How to Prevent Peritoneal Dialysis Catheter Tip Migration: A Japanese Perspective

The prevention of peritoneal dialysis (PD) catheter complications is essential to achieve a successful outcome. In recent years, nephrologists have performed more PD catheter insertion surgeries in Japan. The prevention of catheter complications is crucial for nephrologists who do not have all-around surgical skills. PD catheter tip migration is a common complication and a significant cause of catheter malfunction. Several preventive techniques have been reported for the PD catheter tip migration. This perspective described the following: (1) surgical technique in laparotomy, (2) laparoscopic surgery, (3) peritoneal wall anchor technique, and (4) catheter type selection. We hope that more effective methods of preventing catheter complications will be developed to ensure the success of PD treatment.

Modeling open surgery in mice to explore peritoneal damage, carbon dioxide humidification and desmoidogenesis

BackgroundThe exposure of the peritoneum to desiccation during surgery generates lasting damage to the mesothelial lining which impacts inflammation and tissue repair. We have previously explored open abdominal surgery in mice subjected to passive airflow however, operating theatres employ active airflow. Therefore, we sought an engineering solution to recapitulate the active airflow in mice. Similarly, to the passive airflow studies we investigated the influence of humidified-warm carbon dioxide (CO2) on this damage in the context of active airflow. Additionally, we addressed the controversial role of surgery in exacerbating desmoidogenesis in a mouse model of familial adenomatous polyposis.MethodsAn active airflow mouse-operating module manufactured to produce the equivalent downdraft airflow to that of a modern operating theatre was employed. We quantified mesothelial cell integrity by scanning electron microscopy (SEM) sampled from the peritoneal wall that was subjected to mechanical damage or not, with and without the delivery of humidified-warm CO2. To explore the role of open and laparoscopic surgery in the process of desmoidogenesis we crossed Apcmin/+ C57Bl/6 mice with p53+/− mice to generate animals that developed desmoid tumors with 100% penetrance.ResultsOne hour of active airflow generates substantial damage to peritoneal mesothelial cells and their microvilli as measured at 24 h post intervention, which is significantly greater than that generated by passive airflow. Use of humidified-warm CO2 mostly protects the mesothelium that had not experienced additional mechanical (surgical) damage at 24 h. Maximal damage was evident in all treatment groups regardless of flow or use of gas. At day 10 mechanically-damaged peritoneum remains in mice but is essentially repaired in the gas-treated groups. Regarding desmoidogenesis, operating procedures did not increase the frequency of desmoid tumors but their frequency correlated with time following surgery but not age of mice.ConclusionsActive airflow generates more peritoneal damage than passive airflow and is reduced significantly by the use of humidified-warm CO2. Introduced peritoneal damage is largely repaired in mice by day 10 with gas. Desmoid tumor incidence is not increased substantially by surgery itself but rises over time following surgery compared to non-surgery mice.

Nanofibrous Polydioxanone Depots for Prolonged Intraperitoneal Paclitaxel Delivery

Background: Prolonged chemodrug delivery to the tumor site is a prerequisite to maintaining its localised therapeutic concentrations for effective treatment of malignant solid tumors. Objective: The current study aims to develop implantable polymeric depots through conventional electrospinning for sustained drug delivery, specifically to the peritoneum. Methods: Non-woven electrospun mats were fabricated by simple electrospinning of Polydioxanone solution loaded with the chemodrug, Paclitaxel. The implants were subjected to the analysis of morphology, mechanical properties, degradation and drug release in phosphate buffer and patient-derived peritoneal drain fluid samples. In vivo studies were conducted by surgical knotting of these implants to the peritoneal wall of healthy mice. Results: Non-woven electrospun mats with a thickness of 0.65±0.07 mm, weighing ~ 20 mg were fabricated by electrospinning 15 w/v% polymer loaded with 10 w/w% drug. These implants possessing good mechanical integrity showed a drug entrapment efficiency of 87.82±2.54 %. In vitro drug release studies in phosphate buffer showed a sustained profile for ~4 weeks with a burst of 10 % of total drug content, whereas this amounted to >60% in patient samples. Mice implanted with these depots remained healthy during the study period. The biphasic drug release profile obtained in vivo showed a slow trend, with peritoneal lavage and tissues retaining good drug concentrations for a sustained period. Conclusion: The results indicate that non-woven electrospun mats developed from biodegradable Polydioxanone polymer can serve as ideal candidates for easily implantable drug depots to address the challenges of peritoneal metastasis in ovarian cancer.

Application of Direct Sonoporation from a Defined Surface Area of the Peritoneum: Evaluation of Transfection Characteristics in Mice

In the present study, we developed a sonoporation system, namely “direct sonoporation”, for transfecting the peritoneum from a defined surface area to avoid systematic side effects. Here, the transfection characteristics are explained because there is less information about direct sonoporation. Naked pDNA and nanobubbles were administered to diffusion cell attached to the visceral and parietal peritoneum from the liver and peritoneal wall surface, respectively. Then, ultrasound was irradiated. Direct sonoporation showed a higher transfection efficacy at the applied peritoneum site from the liver surface while other sites were not detected. Moreover, transgene expression was observed in the peritoneal mesothelial cells (PMCs) at the applied peritoneum site. No abnormality was observed in the inner part of the liver. Although transgene expression of the visceral peritoneum was tenfold higher than that of the parietal peritoneum, transgene expression was observed in the PMCs on both the applied peritoneum sites. These results suggest that direct sonoporation is a site-specific transfection method of the PMCs on the applied peritoneum site without transgene expression at other sites and show little toxicity in the inner tissues at the applied site via cavitation energy. This information is valuable for the development of an intraperitoneal sonoporation device for treatment of peritoneal diseases such as peritoneal fibrosis.

Recycling of residual liquid drug formation following pressurized intra-peritoneal aerosol chemotherapy (PIPAC).

e14215 Background: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is becoming an increasingly widespread approach in which intra-peritoneal chemotherapy (IPC) is delivered in the shape of a chemoaerosol formed by an aerosol creating device. Disadvantages of current PIPAC applications include nearly instant liquid drug accumulation in the recto-uterine pouch. This study aims to investigate the feasibility of respraying the accumulated liquid to prevent local cytotoxicity and tissue trauma as well as to possibly adjust drug concentrations and improve both distribution patterns and penetration levels. Methods: A well-established, previously described postmortem swine model was used. 200ml of doxorubicin solution were aerosolized within the abdominal cavity at a pressure of 12 mm Hg C02 and 37° degrees Celsius. A suction tube was placed in the recto-uterine pouch and accumulating liquid doxorubicin solution following aerosol formation was collected and recycled in consecutive PIPAC repetitions. PIPAC repetitions were performed by using only the remaining liquid drug within the pouch. Consecutive residual volumes within the recto-uterine pouch were measured, as well as tissue penetration rates at different locations of the peritoneal wall. Results: Liquid formation was continuously reduced with each consecutive spray cycle. Tissue penetration rates were significantly higher following the recycling process (p < 0.05). Drug distribution pattern showed a significant improvement following the recycling process vs. after initial aerosol formation (p < 0.05). Conclusions: Respraying the accumulated liquid drug in the recto-uterine pouch is both feasible and important to eliminate liquid accumulation following PIPAC application. Preliminary data gathered in this study suggest that such a recycling process both improves drug distribution and increases penetration levels. However, recycling might also increase the technical complexity of the entire applicational procedure.

Preparation of a Cross-Linked Cartilage Acellular-Matrix Film and Its In Vivo Evaluation as an Antiadhesive Barrier

In this paper, a cartilage acellular-matrix (CAM) is chosen as a biomaterial for an effective antiadhesive barrier to apply between injured tissue and healthy tissues or organs. CAM is cross-linked using glutaraldehyde to create a cross-linked CAM (Cx-CAM) film. Cx-CAM has higher elastic modulus and toughness and more hydrophobic surface properties than CAM before cross-linking. Small intestinal submucosa (SIS), cross-linked SIS (Cx-SIS) as a negative control, and Seprafilm as a positive control are used in an experiment as adhesion barriers. Human umbilical vein endothelial cells (HUVECs) on SIS, Cx-SIS, or in a culture plate get attached and effectively proliferate for 7 days, but Cx-CAM and Seprafilm allow for little or no attachment and proliferation of HUVECs, thus manifesting antiadhesive and antiproliferative effects. In animals with surgical damage to the peritoneal wall and cecum, Cx-CAM and Seprafilm afford little adhesion and negligible inflammation after seven days, as confirmed by hematoxylin and eosin staining and macrophage staining, in contrast to an untreated-injury model, SIS, or Cx-SIS film. Cx-CAM significantly suppresses the formation of blood vessels between the peritoneal wall and cecum, as confirmed by CD31 staining. Overall, the newly designed Cx-CAM film works well as an antiadhesion barrier and has better anti-tissue adhesion efficiency.

Surgical adhesions in mice are derived from mesothelial cells and can be targeted by antibodies against mesothelial markers

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and are a major cause of postsurgical and infectious morbidity. The primary molecular chain of events leading to the initiation of adhesions has been elusive, chiefly due to the lack of an identifiable cell of origin. Using clonal analysis and lineage tracing, we have identified injured surface mesothelium expressing podoplanin (PDPN) and mesothelin (MSLN) as a primary instigator of peritoneal adhesions after surgery in mice. We demonstrate that an anti-MSLN antibody diminished adhesion formation in a mouse model where adhesions were induced by surgical ligation to form ischemic buttons and subsequent surgical abrasion of the peritoneum. RNA sequencing and bioinformatics analyses of mouse mesothelial cells from injured mesothelium revealed aspects of the pathological mechanism of adhesion development and yielded several potential regulators of this process. Specifically, we show that PDPN+MSLN+ mesothelium responded to hypoxia by early up-regulation of hypoxia-inducible factor 1 alpha (HIF1α) that preceded adhesion development. Inhibition of HIF1α with small molecules ameliorated the injury program in damaged mesothelium and was sufficient to diminish adhesion severity in a mouse model. Analyses of human adhesion tissue suggested that similar surface markers and signaling pathways may contribute to surgical adhesions in human patients.

Modified Simple Peritoneal Wall Anchor Technique (Pwat) in Peritoneal Dialysis

BackgroundOutflow obstruction, a common complication in patients with peritoneal dialysis (PD), usually results in unnecessary catheter removal or replacement. This study describes a modified simple method of anchoring a PD catheter on the anterior peritoneal wall without using a laparoscopic system (peritoneal wall anchor technique, PWAT).MethodsWe performed a retrospective cohort study of consecutive PD catheter insertions, and compared the catheter survival rate between the traditional method and the modified simple PWAT. The traditional method was used in 54 cases and the modified simple PWAT was used in 17 cases. The primary endpoint was the occurrence of surgical catheter repair because of outflow obstruction by day 365. The secondary endpoint was the occurrence of catheter migration with obstruction requiring any interventions, including the alpha-replacement method by day 365. Catheter survival was analyzed by Kaplan-Meier survival curves.ResultsMigration-free catheter survival was significantly ( p = 0.02) higher in the PWAT group (100%, 17/17) than in the traditional group (72.2%, 39/54). Catheter survival without surgical repair or cessation of PD was also significantly ( p = 0.04) higher in the PWAT group (100%, 17/17) than in the traditional group (77.8%, 42/54). Similarly, migration-free and surgery-free catheter survival rates in cases with a straight-type catheter in the PWAT group were significantly higher than those in cases with a straight-type catheter in the traditional group.ConclusionsOur results suggest that the modified simple PWAT provides a better catheter survival rate than the traditional method by preventing catheter migration with obstruction in PD.