Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
1.
Nutrients ; 13(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34371859

RESUMO

Almost two in three patients who are aged 75 years and older and scheduled for surgery for colorectal cancer (CRC) are undernourished. Despite evidence that perioperative nutritional management can improve patients outcomes, international guidelines are still insufficiently applied in current practice. In this stepped-wedge cluster-randomized study of five surgical hospitals, we included 147 patients aged 70 years or older with scheduled abdominal surgery for CRC between October 2013 and December 2016. In the intervention condition, an outreach team comprising a geriatrician and a dietician visited patients and staff in surgical wards to assist with the correct application of guidelines. Evaluation, diagnosis, and prescription (according to nutritional status) were considered appropriate and strictly consistent with guidelines in 39.2% of patients in the intervention group compared to only 1.4% in the control group (p = 0.0002). Prescription of oral nutritional supplements during the perioperative period was significantly improved (41.9% vs. 4.1%; p < 0.0001). However, there were no benefits of the intervention on surgical complications or adverse events. A possible benefit of hospital stay reduction will need to be confirmed in further studies. This study highlights the importance of the implementation of quality improvement interventions into current practice for the perioperative nutritional management of older patients with CRC.


Assuntos
Avaliação Geriátrica/métodos , Desnutrição/terapia , Terapia Nutricional/métodos , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/complicações , Neoplasias Colorretais/fisiopatologia , Neoplasias Colorretais/cirurgia , Suplementos Nutricionais , Feminino , Humanos , Masculino , Desnutrição/complicações , Política Nutricional , Terapia Nutricional/normas , Estado Nutricional , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios/normas , Período Pré-Operatório , Melhoria de Qualidade , Resultado do Tratamento
2.
BMJ Open ; 11(7): e046819, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226220

RESUMO

INTRODUCTION: Despite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery (CRS) for peritoneal metastases (PM). Apart from the Peritoneal Cancer Index (PCI), completeness of cytoreduction and tumour grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy (SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilisation of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilisation of these factors in clinical decision making and the extent of peritoneal resection performed for different tumours. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors. METHODS AND ANALYSIS: There is no therapeutic intervention in the study. All patients with biopsy-proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a prespecified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumour nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centres will be studied. ETHICS AND DISSEMINATION: The study protocol has been approved by the Zydus Hospital ethics committee (27 July, 2020) and Lyon-Sud ethics committee (A15-128). TRIAL REGISTRATION NUMBER: CTRI/2020/09/027709; Pre-results.


Assuntos
Neoplasias Colorretais , Neoplasias Ovarianas , Neoplasias Peritoneais , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia , Estudos Observacionais como Assunto , Neoplasias Peritoneais/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
3.
Sci Rep ; 11(1): 14728, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282198

RESUMO

This study aimed to explore the validity of the use of the net clinical benefit (NCB), i.e. the sum of major bleeding and thrombotic events, as a potential surrogate for all-cause mortality in clinical trials assessing antithrombotics. Published randomized controlled trials testing anticoagulants in the prevention or treatment of venous thromboembolism (VTE) and non-valvular atrial fibrillation (NVAF) were systematically reviewed. The validity of NCB as a surrogate endpoint was estimated by calculating the strength of correlation of determination (R2) and its 95% confidence interval (CI) between the relative risks of NCB and all-cause mortality. Amongst the 125 trials retrieved, the highest R2trial values were estimated for NVAF (R2trial = 0.41, 95% CI [0.03; 0.48]), and acute VTE (R2trial = 0.30, 95% CI [0.04; 0.84]). Conversely, the NCB did not correlate with all-cause mortality in prevention studies with medical (R2trial = 0.12, 95% CI [0.00; 0.36]), surgical (R2trial = 0.05, 95% CI [0.00; 0.23]), and cancer patients (R2trial = 0.006, 95% CI [0.00; 1.00]). A weak correlation between NCB and all cause-mortality was found in NVAF and acute VTE, whereas no correlation was observed in clinical situations where the mortality rate was low. Consequently, NCB should not be considered a surrogate outcome for all cause-mortality in anticoagulation trials.

4.
Ann Surg Oncol ; 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34142293

RESUMO

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is performed with a wide variation in methodology, drugs, and other elements vital to the procedure. Adoption of a limited number of regimens could increase the collective experience of peritoneal oncologists, make comparison between studies more meaningful, and lead to a greater acceptance of results from randomized trials. This study aimed to determine the possibility of standardizing HIPEC methodology and regimens and to identify the best method of performing such a standardization. METHODS: A critical review of preclinical and clinical studies evaluating the pharmacokinetic aspects of different HIPEC drugs and drug regimens, the impact of hyperthermia, and the efficacy of various HIPEC regimens as well as studies comparing different regimens was performed. RESULTS: The preclinical and clinical data were limited, and studies comparing different regimens were scarce. Many of the regimens were neither supported by preclinical rationale or data nor validated by a dose-escalating formal phase 1 trial. All the regimens were based on pharmacokinetic data and did not take chemosensitivity of peritoneal metastases into account. Personalized medicine approaches such as patient-derived tumor organoids could offer a solution to this problem, although clinical validation is likely to be challenging. CONCLUSIONS: Apart from randomized trials, more translational research and phases 1 and 2 studies are needed. While waiting for better preclinical and clinical evidence, the best way to minimize heterogeneity is by an expert consensus that aims to identify and define a limited number of regimens for each indication and primary site. The choice of regimen then can be tailored to the patient profile and its expected toxicity and the methodology according regional factors.

5.
Virchows Arch ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34169365

RESUMO

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant peritoneal mesothelioma. A recently described nuclear-grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The present study was undertaken to validate this grading system in epithelioid malignant peritoneal mesothelioma (EMPM) and to compare to combined grade, including nuclear atypia, mitotic count, and tumor necrosis. Cases of EMPM, from 1995 to 2018, were analyzed from 7 French institutions from RENAPE network. Solid growth, tumor necrosis, nuclear atypia, and mitotic count were evaluated by at least 3 pathologists from the RENAPATH group. The predictions in terms of OS and PFS of nuclear grade and combined grade were analyzed. Nuclear grade was computed combining nuclear atypia score and mitotic count into a grade of I-III. Another system combining nuclear atypia score, mitotic score, and tumor necrosis was evaluated and defined as a combined grade I-III. A total of 138 cases were identified. The median follow-up was 38.9 months (range: 1.1-196.6). Nuclear and combined grades III were independently associated with a shorter OS (p < 0.05), and a shorter PFS (p < 0.05). Patients with combined grade I tumors had the best overall and progression-free survivals, in comparison to nuclear grade I. In this large multicentric study, combined grade and nuclear grade were the best independent predictors of OS and PFS in EMPM. These systems should be easily described by pathologists involved into the management of malignant peritoneal mesothelioma, because of their potential therapeutic implications.

6.
Int J Hyperthermia ; 38(1): 805-814, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34039244

RESUMO

BACKGROUND: Multicystic peritoneal mesothelioma (MCPM) is a rare, slowly growing, condition prone to recur after surgery. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) added to complete cytoreductive surgery (CRS) remains controversial and difficult to assess. As patients are mostly reproductive age women, surgical approach, and fertility considerations are important aspects of the management. This observational retrospective review aimed to accurate treatment strategy reflections. METHODS: The RENAPE database (French expert centers network) was analyzed over a 1999-2019 period. MCPM patients treated with CRS were included. A special focus on HIPEC, mini-invasive approach, and fertility considerations was performed. RESULTS: Overall 60 patients (50 women) were included with a median PCI of 10 (4-14) allowing 97% of complete surgery, followed by HIPEC in 82% of patients. A quarter of patients had a laparoscopic approach. Twelve patients (20%) recurred with a 3-year recurrence free survival of 84.2% (95% confidence interval 74.7-95.0). The hazard of recurrence was numerically reduced among patients receiving HIPEC, however, not statistically significant (hazard ratio 0.41, 0.12-1.42, p = 0.200). A severe post-operative adverse event occurred in 22% of patients with five patients submitted to a subsequent reoperation. Among four patients with a childbearing desire, three were successful (two had a laparoscopic-CRS-HIPEC and one a conventional CRS without HIPEC). CONCLUSION: MCPM patients treatment should aim at a complete CRS. The intraoperative treatment options as laparoscopic approach, fertility function sparing and HIPEC should be discussed in expert centers to propose the most appropriate strategy.


Assuntos
Hipertermia Induzida , Mesotelioma , Intervenção Coronária Percutânea , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia do Câncer por Perfusão Regional , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Mesotelioma/tratamento farmacológico , Mesotelioma/cirurgia , Recidiva Local de Neoplasia , Estudos Retrospectivos
7.
Virchows Arch ; 479(4): 765-772, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33855595

RESUMO

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant peritoneal mesothelioma. The relationship between a strong adaptive immune response and a better prognosis in malignant solid tumors is widely known. Due to the low incidence of epithelioid malignant peritoneal mesothelioma (EMPM), very little is known about their immune micro-environment. We encountered several cases of tertiary lymphoid structures in EMPM in a previous study and aimed to investigate in the same series the prevalence, clinicopathological features, and the prognostic impact associated with tertiary lymphoid structures in EMPM (TLS-EMPM). Cases of EMPM, from 1995 to 2018, were retrieved from 7 French institutions from the RENAPE Network. The predictions in terms of overall survival (OS) and progression-free survival (PFS) of TLS-EMPM were analyzed. We report 52 cases of TLS-EMPM among a series of 138 cases of EMPM. TLS-EMPM was significantly associated with neoadjuvant chemotherapy, and was not a prognostic indicator for OS (p = 0.652) and PFS (p = 0.804) in our series. TLS is a component of the host immune response to EMPM significantly associated with neoadjuvant chemotherapy, but was not a predictor of prognosis for overall and progression-free survivals in this series. These findings provide another possible etiology for tertiary lymphoid structures.

8.
J Natl Cancer Inst ; 113(8): 1027-1035, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-33484560

RESUMO

BACKGROUND: Multimodal treatment, including systemic treatment and surgery, improved the prognosis of peritoneal metastasis (PM). Despite all efforts, recurrence rates remain high, and little data are available about clinical behavior or molecular patterns of PM in comparison to hematogenous metastasis. Here, we aimed to analyze recurrence patterns after multimodal treatment for PM from colorectal cancer. METHODS: Patients with colorectal PM undergoing multimodal treatment including systemic chemotherapy and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 2005 and 2017 at 4 centers were analyzed retrospectively. RESULTS: A total of 505 patients undergoing CRS/HIPEC were analyzed. Of the patients, 82.1% received preoperative chemotherapy. Median peritoneal cancer index was 6 (interquartile range = 3-11). Median disease-free and overall survival was 12 (95% confidence interval [CI] = 11 to 14) months and 51 (95% CI = 43 to 62) months, respectively. Disease recurred in 361 (71.5%) patients, presenting as isolated peritoneal recurrence in 24.6%, isolated hematogenous recurrence in 28.3%, and mixed recurrence in 13.9% of patients. Recurrence to the peritoneum was associated with an impaired time from recurrence to death of 21 (95% CI = 18 to 31) months for isolated peritoneal and 22 (95% CI = 16 to 30) months for mixed recurrence, compared with 43 (95% CI = 31 to >121) months for hematogenous recurrence (hazard ratio [HR] = 1.79, 95% CI = 1.27 to 2.53; P = .001; and HR = 2.44, 95% CI = 1.61 to 3.79; P < .001). On multiple logistic regression analysis, RAS mutational status (odds ratio [OR] = 2.42, 95% CI = 1.11 to 5.47; P = .03) and positive nodal stage of the primary (OR = 3.88, 95% CI = 1.40 to 11.86; P = .01) were identified as predictive factors for peritoneal recurrence. CONCLUSIONS: This study highlights the heterogeneity of peritoneal metastasis in patients with colorectal cancer. Recurrent peritoneal metastasis after radical treatment represents a more aggressive subset of metastatic colorectal cancer.

9.
JAMA Surg ; 156(3): e206363, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33502455

RESUMO

Importance: Studies on the prognostic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei (PMP) are currently not available. Objectives: To evaluate outcomes after cytoreductive surgery (CRS) and HIPEC compared with CRS alone in patients with PMP. Design, Setting, and Participants: This cohort study analyzed data from the Peritoneal Surface Oncology Group International (PSOGI) registry, including 1924 patients with histologically confirmed PMP due to an appendiceal mucinous neoplasm. Eligible patients were treated with CRS with or without HIPEC from February 1, 1993, to December 31, 2017, and had complete information on the main prognostic factors and intraperitoneal treatments. Inverse probability treatment weights based on the propensity score for HIPEC treatment containing the main prognostic factors were applied to all models to balance comparisons between the CRS-HIPEC vs CRS-alone groups in the entire series and in the following subsets: optimal cytoreduction, suboptimal cytoreduction, high- and low-grade histologic findings, and different HIPEC drug regimens. Data were analyzed from March 1 to June 1, 2018. Interventions: HIPEC including oxaliplatin plus combined fluorouracil-leucovorin, cisplatin plus mitomycin, mitomycin, and other oxaliplatin-based regimens. Main Outcomes and Measures: Overall survival, severe morbidity (determined using the National Cancer Institute Common Terminology for Adverse Events, version 3.0), return to operating room, and 30- and 90-day mortality. Differences in overall survival were compared using weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards multivariable models. A sensitivity analysis was based on the E-value from the results of the main Cox proportional hazards model. Differences in surgical outcomes were compared using weighted multivariable logistic models. Results: Of the 1924 patients included in the analysis (997 [51.8%] men; median age, 56 [interquartile range extremes (IQRE), 45-65] years), 376 were in the CRS-alone group and 1548 in the CRS-HIPEC group. Patients with CRS alone were older (median age, 60 [IQRE, 48-70] vs 54 [IQRE, 44-63] years), had less lymph node involvement (14 [3.7%] vs 119 [7.7%]), received more preoperative systemic chemotherapy (198 [52.7%] vs 529 [34.2%]), and had higher proportions of high-grade disease (179 [47.6%] vs 492 [31.8%]) and suboptimal cytoreduction residual disease (grade 3, 175 [46.5%] vs 117 [7.6%]). HIPEC was not associated with a higher risk of worse surgical outcomes except with mitomycin, with higher odds of morbidity (1.99; 95% CI, 1.25-3.19; P = .004). HIPEC was associated with a significantly better overall survival in all subsets (adjusted hazard ratios [HRs], 0.60-0.68, with 95% CIs not crossing 1.00). The weighted 5-year overall survival was 57.8% (95% CI, 50.8%-65.7%) vs 46.2% (95% CI, 40.3%-52.8%) for CRS-HIPEC and CRS alone, respectively (weighted HR, 0.65; 95% CI, 0.50-0.83; P < .001; E-value, 2.03). Such prognostic advantage was associated with oxaliplatin plus fluorouracil-leucovorin (HR, 0.42; 95% CI, 0.19-0.93; P = .03) and cisplatin plus mitomycin (HR, 0.57; 95% CI, 0.42-0.78; P = .001) schedules. Conclusions and Relevance: In this cohort study, HIPEC was associated with better overall survival when performed after CRS in PMP, generally without adverse effects on surgical outcomes.

10.
Eur J Surg Oncol ; 47(1): 123-127, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32561204

RESUMO

BACKGROUND: PIPAC is a recent approach with promising results for patients with peritoneal metastasis (PM). We aimed to evaluate survival and postoperative outcome of patients with unresectable PM from gastric origin treated with chemotherapy and PIPAC. METHODS: A retrospective analysis of a prospective maintained PIPAC database was queried for all patients diagnosed with unresectable PM from gastric cancer who underwent PIPAC before 2018. PIPAC with Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 6-week intervals. Outcome criteria were overall survival and adverse events according to (CTCAE) version4.0. RESULTS: One hundred Sixty-three PIPAC were done in 42 consecutive patients. Twenty-two (52%) of the patients were female. Signet-ring cells were observed in 33/42 patients (78.6%). At the first PIPAC, median age was 51.5 years (32-74). Median PCI was 17 (1-39). Twenty (47.6%) patients underwent more than 2 lines of pre-PIPAC chemotherapy. All patients had systemic chemotherapy alternating with PIPAC. Median consecutive PIPAC procedures were 3 (1-12). Overall and major complications (CTCAE - III, IV) occurred in 10 (6.1%) and 5 procedures (3.1%), respectively. Two patients (4.7%) died within 30 days of a PIPAC procedure, one related to small bowel obstruction and a pulmonary embolism for the other. Overall Survival was 19.1 months. Six (14.3%) patients became resectable during treatment and underwent curative intent CRS and HIPEC. CONCLUSIONS: PIPAC with low-dose cisplatin and doxorubicin is safe and feasible in association with systemic chemotherapy for gastric PM. Survival data are encouraging and justify further clinical studies in this indication.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Nebulizadores e Vaporizadores , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Adulto , Aerossóis , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Eur J Surg Oncol ; 47(1): 128-133, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253545

RESUMO

BACKGROUND: PIPAC is a recent method of intraperitoneal chemotherapy. The aim of this study was to describe the clinical characteristics of the patients who became amenable to CRS & HIPEC after PIPAC treatment. METHODS: All patients diagnosed with unresectable PM who became resectable throughout PIPAC treatment were included. Outcome criteria were adverse events following PIPAC procedure and rate of secondary CRS and HIPEC. RESULTS: Four hundred thirty-seven PIPAC were done in 146 consecutive patients. Among them, 26 patients (17.8%) who underwent 76 PIPAC were scheduled for CRS and HIPEC after reduction of the peritoneal burden. PM were from gastric, peritoneal mesothelioma, ovarian, colorectal and small bowel in 13, 7, 4, 1 and 1 patients, respectively. At the time of the first PIPAC, median age was 58.6 years (32-76.3). Median PCI was 16 (1-39). All patients had systemic chemotherapy in between PIPAC session. Median consecutive PIPAC procedure was 3 (1-8). Complications occurred in 3 PIPAC session (4%) and there was no major complication (CTCAE III or higher). Complete CRS and HIPEC was achieved in 21 patients of the 26 scheduled (14.4%). The remaining 5 patients were considered unresectable at the exploratory laparotomy. Among patients who underwent CRS and HIPEC, with median follow-up of 7 (1-26) months, 14 patients (66.7%) were alive without recurrence, 2 patients (9.5%) were alive with recurrence and 5 patients (23.8%) died. CONCLUSIONS: Complete CRS and HIPEC can be achieved in strictly selected patient with unresectable PM at diagnosis after repeated PIPAC session with palliative intent.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Nebulizadores e Vaporizadores , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Adulto , Aerossóis , Idoso , Cisplatino/administração & dosagem , Terapia Combinada , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Estudos Retrospectivos
12.
Eur J Surg Oncol ; 47(1): 139-142, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-30914289

RESUMO

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising technic for unresectable peritoneal metastasis (PM). Targeted therapies such as bevacizumab have demonstrated their efficacy in advanced colorectal and ovarian cancer. We aimed to evaluate the feasibility and safety of this bidimensional therapeutic association. METHODS: A prospectively maintained PIPAC database was retrospectively analyzed from December 2015 to March 2018. All patients who underwent PIPAC for unresectable PM were selected. Patients with systemic chemotherapy including bevacizumab (BEVA group) were compared with patients with systemic chemotherapy without bevacizumab (NON-BEVA group). Major morbidity and mortality were analyzed. RESULTS: 134 patients underwent 397 PIPAC in Lyon Sud University Hospital. 26 Patients had 88 PIPAC in the BEVA group were compared to 108 patients who had 309 PIPAC in the NON-BEVA group. Patients in the BEVA group demonstrated a higher Peritoneal Cancer Index (PCI 20 vs. 16, p < 0.001). There was no statistical difference in overall 30-day morbidity (BEVA: 13 (14.8%) vs NON-BEVA: 29 (9.4%); p = 0.147). There was no statistical difference for grade III-IV complications (BEVA: 4 (4.5%) vs NON-BEVA 10 (3.2%); P = 0.521). Major complications from BEVA group were as follow, 2 bowel obstructions, one hematoma and one severe hypersensitivity reaction to platinum compound. There was no 30-day mortality in the BEVA group compared to 6 (5.5%) mortality in the NON-BEVA group. CONCLUSION: PIPAC associated with bevacizumab is feasible, safe and well tolerated. The potential oncologic benefit of the concomitant use of bevacizumab and PIPAC remains to be evaluated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Nebulizadores e Vaporizadores , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Aerossóis , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Estudos Retrospectivos
13.
Eur J Surg Oncol ; 47(1): 149-156, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32900609

RESUMO

BACKGROUND: PIPAC is a new treatment modality for peritoneal cancer which has been practiced and evaluated until very recently by few academic centers in a highly standardized manner. Encouraging oncological outcomes and the safety profile have led to widespread adoption. The aim of this study was to assess current PIPAC practice in terms of technique, treatment and safety protocol, and indications. METHODS: A standardized survey with 82 closed-ended questions was sent online to active PIPAC centers which were identified by help of PIPAC training centers and the regional distributors of the PIPAC-specific nebulizer. The survey inquired about center demographics (n = 8), technique (n = 34), treatment and safety protocol (n = 34), and indications (n = 6). RESULTS: Overall, 62 out of 66 contacted PIPAC centers answered the survey (response rate 93%). 27 centers had performed >60 PIPAC procedures. A consensus higher than 70% was reached for 37 items (50%), and higher than 80% for 28 items (37.8%). The topics with the highest degree of consensus were safety and installation issues (93.5% and 80.65%) while chemotherapy and response evaluation were the least consensual topics (63.7 and 59.6%). The attitudes were not influenced by volume, PIPAC starting year, type of activity, or presence of peritoneal metastases program. CONCLUSION: Homogeneous treatment standards of new techniques are important to guarantee safe implementation and practice but also to allow comparison between cohorts and multi-center analysis of merged data including registries. Efforts to avoid diversification of PIPAC practice include regular update of the PIPAC training curriculum, targeted research and a consensus statement.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Nebulizadores e Vaporizadores , Neoplasias Peritoneais/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Aerossóis , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Irinotecano/administração & dosagem , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/secundário , Inquéritos e Questionários
14.
Eur J Surg Oncol ; 46(12): 2292-2310, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32873454

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways have been shown to considerably reduce complications, length of stay and costs after most of surgical procedures by standardised application of best evidence-based perioperative care. The aim was to elaborate dedicated recommendations for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) in a two-part series of guidelines based on expert consensus. The present part I of the guidelines highlights preoperative and intraoperative management. METHODS: The core group assembled a multidisciplinary panel of 24 experts involved in peritoneal surface malignancy surgery representing the fields of general surgery (n = 12), gynaecological surgery (n = 6), and anaesthesia (n = 6). Experts systematically reviewed and summarized the available evidence on 72 identified perioperative care items, following the GRADE (grading of recommendations, assessment, development, evaluation) system. Final consensus (defined as ≥50%, or ≥70% of weak/strong recommendations combined) was reached by a standardised 2-round Delphi process, regarding the strength of recommendations. RESULTS: Response rates were 100% for both Delphi rounds. Quality of evidence was evaluated high, moderate low and very low, for 15 (21%), 26 (36%), 29 (40%) and 2 items, respectively. Consensus was reached for 71/72(98.6%) items. Strong recommendations were defined for 37 items, No consensus could be reached regarding the preemptive use of fresh frozen plasma. CONCLUSION: The present ERAS recommendations for CRS±HIPEC are based on a standardised expert consensus process providing clinicians with valuable guidance. There is an urgent need to produce high quality studies for CRS±HIPEC and to prospectively evaluate recommendations in clinical practice.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Recuperação Pós-Cirúrgica Melhorada , Quimioterapia Intraperitoneal Hipertérmica/métodos , Cuidados Intraoperatórios/métodos , Neoplasias Peritoneais/terapia , Cuidados Pré-Operatórios/métodos , Técnica Delfos , Humanos , Assistência Perioperatória
15.
Eur J Surg Oncol ; 46(12): 2311-2323, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32826114

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways have been shown to considerably reduce complications, length of stay and costs after most of surgical procedures by standardised application of best evidence-based perioperative care. The aim was to elaborate dedicated recommendations for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) in a two-part series of guidelines based on expert consensus. The present part II of the guidelines highlights postoperative management and special considerations. METHODS: The core group assembled a multidisciplinary panel of 24 experts involved in peritoneal surface malignancy surgery representing the fields of general surgery (n = 12), gynaecological surgery (n = 6), and anaesthesia (n = 6). Experts systematically reviewed and summarized the available evidence on 72 identified perioperative care items, following the GRADE (grading of recommendations, assessment, development, evaluation) system. Final consensus (defined as ≥50%, or ≥70% of weak/strong recommendations combined) was reached by a standardised 2-round Delphi process, regarding the strength of recommendations. RESULTS: Response rates were 100% for both Delphi rounds. Quality of evidence was evaluated high, moderate low and very low, for 15 (21%), 26 (36%), 29 (40%) and 2 items, respectively. Consensus was reached for 71/72(98.6%) items. Strong recommendations were defined for 37 items. No consensus could be reached regarding the preemptive use of fresh frozen plasma. CONCLUSION: The present ERAS recommendations for CRS ± HIPEC are based on a standardised expert consensus process providing clinicians with valuable guidance. There is an urgent need to produce high quality studies for CRS ± HIPEC and to prospectively evaluate recommendations in clinical practice.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Recuperação Pós-Cirúrgica Melhorada/normas , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/terapia , Cuidados Pós-Operatórios/normas , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/normas , Técnica Delfos , Humanos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Quimioterapia Intraperitoneal Hipertérmica/normas , Neoplasias Peritoneais/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Operatório
16.
J Clin Oncol ; 38(27): 3129-3137, 2020 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-32716740

RESUMO

PURPOSE: Women with gestational trophoblastic tumors (GTT) resistant to single-agent chemotherapy receive alternative chemotherapy regimens, which, although effective, cause considerable toxicity. All GTT subtypes express programmed death-ligand 1 (PD-L1), and natural killer (NK) cells are involved in trophoblast immunosurveillance. Avelumab (anti-PD-L1) induces NK cell-mediated cytotoxicity. The TROPHIMMUN trial assessed avelumab in women with chemotherapy-resistant GTT. METHODS: In this phase II multicenter trial (ClinicalTrials.gov identifier: NCT03135769), women with GTT who experienced disease progression after single-agent chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks until human chorionic gonadotropin (hCG) normalization, followed by 3 consolidation cycles. Rate of hCG normalization was the primary endpoint (2-step Simon design). RESULTS: Between December 2016 and September 2018, 15 patients were treated. Median age was 34 years; disease stage was I or III in 53.3% and 46.7% of women, respectively; and International Federation of Gynecology and Obstetrics (FIGO) score was 0-4 in 33.3%, 5-6 in 46.7%, and ≥ 7 in 20% of patients. Prior treatment included methotrexate (100%) and actinomycin D (7%). Median follow-up was 25 months, and median number of avelumab cycles was 8 (range, 2-11). Grade 1-2 treatment-related adverse events occurred in 93% of patients, most commonly (≥ 25%) fatigue (33.3%), nausea/vomiting (33.3%), and infusion-related reaction (26.7%). One patient had grade 3 uterine bleeding (treatment unrelated). Eight patients (53.3%) had hCG normalization after a median of 9 avelumab cycles; none subsequently relapsed. Probability of normalization was not associated with disease stage, FIGO score, or baseline hCG. One patient subsequently had a healthy pregnancy. In avelumab-resistant patients (46.7%), hCG was normalized with actinomycin D (42.3%) or combination chemotherapy/surgery (57.1%). CONCLUSION: In patients with single-agent chemotherapy-resistant GTT, avelumab had a favorable safety profile and cured approximately 50% of patients. Avelumab could be a new therapeutic option, particularly in patients who would otherwise receive combination chemotherapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Gonadotropina Coriônica/sangue , Doença Trofoblástica Gestacional/tratamento farmacológico , Adulto , Antibióticos Antineoplásicos/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Dactinomicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Fadiga/induzido quimicamente , Feminino , Seguimentos , Doença Trofoblástica Gestacional/sangue , Humanos , Reação no Local da Injeção/etiologia , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Gravidez , Retratamento , Vômito/induzido quimicamente , Adulto Jovem
17.
Histopathology ; 77(4): 548-559, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32060943

RESUMO

AIMS: The peritoneal regression grading score (PRGS) and peritoneal cytology (PC) assess response to chemotherapy in peritoneal metastasis (PM) in a setting of palliative treatment by pressurized intraperitoneal aerosol chemotherapy (PIPAC). Progression has been defined as an increase of PRGS between first and third PIPAC procedures (iPRGS). iPRGSand positive peritoneal cytology were not associated with prognostic impact. These results may be explained by a lack of statistical power. Also, it is not known whether the mean or the highest PRGS among taken peritoneal biopsies bears the highest clinical value. We therefore conducted the largest prospective study to investigate the prognostic impact of PGRS, PC, and their combination, designated as combined progression index (CPI). METHODS AND RESULTS: Patients with PM who underwent >3 PIPAC (n = 112) between December 2016 and February 2019 were prospectively included. A significant difference in OS and PFS according to CPI (used highest value of PRGS) was found (OS: CPI-, 83.3, 95% CI [49.8; NA] vs. CPI+, 48.1, 95% CI [38.5; 66.4] months; and PFS (respectively, 59.7, 95% CI [43.0; 96.0] vs. 33.7, 95% CI [30.4; 44.2] months). PRGS or PC had no independent prognostic impact. CPI+ was an independent predictor of worse prognosis, in OS (HR = 5.24, 95% CI [2.07; 13.26]), and PFS (HR = 4.41, 95% CI [1.40; 13.88]). CONCLUSIONS: The CPI based on highest PRGS and PC was found to be independently associated with a worse prognosis for OS and for PFS in the setting of peritoneal metastasis. These results indicate that it should be of interest to systematically take peritoneal fluid for cytological examination and to implement the CPI in the therapeutic decision-making process in the context of PIPAC.

18.
EBioMedicine ; 51: 102574, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31877416

RESUMO

BACKGROUND: In colorectal cancer, hPG80 (progastrin) is released from tumor cells, promotes cancer stem cells (CSC) self-renewal and is detected in the blood of patients. Because the gene GAST that encodes hPG80 is a target gene of oncogenic pathways that are activated in many tumor types, we hypothesized that hPG80 could be expressed by tumors from various origins other than colorectal cancers, be a drug target and be detectable in the blood of these patients. METHODS: hPG80 expression was monitored by fluorescent immunohistochemistry and mRNA expression in tumors from various origins. Cancer cell lines were used in sphere forming assay to analyze CSC self-renewal. Blood samples were obtained from 1546 patients with 11 different cancer origins and from two retrospective kinetic studies in patients with peritoneal carcinomatosis or hepatocellular carcinomas. These patients were regularly sampled during treatments and assayed for hPG80. FINDINGS: We showed that hPG80 was present in the 11 tumor types tested. In cell lines originating from these tumor types, hPG80 neutralization decreased significantly CSC self-renewal by 28 to 54%. hPG80 was detected in the blood of patients at significantly higher concentration than in healthy blood donors (median hPG80: 4.88 pM versus 1.05 pM; p < 0.0001) and shown to be correlated to GAST mRNA levels in the matched tumor (i.e., lung cancers, Spearman r = 0.8; p = 0.0023). Furthermore, we showed a strong association between longitudinal hPG80 concentration changes and anti-cancer treatment efficacy in two independent retrospective studies. In the peritoneal carcinomatosis cohort, median hPG80 from inclusion to the post-operative period decreased from 5.36 to 3.00 pM (p < 0.0001, n = 62) and in the hepatocellular carcinoma cohort, median hPG80 from inclusion to remission decreased from 11.54 pM to 1.99 pM (p < 0.0001, n = 63). INTERPRETATION: Because oncogenic hPG80 is expressed in tumor cells from different origins and because circulating hPG80 in the blood is related to the burden/activity of the tumor, it is a promising cancer target for therapy and for disease monitoring. FUNDINGS: ECS-Progastrin.


Assuntos
Gastrinas/sangue , Neoplasias/sangue , Neoplasias/genética , Oncogenes , Precursores de Proteínas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antineoplásicos/imunologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/genética , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia , Especificidade de Órgãos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Adulto Jovem
19.
Cytopathology ; 31(1): 5-11, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31713897

RESUMO

OBJECTIVE: Diffuse malignant peritoneal mesothelioma (DMPM), represents 30% of all malignant mesothelioma, and is characterised by a difficult diagnosis and different presentations. Immunohistochemistry has improved the diagnostic sensitivity and specificity in the differential diagnosis between metastatic adenocarcinoma and malignant mesothelioma, and loss of BRCA-1-associated protein 1 (BAP1) expression is correlated with BAP1 somatic or constitutional genetic defects. Furthermore, cyclin-dependent kinase inhibitor 2A (CDKN2A) is frequently lost in DMPM. In the present study, we assessed the value of integrating BAP1 in the panel of antibodies used for the diagnosis of DMPM in cytological samples. Since p16 fluorescent in situ hybridisation (FISH) assay could constitute an additional useful adjunct, results of BAP1 immunostaining and p16 FISH assays have been compared. METHODS: Forty-eight DMPM patients and 71 peritoneal carcinomatosis patients were included. BAP1 immunohistochemical and CDKN2A FISH techniques were performed on tissue specimens of DMPM (n = 48) and peritoneal carcinomatosis (n = 71) then on cell-block of DMPM (n = 16), peritoneal carcinomatosis (n = 25) and peritoneal benign effusion (n = 5). RESULTS: Loss of BAP1 expression was observed in 56.3% of DMPM while none of the peritoneal carcinoma specimens showed BAP1 loss of expression. CDKN2A loss was observed in 34.9% DMPM and 2.1% peritoneal carcinoma. Although BAP1 immunostaining was successful in 100% of cytological DMPM samples, CDKN2A deletion status could be obtained for 75% of DMPM cases. CONCLUSION: BAP1 immunostaining represents an objective and reproducible diagnostic biomarker for peritoneal mesothelioma in effusion cytology specimens and should be preferred to CDKN2A FISH analysis on these precious samples.


Assuntos
Carcinoma/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Mesotelioma Maligno/genética , Neoplasias Peritoneais/genética , Peritônio/patologia , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Líquido Ascítico/patologia , Biomarcadores Tumorais/genética , Biópsia/métodos , Carcinoma/patologia , Citodiagnóstico/métodos , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica/métodos , Mesotelioma Maligno/patologia , Neoplasias Peritoneais/patologia
20.
Lancet Oncol ; 20(7): e368-e377, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31267971

RESUMO

Pressurised intraperitoneal aerosol chemotherapy (PIPAC) was introduced as a new treatment for patients with peritoneal metastases in November, 2011. Reports of its feasibility, tolerance, and efficacy have encouraged centres worldwide to adopt PIPAC as a novel drug delivery technique. In this Review, we detail the technique and rationale of PIPAC and critically assess its evidence and potential indications. A systematic search was done to identify all relevant literature on PIPAC published between Jan 1, 2011, and Jan 31, 2019. A total of 106 articles or reports on PIPAC were identified, and 45 clinical studies on 1810 PIPAC procedures in 838 patients were included for analysis. Repeated PIPAC delivery was feasible in 64% of patients with few intraoperative and postoperative surgical complications (3% for each in prospective studies). Adverse events (Common Terminology Criteria for Adverse Events greater than grade 2) occurred after 12-15% of procedures, and commonly included bowel obstruction, bleeding, and abdominal pain. Repeated PIPAC did not have a negative effect on quality of life. Using PIPAC, an objective clinical response of 62-88% was reported for patients with ovarian cancer (median survival of 11-14 months), 50-91% for gastric cancer (median survival of 8-15 months), 71-86% for colorectal cancer (median survival of 16 months), and 67-75% (median survival of 27 months) for peritoneal mesothelioma. From our findings, PIPAC has been shown to be feasible and safe. Data on objective response and quality of life were encouraging. Therefore, PIPAC can be considered as a treatment option for refractory, isolated peritoneal metastasis of various origins. However, its use in further indications needs to be validated by prospective studies.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Peritoneais/tratamento farmacológico , Aerossóis , Humanos , Neoplasias Peritoneais/secundário , Pressão
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...