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  • 1
    In: Pleura and Peritoneum, Walter de Gruyter GmbH, Vol. 6, No. 3 ( 2021-09-27), p. 131-136
    Abstract: Biopsy morphology (surface/depth ratio) and sample processing might affect pharmacological measurements in peritoneal tissue. Methods This is an ex-vivo study on inverted bovine urinary bladders (IBUB). We compared cisplatin (CIS) and doxorubicin (DOX) concentration in 81 standardized transmural punch biopsies of different diameters (6 and 12 mm). Then, we assessed the effect of dabbing the peritoneal surface before analysis. After automatized tissue homogenization with ceramic beads followed by lyophilisation, DOX concentration was quantified by high-performance liquid chromatography (HPLC), CIS concentration by atomic absorption spectroscopy. Experiments were performed in triplicate; the analysis was blinded to the sample origin. Comparisons were performed using non-parametric tests. Results Concentrations are given in mean (CI 5–95%). Results were reproducible between experiments (for CIS p=0.783, for DOX p=0.235) and between different localizations within the IBUB (for CIS p=0.032, for DOX p=0.663). Biopsy diameter had an influence on CIS tissue concentration (6 mm biopsies: 23.2 (20.3–26.1), vs. 12 mm biopsies: 8.1 (7.2–9.2) ng/mg, p 〈 0.001) but not on DOX: (0.46, 0.29–0.62) vs. 0.43 (0.33–0.54) ng/mg respectively, p=0.248). Dabbing the peritoneal surface reduced DOX tissue concentration (dry biopsies: 0.28 (0.12–0.43) vs. wet biopsies: 0.64 (0.35–0.93) ng/mg, p=0.025) but not CIS (23.5 (19.0–28.0) vs. 22.9 (18.9–26.9) ng/mg, respectively, p=0.735). Conclusions Measurements of drug concentration in peritoneal tissue can be influenced by the biopsy’s surface/depth ratio and after drying the biopsy’s surface . This influence can reach a factor three, depending on the drug tested . The biopsy technique and the pre-analytical sample preparation should be standardized to ensure reliable pharmacological measurements in peritoneal tissue.
    Type of Medium: Online Resource
    ISSN: 2364-768X
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2021
    detail.hit.zdb_id: 2861909-2
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  • 2
    Online Resource
    Online Resource
    Walter de Gruyter GmbH ; 2019
    In:  Pleura and Peritoneum Vol. 4, No. 1 ( 2019-03-26)
    In: Pleura and Peritoneum, Walter de Gruyter GmbH, Vol. 4, No. 1 ( 2019-03-26)
    Abstract: Detachment of cells from the extracellular matrix into the peritoneal cavity initiates a cascade of metabolic alterations, leading usually to cell death by apoptosis, so-called anoikis . Glycolytic enzymes enable the switch from oxidative phosphorylation to aerobic glycolysis and allow resistance to anoikis of shed tumour cells. These enzymes also have moonlighting activities as protein kinases and transcription factors. Phosphoglycerate kinase (PGK) and pyruvate kinase are the only glycolytic enzymes generating ATP in the hexokinase pathway. Hypoxia, EGFR activation, expression of K-Ras G12V and B-Raf V600E induce mitochondrial translocation of phosphoglycerate kinase 1 (PGK1). Mitochondrial PGK1 acts as a protein kinase to phosphorylate pyruvate dehydrogenase kinase 1 (PDHK1), reducing mitochondrial pyruvate utilization, suppressing reactive oxygen species production, increasing lactate production and promoting tumourigenesis. PGK1 also plays a role as a transcription factor once transported into the nucleus. Resistance to anoikis is also facilitated by metabolic support provided by cancer-associated fibroblasts (CAFs). Our series of experiments in-vitro and in the animal model showed that PGK1 knock-out or inhibition is effective in controlling development and growth of peritoneal metastasis (PM) of gastric origin, establishing a causal role of PGK1 in this development. PGK1 also increases CXCR4 and CXCL12 expression, which is associated with a metastatic phenotype and plays a role in the metastatic homing of malignant cells. Thus, PGK1, its modulators and target genes may be exploited as therapeutic targets for preventing development of PM and for enhancing cytotoxic effects of conventional systemic chemotherapy.
    Type of Medium: Online Resource
    ISSN: 2364-768X , 2364-7671
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2019
    detail.hit.zdb_id: 2861909-2
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  • 3
    In: European Journal of Surgical Oncology, Elsevier BV, Vol. 46, No. 4 ( 2020-04), p. 613-619
    Type of Medium: Online Resource
    ISSN: 0748-7983
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2002481-2
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  • 4
    In: European Journal of Surgical Oncology, Elsevier BV, Vol. 47, No. 6 ( 2021-06), p. 1434-1440
    Type of Medium: Online Resource
    ISSN: 0748-7983
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2002481-2
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  • 5
    Online Resource
    Online Resource
    Walter de Gruyter GmbH ; 2017
    In:  Pleura and Peritoneum Vol. 2, No. 4 ( 2017-12-20), p. 153-161
    In: Pleura and Peritoneum, Walter de Gruyter GmbH, Vol. 2, No. 4 ( 2017-12-20), p. 153-161
    Abstract: The parietal peritoneum (PP) is innervated by somatic and visceral afferent nerves. PP receives sensitive branches from the lower intercostal nerves and from the upper lumbar nerves. Microscopically, a dense network of unmyelinated and myelinated nerve fibers can be found all over the PP. The unmyelinated fibers are thin and are ending just underneath the PP. The myelinated fibers can penetrate the PP to reach the peritoneal cavity, where they lose their myelin sheath and are exposed to somatic and nociceptive stimuli. PP is sensitive to pain, pressure, touch, friction, cutting and temperature. Noxious stimuli are perceived as a localized, sharp pain. The visceral peritoneum (VP) itself is not innervated, but the sub-mesothelial tissue is innervated by the autonomous nerve system. In contrast to the PP, the visceral submesothelium also receives fibers from the vagal nerve, in addition to the spinal nerves. VP responds primarily to traction and pressure; not to cutting, burning or electrostimulation. Painful stimuli of the VP are poorly localized and dull. Pain in a foregut structure (stomach, duodenum or biliary tract) is referred to the epigastric region, pain in a midgut structure (appendix, jejunum, or ileum) to the periumbilical area and pain from a hindgut source (distal colon or rectum) is referred to the lower abdomen or suprapubic region. Peritoneal adhesions can contain nerve endings. Neurotransmitters are acetylcholine, VIP, serotonin, NO, encephalins, CGRP and substance P. Chronic peritoneal pain can be exacerbated by neurogenic inflammation, e.g. by endometriosis.
    Type of Medium: Online Resource
    ISSN: 2364-768X , 2364-7671
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2017
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  • 6
    In: Surgical Endoscopy, Springer Science and Business Media LLC, Vol. 35, No. 8 ( 2021-08), p. 4901-4901
    Abstract: A correction to this paper has been published: https://doi.org/10.1007/s00464-021-08577-w
    Type of Medium: Online Resource
    ISSN: 0930-2794 , 1432-2218
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1463171-4
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  • 7
    In: Therapeutic Advances in Medical Oncology, SAGE Publications, Vol. 11 ( 2019-01), p. 175883591984640-
    Abstract: Efficacy of second-line systemic chemotherapy in recurrent gastric cancer with peritoneal metastasis (RGCPM) is limited. We assessed the feasibility, safety and possible efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with RGCPM after ⩾1 line of palliative intravenous chemotherapy. Methods: In this open-label, single-arm, monocentric phase II ICH-GCP clinical trial, patients were scheduled for three courses of PIPAC with cisplatin 7.5 mg/m 2 and doxorubicin 1.5 mg/m 2 (PIPAC C/D) every 6 weeks. Patients with bowel obstruction or extraperitoneal metastasis were ineligible. The primary endpoint was clinical benefit rate (CBR) by Response Evaluation Criteria in Solid Tumors based on clinical records. Secondary endpoints included overall survival (OS), median time to progression (TTP), peritoneal carcinomatosis index (PCI), histological regression and ascites volume. Safety and tolerability were assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4, quality of life (QoL) by EORTC-QLQ30 questionnaire. Results: A total of 25 patients were enrolled and available for the analysis of the primary endpoint. Of those 25 patients, 10 (40%) had a radiological complete, partial response or stable disease. Median OS [intention to treat (ITT)] was 6.7 months, median TTP was 2.7 months. Complete or major regression on histology were observed in 9/25 patients (36%, ITT) or 6/6 [100%, per protocol (PP)] patients. There were no suspected unexpected serious adverse reactions, no treatment-related deaths, no CTCAE grade 4 toxicity and three (12%) grade 3 toxicities. Changes in the QLQ-C30 scores during PIPAC C/D therapy were small and not significant. Conclusions: PIPAC C/D was well tolerated and active in patients with RGCPM. Survival was encouraging. Randomized controlled trials should now be designed in this indication.
    Type of Medium: Online Resource
    ISSN: 1758-8359 , 1758-8359
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
    detail.hit.zdb_id: 2503443-1
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  • 8
    In: Cancers, MDPI AG, Vol. 12, No. 1 ( 2019-12-20), p. 34-
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 9
    In: Pleura and Peritoneum, Walter de Gruyter GmbH, Vol. 1, No. 3 ( 2019-04-24), p. 145-158
    Abstract: The peritoneum consists of a layer of mesothelial cells on a connective tissue base which is perfused with circulatory and lymphatic vessels. Total effective blood flow to the human peritoneum is estimated between 60 and 100 mL/min, representing 1–2 % of the cardiac outflow. The parietal peritoneum accounts for about 30 % of the peritoneal surface (anterior abdominal wall 4 %) and is vascularized from the circumflex, iliac, lumbar, intercostal, and epigastric arteries, giving rise to a quadrangular network of large, parallel blood vessels and their perpendicular offshoots. Parietal vessels drain into the inferior vena cava. The visceral peritoneum accounts for 70 % of the peritoneal surface and derives its blood supply from the three major arteries that supply the splanchnic organs, celiac and superior and inferior mesenteric. These vessels give rise to smaller arteries that anastomose extensively. The visceral peritoneum drains into the portal vein. Drugs absorbed are subject to first-pass hepatic metabolism. Peritoneal inflammation and cancer invasion induce neoangiogenesis, leading to the development of an important microvascular network. Anatomy of neovessels is abnormal and characterized by large size, varying diameter, convolution and blood extravasation. Neovessels have a defective ultrastructure: formation of large “mother vessels” requires degradation of venular and capillary basement membranes. Mother vessels give birth to numerous “daughter vessels”. Diffuse neoangiogenesis can be observed before appearance of macroscopic peritoneal metastasis. Multiplication of the peritoneal capillary surface by neoangiogenesis surface increases the part of cardiac outflow directed to the peritoneum.
    Type of Medium: Online Resource
    ISSN: 2364-768X , 2364-7671
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2019
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  • 10
    Online Resource
    Online Resource
    Walter de Gruyter GmbH ; 2016
    In:  Pleura and Peritoneum Vol. 1, No. 4 ( 2016-12-1), p. 193-201
    In: Pleura and Peritoneum, Walter de Gruyter GmbH, Vol. 1, No. 4 ( 2016-12-1), p. 193-201
    Abstract: The peritoneal cavity (cavum peritonei) is incompletely divided into spaces and recessus (or fossae), which are playing an important role in health and disease. Peritoneal subspaces are determined by the parietal attachments of the abdominal organs, the ligaments and mesenteries. These include the splenorenal, the falciform, the triangular, the gastrosplenic, the phrenicocolic and the gastrocolic ligaments; the greater omentum and the lesser omentum (formed by the gastrohepatic and hepatoduodenal ligaments); the small bowel mesenterium and the mesocolon. These ligaments and mesenteries divide the peritoneal cavity into several distinct anatomic and functional regions. The supramesocolic compartment is divided into a bilateral subphrenic space and a subhepatic space continuing into the lesser sac (bursa omentalis). The inframesolic compartment is divided into a left and right region by the mesentery. The right paracolic gutter communicates with the pelvis and with the right suphrenic space. The left paracolic gutter is separated from the left subphrenic space by the phrenocolic ligament. The peritoneal space is virtual, is completely occupied by the intraabdominal organs and can only be visualized by radiological means in the presence of air (organ perforation), liquid (ascites, pus, bile, gastrointestinal fluids) or tumor invasion. Peritoneal morphology has numerous pathophysiological implications: it impacts on the propagation of intraabdominal infections, determines the spreading of peritoneal metastasis and can cause bowel volvulus. Internal hernias can arise at the junction between intraperitoneal and extraperitoneal bowel segments, in particular into the left paraduodenal recessus. Knowledge of peritoneal morphology is a precondition for developing locoregional therapeutic strategies in peritoneal disease and for effective peritoneal dialysis.
    Type of Medium: Online Resource
    ISSN: 2364-7671 , 2364-768X
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2016
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