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1.
Gastric Cancer ; 23(4): 639-647, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32103376

RESUMEN

BACKGROUND: There is no consensual definition for gastric linitis plastica (GLP). We aim to construct a diagnostic score to distinguish this rare tumor from usual gastric adenocarcinomas. METHODS: In this retrospective study, all patients who had gastrectomy for cancer between 2007 and 2017 in French tertiary centers were included. The outcome was a diagnosis of GLP based on pathological review of the surgical specimen. The diagnostic score was created by using variables that were most frequently associated with GLP using penalized logistic regression on multiply imputed datasets. We used discrimination measures to assess the performances of the score. Internal validation was performed using bootstrapping methods to correct for over-optimism. RESULTS: 220 patients including 71 linitis plastica (female 49%, median age 57 years) were analyzed. The six parameters retained in the diagnosis score were the presence of large folds and/or parietal thickening on at least one segment, pangastric infiltration and presence of gastric stenosis on the upper endoscopy, circumferential thickening on at least one segment and thickening of the third hyperechogenic layer on endoscopic ultrasound and the presence of signet ring cells on endoscopic biopsies. The area under the ROC curve (AUC) was 0.967 with a sensitivity of 94% [89.9-97.3] and a specificity of 88.7% [81.7-95.8] for a threshold of 2.75. After internal validation, the corrected AUC was 0.959. CONCLUSION: It is the first study validating a pre-therapeutic diagnostic score (Saint Louis linitis score) with an excellent ability to discriminate GLP from non-GLP adenocarcinomas. An external validation is necessary to confirm our data.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Gastrectomía/métodos , Linitis Plástica/diagnóstico , Neoplasias Gástricas/diagnóstico , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Linitis Plástica/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , Neoplasias Gástricas/terapia
2.
Br J Surg ; 106(9): 1237-1247, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31183866

RESUMEN

BACKGROUND: BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF-mutated CRLMs. METHODS: The study included patients who underwent resection for BRAF-mutated CRLMs in 24 centres between 2012 and 2016. A case-matched comparison was made with 183 patients who underwent resection of CRLMs with wild-type BRAF during the same interval. RESULTS: Sixty-six patients who underwent resection for BRAF-mutated CRLMs in 24 centres were compared with 183 patients with wild-type BRAF. The 1- and 3-year disease-free survival (DFS) rates were 46 and 19 per cent for the BRAF-mutated group, and 55·4 and 27·8 per cent for the group with wild-type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1- and 3-year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild-type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild-type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF-mutated group (48 versus 29·8 per cent; P = 0·034). CONCLUSION: These results support surgical treatment for resectable BRAF-mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non-metastatic colorectal cancer.


Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Hepáticas/secundario , Recurrencia Local de Neoplasia/genética , Proteínas Proto-Oncogénicas B-raf/genética , Anciano , Estudios de Casos y Controles , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Femenino , Hepatectomía , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Mutación/genética , Análisis de Supervivencia
3.
Ann Oncol ; 29(5): 1211-1219, 2018 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-29438522

RESUMEN

Background: RAS mutations are currently sought for in tumor samples, which takes a median of almost 3 weeks in western European countries. This creates problems in clinical situations that require urgent treatment and for inclusion in therapeutic trials that need RAS status for randomization. Analysis of circulating tumor DNA might help to shorten the time required to determine RAS mutational status before anti-epidermal growth factor receptor antibody therapy for metastatic colorectal cancer. Here we compared plasma with tissue RAS analysis in a large prospective multicenter cohort. Patients and methods: Plasma samples were collected prospectively from chemotherapy-naive patients and analyzed centrally by next-generation sequencing (NGS) with the colon lung cancer V2 Ampliseq panel and by methylation digital PCR (WIF1 and NPY genes). Tumoral RAS status was determined locally, in parallel, according to routine practice. For a minimal κ coefficient of 0.7, reflecting acceptable concordance (precision ± 0.07), with an estimated 5% of non-exploitable data, 425 subjects were necessary. Results: From July 2015 to December 2016, 425 patients were enrolled. For the 412 patients with available paired plasma and tumor samples, the κ coefficient was 0.71 [95% confidence interval (CI), 0.64-0.77] and accuracy was 85.2% (95% CI, 81.4% to 88.5%). In the 329 patients with detectable ctDNA (at least one mutation or one methylated biomarker), the κ coefficient was 0.89 (95% CI, 0.84-0.94) and accuracy was 94.8% (95% CI, 91.9% to 97.0%). The absence of liver metastases was the main clinical factor associated with inconclusive circulating tumor DNA results [odds ratio = 0.11 (95% CI, 0.06-0.21)]. In patients with liver metastases, accuracy was 93.5% with NGS alone and 97% with NGS plus the methylated biomarkers. Conclusion: This prospective trial demonstrates excellent concordance between RAS status in plasma and tumor tissue from patients with colorectal cancer and liver metastases, thus validating plasma testing for routine RAS mutation analysis in these patients. Clinical Trial registration: Clinicaltrials.gov, NCT02502656.


Asunto(s)
Biomarcadores de Tumor/sangre , ADN Tumoral Circulante/genética , Neoplasias Colorrectales/sangre , Neoplasias Hepáticas/sangre , Proteínas ras/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Selección de Paciente , Valor Predictivo de las Pruebas , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto Joven
4.
Dis Esophagus ; 30(5): 1-7, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-28375444

RESUMEN

Esophageal stricture formation after extensive endoscopic resection remains a major limitation of endoscopic therapy for early esophageal neoplasia. This study assessed a recently developed self-assembling peptide (SAP) matrix as a wound dressing after endoscopic resection for the prevention of esophageal stricture. Ten pigs were randomly assigned to the SAP or the control group after undergoing a 5-cm-long circumferential endoscopic submucosal dissection of the lower esophagus. Esophageal diameter on endoscopy and esophagogram, weight variation, and histological measurements of fibrosis, granulation tissue, and neoepithelium were assessed in each animal. The rate of esophageal stricture at day 14 was 40% in the SAP-treated group versus 100% in the control group (P = 0.2). Median interquartile range (IQR) esophageal diameter at day 14 was 8 mm (2.5-9) in the SAP-treated group versus 4 mm (3-4) in the control group (P = 0.13). The median (IQR) stricture indexes on esophagograms at day 14 were 0.32 (0.14-0.48) and 0.26 (0.14-0.33) in the SAP-treated and control groups, respectively (P = 0.42). Median (IQR) weight variation during the study was +0.2 (-7.4; +1.8) and -3.8 (-5.4; +0.6) in the SAP-treated and control groups, respectively (P = 0.9). Fibrosis, granulation tissue, and neoepithelium were not significantly different between the groups. The application of SAP matrix on esophageal wounds after a circumferential endoscopic submucosal dissection delayed the onset of esophageal stricture in a porcine model.


Asunto(s)
Estenosis Esofágica/prevención & control , Esofagectomía/efectos adversos , Matriz Extracelular/química , Complicaciones Posoperatorias/prevención & control , Técnicas de Cierre de Heridas , Animales , Modelos Animales de Enfermedad , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Estenosis Esofágica/etiología , Esofagectomía/métodos , Esófago/cirugía , Péptidos , Complicaciones Posoperatorias/etiología , Distribución Aleatoria , Porcinos , Resultado del Tratamiento
5.
Ann Oncol ; 27(12): 2172-2184, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27803003

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) reactivation is a well-known risk during chemotherapy for hematological malignancies with reported rates ranging between 14% and 72%. However, there is a paucity of data regarding HBV infection management and reactivation risk in patients receiving systemic treatments for solid tumors. DESIGN: We conducted a PubMed search for publications from January 1990 until May 2016 related to HBV reactivation. The search terms were 'hepatitis B reactivation', cross-referenced with 'chemotherapy', then 'hepatitis B' cross-referenced with International Non-proprietary Name of each of the most used chemotherapy drugs in solid tumors. RESULTS: From these data, a grading of HBV reactivation risk and recommendations for management are given for most frequently used anticancer drugs in solid tumors. CONCLUSION: Most drugs used for the treatment of solid tumors can induce hepatitis B reactivation in HBs antigen-positive patients. HBV screening can be recommended before systemic treatment initiation. Pre-emptive antiviral treatment can reduce the risk of HBV reactivation and prevent chemotherapy disruption.


Asunto(s)
Antineoplásicos/efectos adversos , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B/patología , Neoplasias/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Doxorrubicina/efectos adversos , Hepatitis B/inducido químicamente , Hepatitis B/virología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/patogenicidad , Humanos , Neoplasias/complicaciones , Neoplasias/virología , Rituximab/efectos adversos , Activación Viral/efectos de los fármacos
6.
Ann Surg Oncol ; 22(1): 295-301, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25037971

RESUMEN

BACKGROUND: First-line treatment with FOLFIRINOX significantly increases overall survival (OS) in patients with metastatic pancreatic adenocarcinoma (PA) compared with gemcitabine. The aim of this observational cohort was to evaluate the tolerability and efficacy of this regimen in unresectable locally advanced PA (LAPA). PATIENTS AND METHODS: From February 2010 to February 2012, all consecutive patients from 11 French centers treated by FOLFIRINOX for a histologically proven LAPA were prospectively enrolled. Unresectability was defined independently by each center's multidisciplinary staff at diagnosis. Absence of metastatic disease was confirmed by chest-abdomen-pelvis computed tomography scan. FOLFIRINOX was delivered every 2 weeks as previously reported until progressive disease, major toxicity, or consolidation treatment by radiotherapy and/or surgery. RESULTS: Seventy-seven patients were enrolled. They received a median number of five cycles (1-30). Grade 3-4 toxicities were neutropenia (11 %), nausea (9 %), diarrhea (6 %), fatigue (6 %), and anemia (1 %). Grade 2-3 sensory neuropathy occurred in 25 % of patients. No toxic death was reported and only 6 % of patients had to stop treatment because of toxicity. Disease control rate was 84 with 28 % of objective response (Response Evaluation Criteria in Solid Tumors). Seventy-five percent of patients received a consolidation therapy: 70 % had radiotherapy and 36 % underwent a surgical resection, with a curative intent. Within the whole cohort, 1-year OS rate was 77 % (95 % CI 65-86) and 1-year progression-free survival rate was 59 % (95 % CI 46-70). CONCLUSION: First-line FOLFIRINOX for LAPA seems to be effective and have a manageable toxicity profile. These promising results will have to be confirmed in a phase III randomized trial.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Irinotecán , Leucovorina/administración & dosificación , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Gemcitabina
7.
Invest New Drugs ; 33(1): 257-68, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25344452

RESUMEN

INTRODUCTION: Sunitinib is a multikinase inhibitor active in various cancers types including renal cancers and endocrine tumors. The study analyzed the influence of the lean body mass (LBM) and of pharmacogenetic variants on the exposure to sunitinib and its active metabolite, SU12662, and on sunitinib toxicity and clinical activity. MATERIALS AND METHODS: Exposure to sunitinib and SU12662 was assessed on days 10 and 21 during the first treatment cycle. Acute toxicity was graded using the NCI 4.0 CTCAE ver. 4.0. The LBM and 14 common single nucleotide polymorphisms in the CYP3A4/3A5, NR1I2, NR1I3, ABCB1, and ABCG2 genes were analyzed according to the drug exposure at day 10. Determinants (including sunitinib exposure and pharmacogenetic variants) for toxicities were assessed, as well as the relationship between drug exposure and survival in renal cancer patients. RESULTS: Ninety-two patients (60 % with renal cancer) were assessable for pharmacokinetics, toxicity and survival, and 66 for genetic analysis. The LBM (p < 0.0001) and a polymorphism in the ABCG2 transporter (421C>A) (p = 0.014) were two independent parameters accounting for the variability of composite (sunitinib + SU12662) exposure. Advanced age (OR = 1.47 [1.01-2.15], p = 0.048) and high sunitinib exposure (OR = 1.16 [1.05-1.28], p = 0.005) were independently associated with any grade ≥ 3 acute toxicity, and high SU12662 exposure was associated with grade ≥ 2 thrombocytopenia (OR = 1.27 [1.03-1.57], p = 0.028). A high composite area under the curve (AUC) >1,973 ng/mL∙h at day 21 was associated with a doubled survival (35.2 vs 16.7 months; log-rank p = 0.0051) in renal cancer patients. CONCLUSIONS: This study indicates that LBM and drug monitoring may be helpful in the management of sunitinib-treated patients.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Inhibidores de la Angiogénesis , Peso Corporal , Indoles , Proteínas de Neoplasias/genética , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas , Pirroles , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/farmacocinética , Inhibidores de la Angiogénesis/uso terapéutico , Receptor de Androstano Constitutivo , Citocromo P-450 CYP3A/genética , Femenino , Humanos , Indoles/efectos adversos , Indoles/sangre , Indoles/farmacocinética , Indoles/uso terapéutico , Masculino , Persona de Mediana Edad , Neoplasias/genética , Neoplasias/metabolismo , Farmacogenética , Polimorfismo Genético , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirroles/efectos adversos , Pirroles/sangre , Pirroles/farmacocinética , Pirroles/uso terapéutico , Receptores de Esteroides/genética , Sunitinib , Resultado del Tratamiento
8.
Int J Surg ; 110(7): 4259-4265, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38573078

RESUMEN

INTRODUCTION: Duodenal neuroendocrine tumours (D-NETs) have a low incidence; however, their diagnosis has been increasing. Features such as tumour location, size, type, histological grade, and stage were used to adapt the treatment to either endoscopic (ER) or surgical (SR) resections. There is no consensus regarding the definitive treatment. The authors' study aimed to describe the management of non-metastatic, well-differentiated D-NETs in France and its impact on patient survival. METHODS: A registry-based multicenter study using prospectively collected data between 2000 and 2019, including all patients managed for non-metastatic G1 and G2 D-NETs, was conducted in the GTE group. RESULTS: A total of 153 patients were included. Fifty-eight benefited from an ER, and 95 had an SR. No difference in recurrence-free survival (RFS) was observed regardless of treatment type. There was no significant difference between the two groups (ER vs. SR) in terms of location, size, grade, or lymphadenopathy, regardless of the type of incomplete resection performed or regarding the pre-therapeutic assessment of lymph node invasion in imaging. The surgery allowed for significantly more complete resection (patients with R1 resection in the SR group: 9 vs. 14 in the ER group, P <0.001). Among the 51 patients with positive lymph node dissection after SR, tumour size was less than or equal to 1 cm in 25 cases. Surgical complications were more numerous ( P =0.001). In the sub-group analysis of G1-G2 D-NETs between 11 and 19 mm, there was no significant difference in grade ( P =0.977) and location ( P =0.617) between the two groups (ER vs. SR). No significant difference was found in both morphological and functional imaging, focusing on the pre-therapeutic assessment of lymph node invasion ( P =0.387). CONCLUSION: Regardless of the resection type (ER or SR) of G1-G2 non-metastatic D-NETs, as well as the type of management of incomplete resection, which was greater in the ER group, long-term survival results were similar between ER and SR. Organ preservation seems to be the best choice owing to the slow evolution of these tumours.


Asunto(s)
Neoplasias Duodenales , Tumores Neuroendocrinos , Humanos , Femenino , Masculino , Francia , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/terapia , Persona de Mediana Edad , Neoplasias Duodenales/cirugía , Neoplasias Duodenales/patología , Neoplasias Duodenales/mortalidad , Anciano , Adulto , Estudios de Cohortes , Sistema de Registros
9.
Br J Cancer ; 107(3): 455-61, 2012 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-22767146

RESUMEN

BACKGROUND: Inter-patient pharmacokinetic variability can lead to suboptimal drug exposure, and therefore might impact the efficacy of sorafenib. This study reports long-term pharmacokinetic monitoring of patients treated with sorafenib and a retrospective pharmacodynamic/pharmacokinetic analysis in melanoma patients. PATIENTS AND METHODS: Heavily pretreated patients with stage IV melanoma were started on sorafenib 400 mg twice daily (bid). In the absence of limiting toxicity, dose escalation of 200 mg bid levels was done every 2 weeks. Plasma sorafenib measurement was performed at each visit, allowing a retrospective pharmacodynamic/pharmacokinetic analysis for safety and efficacy. RESULTS: In all, 19 of 30 patients underwent dose escalation over 400 mg bid, and 28 were evaluable for response. The overall disease control rate was 61% (95% confidence interval (CI): 42.6-78.8), including three confirmed responses (12%). Disease control rate and progression-free survival (PFS) were improved in patients with high vs low exposure (80% vs 32%, P=0.02, and 5.25 vs 2.5 months, P=0.005, hazard ratio (HR)=0.28 (95% CI: 0.11-0.73)). In contrast, drug dosing had no effect on PFS. In multivariate analysis, drug exposure was the only factor associated with PFS (HR=0.36 (95% CI: 0.13-0.99)). Diarrhoea and anorexia were correlated with drug dosing, while hypertension and hand-foot skin reaction were correlated with drug exposure. CONCLUSIONS: Although sorafenib had modest efficacy in melanoma, these results suggest a correlation between exposure and efficacy of sorafenib. Therefore, dose optimisation in patients with low exposure at standard doses should be evaluated in validated indications.


Asunto(s)
Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Bencenosulfonatos/farmacocinética , Bencenosulfonatos/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Piridinas/farmacocinética , Piridinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Antineoplásicos/sangre , Bencenosulfonatos/efectos adversos , Bencenosulfonatos/sangre , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Melanoma/sangre , Persona de Mediana Edad , Análisis Multivariante , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Piridinas/efectos adversos , Piridinas/sangre , Estudios Retrospectivos , Sorafenib
10.
Ann Oncol ; 23(1): 200-205, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21427067

RESUMEN

BACKGROUND: Oxaliplatin neurosensory toxicity is dose limiting and may present as acute symptoms and/or cumulative peripheral neuropathy. PATIENTS AND METHODS: From October 2005 to May 2008, patients with oxaliplatin-induced acute neurotoxicity were randomized into a double-blind study, to receive either venlafaxine 50 mg 1 h prior oxaliplatin infusion and venlafaxine extended release 37.5 mg b.i.d. from day 2 to day 11 or placebo. Neurotoxicity was evaluated using numeric rating scale (NRS) for pain intensity and experienced relief under treatment, the Neuropathic Pain Symptom Inventory and the oxaliplatin-specific neurotoxicity scale. The primary end point was the percentage of patients with a 100% relief under treatment. RESULTS: Forty-eight patients were included (27 males, median age: 67.6 years). Most patients had colorectal cancer (72.9%). Median number of cycles administered at inclusion was 4.5 (mean cumulative oxaliplatin dose: 684.6 mg). Twenty out of 24 patients in arm A (venlafaxine) and 22 out of 24 patients in arm B (placebo) were assessable for neurotoxicity. Based on the NRS, full relief was more frequent in the venlafaxine arm: 31.3% versus 5.3% (P=0.03). Venlafaxine side-effects included grade 1-2 nausea (43.1%) and asthenia (39.2%) without grade 3-4 events. CONCLUSION: Venlafaxine has clinical activity against oxaliplatin-induced acute neurosensory toxicity.


Asunto(s)
Antineoplásicos/efectos adversos , Ciclohexanoles/uso terapéutico , Síndromes de Neurotoxicidad/prevención & control , Compuestos Organoplatinos/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/tratamiento farmacológico , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxaliplatino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Clorhidrato de Venlafaxina
11.
ESMO Open ; 7(6): 100638, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36399952

RESUMEN

Metastatic pancreatic ductal adenocarcinoma (PDAC) is a major health burden due to its increasing incidence and poor prognosis. PDAC is characterized by a low tumor mutational burden, and its molecular pathogenesis is driven by Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. Response to DNA damage through homologous repair is defective in 15% of tumors. Chemotherapy using FOLFIRINOX (folinic acid, fluorouracil, irinotecan, oxaliplatin) or gemcitabine-nab-paclitaxel significantly improves life expectancy, but the median overall survival remains <1 year. Targeted therapies are not efficient in the overall population of patients with metastatic PDAC. Improvements in overall survival or progression-free survival, however, have been demonstrated in subgroups carrying certain mutations. Maintenance therapy with poly-ADP-ribose polymerase (PARP) inhibitors increases progression-free survival in patients with germline mutations in BRCA1/2. Sotorasib shows signs of efficacy against tumors carrying the KRAS G12C mutation, and targeted therapies may also benefit patients with KRAS-wild-type PDAC. Combining targeted therapies with chemotherapy holds promise because of potential synergistic effects. These associations, however, have not yet demonstrated clinical benefit. Checkpoint inhibitors are not effective against metastatic PDAC. Combined immunotherapies attempt to restore their efficacy but have not succeeded yet. Other immunotherapies are emerging such as therapeutic vaccines or chimeric antigen receptor (CAR) T cells, but these strategies remain to be evaluated in large trials. In the future, treatment personalization based on tumor-derived organoids could potentially further improve treatment efficiency.


Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Inmunoterapia , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogénicas p21(ras) , Metástasis de la Neoplasia , Neoplasias Pancreáticas
13.
Endoscopy ; 43(8): 723-6, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21437855

RESUMEN

Cowden syndrome is characterized by diffuse hamartomas involving the whole digestive tract. The gastrointestinal expression of the disease is inconstant, but hamartomatous polyposes are frequent. In a multicenter study we studied the endoscopic appearance of Cowden syndrome--as defined by fulfillment of international consortium criteria--in 10 patients. In 6 of the 10 patients the connection with Cowden syndrome was made retrospectively on the basis of the gastrointestinal endoscopic findings. All patients had upper and lower gastrointestinal tract involvement. Mean follow-up duration was 9.5 years (range: 2-26 years). Mean age was 37 years (range: 18-56 years). Polyps of the upper gastrointestinal tract were hamartomas, ganglioneuromas, lipomas, and adenomas. Diffuse glycogenic acanthosis was reported in nine patients. Besides the classical hamartomatous polyposis, diffuse macroscopic esophageal acanthosis and microscopic ganglioneuromatosis are other key findings associated with a diagnosis of Cowden syndrome. Physicians should be aware of these characteristics in order to diagnose Cowden syndrome early.


Asunto(s)
Adenoma/patología , Pólipos del Colon/patología , Enfermedades del Esófago/patología , Ganglioneuroma/patología , Síndrome de Hamartoma Múltiple/patología , Neoplasias Intestinales/patología , Neoplasias Gástricas/patología , Adolescente , Adulto , Colonoscopía , Endoscopía del Sistema Digestivo , Femenino , Glucógeno , Síndrome de Hamartoma Múltiple/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
14.
Gastroenterol Clin Biol ; 34(10): 541-8, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20739131

RESUMEN

OBJECTIVES: In 2004, the French health authorities published guidelines on the indications for colonoscopy. However, no study has evaluated the awareness of healthcare practitioners of these guidelines. The aim of this study was to determine the level of awareness of the ANAES guidelines among French gastroenterologists. PATIENTS AND METHODS: A questionnaire comprising 20 multiple choice questions (MCQ) was presented to a group of 79 gastroenterologists between February and June in 2008. The questions covered screening tests for colon cancer (one question), endoscopic mucosal resection (two questions) and the ANAES guidelines (17 questions). According to the number of colonoscopies performed per year (less than 100, 100-500, more than 500), the answers to these questions were analyzed separately. RESULTS: Among the practitioners carrying out less than 100, 100-500 and more than 500 colonoscopies per year, the guidelines for colon cancer screening were known by 33, 50 and 56%, respectively, the quality criteria for endoscopic mucosal resection by 0, 0 and 3.7%, respectively, and the ANAES guideline indications for colonoscopy by 34.3, 51.2 and 48.9%, respectively (P<0.001). The ANAES guidelines were significantly better known by practitioners who were performing more than 100 colonoscopies per year, while the indications for control colonoscopy were less often correctly anticipated. No differences were found concerning postponed indications. CONCLUSION: The ANAES guidelines consists of the following elements: (1) awareness of the ANAES guidelines is poor, with control colonoscopy being correctly anticipated in just over a third of the gastroenterologists; (2) performing more than 100 colonoscopies per year improves knowledge of the ANAES guidelines; and (3) the ANAES guidelines need to be simplified and should be covered by continuing medical education.


Asunto(s)
Colonoscopía/estadística & datos numéricos , Colonoscopía/normas , Adhesión a Directriz/normas , Acreditación , Neoplasias Colorrectales/diagnóstico , Francia , Adhesión a Directriz/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Encuestas Epidemiológicas , Humanos , Guías de Práctica Clínica como Asunto , Garantía de la Calidad de Atención de Salud/normas , Sociedades Médicas , Encuestas y Cuestionarios
15.
Pharmacol Ther ; 210: 107517, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32109491

RESUMEN

Biliary tract cancers (BTCs) represent a heterogeneous group that includes intrahepatic cholangiocarcinomas (CCAs), perihilar-CCAs or Klatskin tumors, extrahepatic-CCAs, and gallbladder adenocarcinoma. These entities have distinct demographics, risk factors, clinical presentation, and molecular characteristics. In advanced BTCs, the recommendations are mainly supporting a doublet chemotherapy regimen using cisplatin/gemcitabine (CisGem) with a 5-year overall survival rate close to 5% and median overall survival (mOS) of less than a year. The lack of overall efficacy stresses the need for personalized therapies. Recently, whole-genome and transcriptome sequencing highlighted the diversity of BTCs' subtypes. Distinct genetic alterations were retrieved according to the localization, with a high rate of potentially actionable alterations. Targeted therapies and immunotherapy have since then been tested for BTCs, trying to propose a more personalized treatment. This review describes the different therapeutic options, validated and in development, for patients with advanced BTCs.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/terapia , Inmunoterapia , Terapia Molecular Dirigida , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Sistema Biliar/genética , Neoplasias del Sistema Biliar/inmunología , Neoplasias del Sistema Biliar/mortalidad , Biomarcadores de Tumor/genética , Toma de Decisiones Clínicas , Humanos , Inmunoterapia/efectos adversos , Inmunoterapia/mortalidad , Terapia Molecular Dirigida/efectos adversos , Terapia Molecular Dirigida/mortalidad , Medicina de Precisión , Resultado del Tratamiento , Microambiente Tumoral
16.
Diagn Interv Imaging ; 101(9): 565-575, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32146131

RESUMEN

PURPOSE: To report the computed tomography (CT) features of pancreatic acinar cell carcinoma (ACC) and identify CT features that may help discriminate between pancreatic ACC and pancreatic ductal adenocarcinoma (PDA). MATERIALS AND METHODS: The CT examinations of 20 patients (13 men, 7 women; mean age, 66.5±10.7 [SD] years; range: 51-88 years) with 20 histopathologically proven pancreatic ACC were reviewed. CT images were analyzed qualitatively and quantitatively and compared to those obtained in 20 patients with PDA. Comparisons were performed using univariate analysis with a conditional logistic regression model. RESULTS: Pancreatic ACC presented as an enhancing (20/20; 100%), oval (15/20; 75%), well-delineated (14/20; 70%) and purely solid (13/20; 65%) pancreatic mass with a mean diameter of 52.6±28.0 (SD) mm (range: 24-120mm) in association with visible lymph nodes (14/20; 70%). At univariate analysis, well-defined margins (Odds ratio [OR], 7.00; P=0.005), nondilated bile ducts (OR, 9.00; P=0.007), visible lymph nodes (OR, 4.33; P=0.028) and adjacent organ involvement (OR, 5.67; P=0.02) were the most discriminating CT features to differentiate pancreatic ACC from PDA. When present, lymph nodes were larger in patients with pancreatic ACC (14±4.8 [SD]; range: 7-25mm) than in those with PDA (8.8±4.1 [SD]; range: 5-15mm) (P=0.039). CONCLUSION: On CT, pancreatic ACC presents as an enhancing, predominantly oval and purely solid pancreatic mass that most frequently present with no bile duct dilatation, no visible lymph nodes, no adjacent organ involvement and larger visible lymph nodes compared to PDA.


Asunto(s)
Carcinoma de Células Acinares , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Anciano , Carcinoma de Células Acinares/diagnóstico por imagen , Carcinoma Ductal Pancreático/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Páncreas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X
17.
Gastroenterol Clin Biol ; 33(2): 103-8, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18783903

RESUMEN

OBJECTIVES: To produce valid information, an evaluation of professional practices has to assess the quality of all practices before, during and after the procedure under study. Several auditing techniques have been proposed for colonoscopy. The purpose of this work is to describe a straightforward original validated method for the prospective evaluation of professional practices in the field of colonoscopy applicable in all endoscopy units without increasing the staff work load. METHODS: Pertinent quality-control criteria (14 items) were identified by the endoscopists at the Cochin Hospital and were compatible with: findings in the available literature; guidelines proposed by the Superior Health Authority; and application in any endoscopy unit. Prospective routine data were collected and the methodology validated by evaluating 50 colonoscopies every quarter for one year. RESULTS: The relevance of the criteria was assessed using data collected during four separate periods. The standard checklist was complete for 57% of the colonoscopy procedures. The colonoscopy procedure was appropriate according to national guidelines in 94% of cases. These observations were particularly noteworthy: the quality of the colonic preparation was insufficient for 9% of the procedures; complete colonoscopy was achieved for 93% of patients; and 0.38 adenomas and 0.045 carcinomas were identified per colonoscopy. CONCLUSION: This simple and reproducible method can be used for valid quality-control audits in all endoscopy units. In France, unit-wide application of this method enables endoscopists to validate 100 of the 250 points required for continuous medical training. This is a quality-control tool that can be applied annually, using a random month to evaluate any changes in routine practices.


Asunto(s)
Colonoscopía , Garantía de la Calidad de Atención de Salud/métodos , Neoplasias del Colon/diagnóstico , Colonoscopía/métodos , Colonoscopía/normas , Francia , Humanos , Auditoría Médica/métodos , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Garantía de la Calidad de Atención de Salud/normas
19.
Endoscopy ; 40(9): 764-8, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18535938

RESUMEN

Esophageal lichen planus is a rare condition. Its risk of malignant transformation is unknown. We report a series of eight patients with esophageal lichen planus referred to our unit between 1990 and 2005. Clinical, endoscopic, radiological and histological data of these patients were retrospectively reviewed. Seven patients were women. All patients had oral lichen planus. Endoscopic lesions were located in the upper third of the esophagus in seven patients and in the mid third in two patients. Five patients had esophageal stricture. Seven patients had peeling, friable esophageal mucosa. Histological examination of esophageal biopsies found characteristic features of lichen planus in two patients and nonspecific changes in five patients. All patients received corticosteroids. Patients with stricture underwent esophageal dilation. Esophageal perforation after dilation occurred in one patient. Corticosteroids improved dysphagia in all patients; steroid dependence occurred in two patients with stricture. One patient had an esophageal verrucous carcinoma, which was treated with radiotherapy and chemotherapy. Upper endoscopy should be performed in patients with mucosal lichen planus presenting with dysphagia to assess esophageal involvement. Esophageal strictures are frequent and require dilation. Corticosteroids are the first-line treatment, but steroid dependence may occur. Cancer can arise on esophageal lichen planus and justifies endoscopic follow-up.


Asunto(s)
Enfermedades del Esófago/diagnóstico , Liquen Plano/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Carcinoma Verrugoso/diagnóstico , Diagnóstico Diferencial , Enfermedades del Esófago/patología , Neoplasias Esofágicas/diagnóstico , Estenosis Esofágica/diagnóstico , Estenosis Esofágica/patología , Esofagoscopía , Femenino , Humanos , Liquen Plano/patología , Masculino , Persona de Mediana Edad
20.
Gastroenterol Clin Biol ; 32(1 Pt. 1): 11-4, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18341972

RESUMEN

Brunner's Gland Hamartoma (BGH) is a benign tumor of the duodenum that can lead to gastrointestinal bleeding and intestinal obstruction. Endoscopic resection has seldom been reported. We describe the case of a duodenal obstruction caused by a large BGH (6 cm x 4 cm). We report a 57-year-old woman hospitalized for tarry stools, weight loss and anorexia. Endoscopy revealed a large BGH (6 cm x 4 cm). Endoscopic ultrasound (EUS) revealed a submucosal duodenal tumor. In this paper, we report a case of large hyperplasia of BGH, successfully treated by endoscopic technique.


Asunto(s)
Glándulas Duodenales/cirugía , Enfermedades Duodenales/cirugía , Duodenoscopía/métodos , Hamartoma/cirugía , Obstrucción Duodenal/cirugía , Electrocirugia , Endosonografía , Femenino , Estudios de Seguimiento , Humanos , Hiperplasia , Persona de Mediana Edad , Pólipos/cirugía , Tomografía Computarizada por Rayos X
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