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1.
Langenbecks Arch Surg ; 409(1): 192, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900214

RESUMO

PURPOSE: Gastric outlet obstruction (GOO) is mainly due to advanced malignant disease. GOO can be treated by surgical gastroenterostomy (SGE), endoscopic enteral stenting (EES), or endoscopic ultrasound-guided gastroenterostomy (EUS-GE) to improve the quality of life. METHODS: Between 2009 and 2022, patients undergoing SGE or EUS-GE for GOO were included at three centers. Technical and clinical success rates, post-procedure adverse events (AEs), length of hospital stay (LOS), 30-day all-cause mortality, and recurrence of GOO were retrospectively analyzed and compared between SGE and EUS-GE. Predictive factors for technical and clinical failure after SGE and EUS-GE were identified. RESULTS: Of the 97 patients included, 56 (57.7%) had an EUS-GE and 41 (42.3%) had an SGE for GOO, with 62 (63.9%) GOO due to malignancy and 35 (36.1%) to benign disease. The median follow-up time was 13,4 months (range 1 days-106 months), with no difference between the two groups (p = 0.962). Technical (p = 0.133) and clinical (p = 0.229) success rates, severe morbidity (p = 0.708), 30-day all-cause mortality (p = 0.277) and GOO recurrence (p = 1) were similar. EUS-GE had shorter median procedure duration (p < 0.001), lower post-procedure ileus rate (p < 0.001), and shorter median LOS (p < 0.001) than SGE. In univariate analysis, no risk factors for technical or clinical failure in SGE were identified and abdominal pain reported before the procedure was a risk factor for technical failure in the EUS-GE group. No risk factor for clinical failure was identified for EUS-GE. In the subgroup of GOO due to benign disease, SGE was associated with better technical success (p = 0.035) with no difference in clinical success rate compared to EUS-GE (p = 1). CONCLUSION: EUS-GE provides similar long-lasting symptom relief as SGE for GOO whether for benign or malignant disease. SGE may still be indicated in centers with limited experience with EUS-GE or may be reserved for patients in whom endoscopic technique fails.


Assuntos
Obstrução da Saída Gástrica , Gastroenterostomia , Humanos , Obstrução da Saída Gástrica/cirurgia , Obstrução da Saída Gástrica/etiologia , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Gastroenterostomia/métodos , Resultado do Tratamento , Endossonografia , Tempo de Internação , Adulto , Idoso de 80 Anos ou mais , Stents
2.
Dig Endosc ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39253824

RESUMO

OBJECTIVES: Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) is an alternative to duodenal stenting and surgical GJ (SGGJ) in malignant gastric outlet obstruction (MGOO). European Society of Gastrointestinal Endoscopy guidelines restricted EUS-GJ for MGOO only, because of misdeployment. The aim was to evaluate its outcomes focusing on benign indications. METHODS: This was a retrospective study conducted from 2016 to 2023 in a tertiary center. Patients included had malignant or benign GOO indicated for EUS-GJ. Techniques were the direct approach until August 2021, and the wire endoscopic simplified technique (WEST) afterwards. The main objective was to compare outcomes in benign vs. MGOO. Secondary end-points were technical success, adverse events rates, and describing the evolution of techniques and indications. RESULTS: In all, 87 patients were included, 46 men, mean age 66 ± 16.2 years. Indications were malignant in 60.1% and benign in 39.1%. The EUS-GJ technique was direct in 33 patients (37.9%) and WEST in 54 (62.1%). No difference was found in terms of technical, clinical, or adverse events rates. The initial technical success rate was 88.5%. The final technical and clinical success rates were 96.6% and 94.25%, respectively. In the last year, benign exceeded malignant indications (70.4% vs. 29.6%, P < 0.05). Seven misdeployments occurred, six being addressed with the rescue technique. The misdeployment rate was significantly decreased using the WEST approach compared to the direct one: 3.7% vs. 18% (P < 0.05). The severe postoperative adverse events rate was 2.3%. CONCLUSION: This study demonstrated similar outcomes of EUS-GJ between benign and MGOO, with a decreasing misdeployment rate (<4%) applying WEST. This represents an additional step towards recommending EUS-GJ in benign indications.

3.
Gastrointest Endosc ; 98(3): 392-399.e1, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37059368

RESUMO

BACKGROUND AND AIMS: EUS-guided radiofrequency ablation (EUS-RFA) has been described as a potentially curative option for solid and cystic pancreatic neoplasms. We aimed to assess the safety and efficacy of pancreatic EUS-RFA in a large study population. METHODS: A retrospective study retrieving all consecutive patients who underwent pancreatic EUS-RFA during 2019 and 2020 in France was conducted. Indication, procedural characteristics, early and late adverse events (AEs), and clinical outcomes were recorded. Risk factors for AEs and factors related to complete tumor ablation were assessed on univariate and multivariate analyses. RESULTS: One hundred patients (54% men, 64.8 ± 17.6 years old) affected by 104 neoplasms were included. Sixty-four neoplasms were neuroendocrine neoplasms (NENs), 23 were metastases, and 10 were intraductal papillary mucinous neoplasms with mural nodules. No procedure-related mortality was observed, and 22 AEs were reported. Proximity of pancreatic neoplasms (≤1 mm) to the main pancreatic duct was the only independent risk factor for AEs (odds ratio [OR), 4.10; 95% confidence interval [CI), 1.02-15.22; P = .04). Fifty-nine patients (60.2%) achieved a complete tumor response, 31 (31.6%) a partial response, and 9 (9.2%) achieved no response. On multivariate analysis, NENs (OR, 7.95; 95% CI, 1.66-51.79; P < .001) and neoplasm size <20 mm (OR, 5.26; 95% CI, 2.17-14.29; P < .001) were independently related to complete tumor ablation. CONCLUSIONS: The results of this large study confirm an overall acceptable safety profile for pancreatic EUS-RFA. Close proximity (≤1 mm) to the main pancreatic duct represents an independent risk factor for AEs. Good clinical outcomes in terms of tumor ablation were observed, especially for small NENs.


Assuntos
Neoplasias Císticas, Mucinosas e Serosas , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Ablação por Radiofrequência , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos Retrospectivos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Ablação por Radiofrequência/métodos , Tumores Neuroendócrinos/cirurgia , Fatores de Risco
4.
Endoscopy ; 55(11): 991-999, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37380033

RESUMO

BACKGROUND: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using lumen-apposing metal stents (LAMSs) appears to be effective and safe in gastric outlet obstruction (GOO); however, the EUS-GE procedure is not standardized, with the use of assisted or direct methods still debated. The aim of this study was to compare the outcomes of EUS-GE techniques focusing on an assisted with orointestinal drain wireless endoscopic simplified technique (WEST) and the nonassisted direct technique over a guidewire (DTOG). METHOD: This was a multicenter European retrospective study involving four tertiary centers. Consecutive patients who underwent EUS-GE for GOO between August 2017 and May 2022 were included. The primary aim was to compare the technical success and adverse event (AE) rates of the different EUS-GE techniques. Clinical success was also analyzed. RESULTS: 71 patients (mean [SD] age 66.2 10 years; 42.3 % men; 80.3 % malignant etiology) were included. Technical success was higher in the WEST group (95.1 % vs. 73.3 %; estimate of relative risk from odds ratio (eRR) 3.2, 95 %CI 0.94-10.9; P = 0.01). The rate of AEs was lower in the WEST group (14.6 % vs. 46.7 %; eRR 2.3, 95 %CI 1.2-4.5; P = 0.007). Clinical success was comparable between the two groups at 1 month (97.5 % vs. 89.3 %). The median follow-up was 5 months (range 1-57). CONCLUSION: The WEST resulted in a higher technical success rate with fewer AEs, with clinical success comparable with the DTOG. Therefore, the WEST (with an orointestinal drain) should be preferred when performing EUS-GE.


Assuntos
Obstrução da Saída Gástrica , Gastroenterostomia , Masculino , Humanos , Idoso , Feminino , Estudos Retrospectivos , Resultado do Tratamento , Gastroenterostomia/métodos , Endossonografia/métodos , Stents/efeitos adversos , Obstrução da Saída Gástrica/etiologia , Ultrassonografia de Intervenção/métodos
5.
Scand J Gastroenterol ; 57(1): 112-118, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34565279

RESUMO

BACKGROUND: Pelvic collections may occur after surgery or in medical diseases. EUS transmural (TM) treatment has been shown as highly effective and safe, becoming an alternative to surgery or radiology. We aimed to assess the results of EUS management of pelvic collections. METHODS: Retrospective, single-center observational study conducted between 2004 and 2018. Patients with symptomatic collections treated by EUS-TM approach were enrolled. The procedures were performed with a therapeutic EUS-scope, following two possible options: puncture-aspiration-injection of antibiotics PAIA (group 1) or EUS-drainage by plastic double pigtail stents (DPS) with an ano-cavitary drain (ACD) or lumen-apposing metal Stent (LAMS) (group 2). The main objective was to assess the clinical effectiveness based on symptoms and collection resolution. RESULTS: Seventy-three patients were included. Mean age was 42.5 years [12-87]. 30 patients in group 1 (41%) underwent PAIA and 43 in group 2 (59%) underwent DPS ± ACD in 41 patients (95%) and LAMS in 2. The collection was postoperative in 58%. The mean size was 48.9 mm [8-120], 33 +/- 17 mm in group 1, compared to 67 ± 21 mm in group 2 (p < .0001). All the procedures were technically successful. Overall clinical success was 96% (93% in group 1 (28/30), 98% (42/43) in group 2). Failures occurred in 2 post sigmoiditis abscesses and 1 ileo-colic Crohn's disease. No adverse event was reported. During the median follow-up of 7.5 years [4.4-8.9], no patient had recurrence. CONCLUSIONS: EUS-TM with either PAIA or drainage depending on the collection size is confirmed to be highly effective and safe.


Assuntos
Drenagem , Endossonografia , Adulto , Algoritmos , Drenagem/efeitos adversos , Humanos , Punções , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do Tratamento
6.
Gut ; 69(4): 681-690, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31780575

RESUMO

OBJECTIVE: Diagnostic tests, such as Immunoscore, predict prognosis in patients with colon cancer. However, additional prognostic markers could be detected on pathological slides using artificial intelligence tools. DESIGN: We have developed a software to detect colon tumour, healthy mucosa, stroma and immune cells on CD3 and CD8 stained slides. The lymphocyte density and surface area were quantified automatically in the tumour core (TC) and invasive margin (IM). Using a LASSO algorithm, DGMate (DiGital tuMor pArameTErs), we detected digital parameters within the tumour cells related to patient outcomes. RESULTS: Within the dataset of 1018 patients, we observed that a poorer relapse-free survival (RFS) was associated with high IM stromal area (HR 5.65; 95% CI 2.34 to 13.67; p<0.0001) and high DGMate (HR 2.72; 95% CI 1.92 to 3.85; p<0.001). Higher CD3+ TC, CD3+ IM and CD8+ TC densities were significantly associated with a longer RFS. Analysis of variance showed that CD3+ TC yielded a similar prognostic value to the classical CD3/CD8 Immunoscore (p=0.44). A combination of the IM stromal area, DGMate and CD3, designated 'DGMuneS', outperformed Immunoscore when used in estimating patients' prognosis (C-index=0.601 vs 0.578, p=0.04) and was independently associated with patient outcomes following Cox multivariate analysis. A predictive nomogram based on DGMuneS and clinical variables identified a group of patients with less than 10% relapse risk and another group with a 50% relapse risk. CONCLUSION: These findings suggest that artificial intelligence can potentially improve patient care by assisting pathologists in better defining stage III colon cancer patients' prognosis.


Assuntos
Adenocarcinoma/patologia , Inteligência Artificial , Neoplasias do Colo/patologia , Interpretação de Imagem Assistida por Computador , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Humanos , Linfócitos do Interstício Tumoral , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico
7.
Br J Cancer ; 122(7): 957-962, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015513

RESUMO

BACKGROUND: Identifying patients with metastatic colorectal cancer who will have an early disease progression during induction chemotherapy (IC) and identifying patients who may have a chemotherapy-free interval (CFI) after IC are two major challenges. METHODS: A logistic model was used to identify factors associated with early progression during IC and with short duration of the first CFI in 488 patients enrolled in the PRODIGE 9 trial. Independent factors were defined with a threshold 0.10. RESULTS: In multivariate analysis, baseline leukocytes >10 × 109/L (OR = 1.98 [1.02-3.8], p = 0.04), and stable or increasing CEA at 2 months (OR = 3.61 [1.68-7.75], p = 0.01) were independent factors associated with progression during IC. Male gender (OR = 1.725 [0.92-3.325], p = 0.09) and no tumour response at first evaluation (OR = 1.90 [0.96-3.76], p = 0.07) were significantly associated with a short CFI. The presence of BRAF V600E mutation was also associated with short CFI (OR = 4.59 [0.95; 22.3], p = 0.058). CONCLUSION: High baseline leukocyte count and the lack of CEA decrease level at first evaluation were associated with early progression, and could be in favour of early chemotherapy intensification. Male gender, no tumour response at first evaluation and BRAF mutation are associated with a short CFI, and may be considered for maintenance chemotherapy after IC. CLINICAL TRIAL NUMBER: NCT00952029.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Quimioterapia de Indução/métodos , Idoso , Progressão da Doença , Feminino , Humanos , Masculino
8.
Endoscopy ; 51(9): 836-842, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30669161

RESUMO

BACKGROUND: Pancreatic neuroendocrine tumors (NETs) and intraductal pancreatic mucinous neoplasia (IPMN) with worrisome features are surgically managed. Endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA) has recently been developed. The safety of EUS-RFA was the primary end point of this study, its efficacy the secondary end point. METHODS: This was a prospective multicenter study that was planned to include 30 patients with a 1-year follow-up with either a NET < 2 cm or a pancreatic cystic neoplasm (PCN), either a branch duct IPMN with worrisome features or a mucinous cystadenoma (MCA). EUS-RFA was performed with an 18G RFA cooling needle. RESULTS: 12 patients had 14 NETs (mean size 13.1 mm, range 10 - 20 mm); 17 patients had cystic tumors (16 IPMNs, 1 MCA; mean size 28 mm, range 9 - 60 mm). Overall three adverse events occurred (10 %), two of these in the first two patients (one pancreatitis, one small-bowel perforation). After these initial patients, modifications in the protocol resulted in a decrease in complications (3.5 %), with one patient having a pancreatic ductal stenosis. Among the 14 NETs, at 1-year follow-up 12 had completely disappeared (86 % tumor resolution), with three patients having a delayed response. Among the 17 PCNs, at 12 months, there were 11 complete disappearances and one diameter that decreased by > 50 % (significant response rate 71 %). All 12 mural nodules showed complete resolution. CONCLUSIONS: EUS-RFA of pancreatic NETs or PCNs is safe with a 10 % complication rate, which can be decreased by improved prophylaxis for the procedure.


Assuntos
Ablação por Cateter , Endossonografia , Tumores Neuroendócrinos/cirurgia , Cisto Pancreático/cirurgia , Neoplasias Pancreáticas/cirurgia , Ultrassonografia de Intervenção , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Estudos Prospectivos , Resultado do Tratamento
9.
Future Oncol ; 15(22): 2635-2643, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31339047

RESUMO

Despite rectal cancer being unusual before 40, fertility preservation (FP) remains a major concern for these reproductive-age women. Treatment usually involves pelvic radiotherapy, neoadjuvant chemotherapy, and surgery of rectum and mesorectum resection, at high risk of impairing fertility in women with risks of premature ovarian failure and radio-induced uterus damage. To date, there is no consensus on FP strategy for rectal cancer. We shared experiences between oncofertility experts from a French research network Groupe de Recherche et d'Etude en Cryoconservation Ovarienne et Testiculaire about a case of rectal cancer in a young woman. Indications, advantages and disadvantages of different FP strategies were discussed: ovarian transposition, cryopreservation of ovarian cortex and oocyte vitrification. This case was the starting point that led to the development of a French multidisciplinary e-meeting for sharing experiences and for suggesting the best strategy when faced with a complex oncofertility case.


Assuntos
Criopreservação/métodos , Preservação da Fertilidade/métodos , Neoplasias Retais/terapia , Reprodução , Adulto , Feminino , França/epidemiologia , Humanos , Oócitos/crescimento & desenvolvimento , Oócitos/patologia , Ovário/crescimento & desenvolvimento , Ovário/patologia , Neoplasias Retais/complicações , Neoplasias Retais/epidemiologia , Neoplasias Retais/patologia , Vitrificação
11.
Am J Pathol ; 185(4): 1022-32, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25765988

RESUMO

A major impediment to the effective treatment of patients with pancreatic ductal adenocarcinoma (PDAC) is the molecular heterogeneity of this disease, which is reflected in an equally diverse pattern of clinical outcome and in responses to therapies. We developed an efficient strategy in which PDAC samples from 17 consecutive patients were collected by endoscopic ultrasound-guided fine-needle aspiration or surgery and were preserved as breathing tumors by xenografting and as a primary culture of epithelial cells. Transcriptomic analysis was performed from breathing tumors by an Affymetrix approach. We observed significant heterogeneity in the RNA expression profile of tumors. However, the bioinformatic analysis of these data was able to discriminate between patients with long- and short-term survival corresponding to patients with moderately or poorly differentiated PDAC tumors, respectively. Primary culture of cells allowed us to analyze their relative sensitivity to anticancer drugs in vitro using a chemogram, similar to the antibiogram for microorganisms, establishing an individual profile of drug sensitivity. As expected, the response was patient dependent. We also found that transcriptomic analysis predicts the sensitivity of cells to the five anticancer drugs most frequently used to treat patients with PDAC. In conclusion, using this approach, we found that transcriptomic analysis could predict the sensitivity to anticancer drugs and the clinical outcome of patients with PDAC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Antineoplásicos/uso terapêutico , Perfilação da Expressão Gênica , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Adenocarcinoma/patologia , Animais , Antineoplásicos/farmacologia , Biópsia por Agulha Fina , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Endoscopia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Neoplasias Pancreáticas/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Coloração e Rotulagem , Análise de Sobrevida , Transcriptoma/genética , Resultado do Tratamento , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias Pancreáticas
13.
Endoscopy ; 48(2): 179-83, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26427001

RESUMO

BACKGROUND AND STUDY AIMS: The rendezvous endoscopic approach, already described, might be an interesting technique in complete esophageal obstructions (CEO). PATIENTS AND METHODS: This retrospective report on nine patients referred because of CEO classified patients into two groups based on length of their esophageal disruption: the long (> 5 cm) group were three patients (esophageal stripping at stent removal [n = 2] and caustic ingestion [n = 1]; two patients having superior esophageal sphincter [SES] destruction); the short (< 5 cm) group were six patients (anastomotic or post-radiotherapy). The procedures were performed under radiographic guidance. RESULTS: All the reconstructions were successful. In four patients, a neo-SES was created, by transillumination (n = 2) or surgery (n = 2). The first dilation was performed by hydrostatic balloon, with additional metal stents (n = 4) and nasogastric tubes (n = 2) used. All the patients were able to eat after the procedure. Two delayed bleeds occurred, which were managed endoscopically. The patients underwent a median of seven dilations (range 3 - 55) over 8 months (2 - 32 months), with dilations ongoing in five patients, but all able to eat normally. CONCLUSION: Endoscopic rendezvous for CEO is safe and effective, even in patients with long disruptions and complete loss of SES.


Assuntos
Estenose Esofágica/cirurgia , Esofagoplastia/métodos , Esofagoscopia/métodos , Stents , Idoso , Estenose Esofágica/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
16.
Lancet Oncol ; 12(11): 1032-44, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21903473

RESUMO

BACKGROUND: The optimum use of cytotoxic drugs for advanced colorectal cancer has not been defined. Our aim was to investigate whether combination treatment is better than the sequential administration of the same drugs in patients with advanced colorectal cancer. METHODS: In this open-label, randomised, phase 3 trial, we randomly assigned patients (1:1 ratio) with advanced, measurable, non-resectable colorectal cancer and WHO performance status 0-2 to receive either first-line treatment with bolus (400 mg/m(2)) and infusional (2400 mg/m(2)) fluorouracil plus leucovorin (400 mg/m(2)) (simplified LV5FU2 regimen), second-line LV5FU2 plus oxaliplatin (100 mg/m(2)) (FOLFOX6), and third-line LV5FU2 plus irinotecan (180 mg/m(2)) (FOLFIRI) or first-line FOLFOX6 and second-line FOLFIRI. Chemotherapy was administered every 2 weeks. Randomisation was done centrally using minimisation (minimisation factors were WHO performance status, previous adjuvant chemotherapy, number of disease sites, and centre). The primary endpoint was progression-free survival after two lines of treatment. Analyses were by intention-to-treat. This trial is registered at ClinicalTrials.gov, NCT00126256. FINDINGS: 205 patients were randomly assigned to the sequential group and 205 to the combination group. 161 (79%) patients in the sequential group and 161 (79%) in the combination group died during the study. Median progression-free survival after two lines was 10·5 months (95% CI 9·6-11·5) in the sequential group and 10·3 months (9·0-11·9) in the combination group (hazard ratio 0·95, 95% CI 0·77-1·16; p=0·61). All six deaths caused by toxic effects of treatment occurred in the combination group. During first-line chemotherapy, significantly fewer severe (grade 3-4) haematological adverse events (12 events in 203 patients in sequential group vs 83 events in 203 patients in combination group; p<0·0001) and non-haematological adverse events (26 events vs 186 events; p<0·0001) occurred in the sequential group than in the combination group. INTERPRETATION: Upfront combination chemotherapy is more toxic and is not more effective than the sequential use of the same cytotoxic drugs in patients with advanced, non-resectable colorectal cancer. FUNDING: Sanofi-Aventis France.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Distribuição de Qui-Quadrado , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , França , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
17.
BMC Cancer ; 11: 496, 2011 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-22117530

RESUMO

BACKGROUND: We analyzed the influence of 8 germinal polymorphisms of candidate genes potentially related to EGFR signalling (EGFR, EGF, CCND1) or antibody-directed cell cytotoxicity (FCGR2A and FCGR3A) on outcome of colorectal cancer (CRC) patients receiving cetuximab-based therapy. METHODS: Fifty-eight advanced CRC patients treated with cetuximab-irinotecan salvage therapy between 2001 and 2007 were analyzed (mean age 60; 50 PS 0-1). The following polymorphisms were analyzed on blood DNA: EGFR (CA repeats in intron 1, -216 G > T, -191C > A, R497K), EGF (A61G), CCND1 (A870G), FCGR2A (R131H), FCGR3A (F158V). Statistical analyses were conducted on the total population and on patients with wt KRas tumors. All SNPs were considered as ternary variables (wt/wt vs wt/mut vs mut/mut), with the exception of -191C > A EGFR polymorphism (AA patient merged with CA patients). RESULTS: Analysis of skin toxicity as a function of EGFR intron 1 polymorphism showed a tendency for higher toxicity in patients with a low number of CA-repeats (p = 0.058). CCND1 A870G polymorphism was significantly related to clinical response, both in the entire population and in KRas wt patients, with the G allele being associated with a lack of response. In wt KRas patients, time to progression (TTP) was significantly related to EGFR -191C > A polymorphism with a longer TTP in CC patients as compared to others, and to CCND1 A870G polymorphism with the G allele being associated with a shorter TTP; a multivariate analysis including these two polymorphisms only retained CCND1 polymorphism. Overall survival was significantly related to CCND1 polymorphism with a shorter survival in patients bearing the G allele, and to FCGR3A F158V polymorphism with a shorter survival in VV patients (in the entire population and in KRas wt patients). FCGR3A F158V and CCND1 A870G polymorphisms were significant independent predictors of overall survival. CONCLUSIONS: Present original data obtained in wt KRas patients corresponding to the current cetuximab-treated population clearly suggest that CCND1 A870G polymorphism may be used as an additional marker for predicting cetuximab efficacy, TTP and overall survival. In addition, FCGR3A F158V polymorphism was a significant independent predictor of overall survival.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos/efeitos adversos , Carcinoma/mortalidade , Cetuximab , Neoplasias Colorretais/mortalidade , Ciclina D1/genética , Progressão da Doença , Fator de Crescimento Epidérmico/genética , Receptores ErbB/genética , Feminino , Humanos , Íntrons/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Receptores de IgG/genética , Dermatopatias/induzido quimicamente , Análise de Sobrevida
18.
Gut ; 59(11): 1527-34, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20947887

RESUMO

PURPOSE: Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma. Although the 5-fluorouracil (5FU), folinic acid and cisplatin combination (LV5FU2-CDDP) is an option, the optimal order of the regimens must be determined. The first strategic phase III trial comparing LV5FU2-CDDP followed by gemcitabine versus gemcitabine followed by LV5FU2-CDDP was conducted. METHODS: Patients with metastatic pancreatic adenocarcinoma, performance status (PS) 0-2, without prior chemotherapy were randomly assigned (1:1) to receive either LV5FU2-CDDP followed by gemcitabine at disease progression or toxicity (Arm A), or the opposite sequence (Arm B). 202 patients had to be included and 170 deaths had to be observed to detect an expected improvement in median overall survival (OS) from 6.5 to 10 months in Arm A (two-sided α = 5% and ß = 20%). RESULTS: 202 patients were included (Arm A, 102; Arm B, 100). Median age, male/female ratio, PS 0-1 and previous surgery were similar in the two arms. After a median follow-up of 44 months, median OS in Arm A was 6.6 months versus 8.0 months in Arm B (p = 0.85). Median progression-free survival was similar between Arms A and B. More grade 3/4 toxicities were observed when LV5FU2-CDDP was administered as a first-line treatment compared with gemcitabine: 79% versus 64% (p = 0.018). CONCLUSION: This trial did not show any strategic advantage to using LV5FU2-CDDP as a first-line treatment and suggests that gemcitabine remains the standard first-line treatment. Sixty-one per cent of patients were able to receive a second line of chemotherapy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/patologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , França , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Gencitabina
19.
Endosc Int Open ; 9(8): E1178-E1185, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34447860

RESUMO

Background and study aims Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) for pancreatic neuroendocrine tumors (NETs) and intraductal pancreatic mucinous neoplasia (IPMN) with worrisome features or high-risk stigmata (WF/HRS) has been evaluated in few series with short-term outcomes. This study's primary endpoint was to assess the long-term efficacy of EUS-RFA in patients with NETs or pancreatic cystic neoplasms (PCNs) over at least 3 years. Patients and methods Twelve patients had 14 NETs with a mean 13.4-mm size (10-20) and 17 patients had a cystic tumor (16 IPMN, 1 MCA) with a 29.1-mm mean size (9-60 were included. They were treated with EUS-guided RFA, evaluated prospectively at 1 year, and followed annually for at least 3 years. Results The mean duration of follow-up was 42.9 months (36-53). Four patients died during follow-up (17-42 months) from unrelated diseases. At 1-year follow-up, and 85.7 % complete disappearance was seen in 12 patients with 14 NETs. At the end of follow-up (45.6 months), complete disappearance of tumors was seen in 85.7 % of cases. One case of late liver metastasis occurred in a patient with initial failure of EUS-RFA. At 1-year follow-up, a significant response was seen in 70.5 % of 15 patients with PCNs. At the end of the follow-up, there was a significant response in 66.6 % with no mural nodules. Two cases of distant pancreatic adenocarcinoma unrelated to IPMN occurred. Conclusions EUS-RFA results for pancreatic NETs or PCNs appear to be stable during 42 months of follow-up.

20.
Expert Rev Pharmacoecon Outcomes Res ; 19(5): 601-608, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30739558

RESUMO

Objectives: This study compared the cost and quality of life (QoL) of 407 advanced colorectal cancer patients, randomly assigned to receive LV5FU2 followed by FOLFOX6 (sequential strategy) or FOLFOX6 followed by FOLFIRI (combination strategy). Methods: Costs were compared from the French health insurance perspective, until the end of the second line of treatment. Consumed resources, collected during the trial, included medicines, hospitalizations, examinations, and transportation. Valuations were made using 2009 and 2016 tariffs. QoL was assessed using the QLQ-C30 questionnaire and clinically significant variations were searched. Results: In 2009, the mean cost per patient was significantly lower for the sequential strategy compared to the combination strategy (18,061€ and 23,119€, p = 0.001). In 2016, the difference was no longer significant (16,876€ and 18,090€, p = 0.41) because oxaliplatin and irinotecan became generics. The QoL analysis (292 patients) showed that there was significantly less improvement of global health status in the sequential strategy than in the combination strategy (29% and 42%; p = 0.02) during first-line therapy. No significant differences were observed for emotional functioning (p = 0.45) and physical functioning (p = 0.07) or during second-line therapy. Conclusion: The choice to treat patients with advanced colorectal cancer using one or the other strategy cannot be based on costs or QoL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Camptotecina/economia , Neoplasias Colorretais/economia , Neoplasias Colorretais/patologia , Custos de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/economia , França , Nível de Saúde , Humanos , Leucovorina/administração & dosagem , Leucovorina/economia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/economia , Estudos Prospectivos , Inquéritos e Questionários
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