Title Page -- Copyright Page -- Preface -- Acknowledgments -- Table of Contents -- List of contributors -- 1 Introduction -- Bibliography -- 2 Peritoneal carcinomatosis: a neglected disease -- 2.1 An unmet medical need -- 2.2 Role of the physician in provision of care in advanced peritoneal cancer -- 2.3 Palliative care in peritoneal carcinomatosis -- Bibliography -- 3 Normal and diseased peritoneum -- 3.1 Ontology -- 3.2 Anatomy -- 3.2.1 Blood supply -- 3.2.2 Lymphatics -- 3.2.3 Lymphatic stomata -- 3.2.4 Milky spots -- 3.2.5 Greater omentum -- 3.2.6 Peritoneal nerves -- 3.3 Physiology of peritoneum -- 3.3.1 Peritoneum-plasma barrier -- 3.3.2 Intraperitoneal Hydrostatic Pressure -- 3.4 Pathophysiology of peritoneal carcinomatosis -- 3.4.1 Epithelial-mesenchymal transition -- 3.4.2 Interstitial intratumoral fluid pressure -- 3.4.3 Ascites -- 3.4.4 Hormonal changes -- Bibliography -- 4 Diagnosis and staging of peritonealcarcinomatosis -- 4.1 Diagnostic workup -- 4.2 Imaging studies -- 4.2.1 Computer tomography (CT scan) -- 4.2.2 Magnetic Resonance Imaging (MRI) -- 4.2.3 Ultrasound -- 4.2.4 FDG-Positron emission tomography (PET) -- 4.3 Diagnostic laparoscopy -- 4.3.1 Peritoneal Cancer Index -- 4.4 Peritoneal or pleural cytology -- 4.4.1 Gastric cancer -- 4.4.2 Ovarian cancer -- 4.4.3 Colorectal cancer -- Bibliography -- 5 Therapy of peritoneal carcinomatosis -- 5.1 Systemic palliative chemotherapy -- 5.2 Intraperitoneal chemotherapy -- 5.3 Drug uptake into tumoral tissue -- 5.3.1 Diffusion -- Parameters of diffusion through tissue -- 5.3.2 Convection -- 5.4 Effect of peritonectomy on drug clearance -- 5.5 Influence of intraperitoneal drug concentration -- 5.6 Tissue penetration of various drugs -- 5.6.1 Doxorubicin (see also page 199) -- 5.6.2 Cisplatinum (see also page 198) -- 5.6.3 Oxaliplatinum -- 5.6.4 Taxanes (Paclitaxel, Docetaxel).

5.7 Perioperative intraperitoneal chemotherapy -- 5.7.1 CHPP -- 5.7.2 NIPS -- 5.7.3 EIPL -- 5.7.4 EPIC -- 5.8 Intraperitoneal chemotherapy for ascites -- 5.9 Limitations of intraperitoneal chemotherapy -- 5.9.1 Poor drug penetration -- 5.9.2 Poor surface exposition -- 5.9.3 Local toxicity -- 5.9.4 Peritoneal sclerosis -- 5.10 Intraperitoneal immunotherapy -- 5.10.1 Catumaxomab -- 5.10.2 Bevacizumab -- 5.10.3 Immunoradiotherapy -- 5.11 Intraperitoneal cytolytic virotherapy -- 5.12 Nanodrugs -- 5.13 Combined CRS with HIPEC -- 5.13.1 Cytoreductive surgery (CRS) -- Completeness of Cytoreduction Score -- 5.13.2 Hyperthermic IntraPEritoneal Chemotherapy HIPEC) -- 5.13.3 Colorectal cancer -- 5.13.4 Ovarian Cancer -- 5.13.5 Gastric Cancer -- 5.13.6 Learning curve and expertise -- 5.13.7 Evidence of cost effectiveness -- 5.13.8 Safety -- 5.13.9 Indications for CRS and HIPEC -- Bibliography -- 6 Assessing tumor response in peritoneal carcinomatosis -- 6.1 Natural history of peritoneal carcinomatosis -- 6.2 RECIST criteria -- 6.2.1 RECIST criteria in peritoneal carcinomatosis -- 6.3 Laparoscopy in peritoneal carcinomatosis -- 6.4 Histology for determining tumor response -- 6.5 Tumor markers for determining tumor response -- 6.5.1 Gastric cancer -- 6.5.2 Ovarian cancer -- 6.5.3 Colorectal cancer -- 6.6 Determining clinical benefit rate in peritoneal carcinomatosis -- Bibliography -- 7 Principle of therapeutic capnoperitoneum -- 7.1 Material and methods -- 7.1.1 Design of the prototype -- 7.2 Results -- 7.2.1 In vitro trial -- Kinds of solutions -- Influence of viscosity -- Maximal flow -- Droplet size -- 7.2.2 In vivo trial -- Surgical procedure -- Drug distribution -- Unexpected problems -- 7.3 Discussion -- 7.3.1 Increasing exposure of the peritoneal surface -- 7.3.2 Increasing hydrostatic intraabdominal pressure.

7.3.3 Applications of therapeutic capnoperitoneum -- Prevention of local recurrence after cancer surgery -- Prevention of port-site recurrences -- Intraperitoneal and intrapleural chemotherapy -- Modulation of tumor immunogeneity -- Benign disease: infections and adhesions -- Perioperative analgesia -- Remaining challenges -- Bibliography -- 8 PIPAC Technology -- 8.1 Aerosol -- 8.2 Pressure -- 8.3 Micropump -- 8.4 High-pressure injector -- 8.5 Training and documentation -- 8.6 Limited sales -- Bibliography -- 9 Preclinical experiments -- 9.1 Xenograft intraperitoneal model in the pig -- 9.1.1 Material and methods -- 9.1.2 Anesthesia -- 9.1.3 Operative procedure: sigmoid colectomy -- 9.1.4 Postoperative care -- 9.1.5 Cell line -- 9.1.6 Labeling of HeLa cells -- 9.1.7 Immunohistochemistry -- 9.1.8 In vitro study of chromate toxicity -- 9.1.9 Intraoperative complications -- 9.1.10 Port site recurrence -- 9.1.11 Postoperative course -- 9.1.12 Discussion -- Bibliography -- 9.2 Staining experiments with aerosolized methylene blue in the pig -- 9.2.1 Introduction -- 9.2.2 Material and Methods -- Study design -- Nebulizer -- Animal model -- Experimental protocol -- 9.2.3 Results -- 9.2.4 Discussion -- Bibliography -- 9.3 Ex vivo experiments with Dbait on diseased peritoneum -- 9.3.1 Material and methods -- 9.3.2 Study design -- 9.3.3 Nebulizer -- 9.3.4 Patient characteristics, cytoreduction, and intraperitoneal hyperthermic chemotherapy -- 9.3.5 Tumor characteristics -- 9.3.6 Experimental protocol -- 9.3.7 Microscopic analysis -- 9.3.8 Results -- 9.3.9 Discussion -- Bibliography -- 10 First PIPAC in-human application -- 10.1 Introduction -- 10.2 Methods -- 10.2.1 Patients -- 10.2.2 Surgical procedures -- 10.2.3 Safety and Efficacy assessments -- 10.2.4 Histology and immunohistochemistry -- 10.2.5 Clinical Pharmacology -- 10.3 Results -- 10.3.1 Patient 1.

10.3.2 Patient 2 -- 10.3.3 Patient 3 -- 10.4 Safety -- 10.5 Clinical Pharmacology -- 10.6 Discussion -- Bibliography -- 11 Renal and liver toxicities -- 11.1 Patients and methods -- 11.1.1 Study Design -- 11.1.2 Ethics -- 11.1.3 Patients -- 11.1.4 Therapy -- 11.1.5 Sampling -- 11.2 Statistical Analysis -- 11.3 Results -- 11.4 Discussion -- Bibliography -- 12 PIPAC in ovarian cancer -- 12.1 Off-label use -- 12.1.1 Patients and methods -- 12.1.2 Results -- 12.1.3 Discussion -- Bibliography -- 12.2 PIPAC-OV1: a Phase-2 trial in the third-line palliative situation -- 12.2.1 Objectives -- 12.2.2 Study design -- 12.2.3 Target subject population -- 12.2.4 Investigational product, dosage, and mode of administration -- 12.2.5 Duration of treatment -- 12.2.6 Endpoints -- Primary outcome variable: -- Secondary outcome variables: -- 12.2.7 Patient reported outcomes (PROs) -- 12.2.8 Pharmacokinetics -- 12.2.9 Safety -- 12.2.10 Statistical methods -- 12.2.11 Current stage -- 12.3 PIPAC-OV2: a Phase-1 dose-finding study -- 12.4 PIPAC-OV3: a prospective Phase-2-3 randomized trial -- Bibliography -- 13 PIPAC in gastric cancer -- 13.1 Off-label use -- 13.2 Results -- 13.3 Discussion -- Bibliography -- 13.4 PIPAC-GA1: a Phase-2 trial in the third-line palliative situation -- 13.4.1 Objectives -- 13.4.2 Study design -- 13.4.3 Target subject population -- 13.4.4 Investigational product, dosage and mode of administration -- 13.4.5 Duration of treatment -- 13.4.6 Study endpoints -- Primary outcome variable -- Secondary outcome variables -- Patient reported outcomes (PROs) -- Safety -- Biological monitoring -- Statistical methods -- 13.4.7 Current stage -- Bibliography -- 14 PIPAC in colorectal cancer -- 14.1 Patients and methods -- 14.2 Results -- 14.3 Discussion -- Bibliography -- 15 PIPAC in mesothelioma -- 15.1 Patients and methods -- 15.2 Results -- 15.3 Conclusions.

Bibliography -- 16 Quality of Life after PIPAC -- Bibliography -- 17 PIPAC and HIPEC -- 17.1 PIPAC as a neoadjuvant therapy before HIPEC -- Bibliography -- 18 Pressurized IntraThoracic Aerosol Chemotherapy PITAC) -- 18.1 Patients -- 18.2 Technique -- 18.2.1 First in-human use -- 18.3 Results -- Bibliography -- 19 Future applications of therapeutic capnoperitoneum -- 19.1 Study design -- 19.2 Regulatory background and animals -- 19.2.1 Staining -- 19.2.2 Macroscopy -- 19.2.3 Microscopic analysis -- 19.3 Pressurized IntraVesical Aerosol Chemotherapy PIVAC) -- 19.4 Pressurized IntraLuminal Aerosol Chemotherapy PILAC) -- 19.5 Discussion -- Bibliography -- 20 Occupational health and safety aspects -- 20.1 Methods -- 20.1.1 Ethical, legal and regulatory background -- 20.1.2 Methodology -- 20.1.3 Nebulizer -- 20.1.4 Operating room characteristics -- 20.1.5 Chemotherapy -- 20.1.6 Experimental protocol -- Toxicology analysis -- 20.2 Results -- 20.2.1 Identification of hazardous substances and dose -- 20.2.2 Identification of possible exposure ways -- 20.2.3 First PIPAC simulation with NaCl 0.9% solution -- 20.2.4 Second PIPAC simulation with smoke and an artificial leak -- 20.2.5 Information and training of the team of volunteers -- 20.2.6 Performance of the first PIPAC procedures with chemotherapy -- 20.3 Conclusions -- 20.4 Second assessement -- 20.5 Biological monitoring -- Bibliogaphy -- 21 PIPAC: Risks and dangers -- 21.1 Bowel access lesions -- 21.2 Simultaneous PIPAC and cytoreductive surgery -- 21.3 Port-site metastases -- 21.4 Tumor invasion of the laparotomy scar -- 21.5 Subcutaneous toxic emphysema -- 21.6 Therapy-resistant ascites -- 21.7 Small bowel obstruction -- 21.8 Secondary CRS and HIPEC -- Bibliography -- 22 Outlook -- 22.1 Radio- and Chemosensibilizers -- 22.2 Nanodrugs -- 22.3 Multimodal therapy -- 22.4 Preventive application in cancer.

22.5 Applications outside cancer therapy.