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1.
Lancet Oncol ; 22(2): 256-266, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33476595

RESUMO

BACKGROUND: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone. METHODS: We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18-70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m2) or open (460 mg/m2) abdomen techniques, and systemic chemotherapy (400 mg/m2 fluorouracil and 20 mg/m2 folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov, NCT00769405, and is now completed. FINDINGS: Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0-77·1), median overall survival was 41·7 months (95% CI 36·2-53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1-49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63-1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035). INTERPRETATION: Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases. FUNDING: Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/patologia , Terapia Combinada/efeitos adversos , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , França , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Resultado do Tratamento
2.
Nat Med ; 27(1): 141-151, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33398161

RESUMO

Intratumoral heterogeneity (ITH) is a fundamental property of cancer; however, the origins of ITH remain poorly understood. We performed single-cell transcriptome profiling of peritoneal carcinomatosis (PC) from 15 patients with gastric adenocarcinoma (GAC), constructed a map of 45,048 PC cells, profiled the transcriptome states of tumor cell populations, incisively explored ITH of malignant PC cells and identified significant correlates with patient survival. The links between tumor cell lineage/state compositions and ITH were illustrated at transcriptomic, genotypic, molecular and phenotypic levels. We uncovered the diversity in tumor cell lineage/state compositions in PC specimens and defined it as a key contributor to ITH. Single-cell analysis of ITH classified PC specimens into two subtypes that were prognostically independent of clinical variables, and a 12-gene prognostic signature was derived and validated in multiple large-scale GAC cohorts. The prognostic signature appears fundamental to GAC carcinogenesis and progression and could be practical for patient stratification.


Assuntos
Adenocarcinoma/secundário , Neoplasias Gástricas/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Linhagem da Célula/genética , Cromossomos Humanos Par 17/genética , Estudos de Coortes , Variações do Número de Cópias de DNA , Feminino , Perfilação da Expressão Gênica , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Prognóstico , RNA-Seq , Análise de Célula Única , Neoplasias Gástricas/genética
3.
Nat Commun ; 12(1): 179, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420057

RESUMO

Accurate prediction of peritoneal metastasis for gastric cancer (GC) with serosal invasion is crucial in clinic. The presence of collagen in the tumour microenvironment affects the metastasis of cancer cells. Herein, we propose a collagen signature, which is composed of multiple collagen features in the tumour microenvironment of the serosa derived from multiphoton imaging, to describe the extent of collagen alterations. We find that a high collagen signature is significantly associated with a high risk of peritoneal metastasis (P < 0.001). A competing-risk nomogram including the collagen signature, tumour size, tumour differentiation status and lymph node metastasis is constructed. The nomogram demonstrates satisfactory discrimination and calibration. Thus, the collagen signature in the tumour microenvironment of the gastric serosa is associated with peritoneal metastasis in GC with serosal invasion, and the nomogram can be conveniently used to individually predict the risk of peritoneal metastasis in GC with serosal invasion after radical surgery.


Assuntos
Colágeno/uso terapêutico , Metástase Linfática/patologia , Nomogramas , Neoplasias Peritoneais/patologia , Membrana Serosa/patologia , Neoplasias Gástricas/patologia , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Peritoneais/cirurgia , Peritônio/patologia , Período Pós-Operatório , Membrana Serosa/cirurgia , Neoplasias Gástricas/cirurgia , Microambiente Tumoral
4.
Lancet Oncol ; 22(2): 277-288, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33357510

RESUMO

BACKGROUND: Platinum-based neoadjuvant chemotherapy followed by delayed primary surgery (DPS) is an established strategy for women with newly diagnosed, advanced-stage epithelial ovarian cancer. Although this therapeutic approach has been validated in randomised, phase 3 trials, evaluation of response to neoadjuvant chemotherapy using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and cancer antigen 125 (CA125) has not been reported. We describe RECIST and Gynecologic Cancer InterGroup (GCIG) CA125 responses in patients receiving platinum-based neoadjuvant chemotherapy followed by DPS in the ICON8 trial. METHODS: ICON8 was an international, multicentre, randomised, phase 3 trial done across 117 hospitals in the UK, Australia, New Zealand, Mexico, South Korea, and Ireland. The trial included women aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, life expectancy of more than 12 weeks, and newly diagnosed International Federation of Gynecology and Obstetrics (FIGO; 1988) stage IC-IIA high-grade serous, clear cell, or any poorly differentiated or grade 3 histological subtype, or any FIGO (1988) stage IIB-IV epithelial cancer of the ovary, fallopian tube, or primary peritoneum. Patients were randomly assigned (1:1:1) to receive intravenous carboplatin (area under the curve [AUC]5 or AUC6) and intravenous paclitaxel (175 mg/m2 by body surface area) on day 1 of every 21-day cycle (control group; group 1); intravenous carboplatin (AUC5 or AUC6) on day 1 and intravenous dose-fractionated paclitaxel (80 mg/m2 by body surface area) on days 1, 8, and 15 of every 21-day cycle (group 2); or intravenous dose-fractionated carboplatin (AUC2) and intravenous dose-fractionated paclitaxel (80 mg/m2 by body surface area) on days 1, 8, and 15 of every 21-day cycle (group 3). The maximum number of cycles of chemotherapy permitted was six. Randomisation was done with a minimisation method, and patients were stratified according to GCIG group, disease stage, and timing and outcome of cytoreductive surgery. Patients and clinicians were not masked to group allocation. The scheduling of surgery and use of neoadjuvant chemotherapy were determined by local multidisciplinary case review. In this post-hoc exploratory analysis of ICON8, progression-free survival was analysed using the landmark method and defined as the time interval between the date of pre-surgical planning radiological tumour assessment to the date of investigator-assessed clinical or radiological progression or death, whichever occurred first. This definition is different from the intention-to-treat primary progression-free survival analysis of ICON8, which defined progression-free survival as the time from randomisation to the date of first clinical or radiological progression or death, whichever occurred first. We also compared the extent of surgical cytoreduction with RECIST and GCIG CA125 responses. This post-hoc exploratory analysis includes only women recruited to ICON8 who were planned for neoadjuvant chemotherapy followed by DPS and had RECIST and/or GCIG CA125-evaluable disease. ICON8 is closed for enrolment and follow-up, and registered with ClinicalTrials.gov, NCT01654146. FINDINGS: Between June 6, 2011, and Nov 28, 2014, 1566 women were enrolled in ICON8, of whom 779 (50%) were planned for neoadjuvant chemotherapy followed by DPS. Median follow-up was 29·5 months (IQR 15·6-54·3) for the neoadjuvant chemotherapy followed by DPS population. Of 564 women who had RECIST-evaluable disease at trial entry, 348 (62%) had a complete or partial response. Of 727 women who were evaluable by GCIG CA125 criteria at the time of diagnosis, 610 (84%) had a CA125 response. Median progression-free survival was 14·4 months (95% CI 9·2-28·0; 297 events) for patients with a RECIST complete or partial response and 13·3 months (8·1-20·1; 171 events) for those with RECIST stable disease. Median progression-free survival for women with a GCIG CA125 response was 13·8 months (95% CI 8·8-23·4; 544 events) and 9·7 months (5·8-14·5; 111 events) for those without a GCIG CA125 response. Complete cytoreduction (R0) was achieved in 187 (56%) of 335 women with a RECIST complete or partial response and 73 (42%) of 172 women with RECIST stable disease. Complete cytoreduction was achieved in 290 (50%) of 576 women with a GCIG CA125 response and 30 (30%) of 101 women without a GCIG CA125 response. INTERPRETATION: The RECIST-defined radiological response rate was lower than that frequently quoted to patients in the clinic. RECIST and GCIG CA125 responses to neoadjuvant chemotherapy for epithelial ovarian cancer should not be used as individual predictive markers to stratify patients who are likely to benefit from DPS, but instead used in conjunction with the patient's clinical capacity to undergo cytoreductive surgery. A patient should not be denied surgery based solely on the lack of a RECIST or GCIG CA125 response. FUNDING: Cancer Research UK, UK Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, and Cancer Australia.


Assuntos
Carboplatina/administração & dosagem , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Idoso , Austrália , Antígeno Ca-125 , Carboplatina/efeitos adversos , Intervalo Livre de Doença , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Tubas Uterinas/patologia , Feminino , Humanos , Irlanda , Proteínas de Membrana , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Nova Zelândia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/efeitos adversos , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Critérios de Avaliação de Resposta em Tumores Sólidos
5.
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
6.
Medicine (Baltimore) ; 99(40): e22493, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019445

RESUMO

RATIONALE: Gastrointestinal stromal tumors that present outside the gastrointestinal tract are known for extra-gastrointestinal stromal tumors (EGISTs) and they share the same morphological and immunohistochemical characteristics with gastrointestinal stromal tumors. Here we report a rare case of diffuse primary EGIST arising at peritoneum. PATIENT CONCERNS: A 57-year-old male presented to the hospital with abdominal pain and right lower abdominal tenderness. DIAGNOSIS: The core needle puncture biopsy showed epithelial-like cells and the nuclei were ovoid and focally elongated. Immunohistochemical examination was consistent with a primary EGIST of the peritoneum. INTERVENTIONS: The patient was treated with Imatinib mesylate. OUTCOMES: Five months later, there is no complication resulting from treatment. The follow-up abdominal contrast-enhanced CT showed the lesion was significantly decreased in size, and was evaluated as partial response. The patient continued the treatment with Imatinib as prescribed by the oncologist. LESSONS: EGISTs are rare and should be considered in the differential diagnosis of the peritoneal tumors and immunohistochemistry helps to confirm the diagnosis. Further study with longer follow-up is desired to characterize these uncommon tumors.


Assuntos
Tumores do Estroma Gastrointestinal/patologia , Neoplasias Peritoneais/patologia , Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Mesilato de Imatinib/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/tratamento farmacológico
7.
Anticancer Res ; 40(9): 4913-4919, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878779

RESUMO

BACKGROUND/AIM: A new class of imidazo[2,1-b][1,3,4]thiadiazole compounds have recently been evaluated as inhibitors of phosphorylation of focal adhesion kinase (FAK) in pancreatic cancer. FAK is overexpressed in mesothelioma and has recently emerged as an interesting target for the treatment of this disease. MATERIALS AND METHODS: Ten imidazo[2,1-b][1,3,4]thiadiazole compounds characterized by indole bicycle and a thiophene ring, were evaluated for their cytotoxic activity in two primary cell cultures of peritoneal mesothelioma, MesoII and STO cells. RESULTS: Compounds 1a and 1b showed promising antitumor activity with IC50 values in the range of 0.59 to 2.81 µM in both cell lines growing as monolayers or as spheroids. Their antiproliferative and antimigratory activity was associated with inhibition of phospho-FAK, as detected by a specific ELISA assay in STO cells. Interestingly, these compounds potentiated the antiproliferative activity of gemcitabine, and these results might be explained by the increase in the mRNA expression of the key gemcitabine transporter human equilibrative nucleoside transporter-1 (hENT-1). CONCLUSION: These promising results support further studies on new imidazo[2,1-b][1,3,4]thiadiazole compounds as well as on the role of both FAK and hENT-1 modulation in order to develop new drug combinations for peritoneal mesothelioma.


Assuntos
Antineoplásicos/farmacologia , Desoxicitidina/análogos & derivados , Transportador Equilibrativo 1 de Nucleosídeo/genética , Quinase 1 de Adesão Focal/metabolismo , Imidazóis/farmacologia , Tiadiazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/farmacologia , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imidazóis/síntese química , Imidazóis/química , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Estrutura Molecular , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Fosforilação/efeitos dos fármacos , Tiadiazóis/síntese química , Tiadiazóis/química , Células Tumorais Cultivadas
8.
Oncology ; 98(11): 798-806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32906117

RESUMO

OBJECTIVE: Although chemotherapy has been clinically recommended as the initial treatment for patients with peritoneal dissemination of gastric cancer, poor prognosis has been noted among the same patients. However, the prognostic significance of conversion surgery after chemotherapy remains unclear. The present study therefore aimed to assess the clinical impact of conversion surgery among patients with peritoneal dissemination of gastric cancer. METHODS: A total of 93 patients with peritoneal dissemination of gastric cancer undergoing chemotherapy between February 2002 and October 2019 were retrospectively enrolled and subsequently divided into progressive disease (PD) and non-PD groups based on tumor response to chemotherapy. RESULTS: Among the included patients, 17 developed distant metastases at another site besides peritoneal dissemination. Based on tumor response, 24 and 69 patients were determined to have PD and non-PD, respectively, with the former having significantly poorer prognosis than the latter (p < 0.0001). A total of 19 patients underwent conversion surgery after chemotherapy, with the presence or absence of conversion surgery being significantly correlated with age, first-line chemotherapy regimen, and tumor response (p = 0.0134, p = 0.0337, and p = 0.0024, respectively). Patients in the non-PD group who underwent conversion surgery or chemotherapy alone had 3-year overall survival rates of 55.6 and 6.6%, respectively. Multivariate analysis identified conversion surgery alone as an independent prognostic factor in the non-PD group (p < 0.0001). CONCLUSION: Our retrospective study demonstrated that conversion surgery for gastric cancer with peritoneal dissemination might improve the prognosis of responders who developed no peritoneal dissemination after chemotherapy.


Assuntos
Neoplasias Peritoneais/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Peritoneais/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico
9.
Cancer Imaging ; 20(1): 54, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746917

RESUMO

OBJECTIVE: To establish Greater Omentum Imaging-Reporting and Data System (GOI-RADS) to evaluate the possibility of omental diseases being malignant. METHOD: A retrospective analysis was made of 883 patients who had undergone biopsy of the greater omentum in our center from October 2009 to October 2019. Twelve parameters of ultrasonographic images were evaluated, and the odds ratio of each group calculated. We assigned scores for the direct signs (omental echo, omental structure, and omental nodules) and indirect signs (separation of ascites, echo of ascites, mesenteric lymph nodes, and thickening of parietal peritoneum) of omental lesions. We created an omental score (OS) for each patient and receiver operating characteristic (ROC) curve to analyze its effectiveness in the differential diagnosis of benign and malignant omental diseases. RESULTS: The OS was divided into ≤5, 6, 7, 8, 9, 10, 11, 12, 13, and ≥ 14 points, and the malignant rate was 0, 1.85, 5.56, 30.36, 37.25, 87.72, 96.72, 98.28, 99.08, and 100%, respectively. The area under the ROC curve (AUC) was 0.976. When taking 10 points as the cutoff value to diagnose benign and malignant omental diseases, the sensitivity and specificity was 93.85 and 98.21%, respectively. A grading system was established: grade 1: omental score ≤ 5, malignant rate 0%; grade 2: omental score 6-7, malignant rate ≤ 5.56%; grade 3: omental score 8--9, malignant rate ≤ 37.25%; grade 4: omental score ≥ 10, malignant rate ≥ 87.72. CONCLUSION: GOI-RADS had high sensitivity and specificity in the differential diagnosis of benign and malignant omental lesions. We believe that GOI-RADS will aid the diagnosis of omental diseases based on objective and accurate interpretation of ultrasound features, and also to promote the ultrasonography of omental diseases in clinical application.


Assuntos
Omento/diagnóstico por imagem , Doenças Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Omento/patologia , Doenças Peritoneais/patologia , Neoplasias Peritoneais/patologia , Projetos de Pesquisa , Estudos Retrospectivos
10.
Zhonghua Fu Chan Ke Za Zhi ; 55(8): 521-528, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32854476

RESUMO

Objective: To introduce the technical essentials of cytoreduction surgery (CRS) with extensive peritonectomy ("rolling carpet" surgery) in stage Ⅲc epithelial ovarian cancer (EOC) and evaluate the feasibility and safety of the operation by analyzing the incidence of surgical complications and perioperative mortality. Methods: From December 2017 to December 2019, 30 patients with stage IIIc EOC who underwent "rolled carpet" CRS and 30 patients who underwent traditional CRS at the same period in Sichuan Cancer Hospital were collected. To summarize the key points of "rolled carpet" CRS operation technology, i.e. the extraperitoneal space was the cut path of ovarian cancer operation, and the tumor in the pelvic cavity was dissociated from the extraperitoneal space of the pelvic cavity. The tumor in the pelvic cavity and all the implants or potential metastases on the parietal peritoneum were removed completely. The clinical and pathological characteristics between the two groups were analyzed retrospectively, and the feasibility and safety of "rolling carpet" CRS were evaluated by comparing the operation related indexes and the occurrence of surgical complications between the two groups. Results: (1) Clinicopathological features: the age of patients in "rolling carpet" CRS group and traditional CRS group were respectively (55.4±9.6) and (54.6±9.5) years, and the median peritoneal cancer index (PCI) was 12 (range, 4-24) and 10 (range, 5-18), respectively. There were no statistical significance between the two groups (all P>0.05). (2) Operation related indexes: in the "rolled carpet" CRS group, all patients (100%, 30/30) were performed optimal CRS, reaching completeness of cytoreduction score (CC score), named CC-0 score, and there was no visible residual lesion after operation. While, in the traditional CRS group, 23 patients (77%, 23/30) reached CC-0 score, 5 cases (17%, 6/30) reached CC-1 score, 2 cases (7%, 2/30) reached CC-2 score, and there were statistical significance between the two groups (P=0.011). The median surgical time was 315 minutes (range, 252-446 minutes) vs 268 minutes (range, 215-372 minutes), the median intraoperative blood loss was 589 ml (range, 300-900 ml) vs 450 ml (range, 250-800 ml), the median ICU hospital stay time was 2 days (range, 1-7 days) vs 1 day (range, 0-5 days), the median total hospital stay time was 14 days (range, 9-17 days) vs 12 days (range, 7-15 days). There were no statistical significance between the two groups (all P>0.05). (3) Surgical complications: there were respectively 5 cases (17%, 5/30) and 3 cases (10%, 3/30) complications with Clavien-Dindo grading Ⅰ-Ⅱ, which was significant no difference between the "rolled carpet" CRS group and the traditional CRS groups (P>0.05). No re-operations were needed and the operative mortality was 0. Conclusion: It is safe and feasible to perform "rolled carpet" CRS in patients with advanced stage Ⅲc EOC with peritoneum implantation and metastasis, which could achieve optimal CRS, and has an acceptable incidence of perioperative complications, no perioperative death.


Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Hipertermia Induzida , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Peritônio/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
11.
Clin Nucl Med ; 45(11): 890-891, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32604114

RESUMO

Localized malignant mesothelioma is rare. The prognosis is generally more favorable for this condition than for diffuse malignant mesothelioma. An elderly woman recently complained of abdominal pain, fever, and weight loss. She had no history of asbestos exposure. Her serum CEA level was elevated. Plain CT revealed a mass under the left diaphragm, with liquefaction and necrosis. A contrast-enhanced scan showed circular enhancement of the mass. A subsequent biopsy of the mass revealed a poorly differentiated carcinoma. PET/CT showed a significant FDG-avid subphrenic mass without any indications of metastasis. Postoperative pathological and immunohistochemical examination confirmed a case of malignant mesothelioma.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Mesotelioma/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Feminino , Humanos , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Neoplasias Peritoneais/patologia , Prognóstico
12.
Medicine (Baltimore) ; 99(29): e20940, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702833

RESUMO

RATIONALE: Schwannomas are mesenchymal tumors with low malignant potential that originate from Schwann cells. They can occur in most parts of the body, such as the head, neck, and extremities. Schwannoma in the hepatoduodenal ligament is extremely rare, and only four cases have been reported in the literature. PATIENT CONCERNS: Herein, we describe a 58-year-old female who presented with right epigastric pain for 10 days. Preoperative computed tomographic (CT) revealed a 4.5 cm × 3.8 cm tumor in the hepatic hilar area. DIAGNOSES: Schwannoma in the hepatoduodenal ligament with portal vein invasion. INTERVENTIONS: Intraoperative findings revealed that the tumor was identified in the hepatoduodenal ligament, and the left branch of the portal vein was compressed. Complete tumor resection with reparation of the portal vein was performed for the patient. Postoperative pathological examination confirmed the final diagnosis of benign schwannoma, characterized by abundant spindle-shaped cells and positive reactivity for S-100 protein. OUTCOMES: The patient had a good prognosis and had no recurrence after 37 months of follow-up. LESSONS: Our case of schwannoma in the hepatoduodenal ligament is unique owing to the portal vein invasion, aimed at helping recognize the difficulty of preoperative diagnosis.


Assuntos
Ligamentos/patologia , Neurilemoma/patologia , Omento/patologia , Neoplasias Peritoneais/patologia , Veia Porta/patologia , Feminino , Humanos , Ligamentos/diagnóstico por imagem , Ligamentos/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia , Omento/diagnóstico por imagem , Omento/cirurgia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/cirurgia , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Tomografia Computadorizada por Raios X
13.
Lancet Oncol ; 21(9): 1147-1154, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32717180

RESUMO

BACKGROUND: Diagnosis and treatment of colorectal peritoneal metastases at an early stage, before the onset of signs, could improve patient survival. We aimed to compare the survival benefit of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC), with surveillance, in patients at high risk of developing colorectal peritoneal metastases. METHODS: We did an open-label, randomised, phase 3 study in 23 hospitals in France. Eligible patients were aged 18-70 years and had a primary colorectal cancer with synchronous and localised colorectal peritoneal metastases removed during tumour resection, resected ovarian metastases, or a perforated tumour. Patients were randomly assigned (1:1) to surveillance or second-look surgery plus oxaliplatin-HIPEC (oxaliplatin 460 mg/m2, or oxaliplatin 300 mg/m2 plus irinotecan 200 mg/m2, plus intravenous fluorouracil 400 mg/m2), or mitomycin-HIPEC (mitomycin 35 mg/m2) alone in case of neuropathy, after 6 months of adjuvant systemic chemotherapy with no signs of disease recurrence. Randomisation was done via a web-based system, with stratification by treatment centre, nodal status, and risk factors for colorectal peritoneal metastases. Second-look surgery consisted of a complete exploration of the abdominal cavity via xyphopubic incision, and resection of all peritoneal implants if resectable. Surveillance after resection of colorectal cancer was done according to the French Guidelines. The primary outcome was 3-year disease-free survival, defined as the time from randomisation to peritoneal or distant disease recurrence, or death from any cause, whichever occurred first, analysed by intention to treat. Surgical complications were assessed in the second-look surgery group only. This study was registered at ClinicalTrials.gov, NCT01226394. FINDINGS: Between June 11, 2010, and March 31, 2015, 150 patients were recruited and randomly assigned to a treatment group (75 per group). After a median follow-up of 50·8 months (IQR 47·0-54·8), 3-year disease-free survival was 53% (95% CI 41-64) in the surveillance group versus 44% (33-56) in the second-look surgery group (hazard ratio 0·97, 95% CI 0·61-1·56). No treatment-related deaths were reported. 29 (41%) of 71 patients in the second-look surgery group had grade 3-4 complications. The most common grade 3-4 complications were intra-abdominal adverse events (haemorrhage, digestive leakage) in 12 (23%) of 71 patients and haematological adverse events in 13 (18%) of 71 patients. INTERPRETATION: Systematic second-look surgery plus oxaliplatin-HIPEC did not improve disease-free survival compared with standard surveillance. Currently, essential surveillance of patients at high risk of developing colorectal peritoneal metastases appears to be adequate and effective in terms of survival outcomes. FUNDING: French National Cancer Institute.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Adolescente , Adulto , Idoso , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Hipertermia Induzida/métodos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Fatores de Risco , Cirurgia de Second-Look/métodos , Adulto Jovem
14.
Arch Gynecol Obstet ; 302(4): 793-799, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32653946

RESUMO

PURPOSE: Our aim is to present a review on childbearing following CRS and HIPEC for peritoneal malignancy. METHODS: A review of the English literature, up to December 2019, was conducted, using PubMed/MEDLINE, EmBase and Google Scholar bibliographic databases, following the MOOSE guidelines. The terms "Cytoreductive Surgery", "Hyperthermic Intraperitoneal Chemotherapy", "Peritoneal Carcinomatosis", "Pregnancy", "Fertility Preservation", "Conception" were used. All study designs were eligible for inclusion in the final analysis. RESULTS: In total, 7 studies (5 case reports and 2 case series) were included in the final analysis, reporting on 14 successful pregnancies after CRS and HIPEC. The mean age of patients at the time of CRS/HIPEC was 28.8 ± 5.9 years (range 18-36), while the mean interval between CRS/HIPEC and pregnancy was 29.6 ± 20.3 months (range 9-80 months). Nine patients were treated for pseudomyxoma peritonei, four for primary peritoneal mesothelioma and one for endocrine carcinoma. Mean Peritoneal Carcinomatosis Index was 9.8 ± 7.8 (range 1-26). All patients underwent fertility-sparing CRS (preservation of at least one ovary and the uterus). In 12 cases, conception was spontaneous, whereas two pregnancies were achieved through in-vitro fertilization. One patient developed gestational hypertension, while two labors were preterm. Mean disease-free survival was 64.1 months (range 24-106 months). CONCLUSION: A successful pregnancy is feasible in selected patients, after CRS and HIPEC. Assisted reproduction techniques (IVF using frozen oocytes or frozen embryos, ovarian tissue cryopreservation, preoperative treatment with GnRH analogs) should be discussed pre-operatively with the patient, without, however, compromising overall survival or risking locoregional recurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Preservação da Fertilidade , Hipertermia Induzida/efeitos adversos , Neoplasias Peritoneais/terapia , Peritônio/cirurgia , Técnicas de Reprodução Assistida , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Intervalo Livre de Doença , Neoplasias das Glândulas Endócrinas , Feminino , Humanos , Hipertermia Induzida/métodos , Lactente , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/patologia , Pseudomixoma Peritoneal/terapia , Resultado do Tratamento
15.
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
16.
AJR Am J Roentgenol ; 215(2): 305-312, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32551907

RESUMO

OBJECTIVE. This article discusses the emerging roles of 18F-FDG PET/CT and DWI in the assessment of peritoneal carcinomatosis in ovarian carcinoma from diagnostic accuracy to disease prognostication with gross pathologic correlation. CONCLUSION. PET/CT and DWI have incremental clinical values over conventional modalities with high predictive values of incomplete cytoreduction in ovarian carcinoma. The respective quantitative metrics offer evaluation of tumor burden with prognostic value in ovarian carcinoma.


Assuntos
Imagem de Difusão por Ressonância Magnética , Fluordesoxiglucose F18 , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Imagem Molecular , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Prognóstico
17.
Int J Clin Oncol ; 25(10): 1822-1829, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32591962

RESUMO

PURPOSE: This study aimed to improve the management of ovarian metastases (OM) in colorectal cancer (CRC) by evaluating the clinicopathological characteristics, therapeutic strategies, and prognostic factors associated with OM originating from CRC. METHODS: Medical records of patients who were histopathologically diagnosed with OM of CRC origin were reviewed from January 2011 to December 2018 in our medical center. Data related to clinicopathological characteristics, therapeutic strategies, and survival time were recorded and analyzed. Survival and prognosis analyses were carried out to identify variables significantly associated with the outcomes. RESULTS: Forty-six patients were included in the study with a median follow-up of 14 months. Premenopausal (< 50 years) and colon cancer patients were more likely to develop OM. Synchronous OM was found in 34 patients and elevated carbohydrate antigen 125 value could be seen in 67.4% of patients. Bilateral ovarian involvement (27/46, 58.8%) and combined extra-ovarian metastases (32/46, 69.6%) were common in included patients. Complete cytoreduction surgery (R0 resection) was finally achieved in 19 of included patients and 41 patients received postoperative chemotherapy. However, the overall prognosis remains poor, with a median survival time of only 12 months. In univariate analysis, histological types (P = 0.002), peritoneal metastasis (P < 0.0001), the extent of metastatic lesions (P = 0.0001), and completeness of cytoreduction surgery (P < 0.0001) were found to be closely related to prognosis. Finally, completeness of cytoreduction surgery was considered to be the independent determinant of patients' outcome (HR 0.186, 95% CI 0.047-0.727, P = 0.016) by multivariate analysis. CONCLUSIONS: In multitudinous factors, complete cytoreduction surgery (R0 resection) may provide survival benefits in patients with OM of CRC origin. Thus, it is reasonable to recommend aggressive surgery with curative intent even if extra-ovarian metastases are present. Furthermore, postoperative chemotherapy may exert a positive effect on the treatment, but needs to be confirmed by large-scale trials with more participants in the future.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/secundário , Adulto , Idoso , Antineoplásicos/uso terapêutico , Neoplasias do Colo/patologia , Neoplasias Colorretais/mortalidade , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia , Ovariectomia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Pré-Menopausa , Prognóstico , Estudos Retrospectivos
18.
Anticancer Res ; 40(5): 2933-2939, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366445

RESUMO

BACKGROUND/AIM: Peritoneal fluid (PF) cytology is critical for distinguishing high-grade serous carcinoma (HGSC) from metastatic disease in patients with breast carcinoma who present with peritoneal carcinomatosis (PC). CASE REPORT: A 50-year-old woman underwent surgery and adjuvant therapy for pT1N0 grade 2/2 luminal A breast carcinoma. Sixteen months postoperatively, palliative chemotherapy was administered following a pleural biopsy and diagnosis of metastatic carcinoma. The patient developed PC despite chemotherapy. PF cytology specimens suggested metastatic carcinoma. However, we observed a papillary cellular arrangement during the review of cytology slides. HGSC was confirmed by immunocytochemistry showing positive paired box 8 (PAX8) and Wilms' tumor 1 (WT1) expression and negative GATA-binding protein 3 expression. CONCLUSION: In patients with breast carcinoma history, an awareness of characteristic cytomorphology of HGSC, including a papillary pattern with positive PAX8 and WT1 immunoreactivity, is essential to prevent the misdiagnosis of such cases and in ensuring accurate treatment and management.


Assuntos
Neoplasias da Mama/diagnóstico , Citodiagnóstico/métodos , Neoplasias Peritoneais/diagnóstico , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Neoplasias Peritoneais/patologia
20.
Cancer Immunol Immunother ; 69(10): 2113-2124, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32448982

RESUMO

Metastatic cancer involving spread to the peritoneal cavity is referred to as peritoneal carcinomatosis and has a very poor prognosis. Our previous studies demonstrated a toll-like receptor 4 (TLR4) and C-type lectin receptor (CLR; Mincle/MCL) agonist pairing of monophosphoryl lipid A (MPL) and trehalose-6,6'-dicorynomycolate (TDCM) effectively inhibits peritoneal tumor growth and ascites development through a mechanism dependent upon B1a cell-produced natural IgM, complement, and phagocytes. In the current study, we investigated the requirement for TLR4 and Fc receptor common γ chain (FcRγ), required for Mincle/MCL signaling, in the MPL/TDCM-elicited response. MPL/TDCM significantly increased macrophages and Ly6Chi monocytes in the peritoneal cavity of both TLR4-/- and FcRγ-/- mice, suggesting redundancy in the signals required for monocyte/macrophage recruitment. However, B1 cell activation, antibody secreting cell differentiation, and tumor-reactive IgM production were defective in TLR4-/-, but not FcRγ-/- mice. TRIF was required for production of IgM reactive against tumor- and mucin-related antigens, but not phosphorylcholine, whereas TLR4 was required for production of both types of reactivities. Consistent with this, B1 cells lacking TLR4 or TRIF did not proliferate or differentiate into tumor-reactive IgM-producing cells in vitro and did not reconstitute MPL/TDCM-dependent protection against peritoneal carcinomatosis in CD19-/- mice. Our results indicate a TLR4/TRIF-dependent pathway is required by B1 cells for MPL/TDCM-elicited production of protective tumor-reactive natural IgM. The dependency on TRIF signaling for tumor-reactive, but not phosphorylcholine-reactive, IgM production reveals unexpected heterogeneity in TLR4-dependent regulation of natural IgM production, thereby highlighting important differences to consider when designing vaccines or therapies targeting these specificities.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/fisiologia , Subpopulações de Linfócitos B/imunologia , Fatores Corda/administração & dosagem , Imunoglobulina M/imunologia , Lipídeo A/análogos & derivados , Neoplasias Peritoneais/imunologia , Receptor 4 Toll-Like/fisiologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Subpopulações de Linfócitos B/efeitos dos fármacos , Lipídeo A/administração & dosagem , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/fisiologia , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia
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