Pressurized intra-peritoneal aerosol chemotherapy (PIPAC): increased intraperitoneal pressure does not affect distribution patterns but leads to deeper penetration depth of doxorubicin in a sheep model.

BACKGROUND: Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is an innovative treatment against peritoneal carcinomatosis. Doxorubicin is a common intra-venous chemotherapy used for peritoneal carcinomatosis and for PIPAC. This study evaluated the impact of increased PIPAC intraperitoneal pressure on the distribution and cell penetration of doxorubicin in a sheep model. METHODS: Doxorubicin was aerosolized using PIPAC into the peritoneal cavity of 6 ewes (pre-alpes breed): N = 3 with 12 mmHg intraperitoneal pressure ("group 12") and N = 3 with 20 mmHg ("group 20"). Samples from peritoneum (N = 6), ovarian (N = 1), omentum (N = 1) and caecum (N = 1) were collected for each ewe. The number of doxorubicin positive cells was determined using the ratio between doxorubicine fluorescence-positive cell nuclei (DOXO+) over total number of DAPI positive cell nuclei (DAPI+). Penetration depth (µm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei over the total number of cell nuclei that were stained with DAPI. Penetration depth (µm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei. RESULTS: DOXO+ nuclei were identified in 87% of samples. All omental samples, directly localized in front of the nebulizer head, had 100% DOXO+ nuclei whereas very few nuclei were DOXO+ for caecum. Distribution patterns were not different between the two groups but penetration depth in ovary and caecum samples was significantly deeper in group 20. CONCLUSIONS: This study showed that applying a higher intra-peritoneal pressure during PIPAC treatment leads to a deeper penetration of doxorubicin in ovarian and caecum but does not affect distribution patterns.

Liver Regeneration and Recanalization Time Course following Repeated Reversible Portal Vein Embolization in Swine.

INTRODUCTION: Portal vein embolization (PVE) is an accepted technique to preoperatively increase the volume of the future remnant liver before major hepatectomy. A permanent material is usually preferred since its superiority to induce liver hypertrophy over absorbable material has been demonstrated. Nevertheless, the use of an absorbable material generates a reversible PVE (RPVE) capable of inducing significant liver hypertrophy. In small animal models, the possibility to proceed to a repeated RPVE (RRPVE) has shown to boost liver hypertrophy further. The aim of this preliminary study was to assess the feasibility and the tolerance of RRPVE in a large animal model, in comparison with permanent PVE (PPVE) and single RPVE. METHODS: Six swine (2 per group) were assigned either to single RPVE group (using powdered gelatin sponge), RRPVE group (2 RPVEs separated by 14 days) or PPVE group (using N-butyl-cyanoacrylate). The feasibility and tolerance of the procedures were evaluated using portography, liver function tests and histological analysis. Evolution of liver volumes was assessed with volumetric imaging by computed tomography. RESULTS: Embolization of portal branches corresponding to 75% of total liver volume was performed successfully in all animals. Procedures were well tolerated, inducing moderate changes in portal pressure and transient aminotransferase increase. None of the animals developed portal vein thrombosis. After RPVE, complete recanalization occurred at day 11. RRPVE showed a trend for higher hypertrophy, the non-embolized liver to total liver ratio reaching 5.2 ± 1.0% in the RPVE group, 6.8 ± 0.1% in the RRPVE group and 5.0 ± 0.3% in the PPVE group. DISCUSSION/CONCLUSION: In this preliminary comparative study, RRPVE was as feasible and as well tolerated as the other procedures, and resulted in higher liver hypertrophy.

Comparison of Resonance Frequency Analysis and of Quantitative Ultrasound to Assess Dental Implant Osseointegration.

Dental implants are widely used in the clinic. However, there remain risks of failure, which depend on the implant stability. The aim of this paper is to compare two methods based on resonance frequency analysis (RFA) and on quantitative ultrasound (QUS) and that aim at assessing implant stability. Eighty-one identical dental implants were inserted in the iliac crests of 11 sheep. The QUS and RFA measurements were realized after different healing times (0, 5, 7, and 15 weeks). The results obtained with the QUS (respectively RFA) method were significantly different when comparing two consecutive healing time for 97% (respectively, 18%) of the implants. The error made on the estimation of the healing time when analyzing the results obtained with the QUS technique was around 10 times lower than that made when using the RFA technique. The results corresponding to the dependence of the ISQ versus healing time were significantly different when comparing two directions of RFA measurement. The results show that the QUS method allows a more accurate determination of the evolution of dental implant stability when compared to the RFA method. This study paves the way towards the development of a medical device, thus providing a decision support system to dental surgeons.

Transmission of Bartonella henselae by Ixodes ricinus.

Bartonella spp. are facultative intracellular bacteria associated with several emerging diseases in humans and animals. B. henselae causes cat-scratch disease and is increasingly associated with several other syndromes, particularly ocular infections and endocarditis. Cats are the main reservoir for B. henselae and the bacteria are transmitted to cats by cat fleas. However, new potential vectors are suspected of transmitting B. henselae, in particular, Ixodes ricinus, the most abundant ixodid tick that bites humans in western Europe. We used a membrane-feeding technique to infect I. ricinus with B. henselae and demonstrate transmission of B. henselae within I. ricinus across developmental stages, migration or multiplication of B. henselae in salivary glands after a second meal, and transmission of viable and infective B. henselae from ticks to blood. These results provide evidence that I. ricinus is a competent vector for B. henselae.

Evaluation of dental implant stability in bone phantoms: Comparison between a quantitative ultrasound technique and resonance frequency analysis.

BACKGROUND: Resonance frequency analyses and quantitative ultrasound methods have been suggested to assess dental implant primary stability. PURPOSE: The purpose of this study was to compare the results obtained using these two techniques applied to the same dental implants inserted in various bone phantoms. MATERIALS AND METHODS: Different values of trabecular bone density and cortical thickness were considered to assess the effect of bone quality on the respective indicators (UI and ISQ). The effect of the implant insertion depth and of the final drill diameter was also investigated. RESULTS: ISQ values increase and UI values decrease as a function of trabecular density, cortical thickness and the screwing of the implant. When the implant diameter varies, the UI values are significantly different for all final drill diameters (except for two), while the ISQ values are similar for all final drill diameters lower than 3.2 mm and higher than 3.3 mm. The error on the estimation of parameters with the QUS device is between 4 and 8 times lower compared to that made with the RFA technique. CONCLUSIONS: The results show that ultrasound technique provides a better estimation of different parameters related to the implant stability compared to the RFA technique.

Role of the spleen in Bartonella spp. infection.

Bartonella spp. are intra-erythrocytic pathogens of mammals. In this study, we investigated the role of the spleen, and other tissue and organs in Bartonella infection. Using an in vivo model of mice infection by Bartonella birtlesii, we detected accumulation of bacteria in the spleen, with transient infection of the liver, but failed to detect any bacteria in brain or lymph nodes. We then compared bacteraemia in normal Balb/C mice and in splenectomized mice. Bacteraemia in splenectomized mice was 10-fold higher than in normal mice and lasted 2 weeks longer. In conclusion, the spleen seems to retain and filter infected erythrocytes rather than to be a sanctuary for chronic Bartonella infection.

Vector competence of the tick Ixodes ricinus for transmission of Bartonella birtlesii.

Bartonella spp. are facultative intracellular vector-borne bacteria associated with several emerging diseases in humans and animals all over the world. The potential for involvement of ticks in transmission of Bartonella spp. has been heartily debated for many years. However, most of the data supporting bartonellae transmission by ticks come from molecular and serological epidemiological surveys in humans and animals providing only indirect evidences without a direct proof of tick vector competence for transmission of bartonellae. We used a murine model to assess the vector competence of Ixodes ricinus for Bartonella birtlesii. Larval and nymphal I. ricinus were fed on a B. birtlesii-infected mouse. The nymphs successfully transmitted B. birtlesii to naïve mice as bacteria were recovered from both the mouse blood and liver at seven and 16 days after tick bites. The female adults successfully emitted the bacteria into uninfected blood after three or more days of tick attachment, when fed via membrane feeding system. Histochemical staining showed the presence of bacteria in salivary glands and muscle tissues of partially engorged adult ticks, which had molted from the infected nymphs. These results confirm the vector competence of I. ricinus for B. birtlesii and represent the first in vivo demonstration of a Bartonella sp. transmission by ticks. Consequently, bartonelloses should be now included in the differential diagnosis for patients exposed to tick bites.