Access the full text.
Sign up today, get DeepDyve free for 14 days.
Loading next page...
/lp/hindawi-publishing-corporation/increased-tissue-penetration-of-doxorubicin-in-pressurized-0ReUVKD1gt
References
References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.
- Publisher
- Hindawi Publishing Corporation
- Copyright
- Copyright © 2019 Veria Khosrawipour et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- ISSN
- 2090-1402
- eISSN
- 2090-1410
- DOI
- 10.1155/2019/6185313
- Publisher site
- See Article on Publisher Site
Abstract
Hindawi International Journal of Surgical Oncology Volume 2019, Article ID 6185313, 6 pages https://doi.org/10.1155/2019/6185313 Research Article Increased Tissue Penetration of Doxorubicin in Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) after High-Intensity Ultrasound (HIUS) 1 2 1 1,3 Veria Khosrawipour , So¨ren Reinhard, Alice Martino , Tanja Khosrawipour, 4 5 Mohamed Arafkas, and Agata Mikolajczyk Division of Colorectal Surgery, Department of Surgery, University of California Irvine (UCI), Irvine, CA, USA Department of Bioengineering, University of California, Berkeley (UC Berkeley), Oakland, CA, USA Department of Surgery, University-Hospital Du¨sseldorf, Du¨sseldorf, North-Rhein Westfalia, Germany Department of Plastic Surgery, Ortho-Klinik Dortmund, Dortmund, North-Rhein Westfalia, Germany Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Lower Silesia, Poland Correspondence should be addressed to Alice Martino; alicemm1@hs.uci.edu Received 26 September 2019; Accepted 23 November 2019; Published 12 December 2019 Academic Editor: C.H. Yip Copyright © 2019 Veria Khosrawipour et al. +is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. High-intensity ultrasound (HIUS) has been studied for the past two decades as a new therapeutic option for solid tumor direct treatment and a method for better chemotherapy delivery and perfusion. +is treatment approach has not been tested to our knowledge in peritoneal metastatic therapy, where limited tissue penetration of intraperitoneal chemotherapy has been a main problem. Both liquid instillations and pressurized aerosols are affected by this limitation. +is study was performed to evaluate whether HIUS improves chemotherapy penetration rates. Methods. High-intensity ultrasound (HIUS) was applied for 0, 5, 30, 60, 120, and 300 seconds on the peritoneal tissue samples from fresh postmortem swine. Samples were then treated with doxorubicin via pressurized intraperitoneal aerosol chemotherapy (PIPAC) under 12 mmHg and 37 C temperature. Tissue penetration of doxorubicin was measured using fluorescence microscopy on frozen thin sections. Results. Macroscopic structural changes, identified by swelling of the superficial layer of the peritoneal surface, were observed after 120 seconds of HIUS. Maximum doxorubicin penetration was significantly higher in peritoneum treated with HIUS for 300 seconds, with a depth of 962.88±161.4 μm (p < 0.05). Samples without HIUS had a penetration depth of 252.25±60.41. Tissue penetration was sig- nificantly increased with longer HIUS duration, with up to 3.8-fold increased penetration after 300 sec of HIUS treatment. Conclusion. Our data indicate that HIUS may be used as a method to prepare the peritoneal tissue for intraperitoneal che- motherapy. Higher tissue penetration rates can be achieved without increasing chemotherapy concentrations and preventing structural damage to tissue using short time intervals. More studies need to be performed to analyze the effect of HIUS in combination with intraperitoneal chemotherapy. Various approaches have been made to improve the avail- 1. Introduction ability of chemotherapy in these tumor nodules. Peritoneal metastasis (PM) is a commonly seen manifestation For example, it has been shown that hyperthermia [3] of advanced gastrointestinal and gynecological cancers. It is and intraperitoneal pressure [4] increase drug penetration known that the antitumor effect of intraperitoneal chemo- and efficiency. +ese concepts have already led to new therapy (IPC) is strongly limited by penetration of chemo- therapies like hyperthermic intraperitoneal chemotherapy therapy drugs well below 1mm into peritoneal nodules [1, 2]. (HIPEC) combined with cytoreductive surgery [5]. +e 2 International Journal of Surgical Oncology application of pressure has been proposed and was ulti- was used. In the center of the top cover of the plastic box, a mately applied through pressurized intraperitoneal aerosol 5mm trocar (Kii Balloon Blunt Tip System, Applied chemotherapy (PIPAC) in the treatment of more advanced Medical, Rancho Santa Margarita, CA, USA) was placed.+e peritoneal metastasis [6, 7]. Clinical as well as experimental nozzle of the microcatheter (MC, Olympus, PW-205V studies have also tested irradiation [8–10] and new drug Olympus Surgical Technologies Europe, Hamburg, Ger- formulas [11–13] as alternate methods of increasing che- many) was introduced into the trocar. +e plastic box was motherapy penetration. Despite several attempts to improve kept at a constant temperature of 27 C during the whole penetration rates, these studies have had only limited suc- procedure. Fresh tissue specimens of peritoneum (German cess. For example, application parameters in PIPAC that landrace pigs), each measuring 4.0 ×4.0 ×0.5cm, were may affect chemotherapeutic penetration depth, such as the placed at the center of the plastic box. +e distance between micropump position and dose of doxorubicin, have been the nozzle of the MC and the bottom of the plastic box was tested [14]. Although many of these aforementioned efforts 10cm. +e plastic box was then tightly sealed, and a constant have been made, penetration levels still were mostly de- CO capnoperitoneum of 12mmHg (Olympus UHI-3, scribed to be less than 500 μm [15–17]. Olympus medical life science and industrial divisions, +erefore, further methods for improved drug delivery Olympus Australia, Notting Hill, Australia) was maintained and increasing depth penetration are needed to be de- during the entire PIPAC procedure. 3mg of doxorubicin veloped. In this regard, high intensity ultrasound (HIUS) has were dissolved in 50ml NaCl 0.9% at 27 C and aerosolized. been a very promising method to potentially achieve this goal. HIUS has been investigated for over two decades in 2.3. Microscopic Analysis. After treatments, all tissue sam- solid tumor therapy with promising results in particular ples were rinsed with a sterile NaCl 0.9% solution in order to cases[18–20].Itisalready knownthatHIUS canimprovethe eliminate superficial chemotherapy and immediately frozen perfusion of chemotherapy agents in liver tumors and in liquid nitrogen. Cryosections (10 μm) were prepared from glioblastoma [21, 22]. HIUS systems provide unique ad- different areas of each specimen. Sections were mounted vantages of low invasiveness and absence of radiation. with a ProLong Gold Antifade Mountant (+ermo Fisher However, to our knowledge, its interaction in combi- Scientific) containing 1.5 μg/ml 4’,6-diamidino-2-phenyl- nation with any form of intraperitoneal chemotherapy on indole (DAPI) to stain nuclei. Penetration depth of doxo- the peritoneum has not been thoroughly investigated. It is rubicin was monitored using a Nikon Eclipse 80i known that HIUS enhances the delivery of doxorubicin in a fluorescence microscope (Nikon Instruments Europe B.V. preclinical model of solid pancreatic cancer [23]. We aimed Amsterdam, Netherlands).+edistance betweenthe luminal to evaluate its effect on the penetration depth of doxorubicin surface and the innermost positive staining for doxorubicin in a well-established model of fresh postmortem peritoneal accumulation was measured and reported in micrometers. tissue samples [17, 24]. 2.4. Statistical Analyses. Experiments were independently 2. Materials and Methods performed three times. A total of eight tissue sections per 2.1. High-Intensity Ultrasound. +e experiments were per- tissue sample were subject to doxorubicin penetration mea- formed on commercially available tissue samples; hence, no surement. Prism 7.0 software (GraphPad, La Jolla, CA, USA) approval of the Local Board on Animal Care was required. was utilized to analyze the data. One-way ANOVA with a multiple comparison test wasused for analyses ofindependent Fresh postmortem swine peritoneum was purchased (local pork supplier, Zerniki Wielkie) and cut into proportional groups. A significant p value was considered at p<0.05. sections. Samples were then placed into Petri dishes. and NaCl 0.9% was added until the peritoneal surface was 3. Results covered with 5mm of liquid. High-intensity ultrasound was 3.1. Ex Vivo Experiment. PIPAC and HIUS were applied applied with a metal pen to the center of the peritoneal tissue withoutcomplications.AfterapplyingHIUS, avisualcontrol using a sonicator (Bandelin Sonoplus, UW 2070). +e tip of of the sample was performed. No macroscopic damage of the the penwas held3mmfrom the tissue.Samples weredivided peritoneal surface was observed with shorter HIUS duration. into six groups which were treated for 0 seconds, 5 seconds, However, after 120 seconds, some whitening and swelling of 30 seconds, 60 seconds, 120 seconds, and 300 seconds, re- the peritoneum were noted. Doxorubicin was detected in spectively. Each treatment contained 0.3 seconds of active fluorescence microscopy in both groups. Microscopic and 0.7 seconds of passive interval, with 20kHz frequency, analysis of the different tissue specimens showed a sub- output power of 70W, and 50% of amplitude. stantial difference in the penetration depth of doxorubicin. Tissue penetration levels after HIUS were 361 μm±34.5 μm 2.2. Ex Vivo PIPAC Model. Samples and untreated controls at 5 seconds, 409 μm±69.7 μm at 30 seconds, were placed in a well-described ex vivo model and treated 598 μm±136.9 μm at 60 seconds, 725 μm±126.4 μm at 120 with PIPAC with doxorubicin (PFS , 2mg/ml, Pfizer seconds, and 962 μm±161.4 μm at 300 seconds. Controls Europe, Sandwich, United Kingdom, purity ≥98%). A without HIUS showed penetration levels with (A) commercially available hermetic sealable plastic box with a 252 μm±60.4 μm. Penetration increased significantly with total volume of 3.5 liters, representing the abdominal cavity, longer HIUS duration (A-F vs. controls, p<0.05) and International Journal of Surgical Oncology 3 reached a maximum in the sample (F). +e penetration Doxorubicin penetration aer different time durations of HIUS reached the 1mm level (F) and increased up to 3.8 folds to the control without HIUS (control vs. F, p<0.0001). ∗∗∗ ∗∗ +e differences between the penetration depths observed in this study summarized in Figures 1 and 2 display rep- ∗∗ resentative photos showing doxorubicin fluorescence in the analyzed tissue samples. 4. Discussion In spite of progress in chemotherapeutic regimens and new 0 sec 5 sec 30 sec 60 sec 120 sec 300 sec drug compositions, poor response to systemic and local treatment is observed in a considerable part of patients, Figure 1: Tissue penetration depth of doxorubicin in μm after HIUS treatment for 0, 5, 30, 60, 120, and 300sec ( p<0.01; mainly due to molecular mechanisms and limited drug ∗∗ ∗∗∗ p<0.001; p<0.0001). distribution in the tumor [1, 25]. Pressurized intraperitoneal and pressurized intraluminal aerosol chemotherapies have been introduced to improve the treatment of advanced, multiresistant surface malignancies by overcoming limitations in drug penetration through the use of pressure and microaerosol [26, 27]. However, attempts to further improve were only partially successful, as changes of treatment parameters have only modestly improved pene- tration rates [4, 14]. Adding irradiation and modifying ap- plication modes [10] did not improve performance either, as penetration levels were mostlylimited to the first few hundred microns. However, we know that increasing tissue penetra- tion enhances the antitumor effect with a higher local drug disposition [1]. In our study, we demonstrate the previously unrecognized potential of HIUS to enhance drug penetration to many folds in the peritoneal tissue. In the clinical setting, HIUS is being increasingly used as noninvasive treatment of both primary and metastatic tumors. Besides its effects described here, it has addi- tional antitumor effects including ablation and me- chanical disruption of cancer tissue [28, 29]. HIUS has already been shown to be useful in the treatment of uterine fibroids [30], various solid tumors of pancreas, (a) (b) liver, renal system, and prostate, and breast cancer [31–34]. So far, there have been no or few studies for Figure 2: Microscopic analysis of the penetration depth of potential use in peritoneal metastases (PM). By im- doxorubicin into fresh peritoneal samples of German landrace pigs. proving tissue penetration, higher drug concentrations in Nuclei (blue) were stained with 4’,6-diamindino-2-phenylidole the tumor tissue could be reached without increasing the (DAPI). (a) In-tissue penetration of doxorubicin without HIUS. (b) drug dose, which is important to limit systemic side In-tissue penetration of doxorubicin after 300 seconds HIUS. effects of the chemotherapy. (ePIPAC) versus PIPAC alone did not show any tissue Other attempts to improve current PIPAC and IPC increase or any other change demonstrating the efficancy have been studied recently. One such attempt to improve of PIPAC by adding an electrostatic device. Additionally, overall results is synchronous intravenous chemotherapy. clinical studies could not detect any differences between Feasibility for this kind of bidirectional approach has been these two approaches in terms of biological effect [38]. demonstrated, and results on tumor regression and sur- Data on electrostatic augmentation is scarce, and the vival have been promising [35]. However, it is unclear potential of electrostatic PIPAC is unknown. Analyzing whether this effect is predominantly that of PIPAC or the effects of electrostatic precipitation combined with the rather one of the intravenous chemotherapies. Studies applied aerosol itself is quite a challenge, and while on- indicate that this might be an effect of PIPAC [36], while going studies present new locations and various appli- the effect of the additional intravenous chemotherapy is cations for chemoaerosol [39, 40], there is an ongoing unknown. effort to understand the applied chemoaerosol itself Another attempt to improve PIPAC was the in- [39, 41]. troduction of electrostatic precipitation as an additional +e application of heat in IPC is well studied. Heat has feature to the procedure. A recent study from Giger-Pabst shown to increase cytotoxicity and has therefore been an et al. [37] analyzing the effect of electrostatic PIPAC Doxorubicin penetration in µm 4 International Journal of Surgical Oncology integral part in HIPEC [42]. However, the application of was involved in study design, laboratory analysis, data ac- heat in PIPAC is a technical challenge because heat would quisition, and manuscript drafting. MA was involved in data have to be distributed through the applied gaseous capno- interpretation and critical revision for important intellectual peritoneum. +erefore, it remains unclear if heat has a role content of the manuscript. AM was responsible for super- in PIPAC. Despite these limitations, concepts based on basic vision of the study, drafting, and critical revision for im- physical principles like heat, electrostatic effects, changing portant intellectual content of the manuscript. physical properties of applied substances [39], or mechanic alteration [43] of the biological surface have gained more Acknowledgments interest recently as they seem to have more potential than initially expected. +is study was funded by Institutional Funds. Our data indicate that HIUS plus PIPAC can overcome the 1mm barrier on the peritoneum, which is a very References promising result. HIUS resulted in better penetration of doxorubicin into swine peritoneum samples from 1.4 to 3.8 [1] R. L. Dedrick, C. E. Myers, P. M. Bungay, and V. T. DeVita Jr., folds depending on the duration of HIUS application (5sec “Pharmacokinetic rational for the peritoneal drug adminis- to 300sec). +ese findings require further studies in this field tration in the treatment of ovarian cancer,” Cancer Treatment and ideas for a possible clinical approach to the application Reviews, vol. 6, pp. 1–11, 1978. of HIUS in PM via PIPAC or via any other intraperitoneal [2] G. Los, P. H. Mutsaers, W. J. van der Vijgh, G. S. Baldew, chemotherapy. P. W. de Graaf, and J. G. McVie, “Direct diffusion of cis- diamminedichloroplatinum(II) in intraperitoneal rat tumor after intraperitoneal chemotherapy: a comparison with sys- 5. Conclusions temic chemotherapy,” Cancer Research, vol. 49, pp. 3380– Our data indicate that pretreatment of tissue samples with 3384, 1989. [3] W. F. Morano, M. Khalili, D. S. Chi, W. B. Bowne, and HIUS enhances doxorubicin penetration after the PIPAC J. Esquivel, “Clinical studies in CRS and HIPEC: trials, procedure. Depth of penetration increases with longer du- tribulations, and future directions-a systematic review,” ration of HIUS. +is can be a new promising approach in Journal of Surgical Oncology, vol. 117, no. 2, pp. 245–259, IPC for better outcomes. Further research needs to be conducted for translation of this ex vivo method into clinical [4] V. Khosrawipour, D. Diaz-Carballo, A. H. Acikelli et al., practice. “Cytotoxic effect of different treatment parameters in pres- surized intraperitoneal aerosol chemotherapy (PIPAC) on the Abbreviations in vitro proliferation of human colonic cancer cells,” World Journal of Surgical Oncology, vol. 15, no. 1, p. 43, 2017. CO2: Carbon dioxide [5] R. Rajeev and K. K. Turaga, “Hyperthermic intraperitoneal CRS: Cytoreductive surgery chemotherapy and cytoreductive surgery in the management HIPEC: Hyperthermic intraperitoneal chemotherapy of peritoneal carcinomatosis,” Cancer Control, vol. 23, no. 1, HIUS: High-intensity ultrasounds pp. 36–46, 2016. IAP: Intra-abdominal pressure [6] V. Khosrawipour, T. Khosrawipour, D. Diaz-Carballo, IPC: Intraperitoneal chemotherapy E. Forster, ¨ J. Zieren, and U. Giger-Pabst, “Exploring the PM: Peritoneal metastasis spatial drug distribution pattern of pressurized in- traperitoneal aerosol chemotherapy (PIPAC),” Annals of PIPAC: Pressurized intraperitoneal aerosol chemotherapy Surgical Oncology, vol. 23, no. 4, pp. 1220–1224, 2016. ePIPAC: Electrostatic pressurized intraperitoneal aerosol [7] A. Bellendorf, V. Khosrawipour, T. Khosrawipour et al., chemotherapy “Scintigraphic peritoneography reveals a non-uniform MC: Microcatheter. 99mTc-pertechnetat aerosol distribution pattern for pres- surized intra-peritoneal aerosol chemotherapy (PIPAC) in a Data Availability swine model,” Surgical Endoscopy, vol. 32, no. 1, pp. 166–174, +e data used to support the findings of this study are [8] V. Khosrawipour, U. Giger-Pabst, T. Khosrawipour et al., available from the corresponding author on request. “Effect of irradiation on tissue penetration depth of doxo- rubicin after pressurized intra-peritoneal aerosol chemo- Conflicts of Interest therapy (PIPAC) in a novel ex-vivo model,” Journal of Cancer, vol. 7, no. 8, pp. 910–914, 2016. +e authors have no conflicts of interest or financial ties to [9] V. Khosrawipour, A. Bellendorf, C. Khosrawipour et al., disclose. “Irradiation does not increase the penetration depth of doxorubicin in normal tissue after pressurized intra-perito- Authors’ Contributions neal aerosol chemotherapy (PIPAC) in an ex vivo model,” In Vivo, vol. 30, no. 5, pp. 593–597, 2016. VK was involved in study design, laboratory analysis, and [10] V. Khosrawipour, T. Khosrawipour, Y. Hedayat-Pour et al., data acquisition. SR was responsible for study design, data “Effect of whole-abdominal irradiation on penetration depth analysis, and manuscript drafting. AM was responsible for of doxorubicin in normal tissue after pressurized in- study design, data acquisition, and manuscript drafting. TK traperitoneal aerosol chemotherapy (PIPAC) in a post- International Journal of Surgical Oncology 5 mortem swine model,” Anticancer Research, vol. 37, no. 4, in a preclinical model of pancreatic cancer,” Cancer Research, pp. 1677–1680, 2017. vol. 75, no. 18, pp. 3738–3746, 2015. [11] M. Robella, M. Vaira, M. Argenziano et al., “Exploring the use [24] A. Mikolajczyk, V. Khosrawipour, J. Schubert, H. Chaudhry, of pegylated liposomal doxorubicin (Caelyx ) as pressurized A. Pigazzi, and T. Khosrawipour, “Particle stability during pressurized intra-peritoneal aerosol chemotherapy (PIPAC),” intraperitoneal aerosol chemotherapy (PIPAC),” Frontiers in Anticancer Research, vol. 38, no. 8, pp. 4645–4649, 2018. Pharmacology, vol. 25, no. 10, p. 669, 2019. [25] P. Jacquet and P. H. Sugarbaker, “Peritoneal-plasma barrier,” [12] A. Mikolajczyk, V. Khosrawipour, J. Schubert et al., “Effect of Cancer Treatment and Research, vol. 82, pp. 53–63, 1996. liposomal doxorubicin in pressurized intra-peritoneal aerosol [26] A. Mikolajczyk, V. Khosrawipour, J. Schubert et al., “Feasi- chemotherapy (PIPAC),” Journal of Cancer, vol. 9, no. 23, bility and characteristics of pressurized aerosol chemotherapy pp. 4301–4305, 2018. (PAC) in the bladder as a therapeutical option in early-stage [13] J. Schubert, V. Khosrawipour, H. Chaudry et al., “Comparing urinary bladder cancer,” In Vivo, vol. 32, no. 6, pp.1369–1372, the cytotoxicity of taurolidine, mitomycin C and oxaliplatin on the proliferation of in-vitro colon carzinoma cells fol- [27] D. Gohler, ¨ V. Khosrawipour, T. Khosrawipour et al., lowing Pressurized Intra-peritoneal Aerosol Chemotherapy,” “Technical description of the microinjection pump (MIP) and World Journal of Surgical Oncology, vol. 17, no. 1, p. 93, 2019. granulometric characterization of the aerosol applied for [14] V. Khosrawipour, T. Khosrawipour, T. A. Falkenstein et al., pressurized intraperitoneal aerosol chemotherapy (PIPAC),” “Evaluating the effect of micropump position, internal Surgical Endoscopy, vol. 31, no. 4, pp. 1778–1784, 2017. pressure and doxorubicin dosage on efficacy of pressurized [28] R. D. Alkins and T. G. Mainprize, “High-intensity focused intra-peritoneal aerosol chemotherapy (PIPAC) in an ex vivo ultrasound ablation therapy of gliomas,” Progress in Neuro- model,” Anticancer Research, vol. 36, no. 9, pp. 4595–4600, logical Surgery, vol. 32, pp. 39–47, 2018. [29] E. Maloney and J. H. Hwang, “Emerging HIFU applications in [15] V. Khosrawipour, T. Khosrawipour, A. J. P. Kern et al., cancer therapy,” International Journal of Hyperthermia, “Distribution pattern and penetration depth of doxorubicin vol. 31, no. 3, pp. 302–309, 2015. after pressurized intraperitoneal aerosol chemotherapy [30] L. Zhang, W. Zhang, F. Orsi, W. Chen, and Z. Wang, “Ul- (PIPAC) in a postmortem swine model,” Journal of Cancer trasound-guided high intensity focused ultrasound for the Research and Clinical Oncology, vol. 142, no. 11, pp. 2275– treatment of gynaecological diseases: a review of safety and 2280, 2016. efficacy,” International Journal of Hyperthermia, vol. 31, no. 3, [16] T. Khosrawipour, D. Wu, A. Bellendorf et al., “Feasibility of pp. 280–284, 2015. single tumorspot treatment in peritoneal carcinomatosis via [31] B. D. De Senneville, C. Moonen, and M. Ries, “MRI-guided close range doxorubicin impaction in pressurized intra- HIFU methods for the ablation of liver and renal cancers,” peritoneal aerosol chemotherapy (PIPAC),” Journal of Clin- Advances in Experimental Medicine and Biology, vol. 880, ical & Experimental Oncology, vol. 6, no. 3, 2017. pp. 43–63, 2016. [17] V. Khosrawipour, A. Mikolajczyk, J. Schubert, and [32] L. Huang, Q. Chen, L. Yu, and D. Bai, “Pyropheophorbide-α T. Khosrawipour, “Pressurized intra-peritoneal aerosol che- methyl ester mediated photodynamic therapy induces apo- motherapy (PIPAC)viaEndoscopical microcatheter system,” ptosis and inhibits LPS-induced inflammation in RAW264.7 Anticancer Research, vol. 38, no. 6, pp. 3447–3452, 2018. macrophages,” Photodiagnosis and Photodynamic :erapy, [18] S. L. Giles, G. Imseeh, I. Rivens, G. R. ter Haar, A. Taylor, and vol. 25, p. 148156, 2019. N. M. deSouza, “MR guided high intensity focused ultrasound [33] L. G. Merckel, F. M. Knuttel, R. Deckers et al., “First clinical (MRgHIFU) for treating recurrent gynaecological tumours: a experience with a dedicated MRI-guided high-intensity fo- pilot feasibility study,” :e British Journal of Radiology, cused ultrasound systemfor breast cancerablation,” European vol. 92, no. 1098, Article ID 20181037, 2019. Radiology, vol. 26, no. 11, pp. 4037–4046, 2016. [19] C. An, X. Li, P. Liang et al., “Local tumor control of thor- [34] A. Mortezavi, J. Krauter, D. A. Gu et al., “Extensive histo- acoabdominal wall seeding tumor from hepatocellular car- logical sampling following focal therapy of clinically signifi- cinoma with ultrasound-guided interventional treatment: a cant prostate cancer with high-intensity focused ultrasound,” summarized study,” Journal of Cancer Research and :era- Journal of Urology, vol. 1, p. 101097, 2019. peutics, vol. 15, no. 2, pp. 404–414, 2019. [35] V. Khomyakov, A. Ryabov, A. Ivanov et al., “Bidirectional [20] A. Mikolajczyk, V. Khosrawipour, J. Kulas et al., “Release of chemotherapy in gastric cancer with peritoneal metastasis doxorubicin from its liposomal coating via high intensity combining intravenous XELOX with intraperitoneal che- ultrasound,” Molecular and Clinical Oncology, vol. 11, no. 5, motherapy with low-dose cisplatin and doxorubicin admin- pp. 483–487, 2019. istered as a pressurized aerosol: an open-label, phase-2 study [21] P. C. Lyon, L. F. Griffiths, J. Lee et al., “Clinical trial protocol (PIPAC-GA2),” Pleura Peritoneum, vol. 1, no. 3, pp. 159–166, for TARDOX: a phase I study to investigate the feasibility of targeted release of lyso-thermosensitive liposomal doxoru- [36] S. P. Somashekhar, K. R. Ashwin, C. A. Rauthan, and bicin (+ermoDox ) using focused ultrasound in patients K. C. Rohit, “Randomized control trial comparing quality of with liver tumours,” Journal of :erapeutic Ultrasound, vol. 2, life of patients with end-stage peritoneal metastasis treated no. 5, p. 28, 2017. with pressurized intraperitoneal aerosol chemotherapy [22] Z. Luo, K. Jin, Q. Pang et al., “On-demand drug release from (PIPAC) and intravenous chemotherapy,” Pleura Peritoneum, dual-targeting small nanoparticles triggered by high-intensity vol. 3, no. 3, p. 20180110, 2018. focused ultrasound enhanced glioblastoma-targeting ther- [37] U. Giger-Pabst, P. Bucur, S. Roger et al., “Comparison of apy,” ACS Applied Materials & Interfaces, vol. 9, no. 37, tissue and blood concentrations of oxaliplatin administrated pp. 31612–31625, 2017. by different modalities of intraperitoneal chemotherapy,” [23] T. Li, Y.-N. Wang, T. D. Khokhlova et al., “Pulsed high-in- Annals of Surgical Oncology, vol. 26, no. 13, pp. 4445–4451, tensity focused ultrasound enhances delivery of doxorubicin 2019. 6 International Journal of Surgical Oncology [38] M. Graversen, S. Detlefsen, S. B. Ellebaek, C. Fristrup, P. Pfeiffer, and M. B. Mortensen, “Pressurized intraperitoneal aerosol chemotherapy with one minute of electrostatic pre- cipitation (ePIPAC) is feasible, but the histological tumor response in peritoneal metastasis is insufficient,” European Journal of Surgical Oncology, 2019. [39] T. Khosrawipour, J. Schubert, J. Kulas et al., “Creating nanocrystallized chemotherapy: the differences in pressurized aerosol chemotherapy (PAC) via intracavitary (IAG) and extracavitary aerosol generation (EAG) regarding particle generation, morphology and structure,” Journal of Cancer, [40] V. Khosrawipour, A. Mikolajczyk, R. Paslawski et al., “In- trathoracic aerosol chemotheray via spray-catheter,” Molec- ular and Clinical Oncology, 2019. [41] T. Khosrawipour, J. Schubert, V. Khosrawipour et al., “Par- ticle stability and structure on the peritoneal surface in pressurized intra-peritoneal aerosol chemotherapy (PIPAC) analysed by electron microscopy: first evidence of a new physical concept for PIPAC,” Oncology Letters, vol. 17, no. 6, pp. 4921–4927, 2019. [42] S. Gonzalez-Moreno, ´ L. A. Gonzalez-Bay ´ on, ´ and G. Ortega- Perez, ´ “Hyperthermic intraperitoneal chemotherapy: ratio- nale and technique,” World Journal of Gastrointestinal On- cology, vol. 2, no. 2, pp. 68–75, 2010. [43] J. Schubert, T. Khosrawipour, A. Pigazzi et al., “Evaluation of cell-detaching effect of EDTA in combination with oxaliplatin for a possible application in HIPEC after cytoreductive sur- gery: a preliminary in-vitro study,” Current Pharmaceutical Design, vol. 25, 2019. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018
Journal
International Journal of Surgical Oncology – Hindawi Publishing Corporation
Published: Dec 12, 2019