-
International Journal of Cancer Mar 2015Pseudomyxoma peritonei (PMP) is a relatively rare clinical syndrome characterized by neoplastic epithelial cells growing in the peritoneal cavity and secreting mucinous...
Pseudomyxoma peritonei (PMP) is a relatively rare clinical syndrome characterized by neoplastic epithelial cells growing in the peritoneal cavity and secreting mucinous ascites. Our aim was to explore the molecular events behind this fatal but under-investigated disease. We extracted DNA from 19 appendix-derived PMP tumors and nine corresponding normal tissues, and analyzed the mutational hotspot areas of 48 cancer-related genes by amplicon-based next-generation sequencing (NGS). Further, we analyzed the protein expression of V600E mutated BRAF, MLH1, MSH2, MSH6 and p53 from a larger set of PMP tumors (n = 74) using immunohistochemistry. With NGS, we detected activating somatic KRAS mutations in all of the tumors studied. GNAS was mutated in 63% of the tumors with no marked difference between low-grade and high-grade tumors. Only one (5.3%) tumor showed oncogenic PIK3CA mutation, one showed oncogenic AKT1 mutation, three (15.8%) showed SMAD4 mutations and none showed an APC mutation. P53 protein was aberrantly expressed in higher proportion of high-grade tumors as compared with low-grade ones (31.3 vs. 7.1%, respectively; p = 0.012) and aberrant expression was an independent factor for reduced overall survival (p = 0.002). BRAF V600E mutation was only found in one (1.4%) high-grade tumor by immunohistochemistry (n = 74). All the studied tumors expressed mismatch repair proteins MLH1, MSH2 and MSH6. Our results indicate that KRAS mutations are evident in all and GNAS mutations in most of the PMPs, but BRAF V600E, PIK3CA and APC mutations are rare. Aberrantly expressed p53 is associated with high-grade histology and reduced survival.
Topics: Aged; Biomarkers, Tumor; DNA Mutational Analysis; Female; Gene Expression Profiling; Genomics; High-Throughput Nucleotide Sequencing; Humans; Immunoenzyme Techniques; Male; Mutation; Neoplasm Grading; Peritoneal Neoplasms; Prognosis; Pseudomyxoma Peritonei; Survival Rate
PubMed: 25274248
DOI: 10.1002/ijc.29245 -
Surgical Oncology Dec 2023There are no previous studies on pseudomyxoma peritonei regarding the details of surgical procedures included in cytoreductive surgery and quantitative evaluation for...
BACKGROUND
There are no previous studies on pseudomyxoma peritonei regarding the details of surgical procedures included in cytoreductive surgery and quantitative evaluation for peritoneal metastases by region in the abdominal cavity. This study aimed to describe the characteristics and procedural details involved in cytoreductive surgery, and survival outcomes of patients with pseudomyxoma peritonei originating from appendiceal mucinous neoplasm, and identify differences in the difficulty of cytoreductive surgery based on tumor location.
METHODS
Patient characteristics and survival outcomes were studied through a retrospective review. The complete cytoreduction rate (i), the 5-year survival rate for patients with complete cytoreduction (ii), and an index as a complement (i × ii × 100) were described for patients who had tumors larger than 50 mm in one of the 13 regions of the abdominal cavity.
RESULTS
A total of 989 patients were treated with curative-intent cytoreductive surgery. The median peritoneal cancer index was 18 (interquartile range, 6-29), with complete cytoreduction achieved in 702 patients (71%); the major complication rate was 17%. The median overall survival was 92.9 months, compared to 53.8 months for patients who underwent total gastrectomy and 30.4 months for those who underwent total colectomy. In the 13 abdominal regions, the index scores indicating cytoreduction difficulty were categorized into three risk groups: upper and mid-abdominal (>20), lateral abdominal (10-20), and small bowel (<10).
CONCLUSIONS
Cytoreductive surgery offered favorable survival outcomes, even in cases involving total gastrectomy. The difficulty of achieving complete cytoreduction varied across abdominal regions and was classified into three levels.
Topics: Humans; Pseudomyxoma Peritonei; Peritoneal Neoplasms; Peritoneum; Gastrectomy; Colectomy; Retrospective Studies; Appendiceal Neoplasms; Cytoreduction Surgical Procedures; Hyperthermia, Induced; Combined Modality Therapy
PubMed: 37972508
DOI: 10.1016/j.suronc.2023.102012 -
ANZ Journal of Surgery Dec 2022
Topics: Humans; Pseudomyxoma Peritonei; Appendix; Appendiceal Neoplasms; Peritoneal Neoplasms
PubMed: 36527695
DOI: 10.1111/ans.17971 -
European Radiology Apr 2023This study aimed to identify the diagnostic accuracy of combined ultrasonography (US) and computed tomography (CT) in evaluating the tumor burden of pseudomyxoma...
OBJECTIVES
This study aimed to identify the diagnostic accuracy of combined ultrasonography (US) and computed tomography (CT) in evaluating the tumor burden of pseudomyxoma peritonei (PMP). Besides, we assessed the ability of this combination to predict the likelihood of complete resection.
METHODS
This retrospective study involved 504 patients diagnosed with PMP and scheduled for cytoreduction surgery. We compared tumor burden-quantified as peritoneal cancer index (PCI) by preoperative US and CT (US-CT-PCI)-with surgical findings. Next, we assessed the prognostic value of US-CT PCI and imaging features in determining the completeness of cytoreduction (CCR) score using multivariate analysis.
RESULTS
US-CT PCI demonstrated a high PCI evaluation accuracy under moderate tumor burden. Higher US-CT PCI could predict incomplete resection. In addition, we identified imaging features such as mesenteric involvement as an independent predictor of incomplete resection (hazard ratio (HR) = 2.006; p = 0.007).
CONCLUSIONS
US-CT PCI allowed us to predict the completeness of cytoreductive surgery in patients with PMP. Moreover, the combined US and CT imaging detected several features indicating incomplete cytoreduction.
KEY POINTS
• Ultrasonography (US) can act as a complementary diagnostic modality in peritoneal cancer index (PCI) evaluation by combining CT in the small bowel area and US in the abdominal area. • A modified peritoneal cancer index (US-CT PCI) helps preoperatively evaluate tumor burden with high accuracy and allows to predict incomplete resection. • US-CT PCI of 20 or above and the involvement of particular structures such as mesentery, independently indicate incomplete resection.
Topics: Humans; Pseudomyxoma Peritonei; Peritoneal Neoplasms; Retrospective Studies; Prognosis; Tomography, X-Ray Computed; Ultrasonography; Cytoreduction Surgical Procedures; Hyperthermia, Induced; Combined Modality Therapy
PubMed: 36418618
DOI: 10.1007/s00330-022-09242-z -
Scandinavian Journal of Surgery : SJS :... Jun 2024Pseudomyxoma peritonei (PMP) is a rare disease characterized by progressive build-up of mucinous deposits inside the abdominal cavity. The aim of this study was to...
BACKGROUND AND AIMS
Pseudomyxoma peritonei (PMP) is a rare disease characterized by progressive build-up of mucinous deposits inside the abdominal cavity. The aim of this study was to investigate the effect of disease recurrence on overall survival in patients with PMP after cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC).
METHODS
One-hundred thirty-two consecutive PMP patients treated with CRS + HIPEC at Helsinki University Hospital between 2008 and 2017 were included. The impact of clinicopathological and treatment-related characteristics on recurrence and overall survival was evaluated.
RESULTS
The median follow-up time in the study was 5.04 (range = 0.05-11.60) years. In 121 (91.7%) patients, the disease was classified as low grade and 11 (8.3%) had high-grade disease. In the low-grade group, 26 (21.5%) patients developed a recurrence during follow-up compared to 6 (54.5%) patients in the high-grade group. In the low-grade group, cumulative survival was 98.2%, 91.4%, and 91.4% at 3, 6, and 8 years, respectively. In the high-grade group, cumulative survival was 90.0% and 78.8% at 3 and 6 years, respectively. In patients with recurrent disease, the cumulative survival was 100%, 84.6%, and 84.6% at 3, 6, and 8 years in the low-grade category and 80.0% and 60.0% at 3 and 6 years in the high-grade category, respectively. In the low-grade group, a statistically significant correlation with recurrence but not with overall survival was identified with peritoneal cancer index (PCI), carcinoembryonic antigen (CEA), and the number of affected regions.
CONCLUSION
The recurrence of low-grade PMP does not significantly affect overall survival of patients. Disease extent may not be a prognostic indicator after curative CRS and HIPEC in low-grade PMP.
Topics: Humans; Pseudomyxoma Peritonei; Cytoreduction Surgical Procedures; Female; Male; Middle Aged; Retrospective Studies; Peritoneal Neoplasms; Hyperthermic Intraperitoneal Chemotherapy; Aged; Neoplasm Recurrence, Local; Adult; Combined Modality Therapy; Survival Rate; Finland
PubMed: 37828760
DOI: 10.1177/14574969231200653 -
Cancer Medicine Dec 2015Pseudomyxoma peritonei (PMP) is a rare disease exhibiting a distinct clinical feature caused by cancerous cells that produce mucinous fluid in the abdominal cavity. PMPs...
Pseudomyxoma peritonei (PMP) is a rare disease exhibiting a distinct clinical feature caused by cancerous cells that produce mucinous fluid in the abdominal cavity. PMPs originate most frequently from the appendix and less frequently from the ovary. This disease can range from benign to malignant, and histologically, PMP is classified into two types: disseminated peritoneal adenomucinosis (DPAM) representing the milder phenotype, and peritoneal mucinous adenocarcinomas (PMCA) representing the aggressive phenotype. Although histological classification is clinically useful, the pathogenesis of PMP remains largely unknown. To elucidate the molecular mechanisms underlying PMP, we analyzed 18 PMP tumors comprising 10 DPAMs and 8 PMCAs. DNA was extracted from tumor and matched non-tumorous tissues, and was sequenced using Ion AmpliSeq Cancer Panel containing 50 cancer-related genes. Analysis of the data identified a total of 35 somatic mutations in 10 genes, and all mutations were judged as pathological mutations. Mutations were frequently identified in KRAS (14/18) and GNAS (8/18). Interestingly, TP53 mutations were found in three of the eight PMCAs, but not in the DPAMs. PIK3CA and AKT1 mutations were also identified in two PMCAs, but not in the DPAMs. These results suggested that KRAS and/or GNAS mutations are common genetic features of PMP, and that mutations in TP53 and/or genes related to the PI3K-AKT pathway may render malignant properties to PMP. These findings may be useful for the understanding of tumor characteristics, and facilitate the development of therapeutic strategies.
Topics: Aged; Aged, 80 and over; Biomarkers; Combined Modality Therapy; DNA Mutational Analysis; Female; Gene Expression Profiling; Humans; Immunohistochemistry; Male; Middle Aged; Mutation; Neoplasm Grading; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Transcriptome; Tumor Suppressor Protein p53
PubMed: 26475379
DOI: 10.1002/cam4.542 -
ANZ Journal of Surgery Sep 2019Appendiceal epithelial neoplasms are rare cancers. Management of peritoneal disease from appendiceal neoplasms has historically been with debulking surgery. In recent... (Review)
Review
BACKGROUND
Appendiceal epithelial neoplasms are rare cancers. Management of peritoneal disease from appendiceal neoplasms has historically been with debulking surgery. In recent decades, the advent of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of care. Here, we report our single institution 10-year experience with CRS and HIPEC for appendiceal neoplasms.
METHODS
This is a retrospective review from 1 January 2008 to 1 June 2017 of all patients undergoing CRS and HIPEC for appendiceal neoplasms. Institutional ethics approval was granted for this project.
RESULTS
One hundred and seventy-two patients underwent 208 CRSs during this time. Overall, 83.72% of patients had one CRS and HIPEC procedure. Pseudomyxoma peritonei from a perforated appendiceal mucinous neoplasm accounted for 67.9% of cases. The median peritoneal carcinomatosis index (PCI) was 14, with complete cytoreduction achieved in 74.2% of patients. Fifty-four percent of patients had at least one complication, with one (0.5%) peri-operative mortality in our cohort. For the entire cohort, the median overall survival was 104 months and a 5-year survival of 75%. In those having a complete cytoreduction, 5-year survival was 90%, with a median disease free interval of 63 months. PCI and completeness of cytoreduction were independent predictors of overall survival.
CONCLUSION
Our results demonstrate that CRS and HIPEC for appendiceal neoplasms are safe and effective. Despite carrying some morbidity, it offers patients an excellent disease free and overall survival.
Topics: Antibiotics, Antineoplastic; Appendiceal Neoplasms; Australia; Chemotherapy, Cancer, Regional Perfusion; Cytoreduction Surgical Procedures; Female; Humans; Hyperthermia, Induced; Laparotomy; Male; Middle Aged; Mitomycin; Perioperative Period; Peritoneal Neoplasms; Prospective Studies; Pseudomyxoma Peritonei; Retrospective Studies; Survival Analysis
PubMed: 30685879
DOI: 10.1111/ans.14985 -
Advances in Anatomic Pathology Jan 2018Despite advances in our understanding of appendiceal mucinous neoplasms and their relationship to the pseudomyxoma peritonei syndrome, the classification of mucinous... (Review)
Review
Despite advances in our understanding of appendiceal mucinous neoplasms and their relationship to the pseudomyxoma peritonei syndrome, the classification of mucinous tumors of the appendix is still confusing. This review will provide an update on the various classification systems that have been recently proposed for appendiceal mucinous neoplasia, with a particular emphasis on how to handle and report the histologic findings for these tumors using the newly published Peritoneal Surface Oncology Group International (PSOGI) and American Joint Committee on Cancer (AJCC) eighth edition guidelines. A simplified approach to diagnostic reporting of appendiceal mucinous neoplasms based on the 3-tier AJCC grading scheme is detailed and specific criteria for assessing grade in appendiceal mucinous neoplasia will be outlined. In addition, histologic mimics of appendiceal mucinous neoplasia and how to distinguish these mimics from mucinous neoplasia will be discussed. Finally, despite improvements in diagnostic terminology, significant challenges in classifying appendiceal mucinous neoplasia persist and diagnostic strategies will be detailed to assist practicing pathologists in these challenging scenarios.
Topics: Adenocarcinoma, Mucinous; Appendiceal Neoplasms; Female; Humans; Neoplasm Staging; Ovarian Neoplasms; Peritoneal Neoplasms; Pseudomyxoma Peritonei
PubMed: 29016471
DOI: 10.1097/PAP.0000000000000178 -
Journal of Clinical Medicine Jun 2023Pseudomyxoma peritonei (PMP) is a rare malignant growth characterized by the production of mucin and the potential for peritoneal relapse. This study aimed to...
Pseudomyxoma peritonei (PMP) is a rare malignant growth characterized by the production of mucin and the potential for peritoneal relapse. This study aimed to investigate the immunohistochemical and biological characteristics of mucin in patients with cellular and acellular PMP. We prospectively analyzed mucin specimens obtained from our patient cohort and described the composition and type of mucin present in each sample. A metagenomic analysis of the samples was performed to investigate the bacterial composition of the PMP microbiome. Secreted mucins 2 and 5AC and membrane-associated mucin-1 were the primary components of mucin in both cellular and acellular tumor specimens. The metagenomic study revealed a predominance of the phylum and the genus . Notably, , a species not previously reported in the human microbiome, was found to be the most abundant organism in the mucin of pseudomyxoma peritonei. Our findings suggest that the presence of MUC-2 and mucin colonization by Pseudomonas are characteristic features of both cellular and acellular disease. These results may have significant implications for the diagnosis and treatment of this rare entity.
PubMed: 37373701
DOI: 10.3390/jcm12124007 -
Human Pathology Aug 2016Pseudomyxoma peritonei is a fatal clinical syndrome with mucinous tumor cells disseminated into peritoneal cavity and secreting abundant mucinous ascites. The serum...
Pseudomyxoma peritonei is a fatal clinical syndrome with mucinous tumor cells disseminated into peritoneal cavity and secreting abundant mucinous ascites. The serum tumor markers CEA, CA19-9, and CA125 are used to monitor pseudomyxoma peritonei remission, but their expression at tissue level has not been well characterized. Herein, we analyzed expression of these proteins and the adenocarcinoma marker EpCAM in 92 appendix-derived pseudomyxoma peritonei tumors by immunohistochemistry. All tumors were found to ubiquitously express CEA and EpCAM. In the majority of the tumors (94.6%), CEA showed polarized immunostaining, but in 5 aggressive high-grade tumors containing numerous signet ring cells, a nonpolarized staining was detected. We found preoperative CEA serum values to correlate with peritoneal cancer index. However, the serum values of the advanced cases with nonpolarized staining pattern were normal, and the patients died within 5 years after diagnosis. Thus, serum CEA measurements did not reflect aggressiveness of these tumors. CA19-9 showed strong immunopositivity in most of the tumors (91.3%), and mutated enzyme FUT3 was demonstrated from the cases showing negative or weak staining. CA125 was infrequently expressed by tumor cells (focal staining in 6.5% of the cases), but in most of the cases (79.3%), adjacent nonneoplastic mesothelial cells showed immunopositivity. As a conclusion, CEA and EpCAM are invariably expressed by pseudomyxoma peritonei tumor cells and could be exploited to targeted therapies against this malignancy.
Topics: Biopsy; CA-125 Antigen; CA-19-9 Antigen; Carcinoembryonic Antigen; Epithelial Cell Adhesion Molecule; Fucosyltransferases; Humans; Immunohistochemistry; Membrane Proteins; Mutation; Neoplasm Grading; Peritoneal Neoplasms; Predictive Value of Tests; Pseudomyxoma Peritonei; Time Factors
PubMed: 27038681
DOI: 10.1016/j.humpath.2016.02.022