), sodium (Na+), potassium (K+), chloride (Cl-) and zinc (Zn2+) transporters in GI cancer, with a special emphasis on the roles of the KCNQ1 K+ channel and CFTR Cl- channel in colorectal cancer (CRC). Ca2+ is a ubiquitous second messenger, serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle, apoptosis, and migration. Various members of the TRP superfamily, including TRPM8, TRPM7, TRPM6 and TRPM2, have been implicated in GI cancers, especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon cancer. Voltage-gated sodium channels (VGSCs) are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle cells. The VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC samples. Studies have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer progression. Zn2+ transporters of the ZIP/SLC39A and ZnT/SLC30A families are dysregulated in all major GI organ cancers, in particular, ZIP4 up-regulation in pancreatic cancer (PC). More than 70 K+ channel genes, clustered in four families, are found expressed in the GI tract, where they regulate a range of cellular processes, including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal tract. Several distinct types of K+ channels are found dysregulated in the GI tract. Notable are hERG1 upregulation in PC, gastric cancer (GC) and CRC, leading to enhanced cancer angiogenesis and invasion, and KCNQ1 down-regulation in CRC, where KCNQ1 expression is associated with enhanced disease-free survival in stage II, III, and IV disease. Cl- channels are critical for a range of cellular and tissue processes in the GI tract, especially fluid balance in the colon. Most notable is CFTR, whose deficiency leads to mucus blockage, microbial dysbiosis and inflammation in the intestinal tract. CFTR is a tumor suppressor in several GI cancers. Cystic fibrosis patients are at a significant risk for CRC and low levels of CFTR expression are associated with poor overall disease-free survival in sporadic CRC. Two other classes of chloride channels that are dysregulated in GI cancers are the chloride intracellular channels (CLIC1, 3 & 4) and the chloride channel accessory proteins (CLCA1,2,4). CLIC1 & 4 are upregulated in PC, GC, gallbladder cancer, and CRC, while the CLCA proteins have been reported to be down-regulated in CRC. In summary, it is clear, from the diverse influences of ion channels, that their aberrant expression and/or activity can contribute to malignant transformation and tumor progression. Further, because ion channels are often localized to the plasma membrane and subject to multiple layers of regulation, they represent promising clinical targets for therapeutic intervention including the repurposing of current drugs.


Assuntos
Antineoplásicos/farmacologia , Carcinogênese/patologia , Neoplasias Gastrointestinais/tratamento farmacológico , Canais Iônicos/metabolismo , Animais , Antineoplásicos/uso terapêutico , Carcinogênese/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Intervalo Livre de Doença , Regulação para Baixo , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Humanos , Canais Iônicos/antagonistas & inibidores , Regulação para Cima
4.
Int J Clin Oncol ; 24(11): 1333-1349, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31522313

RESUMO

INTRODUCTION: According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. MATERIALS AND METHODS, AND RESULTS: Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. CONCLUSION: We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival.


Assuntos
Neoplasias Colorretais/diagnóstico , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Gastrointestinais/cirurgia , Animais , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/terapia , Quimiocina CXCL12/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/cirurgia , Cães , Neoplasias Esofágicas/cirurgia , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/mortalidade , Humanos , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/terapia , Cuidados Pós-Operatórios , Receptores CXCR4/metabolismo , Procedimentos Cirúrgicos Reconstrutivos/métodos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
5.
Expert Opin Drug Saf ; 18(11): 1043-1053, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31498687

RESUMO

Introduction: Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs worldwide. However, concerns are growing about the serious adverse events and mortality linked to their long-term use. Areas covered: The authors review the main approved clinical indications and adverse events associated with PPIs, including, among others, pneumonia, Clostridium difficile infection, cardiovascular diseases, bone fractures, kidney diseases, and several nutrient deficiencies. Recent studies have reported that patients taking PPIs displayed increased mortality, linked to cardiovascular diseases, gastrointestinal malignancies, and chronic kidney diseases. Expert opinion: PPIs represent an important advance in the medical treatment of acid-related diseases. PPIs have contributed to profound reductions in hospitalizations and mortality due to upper GI complications. However, concern is growing about the wide range of potentially serious adverse events and mortality linked to chronic PPI use. Nevertheless, the level of evidence on adverse events is low; it is based on observational studies, and most findings have not been confirmed in the limited number of clinical trials available. PPI overuse and off-label prescriptions must be eradicated, but long-term PPI use for clear indications must continue, until we have stronger evidence to support claims of serious adverse events and mortality.


Assuntos
Uso Off-Label/estatística & dados numéricos , Uso Excessivo de Medicamentos Prescritos/prevenção & controle , Inibidores da Bomba de Prótons/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/etiologia , Neoplasias Gastrointestinais/mortalidade , Humanos , Inibidores da Bomba de Prótons/administração & dosagem , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/mortalidade
6.
World J Surg Oncol ; 17(1): 156, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484583

RESUMO

BACKGROUND: Liver resection is a treatment of choice for colorectal and neuroendocrine liver metastases, and laparoscopy is an accepted approach for surgical treatment of these patients. The role of liver resection for patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM), however, is still disputable. Outcomes of laparoscopic liver resection for this group of patients have not been analyzed. MATERIAL AND METHODS: In this retrospective study, patients who underwent laparoscopic liver resection for NCNNLM at Oslo University Hospital between April 2000 and January 2018 were analyzed. Perioperative and oncologic data of these patients were examined. Postoperative morbidity was classified using the Accordion classification. Kaplan-Meier method was used for survival analysis. Median follow-up was 26 (IQR, 12-41) months. RESULTS: Fifty-one patients were identified from a prospectively collected database. The histology of primary tumors was classified as adenocarcinoma (n = 16), sarcoma (n = 4), squamous cell carcinoma (n = 4), melanoma (n = 16), gastrointestinal stromal tumor (n = 9), and adrenocortical carcinoma (n = 2). The median operative time was 147 (IQR, 95-225) min, while the median blood loss was 200 (IQR, 50-500) ml. Nine (18%) patients experienced postoperative complications. There was no 90-day mortality in this study. Thirty-five (68%) patients developed disease recurrence or progression. Seven (14%) patients underwent repeat surgical procedure for recurrent liver metastases. One-, three-, and five-year overall survival rates were 85%, 52%, and 38%, respectively. The median overall survival was 37 (95%CI, 25 to 49) months. CONCLUSION: Laparoscopic liver resection for NCNNLM results in good outcomes and should be considered in patients selected for surgical treatment.


Assuntos
Adenocarcinoma/mortalidade , Carcinoma Adrenocortical/mortalidade , Tumores do Estroma Gastrointestinal/mortalidade , Hepatectomia/mortalidade , Laparoscopia/mortalidade , Neoplasias Hepáticas/mortalidade , Melanoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/cirurgia , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Assistência Perioperatória , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/patologia , Sarcoma/cirurgia , Taxa de Sobrevida
7.
Int J Mol Sci ; 20(15)2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387321

RESUMO

Aberrant function of Smad2, a crucial member of transforming growth factor beta (TGF-ß) signaling, is associated with the development of malignancies, particularly in the gastrointestinal district. However, little is known about its possible prognostic role in such tumor types. With the first meta-analysis on this topic, we demonstrated that the lack of the activated form of Smad2 (phosphor-Smad2 or pSmad2), which was meant to be the C-terminally phosphorylated form, showed a statistically significant association with an increased risk of all-cause mortality in patients with gastrointestinal cancers (RR, 1.58; 95% CI, 1.05-2.37, p = 0.029, I2 = 84%), also after having adjusted for potential confounders (RR, 1.65; 95% CI, 1.24-2.18; p < 0.001; I2 = 4%). This finding highlights the importance of the TGF-ß signaling in this type of cancer. In this line, further studies are needed to explore more in depth this important molecular pathway, focusing also on potential therapeutic strategies based on its effectors or molecular targets.


Assuntos
Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/mortalidade , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Biomarcadores , Humanos , Razão de Chances , Fosforilação , Prognóstico , Viés de Publicação , Transdução de Sinais
8.
Ann Surg Oncol ; 26(11): 3644-3651, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31388777

RESUMO

BACKGROUND: The number of elderly patients with gastrointestinal cancer is rising as the population ages. This study aimed to assess the impact of a preoperative geriatric assessment on postoperative survival and to develop a geriatric prognostic scoring system (GPSS) for elderly patients. METHODS: Patients (n = 544) age 75 years or older who had undergone radical surgery for gastrointestinal cancer were recruited for this observational study. Geriatric assessments (GAs) using the Barthel Index, the Mini-Mental State Examination, Instrumental Activities of Daily Living, the Vitality Index, and the Geriatric Depression Score were administered before surgery. Multivariable analysis was performed using a Cox proportional hazard regression model to identify significant prognostic factors. The GPSS was developed using regression coefficients of the multivariable regression to predict overall survival (OS). Thereafter, 165 consecutive patients were prospectively validated to test the authors' model. RESULTS: The independent predictors of OS appeared to be GA as well as age, type of cancer, clinical stage, performance status, and body mass index. The patients were classified into high- and low-risk groups according to the GPSS. The overall 3-year survival was 79% in the low-risk group and 26% in the high-risk group (hazard ratio [HR], 5.69; 95% confidence interval [CI] 4.35-7.42; p < 0.0001). Furthermore, when GPSS was applied to independent cohorts, the patients in the high-risk group showed significantly poorer prognoses than those in the low-risk group (HR, 4.49; 95% CI 2.65-7.60; p < 0.0001). CONCLUSIONS: Geriatric assessments were closely associated with postoperative OS. The GPSS is useful in predicting postoperative prognosis and may help determine treatment strategies for elderly patients with gastrointestinal cancer.


Assuntos
Atividades Cotidianas , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Neoplasias Gastrointestinais/mortalidade , Avaliação Geriátrica/métodos , Nomogramas , Idoso , Feminino , Seguimentos , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Humanos , Masculino , Prognóstico , Fatores de Risco , Taxa de Sobrevida
9.
Ig Sanita Pubbl ; 75(2): 125-138, 2019.
Artigo em Italiano | MEDLINE | ID: mdl-31377757

RESUMO

An aluminum foundry has been present in the area of the district of Carisio (Piedmont region), Italy since 1975. Environmental analyses have shown that toxic emissions (in particular of dioxin) affect the district of Crocicchio and not the remaining municipality of Carisio. A study was therefore conducted to assess mortality in the population of Carisio and in the rest of the municipality, from 1980 to 2017, by using the Piedmont region as standard population. Excess mortality was found in the Crocicchio district for tumors (+ 88%), lung cancer in men (+ 320%) and total digestive tract tumors (+ 85%). Relative risks also show a higher risk of death caused by the above tumors, with two deaths per year being due to the existing environmental risk. An epidemiological and environmental monitoring plan should be implemented for the years to follow, and measures for the containment of polluting emissions from the site should be introduced immediately.


Assuntos
Alumínio , Carcinógenos Ambientais , Neoplasias Gastrointestinais , Neoplasias Pulmonares , Alumínio/toxicidade , Neoplasias Gastrointestinais/mortalidade , Humanos , Itália , Neoplasias Pulmonares/mortalidade , Masculino , Fatores de Risco
10.
Cancer Control ; 26(1): 1073274819863776, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31319677

RESUMO

Only limited data are available concerning the long-term outcomes of imatinib treatment among Vietnamese or Asian patients with unresectable or recurrent gastrointestinal stromal tumors (GISTs). Our study, which was conducted in 188 patients, aimed to assess the efficacy of imatinib mesylate against unresectable or recurrent GISTs. Imatinib had a high response rate and long survival. Some predictors favorable for progression-free survival and overall survival are good performance status and response with imatinib. Findings are discussed in relation to clinical practice in low- and middle-income country.


Assuntos
Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Gastrointestinais/mortalidade , Tumores do Estroma Gastrointestinal/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Vietnã/epidemiologia
11.
Medicine (Baltimore) ; 98(29): e16520, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335729

RESUMO

BACKGROUND: High pretreatment plasma D-dimer levels can predict poor prognosis in various types of gastrointestinal carcinomas. Our meta-analysis explored the correlation between plasma D-dimer levels and prognosis in gastrointestinal malignancies. METHODS: Two independent reviewers conducted a comprehensive search from PubMed, ScienceDirect, Embase, Web of Science and the Cochrane Library. All articles evaluating the correlation between pretreatment plasma D-dimer levels and prognosis in gastrointestinal malignancies were searched. We chose overall survival (OS) as the primary survival outcome measure and progression-free survival (PFS), disease-free survival (DFS) and cancer-specific survival (CSS) as the secondary survival outcome measures. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) from the eligible publications. RESULTS: We included 30 studies involving 5928 gastrointestinal cancer patients. There was an obvious correlation between high D-dimer levels and poor OS (HR = 2.01, 95% CI = 1.72-2.36, P < .01). High plasma D-dimer levels were correlated with shorter PFS (HR = 1.34, 95% CI = 1.05-1.70, P = .32), DFS (HR =  1.67, 95% CI = 1.12-2.50, P < .01) and CSS rates (HR = 1.93, 95% CI = 1.49-2.49, P = .66). CONCLUSIONS: Elevated pretreatment plasma D-dimer levels might help predict poor prognosis in patients with gastrointestinal malignancies.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Neoplasias Gastrointestinais/sangue , Intervalo Livre de Doença , Neoplasias Gastrointestinais/mortalidade , Humanos , Prognóstico , Intervalo Livre de Progressão
12.
Ann Surg Oncol ; 26(11): 3627-3635, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31292804

RESUMO

OBJECTIVES: This study was designed to assess the short- and long-term outcomes of gastric resection in cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for lower gastrointestinal (GI) malignancies. METHODS: Patients with adenocarcinoma and appendiceal mucinous neoplasms were included. Redo and incomplete cytoreductions were excluded. A total of 756 patients were identified. Of these, 65 underwent gastric resection, 11 underwent wedge, 43 distal, and 11 subtotal and total gastrectomy. Preoperative differences were assessed for and addressed with matching. Perioperative outcomes, overall survival (OS), and risk-free survival (RFS) were assessed in two analyses: first all gastric resections were included and the second excluded wedge resections. Subgroup analysis according to diagnosis subtype was conducted. RESULTS: Demographic analysis revealed that markers of tumor aggression and poor nutrition were prevalent in the gastrectomy group. The matched analysis for gastric resections revealed higher rates of reoperation (38% vs. 22%, p = 0.028). After excluding wedge resections, increased rates of reoperation (40% vs. 22%, 0.019), grade 3/4 morbidity (76% vs. 59%, p = 0.036), and hospital stay (34 vs. 27 days, p = 0.012) were observed. For the unmatched cohort, OS (103 vs. 69 months, p = 0.501) and RFS (17 vs. 18 months, p = 0.181) for patients with CC = 0 were insignificantly different. In comparison for CC > 0, OS (31 vs. 83 months, p < 0.001) and RFS (9 vs. 20 months, p < 0.001) were significantly reduced in gastric resection. For the matched cohort, after excluding wedges, gastrectomy did not significantly decrease OS. However, RFS was decreased (11 vs. 20 months, p = 0.016). CONCLUSIONS: Despite high postoperative morbidity, when complete cytoreduction is achieved, the need for gastric resection is not associated with inferior long-term outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/mortalidade , Gastrectomia/mortalidade , Neoplasias Gastrointestinais/mortalidade , Hipertermia Induzida/mortalidade , Tempo de Internação/estatística & dados numéricos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/terapia , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/cirurgia , Neoplasias do Apêndice/terapia , Terapia Combinada , Feminino , Seguimentos , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Neoplasias Gastrointestinais/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/terapia , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/terapia , Taxa de Sobrevida
13.
World J Surg Oncol ; 17(1): 94, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164139

RESUMO

BACKGROUND: In recent years, some traction-assisted approaches have been introduced to facilitate endoscopic submucosal dissection (ESD) procedures by reducing the procedure time and risks related to the procedure. However, the relative advantages of traction-assisted endoscopic submucosal dissection (T-ESD) are still being debated. This study aimed to assess the efficacy of T-ESD for the treatment of superficial gastrointestinal neoplasms. METHODS: We searched MEDLINE, Embase, and Cochrane library up to March 31, 2019 for randomized controlled trials (RCTs) comparing T-ESD and conventional endoscopic submucosal dissection (C-ESD) for superficial gastrointestinal neoplasms. The main endpoints are en bloc resection, complete resection, procedure time, perforation, and delayed bleeding. Pooled risk ratio (RR), Peto odds ratio (OR), and mean difference (MD) were calculated to compare T-ESD and C-ESD. This study is registered with PROSPERO, number CRD42018108135. RESULTS: A total of 7 RCTs with 1007 patients were included in this meta-analysis. There were no significant differences between the T-ESD and C-ESD groups in the pooled estimate of en bloc resection, complete resection, and delayed bleeding (RR = 1.00, 95% CI 0.99, 1.01, I2 = 0%, P = 0.66; RR = 1.00, 95% CI 0.98, 1.03, I2 = 0%, P = 0.81; OR = 0.95, 95% CI 0.48, 1.86, I2 = 19%, P = 0.87,respectively). The pooled estimate indicated that the procedure time was significantly shorter in the T-ESD group (MD = - 16.19, 95% CI - 29.24, - 3.13, I2 = 87%, P = 0.02) than in the C-ESD group. Compared to C-ESD, T-ESD was associated with lower incidence of perforation (OR = 0.32, 95% CI 0.11, 0.91, I2 = 0%, P = 0.03). CONCLUSIONS: T-ESD is a safe and effective treatment option with a low perforation rate and shorter procedure time than C-ESD for superficial gastrointestinal neoplasms. Future multi-center (including European populations), randomized controlled trials of larger sample size and long-term outcomes of T-ESD are required.


Assuntos
Ressecção Endoscópica de Mucosa/mortalidade , Neoplasias Gastrointestinais/mortalidade , Tração/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento
14.
BMJ ; 365: l1580, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31147311

RESUMO

OBJECTIVE: To estimate all cause mortality and cause specific mortality among patients taking proton pump inhibitors (PPIs). DESIGN: Longitudinal observational cohort study. SETTING: US Department of Veterans Affairs. PARTICIPANTS: New users of PPIs (n=157 625) or H2 blockers (n=56 842). MAIN OUTCOME MEASURES: All cause mortality and cause specific mortality associated with taking PPIs (values reported as number of attributable deaths per 1000 patients taking PPIs). RESULTS: There were 45.20 excess deaths (95% confidence interval 28.20 to 61.40) per 1000 patients taking PPIs. Circulatory system diseases (number of attributable deaths per 1000 patients taking PPIs 17.47, 95% confidence interval 5.47 to 28.80), neoplasms (12.94, 1.24 to 24.28), infectious and parasitic diseases (4.20, 1.57 to 7.02), and genitourinary system diseases (6.25, 3.22 to 9.24) were associated with taking PPIs. There was a graded relation between cumulative duration of PPI exposure and the risk of all cause mortality and death due to circulatory system diseases, neoplasms, and genitourinary system diseases. Analyses of subcauses of death suggested that taking PPIs was associated with an excess mortality due to cardiovascular disease (15.48, 5.02 to 25.19) and chronic kidney disease (4.19, 1.56 to 6.58). Among patients without documented indication for acid suppression drugs (n=116 377), taking PPIs was associated with an excess mortality due to cardiovascular disease (22.91, 11.89 to 33.57), chronic kidney disease (4.74, 1.53 to 8.05), and upper gastrointestinal cancer (3.12, 0.91 to 5.44). Formal interaction analyses suggested that the risk of death due to these subcauses was not modified by a history of cardiovascular disease, chronic kidney disease, or upper gastrointestinal cancer. Taking PPIs was not associated with an excess burden of transportation related mortality and death due to peptic ulcer disease (as negative outcome controls). CONCLUSIONS: Taking PPIs is associated with a small excess of cause specific mortality including death due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. The burden was also observed in patients without an indication for PPI use. Heightened vigilance in the use of PPI may be warranted.


Assuntos
Doenças Cardiovasculares/mortalidade , Neoplasias Gastrointestinais/mortalidade , Úlcera Péptica/prevenção & controle , Inibidores da Bomba de Prótons/uso terapêutico , Insuficiência Renal Crônica/mortalidade , Saúde dos Veteranos/estatística & dados numéricos , Idoso , Causas de Morte , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mortalidade , Fatores de Risco , Estados Unidos/epidemiologia
15.
BMC Palliat Care ; 18(1): 45, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159782

RESUMO

BACKGROUND: This study aimed to analyze the determinants of patients' choice between palliative chemotherapy and best supportive care (BSC) and to investigate how this choice affects overall survival (OS) and length of hospitalization according to Eastern Cooperative Oncology Group (ECOG) performance status (PS). METHODS: An oncologist explained the palliative chemotherapy and BSC options to 129 patients with incurable cancer during their first consultation. Data on the ECOG PS, treatment decision, OS, and the length of hospitalization were retrospectively collected over 4 years. RESULTS: Patients with an ECOG PS of 0-2 chose palliative chemotherapy more often than those with an ECOG PS of 3-4 (P < 0.01). Patients with ≤70 years chose palliative chemotherapy more often than those with > 70 (P < 0.05). And patients with gastric cancer and colon cancer chose palliative chemotherapy more often than those with CUP (carcinoma of unknown primary) (P < 0.05, P < 0.05 respectively). Factors associated with a significantly poorer OS in an adjusted analysis included the ECOG PS and treatment decision (hazard ratios: 0.18 and 0.43; P < 0.001, P < 0.01 respectively). In patients with an ECOG PS of 0-2, palliative chemotherapy was not associated with a longer OS compared with BSC (median OS: 14.5 vs. 6.8 months, respectively; P = 0.144). In patients with an ECOG PS of 3-4, palliative chemotherapy resulted in a significant survival gain compared to with BSC (median OS: 3.8 vs. 1.4 months, respectively; P < 0.05). Strong positive correlations between OS and the length of hospitalization were observed in patients with an ECOG PS of 3-4 who underwent palliative chemotherapy (r2 = 0.683) and the length of hospitalization was approximately one-third of their OS. CONCLUSIONS: The determinants for treatment choice were age, ECOG PS and type of cancer, not sex difference. Oncologists should explain to patients that OS and the length of hospitalization vary according to the ECOG PS when selecting between palliative chemotherapy and BSC.


Assuntos
Tratamento Conservador/normas , Tratamento Farmacológico/normas , Neoplasias Gastrointestinais/mortalidade , Tempo de Internação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Tratamento Conservador/métodos , Tratamento Conservador/estatística & dados numéricos , Tratamento Farmacológico/métodos , Tratamento Farmacológico/estatística & dados numéricos , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Cuidados Paliativos/estatística & dados numéricos , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do Tratamento
16.
Ann Surg Oncol ; 26(11): 3577-3585, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31102094

RESUMO

BACKGROUND: Primary gallbladder neuroendocrine tumors (NETs) are rare, poorly understood cancers infrequently encountered at even the largest of tertiary referral centers. We therefore sought to identify a large cohort of patients with gallbladder NETs using a national database, with the aim of defining treatment modalities employed and survival associated with these uncommon malignancies. METHODS: Patients with primary gallbladder NETs were identified in the National Cancer Database, and clinicopathologic characteristics were recorded. A univariate log-rank survival analysis was completed for patients who underwent resection. Parameters found to be significant were entered into a multivariate accelerated failure time analysis. For context, survival comparisons were included for patients who underwent resections for NETs at any gastrointestinal site and for gallbladder adenocarcinoma. RESULTS: Overall, 754 patients with gallbladder NETs were identified. Patients were predominantly female (n = 518, 69%), White (n = 503, 67%), presented with stage IV disease (n = 295, 39%) and had high-grade lesions (n = 312, 41%). The majority underwent resection (n = 480, 64%), primarily simple cholecystectomy (n = 431, 90%), whereas a minority received multimodal therapy (n = 145, 21%). Among patients who underwent resection, older age (p = 0.001), large cell histology (p = 0.012), and positive margins (p = 0.030) were independently associated with worse overall survival. Patients with gallbladder NETs had improved survival relative to those with gallbladder adenocarcinoma (p = 0.001), but significantly worse survival than patients with NETs from other gastrointestinal sites (p < 0.001). CONCLUSIONS: Primary gallbladder NETs are aggressive lesions that carry a worse prognosis than NETs of other gastrointestinal sites. Older age, positive margins, and large cell histology are associated with abbreviated survival after resection.


Assuntos
Adenocarcinoma/mortalidade , Bases de Dados Factuais , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias Gastrointestinais/mortalidade , Tumores Neuroendócrinos/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Humanos , Masculino , Metástase Neoplásica , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
17.
PLoS One ; 14(5): e0216781, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091247

RESUMO

AIM: Purpose of this study was to evaluate the association of the spatial heterogeneity (asphericity, ASP) in intra-therapeutic SPECT/ CT imaging of somatostatin receptor (SSR) positive metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) for morphological treatment response to peptide receptor radionuclide therapy (PRRT). Secondly, we correlated ASP derived form a pre-therapeutic OctreoScan (ASP[In]) and an intra-therapeutic [177Lu]-SPECT/CT (ASP[Lu]). MATERIALS AND METHODS: Data from first therapy cycle [177Lu-DOTA0-Tyr3]octreotate ([177Lu]-DOTATATE)-PRRT was retrospectively analyzed in 33 patients (m = 20; w = 13; median age, 72 [46-88] years). The evaluation of response to PRRT was performed according to RECIST 1.1 in responding lesions [RL (SD, PR, CR), n = 104] and non-responding lesions [NRL (PD), n = 27]. The association of SSR tumor heterogeneity with morphological response was evaluated by Kruskal-Wallis test and receiver operating characteristic curve (ROC). The optimal threshold for separation (RL vs. NRL) was calculated using the Youden-index. Relationship between pre- and intra-therapeutic ASP was determined with Spearman's rank correlation coefficient (ρ) and Bland-Altman plots. RESULTS: A total of 131 lesions (liver: n = 59, lymph nodes: n = 48, bone: n = 19, pancreas: n = 5) were analyzed. Lesions with higher ASP values showed a significantly poorer response to PRRT (PD, median: 11.3, IQR: 8.5-15.5; SD, median: 3.4, IQR: 2.1-4.5; PR, median 1.7, IQR: 0.9-2.8; CR, median: 0.5, IQR: 0.0-1.3); Kruskal-Wallis, p<0.001). ROC analyses revealed a significant separation between RL and NRL for ASP after 4 months (AUC 0.85, p<0.001) and after 12 months (AUC 0.94, p<0.001). The optimal threshold for ASP was >5.45% (sensitivity 96% and specificity 82%). The correlation coefficient of pre- and intra-therapeutic ASP revealed ρ = 0.72 (p <0.01). The mean absolute difference between ASP[In] and ASP[Lu] was -0.04 (95% Limits of Agreement, -6.1-6.0). CONCLUSION: Pre- and intra-therapeutic ASP shows a strong correlation and might be an useful tool for therapy monitoring.


Assuntos
Neoplasias Gastrointestinais , Proteínas de Neoplasias/metabolismo , Tumores Neuroendócrinos , Octreotida/análogos & derivados , Receptores de Somatostatina/metabolismo , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/mortalidade , Intervalo Livre de Doença , Feminino , Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/mortalidade , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/mortalidade , Octreotida/administração & dosagem , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida
18.
J Surg Oncol ; 120(2): 256-261, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31066052

RESUMO

BACKGROUND: The aim was to describe complicated tumor response (CTR) to tyrosine-kinase inhibitors (TKI) in gastrointestinal stromal tumors (GIST) patients. METHODS: From 2001 to 2017, data from patients with metastatic (group A) or locally advanced (group B) GIST who received TKI at our institution were collected. We defined CTR as bleeding, abscess, or perforation as surgical complications of TKI. Patients who had progressive disease were excluded. Clinical characteristics were assessed, and time of occurrence and mortality rate recorded. RESULTS: Among 470 patients, 30 developed CTR (6.4%), 26 in group A (6.8%) and four in group B (4.5%) (P = 0.43). Bleeding, abscess, and perforation, respectively, were observed in 17 (56.7%), 8 (26.7%), and 5 (16.7%) patients. A conservative approach was possible in 17 (56.7%) cases; four (13.3%) patients received percutaneous drainage, while nine (30%) underwent emergency surgery. The overall rate of mortality was 13.3%. CTR occurred after 1.6 months (median time) from the imatinib mesylate onset in group B and 14 months in group A. CONCLUSIONS: While the risk of CTR in early metastatic patients is virtually nil, patients with locally advanced disease should be monitored carefully. CTR as a consequence of TKI therapy do not prevent patients receiving a potentially curative surgery.


Assuntos
Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Mesilato de Imatinib/efeitos adversos , Complicações Pós-Operatórias/terapia , Inibidores de Proteínas Quinases/efeitos adversos , Sunitinibe/efeitos adversos , Antineoplásicos/efeitos adversos , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
20.
J Surg Res ; 241: 170-177, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31026795

RESUMO

BACKGROUND: Possibly originating from interstitial Cajal cells, gastrointestinal stromal tumors (GISTs) have variable biological behaviors. In this study, we aimed to examine the factors affecting the disease-free survival (DFS) in patients with GIST who underwent operation. MATERIAL AND METHODS: The study included the patients who were followed up and treated for GIST in our oncology clinic between 2002 and 2017. The Armed Forces Institute of Pathology criteria (Miettinen risk score) were used for risk stratification of patients. RESULTS: Seventy-four patients were included to the study, where female patients constituted 52.7%, and the median age was 56 (range: 24-83) y. Most common primary tumor location was the stomach (51.4%), followed by the small intestine (33.8%), colorectum (10.8%), and retroperitoneum (4.1%). Miettinen risk score showed 12 patients (16.7%) at very low risk, 15 patients (20.8%) at low risk, 18 patients (25%) at intermediate risk, and 27 patients (37.5%) at high risk. DFS was significantly lower in patients with small intestine involvement than in cases with stomach involvement (P = 0.004). DFS was significantly lower in patients at high risk than in patients with no high risk (P = 0.034). Small intestine localization (hazard ratio [HR], 8.98; 95% confidence interval [CI], 1.14-8.18), high-risk score (HR, 5.16; 95% CI, 1.42-12.75), c-kit positivity (HR, 0.24; 95% CI, 0.13-0.69), and adjuvant therapy (HR, 0.37; 95% CI, 0.20-0.92) were found to be the most significant factors affecting DFS. CONCLUSIONS: Our study showed negative effects of small intestine localization and high-risk category and positive effects of c-kit positivity and adjuvant therapy on DFS in patients with GIST who underwent operation. When a decision will be made in favor of adjuvant therapy, tumor localization and c-kit mutation should also be considered in addition to risk score.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Neoplasias Gastrointestinais/terapia , Tumores do Estroma Gastrointestinal/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/estatística & dados numéricos , Colo/patologia , Colo/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/mortalidade , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/mortalidade , Humanos , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Proteínas Proto-Oncogênicas c-kit/genética , Reto/patologia , Reto/cirurgia , Espaço Retroperitoneal/patologia , Espaço Retroperitoneal/cirurgia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Estômago/patologia , Estômago/cirurgia , Adulto Jovem
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