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Frontiers in Oncology 2023Pseudomyxoma peritonei (PMP) is a rare malignant disease characterized by a massive multifocal accumulation of mucin within the peritoneal cavity. The current treatment...
INTRODUCTION
Pseudomyxoma peritonei (PMP) is a rare malignant disease characterized by a massive multifocal accumulation of mucin within the peritoneal cavity. The current treatment option is based on complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. However, the recurrence is frequent with subsequent progression and death. To date, most of the studies published in PMP are related to histological and genomic analyses. Thus, the need for further studies unveiling the underlying PMP molecular mechanisms is urgent. In this regard, hypoxia and oxidative stress have been extensively related to tumoral pathologies, although their contribution to PMP has not been elucidated.
METHODS
In this manuscript, we have evaluated, for the first time, the intratumoral real-time oxygen microtension (pO2mt) in the tumor (soft and hard mucin) and surrounding healthy tissue from five PMP patients during surgery. In addition, we measured hypoxia (Hypoxia Inducible Factor-1a; HIF-1α) and oxidative stress (catalase; CAT) markers in soft and hard mucin from the same five PMP patient samples and in five control samples.
RESULTS
The results showed low intratumoral oxygen levels, which were associated with increased HIF-1α protein levels, suggesting the presence of a hypoxic environment in these tumors. We also found a significant reduction in CAT activity levels in soft and hard mucin compared with healthy tissue samples.
DISCUSSION
In conclusion, our study provides the first evidence of low intratumoral oxygen levels in PMP patients associated with hypoxia and oxidative stress markers. However, further investigation is required to understand the potential role of oxidative stress in PMP in order to find new therapeutic strategies.
PubMed: 36776312
DOI: 10.3389/fonc.2023.1076500 -
Experimental Hematology & Oncology Dec 2023Pseudomyxoma peritonei (PMP) is a rare disease characterized by a massive accumulation of mucus in the peritoneal cavity. The only effective treatment is aggressive...
Pseudomyxoma peritonei (PMP) is a rare disease characterized by a massive accumulation of mucus in the peritoneal cavity. The only effective treatment is aggressive surgery, aimed at removing all visible tumors. However, a high percentage of patients relapse, with subsequent progression and death. Recently, there has been an increase in therapies that target mutated oncogenic proteins. In this sense, KRAS has been reported to be highly mutated in PMP, with KRAS being the most common subtype. Here, we tested the efficacy of a small-molecule KRAS inhibitor, MRTX1133, in a high-grade PMP xenograft mouse model carrying a KRAS mutation. The results obtained in this work showed a profound inhibition of tumor growth, which was associated with a reduction in cell proliferation, an increase in apoptosis, and a reduction in the MAPK and PI3K/AKT/mTOR signaling pathways. In conclusion, these results demonstrate the high potency and efficacy of MRTX1133 in KRAS-PMP tumors and provide a rationale for clinical trials.
PubMed: 38066554
DOI: 10.1186/s40164-023-00465-4 -
Cancer Metastasis Reviews Mar 2023Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low... (Review)
Review
Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included KRAS (38-100%), GNAS (17-100%), and TP53 (5-23%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target KRAS and GNAS mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial.
Topics: Humans; Pseudomyxoma Peritonei; Peritoneal Neoplasms; Appendiceal Neoplasms; Genetic Profile; Proto-Oncogene Proteins p21(ras)
PubMed: 36723696
DOI: 10.1007/s10555-023-10088-0 -
Indian Journal of Surgical Oncology Jun 2016The combined treatment concept of cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown to be an efficient therapeutic option for... (Review)
Review
The combined treatment concept of cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown to be an efficient therapeutic option for selected patients with primary and secondary peritoneal carcinomatosis (PC). This strategy represents the standard of care for diseases like pseudomyxoma peritonei and peritoneal mesothelioma, and offers the best long-term results for PC from colorectal cancer. Despite these results, skepticism exists regarding this therapeutic approach partly because of its perceived high toxicity. In this article, we review the current evidence on complications that can occur after CRS and HIPEC and the risk factors associated with increased incidence of morbidity and mortality.
PubMed: 27065713
DOI: 10.1007/s13193-016-0504-6 -
Cancers Apr 2024Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing, inadequately understood neoplasm with a 5-year progression-free survival rate of as low as 48%. It... (Review)
Review
BACKGROUND
Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing, inadequately understood neoplasm with a 5-year progression-free survival rate of as low as 48%. It is characterized by varying degrees of malignancy and the production of mucinous and gelatinous structures. Typically, the development of pseudomyxoma peritonei is associated with the rupture of appendiceal mucinous tumors and other gastrointestinal or ovarian mucinous tumors. The goal of our literature review was to identify various aspects that characterize the ovarian causes of pseudomyxoma peritonei.
MATERIALS AND METHODS
The authors performed an extensive literature search between 1 February 2024 and 2 March 2024 on the following databases: Pubmed, Scopus, Oxford Journals, and Reaxys, and the findings were summarized into seven main clinical and paraclinical situations.
RESULTS
According to our research, the main instances in which pseudomyxoma peritonei can be triggered by an ovarian cause are the following: (1) mucinous cystadenoma; (2) mucinous ovarian cancer; (3) colon cancer with ovarian metastasis; (4) malignant transformation of an ovarian primary mature cystic teratoma; (5) appendiceal mucocele with peritoneal dissemination mimicking an ovarian tumor with peritoneal carcinomatosis; (6) mucinous borderline tumor developing inside an ovarian teratoma; and (7) the association between a mucinous bilateral ovarian cancer and a colonic tumor.
CONCLUSIONS
In our study, we aimed to provide a comprehensive overview of the ovarian causes of pseudomyxoma peritonei, including its epidemiology, imagery characteristics, symptoms, current treatment, and promising future therapies, in the hopes of finding feasible solutions, as a lack of understanding of this mucus-secreting malignant disease increases the risk of delayed diagnosis or uncontrolled deterioration.
PubMed: 38672528
DOI: 10.3390/cancers16081446 -
Modern Pathology : An Official Journal... Jan 2015The classification of appendiceal mucinous neoplasms has been controversial, largely focused on a particular subset of low-grade mucinous tumors that, despite their... (Review)
Review
The classification of appendiceal mucinous neoplasms has been controversial, largely focused on a particular subset of low-grade mucinous tumors that, despite their innocuous appearance, can disseminate to the peritoneal cavity as pseudomyxoma peritonei (PMP). Recent WHO classification of these tumors as low-grade appendiceal mucinous neoplasms acknowledges their unique morphologic appearance and biologic behavior. Still, debate about the use of this term and its parameters continues to impede the adoption of consensus classification for appendiceal mucinous neoplasms. The classification of PMP has also been the subject of debate, with international authorities advocating for the use of malignant terminology to describe all grades of PMP, even though some authorities consider low-grade PMP to be dissemination of adenomatous epithelium in the peritoneum. Recent data also emphasize the importance of histologic grade of the peritoneal tumors in defining prognosis of these patients.
Topics: Appendiceal Neoplasms; Humans; Neoplasms, Glandular and Epithelial; Peritoneal Neoplasms; Pseudomyxoma Peritonei
PubMed: 25560600
DOI: 10.1038/modpathol.2014.129 -
Indian Journal of Surgical Oncology Jun 2023Pleural spread occurs in pseudomyxoma peritonei (PMP) in less than 10% of the patients and is treated by thoracic cytoreductive surgery with or without hyperthermic...
Pleural spread occurs in pseudomyxoma peritonei (PMP) in less than 10% of the patients and is treated by thoracic cytoreductive surgery with or without hyperthermic intrathoracic chemotherapy (HITOC). It is performed both for symptom palliation and disease control and includes pleurectomy and decortication and wedge and segmental lung resections. So far, only unilateral spread treated with a thoracic cytoreductive surgery (CRS) has been reported in literature. We report a patient with bilateral thoracic PMP following a complete abdominal CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) who was treated with bilateral staged thoracic CRS and subsequently had a 4th CRS for abdominal disease. The staged procedure was performed as she was symptomatic due to the thoracic disease and there was disease on all pleural surfaces. HITOC was not performed. Both procedures were uneventful with no major morbidity. The patient is currently disease free nearly 84 months after the first abdominal CRS and 60 months after the second thoracic CRS. Thus, an aggressive CRS in the thorax in patients with PMP can result in a prolongation of survival while preserving the quality of life if the abdominal disease is controlled. A thorough understanding of the disease biology and surgical expertise are both essential for selecting the right patients for these complex procedures and achieving good short- and long-term outcomes.
PubMed: 37359933
DOI: 10.1007/s13193-023-01745-5 -
Innovative Surgical Sciences Mar 2024Treatment of peritoneal surface malignancies makes physicians face demanding and new-fangled problems, as there are many uncertain aspects considering the outcomes of... (Review)
Review
Treatment of peritoneal surface malignancies makes physicians face demanding and new-fangled problems, as there are many uncertain aspects considering the outcomes of affected patients' prognoses. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are associated with favorable long-term outcomes in carefully selected patients with peritoneal metastases (PM). We aim to summarize the current results about the initial malignancies and their peritoneal spreads. The current literature has been scrutinized, and studies between 2016 and 2022 were included wherein long-term, progression-free (PFS), and overall survival (OS) data were considered relevant information. Medline, Embase, and Google Scholar have been the main sources. Hereby, we cover all the primer malignancies: gastric, ovarian, and colorectal cancers with peritoneal metastases (PM), malignant peritoneal mesothelioma, and pseudomyxoma peritonei. Examining the advances in the current peer-reviewed literature about the indications of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), target groups, risk factors, and other influencing elements, we intend to provide a complex state-of-the-art report, establishing the relevant aspects of that emerging treatment method.
PubMed: 38826635
DOI: 10.1515/iss-2023-0055 -
Frontiers in Surgery 2021Pseudomyxoma peritonei (PMP) originating from appendiceal mucinous neoplasm is a rare peritoneal malignancy characterized by the progressive intraperitoneal...
Pseudomyxoma peritonei (PMP) originating from appendiceal mucinous neoplasm is a rare peritoneal malignancy characterized by the progressive intraperitoneal accumulation of mucus leading to death if left untreated. In recent years, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) offered increased survival rates. This study aims to identify the clinical, pathological, and surgical features influencing safety and survival outcomes of patients undergoing CRS and HIPEC for PMP of appendiceal origin. A retrospective analysis of all patients undergoing CRS and HIPEC for PMP of appendiceal origin from January 2015 to May 2019 was conducted at our institution. Study population included 50 patients (74% female, 26% male). The median age at CRS was 60 (38-84). The median peritoneal cancer index (PCI) was 17. Complete cytoreductive surgery (CC 0-1) was achieved in 47 patients (94%). HIPEC chemotherapeutic regimen was based on oxaliplatin for 13 (28%) patients and mitomycin for 34 (72%) patients. We experienced a total of 19 (38%) postoperative complications, of which 14 (74%) of grade I-II and 5 (26%) of grade III-IV, according to the Clavien-Dindo classification. The median follow-up period was 27 months (12-107) from the date of cytoreductive surgery. The mean survival rate was 100 months, with a 5-year OS of 91%. The mean progression-free survival rate was 77 months (0-107), with a 5-year PFS of 63%. Multivariate analysis identified adenocarcinoma histotype and incomplete cytoreduction to significantly worsen progression-free survival, while incomplete cytoreduction was the only independent predictor of poorer overall survival. Complete cytoreduction and appendiceal neoplasm histotype play a crucial role in the survival of patients affected by PMP of appendiceal origin. The rates of morbidity associated with CRS and HIPEC for PMP are acceptable.
PubMed: 34513915
DOI: 10.3389/fsurg.2021.715119 -
Indian Journal of Surgical Oncology Jun 2023To report a case series of patients with pseudomyxoma peritonei (PMP) from urachal mucinous neoplasm (UMN) treated with CRS and HIPEC at a high-volume referral centre,...
UNLABELLED
To report a case series of patients with pseudomyxoma peritonei (PMP) from urachal mucinous neoplasm (UMN) treated with CRS and HIPEC at a high-volume referral centre, along with an updated literature review. Retrospective review of cases treated between 2000 and 2021. A literature review using MEDLINE and Google Scholar databases was performed. Clinical presentation of PMP from UMN is heterogeneous, and common symptoms are abdominal distension, weight loss, fatigue and haematuria. At least one tumour marker among CEA, CA 19.9, and CA 125 was elevated in the six cases reported, and 5/6 had a preoperative working diagnosis of urachal mucinous neoplasm suspected on detailed cross-sectional imaging. Complete cytoreduction was achieved in five cases, while one patient underwent maximal tumour debulking. Histological findings mirrored the findings of PMP from appendiceal mucinous neoplasms (AMN). Overall survival ranged between 43 and 141 months after complete cytoreduction. On literature review, 76 cases have been reported to date. Complete cytoreduction is associated with good prognosis for patients with PMP from UMN. A definitive classification system is still not available.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s13193-022-01694-5.
PubMed: 37359937
DOI: 10.1007/s13193-022-01694-5