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1.
Br J Surg ; 108(10): 1225-1235, 2021 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-34498666

RESUMO

BACKGROUND: The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS: All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS: In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION: In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/secundário , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Adulto Jovem
2.
Surg Endosc ; 34(6): 2803-2806, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32166545

RESUMO

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new intraabdominal technique to approach non-resectable peritoneal carcinomatosis (PC). PIPAC can be performed alone or alternated with systemic chemotherapy to increase tumor regression. We describe our initial experience performed in an expert hyperthermic intraperitoneal chemotherapy (HIPEC) French center to demonstrate the safety and the feasibility of PIPAC. METHODS: Between January 2016 and March 2019, PIPAC was proposed to 43 consecutive patients affected by digestive, ovarian, peritoneal and mammary carcinomatosis. Initially PIPAC was proposed to patients non eligible for cytoreductive surgery for palliative purposes. In five patients we associated PIPAC to systemic chemotherapy to improve tumor regression and enhance the chance of patients to undergo HIPEC. Three PIPAC treatments were supposed to be performed for each patient with an interval of 6 weeks in between each procedure. Peritoneal biopsies were always performed to evaluate microscopic tumor regression. In case of postoperative clinical deterioration or quick tumor progression during the cycles, PIPAC was interrupted. Depending on the primary tumor, chemotherapies used were oxaliplatin or a combination of cisplatin and doxorubicin. RESULTS: Twenty-six (60.4%) patients have already had a surgical resection or intervention of primary cancer removal. In 5 patients abdominal access was impossible. Of the 38 patients operated, seventy-one procedures were performed. In the series, one patient died because of tumor progression. Only one major complication occurred intraoperatively. Two of thirteen patients receiving oxaliplatin had postoperative abdominal pain and needed more drugs assumption and a longer hospitalization. Three patients after a three cycles procedure underwent HIPEC. Nine of the patients who had at least two PIPACs had last biopsies showing a major or complete tumor response. CONCLUSION: PIPAC is a safe and feasible procedure that can be performed in patients with peritoneal carcinomatosis initially not eligible for surgery to reduce tumor invasion or for palliation to reduce symptoms. Contraindications are bowel obstruction and multiple intraabdominal adhesions.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma/tratamento farmacológico , Quimioterapia Intraperitoneal Hipertérmica/métodos , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Aerossóis/administração & dosagem , Carcinoma/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Doxorrubicina/administração & dosagem , Estudos de Viabilidade , Feminino , França , Humanos , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/cirurgia , Resultado do Tratamento
3.
Surg Oncol ; 29: 120-125, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31196475

RESUMO

BACKGROUND: Approximately 20% of initially eligible patients in a HIPEC procedure eventually underwent a simple surgical exploration. These procedures are called 'open & close' (O & C) representing up to 48% of surgery. The objective of this study was to predict the resecability of peritoneal carcinomatosis using a machine-learning model for decision-making support, for eligible patients of HIPEC. METHODS: The study was conducted as an intention to treat based on three databases including a prospective, between January 2000 and December 2015. A propensity score allowed us to obtain two groups of comparable and matched patients. Subsequently, several algorithm models of classification were studied (simple classification, conditional tree, support vector machine, random forest) to determine the model having the best performance and accuracy. RESULTS: Two groups of 155 patients were obtained: one group without resection and one group with resection. Nine criteria of non-resecability reflecting the organ involvement have been retained. They were coded according to their importance. Five classification algorithms were tested. The training data included 218 patients and 92 test data. The random forest model exhibited the best performance with an accuracy of close to 98%. Only two errors of predictions were observed. DISCUSSION: The largest number of patients will allow us to improve the precision prediction. Gathering more data such as biologic, radiologic, and even laparoscopic features, should improve the knowledge of the disease and decrease the number of 'O & C' procedures.


Assuntos
Procedimentos Cirúrgicos de Citorredução/estatística & dados numéricos , Técnicas de Apoio para a Decisão , Laparoscopia/estatística & dados numéricos , Aprendizado de Máquina , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Adulto Jovem
4.
Eur J Cancer ; 65: 69-79, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27472649

RESUMO

PURPOSE: Diffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network. PATIENTS AND METHODS: From 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC). RESULTS: All groups (NA: n = 42; ADJ: n = 16; PO: n = 16; NoC: n = 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (P = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07-4.94; P = 0.033). CONCLUSION: This retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Pulmonares/terapia , Mesotelioma/terapia , Neoplasias Peritoneais/terapia , Adolescente , Adulto , Idoso , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Injeções Intraperitoneais , Neoplasias Pulmonares/mortalidade , Masculino , Mesotelioma/mortalidade , Mesotelioma Maligno , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
5.
Gynecol Oncol ; 142(2): 237-42, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27246305

RESUMO

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) may improve the outcome of patients with initially unresectable ovarian cancer who are eligible for complete cytoreductive surgery (CCRS) after neoadjuvant chemotherapy. The main objective of this multicenter phase-I study was to identify the recommended dose of cisplatin for HIPEC at CCRS after neoadjuvant carboplatin and paclitaxel (CP). METHODS: Patients were treated with 6cycles of CP followed by CCRS and HIPEC using cisplatin heated for one hour at 42°C+/-1°C. Four cisplatin dose-levels were evaluated: 50, 60, 70, 80mg/m(2). Dose-limiting toxicities (DLTs) were defined as a grade≥IIIb adverse event (Dindo classification). The Continual Reassessment Method was used for this dose-finding study, with a target percentage of DLT set at 20%. Twenty-two cycles (15mg/kg/cycle) of maintenance bevacizumab therapy were planned after surgery. RESULTS: Between June-2011 and September-2012, 30 patients were recruited. No DLT occurred at the first three dose-levels (4, 4 and 5 patients at 50, 60 and 70mg/m(2) respectively). At dose-level 4 (80mg/m(2), 17 patients), four DLTs occurred: renal failure (n=2), peritonitis (n=1) and hemorrhage (n=1). Eight weeks after surgery, creatinine clearance was reduced to <30mL/min in 3 patients, all treated at 80mg/m(2), and between 30 and 60mL/min in 6 patients (2, 1, 1 and 2 at the four dose-levels respectively). Twenty patients started maintenance bevacizumab, and 7 received the 22 courses initially planned. CONCLUSIONS: Based on the observed DLTs and prolonged impairment of renal function, we recommend a dose of 70mg/m(2) of cisplatin for HIPEC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Cisplatino/administração & dosagem , Hipertermia Induzida/métodos , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário , Quimioterapia Adjuvante , Cisplatino/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem
6.
Ann Surg Oncol ; 23(6): 1971-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26753751

RESUMO

BACKGROUND: Peritoneal carcinomatosis is an increasingly common finding in gastric carcinoma. Previously, patients were treated as terminal, and median survival was poor. The use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in this context is still highly debatable. OBJECTIVE: The aim of this study was to evaluate the long-term outcomes associated with CRS and HIPEC, and define prognostic factors for cure, if possible. PATIENTS AND METHODS: All patients with gastric carcinomatosis from five French institutions who underwent combined complete CRS and HIPEC and had a minimum follow-up of 5 years were included in this study. Cure was defined as a disease-free interval of more than 5 years from the last treatment until the last follow-up. RESULTS: Of the 81 patients who underwent CRS and HIPEC from 1989 to 2009, 59 had a completeness of cytoreduction score (CCS) of 0 (complete macroscopic resection), and the median Peritoneal Cancer Index (PCI) score was 6. Mitomycin C was the most commonly used drug during HIPEC (88 %). The 5-year overall survival (OS) rate was 18 %, with nine patients still disease-free at 5 years, for a cure rate of 11 %. All 'cured' patients had a PCI score below 7 and a CCS of 0. Factors associated with improved OS on multivariate analysis were synchronous resection (p = 0.02), a lower PCI score (p = 0.12), and the CCS (p = 0.09). CONCLUSION: The cure rate of 11 % for patients with gastric carcinomatosis who are deemed terminal emphasizes that CRS and HIPEC should be considered in highly selected patients (low disease extent and complete CRS).


Assuntos
Adenocarcinoma/terapia , Carcinoma/terapia , Quimioterapia do Câncer por Perfusão Regional , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Peritoneais/terapia , Neoplasias Gástricas/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Prognóstico , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Adulto Jovem
7.
Oncogene ; 35(2): 261-8, 2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-25867070

RESUMO

The occurrence of peritoneal carcinomatosis is a major cause of treatment failure in colorectal cancer and is considered incurable. However, new therapeutic approaches have been proposed, including cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Although HIPEC has been effective in selected patients, it is not known how HIPEC prolongs a patient's lifespan. Here, we have demonstrated that HIPEC-treated tumor cells induce the activation of tumor-specific T cells and lead to vaccination against tumor cells in mice. We have established that this effect results from the HIPEC-mediated exposure of heat shock protein (HSP) 90 at the plasma membrane. Inhibition or blocking of HSP90, but not HSP70, prevented the HIPEC-mediated antitumoral vaccination. Our work raises the possibility that the HIPEC procedure not only kills tumor cells but also induces an efficient anticancer immune response, therefore opening new opportunities for cancer treatment.


Assuntos
Vacinas Anticâncer/farmacologia , Proteínas de Choque Térmico HSP90/metabolismo , Hipertermia Induzida/métodos , Neoplasias Peritoneais/imunologia , Neoplasias Peritoneais/terapia , Animais , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Técnicas de Cocultura , Terapia Combinada , Células Dendríticas/imunologia , Proteínas de Choque Térmico HSP90/genética , Humanos , Camundongos Endogâmicos BALB C , Neoplasias Peritoneais/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Eur J Surg Oncol ; 41(10): 1361-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26263848

RESUMO

BACKGROUND: Over the last two decades, many surgical teams have developed programs to treat peritoneal carcinomatosis with extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Currently, there are no specific recommendations for HIPEC procedures concerning environmental contamination risk management, personal protective equipment (PPE), or occupational health supervision. METHODS: A survey of the institutional practices among all French teams currently performing HIPEC procedures was carried out via the French network for the treatment of rare peritoneal malignancies (RENAPE). RESULTS: Thirty three surgical teams responded, 14 (42.4%) which reported more than 10 years of HIPEC experience. Some practices were widespread, such as using HIPEC machine approved by the European Community (100%), individualized or centralized smoke evacuation (81.8%), "open" abdominal coverage during perfusion (75.8%), and maintaining the same surgeon throughout the procedure (69.7%). Others were more heterogeneous, including laminar flow air circulation (54.5%) and the provision of safety protocols in the event of perfusate spills (51.5%). The use of specialized personal protective equipment is ubiquitous (93.9%) but widely variable between programs. CONCLUSION: Protocols regarding cytoreductive surgery/HIPEC and the associated professional risks in France lack standardization and should be established.


Assuntos
Ar Condicionado/métodos , Antineoplásicos/uso terapêutico , Carcinoma/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Infusões Parenterais/métodos , Neoplasias Peritoneais/terapia , Equipamento de Proteção Individual/estatística & dados numéricos , Padrões de Prática Médica , França , Humanos , Saúde Ocupacional , Gestão de Riscos , Fumaça , Inquéritos e Questionários
9.
Gynecol Obstet Fertil ; 42(9): 622-5, 2014 Sep.
Artigo em Francês | MEDLINE | ID: mdl-25153435

RESUMO

Secondary localization to vagina had a severe prognosis, suggesting a disseminated metatastic disease. We report the case of prevalent vaginal metastasis of adenocarcinoma of the transverse colon. A 65 years old patient has consulted for vaginal mass. After delayed diagnosis, she presented with disseminated metastatic disease with peritoneal carcinomatosis. After neoadjuvant chemotherapy, the following treatment consisted of complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and vaginal adjuvant radiotherapy. No recurrence occurred after one year. Vaginal metastasis of colon cancer are rare. The dark prognosis might justify a systematic gynecological examination of women presenting colorectal neoplasy.


Assuntos
Adenocarcinoma/secundário , Neoplasias do Colo/patologia , Neoplasias Vaginais/secundário , Idoso , Antineoplásicos/administração & dosagem , Colo Transverso , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Radioterapia Adjuvante , Neoplasias Vaginais/tratamento farmacológico , Neoplasias Vaginais/cirurgia
11.
Eur J Surg Oncol ; 39(12): 1435-43, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24209430

RESUMO

BACKGROUND: Despite a high response rate to front-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. Approaches that combine Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with this strategy. PATIENTS AND METHODS: A retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included. RESULTS: The study included 566 patients from 13 centres who underwent 607 procedures between 1991 and 2010. There were 92 patients with advanced EOC (first-line treatment), and 474 patients with recurrent EOC. A complete cytoreductive surgery was performed in 74.9% of patients. Mortality and grades 3 to 4 morbidity rates were 0.8% and 31.3%, respectively. The median overall survivals were 35.4 months and 45.7 months for advanced and recurrent EOC, respectively. There was no significant difference in overall survival between patients with chemosensitive and with chemoresistant recurrence. Peritoneal Cancer Index (PCI) that evaluated disease extent was the strongest independent prognostic factor for overall and disease-free survival in all groups. CONCLUSION: For advanced and recurrent EOC, curative therapeutic approach combining optimal CRS and HIPEC should be considered as it may achieve long-term survival in patients with a severe prognosis disease, even in patients with chemoresistant disease. PCI should be used for patient's selection.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma/tratamento farmacológico , Carcinoma/cirurgia , Quimioterapia do Câncer por Perfusão Regional , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma/secundário , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Fístula do Sistema Digestório/etiologia , Intervalo Livre de Doença , Feminino , França , Humanos , Hipertermia Induzida , Estimativa de Kaplan-Meier , Leucopenia/induzido quimicamente , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Hemorragia Pós-Operatória/etiologia , Modelos de Riscos Proporcionais , Insuficiência Renal/etiologia , Estudos Retrospectivos , Taxa de Sobrevida
12.
Eur J Surg Oncol ; 39(7): 742-7, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23510853

RESUMO

AIM: Primary peritoneal serous carcinoma (PPSC) is a rare condition, histologically identical to ovarian serous carcinoma and often diagnosed at late stage. There is not any standardized treatment for PPSC. A retrospective multicentric study was performed in French speaking centers to evaluate cytoreduction surgery and Hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinomatosis from different origins. The manuscript's aim was to study the particular population with PPSC. METHODS: Between September 1997 and July 2007, 36 patients with PPSC from 9 institutions underwent 39 procedures. RESULTS: Mortality and morbidity rates were 5.6% and 20.6% respectively. The overall survival at 1, 3 and 5 years are respectively 93.6, 71.5 and 57.4%. The median overall survival was not reached. By univariate analysis, the only factor that had prognostic value was PCI (p = 0.03). CONCLUSIONS: The therapeutic approach combining cytoreductive surgery with HIPEC may achieve long-term survival in patients with PPSC.


Assuntos
Carcinoma/mortalidade , Carcinoma/terapia , Quimioterapia do Câncer por Perfusão Regional/métodos , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/terapia , Adulto , Idoso , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma/patologia , Quimioterapia Adjuvante , Estudos de Coortes , Terapia Combinada , Intervalo Livre de Doença , Feminino , França , Humanos , Hipotermia Induzida/métodos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Peritoneais/patologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
13.
Ann Surg Oncol ; 19(13): 4052-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22825772

RESUMO

BACKGROUND: Epithelial ovarian carcinoma is the main cause of death from gynaecological cancers in the western world. The initial response rate to the frontline therapy is high. However, the prognosis of persistent and recurrent disease remains poor. During the two past decades, a new therapeutic approach to peritoneal carcinomatosis has been developed, combining maximal cytoreductive effort with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A retrospective, multicentric study of 246 patients with recurrent or persistent ovarian cancer, treated by cytoreductive surgery and HIPEC in two French centers between 1991 and 2008, was performed. RESULTS: An optimal cytoreductive surgery was possible in 92.2 % of patients. Mortality and morbidity rates were 0.37 % and 11.6 %, respectively. The overall median survival was 48.9 months. There was no significant difference in overall survival in patients with persistent or recurrent disease. In multivariate analysis, performance status was a significant prognostic factor in patients with extensive peritoneal carcinomatosis (peritoneal cancer index >10). CONCLUSIONS: Salvage therapy combining optimal cytoreductive surgery and HIPEC is feasible and may achieve long-term survival in highly selected patients with recurrent ovarian carcinoma, including those with platinum resistant disease, with acceptable morbidity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hipertermia Induzida , Recidiva Local de Neoplasia/terapia , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/terapia , Adulto , Idoso , Carcinoma Epitelial do Ovário , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
14.
Cell Death Dis ; 2: e199, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21881601

RESUMO

Metformin is the most widely used antidiabetic drug because of its proven efficacy and limited secondary effects. Interestingly, recent studies have reported that metformin can block the growth of different tumor types. Here, we show that metformin exerts antiproliferative effects on melanoma cells, whereas normal human melanocytes are resistant to these metformin-induced effects. To better understand the basis of this antiproliferative effect of metformin in melanoma, we characterized the sequence of events underlying metformin action. We showed that 24 h metformin treatment induced a cell cycle arrest in G0/G1 phases, while after 72 h, melanoma cells underwent autophagy as demonstrated by electron microscopy, immunochemistry, and by quantification of the autolysosome-associated LC3 and Beclin1 proteins. In addition, 96 h post metformin treatment we observed robust apoptosis of melanoma cells. Interestingly, inhibition of autophagy by knocking down LC3 or ATG5 decreased the extent of apoptosis, and suppressed the antiproliferative effect of metformin on melanoma cells, suggesting that apoptosis is a consequence of autophagy. The relevance of these observations were confirmed in vivo, as we showed that metformin treatment impaired the melanoma tumor growth in mice, and induced autophagy and apoptosis markers. Taken together, our data suggest that metformin has an important impact on melanoma growth, and may therefore be beneficial in patients with melanoma.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Metformina/farmacologia , Metformina/toxicidade , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Proteína 5 Relacionada à Autofagia , Proteína Beclina-1 , Linhagem Celular Tumoral , Fase G1 , Humanos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Nus , Proteínas Associadas aos Microtúbulos/antagonistas & inibidores , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Fase de Repouso do Ciclo Celular , Transplante Heterólogo
15.
Eur J Surg Oncol ; 36(6): 589-93, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20466507

RESUMO

INTRODUCTION: The aim of the present study was to prospectively evaluate morbidity of intra-peritoneal hyperthermic chemotherapy (HIPEC) using Oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma and, secondly, to study peritoneal recurrence. METHODS: Between 2004 and 2007, 31 patients from 18 to 65 years with FIGO stage IIIC epithelial ovarian carcinoma were treated by surgery and a total of 6 cycles of platinum based chemotherapy. Those patients were eligible for consolidation therapy. We performed a second look laparotomy operation with intra-peritoneal hyperthermic chemotherapy. We used Oxaliplatin 460 mg/m(2) with 2 l/m(2) of dextrose in an open medial laparotomy for a total of 30 min at a temperature of 42-44 degrees C. RESULTS: The grade 3 morbidity rate was 29% (95 CI: 14-45%). Nine patients experienced a total of 13 exploratory laparotomies for intra-abdominal bleeding after HIPEC. Two-year disease free and overall survival were 27% and 67% respectively. As a result of this high level of morbidity the trial was closed. CONCLUSION: Using intra-peritoneal Oxaliplatin associated with hyperthermia as consolidation therapy for advanced ovarian cancer results in a high risk of grade 3 morbidities with only a small benefit on survival.


Assuntos
Antineoplásicos/administração & dosagem , Hipertermia Induzida , Compostos Organoplatínicos/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Adolescente , Adulto , Idoso , Feminino , Hemorragia/cirurgia , Humanos , Infusões Parenterais , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Oxaliplatina , Estudos Prospectivos , Reoperação , Taxa de Sobrevida , Resultado do Tratamento
16.
Eur J Surg Oncol ; 36(5): 456-62, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20227231

RESUMO

OBJECTIVE: To analyze a large series of patients with pseudomyxoma peritonei (PMP) treated with cytoreductive surgery associated with perioperative intraperitoneal chemotherapy (PIC) in 18 French-speaking centers. PATIENTS AND METHODS: From March 1993 to December 2007, 301 patients with diffuse PMP were treated by cytoreductive surgery with PIC. Complete cytoreductive surgery was achieved in 219 patients (73%), and hyperthermic intraperitoneal chemotherapy (HIPEC) was performed in 255 (85%), mainly during the latter period of the study. RESULTS: Postoperative mortality and morbidity were 4.4% and 40%, respectively. The mean follow-up was 88 months. The 5-year overall and disease-free survival rates were 73% and 56%, respectively. The multivariate analysis identified 5 prognostic factors: the extent of peritoneal seeding (p=0.004), the center (p=0.0004), the pathologic grade (p=0.03), gender (p=0.02), and the use of HIPEC (p=0.04). When only the 206 patients with complete cytoreductive surgery were considered, the extent of peritoneal seeding was the only significant prognostic factor (p=0.004). CONCLUSION: This large multicentric retrospective study confirms that cytoreductive surgery combined with PIC (with the use of hyperthermia) should be considered as the gold standard treatment of PMP and should be performed in specialized centers. It underlines the prognostic impact of the extent of peritoneal seeding, especially in patients treated by complete cytoreductive surgery. This prognostic impact appears to be greater than that of the pathologic grade.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/tratamento farmacológico , Pseudomixoma Peritoneal/cirurgia , Adulto , Idoso , Feminino , Fluoruracila/administração & dosagem , França , Humanos , Hipertermia Induzida , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
18.
Ann Chir ; 130(3): 178-80, 2005 Mar.
Artigo em Francês | MEDLINE | ID: mdl-15784222

RESUMO

Aneurysms of pancreaticoduodenal arteries represent only 2% of all aneurysms of digestive arteries. Occurrence of these aneurysms are favoured by stenosis or occlusion of the celiac axis. Aneurysm rupture is frequent and carries a mortality rate of 20%. Computed tomography with intravenous contrast and selective coeliomesenteric arteriography can make the diagnosis of this disease which can be treated by either surgery or embolotherapy. We report the case of a patient with a ruptured aneurysm of the pancreaticoduodenal arcades mimicking a perforated duodenal ulcer, and successfully treated by surgical ligation.


Assuntos
Aneurisma Roto/diagnóstico , Aneurisma Roto/cirurgia , Úlcera Duodenal/diagnóstico , Duodeno/irrigação sanguínea , Ligamentos/patologia , Pâncreas/irrigação sanguínea , Idoso , Aneurisma Roto/complicações , Diagnóstico Diferencial , Feminino , Humanos , Ligadura , Síndrome , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Ann Chir ; 129(6-7): 353-8, 2004.
Artigo em Francês | MEDLINE | ID: mdl-15297225

RESUMO

UNLABELLED: Self-expanding metallic stents is an alternative treatment to colostomy that is the treatment of choice in acute tumoral left colonic obstruction. AIM OF THE STUDY: To compare morbidity, mortality, length of hospital stay and treatment performed after desobstruction using the two methods. PATIENTS AND METHODS: Thirty-three patients admitted for acute obstruction of the left colon were retrospectively separated in two groups depending on the type of intervention performed to treat the obstruction ("colostomy" group: 17 patients and "self-expanding stent group": 16 patients). We studied complications after desobstruction, hospital courses and surgical strategy performed after the acute phase. RESULTS: Time between desobstruction and colectomy was shorter in the "self-expanding stent group" than in the "colostomy group" (18.5 days versus 73 days). Age superior than 75 years and colostomy were the two main factors predicting the risk of definitive colostomy (P < 0.05). Global mean hospital stay was longer in the colostomy group (32.7 days versus 19.3 days, P = 0.02). Two perforations and one local recurrence occurred in the "self-expanding stent group". CONCLUSIONS: Self-expanding metallic stent can decrease the permanent colostomy rate and the number of interventions. The recurrence rate seems to be theoretically increased with the stenting method. Then, colostomy must be done for patients in curative situation. The self-expanding metallic stent should be used as a palliative care.


Assuntos
Colo/patologia , Colo/cirurgia , Colostomia/métodos , Obstrução Intestinal/etiologia , Obstrução Intestinal/terapia , Stents , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Morbidade , Mortalidade , Cuidados Paliativos , Recidiva , Estudos Retrospectivos
20.
J Clin Oncol ; 22(16): 3284-92, 2004 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-15310771

RESUMO

PURPOSE: The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. PATIENTS AND METHODS: A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. RESULTS: The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. CONCLUSION: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/secundário , Neoplasias Colorretais/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Neoplasias Peritoneais/cirurgia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
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