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1.
Int J Mol Sci ; 23(11)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35682890

RESUMO

Ovarian cancer (OC) is one of the most common gynecological cancers, with the worst prognosis and the highest mortality rate. Peritoneal dissemination (or carcinomatosis) accompanied by ascites formation is the most unfavorable factor in the progression and recurrence of OC. Tumor cells in ascites are present as either separate cells or, more often, as cell aggregates, i.e., spheroids which promote implantation on the surface of nearby organs and, at later stages, metastases to distant organs. Malignant ascites comprises a unique tumor microenvironment; this fact may be of relevance in the search for new prognostic and predictive factors that would make it possible to personalize the treatment of patients with OC. However, the precise mechanisms of spheroid formation and carcinomatosis are still under investigation. Here, we summarize data on ascites composition as well as the activity of fibroblasts and macrophages, the key stromal and immune components, in OC ascites. We describe current knowledge about the role of fibroblasts and macrophages in tumor spheroid formation, and discuss the specific functions of fibroblasts, macrophages and T cells in tumor peritoneal dissemination and implantation.


Assuntos
Carcinoma , Neoplasias Ovarianas , Neoplasias Peritoneais , Ascite/patologia , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Microambiente Tumoral
2.
World J Surg Oncol ; 20(1): 171, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35641982

RESUMO

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a generalized term, usually known as "jelly belly" since 1884. Incidence is very low, 1-3 per million people per year. Because of its indolent nature, it is usually diagnosed at an advanced stage, thereby impacting the quality of life. The 5-year survival rate varies from 23 to 86% in world literature. Even 10 years and 20 years of survival have been described. With our experience, we like to propose rename of PMP as abdomino-peritoneal mucinous carcinoma (APM) as we strongly feel the time has come to specify the term and standardize the management strategy. METHODOLOGY: In the premier institute of India and as a tertiary referral center, we experienced the maximum number of advanced cases of APM. From 2012 to 2021, we analyzed all the APM patients based on a prospectively maintained computerized database in the department of surgical oncology and found the reasons for renaming from this traditional one. RESULTS: We included a total of 87 patients who underwent surgical intervention. Thirty-five patients underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), and 52 patients underwent debulking. In CRS-HIPEC patients, CC-0 was achieved in 28 patients (80%), CC-1 in 4 patients (11.4%), and CC-2 in 3 patients (8.6%). Palliative intent HIPEC was done in 3 patients (8.6%). Clavien-Dindo grade III and IV morbidity was observed in 18.8% of patients with 90 days mortality of 5.7%. CONCLUSION: With our long-term experience and advancement of scientific evidence, we like to propose a new name for PMP as APM. We strongly believe this paper will give a clear picture of this rare disease and standard management outlines.


Assuntos
Adenocarcinoma Mucinoso , Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Adenocarcinoma Mucinoso/terapia , Humanos , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/patologia , Qualidade de Vida
4.
Surg Pathol Clin ; 15(2): 259-276, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35715161

RESUMO

This review provides an overview of the pathology of selected benign and malignant lesions of the female peritoneum and their often-encountered differential diagnoses. It includes endometriosis and its related lesions, endosalpingiosis, pseudomyxoma peritonei (PMP) and related ovarian/appendiceal pathology, and malignant and benign mesothelial tumors. The current terminology associated with PMP is also discussed.


Assuntos
Neoplasias do Apêndice , Neoplasias Ovarianas , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Neoplasias do Apêndice/patologia , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia , Peritônio/patologia , Pseudomixoma Peritoneal/diagnóstico , Pseudomixoma Peritoneal/patologia
5.
Int J Biol Sci ; 18(7): 3082-3101, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35541892

RESUMO

Gastric cancer is anatomically proximal to peritoneum. Gastric cancer peritoneal metastasis is a complex biological process which is corresponded with disharmony within dysfunctional adipose tissue and metabolism reprogramming. Laminin gamma 1 (LAMC1) is highly expressed in cancer cells of peritoneal metastatic sites, however, the mechanism of LAMC1-metiated gastric cancer metastases to adipose tissue-rich peritoneum remains unclear. In our study, immunohistochemical staining, single cell sequencing, a co-culture model, luciferase reporter, RNA immunoprecipitation (RIP), Chromatin immunoprecipitation (CHIP) and single-molecular magnetic tweezers assays were conducted, and our results showed that LAMC1 related to Perilipin-1 content was highly expressed in peritoneal metastatic sites and mainly secreted by tumor cells. Gastric cancer cells secreted LAMC1 in an autocrine manner to detached from the primary site and promoted preadipocytes mature, rupture and release of free fatty acids (FFAs) in the peritoneal microenvironment to form pre-metastatic niche by the paracrine pathway. Reversely, differentiated preadipocyte-derived conditioned medium inhibited glycolysis and enhanced fatty acid oxidation (FAO) rate to promote cell proliferation, mesenchymal-epithelial transformation which led to tumor peritoneal colonization. In terms of biological mechanisms, one of differentiated preadipocyte-derived FFAs, palmitic acid-activated STAT3 inhibited miR-193a-3p by binding to its promoter directly; Using single-molecular magnetic tweezers, this binding manner was proved to be stable, reversable and ATP-dependent. Moreover, miR-193a-3p regulated LAMC1 in a post-translational manner. Furthermore, high LAMC1 expression in serum predicted a higher risk of peritoneal metastasis. In conclusion, our results illustrated that palmitic acid/p-STAT3/miR-193a-3p/LAMC1 pathway promotes preadipocyte differentiation, pre-metastatic niche formation and gastric cancer cell colonization to peritoneum.


Assuntos
Adipócitos , Laminina , MicroRNAs , Neoplasias Peritoneais , Neoplasias Gástricas , Adipócitos/metabolismo , Adipócitos/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Laminina/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ácidos Palmíticos , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , Peritônio/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Microambiente Tumoral
6.
Anticancer Res ; 42(6): 2939-2944, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35641285

RESUMO

BACKGROUND/AIM: The aim of the study was to determine outcomes and overall survival (OS) in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for malignant peritoneal mesothelioma (MPM). PATIENTS AND METHODS: This was a retrospective cohort study from a prospectively maintained database of patients that underwent CRS/HIPEC for MPM from April 1999 to December 2021. RESULTS: A total of 81 patients were identified with MPM. Median OS was 53 months with a 1-, 3- and 5-year OS of 76%, 55% and 49% respectively. Multivariate analysis identified lymph node status, PCI and CC score as statistically significant prognostic factors that impact survival. Median OS for PCI 0-20 was 103 months vs. 33 months for PCI 21-39 (p=0.005). Median OS for CC0, CC1 and CC2 were 104, 30 and 2.7 months respectively (p<0.001). Hazard ratio for node-positive disease over node-negative was 2.14 (95% CI=1.07-4.31, p<0.033). Grade III/IV complication rate was 43.2% and mortality 4.9%. CONCLUSION: CRS/HIPEC remains the gold standard for treating patients with MPM with excellent patient OS. Lymph node status, PCI and CC score were independent prognostic factors that affect OS.


Assuntos
Hipertermia Induzida , Mesotelioma Maligno , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Austrália/epidemiologia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
7.
Gynecol Oncol ; 165(3): 560-567, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35606067

RESUMO

OBJECTIVE: Low-grade serous carcinoma (LGSOC) is a rare epithelial ovarian/peritoneal cancer characterized by younger age at diagnosis, relative chemoresistance, prolonged overall survival (OS), and mutations in the mitogen activated protein kinase (MAPK) pathway compared to high-grade serous carcinoma. We describe the genomic profile of LGSOC by next generation sequencing (NGS) and evaluated its potential relationship to clinical outcomes. METHODS: The study included 215 women with LGSOC with: 1) pathologically confirmed LGSOC, 2) availability of NGS data, and 3) adequate clinical data. Clinical subgroups were compared for progression-free survival (PFS) and OS. Multivariable Cox regression analysis was performed. RESULTS: Median age at diagnosis was 46.6 years. The majority had a stage III ovarian primary. One or more mutations were identified in 140 (65.1%) cases; 75 (34.9%) had none. The most common mutations were KRAS (n = 71; 33.0%), NRAS (n = 24; 11.2%), and BRAF (n = 18; 8.4%). Patients with MAPK-mutated tumors (n = 113) (52.6%) had a significantly longer OS compared to those with tumors lacking MAPK pathway mutations (n = 102) (47.4%) [median OS, 147.8 months (95% CI,119.0-176.6) versus 89.5 months (95% CI, 61.4-117.7) (p = 0.01)], respectively. Median OS for patients with MAPK-mutated tumors was also significantly better than for patients whose tumors had no mutations (n = 75) [median OS, 147.8 months (95% CI, 119.0-176.6) versus 78.0 months (95% CI, 57.6-98.3)], respectively (p = 0.001). Median OS for patients with non-MAPK-mutated tumors (n = 27) was 125.1 months (95% CI, 83.9-166.3). In multivariable analysis, having a MAPK mutation was associated with improved OS. CONCLUSIONS: Patients with MAPK-mutated tumors have a significantly improved OS compared to those without MAPK-mutated tumors.


Assuntos
Cistadenocarcinoma Papilar , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Neoplasias Peritoneais , Carcinoma Epitelial do Ovário/genética , Cistadenocarcinoma Seroso/patologia , Feminino , Genômica , Humanos , Mutação , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia
8.
World J Surg Oncol ; 20(1): 147, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538541

RESUMO

BACKGROUND: Pseudomyxoma peritonei (PMP) is an uncommon clinical condition characterized by the presence of mucinous ascites, mainly induced by perforated appendiceal mucinous neoplasms (AMN). The peritoneal surface of the small bowel is usually spared from disease manifestation due to peristaltic movements. Mucinous tumours can disseminate as PMP on the entire peritoneum, but are rarely intraluminal. For the first time in literature, we report a case of intraluminal PMP involving the ileum. CASE PRESENTATION: A 75-year-old male was treated for perforated AMN and disseminated PMP with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. During follow-up, the patient developed intraperitoneal recurrence together with intraluminal depositions in the ileum, both disease manifestations with identical KRAS and SMAD4 mutations. Hereafter, the patient was treated with palliative care. CONCLUSION: This case illustrates the variation in the biological and clinical behaviour of this rare disease. Clinicians should be aware of unusual tumour distribution patterns of PMP, including the presence of mucinous tumour within the small bowel.


Assuntos
Neoplasias do Apêndice , Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Idoso , Neoplasias do Apêndice/patologia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Humanos , Hipertermia Induzida/efeitos adversos , Quimioterapia Intraperitoneal Hipertérmica , Masculino , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/patologia , Estudos Retrospectivos
9.
Clin Oncol (R Coll Radiol) ; 34(7): e305-e311, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35379523

RESUMO

AIMS: Various factors can influence the learning curve of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Initiating CRS and HIPEC programmes in low- and middle-income countries is challenging due to resource constraints and limited availability of expertise. We present our experience of CRS and HIPEC from a learning curve perspective among a cohort 155 peritoneal surface malignancy patients. MATERIALS AND METHODS: Patients undergoing CRS and HIPEC between May 2015 and February 2019 were included in the study. Patients were divided into two consecutive cohorts: the first 73 cases comprised the learning phase, group 1; the subsequent cohort of 82 patients were considered as the implementation phase, group 2. A comparative analysis of clinical and surgical outcome parameters was carried out between the two groups. RESULTS: The clinical spectrum was comparable among group 1/group 2. Most were ovarian (56.8%), colorectal (13.5%) and appendiceal (11.0%) malignancies. Group 2 had a higher number of moderate to high peritoneal cancer index patients (34.1% versus 19.1%), total peritonectomies (48.8% versus 45.2%), multi-visceral resections (colonic 41.5% versus 27.4%, small bowel 25.6% versus 19.1%, diaphragmatic 8.5% versus 6.5% and hepatic resections 8.5% versus 2.7%) and completeness of cytoreduction 0/1 rates (97.6% versus 93.1%). A lower incidence of intraoperative urological injuries (2.6% versus 12.3%) was noticed in group 2 (P = 0.007). Non-significant improvements seen in group 2 included surgery duration (6.0 ± 1.3 h versus 6.4 ± 1.7 h), intensive care unit stay (1.3 ± 1.1 days versus 1.8 ± 1.5 days), overall hospital stay (8.1 ± 0.9 days versus 8.8 ± 1.4 days) and reduction in Clavien-Dindo grade 3-4 complications (25.4% versus 36.9%). CONCLUSIONS: The results of the current study indicate that by implementing standard protocols and mentoring by an experienced team, a learning curve of CRS and HIPEC can be achieved in fewer than 75 cases. The baseline expertise of the treating team can also influence the learning curve.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Humanos , Hipertermia Induzida/métodos , Quimioterapia Intraperitoneal Hipertérmica , Curva de Aprendizado , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Atenção Terciária à Saúde , Resultado do Tratamento
10.
BMC Cancer ; 22(1): 437, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449092

RESUMO

BACKGROUND: Regulatory T cells (Tregs) play an important role in the antitumor immune response in epithelial ovarian cancer (EOC). To understand the immune-inhibitory networks of EOC, we addressed the association between Tregs and immune checkpoint expression on T cells in the tumor microenvironment of EOC. METHODS: A total of 41 patients with stage IIIC and IV EOC were included in the analysis. We harvested cells from malignant ascites and investigated them using multi-color flow cytometry. We categorized the Tregs into 3 groups: effector-type Tregs, naïve Tregs and non-Tregs, based on the expression patterns of CD45RA and Foxp3 in CD4+ T cells. Furthermore, the relationships between the expression of various immune checkpoint molecules, such as PD-1, on CD8+ T cells and each of the Treg subtypes was also evaluated. RESULTS: The median frequency of naïve Tregs, effector-type Tregs and non-Tregs were 0.2% (0-0.8), 2.0% (0-11.4) and 1.5% (0.1-6.3) in CD4+ T cells of malignant ascites from EOC patients, respectively. A high frequency of effector-type Tregs was associated with high-grade serous carcinoma compared with the other histotypes. Patients with higher proportions of effector-type Tregs showed a trend towards increased progression-free survival. We also demonstrated a correlation between a higher proportion of effector-type Tregs and increased PD-1 expression on CD8+ T cells. In addition, C-C chemokine receptor 4 expression was also observed in effector-type Tregs. CONCLUSION: These data suggest that multiple immune-inhibitory networks exist in malignant ascites from EOC patients, suggesting an approach towards combinational immunotherapies for advanced EOC patients.


Assuntos
Neoplasias Ovarianas , Neoplasias Peritoneais , Ascite/patologia , Linfócitos T CD8-Positivos , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T Reguladores , Microambiente Tumoral
11.
J Surg Res ; 277: 60-66, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35468402

RESUMO

INTRODUCTION: Hypophosphatemia following surgery is associated with a higher rate of postoperative complications; however, the significance of postoperative hypophosphatemia after cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) is unknown. METHODS: A prospectively maintained database was queried for all patients who underwent CRS/HIPEC for any histology at the Mount Sinai Health System. The perioperative serum phosphate levels, postoperative complications, and comorbidities were compared between patients with or without major complications. RESULTS: From 2007 to 2018, 327 patients underwent CRS/HIPEC. Most of the patients had low phosphate levels on postoperative day (POD) 2, reaching a median nadir of 2.3 mg/dL on POD 3. Patients with major complications had significantly lower levels of serum phosphate on POD 5-7 compared with patients without complications, with median serum phosphate 2.2 mg/dL (IQR 1.9-2.4) versus 2.7 mg/dL, (IQR 2.3-3), P < 0.01. Hypophosphatemia on POD 5-7 was also more frequent in patients who developed an anastomotic leak, with median serum phosphate 2.2 mg/dL (IQR 1.9-2.6) versus 2.8 mg/dL (IQR 2.2-3.2), P = 0.001. On multivariate analysis, the number of organs resected at surgery, diaphragm resection, postoperative intensive care unit stay, and serum phosphate level <2.4 mg/dL on POD 5-7 were independently associated with a major complication after CRS/HIPEC. CONCLUSIONS: Following CRS/HIPEC, POD 5-7 hypophosphatemia is associated with severe postoperative complications and anastomotic leak.


Assuntos
Hipertermia Induzida , Hipofosfatemia , Neoplasias Peritoneais , Fístula Anastomótica/etiologia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Humanos , Hipertermia Induzida/efeitos adversos , Hipofosfatemia/epidemiologia , Hipofosfatemia/etiologia , Hipofosfatemia/terapia , Morbidade , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Fosfatos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Taxa de Sobrevida
12.
Am J Clin Oncol ; 45(5): 223-231, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35446281

RESUMO

Pseudomyxoma peritonei is an infrequent solid tumor in clinical practice. The low morbidity and deficient understanding of this mucus-secreting malignant disease increase the risks of delayed identification or uncontrollable deterioration. In quite a lot cases, patients go through complete cytoreduction surgery and hyperthermic intraperitoneal chemotherapy could receive a long time survival over 5 years. But the recurrence rate is also hard to overlook. Unlike other types of cancer, the standard treatment for this considerable groups has not been confirmed yet. With the advanced medical progression, studies have been carrying out based on pathogenesis, biological characters, and mutated gene location. All but a few get statistical survival benefits, let alone the breaking progress on research or therapeutic practice in the field. We try to give a comprehensive exposition of pseudomyxoma peritonei around the epidemiology, radiologic features, clinical manifestation, present treatment and promising schemes, hoping to arise much attention and reflection on the feasible solutions, especially for the recrudescent part.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Recidiva Local de Neoplasia/terapia , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/patologia , Pseudomixoma Peritoneal/terapia , Estudos Retrospectivos
13.
Oxid Med Cell Longev ; 2022: 5055684, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273678

RESUMO

Peritoneal metastasis (PM) is one of the main causes of a poor prognosis in patients with advanced gastric cancer (GC). lncRNAs have been confirmed to play a very crucial role in the occurrence, development, and metastasis of many human cancers, including gastric cancer. However, the mechanism of lncRNA in PM of GC is rarely studied. We explored the mechanism of PM of GC through lncRNA gene sequencing and protein profiling analysis to detect PM-associated lncRNAs and proteins. A quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to identify the mRNA expression of SEMA3B-AS1 and BGN in GC tissues and adjacent normal tissues. The biological function of SEMA3B-AS1 in the PM of GC was identified through gain- and loss-of-function assays. Chromatin isolation by RNA purification (ChIRP), RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter, and coimmunoprecipitation (co-IP) assays was carried out to demonstrate the potential mechanism between SEMA3B-AS1 and its downstream genes, including HMGB1, FBXW7, and BGN. Finally, the biological function of SEMA3B-AS1 was demonstrated in animal experiments. The mRNA expression level of SEMA3B-AS1 was downregulated in GC and PM tissues compared to normal stomach tissues; however, BGN was highly expressed at the mRNA level. SEMA3B-AS1 was closely related to PM and the overall survival (OS) of GC patients. Functionally, the overexpression of SEMA3B-AS1 was related to GC progression, PM, and prognosis. Mechanistically, SEMA3B-AS1 could combine with HMGB1 to regulate the transcription of FBXW7, thus facilitating the ubiquitination of BGN. In conclusion, our study demonstrated that the SEMA3B-AS1/HMGB1/FBXW7 axis plays an inhibitory role in the PM of GC by regulating BGN protein ubiquitination. It also provides a new biological marker for the diagnosis and treatment of the PM of GC.


Assuntos
Biglicano/genética , Neoplasias Peritoneais/complicações , RNA Longo não Codificante/genética , Neoplasias Gástricas/secundário , Animais , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Peritoneais/patologia , Prognóstico , Neoplasias Gástricas/patologia , Transfecção , Ubiquitinação
14.
J Obstet Gynaecol Res ; 48(6): 1306-1317, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35343033

RESUMO

AIM: The response with intravenous chemotherapy using cisplatin and paclitaxel in patients with advanced ovarian cancer is often substantial. However, this regression of the malignancy is not durable, and a majority of patients succumb to this disease process. It is possible that alternative types of chemotherapy and alternative routes of chemotherapy administration can improve the results of treatment and perhaps, reduce the morbidity and mortality that patients experience. METHODS: Regional chemotherapy treatments previously presented in the ovarian cancer literature were reviewed and critically analyzed. New methods for chemotherapy delivery for both advanced primary and recurrent ovarian cancer were reviewed. This included hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and normothermic intraperitoneal chemotherapy (NIPEC) long-term. RESULTS: An important addition to perioperative chemotherapy delivery is the simultaneous use of heat with intraperitoneal drug delivery after a complete cytoreductive surgery. Drugs to be considered for HIPEC are cisplatin, gemcitabine, and melphalan. For EPIC, chemotherapy agents to consider include paclitaxel, pemetrexed, gemcitabine, and liposomal doxorubicin. For NIPEC, paclitaxel is the drug of choice usually combined with a systemic agent as bidirectional chemotherapy. Also, pemetrexed, gemcitabine, and liposomal doxorubicin are drugs to be considered for NIPEC in phase I/II trials. CONCLUSIONS: Innovative regimens of regional chemotherapy may improve the outcome of patients with advanced ovarian cancer. These chemotherapy treatments must be integrated with complete cytoreductive surgery and the availability of peritoneal access for repeated delivery of chemotherapy solutions.


Assuntos
Hipertermia Induzida , Neoplasias Ovarianas , Neoplasias Peritoneais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Cisplatino/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Paclitaxel/uso terapêutico , Pemetrexede/uso terapêutico , Neoplasias Peritoneais/patologia
15.
Int J Clin Oncol ; 27(6): 1043-1050, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35262818

RESUMO

BACKGROUND: Appendiceal mucinous neoplasm (AMN) is a rare tumor that may be successfully treated by appendectomy. However, some patients develop recurrence as pseudomyxoma peritonei. The present study investigated the recurrence rate after radial resection for AMN. METHODS: A survey on AMN was sent to 171 institutions, and 286 cases were analyzed. The risk of recurrence was assessed according to clinical parameters. Recurrence rates were compared with data from the literature. RESULTS: There were 250 cases in the low-grade group and 36 in the high-grade group, with perforation being detected in 50 cases. After a median follow-up period of 30 months, recurrence was detected in 17 cases, including 12 with high-grade histology and 10 with perforation. Two patients with low-grade histology and no perforation developed recurrence. Independent prognostic factors for recurrence were high-grade histology (p = 0.0001, RR = 8.56) and perforation (p = 0.0168, RR = 3.45). Four groups were classified by histology and perforation: group A: high-grade, perforation ( +), group B: high-grade, perforation (-), group C: low-grade, perforation ( +), group D: low-grade, perforation (-). Five-year recurrence rates in groups A, B, C, and D were 46.7, 25.9, 13.3, and 1.5%, respectively. All cases of recurrence were detected within 3 years, except for two in group B. CONCLUSIONS: Recurrence in cases with low-grade histology and no perforation was rare; however, a postoperative survey for at least 3 years is required. In contrast, cases with high-grade histology or perforation need to be monitored using a similar approach to colon cancer. Prophylactic CRS + HIPEC may be considered.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias do Apêndice , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Adenocarcinoma Mucinoso/patologia , Neoplasias do Apêndice/patologia , Procedimentos Cirúrgicos de Citorredução , Humanos , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/patologia , Estudos Retrospectivos
16.
J Surg Oncol ; 125(8): 1285-1291, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35253223

RESUMO

BACKGROUND AND OBJECTIVES: Sociodemographic factors have been shown to impact surgical outcomes. However, the effects of these factors on patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) are not well known. This study aims to evaluate the impact of sociodemographic factors on patients undergoing CRS/HIPEC. METHODS: Adult patients at a tertiary center who underwent CRS/HIPEC were evaluated. Perioperative variables were collected and analyzed. A national database was also used to evaluate patients undergoing CRS/HIPEC. RESULTS: There were 90 patients who underwent CRS/HIPEC (32% non-White). There was no statistically significant difference in postoperative complications, length of stay, or discharge disposition based upon race (white vs. non-White patients), socioeconomic status (SES), or insurance type. Nationally, we found that Black and Hispanic patients were less likely to undergo CRS/HIPEC than Non-Hispanic white patients (Black: odds ratio [OR]: 0.60, [confidence interval {CI}: 0.39-0.94]; Hispanic: OR: 0.52, [CI: 0.28-0.98]). However, there were no significant differences in postoperative complications based upon race/ethnicity. CONCLUSION: Sociodemographic factors including race, SES, and insurance status did not impact postoperative outcomes in patients undergoing CRS/HIPEC at our single institution. On a national level, Black and Hispanic patients underwent CRS/HIPEC at lower rates compared to white patients.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Humanos , Hipertermia Induzida/efeitos adversos , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Taxa de Sobrevida
18.
Sci Rep ; 12(1): 4401, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35292681

RESUMO

The objective of this study was to predict the preoperative pathological grading and survival period of Pseudomyxoma peritonei (PMP) by establishing models, including a radiomics model with greater omental caking as the imaging observation index, a clinical model including clinical indexes, and a combined model of these two. A total of 88 PMP patients were selected. Clinical data of patients, including age, sex, preoperative serum tumor markers [CEA, CA125, and CA199], survival time, and preoperative computed tomography (CT) images were analyzed. Three models (clinical model, radiomics model and combined model) were used to predict PMP pathological grading. The models' diagnostic efficiency was compared and analyzed by building the receiver operating characteristic (ROC) curve. Simultaneously, the impact of PMP's different pathological grades was evaluated. The results showed that the radiomics model based on the CT's greater omental caking, an area under the ROC curve ([AUC] = 0.878), and the combined model (AUC = 0.899) had diagnostic power for determining PMP pathological grading. The imaging radiomics model based on CT greater omental caking can be used to predict PMP pathological grading, which is important in the treatment selection method and prognosis assessment.


Assuntos
Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Neoplasias Peritoneais/patologia , Prognóstico , Pseudomixoma Peritoneal/diagnóstico por imagem , Pseudomixoma Peritoneal/patologia , Curva ROC , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
19.
Int J Biol Sci ; 18(5): 1912-1932, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35342344

RESUMO

Patients with peritoneal metastasis (PM) of colorectal cancer (CRC) have poorer overall survival outcomes than those without PM. Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and mediate CRC progression and PM. It is imperative to identify and develop novel therapeutic targets for PM-CRC driven by CAFs. Using lipidomics, we reveal that the abundance of phosphatidylcholine (PC) with unsaturated acyl chains was increased in clinical PM-CRC specimens. Additionally, we found that CAFs were present at a higher relative abundance in primary PM-CRC tumors and that membrane fluidity in CRC cells was increased after incubation with CAF-conditioned medium (CM) through three independent methods: lipidomics, fluorescence recovery after photobleaching (FRAP), and generalized polarization. Then, we found that increased membrane fluidity can enhance glucose uptake and metabolism, as supported by real-time bioenergetics analysis and U-13C glucose labeling. Interestingly, stearoyl-CoA desaturase 1 (SCD), the rate-limiting enzyme in the biosynthesis of unsaturated fatty acids (uS-FAs), was expressed at low levels in PM and associated with poor prognosis in CRC patients. Importantly, by untargeted metabolomics analysis and fatty acid ([U-13C]-stearic acid) tracing analyses, we found that CRC cells take up lipids and lipid-like metabolites secreted from CAFs, which may compensate for low SCD expression. Both in vitro and in vivo experiments demonstrated that sodium palmitate (C16:0) treatment could decrease the CAF-induced change in cell membrane fluidity, limit glucose metabolism, suppress cell invasiveness, and impair tumor growth and intraperitoneal dissemination. An increased C16:0 concentration was shown to induce apoptosis linked to lipotoxicity. Furthermore, C16:0 effectively enhanced the antitumor activity of 5-fluorouracil (5-FU) in vitro and was well tolerated in vivo. Taken together, these findings suggest that adding the saturated fatty acid (S-FA) C16:0 to neoadjuvant chemotherapy may open new opportunities for treating PM-CRC in the future.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Peritoneais , Fibroblastos Associados a Câncer/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias Colorretais/metabolismo , Humanos , Lipídeos , Fluidez de Membrana , Metabolômica , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , Microambiente Tumoral
20.
BMC Med Genomics ; 15(1): 51, 2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35255903

RESUMO

BACKGROUND: Pseudomyxoma peritonei is a rare disease condition mainly caused by primary mucinous tumors from the appendix and rarely from the ovary, such as when mucinous ovarian tumors arise from within a teratoma. Molecular analyses of pseudomyxoma from the appendix showed that KRAS and GNAS pathogenic variants are common genetic features of pseudomyxoma peritonei. However, the origin of the tumors is difficult to be identified via genetic variants alone. This study presents a case of pseudomyxoma peritonei of ovarian origin, which was diagnosed by comprehensive genomic profiling with ploidy analysis in a series of primary, recurrent, and autopsy tumor specimens. CASE PRESENTATION: A 40-year-old woman was diagnosed with Stage IC2 mucinous ovarian tumor of borderline malignancy with mature cystic teratoma, upon clinical pathology. Immunohistochemical analysis suggested that the mucinous tumor was derived from the intestinal component of an ovarian teratoma. Three years later, intraperitoneal recurrence was detected, which subsequently progressed to pseudomyxoma peritonei. Genomic analysis detected KRAS (G12D), GNAS (R201C), and FBXW7 (R367*) variants in the primary tumor. In addition, the tumor showed aneuploidy with loss of heterozygosity (LOH) in all its chromosomes, which suggested that the primary ovarian tumor was derived from germ cells. Existence of one Barr body suggested the existence of uniparental disomy of the tumors throughout the genome, instead of a haploid genotype. All three pathogenic variants remained positive in the initial recurrent tumor, as well as in the paired DNA from the whole blood in pseudomyxoma peritonei. The pathogenic variant of KRAS (G12D) was also identified in the autopsy specimen of the appendix by droplet digital polymerase chain reaction. CONCLUSIONS: This study pathologically and genetically confirmed that the primary ovarian borderline tumor was derived from the intestinal component of an ovarian teratoma, and that the subsequent pseudomyxoma peritonei progressed from the primary ovarian tumor. Integrative genomic analysis was useful to identify cellular origin of tumors, as well as to precisely interpret the process of disease progression.


Assuntos
Neoplasias Ovarianas , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Teratoma , Adulto , Feminino , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Pseudomixoma Peritoneal/genética , Pseudomixoma Peritoneal/patologia , Teratoma/genética , Teratoma/patologia
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