Peritoneal carcinomatosis from colorectal cancer: HIPEC?

Confuorto, G; Giuliano, María Elena; Grimaldi, A.; Viviano, Charles J.

doi:10.1016/j.suronc.2007.10.026

Cited by 23 publications

(19 citation statements)

References 23 publications

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“…Colorectal peritoneal carcinomatosis (CPC), which affects approximately 10% of colorectal cancer patients, is one manifestation of metastatic colorectal cancer (2, 3). Standard treatments involve cytoreductive surgery and perioperative chemotherapy (4).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Promotes Synergy between Mitomycin C and Bortezomib through a Coordinated Process of Bcl-xL Phosphorylation and Mitochondrial Translocation of p53

Song

Dilly

Choudry

et al. 2015

Molecular Cancer Research

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Colorectal peritoneal carcinomatosis (CPC) exhibits severe tumor hypoxia, leading to drug resistance and disease aggressiveness. This study demonstrates that the combination of the chemotherapeutic agent mitomycin C with the proteasome inhibitor bortezomib induced synergistic cytotoxicity and apoptosis, which was even more effective under hypoxia in colorectal cancer cells. The combination of mitomycin C and bortezomib at sub-lethal doses induced activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase and resulted in Bcl-xL phosphorylation at Serine 62, leading to dissociation of Bcl-xL from pro-apoptotic Bak. Interestingly, the intracellular level of p53 became elevated and p53 translocated to the mitochondria during the combinatorial treatment, in particular under hypoxia. The coordinated action of Bcl-xL phosphorylation and p53 translocation to the mitochondria resulted in conformational activation of Bak oligomerization, facilitating cytochrome c release and apoptosis induction. In addition, the combinatorial treatment with mitomycin C and bortezomib significantly inhibited intraperitoneal tumor growth in LS174T cells and increased apoptosis, especially under hypoxic conditions in vivo. This study provides a preclinical rationale for the use of combination therapies for CPC patients. Implications The combination of a chemotherapy agent and proteasome inhibitor at sub-lethal doses induced synergistic apoptosis, in particular under hypoxia, in vitro and in vivo through coordinated action of Bcl-xL and p53 on Bak activation.

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Section: Introductionmentioning

confidence: 99%

Hypoxia Promotes Synergy between Mitomycin C and Bortezomib through a Coordinated Process of Bcl-xL Phosphorylation and Mitochondrial Translocation of p53

Song

Dilly

Choudry

et al. 2015

Molecular Cancer Research

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“…However, the results of multivariate analyses on the abovementioned clinicopathologic factors were reported in 5 publications; in 4 of these, the extent of disease [measured by Peritoneal Cancer Index (PCI)] and the completeness of resection were the factors most related to treatment success and survival [4] . Patients with localization in six or seven regions of the abdomen had a poor prognosis, with a median survival of 5.4 mo vs 29 mo in those with a lower number of regions affected [7] . In a recent retrospective study, in 70 patients, da Silva and Sugarbaker demonstrated, by univariate analysis, that the patients with a PCI < 20 had a median survival of 41 mo compared with 16 mo for patients with PCI > 20 (P = 0.004) [29] .…”

Section: Survival After Crs and Hipecmentioning

confidence: 94%

“…The PC occurs by a sequence of events: the spreading of cancer cells in the peritoneal cavity, their adhesion to the mesothelial surface and the invasion of the subperitoneal space for proliferation and vascular neogenesis [7] . The high incidence of tumour implantation on the peritoneal surface in CRC can occur by intraperitoneal tumour emboli as result of serosal penetration, or can be the consequence of surgical management through leakage of the malignant cells from the lymphatic vessels or through their dissemination due to tumour trauma as result of dissection, with subsequent fibrin entrapment and tumour promotion of the entrapped cells [8] .…”

Section: Natural History Of Peritoneal Carcinomatosismentioning

confidence: 99%

Peritoneal carcinomatosis of colorectal origin

Macrì

Saladino²,

Bartolo³

et al. 2010

WJGO

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Peritoneal carcinomatosis is, after liver metastases, the second most frequent cause of death in colorectal cancer patients and at the present time, is commonly inserted and treated as a stage Ⅳ tumour. Because there is no published data that outlines the impact of new therapeutic regimens on survival of patients with peritoneal surface diffusion, the story of carcinomatosis can be rewritten in light of a new aggressive approach based on the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Also if these treatment perhaps allow to obtain better results than standard therapies, we suggest, that a large prospective randomised control trial is needed to compare long-term and progression-free survival under the best available systemic therapy with or without cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

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“…Pathogenesis of PC involves tumor cells detaching from the primary tumor mass that has invaded the serosa, and gaining access to the peritoneal cavity, subsequently attaching to the peritoneal surface with subperitoneal invasion for proliferation and angiogenesis 89 . Other means of peritoneal dissemination include iatrogenic or spontaneous perforation of the primary cancer 10 or embolism from transected lymphatics and blood vessels during the course of surgical resection 11 .…”

Section: Introductionmentioning

confidence: 99%

Management of Peritoneal Carcinomatosis From Colorectal Cancer

Ihemelandu

Shen

Stewart

et al. 2011

Seminars in Oncology

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The management of peritoneal carcinomatosis from colorectal cancer is evolving. The introduction of new chemotherapeutic and biologic agents has certainly improved the outlook for many patients with metastatic colorectal cancer. Traditionally, patients with limited hepatic or pulmonary metastases were the only candidates for metastasectomy. However, patients with metastasis localized to the peritoneum have been shown to be candidates for metastasectomy with improved clinical outcomes. Cytoreductive surgery with the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) in this cohort of patients offers the only chance for long-term survival. Complete cytoreduction in combination with HIPEC for peritoneal surface disease has been demonstrated to produce survival outcomes similar to liver resection for hepatic metastases. This review will examine recent evidence pertaining to the evolving surgical oncology paradigm for management of colorectal peritoneal carcinomatosis.

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Peritoneal carcinomatosis from colorectal cancer: HIPEC?

Cited by 23 publications

References 23 publications

Hypoxia Promotes Synergy between Mitomycin C and Bortezomib through a Coordinated Process of Bcl-xL Phosphorylation and Mitochondrial Translocation of p53

Hypoxia Promotes Synergy between Mitomycin C and Bortezomib through a Coordinated Process of Bcl-xL Phosphorylation and Mitochondrial Translocation of p53

Peritoneal carcinomatosis of colorectal origin

Management of Peritoneal Carcinomatosis From Colorectal Cancer

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