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1.
Medicine (Baltimore) ; 100(4): e24337, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530226

RESUMO

BACKGROUND: Gastric cancer (GC) has high incidence and mortality worldwide, and peritoneal metastasis is a primary cause of mortality in patients. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a feasible and effective treatment. Traditional Chinese Medicine (TCM) therapies have been combined with HIPEC for certain therapeutic advantages, but there is a lacking of evidence of evidence-based medicine. Therefore, we provide a protocol to evaluate the efficacy and safety of TCM therapies combined with HIPEC in the treatment for peritoneal metastasis of GC. METHODS AND ANALYSIS: From inception until December 2020, a systematic and comprehensive literature search will be conducted in both 3 English databases and 4 Chinese databases. Randomized controlled trials (RCTs) will be included related to TCM therapies combined with HIPEC in the treatment for peritoneal metastasis of GC. Two researchers independently conducted data extraction and literature quality evaluation. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: This study assessed the efficacy and safety of TCM therapies combined with HIPEC in the treatment of peritoneal metastasis of GC by effective rate, Karnofsky Performance Status (KPS), Carcinoemybryonic Angtigen remission rate, and incidence of adverse reactions etc. CONCLUSIONS: This study will provide reliable evidence-based evidence for the clinical application of TCM therapies combined with HIPEC in the treatment for peritoneal metastasis of GC. ETHICS AND DISSEMINATION: Ethical approval is not required, as this study is based on the review of published research. This review will be published in a peer-reviewed journal and disseminated both electronically and in print. REGISTRATION NUMBER: INPLASY2020120048.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medicina Tradicional Chinesa/métodos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Metanálise como Assunto , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Revisões Sistemáticas como Assunto , Resultado do Tratamento
2.
Anticancer Res ; 41(2): 609-617, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517265

RESUMO

BACKGROUND/AIM: Disease recurrence is frequently observed after curative resection of advanced gastric cancer resulting in a poor prognosis. In the present study, we identified a candidate biomarker to predict recurrence and prognosis after curative resection of gastric cancer. MATERIALS AND METHODS: A transcriptome analysis was conducted using surgically resected cancerous tissue from patients with metastatic gastric cancer to identify genes that are upregulated in primary and metastatic tissues. RESULTS: Ring finger protein, transmembrane 2 (RNFT2) mRNA expression was upregulated in primary gastric cancer tissues and metastases compared with non-cancerous tissues. RNFT2 expression in gastric cancer cell lines was positively correlated with the EMT-related molecules GSC, MMP9, and RAC1. The RNFT2 high expression group exhibited a significantly shorter postoperative overall survival. Peritoneal recurrence was significantly higher in the RNFT2 high expression group. CONCLUSION: RNFT2 mRNA expression predicts peritoneal recurrence and is a potential prognostic biomarker for gastric cancer following curative gastrectomy.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Peritoneais/metabolismo , Neoplasias Gástricas/metabolismo , Idoso , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Transição Epitelial-Mesenquimal , Feminino , Gastrectomia , Humanos , Masculino , Proteínas de Membrana/genética , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
3.
Am J Surg Pathol ; 45(1): 45-58, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32769428

RESUMO

Malignant mesothelioma of the peritoneum in women is an uncommon tumor. In this study, we present the clinicopathologic features of 164 such cases seen in our institution over a period of 42 years (1974-2016). Clinical information, pathologic findings, immunohistochemical results, and follow-up were recorded. Hematoxylin and eosin-stained slides were reviewed in all cases. Patients ranged in age from 3 to 85 years, median: 49 years. Most patients presented with abdominal/pelvic pain, although some were asymptomatic, presented with paraneoplastic syndromes or cervical lymphadenopathy. Overall, 9% of patients had a history of direct or indirect exposure to asbestos. In total, 31% and 69% of patients had either a personal or family history of other tumors; most of these tumors are currently recognized as part of a syndrome. Genetic testing information was available in 5 patients: BAP-1 germline mutation (1), type 2 neurofibromatosis (1), Lynch syndrome (1), McCune-Albright syndrome (1), no BAP-1 or TP53 mutation (1). Most cases had gross and microscopic features typical of malignant mesothelioma of the peritoneum in women; however, some had confounding features such as gelatinous appearance, signet ring or clear cells, and well-differentiated papillary mesothelioma-like areas. Calretinin and WT-1 were the markers more frequently expressed, and up to 23% of the cases showed PAX-8 expression. Patients' treatments predominantly included: chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. On multivariate analysis, the predominance of deciduoid cells, nuclear grade 3, and the absence of surgical treatment were associated with worse overall survival (OS). For all patients, the 3- and 5-year OS were 74.3% and 57.4%, respectively. The 3- and 5-year OS for patients treated with cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy were 88.9% and 77.8%, respectively.


Assuntos
/patologia , Neoplasias Peritoneais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , /terapia , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/terapia , Adulto Jovem
4.
Artigo em Inglês | MEDLINE | ID: mdl-33379304

RESUMO

Despite their differences, pleural and peritoneal mesothelioma are frequently lumped together to describe epidemic curves and to forecast future mesothelioma trends. This study aims to describe the malignant peritoneal mesothelioma (MPeM) epidemic in Italy (1996-2016) and to forecast future trends up to 2040 in order to contribute to the assessment of MPeM future burden. All MPeM deaths in Italy from 1996-2016 were collected (as provided by the Italian National Statistical Institute (ISTAT)) in order to estimate MPeM mortality rates for each 3-year period from 1996 to 2016. Poisson age-period-cohort (APC) models were then used to forecast MPeM future trends. Between 2017 and 2040, 1333 MPeM deaths are expected. The number of MPeM deaths, as well as mortality rates, are expected to constantly decrease throughout the considered period. Based on considering the information from this study, it can be concluded that the MPeM epidemic has probably already reached its peak in Italy.


Assuntos
/mortalidade , Neoplasias Peritoneais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Previsões , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade
5.
Medicine (Baltimore) ; 99(31): e20963, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756083

RESUMO

BACKGROUND: The aim of study was to develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) of patients with pseudomyxoma peritonei (PMP) and compare the predictive accuracy with the American Joint Committee on Cancer (AJCC) staging system. METHODS: Data of 4959 PMP patients who underwent surgical resection were collected between 2004 and 2015 from the Surveillance Epidemiology and End Results (SEER) database. All included patients were divided into training (n = 3307) and validation (n = 1652) cohorts. The Kaplan-Meier method and Cox proportional hazard model were applied. Nomograms were validated by discrimination and calibration. Finally, concordance index (C-index) was used to compare the predictive performance of nomograms with that of the AJCC staging system. RESULTS: According to the univariate and multivariate analyses of training sets, both nomograms for predicting OS and CSS combining age, grade, location, N stage, M stage, and chemotherapy were identified. Nomograms predicting OS also incorporated T stage and the number of lymph nodes removed (LNR). The calibration curves showed good consistency between predicted and actual observed survival. Moreover, C-index values demonstrated that the nomograms predicting both OS and CSS were superior to the AJCC staging system in both cohorts. CONCLUSION: We successfully developed and validated prognostic nomograms for predicting OS and CSS in PMP patients. Two nomograms were more accurate and applicable than the AJCC staging system for predicting patient survival, which may help clinicians stratify patients into different risk groups, tailor individualized treatment, and accurately predict patient survival in PMP.


Assuntos
Nomogramas , Neoplasias Peritoneais/diagnóstico , Pseudomixoma Peritoneal/diagnóstico , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias/mortalidade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/cirurgia , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Pseudomixoma Peritoneal/mortalidade , Pseudomixoma Peritoneal/cirurgia , Reprodutibilidade dos Testes , Programa de SEER , Análise de Sobrevida , Adulto Jovem
6.
Ann Surg ; 272(5): 847-854, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32833761

RESUMO

OBJECTIVE: Evaluate at a national level the postoperative mortality (POM), major morbidity (MM) and failure-to-rescue (FTR) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) across time and according to hospital-volume. BACKGROUND: CRS/HIPEC is an effective therapeutic strategy commonly used to treat peritoneal surface malignancies. However, this aggressive approach has the reputation to be associated with a high POM and MM. METHODS: All patients treated with CRS/HIPEC between 2009 and 2018 in France were identified through a national medical database. Patients and perioperative outcomes were analyzed. A cut-off value of the annual CRS/HIPEC caseload affecting the 90-day POM was calculated using the Chi-squared Automatic Interaction Detector method. A multivariable logistic model was used to identify factors mediating 90-day POM. RESULTS: A total of 7476 CRS/HIPEC were analyzed. Median age was 59 years with a mean Elixhauser comorbidity index of 3.1, both increasing over time (P < 0.001). Ninety-day POM was 2.6%. MM occurred in 44.2% with a FTR rate of 5.1%. The threshold of CRS/HIPEC number per center per year above which the 90-day POM was significantly reduced was 45 (3.2% vs 1.9%, P = 0.01). High-volume centers had more extended surgery (P < 0.001) with increased MM (55.8% vs 40.4%, P < 0.001) but lower FTR (3.1% vs 6.3%, P = 0.001). After multivariate analysis, independent factors associated with 90-day POM were: age >70 years (P = 0.002), Elixhauser comorbidity index ≥8 (P = 0.006), lower gastro-intestinal origin, (P < 0.010), MM (P < 0.001), and <45 procedures/yr (P = 0.002). CONCLUSION: In France, CRS/HIPEC is a safe procedure with an acceptable 90-day POM that could even be improved through centralization in high-volume centers.


Assuntos
Competência Clínica , Procedimentos Cirúrgicos de Citorredução , Falha da Terapia de Resgate , Hipertermia Induzida , Oncologia/educação , Neoplasias Peritoneais/terapia , Idoso , Terapia Combinada , Comorbidade , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Complicações Pós-Operatórias/prevenção & controle
7.
Int J Clin Oncol ; 25(9): 1726-1735, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32500467

RESUMO

BACKGROUND: This study investigated the pattern of first recurrence of advanced ovarian cancer before and after the introduction of aggressive surgery. METHODS: We investigated 291 patients with stage III/IV epithelial ovarian, fallopian tube, and peritoneal cancer. Aggressive surgery including gastrointestinal and upper abdominal surgeries was introduced for advanced ovarian cancer in 2008. The site and time until first recurrence were compared between 70 patients treated without aggressive surgery (2000-2007) and 221 patients who underwent aggressive surgery (2008-2016). RESULTS: The intraperitoneal recurrence rate was significantly lower in patients treated during 2008-2016 than in patients treated during 2000-2007 (55% [82/149] vs. 81% [46/57], p < 0.001). The median time to intraperitoneal recurrence was significantly longer during 2008-2016 than during 2000-2007 (36.2 months, 95% confidence interval [CI] 31.7-60.0 vs. 14.6 months, 95% CI 11.3-20.1, log-rank test: p < 0.001). However, extraperitoneal recurrence rate was significantly higher during 2008-2016 than during 2000-2007 (27% [40/149] vs. 2% [1/57], p < 0.001). Extraperitoneal recurrence occurred during 2008-2016 in the pleura/lungs and the para-aortic lymph nodes above the renal vessels. Cox proportional hazards regression analysis revealed that treatment period (HR 0.49, 95% CI 0.34-0.71, p < 0.001) and bevacizumab use (HR 0.58, 95% CI 0.39-0.87, p = 0.009) were independently associated with intraperitoneal recurrence; stage IV disease (HR 1.87, 95% CI 1.14-3.06, p = 0.034) was independently associated with extraperitoneal recurrence. CONCLUSION: Aggressive surgery reduced intraperitoneal recurrence and prolonged time to recurrence, contributing to better patient survival.


Assuntos
Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/secundário , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Feminino , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Estudos Retrospectivos
8.
J Surg Oncol ; 122(3): 388-398, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32383206

RESUMO

BACKGROUND: Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is indicated for patients with peritoneal dissemination of appendiceal cancer. The role of neoadjuvant chemotherapy (NAC) before CRS-HIPEC remains controversial. METHODS: A retrospective review of adult patients who underwent CRS ± HIPEC for metastatic appendiceal cancer between 2000-2017 was performed. Patients who received NAC followed by surgery were compared with those who underwent surgery first (SF) with and without 1:1 propensity score matching (PSM). RESULTS: Among 803 patients with appendiceal cancer who underwent CRS ± HIPEC, 225 (28%) received NAC, and 578 (72%) underwent SF. After PSM (n = 186), median overall survival (OS) did not differ (NAC: 40 vs SF: 56 months; P = .210) but recurrence-free survival (RFS) was worse among patients who received NAC (14 vs 22 months; P = .007). NAC was independently associated with worse OS (hazards ratio [HR], 1.81; 95% confidence interval [CI], 1.03-3.18) and RFS (HR, 1.93; 95% CI, 1.25-2.99). CONCLUSION: In this multi-institutional retrospective analysis of patients with peritoneal dissemination from appendiceal cancer, the use of NAC before CRS-HIPEC was associated with worse OS and RFS even after PSM and multivariable regression. Immediate surgery should be considered for patients with disease amenable to complete cytoreduction.


Assuntos
Neoplasias do Apêndice/tratamento farmacológico , Neoplasias do Apêndice/cirurgia , Hipertermia Induzida/métodos , Idoso , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia
9.
J Surg Res ; 253: 262-271, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32388389

RESUMO

BACKGROUND: Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be beneficial in treating limited peritoneal carcinomatosis (PC) from colorectal cancer (CRC). Perfusate volume directly affects treatment concentration and therefore is a key parameter defining HIPEC; yet little is known about the impact of perfusate concentration on systemic toxicity and treatment morbidity. MATERIALS AND METHODS: PC was induced through intraperitoneal injection of human CRC cell lines. A novel perfusion model was developed to treat athymic nude mice with continuous circulation of adequately miniaturized volumes of heated perfusate. Oxaliplatin HIPEC was performed applying different volumes of perfusate with fixed doses or fixed concentrations. Early postoperative mortality and morbidity were assessed as well as long-term survival. In addition, antiproliferative and proapoptotic effects of HIPEC were determined in vitro and in vivo. RESULTS: Perfusate concentration crucially affected the toxicity of fixed-dose oxaliplatin HIPEC as indicated by postoperative weight loss and early postoperative mortality. Applying different perfusate volumes at a fixed concentration did not influence toxicity. Adequately miniaturized HIPEC with oxaliplatin did not exert relevant cytotoxic effects toward PC arising from human CRC cells in vivo. CONCLUSIONS: We describe a novel murine model that adequately miniaturizes all physical parameters of HIPEC as applied in humans. HIPEC drug concentration is a crucial parameter determining excess toxicity and should be better standardized. HIPEC with oxaliplatin fails to induce relevant antitumor activity or to improve survival in this murine model of PC from CRC.


Assuntos
Quimioterapia do Câncer por Perfusão Regional/métodos , Neoplasias Colorretais/patologia , Hipertermia Induzida/métodos , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/terapia , Animais , Linhagem Celular Tumoral , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Procedimentos Cirúrgicos de Citorredução , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Camundongos , Oxaliplatina/toxicidade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Peritônio/efeitos dos fármacos , Peritônio/patologia , Falha de Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Eur J Cancer ; 133: 33-46, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32434109

RESUMO

BACKGROUND: To examine the association between malignant peritoneal cytology and survival in women with early-stage endometrioid endometrial cancer. METHODS: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program from 2010 to 2016. Women with stage I endometrioid endometrial cancer who had peritoneal cytology testing at hysterectomy were examined (N = 24,800). Characteristics and survival related to malignant peritoneal cytology were assessed. The propensity score inverse probability of treatment weighting was used to balance the measured covariates. FINDINGS: Malignant peritoneal cytology was reported in 1081 (4.4%) women. In multivariable analysis, stage IB disease and moderately/poorly differentiated tumours were associated with an increased likelihood of malignant peritoneal cytology (both P < 0.05). In a weighted model, malignant peritoneal cytology was associated with decreased cause-specific survival (5-year rates, 92.1% versus 96.8%, hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.56-2.52) and overall survival (89.4% versus 93.1%, HR 1.41, 95% CI 1.16-1.72). In sensitivity analyses, malignant peritoneal cytology was associated with decreased overall survival in the high-intermediate-risk group (5-year rates, 77.8% versus 83.6%, HR 1.57, 95% CI 1.20-2.06) and decreased cause-specific survival in the low-risk group (95.4% versus 98.0%, HR 1.64, 95% CI 1.01-2.68). In the high-intermediate-risk group with malignant peritoneal cytology, postoperative chemotherapy was associated with improved overall survival compared to whole pelvic radiotherapy (5-year rates, 82.7% versus 64.6%, HR 0.36, 95% CI 0.14-0.96). This association was not observed in negative cytology cases (81.5% versus 79.7%, HR 0.78, 95% CI 0.53-1.14). INTERPRETATION: Malignant peritoneal cytology may be associated with decreased survival in stage I endometrioid endometrial cancer.


Assuntos
Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Peritônio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Citodiagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico , Estadiamento de Neoplasias , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Programa de SEER , Análise de Sobrevida , Estados Unidos/epidemiologia
11.
Int J Clin Oncol ; 25(9): 1718-1725, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32447473

RESUMO

BACKGROUND: Occurrence of hypersensitivity reaction (HSR) in patients having received multiple doses of carboplatin has been reported. Several studies demonstrated reduction of carboplatin-associated HSR with in combination with pegylated liposomal doxorubicin (PLD). The objective of this study was to determine the suppressive effect on carboplatin-induced HSR via combined treatment with PLD within clinical practice. METHODS: We reviewed the medical records of women with primary or recurrent ovarian, fallopian tube, or peritoneal cancer treated with carboplatin containing regimen at our hospital between January 2009 and March 2019. We compared the incidence of carboplatin-induced HSR among patients who received more than one cycle of PLD plus carboplatin (PLD-C) therapy (i.e., PLD-C group) versus patients who never received PLD-C therapy (non-PLD-C group). RESULTS: A total of 414 women were included in this study (48: PLD-C group, 366: non-PLD-C group). Carboplatin-induced HSR occurred in 34 total patients (8.2%) [1/48 (2.1%) in the PLD-C group and 33/366 (9.0%) in the non-PLD-C group], with a median cycle number of carboplatin administration at onset of HSR being 9. Incidences of carboplatin-induced HSR within the PLD-C versus non-PLD-C group at the 8th, 12th, and 16th cycles of carboplatin administration were 2.2% vs 11.2%, 2.2% vs 28.6%, and 2.2% vs 39.1%, respectively [hazard ratio: 19.2 (95% confidence interval: 9.82-39.4), p < 0.0001]. CONCLUSION: Based on the data analyzed here, a suppressive effect on carboplatin-induced HSR via combination therapy with PLD was confirmed within clinical practice.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/efeitos adversos , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Neoplasias das Tubas Uterinas/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Neoplasias Peritoneais/mortalidade , Polietilenoglicóis/administração & dosagem , Adulto Jovem
12.
Eur J Cancer ; 130: 114-125, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32179446

RESUMO

BACKGROUND: Regarding the comparison between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) for stage III/IV ovarian, tubal and peritoneal cancers, EORTC55971 and CHORUS studies demonstrated noninferiority of NACT. Previously, we reported reduced invasiveness of NACT in JCOG0602. This is a final analysis including the primary endpoint of overall survival (OS). METHODS: Patients were randomised to PDS (PDS followed by 8x paclitaxel and carboplatin, i.e. TC regimen) or NACT (4x TC, interval debulking surgery [IDS], 4x TC). The primary endpoint was OS. The noninferiority hazard ratio (HR) margin for NACT compared with PDS was 1·161. The planned sample size was 300. FINDINGS: Between 2006 and 2011, 301 patients were randomised, 149 to PDS and 152 to NACT. The median OS was 49·0 and 44·3 months in the PDS and NACT. HR for NACT was 1·052 [90·8% confidence interval (CI) 0·835-1·326], and one-sided noninferiority p-value was 0·24. Median progression-free survival was 15·1 and 16·4 months in the PDS and NACT (HR: 0·96 [95%CI 0·75-1·23]). In the PDS arm, 147/149 underwent PDS and 49/147 underwent IDS. In the NACT arm 130/152 underwent IDS. Complete resection was achieved in 12% (17/147) of PDS and 31% (45/147) of PDS ± IDS in the PDS arm and in 64% (83/130) of IDS in the NACT arm. Optimal surgery (residual tumour <1 cm) was achieved in 37% (55/147), 63% (92/147), and 82% (107/130 respectively. In the NACT, PS 2/3, serum albumin ≤2·5, CA125 > 2000 an institution with low study activity was advantageous, whereas clear/mucinous histology was disadvantageous for OS. INTERPRETATION: The noninferiority of NACT was not confirmed. NACT may not always be a substitute for PDS. However, as our study had smaller numbers, the noninferiority of the previous studies cannot be denied. FUNDING: Ministry of Health, Labour and Welfare, Japan and the National Cancer Center, Japan. CLINICAL TRIAL INFORMATION: UMIN000000523.


Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias das Tubas Uterinas/cirurgia , Terapia Neoadjuvante/métodos , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Carcinoma Epitelial do Ovário/mortalidade , Neoplasias das Tubas Uterinas/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Peritoneais/mortalidade
13.
Virchows Arch ; 477(4): 535-544, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32179982

RESUMO

Peritoneal metastases of high-grade serous ovarian cancer (HGSOC) are small-sized deposits with superficial growth toward the peritoneal cavity. It is unknown whether integrity of the peritoneal elastic lamina (PEL) correlates with the peritoneal tumor microenvironment (pTME) and whether neoadjuvant chemotherapy (NACT) affects the pTME. We explored integrity of PEL, composition of pTME, effects of NACT, and the prognostic implications in patients with extensive peritoneal metastases of HGSOC. Peritoneal samples (n = 69) were collected during cytoreductive surgery between 2003 and 2016. Clinical data were collected from medical charts. Integrity of PEL was evaluated with elastic stains. T cell (CD3, CD8) and M2-macrophage markers (CD163) were scored using algorithms created in definiens tissue studio. Patients with a disrupted PEL (n = 39; 57%), more often had residual disease after surgery (p = 0.050), compared to intact PEL. An intact PEL was associated with increased intraepithelial (ie) CD8+ cells (p = 0.032), but was not correlated with improved survival. After NACT, increased ieCD3+ cells were shown, compared to no-NACT (p = 0.044). Abundance of total CD3+ and CD8+ cells were associated with PFS (multivariate HR 0.40; 95%CI 0.23-0.69 and HR 0.49; 95%CI 0.29-0.83) and OS (HR 0.33; 95%CI 0.18-0.62 and HR 0.36; 95%CI 0.20-0.64). M2-macrophage infiltration was not correlated with survival. NACT increases abundance of ieCD3+ cells in peritoneal metastases of HGSOC. Increase of CD3+ and CD8+ cells is associated with improved PFS and OS. This suggests that CD3+ and CD8+ cells may function as prognostic biomarkers. Their role as predictive biomarker for chemotherapy or immunotherapy response in HGSOC warrants further research.


Assuntos
Terapia Neoadjuvante , Neoplasias Císticas, Mucinosas e Serosas/tratamento farmacológico , Neoplasias Císticas, Mucinosas e Serosas/secundário , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Microambiente Tumoral , Idoso , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Complexo CD3/análise , Linfócitos T CD8-Positivos/imunologia , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/imunologia , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Gradação de Tumores , Invasividade Neoplásica , Neoplasias Císticas, Mucinosas e Serosas/imunologia , Neoplasias Císticas, Mucinosas e Serosas/mortalidade , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/imunologia , Neoplasias Peritoneais/mortalidade , Estudos Prospectivos , Receptores de Superfície Celular/análise , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
14.
Arch Gynecol Obstet ; 301(4): 1027-1035, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32144573

RESUMO

PURPOSE: Presence of circulating tumor cells (CTCs) is associated with impaired clinical outcome in several solid cancers. Limited data are available on the significance of CTCs in gynaecological malignancies. The aims of the present study were to evaluate the dynamics of CTCs in patients with ovarian, fallopian tube and peritoneal cancer during chemotherapy and to assess their clinical relevance. METHODS: 43 patients with ovarian, fallopian tube and peritoneal cancer were included into this prospective study. Patients received chemotherapy according to national guidelines. CTC analysis was performed using the CellSearch system prior to chemotherapy, after three and six cycles. RESULTS: In 26% of the patients, ≥ 1CTC per 7.5 ml of blood was detected at baseline (17% of patients with de novo disease, compared to 35% in recurrent patients). Presence of CTCs did not correlate with other factors. After three cycles of therapy, CTC positivity rate declined to 4.8%. After six cycles, no patient showed persistent CTCs. Patients with ≥ 1 CTC at baseline had significantly shorter overall survival and progression-free survival compared to CTC-negative patients (OS: median 3.1 months vs. not reached, p = 0.006, PFS: median 3.1 vs. 23.1 months, p = 0.005). When only the subgroup with newly diagnosed cancer was considered, the association between CTC status and survival was not significant (OS: mean 17.4 vs. 29.0 months, p = 0.192, PFS: 14.3 vs. 26.9 months, p = 0.085). Presence of ≥ 1 CTC after three cycles predicted shorter OS in the entire patient cohort (p < 0.001). CONCLUSIONS: Hematogenous tumor cell dissemination is a common phenomenon in ovarian, fallopian tube and peritoneal cancer. CTC status before start of systemic therapy correlates with clinical outcome. Chemotherapy leads to a rapid decline in CTC counts; further research is needed to evaluate the clinical value of CTC monitoring after therapy.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias das Tubas Uterinas/fisiopatologia , Células Neoplásicas Circulantes/patologia , Neoplasias Ovarianas/fisiopatologia , Neoplasias Peritoneais/fisiopatologia , Neoplasias das Tubas Uterinas/mortalidade , Feminino , Humanos , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/mortalidade , Prognóstico , Estudos Prospectivos , Análise de Sobrevida
15.
Z Gastroenterol ; 58(2): 146-151, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-32050285

RESUMO

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare diagnosis, found more frequently in men than in women. Symptoms are unspecific abdominal disorders making that diagnosis difficult to set. Causes of DMPM are yet to be discovered in entirety. Asbestos exposure is the reason for approximately 7 % of all peritoneal mesotheliomas. Until the evaluation of systematic cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) DMPM was a fatal diagnosis with a median overall survival (OS) of 4-13 months. The prognosis of DMPM dramatically improved with implementation of CRS and HIPEC to an OS of 30-92 month nowadys. CRS and HIPEC were performed in this case.


Assuntos
Antineoplásicos/administração & dosagem , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida/métodos , Mesotelioma/terapia , Neoplasias Peritoneais/terapia , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Masculino , Mesotelioma/tratamento farmacológico , Mesotelioma/mortalidade , Mesotelioma/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/cirurgia , Prognóstico , Taxa de Sobrevida
16.
Arch Gynecol Obstet ; 301(3): 779-785, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32034508

RESUMO

PURPOSE: In this study, the prognostic value of serum HE4 was investigated in patients with advanced ovarian, fallopian tube, and peritoneal carcinoma. METHODS: Serum HE4 and CA125 levels were measured in both patients and controls, and the response of treatment and the detection of recurrence were evaluated by serum HE4 and CA125 levels in the patients. RESULTS: The results showed that the levels of serum HE4 and CA125 were significantly higher in advanced patients than those seen in benign disease controls (p < 0.001). Compared with CA125, HE4 had higher specificity, but lower sensitivity. Furthermore, serum HE4 was closely associated with the response of treatment and recurrence, the effective response rate for therapy treatment showed by HE4 was higher than CA125, and a serum HE4 level was correlated with a sensitivity of 82.8% and a specificity of 99%, a positive predictive value (PPV) of 97.7%, and a negative predictive value (NPV) of 77.9% to show the presence of recurrence; the accuracy of HE4 for recurrence prediction after treatment was 88.6%. CONCLUSIONS: Our study indicated that serum HE4 levels are effective for diagnosis, evaluating the response of treatment and predicting recurrence in patients with advanced ovarian, fallopian tube, and peritoneal carcinoma.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias das Tubas Uterinas/sangue , Neoplasias Ovarianas/sangue , Neoplasias Peritoneais/sangue , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/genética , Adulto , Idoso , Neoplasias das Tubas Uterinas/mortalidade , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Prognóstico , Análise de Sobrevida
17.
BMC Cancer ; 20(1): 105, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041558

RESUMO

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is used in the palliative treatment of peritoneal metastasis. The combination of intraperitoneal and systemic chemotherapy seems rational, and the aim of this systematic review was to compare PIPAC directed monotherapy with a bidirectional treatment approach (PIPAC in combination with systemic chemotherapy). Main outcomes were survival and quality of life. METHODS: A systematic literature search in Medline, Embase, Cochrane and the "Pleura and Peritoneum" was conducted and analyzed according to PRISMA guidelines. Studies in English reporting on bidirectional treatment with PIPAC and systemic chemotherapy and published before April 2019 were included. RESULTS: Twelve studies with a total of 386 patients were included. None were specifically designed to compare mono- versus bidirectional treatment, but 44% of the patients received bidirectional treatment. This was more frequent in women (non-gynecological cancers) and one-third of the bidirectional treated patients had received no prior chemotherapy. Data from the included studies provided no conclusions regarding survival or quality of life. CONCLUSION: Bidirectional treatment with PIPAC and systemic chemotherapy is practised and feasible, and some patients are enrolled having received no prior systemic chemotherapy for their PM. The difficulty in drawing any conclusions based on this systematic review has highlighted the urgent need to improve and standardize reports on PIPAC directed therapy. We have, therefore, constructed a list of items to be considered when reporting on clinical PIPAC research. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews, PROSPERO. Registration number: 90352, March 5, 2018.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infusões Parenterais/métodos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Aerossóis , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos como Assunto , Humanos , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/mortalidade , Prognóstico , Qualidade de Vida , Resultado do Tratamento
18.
Clin Exp Metastasis ; 37(2): 325-332, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32002724

RESUMO

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) represents a novel approach to deliver intraperitoneal chemotherapy. We report our experience with PIPAC in patients with peritoneal metastasis (PM) from gastric cancer (GC). Data from GC patients (n = 20) included in the prospective PIPAC-OPC1 and PIPAC-OPC2 studies are reported. All patients had received prior systemic chemotherapy. The mean peritoneal cancer index (PCI) was 10.5 (range 0-39) and nine patients had diffuse GC. PIPAC with cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were administered at 4-6-week intervals. Outcome criteria were objective tumour response, survival and adverse events. Twenty patients had 52 PIPAC procedures with a median follow-up of 10.4 months (3.3-26.5). Median survival from the time of PM diagnosis and after the first PIPAC procedure was 11.5 months and 4.7 months, respectively. Fourteen patients had repeated PIPAC (> 2), and the objective tumour response according to the histological peritoneal regression grading score (PRGS) was observed in 36%, whereas 36% had stable disease. Ten patients completed the three prescheduled sessions (per protocol group) and 40% of those displayed an objective tumour response, while 20% had stable disease. Only minor postoperative complications were noted, and none were considered causally related to the PIPAC treatment. PIPAC with low-dose cisplatin and doxorubicin can induce a quantifiable objective tumour response in selected patients with PM from GC. Survival data are encouraging and warrant further clinical studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Peritônio/patologia , Neoplasias Gástricas/tratamento farmacológico , Administração Tópica , Adulto , Aerossóis , Idoso , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Peritônio/efeitos dos fármacos , Pressão , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do Tratamento
19.
World J Surg Oncol ; 18(1): 25, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005250

RESUMO

BACKGROUND: Malignant gastric outlet obstruction (GOO) is commonly associated with the presence of peritoneal carcinomatosis (PC) and preferably treated by surgical gastrojejunostomy (GJJ) in patients with good performance. Here, we aim to investigate the role of PC as a risk factor for perioperative morbidity and mortality in patients with GOO undergoing GJJ. METHODS: Perioperative data of 72 patients with malignant GOO who underwent palliative GJJ at our institution between 2010 and 2019 were collected within an institutional database. To compare perioperative outcomes of patients with and without PC, extensive group analyses were carried out. RESULTS: A set of 39 (54.2%) patients was histologically diagnosed with concomitant PC while the remaining 33 (45.8%) patients showed no clinical signs of PC. In-house mortality due to surgical complications was significantly higher in patients with PC (9/39, 23.1%) than in patients without PC (2/33, 6.1%, p = .046). Considerable differences were observed in terms of surgical complications such as anastomotic leakage rates (2.8% vs. 0%, p = .187), delayed gastric emptying (33.3% vs. 15.2%, p = .076), paralytic ileus (23.1% vs. 9.1%, p = .113), and pneumonia (17.9% vs. 12.1%, p = .493) without reaching the level of statistical significance. CONCLUSIONS: PC is an important predictor of perioperative morbidity and mortality patients undergoing GJJ for malignant GOO.


Assuntos
Derivação Gástrica/mortalidade , Obstrução da Saída Gástrica/mortalidade , Neoplasias Peritoneais/mortalidade , Qualidade de Vida , Neoplasias Gástricas/mortalidade , Idoso , Feminino , Seguimentos , Obstrução da Saída Gástrica/patologia , Obstrução da Saída Gástrica/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Período Perioperatório , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
20.
Can J Surg ; 63(1): E71-E79, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32080999

RESUMO

Background: Peritoneal recurrences after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for appendiceal and colorectal cancers are frequent. This study aimed to evaluate the safety, technical feasibility and perioperative and long-term outcomes of repeat CRS/HIPEC in patients with recurrent peritoneal carcinomatosis of colorectal and appendiceal origin. Methods: Data were collected from patients treated from 2000 to 2016 for recurrent peritoneal carcinomatosis from appendiceal or colorectal cancer with CRS/HIPEC at 2 specialist centres. Data on demographics, procedure details, morbidity and survival were recorded. Analyses compared the iterations of CRS/HIPEC to assess the safety and effectiveness of repeat surgery. Results: Of all patients who underwent CRS/HIPEC in the 2 centres, 37 patients underwent a repeat procedure. Operative time was similar for the first and second surgeries (412.1 v. 412.5 min, p = 0.74) but patients had a significantly lower peritoneal carcinoma index score with the second surgery (21.8 in the first iteration v. 9.53 in the second iteration, p < 0.001) and significantly less blood loss (1762 mL in the first iteration v. 790 mL in the second iteration, p = 0.001). There was a nonsignificant decrease in grade III­IV complications and there was no 30-day mortality associated with repeat procedures. For patients with colorectal cancer, median disease-free survival was 9.6 months and median overall survival was 40 months. For patients with appendiceal cancer, median disease-free survival was 15 months and overall survival was 64.4 months. Conclusion: Repeat CRS/HIPEC procedures for recurrent appendiceal and colorectal peritoneal carcinomatosis are safe in well-selected patients, without increased morbidity or mortality, and they are associated with significant long-term survival, particularly for patients with appendiceal cancers. These results support the use of repeat CRS/HIPEC in these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Apêndice/terapia , Carcinoma/terapia , Neoplasias Colorretais/terapia , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Recidiva Local de Neoplasia/terapia , Avaliação de Resultados em Cuidados de Saúde , Neoplasias Peritoneais/terapia , Reoperação , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Canadá/epidemiologia , Carcinoma/mortalidade , Carcinoma/secundário , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Terapia Combinada , Estudos Transversais , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/mortalidade , Estudos de Viabilidade , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Reoperação/efeitos adversos , Reoperação/mortalidade , Estudos Retrospectivos
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