Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment

Our plain-English summary of Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment, by I. Opitz, D. Lardinois, S. Arni, et al (European Journal of Cardio-thoracic Surgery, 2007).

The study

• Authors: I. Opitz, D. Lardinois, S. Arni, S. Hillinger, P. Vogt, B. Odermatt, V. Rousson, W. Weder
• Journal: European Journal of Cardio-thoracic Surgery
• Published: 2007;31(5):773-8
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Local recurrence remains a major problem in the treatment of malignant pleural mesothelioma. The aim of the underlying study was to establish a standardised local recurrence model in rats which enables to study different intrapleural therapies.

Materials And Methods: Fifty microlitre containing 1 x 10(6) cells of a syngeneic rat malignant mesothelioma cell line (II-45), established from mesothelioma in Fischer 344 rats exposed to asbestos, were inoculated subpleurally via a left-sided thoracotomy. Tumour size was assessed 6 days later and the tumour nodule completely resected. Evaluation of recurrence at the resection site was performed after 10 days (n=6) and 6 days (n=6). The recurrent nodule was histopathologically confirmed. In a second experiment, this new recurrence model was evaluated for the effect of intrapleural therapy with different agents: 4 ml of cisplatin-solution (100mg(2)/kg BW), cisplatin combined with the fibrin-based sealant Vivostat, 4 ml taurolidine 2%, repeated injection of 1 microg of the chemokine CCL-19 at the tumour site and 4 ml povidone-iodine in a dilution 1:10. In a control group, the chest cavity was filled with 4 ml 0.9% NaCl. The primary endpoint was the extent of tumour recurrence.

Results: Six days after inoculation, all animals presented a standardised tumour nodule at the injection site of a mean diameter of 5.1 (+/-0.8)mm. Evaluation of the recurrence after 10 days showed a relapse directly at the resection site, but additional tumour nodules on the ipsi- and contralateral chest wall were found and histologically confirmed. The animals that were sacrificed 6 days after resection of the tumour nodule showed a recurrence only at the resection site with no macroscopic or microscopic evidence of other tumour. Resection of the tumour nodule combined with intrapleural application of the different agents lead to clear reduction of recurrence. The strongest effect was observed after intrapleural application of cisplatin-Vivostat with significant decrease of the longest, widest and thickest diameter of the recurrence.

Conclusions: With this new recurrence model for investigation of malignant pleural mesothelioma in rats, we were able to investigate new intrapleural therapies after pneumonectomy. The intrapleural application of cisplatin-Vivostat significantly reduced the extent of local recurrence.

In plain English

This animal experiment, done at the University Hospital Zurich, aimed to build a rat model of malignant pleural mesothelioma returning after surgery. The authors injected male Fischer 344 rats under the chest lining with a rat mesothelioma cell line grown from peritoneal mesothelioma in asbestos-exposed rats. The article does not name a fiber type. After 6 days every rat had a nodule averaging 5.1 mm across, which was removed. Rats examined 10 days later had regrowth at the removal site plus nodules on both chest walls. Those examined after 6 days had regrowth only at the removal site. In a second experiment, the nodule and left lung were removed and the chest was filled with a treatment or salt solution (control); CCL-19, a chemokine, was instead injected at the removal site, then again on days 3 and 5. Tumour returned in all animals. Cisplatin combined with a fibrin sealant (Vivostat) gave the largest reduction in regrowth size, and cisplatin alone reduced thickness and length. Reductions with taurolidine, povidone-iodine and CCL-19 were not statistically significant. The authors said the povidone-iodine results may not be representative.

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: Animal experiment: development of a rat model of local recurrence of malignant pleural mesothelioma, followed by a randomised comparison of intrapleural treatments after tumour resection and pneumonectomy
• Who was studied: Male Fischer 344 rats at the University Hospital Zurich. In the model-building part, 6 rats were examined 10 days and 6 rats 6 days after tumour resection. In the treatment part, the groups were: control n = 6, cisplatin-Vivostat n = 7, cisplatin solution n = 7, taurolidine n = 7, CCL-19 n = 7, povidone-iodine n = 6, plus 2 rats given Vivostat alone. Two animals died around the time of surgery.
• Exposure: Rats were not exposed to asbestos in this study. They were injected with a rat mesothelioma cell line (II-45) originally cultured from experimental asbestos-exposed peritoneal mesothelioma in rats; no fiber type is named. Treatments given after surgery were cisplatin solution, cisplatin with the fibrin sealant Vivostat, 2% taurolidine, diluted povidone-iodine (PVP-I) or 0.9% sodium chloride (control), each filling the chest cavity. The chemokine CCL-19 was instead injected at the resection site, with repeat injections through the chest wall on days 3 and 5.
• Main results:
  • All rats in the model-building part had a tumour nodule at the injection site 6 days after inoculation, with a mean diameter of 5.1 (0.8) mm.
  • In rats examined 10 days after resection, tumour recurred at the resection site and further nodules were found on the same-side and opposite-side chest wall.
  • In rats examined 6 days after resection, recurrence was seen only at the resection site.
  • In the treatment experiment, tumour recurred at the resection site in all animals.
  • Mean width of recurrence was 15.5 (SD 1.8) in the control group and 4.86 (SD 1.68) in the cisplatin-Vivostat group. Mean length was 25.3 (6.3) versus 13.9 (3.9). Mean thickness was 5.7 (2.7) versus 1.61. The ANOVA P-values across all groups were 0.006 for length, 0.0001 for width and 0.001 for thickness. Units are not printed in the table. The authors reported that cisplatin-Vivostat gave the strongest and most significant reduction in all three dimensions.
  • Cisplatin solution had a significant effect on the thickness and length of the recurrence.
  • In the taurolidine group, only tumour length showed a trend toward a significant effect (P = 0.06).
  • In the PVP-I and CCL-19 groups, recurrence size was reduced, but the reduction was not statistically significant.
  • Necrosis (dead tumour tissue) was found in all tumours of the cisplatin-Vivostat and cisplatin-solution animals, in 6 of 7 taurolidine animals, and in 50% of animals in the other groups.
  • IL-6 levels in stimulated spleen cell cultures were significantly lower in the treatment groups than in the control group (P = 0.03). The authors found no trends in cytokines measured in tumour tissue.
• The authors' conclusion: The authors concluded that they had established a local recurrence model of malignant pleural mesothelioma in immune-competent rats. They also concluded that intrapleural cisplatin combined with the fibrin sealant Vivostat caused the strongest and most significant reduction of recurrence in length, width and thickness.
• Limitations the authors state:
  • In the povidone-iodine group, the pathologist had difficulty telling tumour apart from neighbouring inflammatory tissue, so the data for this group may not be representative.
  • Attempts to stain the fluorescent dye used to label tumour cells failed.
  • The tumour biopsy specimens were probably too small to measure cytokine production in tumour tissue.
  • The lack of a significant CCL-19 effect may reflect the use of the human form of the chemokine in rats, or an inaccurate injection technique.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Malignant Mesothelioma, Mesothelioma, Thoracotomy, Cisplatin, Pneumonectomy.

Related studies

• Bioluminescence imaging for in vivo monitoring of local recurrence mesothelioma model — Y. Shi, A. Hollenstein, et al. (2011)
• Taurolidine and oxidative stress: a rationale for local treatment of mesothelioma — N. Aceto, P. Bertino, et al. (2009)
• Combined hyaluronate-based films loaded with pemetrexed and cisplatin for the treatment of malignant pleural mesothelioma: Preliminary evaluation in an orthotopic tumor recurrence model — F. Sonvico, S. Barbieri, et al. (2018)
• Percutaneous Cryoablation for the Treatment of Recurrent Malignant Pleural Mesothelioma: Safety, Early-Term Efficacy, and Predictors of Local Recurrence — F. Abtin, M.T. Quirk, et al. (2017)
• Recurrence of malignant pleural mesothelioma at the resection borders--local or distant recurrence? — S. Bölükbas, M. Eberlein, et al. (2013)
• Recurrence of malignant pleural mesothelioma at the resection borders--local or distant recurrence? — D. Gomez, A. Tsao, et al. (2013)

Browse more research in European Journal of Cardio-thoracic Surgery, or return to medical research.