Abstract
Background: Cytoreductive surgery (CRS) in combination with
hyperthermic intraperitoneal chemotherapy (HIPEC) is an option in
advanced peritoneal sarcomatosis. Nevertheless, CRS and HIPEC are not
successful in all patients. An enhancement of HIPEC using photodynamic
therapy might be beneficial. Therefore, a combination of the
photosensitizer Hypericin (HYP) with HIPEC was evaluated in an animal
model.
Procedure: An established HIPEC animal model for
rhabdomyosarcoma (NOD/LtSz-scid IL2Rγnullmice, n=80) was used. All
groups received HYP (100 µg/200 µl) intraperitoneally with and without
cisplatin-based (30 or 60 mg/m2) HIPEC (37 or 42 °C,
for 60 min) (five groups, each n=16). Tumor dissemination was documented
visually and by using HYP-based fluorescence guidance. HYP-based
photodynamic therapy (PDT) of the tumor was performed. Finally, tissue
samples were evaluated regarding proliferation (Ki-67) and apoptosis
(TUNEL).
Results: HYP uptake even in smallest tumor nodes
(< 1 mm) was found. HYP-based fluorescence guidance allowed a
better tumor detection in comparison to visual inspection.
Immunohistochemistry revealed HYP penetration across the tumor surface.
HYP-based PDT without HIPEC induced marginal apoptotic effects at the
tumor surface. Combining HYP with HIPEC revealed cisplatin concentration
dependent decrease in proliferation capacity and induction of apoptosis
across determined cell layers of the tumor surfaces.
Conclusion: HYP as fluorescent photosensitizer offers an
intraoperative diagnostic advantage detecting intraperitoneal tumor
dissemination. The combination of HYP and cisplatin-based HIPEC was
feasible in vivo showing enhanced effects on tumor proliferation
and apoptosis induction across the tumor surface. Further studies
combining HYP and HIPEC will follow to establish a clinical application.