Cellular Response and Clinical Aspects of Peritoneal Carcinomatosis for Colorectal Cancer Patients
(2026) In Lund University, Faculty of Medicine Doctoral Dissertation Series- Abstract
- Background: Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is a metastatic condition associated with poor prognosis. Tumor dissemination within the peritoneal cavity is influenced by inflammatory responses, immune activation, and tumor-matrix interactions, particularly following surgical trauma. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment in selected patients, yet recurrence and postoperative morbidity remain major challenges.
Aim: This thesis aimed to investigate cellular mechanisms involved in peritoneal tumor establishment and to evaluate clinical outcomes and complications related to CRS and HIPEC.
Methods: This thesis comprises... (More) - Background: Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is a metastatic condition associated with poor prognosis. Tumor dissemination within the peritoneal cavity is influenced by inflammatory responses, immune activation, and tumor-matrix interactions, particularly following surgical trauma. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment in selected patients, yet recurrence and postoperative morbidity remain major challenges.
Aim: This thesis aimed to investigate cellular mechanisms involved in peritoneal tumor establishment and to evaluate clinical outcomes and complications related to CRS and HIPEC.
Methods: This thesis comprises four studies. One preclinical study used an experimental murine model to examine chemokine signaling and integrin-mediated adhesion in PC following surgical trauma using functional assays, in vivo experiments, and flow cytometry. Three clinical studies used retrospective institutional cohorts and population-based registry data to evaluate oncological outcomes, learning curve, postoperative complications, and preventive strategies.
Results: Experimental studies demonstrated that CXCR2 and αV integrin signaling promote peritoneal tumor adhesion and metastasis after surgical trauma. Clinically, CRS and HIPEC were implemented in a medium-volume center with outcomes comparable to high-volume institutions. Prophylactic sodium thiosulfate (ST) was associated with reduced incidence and severity of acute kidney injury (AKI) following Oxaliplatin-based HIPEC. Adjuvant chemotherapy did not reduce the risk of metachronous peritoneal metastases in patients with radically resected nodenegative T4 colon cancer.
Conclusions: Peritoneal dissemination of CRC is driven by defined cellular mechanisms and is influenced by surgical intervention. CRS and HIPEC can be implemented in a medium-volume center with outcomes comparable to highvolume institutions, without increased morbidity. Prophylactic ST reduces AKI after Oxaliplatin-based HIPEC. Adjuvant chemotherapy does not prevent metachronous peritoneal metastases after radical resection of node-negative T4 colon cancer. (Less)
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https://lup.lub.lu.se/record/6374705a-e9a8-4cfb-b6a1-140c695b2a26
- author
- Algethami, Nader LU
- supervisor
- opponent
-
- Associate Professor of Surgery Folkesson, Joakim, Uppsala University, Sweden
- organization
- publishing date
- 2026
- type
- Thesis
- publication status
- published
- subject
- keywords
- cytoreductive surgery, Hyperthermic intraperiotneal chemotherapy, peritoneal carcinomatosis, CXCR2, Chemokine, learning curve, postoperative complications, acute kidney injury, sodium thiosulfate, adjuvant chemotherapy, colon cancer
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2026:33
- pages
- 92 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Kvinnoklinikens aula, Jan Waldenströms gata 47, Skånes Universitetssjukhus i Malmö
- defense date
- 2026-03-13 13:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-831-3
- language
- English
- LU publication?
- yes
- id
- 6374705a-e9a8-4cfb-b6a1-140c695b2a26
- date added to LUP
- 2026-02-18 20:53:19
- date last changed
- 2026-02-19 10:54:36
@phdthesis{6374705a-e9a8-4cfb-b6a1-140c695b2a26,
abstract = {{Background: Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is a metastatic condition associated with poor prognosis. Tumor dissemination within the peritoneal cavity is influenced by inflammatory responses, immune activation, and tumor-matrix interactions, particularly following surgical trauma. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment in selected patients, yet recurrence and postoperative morbidity remain major challenges. <br/><br/>Aim: This thesis aimed to investigate cellular mechanisms involved in peritoneal tumor establishment and to evaluate clinical outcomes and complications related to CRS and HIPEC.<br/><br/>Methods: This thesis comprises four studies. One preclinical study used an experimental murine model to examine chemokine signaling and integrin-mediated adhesion in PC following surgical trauma using functional assays, in vivo experiments, and flow cytometry. Three clinical studies used retrospective institutional cohorts and population-based registry data to evaluate oncological outcomes, learning curve, postoperative complications, and preventive strategies.<br/><br/>Results: Experimental studies demonstrated that CXCR2 and αV integrin signaling promote peritoneal tumor adhesion and metastasis after surgical trauma. Clinically, CRS and HIPEC were implemented in a medium-volume center with outcomes comparable to high-volume institutions. Prophylactic sodium thiosulfate (ST) was associated with reduced incidence and severity of acute kidney injury (AKI) following Oxaliplatin-based HIPEC. Adjuvant chemotherapy did not reduce the risk of metachronous peritoneal metastases in patients with radically resected nodenegative T4 colon cancer.<br/><br/>Conclusions: Peritoneal dissemination of CRC is driven by defined cellular mechanisms and is influenced by surgical intervention. CRS and HIPEC can be implemented in a medium-volume center with outcomes comparable to highvolume institutions, without increased morbidity. Prophylactic ST reduces AKI after Oxaliplatin-based HIPEC. Adjuvant chemotherapy does not prevent metachronous peritoneal metastases after radical resection of node-negative T4 colon cancer.}},
author = {{Algethami, Nader}},
isbn = {{978-91-8021-831-3}},
issn = {{1652-8220}},
keywords = {{cytoreductive surgery; Hyperthermic intraperiotneal chemotherapy; peritoneal carcinomatosis; CXCR2; Chemokine; learning curve; postoperative complications; acute kidney injury; sodium thiosulfate; adjuvant chemotherapy; colon cancer}},
language = {{eng}},
number = {{2026:33}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Cellular Response and Clinical Aspects of Peritoneal Carcinomatosis for Colorectal Cancer Patients}},
url = {{https://lup.lub.lu.se/search/files/242664389/Avhandling_Nader_Algethami_LUCRIS.pdf}},
year = {{2026}},
}