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Intraperitoneal Chemotherapy for Peritoneal Metastases: Technical Innovations, Preclinical and Clinical...
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Intraperitoneal Chemotherapy for Peritoneal Metastases: Technical Innovations, Preclinical and Clinical Advances and Future Perspectives

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Survivorship and Quality of Life".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 13563

Special Issue Editors

Prof. Clemens B. Tempfer

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Guest Editor
Department of Gynecology and Obstetrics, Ruhr-Universität Bochum, Bochum, Germany and Comprehensive Cancer Center of the Ruhr-Universität Bochum (RUCCC), 44708 Bochum, Germany
Interests: endometrial cancer; ovarian cancer; intraperitoneal chemotherapy; cervical dysplasia
Special Issues, Collections and Topics in MDPI journals
Dr. Urs Giger-Pabst

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Guest Editor
Senior Consultant Surgeon Special Surgical Oncology and Peritonealcarcinomatosis Department of General-, Visceral- and Transplant Surgery, University Hospital Münster Albert-Schweitzer-Campus 1, Bldg. W1 48149, Münster, Germany.
Interests: GI-Cancer Surgery, Peritoneal Metastasis, HIPEC, PIPAC, Aerosol-Technology, Technical Innovations for Intraperitoneal Aerosol Therapy, Small Animal PM Models, Small Animal Cancer Imaging, Clinical Trials
Prof. Mehdi Ouaissi

E-Mail Website
Guest Editor
Department of Digestive, Oncological, Endocrine, and Hepatic Surgery, and Hepatic Transplantation, Trousseau Hospital, CHRU Trousseau, F-37170 Chambray-les-Tours, France

Special Issue Information

Dear Colleagues,

Since several decades, liquid intraperitoneal chemotherapy (LIP) has become an important part of the multimodal treatment approach to patients suffering from peritoneal metastases (PM). In most cases, LIP is delivered as heated liquid intraperitoneal chemotherapy (HIPEC) in combination with cytoreductive surgery. However, clinical data and the exact role of LIP/HIPEC to manage PM patients remain conflicting.
Almost one decade ago, the delivery of intraperitoneal chemotherapy as a pressurized aerosol (PIPAC) has been introduced. Although PIPAC has been rapidly integrated into the daily clinical management of PM patients, there is still a lack of solid preclinical and clinical data. Nevertheless, there are now numerous clinical trials under progress but without a preclinical proof of concept of PIPAC and based on empiric treatment parameters. Therefore, there is a clear need for detailed preclinical data of all aspects about PIPAC technology.
The aim of this Special Issue is to give the reader a deeper inside into ongoing preclinical and clinical research about LIP and PIPAC. A strong focus will be furthermore given to nanotechnology, hydrocolloids and cold plasma technology which will hopefully become new treatment options in the near future to reinforce the fight against this devasting disease.

Prof. Clemens B. Tempfer
Dr. Urs Giger-Pabst
Prof. Mehdi Ouaissi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Intraperitoneal Chemotherapy (IPC)
  • Peritoneal Metastases (PM)
  • HIPEC
  • PIPAC
  • Intraperitoneal Aerosol Generation Technology
  • Granulometry
  • Small Animal PM Models
  • Small Animal PM Imaging
  • PIPAC Animal Models
  • In-silico HIPEC/PIPAC Models
  • Animal Testing Substitution Models
  • Pharmacokinetics
  • Nanodrugs
  • Hydrocolloids
  • Liposomes
  • New Drug Development
  • Cold Atmospheric Plasma-Activated Solutions
  • Clinical Trials

Published Papers (4 papers)

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Research

11 pages, 1280 KiB  
Article
Anti-Angiogenic Treatment in Pseudomyxoma Peritonei—Still a Strong Preclinical Rationale
by Yvonne Andersson, Karianne G. Fleten, Torveig W. Abrahamsen, Wenche Reed, Ben Davidson and Kjersti Flatmark
Cancers 2021, 13(11), 2819; https://doi.org/10.3390/cancers13112819 - 5 Jun 2021
Cited by 5 | Viewed by 2804
Abstract
Pseudomyxoma peritonei (PMP) is a rare, slow-growing cancer characterized by progressive accumulation of intraperitoneal mucinous tumor deposits. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) cures approximately 50% of patients, but in unresectable and recurrent cases, treatment options are limited. Anti-angiogenic treatment is being [...] Read more.
Pseudomyxoma peritonei (PMP) is a rare, slow-growing cancer characterized by progressive accumulation of intraperitoneal mucinous tumor deposits. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) cures approximately 50% of patients, but in unresectable and recurrent cases, treatment options are limited. Anti-angiogenic treatment is being explored as a potential therapeutic option. Using PMP patient samples, microvessel densities (immunostaining for CD31 and CD105) and pro-angiogenic factors were analyzed, and the proliferative response upon incubation with human umbilical cord vascular endothelial cells (HUVEC) was determined. Growth inhibition by anti-angiogenic drugs was analyzed in patient-derived xenograft models of PMP. PMP tumor tissues were found to be highly vascularized and contained key pro-angiogenic factors, in particular related to vascular endothelial growth factor (VEGF) signaling, but interestingly, high levels of fibroblast growth factor 2 were also detected. HUVEC proliferation was stimulated upon incubation with fresh tumor samples and the observed proliferation could be inhibited by VEGF pathway inhibitor bevacizumab. In xenograft models the two VEGF pathway inhibitors, bevacizumab and aflibercept, inhibited tumor growth. This work reemphasizes the importance of angiogenesis as a major driver in PMP and strengthens the preclinical rationale for continued exploration of angiogenesis inhibition in the hope of providing novel treatment to a group of patients that have few other treatment options. Full article
(This article belongs to the Special Issue Intraperitoneal Chemotherapy for Peritoneal Metastases: Technical Innovations, Preclinical and Clinical Advances and Future Perspectives)
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10 pages, 263 KiB  
Article
Mid-Term Audit of a National Peritoneal Surface Malignancy Program Implementation in a Low Middle Income Country: The Moroccan Experience
by Amine Souadka, Hajar Essangri, Mohammed Anass Majbar, Amine Benkabbou, Saber Boutayeb, Laila Amrani, Abdelilah Ghannam, Brahim El Ahmadi, Zakaria Houssaïn Belkhadir, Raouf Mohsine, Abdelilah Souadka and Dominique Elias
Cancers 2021, 13(5), 1088; https://doi.org/10.3390/cancers13051088 - 3 Mar 2021
Cited by 10 | Viewed by 1941
Abstract
Implementing a multimodal management of peritoneal surface malignancies is a steep and complex process, especially as complete cytoreductive surgery (CRS) is the backbone and the major prognostic factor for hyperthermic intraperitoneal chemotherapy (HIPEC) procedures. The implementation of such a program is a challenging [...] Read more.
Implementing a multimodal management of peritoneal surface malignancies is a steep and complex process, especially as complete cytoreductive surgery (CRS) is the backbone and the major prognostic factor for hyperthermic intraperitoneal chemotherapy (HIPEC) procedures. The implementation of such a program is a challenging process, particularly in low-middle income (LMIC) countries where ressource restrictions may represent a major hurdle to HIPEC appliances acquisition. Herein is the first audit of the implementation of a national peritoneal malignancy program in a north African country. The audit process was performed according to the three implementation steps, namely initiation (“1”:2005–2008), transition (“2”:2009–2013) and consolidation (“3”:2014–2017). We included all consecutive CRS without HIPEC performed with curative intent for ovarian, gastric, colorectal and pseudomyxoma peritonei type of malignancies with an Eastern Cooperative Oncology Group (ECOG) performance Status ≤ 2. Target outcomes for incomplete cytoreduction (ICRS), serious complications ≥ 3b according to the Clavien-Dindo scoring, and early oncologic failure (EOF; disease progression within 2 years of treatment) were compared between the three phases. Independent risk factors correlated to these three outcomes were calculated using a logistic regression model.198 CRS procedures were completed with 49, 60 and 89 cases performed in the three phases, respectively. Overall, patients were comparable except for ECOG and ASA scores which were more severe in the third phase. The comparison of ICRS, serious complications and EOF rates showed a significant reduction between the three phases with (34%, 18% and 4% p = <0.001), (30.6%, 20% and 11.2%, p = 0.019) and (38.8%, 23.3% and 12.4% p = 0.002) respectively. Undergoing CRS in phase 3 on the other hand was a predictive factor of better short term surgical and oncological outcomes and completeness of cytoreduction, while ECOG performance status and spleno-pancreatectomy were also predictive factors of serious complications. Full article
(This article belongs to the Special Issue Intraperitoneal Chemotherapy for Peritoneal Metastases: Technical Innovations, Preclinical and Clinical Advances and Future Perspectives)
13 pages, 3309 KiB  
Article
Establishment of a Mouse Ovarian Cancer and Peritoneal Metastasis Model to Study Intraperitoneal Chemotherapy
by Günther A. Rezniczek, Jonathan Buggisch, Julien Sobilo, Alexandre Launay, Stéphanie Lerondel, Alain Le Pape, Mehdi Ouaissi, Daniel Göhler, Metin Senkal, Urs Giger-Pabst and Clemens B. Tempfer
Cancers 2020, 12(12), 3818; https://doi.org/10.3390/cancers12123818 - 17 Dec 2020
Cited by 11 | Viewed by 4643
Abstract
Intraperitoneal chemotherapy (IPC) is a locoregional treatment option in patients with peritoneal metastases (PM). Here, we present an ovarian cancer (OC)-derived PM mouse model for the study of different forms of IPC. Xenograft cell proliferation (luciferase-transfected OVCAR3 and SKOV3 clones) and growth kinetics [...] Read more.
Intraperitoneal chemotherapy (IPC) is a locoregional treatment option in patients with peritoneal metastases (PM). Here, we present an ovarian cancer (OC)-derived PM mouse model for the study of different forms of IPC. Xenograft cell proliferation (luciferase-transfected OVCAR3 and SKOV3 clones) and growth kinetics were assessed using PET scan, bioluminescence imaging (BLI), and histological tumor analysis. Liquid IPC was achieved by intraperitoneal injection with/without capnoperitoneum (6–7 mmHg). Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was mimicked using an intratracheal drug aerosol administration system (micro-nozzle), which, as demonstrated by ex vivo granulometric analysis using laser diffraction spectrometry, produced a polydisperse, bimodal aerosol with a volume-weighted median diameter of (26.49 ± 2.76) µm. Distribution of Tc-99m-labeled doxorubicin in mice was characterized using SPECT and was dependent on the delivery mode and most homogeneous when the micro-nozzle was used. A total of 2 mg doxorubicin per kg body weight was determined to be the optimally effective and tolerable dose to achieve at least 50% tumor reduction. Repeated PIPAC (four times at seven-day-intervals) with doxorubicin in SKOV3-luc tumor-bearing mice resulted in halted tumor proliferation and tumor load reduced after the second round of PIPAC versus controls and the number of tumor nodules was significantly reduced (27.7 ± 9.5 vs. 57.3 ± 9.5; p = 0.0003). Thus, we established the first mouse model of OC PM for the study of IPC using a human xenograft with SKOV3 cells and an experimental IPC setup with a miniaturized nozzle. Repeated IPC was feasible and demonstrated time-dependent anti-tumor activity. Full article
(This article belongs to the Special Issue Intraperitoneal Chemotherapy for Peritoneal Metastases: Technical Innovations, Preclinical and Clinical Advances and Future Perspectives)
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14 pages, 231 KiB  
Article
Total Pelvic Exenteration, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy for Rectal Cancer with Associate Peritoneal Metastases: Surgical Strategies to Optimize Safety
by Jean-Jacques Tuech, Jean Pinson, François-Xavier Nouhaud, Gregory Wood, Thomas Clavier, Jean-Christophe Sabourin, Frederic Di Fiore, Matthieu Monge, Eloïse Papet and Julien Coget
Cancers 2020, 12(11), 3478; https://doi.org/10.3390/cancers12113478 - 23 Nov 2020
Cited by 13 | Viewed by 2922
Abstract
Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a curative treatment option for patients with peritoneal carcinomatosis. Total pelvic exenteration (TPE) is an established treatment option for locally advanced pelvic malignancy. These two procedures have high mortality and morbidity, and therefore, [...] Read more.
Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a curative treatment option for patients with peritoneal carcinomatosis. Total pelvic exenteration (TPE) is an established treatment option for locally advanced pelvic malignancy. These two procedures have high mortality and morbidity, and therefore, their combination is not currently recommended. Herein, we reported our experience on TPE associated with CRS/HIPEC with a critical analysis for rectal cancer with associate peritoneal metastases. Methods: From March 2006 to August 2020, 319 patients underwent a CRS/HIPEC in our hospital. Among them, 16 (12 men and four women) underwent an associated TPE. The primary endpoints were perioperative morbidity and mortality. Results: There was locally recurrent rectal cancer in nine cases, six locally advanced primary rectal cancer, and a recurrent appendiceal adenocarcinoma. The median Peritoneal Cancer Index (PCI) was 8. (4–16). Mean duration of the surgical procedure was 596 min (420–840). Complete cytoreduction (CC0) was achieved in all patients, while clear resection (R0) margins on the resected pelvic organs were achieved in 81.2% of cases. The median hospital stay was 46 days (26–129), and nine patients (56.2%) experienced severe complications (grade III to V) that led to death in two cases (12.5%). The total reoperation rate for patients was 6/16 (37.5%) and 3/16 (18.75%) with percutaneous radiological-guided drainage. Conclusions: In summary, TPE/extended TPE (ETPE) associated with CRS/HIPEC may be a reasonable procedure in selected patients at expert centers. Pelvic involvement should not be considered a definitive contraindication for CRS/HIPEC in patients with resectable peritoneal surface diseases if a R0 resection could be achieved on all sites. However, the morbidity and the mortality are high with this combination of treatment, and further research is needed to assess the oncologic benefit and quality of life before such a radical approach can be recommended. Full article
(This article belongs to the Special Issue Intraperitoneal Chemotherapy for Peritoneal Metastases: Technical Innovations, Preclinical and Clinical Advances and Future Perspectives)
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