Theoretical considerations as well as comprehensive preclinical and clinical data suggest that optimizing physical parameters of intraperitoneal drug delivery might help to circumvent initial or acquired resistance of peritoneal metastasis (PM) to chemotherapy. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel minimally invasive drug delivery system systematically addressing the current limitations of intraperitoneal chemotherapy. The rationale behind PIPAC is: (1) optimizing homogeneity of drug distribution by applying an aerosol rather than a liquid solution; (2) applying increased intraperitoneal hydrostatic pressure to counteract elevated intratumoral interstitial fluid pressure; (3) limiting blood outflow during drug application; (4) steering environmental parameters (temperature, pH, electrostatic charge etc.) in the peritoneal cavity for best tissue target effect. In addition, PIPAC allows repeated application and objective assessment of tumor response by comparing biopsies between chemotherapy cycles. Although incompletely understood, the reasons that allow PIPAC to overcome established chemoresistance are probably linked to local dose intensification. All pharmacological data published so far show a superior therapeutic ratio (tissue concentration/dose applied) of PIPAC vs. systemic administration, of PIPAC vs. intraperitoneal liquid chemotherapy, of PIPAC vs. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) or PIPAC vs. laparoscopic HIPEC. In the initial introduction phase, PIPAC has been used in patients who were quite ill and had already failed multiple treatment regimes, but it may not be limited to that group of patients in the future. Rapid diffusion of PIPAC in clinical practice worldwide supports its potential to become a game changer in the treatment of chemoresistant isolated PM of various origins.

An important and most likely active role in the pathogenesis of psoriasis has been attributed to changes in cutaneous blood vessels. The purpose of this study was to use confocal laser-scanning microscopy (CLSM) to investigate dermal capillaries in psoriatic and normal skin. The structures of the capillary loops in 5 healthy participants were compared with those in affected skin of 13 psoriasis patients. The diameters of the capillaries and papillae were measured for each group with CLSM. All investigated psoriasis patients showed elongated, widened, and tortuous microvessels in the papillary dermis, whereas all healthy controls showed a single capillary loop in each dermal papilla. The capillaries of the papillary loop and the dermal papilla were significantly enlarged in the psoriatic skin lesions (diameters 24.39±2.34 and 146.46±28.52  μm, respectively) in comparison to healthy skin (diameters 9.53±1.8 and 69.48±17.16  μm, respectively) (P<0.001). CLSM appears to represent a promising noninvasive technique for evaluating dermal capillaries in patients with psoriasis. The diameter of the vessels could be seen as a well-quantifiable indicator for the state of psoriatic skin. CLSM could be useful for therapeutic monitoring to delay possible recurrences.

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Patients with peritoneal metastasis (PM) of gastrointestinal and gynecological origin present with a nutritional deficit characterized by increased resting energy expenditure (REE), loss of muscle mass, and protein catabolism. Progression of peritoneal metastasis, as with other advanced malignancies, is associated with cancer cachexia anorexia syndrome (CAS), involving poor appetite (anorexia), involuntary weight loss, and chronic inflammation. Eventual causes of mortality include dysfunctional metabolism and energy store exhaustion. Etiology of CAS in PM patients is multifactorial including tumor growth, host response, cytokine release, systemic inflammation, proteolysis, lipolysis, malignant small bowel obstruction, ascites, and gastrointestinal side effects of drug therapy (chemotherapy, opioids). Metabolic changes of CAS in PM relate more to a systemic inflammatory response than an adaptation to starvation. Metabolic reprogramming is required for cancer cells shed into the peritoneal cavity to resist anoikis (i.e., programmed cell death). Profound changes in hexokinase metabolism are needed to compensate ineffective oxidative phosphorylation in mitochondria. During the development of PM, hypoxia inducible factor-1α (HIF-1α) plays a key role in activating both aerobic and anaerobic glycolysis, increasing the uptake of glucose, lipid, and glutamine into cancer cells. HIF-1α upregulates hexokinase II, phosphoglycerate kinase 1 (PGK1), pyruvate dehydrogenase kinase (PDK), pyruvate kinase muscle isoenzyme 2 (PKM2), lactate dehydrogenase (LDH) and glucose transporters (GLUT) and promotes cytoplasmic glycolysis. HIF-1α also stimulates the utilization of glutamine and fatty acids as alternative energy substrates. Cancer cells in the peritoneal cavity interact with cancer-associated fibroblasts and adipocytes to meet metabolic demands and incorporate autophagy products for growth. Therapy of CAS in PM is challenging. Optimal nutritional intake alone including total parenteral nutrition is unable to reverse CAS. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) stabilized nutritional status in a significant proportion of PM patients. Agents targeting the mechanisms of CAS are under development.