Background
Peritoneal metastasis (PM) is an ongoing challenge in surgical oncology. Current therapeutic options, including intravenous and intraperitoneal (i.p.) chemotherapies display limited ...clinical efficacy, resulting in an overall poor prognosis in affected patients. Combined hyperthermia and dehydration induced by a high-flow, gas-based i.p. hyperthermic procedure could be a novel approach in PM treatment. Our study is the first to evaluate the therapeutic potential of i.p. dehydration, hyperthermia, as well as the combination of both mechanisms in an
in-vivo
setting.
Methods
For this study, three swine were subjected to diagnostic laparoscopy under a high-flow air stream at 48°, 49° and 50°Celsius (C). Hygrometry of the in- and outflow airstream was measured to calculate surface evaporation and i.p. dehydration. To analyze the effects of this concept,
in vitro
colon cancer cells (HT-29) were treated with hyperthermia and dehydration. Cytotoxicity and cell viability were measured at different time intervals. Additionally, structural changes of dehydrated cells were analyzed using scanning electron microscopy.
Results
According to our results, both dehydration and hyperthermia were cytotoxic to HT-29 cells. However, while dehydration reduced cell viability, hyperthermia did not. However, dehydration effects on cell viability were significantly increased when combined with hyperthermia (p<0.01).
Conclusions
Changes to the physiological milieu of the peritoneal cavity could significantly reduce PM. Therefore, limited dehydration of the abdominal cavity might be a feasible, additional tool in PM treatment. Further studies are required to investigate dehydration effects and their applicability in PM management.
Background
While hyperthermic intraperitoneal (i.p) applications are highly efficient in treating peritoneal metastases (PM), they are currently limited to temperatures of 41 – 43° Celsius (C). First ...data on gas-based i.p. hyperthermia is promising, as this novel method allows a significant temperature rise in superficial peritoneal layers without increasing core temperatures. Until now, key mechanisms of this novel tool, e.g. thermodynamic energy transfer, have not been investigated. This study aims to explore the volume of thermodynamic energy transfer during gas-based i.p. hyperthermia at 48-50°C and its peritoneal effects.
Methods
For this study, three swine were subjected to gas-based i.p. hyperthermia at varying temperatures (48°, 49° and 50°C) in a diagnostic laparoscopy setting with a high-flow air stream. Temperatures of the i.p. cavity, in- and outflow airstream at the trocar were measured and the thermodynamic energy transfer was calculated. Tissue samples were collected on postoperative day 7 for histopathologic analyses.
Results
According to our data, temperatures within the intraabdominal cavity and at the outflow site remain relatively stable at < 40°C. An increase in thermodynamic energy transfer is observed with increasing applied temperatures. Gas-based i.p. hyperthermia induced capillary coagulation and white blood cell infiltration within peritoneal layers.
Conclusions
Gas-based i.p. hyperthermia is an innovative approach which enables the i.p. delivery of specific amounts of thermodynamic energy. Following this procedure, our data indicate remarkable histologic changes on the superficial peritoneal layer most likely attributable to the applied thermodynamic energy. Further studies are required to investigate how these findings can be applied in PM management.
Background:
For decades, intraperitoneal chemotherapy (IPC) has been delivered into the abdominal cavity as a liquid solution. Recently the concept of foam as a carrier-solution for IPC was ...suggested. This
in-vivo
swine study aims to evaluate the safety, intraoperative parameters, limitations and postoperative complications of foam-based intraperitoneal chemotherapy (FBIC).
Methods:
Three 65-day-old swine received FBIC with doxorubicin in a laparoscopy setting. Intraoperative parameters were monitored throughout the procedure and an extensive postoperative laboratory monitoring was conducted for 7 days. At day seven an autopsy was performed for further evaluation.
Results:
The insufflation of FBIC caused a temporary rise in blood pressure and a simultaneous drop in heart rate. Capnography detected a continuous increase in end-tital CO
2
levels. A temporary drop of intraabdominal temperature was noted. Postoperative blood and serum laboratory results did not indicate any organ failure. No indication of intraperitoneal infections was noted and no structural tissue changes were visible in the autopsy.
Discussion:
The application of FBIC appears to be a feasible approach regarding intraoperative anesthesiology and postoperative surgical management. A lack of postoperative structural changes on the seventh day were a promising sign of safety and biocompatibility. Surgical reintervention would have been possible. To discuss a possible clinical application, further studies are required to investigate long-term safety, pharmacodynamics and the antitumoral potential of FBIC.
The critically low hepatic iron stores of newborn piglets are considered to be a major cause of neonatal iron deficiency in modern breeds of domestic pig (Sus domestica). The main factor believed to ...contribute to this phenomenon is large litter size, which has been an objective of selective breeding of pigs for decades. As consequence, iron transferred from the pregnant sow has to be distributed among a greater number of fetuses.
Here, we investigated whether litter size influences red blood cell (RBC) indices and iron parameters in Polish Large White (PLW) piglets and gilts. Small and large litters were produced by the transfer of different numbers of embryos, derived from the same superovulated donor females, to recipient gilts. Piglets from large litters obtained following routine artificial insemination were also examined. Our results clearly demonstrated that varying the number of piglets in a litter did not affect the RBC and iron status of 1-day-old piglets, with all showing iron deficiency anemia. In contrast, gilts with small litters displayed higher RBC and iron parameters compared to mothers with large litters. A comparative analysis of the RBC status of wild boars (having less than half as many piglets per litter as domestic pigs) and PLW pigs, demonstrated higher RBC count, hemoglobin level and hematocrit value of both wild boar sows and piglets, even compared to small-litter PLW animals.
These findings provide evidence that RBC and iron status in newborn PLW piglets are not primarily determined by litter size, and indicate the need to study the efficiency of iron transport across the placenta in domestic pig and wild boar females.
For decades, both intraperitoneal and pleural chemotherapy (IPC) have been delivered as a liquid solution. Recent studies suggest that foam carriers outperform liquid carriers for locoregional ...chemotherapy. For the first time, this study aims to evaluate the feasibility, safety, and characteristics of foam-based intrathoracic chemotherapy (FBiTC) in an in vivo setting.
In this study, contrast-enhanced FBiTC with doxorubicin was delivered via video-assisted thoracoscopy (VAT) in three swine under general anesthesia. Intraoperative and postoperative parameters, blood analyses, vital signs, and anesthesiologic data were collected. Additionally, an intraoperative computer tomography (CT) scan was performed, and histological tissue sections were collected and further analyzed using fluorescence microscopy.
FBiTC was delivered without major complications. End-tidal capnometry detected increased CO
levels with reduced peripheral oxygen saturation and increased blood pressure and heart rate. No major intra- or postoperative complications were observed. CT scans confirmed a multidirectional distribution pattern of foam. Postoperative laboratory workup did not reveal any critical changes in hemoglobin, white blood count, or platelets. There was no evidence of critical kidney impairment or liver function. Fluorescence microscopy of tissue specimen detected doxorubicin in pleural tissues.
Our preliminary results are encouraging and indicate that FBiTC is feasible. However, to consider a possible clinical application, further studies are required to investigate the pharmacologic, pharmacodynamic, and physical properties of FBiTC and to ensure the safety of the overall procedure regarding oxygenation levels and capnography parameters.
Implantation of composite scaffolds could be potentially associated with the risk of hemostatic disturbances in a recipient. However, there is a lack of information on possible alterations in ...clotting mechanisms resulting from such a procedure. The aim of the present work was to investigate changes in hemostatic parameters in sheep implanted with a scaffold composed of poly(ε-caprolactone) and hydroxyapatite and tricalcium phosphate (9:4.5:4.5), settled previously with mesenchymal stem cells stimulated by fibroblast growth factor-2 and bone morphogenetic protein-2. Nine Merino sheep were examined for 7 days, and measurements of clotting times (PT, aPTT), activities of antithrombin, protein C and clotting factors II-XII, and concentrations of fibrinogen and D-dimer were carried out before and 1 h, 24 h, 3 days and 7 days after scaffold implantation. The introduction of scaffold initially resulted in a slowdown of the clotting processes (most evident 24 h after surgery); PT and aPTT increased to 14.8 s and 33.9 s, respectively. From the third day onwards, most of these alterations began to return to normal values. The concentration of fibrinogen rose throughout the observation period (up to 8.4 g/L), mirroring the ongoing inflammatory reaction. However, no signals of significant disturbances in hemostatic processes were detected in the sheep tested.
For decades, intraperitoneal chemotherapy (IPC) was used as a liquid solution for the treatment of peritoneal metastasis. Due to its advantageous physical properties, foam-based intraperitoneal ...chemotherapy (FBIC) was recently proposed as a treatment for peritoneal metastasis. For the first time, this study intends to examine the feasibility, expansion, drug distribution, and penetration of FBIC in vivo. Three swine received contrast-enhanced FBIC doxorubicin delivered using a bicarbonate carrier system. During the procedure, intraoperative blood analyses and periumbilical diameter, as well as foam distribution, penetration, and expansion of the FBIC were analyzed. The swine received an abdominal CT scan to evaluate the contrast distribution. Furthermore, a hematoxylin-eosin (HE) staining of peritoneal samples was performed, and fluorescence microscopy was conducted. FBIC was performed without complications. The periumbilical diameter peaked after 5 min and then decreased. Blood analyses showed changes in blood parameters, with a reduction in the pH levels of serum calcium and potassium. CT scan detected contrast-enhanced FBIC throughout the abdominal cavity. Fluorescence microscopy confirmed that all areas were exposed to doxorubicin and no pathologies were detected in the HE histology. Our preliminary results are quite encouraging and indicate that FBIC is a feasible approach. However, in order to discuss possible clinical applications, further studies are required to investigate the pharmacologic, pharmacodynamic, and physical properties of FBIC.
The aim of this study was to evaluate the effects of high intensity laser therapy (HILT) on tendon and ligament injury treatment in horses. Twenty six horses with tendinopathies were randomly ...assigned to a HILT treated or to a non-treated group. Each horse was subjected to the same rehabilitation programme. Horses from the treatment group underwent a series of fifteen HILT treatments with the same parameters. Clinical and ultrasound assessments were performed by the same veterinarian and were carried out before (day 0), during (day 13–15) and after treatment (day 38–40). Clinical evaluation included: pain, swelling and lameness of the affected limb. The ultrasound examination evaluated lesion echogenicity and lesion percentage. After the treatment, pain, swelling and lameness were significantly improved by HILT compared with the control group (p = 0.023, 0.008 and 0.044, respectively). No significant changes were found in lesion echogenicity degree between both groups in measurements taken during treatment (p = 0.188) and after treatment (p = 0.070). For lesion percentage reduction, the statistical modelling showed a significant improvement in the HILT group compared with the control group during (p = 0.038) and after treatment (p = 0.019). In conclusion, HILT promoted analgesic and anti-oedema effects, with visual lameness reduction in horses with tendon and ligament injuries, and reduced lesion percentage but did not influence change in lesion echogenicity.
Background
43°Celsius (C) is currently the highest temperature used in the treatment of peritoneal metastasis (PM). Despite sufficient data on water- based hyperthermic solutions in PM treatment, ...there is currently no information on gas-based hyperthermia extending beyond 43°C. This study is the first to provide
in-vivo
data on different organ systems during and after intraperitoneal gas-based hyperthermia beyond 43°C. The aim of this study is to explore
in-vivo
feasibility, safety, and efficacy of this novel concept from a biological perspective.
Methods
For this study, three swine were subjected to laparoscopy and subsequent gas-based intraperitoneal hyperthermia at 48°, 49° and 50°C under a high-flow air stream. Intraoperative data from multiple temperature sensors were analysed. Additionally, intraoperative anaesthesiologic and gasometrical data was analysed. Postoperatively, swine were monitored for one week and laboratory work-up was performed on postoperative days 1, 3 and 7.
Results
During gas-based intraperitoneal hyperthermia, anesthesiologic parameters did not exhibit critical values. No intra- or postoperative complications were observed. Distinct temperature measurements on the skin, cystohepatic triangle and esophagus did not display any temperature increase. Postoperative laboratory workup did not show any changes in hemoglobin, white blood cell count, platelets, or kidney function.
Discussion
Based on our data, there are no safety concerns for the application of gas-based hyperthermia between 48 - 50°C. In fact, no critical systemic temperature increase was observed. With respect to possible limitations, further
in-vivo
studies are required to evaluate whether gas-based intraperitoneal hyperthermia may be a therapeutic option for PM patients.
Disorders of the locomotive system, especially those occurring due to degenerative changes of the joints, are serious problems in daily veterinary medical practice. Steroid injections are the main ...way of treating these disorders. However, this approach brings usually only temporary effects of pain relief, and may cause many side effects. Alternative therapies focus on regeneration of damaged tissue using adult mesenchymal stem cells (MSCs). Since 2002, the great plasticity and immunomodulatory properties of MSCs isolated from adipose tissue (AdMSCs) have been used successfully in the treatment of degenerative joint diseases (DJD) of both dogs and horses. Possible simultaneous application of steroid therapy and stem cell transplantation could improve the commonly used clinical procedure. In this paper, the influence of the two steroid drugs (betamethasone and methylprednisolone) on AdMSCs was evaluated on the basis of morphology and proliferation rate. Both steroids positively influenced the viability and proliferation state of cells in a concentration of 0.01 mg/ml and 0.1 mg/ml, respectively. However, the concentration of 1 mg/ml had a cytotoxic effect. Moreover, the lower dosage of steroid drugs used in the experiment did not affect the morphology of cells and significantly increased cellular activity. In conclusion, our data demonstrate the stimulating effect of steroid drugs on cell morphology, proliferation rate and cytophysiological activity. These findings may influence the use of stem cells and steroids in applied regenerative veterinary medical practice in the future.
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