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This review summarises the recent evidence on preoperative therapeutic strategies in pancreatic cancer and discusses the rationale for an imminent need for a personalised therapeutic approach in non-metastatic disease. The molecular diversity of pancreatic cancer and its influence on prognosis and treatment response, combined with the failure of 'all-comer' treatments to significantly impact on patient outcomes, requires a paradigm shift towards a genomic-driven approach. This is particularly important in the preoperative, potentially curable setting, where a personalised treatment allocation has the substantial potential to reduce pancreatic cancer mortality.
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Neoplasias Pancreáticas , Medicina de Precisão , Biomarcadores Tumorais/genética , Humanos , Terapia Neoadjuvante , Neoplasias Pancreáticas/cirurgia , PrognósticoRESUMO
BACKGROUND: Homologous recombination repair deficiency (HRD) is a frequent feature of high-grade serous ovarian, fallopian tube and peritoneal carcinoma (HGSC) and is associated with sensitivity to PARP inhibitor (PARPi) therapy. HRD testing provides an opportunity to optimise PARPi use in HGSC but methodologies are diverse and clinical application remains controversial. MATERIALS AND METHODS: To define best practice for HRD testing in HGSC the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project that incorporated a systematic review approach. The main aims were to (i) define the term 'HRD test'; (ii) provide an overview of the biological rationale and the level of evidence supporting currently available HRD tests; (iii) provide recommendations on the clinical utility of HRD tests in clinical management of HGSC. RESULTS: A broad range of repair genes, genomic scars, mutational signatures and functional assays are associated with a history of HRD. Currently, the clinical validity of HRD tests in ovarian cancer is best assessed, not in terms of biological HRD status per se, but in terms of PARPi benefit. Clinical trials evidence supports the use of BRCA mutation testing and two commercially available assays that also incorporate genomic instability for identifying subgroups of HGSCs that derive different magnitudes of benefit from PARPi therapy, albeit with some variation by clinical scenario. These tests can be used to inform treatment selection and scheduling but their use is limited by a failure to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies. Existing tests lack negative predictive value and inadequately address the complex and dynamic nature of the HRD phenotype. CONCLUSIONS: Currently available HRD tests are useful for predicting likely magnitude of benefit from PARPis but better biomarkers are urgently needed to better identify current homologous recombination proficiency status and stratify HGSC management.
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Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Biomarcadores , Carcinoma Epitelial do Ovário , Feminino , Recombinação Homóloga , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêuticoRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients. Baseline and follow-up levels were assessed in 372 additional metastatic PDAC patients who received nab-paclitaxel with gemcitabine (n = 184) or gemcitabine monotherapy (n = 188) in the phase III MPACT trial. Increased levels of ADAM12 were found in PDAC patients compared to healthy controls (p < 0.0001, n = 157 and n = 38). High levels of ADAM12 significantly associated with poor outcome in resected PDAC (HR 2.07, p = 0.04). In the MPACT trial survival was significantly longer for patients who received nab-paclitaxel and had undetectable ADAM12 levels before treatment (OS 12.3 m vs 7.9 m p = 0.0046). Consistently undetectable or decreased ADAM12 levels during treatment significantly associated with longer survival as well (OS 14.4 m and 11.2 m, respectively vs 8.3, p = 0.0054). We conclude that ADAM12 is a blood-borne proxy for stromal activation, the levels of which have prognostic significance and correlate with treatment benefit.
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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a dismal disease, with very little improvement in survival over the past 50 years. Recent large-scale genomic studies have improved understanding of the genomic and transcriptomic landscape of the disease, yet very little is known about molecular heterogeneity according to tumour location in the pancreas; body and tail PDACs especially tend to have a significantly worse prognosis. The aim was to investigate the molecular differences between PDAC of the head and those of the body and tail of the pancreas. METHODS: Detailed correlative analysis of clinicopathological variables, including tumour location, genomic and transcriptomic data, was performed using the Australian Pancreatic Cancer Genome Initiative (APGI) cohort, part of the International Cancer Genome Consortium study. RESULTS: Clinicopathological data were available for 518 patients recruited to the APGI, of whom 421 underwent genomic analyses; 179 of these patients underwent whole-genome and 96 RNA sequencing. Patients with tumours of the body and tail had significantly worse survival than those with pancreatic head tumours (12·1 versus 22·0 months; P = 0·001). Location in the body and tail was associated with the squamous subtype of PDAC. Body and tail PDACs enriched for gene programmes involved in tumour invasion and epithelial-to-mesenchymal transition, as well as features of poor antitumour immune response. Whether this is due to a molecular predisposition from the outset, or reflects a later time point on the tumour molecular clock, requires further investigation using well designed prospective studies in pancreatic cancer. CONCLUSION: PDACs of the body and tail demonstrate aggressive tumour biology that may explain worse clinical outcomes.
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Carcinoma Ductal Pancreático/genética , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Feminino , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Patologia Molecular/métodos , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , TranscriptomaRESUMO
The incidence of pancreatic ductal adenocarcinoma (PDAC) is steadily increasing and the annual death-to-incidence ratio approaches one. This is a figure that has not changed for several decades. Surgery remains the only chance of cure; however, only less than 20% of patients are amenable to operative resection. Despite successful surgical resection, the majority of the patients still succumb to recurrent metastatic disease. Therefore, there is an urgent need to develop novel therapeutic strategies and to better select patients for current therapies. In this review, we will discuss current management by highlighting the landmark clinical trials that have shaped current care. We will then discuss the challenges of therapeutic development using the current randomized-controlled trial paradigm when confronted with the molecular heterogeneity of PDAC. Finally, we will discuss strategies that may help to shape the management of PDAC in the near future.
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Genômica , Neoplasias Pancreáticas/genética , Antineoplásicos/uso terapêutico , Biomarcadores , Carcinoma Ductal Pancreático/genética , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Progressão da Doença , Genômica/métodos , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Medicina de Precisão , Resultado do TratamentoRESUMO
BACKGROUND: Adjuvant chemotherapy improves survival for patients with resected pancreatic cancer. Elderly patients are under-represented in Phase III clinical trials, and as a consequence the efficacy of adjuvant therapy in older patients with pancreatic cancer is not clear. We aimed to assess the use and efficacy of adjuvant chemotherapy in older patients with pancreatic cancer. METHODS: We assessed a community cohort of 439 patients with a diagnosis of pancreatic ductal adenocarcinoma who underwent operative resection in centres associated with the Australian Pancreatic Cancer Genome Initiative. RESULTS: The median age of the cohort was 67 years. Overall only 47% of all patients received adjuvant therapy. Patients who received adjuvant chemotherapy were predominantly younger, had later stage disease, more lymph node involvement and more evidence of perineural invasion than the group that did not receive adjuvant treatment. Overall, adjuvant chemotherapy was associated with prolonged survival (median 22.1 vs 15.8 months; P<0.0001). Older patients (aged ≥70) were less likely to receive adjuvant chemotherapy (51.5% vs 29.8%; P<0.0001). Older patients had a particularly poor outcome when adjuvant therapy was not delivered (median survival=13.1 months; HR 1.89, 95% CI: 1.27-2.78, P=0.002). CONCLUSION: Patients aged ≥70 are less likely to receive adjuvant therapy although it is associated with improved outcome. Increased use of adjuvant therapy in older individuals is encouraged as they constitute a large proportion of patients with pancreatic cancer.
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Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Fatores Etários , Idoso , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante , Estudos de Coortes , Feminino , Humanos , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Metástase Linfática , Masculino , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , PrognósticoRESUMO
Myc oncoproteins are commonly upregulated in human cancers of different organ origins, stabilized by Aurora A, degraded through ubiquitin-proteasome pathway-mediated proteolysis, and exert oncogenic effects by modulating gene and protein expression. Histone deacetylases are emerging as targets for cancer therapy. Here we demonstrated that the class III histone deacetylase SIRT2 was upregulated by N-Myc in neuroblastoma cells and by c-Myc in pancreatic cancer cells, and that SIRT2 enhanced N-Myc and c-Myc protein stability and promoted cancer cell proliferation. Affymetrix gene array studies revealed that the gene most significantly repressed by SIRT2 was the ubiquitin-protein ligase NEDD4. Consistent with this finding, SIRT2 repressed NEDD4 gene expression by directly binding to the NEDD4 gene core promoter and deacetylating histone H4 lysine 16. Importantly, NEDD4 directly bound to Myc oncoproteins and targeted Myc oncoproteins for ubiquitination and degradation, and small-molecule SIRT2 inhibitors reactivated NEDD4 gene expression, reduced N-Myc and c-Myc protein expression, and suppressed neuroblastoma and pancreatic cancer cell proliferation. Additionally, SIRT2 upregulated and small-molecule SIRT2 inhibitors decreased Aurora A expression. Our data reveal a novel pathway critical for Myc oncoprotein stability, and provide important evidences for potential application of SIRT2 inhibitors for the prevention and therapy of Myc-induced malignancies.
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Proteínas Proto-Oncogênicas c-myc/metabolismo , Sirtuína 2/metabolismo , Aurora Quinases , Linhagem Celular Tumoral , Proliferação de Células , Complexos Endossomais de Distribuição Requeridos para Transporte , Expressão Gênica , Humanos , Naftóis/farmacologia , Ubiquitina-Proteína Ligases Nedd4 , Fenilpropionatos/farmacologia , Fosforilação , Ligação Proteica , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Estabilidade Proteica , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/genética , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Sirtuína 2/antagonistas & inibidores , Sirtuína 2/genética , Ubiquitina-Proteína Ligases , Ubiquitinação , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND AND STUDY AIMS: Transanal endoscopic microsurgery (TEM) has been shown to be highly effective for early rectal cancer, and endoscopic submucosal dissection (ESD) has been introduced to treat noninvasive colorectal neoplasia. The aim of this study was to compare the outcomes of ESD and TEM for superficial early rectal cancer. PATIENTS AND METHODS: We retrospectively analyzed 63 patients with nonpolypoid rectal high grade dysplasia or submucosa-invading cancer who were treated with ESD or TEM, and compared clinical outcomes and safety between the treatment groups. RESULTS: 30 patients underwent ESD and 33 underwent TEM. For ESD compared with TEM, en bloc resection rates were 96.7% vs. 100% (P = 0.476) and R0 resection rates were 96.7 % vs. 97.0 % (P = 1.000). There were no cases of local recurrence or distant metastasis in either group. Antibiotics were required in 11 patients (36.7%) in the ESD group and 33 (100%) in the TEM group (P < 0.001). There was no difference in net procedure time although ESD was associated with shorter total procedure time and hospital stay than TEM, with mean (standard deviation [SD]) 84.0 (51.2) vs. 116.4 (58.5) min (P = 0.0023), and 3.6 (1.2) vs. 6.6 (3.5) days (P < 0.001), respectively. There were no significant differences in complications between the two groups. CONCLUSIONS: Both ESD and TEM are effective and oncologically safe for treating nonpolypoid rectal high grade dysplasia and submucosa-invading cancers. ESD has the additional advantages of minimal invasiveness and avoidance of anesthesia. Therefore, ESD could be recommended as a treatment option for superficial early rectal cancers.
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Microcirurgia/métodos , Proctoscopia/métodos , Neoplasias Retais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Complicações Pós-Operatórias , Lesões Pré-Cancerosas/cirurgia , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Current staging methods for pancreatic cancer (PC) are inadequate, and biomarkers to aid clinical decision making are lacking. Despite the availability of the serum marker carbohydrate antigen 19.9 (CA19.9) for over two decades, its precise role in the management of PC is yet to be defined, and as a consequence, it is not widely used. METHODS: We assessed the relationship between perioperative serum CA19.9 levels, survival and adjuvant chemotherapeutic responsiveness in a cohort of 260 patients who underwent operative resection for PC. RESULTS: By specifically assessing the subgroup of patients with detectable CA19.9, we identified potential utility at key clinical decision points. Low postoperative CA19.9 at 3 months (median survival 25.6 vs 14.8 months, P=0.0052) and before adjuvant chemotherapy were independent prognostic factors. Patients with postoperative CA 19.9 levels>90 U/ml did not benefit from adjuvant chemotherapy (P=0.7194) compared with those with a CA19.9 of ≤90 U/ml (median 26.0 vs 16.7 months, P=0.0108). Normalization of CA19.9 within 6 months of resection was also an independent favorable prognostic factor (median 29.9 vs 14.8 months, P=0.0004) and normal perioperative CA19.9 levels identified a good prognostic group, which was associated with a 5-year survival of 42%. CONCLUSIONS: Perioperative serum CA19.9 measurements are informative in patients with detectable CA19.9 (defined by serum levels of >5 U/ml) and have potential clinical utility in predicting outcome and response to adjuvant chemotherapy. Future clinical trials should prioritize incorporation of CA19.9 measurement at key decision points to prospectively validate these findings and facilitate implementation.
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Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Carcinoma Ductal Pancreático/sangue , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/terapia , Quimioterapia Adjuvante , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Período Perioperatório , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
BACKGROUND AND STUDY AIM: Rectal carcinoids are low-grade malignancies that are usually treated by endoscopic resection. However, on pathologic examination, resection margins that are positive for carcinoid cells are frequently found. Patient outcomes were reviewed after endoscopic resection of rectal carcinoids and the clinical significance of possible residual disease, as defined by pathologic and endoscopic examination, was evaluated. PATIENTS AND METHODS: The medical records and endoscopic findings of 347 patients presenting with rectal carcinoids to 14 university hospitals in Korea between January 1999 and June 2007 were retrospectively analyzed. RESULTS: A total of 304 patients were treated with endoscopic resection, and 43 patents were treated with surgery. In the endoscopic resection group, the complete resection rate was 88.2% based on endoscopic appearance (CR-E) and 60.2% based on pathologic evaluation (CR-P). The agreement between CR-E and CR-P was low (κ=0.192). No residual tumors were found in 77 of 85 patients (90.6%) who were CR-E but not CR-P and who had endoscopic biopsy taken at 24-month follow-up. The receiver-operating characteristic curve identified an optimal cut-off value of 10.5 mm, at which the sensitivity and the specificity for metastasis were 100% and 89%, respectively. The risk factors for metastasis by multivariate analysis were tumor size, increased mitotic rate, and lymphovascular invasion. CONCLUSIONS: Endoscopic resection is a safe and effective modality for treating well-differentiated rectal carcinoids smaller than 10 mm in diameter. Discrepancies were observed between CR-E and CR-P. The risk factors for metastasis were tumor size, increased mitotic rate, and lymphovascular invasion.
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Tumor Carcinoide/patologia , Tumor Carcinoide/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasos Sanguíneos/patologia , Tumor Carcinoide/diagnóstico por imagem , Colonoscopia , Tomada de Decisões , Endossonografia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Invasividade Neoplásica , Metástase Neoplásica , Neoplasia Residual , Curva ROC , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/secundário , Reoperação , Estudos Retrospectivos , Carga Tumoral , Adulto JovemRESUMO
BACKGROUND/OBJECTIVES: This study was aimed to assess the beneficial effects on metabolic syndrome of functional yogurt NY-YP901 (Namyang Dairy Product Co. Ltd and Nutra R&BT Inc., Seoul, Korea) supplemented with mixture of Streptococcus thermophilus, Lactobacillus acidophilus, Bifidobacterium infantis and extra-ingredients containing Bifidobacterium breve (CBG-C2), Enterococcus faecalis FK-23, fibersol-2 and so on. SUBJECTS/METHODS: This study was designed as an 8-week randomized, double-blind, placebo-controlled, parallel study. Treatment and control groups consumed a functional yogurt NY-YP901 (150 ml) and a placebo yogurt twice a day, respectively, for 8 weeks. Body weight and body mass index (BMI), blood pressure, lipid profiles, fasting glucose with HbA1C and waist circumference were measured before and after treatment. Inclusion criteria were healthy individuals between the ages 20-65 years old who submitted an informed consent. RESULTS: During the period August 2009 to December 2009, 101 healthy participants (31 males and 70 females) finished the study. Treatment group were 53 individuals, and the control group were 48 individuals. In the treatment group consuming NY-YP901, statistically significant beneficial changes were observed in body weight (treatment group vs control group=-0.24±1.50 vs +0.64±1.39 kg, P<0.05), BMI (-0.10±0.58 vs +0.24±0.50 kg/m(2), P<0.05 ) and low-density lipoprotein (LDL)-cholesterol (-7.71±14.14 vs -0.43±15.32 mg/dl, P<0.05) after 8 weeks. The change in other parameters was not different between the treatment and the control groups. CONCLUSIONS: The functional yogurt NY-YP901 reduced LDL-cholesterol, body weight and BMI in the subjects at a 300-ml consumption daily for 8 weeks. From these findings, regular intake of functional yogurt NY-YP901 may be consequently related to improve metabolic syndrome.
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Alimentos Formulados/microbiologia , Síndrome Metabólica/dietoterapia , Probióticos/uso terapêutico , Iogurte/microbiologia , Adulto , Bifidobacterium , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Método Duplo-Cego , Enterococcus faecalis , Feminino , Alimentos Formulados/análise , Humanos , Lactobacillus acidophilus , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Polissacarídeos/administração & dosagem , Polissacarídeos/uso terapêutico , Probióticos/administração & dosagem , República da Coreia/epidemiologia , Risco , Streptococcus thermophilus , Redução de Peso , Iogurte/análiseRESUMO
Myc oncoproteins and histone deacetylases (HDACs) modulate gene transcription and enhance cancer cell proliferation, and HDAC inhibitors are among the most promising new classes of anticancer drugs. Here, we show that N-Myc and c-Myc upregulated HDAC2 gene expression in neuroblastoma and pancreatic cancer cells, respectively, which contributed to N-Myc- and c-Myc-induced cell proliferation. Cyclin G2 (CCNG2) was commonly repressed by N-Myc and HDAC2 in neuroblastoma cells and by c-Myc and HDAC2 in pancreatic cancer cells, and could be reactivated by HDAC inhibitors. 5-bromo-2'-deoxyuridine incorporation assays showed that transcriptional repression of CCNG2 was, in part, responsible for N-Myc-, c-Myc- and HDAC2-induced cell proliferation. Dual crosslinking chromatin immunoprecipitation assay demonstrated that N-Myc acted as a transrepressor by recruiting the HDAC2 protein to Sp1-binding sites at the CCNG2 gene core promoter. Moreover, HDAC2 was upregulated, and CCNG2 downregulated, in pre-cancerous and neuroblastoma tissues from N-Myc transgenic mice, and c-Myc overexpression correlated with upregulation of HDAC2 and repression of CCNG2 in tumour tissues from pancreatic cancer patients. Taken together, our data indicate the critical roles of upregulation of HDAC2 and suppression of CCNG2 in Myc-induced oncogenesis, and have significant implications for the application of HDAC inhibitors in the prevention and treatment of Myc-driven cancers.
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Histona Desacetilase 2/genética , Proteínas Proto-Oncogênicas c-myc/fisiologia , Transcrição Gênica , Regulação para Cima , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células , Imunoprecipitação da Cromatina , Ciclina G2/genética , Primers do DNA , Humanos , Camundongos , Camundongos Transgênicos , Neuroblastoma/patologia , Neoplasias Pancreáticas/patologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Although endoscopy is recommended for patients with iron deficiency anaemia, there is, currently, no consensus on the role of endoscopy for iron-deficient patients without anaemia. The goal of this study was to determine the prevalence of serious gastrointestinal (GI) lesions, identified by endoscopy in patients with iron deficiency and anaemia compared with patients with iron deficiency without anaemia. METHODS: One thousand five hundred and eighteen patients with a ferritin value of
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Anemia Ferropriva/patologia , Duodenoscopia/normas , Esofagoscopia/normas , Gastroenteropatias/patologia , Gastroscopia/normas , Deficiências de Ferro , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Duodenoscopia/métodos , Esofagoscopia/métodos , Feminino , Gastroenteropatias/sangue , Gastroenteropatias/diagnóstico , Hemorragia Gastrointestinal/sangue , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/patologia , Gastroscopia/métodos , Humanos , Ferro/sangue , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: To achieve en bloc resection for large lesions, endoscopic mucosal resection after circumferential precutting and endoscopic submucosal dissection techniques have been developed. AIM: To compare endoscopic submucosal dissection with endoscopic mucosal resection after circumferential precutting in terms of the clinical efficacy and safety. PATIENTS AND METHODS: 346 consecutive patients underwent their first endoscopic mucosal resection after circumferential precutting (103 patients) or endoscopic submucosal dissection (243 patients) for early gastric cancer and their clinical outcomes were compared. RESULTS: For early gastric cancer >or=20mm endoscopic submucosal dissection group demonstrated significantly higher en bloc resection and en bloc plus R0 resection rate compared with endoscopic mucosal resection after circumferential precutting group. For early gastric cancer with size of 10-19 mm, endoscopic submucosal dissection group also showed significantly higher en bloc resection rate. For early gastric cancer <20mm, however, en bloc plus R0 resection rate for endoscopic mucosal resection after circumferential precutting group was comparable to that for endoscopic submucosal dissection group. In case of R0 resection of intramucosal differentiated cancer, neither group showed local recurrence during the median 29 and 17 months of follow-up. Two groups did not show significant difference in the bleeding or perforation rates. CONCLUSION: For early gastric cancer <20mm endoscopic mucosal resection after circumferential precutting may be considered as an alternative choice to endoscopic submucosal dissection. However, for early gastric cancer >or=20mm endoscopic submucosal dissection should be considered as the first choice for treating early gastric cancer.
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Mucosa Gástrica/cirurgia , Gastroscopia/métodos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletrocirurgia , Feminino , Mucosa Gástrica/patologia , Gastroscopia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
BACKGROUND: 5-Aminosalicylic acid lacks the well-known side effects associated with the long-term use of non-steroidal anti-inflammatory drugs. We investigated anti-carcinogenic mechanisms of 5-aminosalicylic acid on a colon cancer cell line. METHODS: MTT analysis was performed for various colon cancer cell lines. The expression of NF-kappaB and metalloproteinases was examined in either HT-29 cells treated with IL-1beta and/or 5-aminosalicylic acid. Matrigel assay was used to evaluate invasive potential of HT-29 cells. Analysis of a cDNA microarray containing 8700 genes was performed to identify the alteration of gene expression in response to treatment to 5-aminosalicylic acid. RESULTS: The use of MTT analysis showed that 5-aminosalicylic acid suppressed the growth of HT-29 cells. The activity of NF-kappaB was also decreased by combined-treatment with IL-1beta and 5-aminosalicylic acid. The use of an ELISA and zymography demonstrated that MMP-2 and MMP-9 enzyme activity were decreased in HT-29 cells by treatment with various concentration of 5-aminosalicylic acid. A matrigel analysis demonstrated that 5-aminosalicylic acid treatment on HT-29 significantly inhibited the invasiveness of the cells. In cDNA microarray, 163 genes following 5-aminosalicylic acid exposure showed altered expression. CONCLUSIONS: This study indicated that 5-aminosalicylic acid suppresses the growth of human colon cancer cells and is able to inhibit MMPs expression via NF-kappaB mediated cell signals and invasiveness.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Neoplasias do Colo/patologia , Neoplasias do Colo/prevenção & controle , Mesalamina/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/enzimologia , Regulação para Baixo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Metaloproteases/efeitos dos fármacos , Metaloproteases/genética , NF-kappa B/efeitos dos fármacos , Invasividade Neoplásica/prevenção & controle , Análise de Sequência com Séries de OligonucleotídeosRESUMO
BACKGROUND AND STUDY AIMS: Although capsule endoscopy has become a central diagnostic tool for small-bowel evaluation, retention of a capsule remains a major concern. This study attempted to investigate the incidence and clinical outcomes of capsule retention, and to determine the factors predictive of spontaneous capsule passage after retention. PATIENTS AND METHODS: Through a nationwide multicenter survey, we retrospectively reviewed the records of 1291 patients who had a capsule endoscopy between February 2002 and July 2006 in Korea. Clinical and procedural characteristics and postprocedural outcomes were analyzed for the cases with capsule retention. RESULTS: Capsule retention occurred in 2.5 % of total cases (32/1291). The major diseases accompanying capsule retention were Crohn's disease, malignant tumors, and tuberculous enterocolitis, in decreasing order. In 11 of the 32 patients (34.4 %), early surgical or endoscopic interventions were instituted for diagnosis or treatment of diseases before retention symptoms developed. The remaining 21 (65.6 %) patients initially received medical treatments. Of these, 10 (31.3 %) ultimately underwent surgical intervention due to the development of symptoms of intestinal obstruction or medical treatment failure. The other 11 (34.4 %) eventually passed the capsule. The presence of a larger lumen diameter (greater than two-thirds of the capsule diameter) at the stricture site was associated with spontaneous passage. CONCLUSIONS: Our large-scale study suggests that retention occurs infrequently during capsule endoscopy. Moreover, a retained capsule might indicate the best intervention for the offending pathology, or it may spontaneously pass in the long run, particularly in patients with less small bowel stricture.
Assuntos
Cápsulas Endoscópicas/efeitos adversos , Endoscopia por Cápsula/efeitos adversos , Corpos Estranhos/epidemiologia , Enteropatias/diagnóstico , Obstrução Intestinal/epidemiologia , Intestino Delgado , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscopia por Cápsula/métodos , Falha de Equipamento , Feminino , Corpos Estranhos/etiologia , Pesquisas sobre Atenção à Saúde , Humanos , Incidência , Obstrução Intestinal/etiologia , Coreia (Geográfico) , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Probabilidade , Prognóstico , Estudos Retrospectivos , Medição de RiscoRESUMO
BACKGROUND AND STUDY AIMS: Primary NK-/T-cell lymphoma of the gastrointestinal tract is a very rare disease with a poor prognosis. The aim of this study was to determine the clinical and endoscopic characteristics of patients with primary gastrointestinal NK-/T-cell lymphoma. PATIENTS AND METHODS: The clinical features of 14 patients with primary gastrointestinal NK-/T-cell lymphoma and the endoscopic findings in 11 of these patients were reviewed. Their median age was 42 years (range 23-78) at the time of diagnosis. RESULTS: The initial presenting symptoms of primary gastrointestinal NK-/T-cell lymphoma were gastrointestinal bleeding (n = 6, 42%), abdominal pain (n = 4, 29%), and epigastric soreness (n = 4, 29%). The disease was at an advanced stage at the time of diagnosis: stage II in 5 patients (36%); stage III in 4 (28%); and stage IV in 5 (36%). Initial treatment was with chemotherapy (n = 8, 57%) or surgical resection (n = 5, 36%). The median survival for all patients was 9 months. On endoscopy in 11 patients, the anatomic location of the primary lesion was found to be: stomach, n = 3 (27%); esophagus, n = 2 (18%); duodenum, n = 1 (9%); and the ileocolonic area, n = 5 (46%). These lesions were ulceroinfiltrative in 4 cases (36%), ulcerative in 3 cases (27%), superficial/erosive in 3 cases (27%), and infiltrative in 1 case (9%). No prominent fungating mass was seen in any patient. CONCLUSIONS: Primary gastrointestinal NK-/T-cell lymphoma was endoscopically characterized by superficial/erosive, ulcerative, or ulceroinfiltrative lesions without fungating mass. The most common presenting symptom was gastrointestinal bleeding. Despite aggressive treatments, the prognosis was very poor.
Assuntos
Endoscopia Gastrointestinal , Neoplasias Gastrointestinais/patologia , Células Matadoras Naturais/patologia , Linfoma de Células T/patologia , Adulto , Idoso , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Análise de SobrevidaRESUMO
BACKGROUND: There is little agreement about the efficacy of nonsurgical treatment for abscess associated with Crohn's disease. Furthermore, there is no study on characteristics of abscess or patient that nonsurgical treatment could be worth trying as initial treatment. AIMS: To evaluate the outcome of nonsurgical treatment in Crohn's disease-related abscess and identify factor leading to failure of nonsurgical treatment of this complication. PATIENTS: Twenty-four patients, who consecutively admitted for Crohn's disease-related abscess to our institution during a 7-year period, underwent nonsurgical treatment as initial therapy. METHODS: Outcome data such as recurrence and intractability, and clinical features were retrospectively analysed. Univariate analysis with patient-related factors and abscess-related factors was performed for risk factor identification. RESULTS: Median follow-up period was 47.5 months. Of the eligible patients, 19 patients were treated medically and 5 patients underwent percutaneous catheter drainage with medical treatment. Overall success rate of nonsurgical treatment in our centre was 66.7%. The cumulative recurrence rate at 7 months was 12.5%. All recurrences occurred within 7 months from complete resolution on follow-up imaging. Univariate analysis showed that the significant factors which lead to failure of nonsurgical treatment were presence of associated fistula and concurrent steroid use (P=0.019 and P=0.019, respectively). CONCLUSION: Nonsurgical treatment can be considered as initial treatment modality for the Crohn's disease-related abscess without concurrent steroid therapy or relevant fistula.