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Oncology Jan 2024Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites produced by neoplasms in the abdominal cavity....
INTRODUCTION
Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites produced by neoplasms in the abdominal cavity. Since the prognosis of patients with PMP remain unsatisfactory, the development of effective therapeutic drug(s) is a matter of pressing concern. Genetic analyses of PMP have clarified the frequent activation of GNAS and/or KRAS. However, the involvement of global epigenetic alterations in PMPs has not been reported.
METHODS
To clarify the genetic background of the 15 PMP tumors, we performed genetic analysis using AmpliSeq Cancer HotSpot Panel v2. We further investigated global DNA methylation in the 15 tumors and eight non-cancerous colonic epithelial cells using Methylation EPIC array BeadChip (Infinium 850k) containing a total of 865,918 probes.
RESULTS
This is the first report of comprehensive DNA methylation profiles of PMPs in the world. We clarified that the 15 PMPs could be classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME), and that genes associated with neuronal development and synaptic signaling may be involved in the development of PMPs. In addition, we identified a set of hypermethylation marker genes such as HOXD1 and TSPYL5 in the 15 PMPs.
CONCLUSIONS
These findings may help the understanding of the molecular mechanism(s) of PMP and contribute to the development of therapeutic strategies for this life-threatening disease.
PubMed: 38262376
DOI: 10.1159/000536219 -
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 -
ANZ Journal of Surgery Apr 2024Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard of care for selected cases of peritoneal surface malignancy. However,...
BACKGROUND
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard of care for selected cases of peritoneal surface malignancy. However, due to its morbidity and learning curve, it is only delivered in six centres in Australia and Aotearoa New Zealand (AoNZ). In this study, we report peri-operative morbidity and mortality following CRS/HIPEC at Waikato and Braemar Hospitals, which have treated patients from all regions of AoNZ since 2008.
METHODS
We retrospectively reviewed a database of all patients undergoing CRS and HIPEC from 01/01/2008 to 01/11/2020 at Waikato and Braemar Hospitals.
RESULTS
Two-hundred and forty procedures were performed for 221 patients with a mean age of 55, including 22 (9.2%) re-do procedures. One hundred and eighty-six cases were European, 32 were Māori, and 16 were Pasifika. There were 152 pseudomyxoma peritonei, 39 colorectal adenocarcinomas, 29 appendiceal cancers, 8 ovarian cancers, 6 peritoneal mesothelioma, and 6 other tumour types. The median PCI was 16. HIPEC was administered to 196 out of 196 CC0/1 cases (100%) and 3 out of 44 CC2/3 cases (6.8%). Fifty-six cases (23.3%) had at least one major complication. There were two mortalities (0.8%) within 30 days. The median length of stay was 11 days. Operative duration was identified as an independent risk factor for major complications. There was considerable variation in the number of referrals from different regions of AoNZ. Over time, a decline in major complication rate is seen with increased case volume.
CONCLUSION
The Waikato region has achieved favourable short-term outcomes following CRS/HIPEC.
Topics: Female; Humans; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytoreduction Surgical Procedures; Hyperthermic Intraperitoneal Chemotherapy; New Zealand; Peritoneal Neoplasms; Retrospective Studies; Survival Rate
PubMed: 38240147
DOI: 10.1111/ans.18833 -
Pathology, Research and Practice Feb 2024Epithelial-mesenchymal transition (EMT), angiogenesis, cell adhesion and extracellular matrix (ECM) interaction are essential for colorectal cancer (CRC) metastasis. Low...
Epithelial-mesenchymal transition (EMT), angiogenesis, cell adhesion and extracellular matrix (ECM) interaction are essential for colorectal cancer (CRC) metastasis. Low grade mucinous neoplasia of the appendix (LAMN) and its advanced state low grade pseudomyxoma peritonei (lgPMP) show local aggressiveness with very limited metastatic potential as opposed to CRC. To better understand the underlying processes that foster or impede metastatic spread, we compared LAMN, lgPMP, and CRC with respect to their molecular profile with subsequent pathway analysis. LAMN, lgPMP and (mucinous) CRC cases were subjected to transcriptomic analysis utilizing Poly(A) RNA sequencing. Successfully sequenced cases (LAMN n = 10, 77%, lgPMP n = 13, 100% and CRC n = 8, 100%) were investigated using bioinformatic and statistical tests (differential expression analysis, hierarchical clustering, principal component analysis and gene set enrichment analysis). We identified a gene signature of 28 genes distinguishing LAMN, lgPMP and CRC neoplasias. Ontology analyses revealed that multiple pathways including EMT, ECM interaction and angiogenesis are differentially regulated. Fifty-three significantly differentially regulated gene sets were identified between lgPMP and CRC followed by CRC vs. LAMN (n = 21) and lgPMP vs. LAMN (n = 16). Unexpectedly, a substantial enrichment of the EMT gene set was observed in lgPMP vs. LAMN (FDR=0.011) and CRC (FDR=0.004). Typical EMT markers were significantly upregulated (Vimentin, TWIST1, N-Cadherin) or downregulated (E-Cadherin) in lgPMP. However, MMP1 and MMP3 levels, associated with EMT, ECM and metastasis, were considerably higher in CRC. We show that the different tumor biological behaviour and metastatic spread pattern of midgut malignancies is reflected in a different gene expression profile. We revealed a strong activation of the EMT program in non-metastasizing lgPMP vs. CRC. Hence, although EMT is considered a key step in hematogenous spread, successful EMT does not necessarily lead to hematogenous dissemination. This emphasizes the need for further pathway analyses and forms the basis for mechanistic and therapy-targeting research.
Topics: Humans; Pseudomyxoma Peritonei; Transcriptome; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Peritoneal Neoplasms; Gene Expression Profiling; Cell Line, Tumor; Cell Movement
PubMed: 38232629
DOI: 10.1016/j.prp.2024.155129 -
Annals of Surgical Oncology Apr 2024
Topics: Female; Humans; Pseudomyxoma Peritonei; Peritoneal Neoplasms; Appendiceal Neoplasms; Ovary; Ovarian Neoplasms
PubMed: 38200386
DOI: 10.1245/s10434-024-14927-4 -
Asian Journal of Surgery Apr 2024
Topics: Humans; Pseudomyxoma Peritonei; Appendiceal Neoplasms; Peritoneal Neoplasms
PubMed: 38182506
DOI: 10.1016/j.asjsur.2023.12.114 -
Orphanet Journal of Rare Diseases Jan 2024To explore the application value of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with incomplete cytoreduction for appendiceal pseudomyxoma peritonei...
BACKGROUND
To explore the application value of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with incomplete cytoreduction for appendiceal pseudomyxoma peritonei (PMP).
METHODS
We retrospectively analyzed the clinical data of 526 patients with incomplete cytoreduction for appendiceal PMP to discover its prognostic factors, and the therapeutic value of HIPEC.
RESULTS
The 5-year and 10-year overall survival rates of patients after cytoreductive surgery (CRS) treated with HIPEC were significantly higher than those without HIPEC (5y-OS: 58% vs. 48%, 10y-OS: 37% vs. 16%, P = 0.032). The median progression-free survival (PFS) following CRS was 20 months, with a 20% 3-year PFS. The median PFS following CRS + HIPEC was 33 months, with a 60% 3-year PFS (P = 0.000). Univariate analysis indicated that HIPEC, gender, completeness of cytoreduction (CCR) and pathological grade had statistical difference. Multivariate analysis showed that CRS without HIPEC and high pathological grade were independent risk factors for poor prognosis and rapid tumor progression.
CONCLUSIONS
HIPEC may prolong the survival in patients with incomplete cytoreduction for low-grade appendiceal PMP. High pathological grade indicates poor survival and rapid tumor progression.
Topics: Humans; Pseudomyxoma Peritonei; Hyperthermic Intraperitoneal Chemotherapy; Cytoreduction Surgical Procedures; Peritoneal Neoplasms; Appendiceal Neoplasms; Retrospective Studies; Hyperthermia, Induced; Survival Rate
PubMed: 38178189
DOI: 10.1186/s13023-023-02995-w -
In Vivo (Athens, Greece) 2024Appendiceal mucinous neoplasms (AMNs) are tumors with dysplastic mucinous epithelium, a pushing growth pattern but no infiltrative invasion to the appendiceal wall. Some...
BACKGROUND/AIM
Appendiceal mucinous neoplasms (AMNs) are tumors with dysplastic mucinous epithelium, a pushing growth pattern but no infiltrative invasion to the appendiceal wall. Some AMNs are associated with pseudomyxoma peritonei, characterized by intraperitoneal mucinous involvement. Recent studies have demonstrated that LAMNs confined to the appendix have low or no risk for disease recurrence, progression, and peritoneal involvement during follow up.
CASE REPORT
Here, we present two extremely rare cases with confined low grade appendiceal mucinous neoplasm (pTis and pT3) and simultaneous extraperitoneal subcutaneous or ovary involvement at the time of diagnosis.
CONCLUSION
Our cases demonstrate that although the primary tumor is limited to the appendix, coexisting distant metastasis may occur on very rare occasions.
Topics: Female; Humans; Peritoneal Neoplasms; Neoplasm Recurrence, Local; Appendiceal Neoplasms; Pseudomyxoma Peritonei; Ovary
PubMed: 38148061
DOI: 10.21873/invivo.13438 -
Human Cell Mar 2024Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is...
Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP. However, 50% of patients with PMP experience a recurrence, and 30-40% are unable to receive the standard treatment due to invasive diseases. Therefore, novel therapies are required for their treatment. Although patient-derived cell lines are important tools for basic and pre-clinical research, PMP cell lines derived from patients with HGMCP-S have never been reported. Thus, we established a novel PMP cell line NCC-PMP2-C1, using surgically resected tumor tissue from a patient with HGMCP-S. NCC-PMP2-C1 cells were maintained for more than five months and passaged 30 times under culture conditions. NCC-PMP2-C1 cells exhibited multiple deletions and somatic mutations, slow growth, histological features, and dissemination of tumor cells in nude mice. Screening for the anti-proliferative effects of anti-cancer drugs on cells revealed that bortezomib, mubritinib, and romidepsin had a significant response against NCC-PMP2-C1 cells. Thus, the NCC-PMP2-C1 cell line is the first PMP cell line harboring signet ring cells and will be a valuable resource for basic and preclinical studies of HGMCP-S.
Topics: Animals; Mice; Humans; Pseudomyxoma Peritonei; Mice, Nude; Peritoneal Neoplasms; Adenocarcinoma, Mucinous; Carcinoma, Signet Ring Cell; Myelin P2 Protein
PubMed: 38143259
DOI: 10.1007/s13577-023-01015-0 -
ANZ Journal of Surgery Apr 2024
Topics: Humans; Pseudomyxoma Peritonei; Urachus; Peritoneal Neoplasms; Adenocarcinoma, Mucinous; Neoplasms, Cystic, Mucinous, and Serous; Appendiceal Neoplasms
PubMed: 38135894
DOI: 10.1111/ans.18829