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Microwave ablation systems allow for performing tumoral destruction in oncology. The objective of this study was to assess the early response and reliability of the microwave ablation zone size at one month for liver, kidney and lung lesions, as compared to the manufacturer's charts. Patients who underwent microwave ablation with the EmprintTM ablation system for liver, kidney and lung lesions between June 2016 and June 2018 were retrospectively reviewed. Local response and ablation zone size (major, L, and minor, l, axes) were evaluated on the one-month follow-up imaging. Results were compared to the manufacturers' charts using the Bland-Altman analysis. Fifty-five patients (mean age 68 ± 11 years; 95 lesions) were included. The one-month complete response was 94%. Liver ablations showed a good agreement with subtle, smaller ablation zones (L: -2 ± 5.7 mm; l: -5.2 ± 5.6 mm). Kidney ablations showed a moderate agreement with larger ablations for L (L: 8.69 ± 7.94 mm; l: 0.36 ± 4.77 mm). Lung ablations showed a moderate agreement, with smaller ablations for l (L: -5.45 ± 4.5 mm; l: -9.32 ± 4.72 mm). With 94% of early complete responses, the system showed reliable ablations for liver lesions, but larger ablations for kidney lesions, and smaller for lung lesions.
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Fígado , Micro-Ondas , Idoso , Humanos , Rim/diagnóstico por imagem , Rim/cirurgia , Fígado/diagnóstico por imagem , Fígado/cirurgia , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Micro-Ondas/uso terapêutico , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone. METHODS: We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18-70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m2) or open (460 mg/m2) abdomen techniques, and systemic chemotherapy (400 mg/m2 fluorouracil and 20 mg/m2 folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov, NCT00769405, and is now completed. FINDINGS: Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0-77·1), median overall survival was 41·7 months (95% CI 36·2-53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1-49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63-1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035). INTERPRETATION: Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases. FUNDING: Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.
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Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/patologia , Terapia Combinada/efeitos adversos , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , França , Humanos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Resultado do TratamentoRESUMO
In a previous phase II study (THERAPY), cetuximab and trastuzumab combination, as second-line after progression with gemcitabine, showed disease stabilization in 27% of 33 patients with pancreatic carcinoma. In the present phase II multicenter study, we assessed the efficacy and tolerance of gemcitabine, trastuzumab plus erlotinib as first-line treatment of metastatic pancreatic cancer. The primary endpoint was disease control rate (DCR, RECIST v.1); secondary endpoints were progression-free (PFS), overall (OS) survival and toxicity (NCI-CTCAE v3.0). Ancillary study addressed the predictive value of both EGFR/HER2 expression and KRAS mutational status. Sixty-three patients from four centers were included (62 evaluable for toxicity, 59 for efficacy), median age was 62 years (35-77), 59.7% men. The median treatment duration was 16.1 weeks (2.1-61). Eleven patients (19%) reported a partial tumor response, and 33 (56%) disease stabilization. DCR was 74.6% (95%CI: 61.8-85.0; 44/59 patients). After a median follow-up of 23.3 months (0.6-23.6), median PFS was 3.5 months (95%CI: 2.4-3.8) and median OS 7.9 months (95%CI: 5.1-10.2). PFS was significantly longer in patients with grade ≥ 2 cutaneous toxicities vs patients with grade 0-1 toxicities (HR = 0.55, 95%CI: 0.33-0.92, P = .020). Expression of EGFR and HER2 was correlated with PFS and OS in multivariate analysis; HER2 expression was correlated with the tumor response. Main severe toxicities were neutropenia (32%), cutaneous rash (37%) and thrombosis/embolisms (35.5%). This triplet combination is effective in terms of disease control, PFS and OS, and acceptable for safety. A larger study to investigate this combination compared to the standard regimen should be discussed.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/análogos & derivados , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Trastuzumab/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Receptores ErbB/genética , Cloridrato de Erlotinib/efeitos adversos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/genética , Receptor ErbB-2/genética , Análise de Sobrevida , Trastuzumab/efeitos adversos , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: Changes in calcium metabolism and calcium urinary excretion during chemotherapy have not been thoroughly assessed in patients with early breast cancer (EBC), a population who frequently present vitamin D insufficiency. As hypercalciuria is a classical contra-indication to vitamin D (VD) supplementation, this study evaluated changes in VD and calcium metabolism parameters in patients with EBC undergoing adjuvant chemotherapy (CT). METHODS: In patients with EBC who received six cycles of adjuvant CT, VD and calcium parameters were monitored at inclusion, and then every 3 weeks, at each CT cycle initiation. The primary endpoint was the percentage of patients showing hypercalciuria during adjuvant CT (between Day 1, Cycle 1 [D1C1] and Day 1, Cycle 6 [D1C6]). RESULTS: The primary endpoint could be evaluated in 82 patients. Most patients (n = 66, 80.5%) had VD insufficiency (< 30 ng/mL) at baseline. Hypercalciuria was detected in 29 patients (35.4%; 95% CI: 25.6-46.5) between D1C1 and D1C6, but was not clinically significant in any of the affected patients. The percentage of hypercalciuria events was not different between patients with sufficient and insufficient baseline VD levels (34.8% vs. 37.5%), and between patients who received or not VD supplementation (37.5% vs. 34.5%,). CONCLUSIONS: This comprehensive study on VD and calcium parameter changes in patients with EBC during adjuvant chemotherapy shows that hypercalciuria is a frequent abnormality in this setting, although asymptomatic. Therefore, it should not be considered as a limitation for high dose VD supplementation in this population. TRIAL REGISTRATION: EudraCT:2014-A01454-43 . Registered 29 august 2016.
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Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Cálcio/metabolismo , Vitamina D/metabolismo , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto JovemRESUMO
PURPOSE: To evaluate the feasibility of prostatic artery embolization in patients with low-risk prostate cancer (PC) under active surveillance (AS). METHODS: This monocentric prospective pilot study, running from June 2018 to June 2019, included 10 patients with low-risk PC under AS, median age 72 years (range, 62-77 years), with a unilateral focal lesion visible on magnetic resonance (MR) imaging, with Prostate Imaging Reporting and Data System v2 score ≥3/5 confirmed by multiparametric MR imaging-targeted biopsy and Gleason score 6. The patients underwent unilateral prostatic artery embolization with 300-500 µm Embospheres in the affected prostatic lobe. The primary endpoint was technical feasibility (prostate and no off-target ischemia in the imaging). The secondary endpoints included safety, negative biopsies/MR imaging response/functional outcomes at 6 months, and oncologic efficacy at 1 year. RESULTS: Embolization was successfully achieved in all patients; prostate ischemia was confirmed on multiparametric MR imaging, and no off-target ischemia was reported. No major complications were reported. Four patients (40%) presented with both negative targeted and systematic biopsies at 6 months. No lesions were seen on the MR imaging in 30% of patients. The mean International Prostate Symptom Score and International Index of Erectile Function score were 7 and 19 and 5 and 20 at baseline and 6 months, respectively, with no significant difference. Nine patients (90%) were still under AS at 1 year. One patient (10%) had PC progression outside the target lesion and was switched over to curative radiotherapy. CONCLUSIONS: Prostatic artery embolization is feasible and appears safe for prostate cancer patients under AS, with no impact on erectile function or continence status. These results justify the pursuit of further studies.
Assuntos
Embolização Terapêutica , Próstata/irrigação sanguínea , Neoplasias da Próstata/irrigação sanguínea , Neoplasias da Próstata/terapia , Conduta Expectante , Idoso , Embolização Terapêutica/efeitos adversos , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: Health-related quality of life (HRQoL) is assessed by self-administered questionnaires throughout the care process. Classically, two longitudinal statistical approaches were mainly used to study HRQoL: linear mixed models (LMM) or time-to-event models for time to deterioration/time until definitive deterioration (TTD/TUDD). Recently, an alternative strategy based on generalized linear mixed models for categorical data has also been proposed: the longitudinal partial credit model (LPCM). The objective of this article is to evaluate these methods and to propose recommendations to standardize longitudinal analysis of HRQoL data in cancer clinical trials. METHODS: The three methods are first described and compared through statistical, methodological, and practical arguments, then applied on real HRQoL data from clinical cancer trials or published prospective databases. In total, seven French studies from a collaborating group were selected with longitudinal collection of QLQ-C30. Longitudinal analyses were performed with the three approaches using SAS, Stata and R software. RESULTS: We observed concordant results between LMM and LPCM. However, discordant results were observed when we considered the TTD/TUDD approach compared to the two previous methods. According to methodological and practical arguments discussed, the approaches seem to provide additional information and complementary interpretations. LMM and LPCM are the most powerful methods on simulated data, while the TTD/TUDD approach gives more clinically understandable results. Finally, for single-item scales, LPCM is more appropriate. CONCLUSION: These results pledge for the recommendation to use of both the LMM and TTD/TUDD longitudinal methods, except for single-item scales, establishing them as the consensual methods for publications reporting HRQoL.
Assuntos
Neoplasias/terapia , Qualidade de Vida/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Neoplasias/psicologia , Inquéritos e QuestionáriosRESUMO
Background : In France, home parenteral nutrition (HPN) is managed by two parallel healthcare systems : in approved specialist centers (HPN > 12 weeks), and outside of these approved specialist centers (HPN<12 weeks).Objective : To prospectively evaluate infectious and vascular complications in adult cancer patients undergoing HPN administered via a central venous line, outside of approved specialist HPN centers.Methods : Our observational prospective study included adult patients with cancer, hospitalized for 48 hours or more, and under HPN. They had a WHO performance status of ≤ 2 and had had a nutritional consultation before discharge.Results : 25 patients were included in the study, with a median age of 63 years [19-74]. Weight loss of ≥ 5% was reported in 79% of patients. The Ingesta score was < 7 in 96% of cases. 87% of patients presented chill or body temperature variation episodes, with a median of 2 episodes [1-6] per patient. The median delay between end of hospitalization and the first chill episode was 11 days [1-85]. A vascular complication (obstruction without thrombosis) was reported in one patient.Discussion : This high number of infectious episodes requires improvement of patient care when it comes to strictly adhering to the recommendations. Getting the approved specialist HPN centers to work together and share care protocols could be the first important step.
RESUMO
Background : In France, home parenteral nutrition (HPN) is managed by two parallel healthcare systems : in approved specialist centers (HPN > 12 weeks), and outside of these approved specialist centers (HPN<12 weeks). Objective : To prospectively evaluate infectious and vascular complications in adult cancer patients undergoing HPN administered via a central venous line, outside of approved specialist HPN centers. Methods : Our observational prospective study included adult patients with cancer, hospitalized for 48 hours or more, and under HPN. They had a WHO performance status of ≤ 2 and had had a nutritional consultation before discharge. Results : 25 patients were included in the study, with a median age of 63 years [1974]. Weight loss of ≥ 5% was reported in 79% of patients. The Ingesta score was < 7 in 96% of cases. 87% of patients presented chill or body temperature variation episodes, with a median of 2 episodes [16] per patient. The median delay between end of hospitalization and the first chill episode was 11 days [185]. A vascular complication (obstruction without thrombosis) was reported in one patient. Discussion : This high number of infectious episodes requires improvement of patient care when it comes to strictly adhering to the recommendations. Getting the approved specialist HPN centers to work together and share care protocols could be the first important step.
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Neoplasias/enfermagem , Enfermeiros Especialistas , Papel do Profissional de Enfermagem , Nutrição Parenteral no Domicílio/enfermagem , Adulto , Idoso , França , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Sorafenib remains one major first-line therapeutic options for advanced hepatocellular carcinoma (aHCC), with modest efficacy. We investigated the addition of gemcitabine and oxaliplatin (GEMOX) to sorafenib in aHCC patients. METHODS: Our multicentre phase II trial randomised aHCC first-line patients to sorafenib (400 mg BID) or sorafenib-GEMOX every 2 weeks (1000 mg/m2 gemcitabine; 100 mg/m2 oxaliplatin). Primary endpoint was the 4-month progression-free survival (PFS) rate. RESULTS: Ninety-four patients were randomised (sorafenib-GEMOX: n = 48; sorafenib: n = 46). Median age was 64 years, PS 0 (69%) or 1 (31%), 63% patients had cirrhosis, 29% portal vein thrombosis and 70% extra-hepatic disease. Median duration of sorafenib treatment was 4 months (1-51); median number of GEMOX cycles was 7 (1-16). The 4-month PFS rates were 64% and 61% in the sorafenib-GEMOX and sorafenib arms, respectively; median PFS and OS were 6.2 (95% CI: 3.8-6.8) and 13.5 (7.5-16.2) months, and 4.6 (3.9-6.2) months and 14.8 (12.2-22.2), respectively. The ORR/DCR were 9%/70% and 15%/77% in the sorafenib-GEMOX and sorafenib alone arms, respectively. Main toxicities were (sorafenib-GEMOX/sorafenib) neutropenia (23%/0), thrombocytopenia (33%/0), diarrhoea (18%/9), peripheral neuropathy (5%/0) and hand-foot syndrome (5%/18). CONCLUSIONS: Addition of GEMOX had an inpact on ORR and was well-tolerated as frontline systemic therapy. The benefit on PFS seems moderate; no subsequent study was planned.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Sorafenibe/administração & dosagem , GencitabinaRESUMO
BACKGROUND: Metastatic breast cancer (MBC) prognosis is variable, depending on several clinical and biological factors. A better prediction of a patient's outcome could allow for a more accurate choice of treatments. The role of serum biomarkers in predicting outcome remains unclear in this setting. Tau, a microtubule-associated protein, is a neuronal marker that is also expressed in normal breast epithelial cells and cancer cells. Its tissue expression is associated with prognosis in MBC. However, the prognostic value of Tau serum levels in these patients is unknown. We aimed at evaluating the prognostic value of Tau (and other classical biomarkers) in MBC patients, and to assess its association with the presence of brain metastases (BM). METHODS: 244 MBC patients treated at our institution (2007-2015) were retrospectively selected. The usual MBC clinical and pathological variables were collected, altogether with CA15-3, CEA and HER2 extra-cellular domain (ECD) serum levels. Tau serum levels were measured with a novel immunoassay (digital ELISA) using Single Molecule Array (Simoa) technology. Overall survival (OS) was estimated with the Kaplan-Meier method. To investigate prognostic factors, a multivariate analysis was performed. Cut-offs were set using the Youden index method associated with receiver-operating characteristics (ROC) curves to evaluate the accuracy of biomarkers to identify patients with BM. RESULTS: With a median follow-up of 40.8 months, median OS was 15.5 months (95%CI 12.4-20.2). Elevated serum levels of Tau were independently associated with a poor outcome in the whole population as well as in patients with (n = 86) and without BM (n = 158). Median serum Tau levels tended to be higher in patients with BM (p = 0.23). In univariate analysis, patients with BM had an increased risk of serum Tau > 3.17 pg/mL (OR = 2.2, p = 0.049). In multivariate analysis, high values of Tau (OR = 3.98, p = 0.034) accurately identified patients with BM in our cohort. CONCLUSIONS: Tau is a new biomarker of interest in MBC. Its serum level could represent an independent prognostic factor in these patients (both with and without BM). It also seems to be associated with the presence of BM. A validation of these results in an independent set of MBC patients is necessary to confirm these findings.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundário , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Proteínas tau/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/sangue , Neoplasias da Mama/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaAssuntos
AVC Isquêmico , Trombectomia , Humanos , França/epidemiologia , Feminino , AVC Isquêmico/mortalidade , AVC Isquêmico/epidemiologia , Masculino , Prognóstico , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/epidemiologiaRESUMO
γ-Tubulin is critical for microtubule (MT) assembly and organization. In metazoa, this protein acts in multiprotein complexes called γ-Tubulin Ring Complexes (γ-TuRCs). While the subunits that constitute γ-Tubulin Small Complexes (γ-TuSCs), the core of the MT nucleation machinery, are essential, mutation of γ-TuRC-specific proteins in Drosophila causes sterility and morphological abnormalities via hitherto unidentified mechanisms. Here, we demonstrate a role of γ-TuRCs in controlling spindle orientation independent of MT nucleation activity, both in cultured cells and in vivo, and examine a potential function for γ-TuRCs on astral MTs. γ-TuRCs locate along the length of astral MTs, and depletion of γ-TuRC-specific proteins increases MT dynamics and causes the plus-end tracking protein EB1 to redistribute along MTs. Moreover, suppression of MT dynamics through drug treatment or EB1 down-regulation rescues spindle orientation defects induced by γ-TuRC depletion. Therefore, we propose a role for γ-TuRCs in regulating spindle positioning by controlling the stability of astral MTs.
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Proteínas Associadas aos Microtúbulos/fisiologia , Microtúbulos/metabolismo , Fuso Acromático/fisiologia , Tubulina (Proteína)/fisiologia , Animais , Animais Geneticamente Modificados , Células Cultivadas , Drosophila , Células HeLa , Humanos , Complexos Multiproteicos/fisiologiaRESUMO
OBJECTIVE: The aim of this study is to compare robotic total mesorectal excision (R-TME) with laparoscopic TME (L-TME) in a series of consecutive rectal cancer patients. BACKGROUND: R-TME and L-TME have drawn contradictory reports. A recent phase III trial (ROLARR) concluded that R-TME performed by surgeons with varying experience did not confer an advantage in rectal cancer resection. PATIENTS AND METHODS: In this retrospective single-center cohort study (8/2008 to 4/2015), data were prospectively registered. A total of 200 L-TME and 200 R-TME were operated consecutively without selection. The primary outcome was the conversion rate to open laparotomy or transanal TME. The secondary endpoints were type of anastomosis, operative time, postoperative morbidity, circumferential radial (CRM) and distal margins, quality of life, bladder and sexual dysfunction, and oncological outcomes. RESULTS: Baseline characteristics were well balanced. Type of anastomosis [colo-anal anastomosis (CAA) 40% vs 49%; p < 0.001], transanal TME (5% vs 13%; p = 0.005), and conversion rate (2% vs 9.5%; odd ratio (OR): 0.19 [95% confidence interval (CI): 0.05-0.60]) were significantly different. Intersphincteric resection (39% vs 47%), diverting stoma (66.5% vs 68%), CRM involvement, median operative time (243 vs 232 min), and R0 resection rate were similar. Conversion risk was lower for R-TME in male patients and those with small tumors (< 5 cm). The 3-year overall survival rate was 84.1% [77.3-88.9%] and 88.4% [82.9-92.2%] in the R-TME and L-TME group. No significant differences were reported in quality of life, and urinary or sexual function. CONCLUSIONS: R-TME is less likely to be converted to open surgery than L-TME; operative time and curative pathologic criteria are equivalent. Future prospective trial should compare standardized procedures performed by experienced surgeons for subgroups of high-risk patients.
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Adenocarcinoma/cirurgia , Canal Anal/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Laparoscopia/métodos , Tratamentos com Preservação do Órgão/métodos , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Canal Anal/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Neoplasias Retais/patologia , Estudos RetrospectivosRESUMO
OBJECTIVES: We conducted a phase 2 trial to assess the feasibility of interval cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in patients with stage III and IV pleural ovarian carcinoma in first-line treatment with no macroscopic residual disease after surgery. METHODS: Patients could be treated either with primary CS with HIPEC followed by 6 conventional cycles of chemotherapy or with 3 or 4 cycles of neoadjuvant chemotherapy before CS with HIPEC and 3 postoperative chemotherapy cycles. Hyperthermic intraperitoneal chemotherapy was performed with cisplatin (50 mg/m) for 60 minutes, only in case of complete cytoreduction. RESULTS: Nineteen patients were included in the study, and they all underwent neoadjuvant chemotherapy before CS. Sixteen patients underwent complete CS with HIPEC. There was no mortality, and morbidity of CS with HIPEC was acceptable. The HIPEC procedure did not prevent the administration of the standard first-line treatment. In the 16 patients who underwent CS with HIPEC, the outcomes were very good. CONCLUSION: Our study shows an acceptable toxicity of adding HIPEC to the standard first-line treatment in patients with stage III ovarian carcinoma treated with interval CS. Further studies are needed to confirm the role of HIPEC in the treatment of ovarian carcinoma.
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Cisplatino/administração & dosagem , Hipertermia Induzida/métodos , Neoplasias Ovarianas/terapia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Infusões Parenterais , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais , Projetos Piloto , Estudos ProspectivosRESUMO
Reproductive techniques such as prenatal diagnosis (PND) or preimplantation genetic diagnosis (PGD), although debated, are legally forbidden in France in case of Lynch syndrome. The preference of mutation carriers about their reproductive options is not systematically considered in France. We aimed to prospectively assess the reproductive preferences of mismatch repair mutation carriers consulting in our institution (2003-2010, n = 100). We also considered the short- and long-term post-disclosure psychological impact using the Impact of Events Scale-Revised questionnaire to measure the prevalence of posttraumatic stress disorder (PTSD) in those patients. Complete data were obtained for 34 respondents (17 males, 17 females, median age of 33.5 years [22-59]). Seventeen respondents (57 %) preferred spontaneous natural conception versus 28 % and 35 % choosing PND and PGD, respectively. At results disclosure, respondents mainly explained their distress by fear of premature death (43 %) and transmitting mutated genes (42 %). One year later, this last fear remained predominant in 55 % of subjects. None of the main socio-demographical, psychological or medical variables (including fear of transmitting mutations) was significantly associated with the reproductive preferences. Results disclosure had a real and time-decreasing psychological impact on mutation carriers. Reproductive techniques, expected to decrease the hereditary risk, were not significantly preferred to natural conception.
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Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/psicologia , Tomada de Decisões , Mutação , Reprodução , Adulto , Reparo de Erro de Pareamento de DNA , Revelação , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Diagnóstico Pré-Implantação , Diagnóstico Pré-Natal/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Inquéritos e Questionários , Adulto JovemRESUMO
To dissect secretory traffic, we developed the retention using selective hooks (RUSH) system. RUSH is a two-state assay based on the reversible interaction of a hook protein fused to core streptavidin and stably anchored in the donor compartment with a reporter protein of interest fused to streptavidin-binding peptide (SBP). Biotin addition causes a synchronous release of the reporter from the hook. Using the RUSH system, we analyzed different transport characteristics of various Golgi and plasma membrane reporters at physiological temperature in living cells. Using dual-color simultaneous live-cell imaging of two cargos, we observed intra- and post-Golgi segregation of cargo traffic, consistent with observation in other systems. We show preliminarily that the RUSH system is usable for automated screening. The system should help increase the understanding of the mechanisms of trafficking and enable screens for molecules that perturb pathological protein transport.
Assuntos
Proteínas de Transporte/metabolismo , Membrana Celular/metabolismo , Complexo de Golgi/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Microscopia Confocal/métodos , Estreptavidina/metabolismo , Transporte Biológico , Membrana Celular/ultraestrutura , Complexo de Golgi/ultraestrutura , Células HeLa , Humanos , Microscopia Imunoeletrônica , Transfecção/métodosRESUMO
Background: A nation-wide study recently published the dose reference levels for the main CT-guided interventional procedures in 5001 patients. We assessed the impact of patient's age, sex and targeted organ on the patient dose during thoracic and abdominopelvic biopsies and punctures/drainages. Patients and methods: Data were extracted from the previous nationwide study. All biopsies, punctures and drainages for thoracic or abdominopelvic locations performed between January 2017 and June 2019 in all participating centers were included in the study. Multivariable analyses were carried out using a linear regression of the dose-length product (DLP) log, adjusted to age, sex, anatomical location, number of helical acquisitions and inclusion center. Results: Of the 5001 patients of the initial study, 2383 benefited from thoracic or abdominopelvic procedures, including 674 percutaneous destructions excluded. 1709 patients (44 centers), 1045 men, 664 women, median age 64.4 ± 14.0 years were included. The mean DLP was 751.2 ± 642.7mGy.cm. It was significantly higher in men than women (p = 0.0005) and higher for abdominopelvic procedures than for thoracic locations (p<0.0001). Conclusion: Doses delivered to patients for abdominal and thoracic biopsies and punctures/drainages performed under CT guidance depend on gender and location. Furthers studies taking into account the patient's morphology and anatomical location of the procedure would allow proposing finer dose reference levels.