Intraperitoneal cytokine level in patients with peritoneal surface malignancies. A study of the RENAPE (French Network for Rare Peritoneal Malignancies)

Our plain-English summary of Intraperitoneal cytokine level in patients with peritoneal surface malignancies. A study of the RENAPE (French Network for Rare Peritoneal Malignancies), by V. Vlaeminck-Guillem, J. Bienvenu, S. Isaac, et al (Annals of Surgical Oncology, 2013).

The study

• Authors: V. Vlaeminck-Guillem, J. Bienvenu, S. Isaac, B. Grangier, F. Golfier, G. Passot, N. Bakrin, C. Rodriguez-Lafrasse, F.N. Gilly, O. Glehen
• Journal: Annals of Surgical Oncology
• Published: 2013;20(8):2655-62
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Prognosis of peritoneal surface malignancies is influenced by the adequacy of surgical and chemotherapeutic treatment and by tumor spread at the time of diagnosis. By promoting morphological changes in the mesothelium, inflammatory cytokines reflect tumor biology and could be evaluated as biomarkers. Our objective was to evaluate intraperitoneal levels of IL-6, IL-8, IL-10, TNF-alpha, and sICAM in patients with pseudomyxoma peritonei and peritoneal mesothelioma.

Methods: Serum and peritoneal fluid samples were prospectively collected in patients managed for peritoneal surface malignancies including pseudomyxoma peritonei (PMP), mesotheliomas, and other rare primitive peritoneal cancers (cancer group) and patients who underwent intraperitoneal laparoscopic surgical procedures for benign diseases (noncancer group). Samples were analyzed for IL-6, IL-8, IL-10, TNF-alpha, and sICAM concentrations. Correlations were assessed with tumor spread related clinical scores.

Results: In both patient groups, intraperitoneal cytokine levels were higher than serum levels. Cancer patients had significantly higher intraperitoneal cytokine levels than noncancer patients. Peritoneal levels tended to increase in cancer patients with free tumor cells in peritoneal fluid. They were significantly higher in patients with tumor implants ≥2 cm and/or patients with peritoneal carcinomatosis index (PCI) >19. Furthermore, patients with malignant pseudomyxoma peritonei (grades II and III) had higher levels than patients with nonmalignant disease (grade I).

Conclusions: Assessment of intraperitoneal IL-6, IL-8, IL-10, TNF-alpha, and sICAM levels can be performed in patients with peritoneal surface malignancies. They can be considered as both diagnostic and prognostic biomarkers that could be used as useful adjuncts for therapeutic decision making.

In plain English

This French study measured five inflammation-related proteins (IL-6, IL-8, IL-10, TNF-alpha and sICAM-1) in blood and in fluid from the abdominal cavity (peritoneal fluid), both collected during surgery. It included 70 cancer patients: 46 with pseudomyxoma peritonei, 19 with peritoneal mesothelioma, 4 with secondary peritoneal carcinomatosis and 1 with peritoneal sarcomatosis. It also included 19 patients operated on for benign conditions. The article does not discuss asbestos. Four of the five proteins had significantly higher average levels in peritoneal fluid than in blood; sICAM-1 did not. In peritoneal fluid, all five proteins had higher median levels in cancer patients than in non-cancer patients. For mesothelioma patients alone, the difference was significant only for IL-10, IL-6 and sICAM-1. Among cancer patients, levels were significantly higher in those with more extensive disease or more tumor left after surgery. The authors concluded that these levels could be indicative of disease aggressiveness, but said larger studies and survival studies are needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective biomarker study comparing peritoneal fluid and blood protein levels in cancer patients with those in non-cancer surgical patients, and relating levels to measures of disease extent
• Who was studied: 89 patients treated at hospitals in Lyon, France (dates not stated): 46 with pseudomyxoma peritonei, 19 with peritoneal mesothelioma (15 epithelioid, 2 cystic, 2 papillary), 4 with secondary peritoneal carcinomatosis, 1 with primitive peritoneal sarcomatosis, and 19 non-cancer control patients operated on for benign conditions such as endometriosis, appendicitis, ovarian cyst or infertility; 59 women and 30 men
• Exposure: No asbestos or other environmental or occupational exposure was studied. The measured variables were levels of IL-6, IL-8, IL-10, TNF-alpha and sICAM-1 in serum and peritoneal fluid.
• Main results:
  • In all patients, each protein except sICAM-1 had a significantly higher average level in peritoneal fluid than in blood
  • In blood, levels did not differ significantly between the 70 cancer patients and the 19 non-cancer patients, except IL-6, which was higher in cancer patients
  • In peritoneal fluid, all five proteins had higher median levels in the 70 cancer patients than in the 19 non-cancer patients
  • Compared with non-cancer patients, the 19 peritoneal mesothelioma patients had significantly higher peritoneal fluid levels only for IL-10, IL-6 and sICAM-1. For pseudomyxoma peritonei patients, the differences were significant for all proteins.
  • Protein levels did not differ between pseudomyxoma peritonei patients and mesothelioma patients
  • The 15 patients with epithelioid peritoneal mesothelioma tended to have higher peritoneal fluid levels than the 4 with other types. The difference was significant only for TNF-alpha.
  • Of 67 cancer patients with fluid cytology available, 30 had free tumor cells in peritoneal fluid. Their median levels trended higher, significantly only for TNF-alpha (median 23 vs 13 in the 37 without tumor cells, p = .019).
  • Cancer patients with tumor implants of 2 cm or larger (46 patients) had significantly higher median peritoneal fluid levels than those with smaller implants
  • Among 60 cancer patients with a peritoneal carcinomatosis index (PCI) available, all median peritoneal fluid levels were significantly higher in the 30 with PCI above 19 than in the 30 with PCI of 19 or less. For example, median IL-6 was 3,913 vs 283 (units not stated in the text).
  • The 26 patients with grade II or III pseudomyxoma peritonei had significantly higher median peritoneal fluid levels than the 20 grade I patients
  • The 34 cancer patients with substantial residual tumor after surgery (CC-2 or CC-3) had significantly higher median peritoneal fluid levels than the 31 with CC-0 or CC-1 (per Table 2)
  • Among pseudomyxoma peritonei patients, those with no or only minor prior surgery (prior surgical score 0, n = 27) had significantly higher median peritoneal IL-10 than those with prior surgical score of 1 or more (n = 19)
• The authors' conclusion: The authors concluded that these proteins can be readily measured in the peritoneal fluid of patients with pseudomyxoma peritonei or peritoneal mesothelioma, that levels were higher in cancer patients than in non-cancer controls, and that peritoneal levels could be indicative of disease aggressiveness. They said survival studies are needed to assess whether the levels could be used in treatment decisions.
• Limitations the authors state:
  • The authors stated that larger studies are needed to establish whether peritoneal cytokine levels indicate disease aggressiveness
  • The authors stated that survival studies are still needed before the levels could be used for treatment decision making

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Cytokine, Prognosis, Mesothelium, Biomarker, Peritoneal Mesothelioma, Mesothelioma.

Related studies

• Postoperative outcomes of laparoscopic vs open cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of peritoneal surface malignancies — G. Passot, N. Bakrin, et al. (2014)
• What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: A 25-year experience with 1,125 procedures — G. Passot, D. Vaudoyer, et al. (2016)
• Quality of life after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: a prospective study of 216 patients — G. Passot, N. Bakrin, et al. (2014)
• Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis: the Danish experience — L.H. Iversen, P.C. Rasmussen, et al. (2013)
• Intraperitoneal chemotherapy for peritoneal surface malignancy: experience with 1,000 patients — E.A. Levine, J.H. Stewart, et al. (2014)
• Risk of definitive stoma after surgery for peritoneal malignancy in 958 patients: comparative study between complete cytoreductive surgery and maximal tumor debulking — S. Riss, K. Chandrakumaran, et al. (2015)

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