RESUMO
BACKGROUND: There is a paucity of targeted therapies for patients with pseudomyxoma peritonei (PMP) secondary to low-grade appendiceal mucinous neoplasms (LAMNs). Dysregulated metabolism has emerged as a hallmark of cancer, and the relationship of metabolomics and cancer is an area of active scientific exploration. We sought to characterize phenotypic differences found in peritoneal metastases (PM) derived from LAMN versus adenocarcinoma. METHODS: Tumors were washed with phosphate-buffered saline (PBS), microdissected, then dissociated in ice-cold methanol dried and reconstituted in pyridine. Samples were derivatized in tert-butyldimethylsilyl (TBDMS) and subjected to gas chromatography-coupled mass spectrometry. Metabolites were assessed based on a standard library. RNA sequencing was performed, with pathway and network analyses on differentially expressed genes. RESULTS: Eight peritoneal tumor samples were obtained and analyzed: LAMNs (4), and moderate to poorly differentiated adenocarcinoma (colon [1], appendix [3]). Decreases in pyroglutamate, fumarate, and cysteine in PM from LAMNs were found compared with adenocarcinoma. Analyses showed the differential gene expression was dominated by the prevalence of metabolic pathways, particularly lipid metabolism. The gene retinol saturase (RETSAT), downregulated by LAMN, was involved in the multiple metabolic pathways that involve lipids. Using network mapping, we found IL1B signaling to be a potential top-level modulation candidate. CONCLUSIONS: Distinct metabolic signatures may exist for PM from LAMN versus adenocarcinoma. A multitude of genes are differentially regulated, many of which are involved in metabolic pathways. Additional research is needed to identify the significance and applicability of targeting metabolic pathways in the potential development of novel therapeutics for these challenging tumors.
Assuntos
Adenocarcinoma Mucinoso , Adenocarcinoma , Neoplasias do Apêndice , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Neoplasias Peritoneais/secundário , Adenocarcinoma Mucinoso/patologia , Neoplasias do Apêndice/genética , Neoplasias do Apêndice/patologia , Pseudomixoma Peritoneal/patologia , Redes e Vias MetabólicasRESUMO
BACKGROUND/AIM: To evaluate the clinical desire for pressurized intraperitoneal aerosol chemotherapy (PIPAC) in South Korea. PATIENTS AND METHODS: We performed an online survey on surgical oncologists between November and December 2019 using a questionnaire consisting of 20 questions. RESULTS: A total of 164 respondents answered the questionnaire. Among those specialized in ovarian cancer, pseudomyxoma peritonei, and malignant mesothelioma 41.7-50% preferred PIPAC for the curative treatment of primary diseases, whereas 32.7-33.3% majoring in colorectal and hepatobiliary cancers chose it for the palliative treatment of recurrent diseases. Furthermore, 66.7-95.2% considered PIPAC appropriate for the cancers they specialized in, and 76-78.7% expected a treatment response of more than 50% and considered grade 1 or 2 complications acceptable. Most respondents answered the reasonable costs to purchase and implement PIPAC once at between 1,000,000-5,000,000 South Korean Won (KRW). CONCLUSION: Most Korean surgical oncologists expected relatively high tumor response rates with minor toxicities through the repeated implementation of PIPAC.
Assuntos
Infusões Parenterais/métodos , Mesotelioma Maligno/cirurgia , Oncologistas/psicologia , Neoplasias Ovarianas/cirurgia , Pseudomixoma Peritoneal/cirurgia , Aerossóis/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Custos e Análise de Custo , Doxorrubicina/uso terapêutico , Feminino , Humanos , Masculino , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma Maligno/patologia , Metástase Neoplásica , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Oxaliplatina/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/tratamento farmacológico , Pseudomixoma Peritoneal/patologia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Low grade appendiceal mucinous neoplasm (LAMN) is the primary source of pseudomyxoma peritonei (PMP). PMP may develop after seemingly complete resection of primary tumor by appendectomy, which is unpredictable due to lack of reliable prognostic indicators. We retrospectively reviewed 154 surgically resected LAMNs to explore if any of the macroscopic and microscopic characteristics may be associated with increasing risk of PMP development. Our major findings include: (1) As compared to those without PMP, the cases that developed PMP were more frequent to have (a) smaller luminal diameter (<1 cm) and thicker wall, separate mucin aggregations, and microscopic perforation/rupture, all suggestive of luminal mucin leakage; (b) microscopic acellular mucin presenting on serosal surface and not being confined to mucosa; and (c) neoplastic epithelium dissecting outward beyond mucosa, however, with similar frequency of neoplastic cells being present in muscularis propria. (2) Involvement of neoplastic cells or/and acellular mucin at surgical margin did not necessarily lead to tumor recurrence or subsequent PMP, and clear margin did not absolutely prevent PMP development. (3) Coexisting diverticulum, resulted from neoplastic or non-neoplastic mucosa being herniated through muscle-lacking vascular hiatus of appendiceal wall, was seen in a quarter of LAMN cases, regardless of PMP. The diverticular portion of tumor involvement was often the weakest point where rupture occurred. In conclusion, proper evaluation of surgical specimens with search for mucin and neoplastic cells on serosa and for microscopic perforation, which are of prognostic significance, should be emphasized.
Assuntos
Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Apendicectomia/métodos , Neoplasias do Apêndice/patologia , Pseudomixoma Peritoneal/patologia , Adenocarcinoma Mucinoso/complicações , Adenocarcinoma Mucinoso/ultraestrutura , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Divertículo/etiologia , Divertículo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucinas/ultraestrutura , Gradação de Tumores/métodos , Recidiva Local de Neoplasia/prevenção & controle , Patologia Cirúrgica/métodos , Prognóstico , Pseudomixoma Peritoneal/diagnóstico , Pseudomixoma Peritoneal/etiologia , Estudos Retrospectivos , Gestão de Riscos , Membrana Serosa/patologia , Membrana Serosa/ultraestrutura , Adulto JovemAssuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Mitomicina/administração & dosagem , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Adulto , Terapia Combinada/economia , Terapia Combinada/métodos , Procedimentos Cirúrgicos de Citorredução/economia , Feminino , Humanos , Hipertermia Induzida/economia , Índia , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia , Peritônio/diagnóstico por imagem , Peritônio/patologia , Peritônio/cirurgia , Pseudomixoma Peritoneal/diagnóstico , Pseudomixoma Peritoneal/patologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Low-grade appendiceal mucinous neoplasms are rare. Both classification and management vary. This study aimed to follow up on patients with a diagnosis of LAMN after primary surgery with computer tomography (CT) scans to examine the risk for the development of pseudomyxoma peritonei (PMP). METHODS: This population-based prospective study investigated patients who underwent appendectomy between 2007 and 2013 and had histology results demonstrating the presence of LAMN. The patients were followed up with a CT scan every 6 months for 2 years, until December 2015. RESULTS: The study investigated 41 patients (20 females) with a median age of 65 years (range 20-87 years). The entire appendix was processed and examined, with results showing that 12 were perforated, and 3 had a positive margin. Extra-appendiceal mucin on the surface of the appendix was found in ten cases, and in two cases, extra-mucinous epithelial cells were detected. During a median follow-up period of 5.1 years (range 2-8.6 years), none of the patients experienced the development of PMP. CONCLUSIONS: These data suggest that for patients with LAMN confined to the appendix, involvement of the appendectomy margin or perforation with mucin locally, even with epithelial cells, did not predict the development of PMP, and a conservative approach seems justified. No reoperation was needed, and regular follow-up evaluation with CT scans was sufficient.
Assuntos
Adenocarcinoma Mucinoso/patologia , Apendicectomia , Neoplasias do Apêndice/patologia , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/patologia , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Apêndice/diagnóstico por imagem , Neoplasias do Apêndice/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/cirurgia , Estudos Prospectivos , Pseudomixoma Peritoneal/diagnóstico por imagem , Pseudomixoma Peritoneal/cirurgia , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Pseudomyxoma peritonei is a clinical entity characterized by a gelatinous ascite associated with mucinous tumor deposits spreading on peritoneal surface and potentially invading abdominal organs. It is considered as a tumor process linked, in most of cases, to a mucinous appendiceal neoplasm. Pseudomyxoma peritonei may benefit from a therapeutic strategy combining cytoreductive surgery and intra-peritoneal chemotherapy, which has led to a major prognosis improvement. Different classifications are available and the last one corresponds to the WHO 2010 version, which individualizes pseudomyxoma peritonei in two classes: low grade and high grade mucinous carcinoma. The very low frequency of this entity and its specific therapeutic strategy need specific health care centres, as well as physicians and pathologists collaborating through dedicated networks. The aim of this article is to summarize the pathology, causes, mechanisms and therapeutic approaches of pseudomyxoma peritonei, as well as their interfaces with dedicated networks.
Assuntos
Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/patologia , Pseudomixoma Peritoneal/terapia , Humanos , Neoplasias Peritoneais/classificação , Pseudomixoma Peritoneal/classificaçãoRESUMO
Intrathoracic spread in patients with pseudomyxoma peritonei (PP) is rare. We reviewed 101 patients uniformly treated at our institution for PP of appendiceal origin. In that study, we suggested mucinous carcinoma peritonei (MCP) as the pathologic terminology for all cases of PP. Four patients had pathologically documented pleuropulmonary involvement. We subsequently examined another patient with pleural invasion. Of 5 patients, 3 had low-grade histologic features in the peritoneum; these showed variably proliferative, bland-appearing neoplastic cells arising from low-grade appendiceal mucinous neoplasms. In 2 cases, 1 or more pulmonary parenchymal metastases of low histologic grade developed. The lack of pleural involvement argued against transdiaphragmatic tumor extension. The third patient with low-grade MCP had direct extension through the left diaphragm involving the left pleural and pericardial spaces without pulmonary parenchymal involvement. In the 2 patients with high-grade MCP, right-sided pleural effusions developed. Neither patient had documented injury to the diaphragm. Pleural cytologic examination revealed high-grade adenocarcinoma cells singly, in small clusters, and in large spheres. The smear backgrounds contained wispy mucin. None of the 5 patients developed thoracic lymph nodal metastases. Although rare, mucinous neoplasms from PP may involve the thorax.