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Inflammation plays an important role in the pathogenesis of peritoneal carcinosis. Patients with elevated levels of different inflammation cytokines show a worse prognosis at the time of diagnosis. In women, ovarian and colon cancer are the main causes of peritoneal carcinosis and a comparison of these two different types of peritoneal invasion have not been conducted yet. We found interesting studying the role of immune response, in particular tumour-associated antigens (TAA) that modulate the metastatic process. We will investigate also mitochondrial defects, such as mutations in mt-DNA, potentially involved in carcinogenesis.
At the time of hospitalization all the patients will undergo a complete clinical evaluation with determination of biochemical parameters such as fasting blood glucose, blood count, hs-CRP, AST and ALT, uric acid, creatinine and BUN. An extra blood aliquot will be collected to assess the serum biomarkers under investigation.
During surgery two samples of peritoneal tissue macroscopically undamaged will be collected. On those samples will be executed separation of adipocytes cells, RNA and protein extraction for measuring of inflammatory and neoplastic biomarkers, determination of P2X7R-inflammasome activity and mitochondrial DNA analyse.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ovarian cancer | Patients affected by ovarian cancer will be stratified according to BRCA1 and BRCA2 mutational status. |
| |
| Colon cancer | Patients affected by colon cancer will be similarly stratified according to BRAF and KRAS mutational status and to the presence of low-grade or high-grade microsatellite instability (MSI). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cytoreductive surgery | Procedure | Partial removal of peritoneal tissue involved by neoplastic invasion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Immune biomarkers level | Serum level of different immune related biomarkers (such as CD4, CD8, CUZD1, LAG3, PD1, PDL1, IMP1 and p62/IMP2) will be determined using ELISA. | Each patients will be assessed at baseline |
| Metastatic mediators level | Peritoneal expression of cytokines related to metastatic process (such as IL6, IL2, TNFα, TGFβ1, VEGF, CD68, FGFR1, CCL2/MCP-1, CD73) will be determined using real time-PCR. | Each patients will be assessed at baseline |
| P2X7R-inflammasome activity | Peritoneal expression of NLRP3-ASC will be determine using RT-PCR | Each patients will be assessed at baseline |
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Inclusion Criteria:
Exclusion Criteria:
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The study consecutively enrolled 30 patients undergoing surgical treatment for peritoneal carcinosis: 15 patients affected by high grade ovarian cancer and 15 patients affected by colon cancer. Patients will be enrolled among those referring to the Gynaecologic Unit and the General Surgery Unit, University Hospital of Pisa, Italy.
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| Name | Affiliation | Role |
|---|---|---|
| Anna Solini, MD, PhD | University of Pisa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pisa | Pisa | 56125 | Italy |
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| ID | Term |
|---|---|
| D010534 | Peritoneal Neoplasms |
| D010051 | Ovarian Neoplasms |
| D003110 | Colonic Neoplasms |
| ID | Term |
|---|---|
| D000008 | Abdominal Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004067 | Digestive System Neoplasms |
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| ID | Term |
|---|---|
| D065426 | Cytoreduction Surgical Procedures |
| ID | Term |
|---|---|
| D013514 | Surgical Procedures, Operative |
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peritoneal biopsy
| D004066 |
| Digestive System Diseases |
| D010532 | Peritoneal Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |