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Journal of Cancer Research and Clinical... Sep 2020Pseudomyxoma peritonei (PMP) is a rare clinical malignancy syndrome characterized by the uncontrollable accumulation of copious mucinous ascites in the peritoneal... (Review)
Review
PURPOSE
Pseudomyxoma peritonei (PMP) is a rare clinical malignancy syndrome characterized by the uncontrollable accumulation of copious mucinous ascites in the peritoneal cavity, resulting in "jelly belly". The mechanism of tumor progression and mucin hypersecretion remains largely unknown, but GNAS mutation is a promising contributor. This review is to systemically summarize the biological background and variant features of GNAS, as well as the impacts of GNAS mutations on mucin expression, tumor cell proliferation, clinical-pathological characteristics, and prognosis of PMP.
METHODS
NCBI PubMed database (in English) and WAN FANG DATA (in Chinese) were used for literature search. And NCBI Gene and Protein databases, Ensembl Genome Browser, COSMIC, UniProt, and RCSB PDB database were used for gene and protein review.
RESULTS
GNAS encodes guanine nucleotide-binding protein α subunit (Gsα). The mutation sites of GNAS mutation in PMP are relatively stable, usually at Chr20: 57,484,420 (base pair: C-G) and Chr20: 57,484,421 (base pair: G-C). Typical GNAS mutation results in the reduction of GTP enzyme activity in Gsα, causing failure to hydrolyze GTP and release phosphoric acid, and eventually the continuous binding of GTP to Gsα. The activated Gsα could thus continuously promote mucin secretion through stimulating the cAMP-PKA signaling pathway, which is a possible mechanism leading to elevated mucin secretion in PMP.
CONCLUSION
GNAS mutation is one of the most important molecular biological features in PMP, with major functions to promote mucin hypersecretion.
Topics: Biomarkers, Tumor; Cell Proliferation; Chromogranins; GTP-Binding Protein alpha Subunits, Gs; Humans; Mucins; Mutation; Peritoneal Neoplasms; Prognosis; Pseudomyxoma Peritonei; Signal Transduction
PubMed: 32700107
DOI: 10.1007/s00432-020-03321-8 -
Journal of Cancer Research and... Jan 2024Pseudomyxoma peritonei (PMP) is an unusual clinical condition typically presenting with widespread mucinous neoplastic lesions within the peritoneum resulting in gelatin...
BACKGROUND
Pseudomyxoma peritonei (PMP) is an unusual clinical condition typically presenting with widespread mucinous neoplastic lesions within the peritoneum resulting in gelatin material-rich ascites. It was first described by Werth in 1884. Ever since, its clinical presentation, definition, site of origin, and prognosis have been a subject of debate. However, many histopathologic, immunohistochemical, and genetic studies have attempted to locate the primary lesion in the appendix in both genders.
OBJECTIVES
To analyze the histological origin and survival outcomes of pseudomyxoma peritonei in patients treated at a regional cancer center.
MATERIALS AND METHODS
Fifteen cases of PMP were diagnosed during the five-year study period. The demographic and clinicopathological details were retrieved; the slides were reviewed and histological parameters reassessed. Descriptive statistics were used to express proportions. Continuous variables were recorded as mean (SD) or median (IQR). Kaplan-Meier (KM) curve was used to estimate overall survival.
RESULTS
Mean age for PMP was found to be 47.5 years for low grade Mucinous Carcinoma Peritonei (MCP), 54.2 years for high grade MCP, and 58 years for high grade MCP with signet ring cells. Most common overall presentation was abdominal distension in 53.3% (8/15) of cases, followed by acute appendicitis in 20% (3/15) cases. PMP was detected synchronous with the primary tumor in 9/15 cases (60%). Primary lesion in the appendix was grossly identified in 7/15 cases, while it was not explored in the remaining eight cases. Yet, by combined clinical, radiological, histopathological, and immunohistochemical analysis, we identified that most of the cases (14/15) had an appendiceal origin (93.3%). The overall survival for 12 months was 50% and for 18 months was 37%.
CONCLUSION
The surgeon and radiologist may well bear in mind the most common possibility of an appendiceal origin for PMP and resect the appendix, irrespective of the presence of a grossly or radiologically detectable lesions. We emphasize that immunohistochemistry helped to detect the site of origin even when the primary was occult.
PubMed: 38261429
DOI: 10.4103/jcrt.jcrt_191_23 -
World Journal of Gastrointestinal... Sep 2019Pseudomyxoma peritonei (PMP) is a disease surrounded by misunderstanding and controversies. Knowledge about the etymology of pseudomyxoma is useful to remove the... (Review)
Review
Pseudomyxoma peritonei (PMP) is a disease surrounded by misunderstanding and controversies. Knowledge about the etymology of pseudomyxoma is useful to remove the ambiguity around that term. The word pseudomyxoma derives from pseudomucin, a type of mucin. PMP was first described in a case of a woman alleged to have a ruptured pseudomucinous cystadenoma of the ovary, a term that has disappeared from today's classifications of cystic ovarian neoplasms. It is known today that in the majority of cases, the origin for PMP is an appendiceal neoplasm, often of low histological grade. Currently, ovarian tumors are wrongly being considered a significant recognized etiology of PMP. PMP classification continues to be under discussion, and experts' panels strive for consensus. Malignancy is also under discussion, and it is shown in this review that there is a long-standing historical reason for that. Surgery is the main tool in the treatment armamentarium for PMP, and the only therapy with potential curative option.
PubMed: 31572561
DOI: 10.4240/wjgs.v11.i9.358 -
Frontiers in Oncology 2021To describe the clinicopathological characteristics of mucinous ovarian cancer (MOC)-derived pseudomyxoma peritonei (PMP) and identify prognostic factors for survival.
OBJECTIVE
To describe the clinicopathological characteristics of mucinous ovarian cancer (MOC)-derived pseudomyxoma peritonei (PMP) and identify prognostic factors for survival.
METHODS
Medical records from patients with MOC-derived PMP who attended the Aerospace Center Hospital, Beijing, China between January 2009, and December 2019 were retrospectively reviewed. Survival analysis was performed with the Kaplan-Meier method, the log-rank test, and a Cox proportional hazards model.
RESULTS
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for PMP originating from MOC were performed on 22 patients, who had a median age of 52 years at the time of surgery. At the last follow-up in June 2020, 9 (41%) patients were still alive. Median OS was 12 months (range, 1 to 102 months), and the 2-, 3-, and 5-year survival rates were 23, 9, and 5%, respectively.
CONCLUSION
Histopathologic subtype and PCI may be applied as predictors of prognosis in patients with MOC-derived PMP. Patients with high-grade disease could benefit from completeness of cytoreduction (CCR) 0/1.
PubMed: 33968739
DOI: 10.3389/fonc.2021.641053 -
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 -
World Journal of Gastrointestinal... May 2024We recently read with great interest a study by Zhang in the W. In our practice, we focus specifically on examining appendiceal mucinous neoplasms (AMNs) with...
We recently read with great interest a study by Zhang in the W. In our practice, we focus specifically on examining appendiceal mucinous neoplasms (AMNs) with endoscopic ultrasound (EUS) using different scopes. AMNs are rare neoplastic lesions characterized by an accumulation of mucin inside a cystic dilatation of the appendix. Clinically, they can present as nonspecific acute appendicitis. AMNs can turn into a life-threatening condition, termed pseudomyxoma peritonei, in which the ruptured appendix causes accumulation of mucin in the abdomen. Therefore, accurate and rapid diagnosis of AMN is essential. EUS is able to confirm and stage AMNs; although, EUS examination was once limited to the rectal and anal regions due to the conventional oblique-view scopes. With the emergence of new forward-view linear echoendoscopes and instruments like EUS miniprobes and overtubes, the scope of examination is changing. Herein, we discuss the feasibility of using the curved linear array echoendoscopes to examine cecal and appendiceal orifice lesions.
PubMed: 38813577
DOI: 10.4253/wjge.v16.i5.232 -
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 -
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