PIPAC versus HIPEC: cisplatin spatial distribution and diffusion in a swine model.

Purpose: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach for delivering intraperitoneal chemotherapy and offers perspective in the treatment of peritoneal carcinomatosis. Concept is based on a 12 mmHg capnoperitoneum loaded with drug changed in microdoplets. It was postulated to guarantee a more homogeneous drug distribution and tissular uptake than hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to compare cisplatin peritoneal distribution and pharmacokinetic between HIPEC and PIPAC procedures in a healthy swine model.Methods: Two groups of eight pigs underwent either HIPEC with cisplatin (70 mg/m2) at 43 °C for 60 min, or PIPAC with cisplatin (7.5 mg/m2) for 30 min. Postoperatively, peritoneal areas were biopsied allowing peritoneal cavity cartography. Tissular and plasmatic cisplatin concentrations were analyzed.Results: Cisplatin distribution was heterogeneous in both the groups with higher concentrations obtained closed to the delivery sites. Median total platinum peritoneal concentration by pig was higher in the HIPEC group than in the PIPAC group (18.0 µg/g versus 4.3 µg/g, p < .001) but the yield was 2.2 times better with PIPAC. Platinum concentrations were higher in the HIPEC group in all stations. At each time-point, cisplatin plasmatic concentrations were higher in the HIPEC group (p < .001) but beneath the toxicity threshold.Conclusions: With doses used in clinical practice, HIPEC guaranteed a higher cisplatin peritoneal uptake than PIPAC in this swine model. Spatial drug distribution was heterogeneous with both technics, with hotspots closed to the drug delivery sites. Nevertheless, considering the dose ratio, IP drug uptake yield was better with PIPAC.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) might increase the risk of anastomotic leakage compared to HIPEC: an experimental study.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) and hyperthermic intraperitoneal chemotherapy (HIPEC) are technics proposed to treat patients with peritoneal carcinomatosis, in different settings. There is some concern about an over-risk of anastomotic leakage (AL) with PIPAC jeopardizing a combination with cytoreductive surgery. This study used a healthy swine model to compare the postoperative AL rate between PIPAC and HIPEC with digestive resection and to analyze macrocirculation and microcirculation parameters. METHODS: Segmental colonic resection with a handsewn anastomosis was performed on 16 healthy pigs; 8 pigs had a PIPAC procedure with 7.5 mg/m2 cisplatin (PIPAC group), and 8 pigs had a closed HIPEC procedure with 70 mg/m2 cisplatin and 42 °C as the target intraperitoneal temperature (HIPEC group). Pigs were kept alive for 8 days, then sacrificed and autopsied to look for AL, which was defined as local abscess or digestive fluid leakage when pressure was applied to the anastomosis. Food intake, weight, and core temperature were monitored postoperatively. Macrocirculation (heart rate, systolic blood pressure) and microcirculation parameters (percentage of perfused vessels, perfused vessels density, DeBacker score) were evaluated intraoperatively at five timepoints. Results were compared between pigs with AL and those without. RESULTS: The HIPEC group had no AL, but 3 of 8 pigs (37.5%) had AL in the PIPAC group (p = 0.20). Heart rate and core temperature showed perioperative increases in the HIPEC group. Intraoperatively, heart rate was higher in the HIPEC group at the two last timepoints (123 vs. 93 bpm, p = 0.031, and 110 vs. 85 bpm, p = 0.010, at timepoints 3 and 4, respectively). Other macrocirculatory and microcirculatory parameters showed no significant differences. CONCLUSION: In this healthy swine model, PIPAC might have increased AL incidence compared to HIPEC. This potential over-risk did not seem to be related to changes in the microcirculation. PIPAC should probably not be used with digestive resection and should be avoided in cases of perioperative serosal injury.

An Analysis of Lateral Crural Repositioning and Its Effect on Alar Rim Position.

IMPORTANCE: Cephalically malpositioned lateral crura are a frequent cause of alar rim retraction during both primary and revision rhinoplasty. OBJECTIVE: To demonstrate the efficacy of lateral crural repositioning as an isolated maneuver as and combined with adjunctive grafts for lowering the alar rim. DESIGN, SETTING, AND PARTICIPANTS: From August through December 2014, we retrospectively reviewed the cases of 54 patients (102 hemi-noses) who had lateral crural repositioning performed by the same surgeon between 2007 and 2013. Only patients with standardized photographs taken preoperatively and at least 6 months postoperatively were included in the study. INTERVENTIONS: All primary and revision cases were completed via an open rhinoplasty approach and had lateral crural repositioning performed. MAIN OUTCOMES AND MEASURES: Preoperative and postoperative photographs were compared using Adobe Photoshop CS via a modified Gunter technique to measure the degree of alar rim retraction on lateral views. The change in angle was then calculated, and statistical analysis conducted using a paired t test. RESULTS: A total of 54 patients (102 hemi-noses) met inclusion criteria; 42 (79%) were women, and the average patient age was 41.3 years. Forty-five (83%) of the cases were revision rhinoplasties, and the average time to obtaining postoperative photographs was 11.3 months. The mean (SD) anterior nostril apex angles preoperatively (31.3° [8.9°]) and postoperatively (24.5° [6.8°]) indicated a net decrease of 6.8° (P < .001). Excluding patients who had other rim-lowering grafts (alar rim and/or composite grafts), we saw a similar result comparing preoperative (31.1° [8.2°]) and postoperative (24.5° [6.7°]) angles, with a net decrease of 6.6° degrees (P < .001). When examining patients who underwent lateral crural repositioning alone compared with those who also had lateral crural strut grafts, we saw a decrease of 6.9° (P < .001) and 6.7° degrees (P < .001), respectively. CONCLUSIONS AND RELEVANCE: Repositioning of the lower lateral cartilages results in a statistically significant lowering of the alar rim. Our data suggest that when combined with lateral crural repositioning, the addition of adjunctive grafts does not add significantly to the rim-lowering effect. LEVEL OF EVIDENCE: 3.

Low WSS Induces Intimal Thickening, while Large WSS Variation and Inflammation Induce Medial Thinning, in an Animal Model of Atherosclerosis.

OBJECTIVE: Atherosclerotic plaque development in the arterial wall is the result of complex interaction between the wall's endothelial layer and blood hemodynamics. However, the interaction between hemodynamic parameters and inflammation in plaque evolution is not yet fully understood. The aim of the present study was to investigate the relation between wall shear stress (WSS) and vessel wall inflammation during atherosclerotic plaque development in a minipig model of carotid stenosis. METHODS: A surgical procedure was performed to create left common carotid artery stenosis by placement of a perivascular cuff in minipigs under atherogenic diet. Animals were followed up on 3T MRI, 1 week after surgery and 3, 6, and 8 months after initiation of the diet. Computational fluid dynamics simulation estimated WSS distribution for the first imaging point. Vascular geometries were co-registered for direct comparison of plaque development and features (Gadolinium- and USPIO-Contrast Enhanced MRI, for permeability and inflammation respectively) with the initial WSS. Histological analysis was performed and sections were matched to MR images, based on spatial landmarks. RESULTS: Vessel wall thickening, permeability and inflammation were observed distally from the stenosis. They were eccentric and facing regions of normal wall thickness. Histological analysis confirmed eccentric plaque formation with lipid infiltration, intimal thickening and medial degradation. High phagocytic activity in the stenosis region was co-localized with high WSS, corresponding to intense medial degradation observed on histology samples. CONCLUSION: Lower WSS promotes atherosclerotic plaque development distal to an induced stenosis. Vascular and perivascular inflammation locations were predominant in the high WSS stenosis segment, where medial thinning was the major consequence.

Endoluminal MR-guided ultrasonic applicator embedding cylindrical phased-array transducers and opposed-solenoid detection coil.

PURPOSE: MR-guided high-intensity contact ultrasound (HICU) was suggested as an alternative therapy for esophageal and rectal cancer. To offer high-quality MR guidance, two prototypes of receive-only opposed-solenoid coil were integrated with 64-element cylindrical phased-array ultrasound transducers (rectal/esophageal). METHODS: The design of integrated coils took into account the transducer geometry (360° acoustic window within endoluminal space). The rectal coil was sealed on a plastic support and placed reversibly on the transducer head. The esophageal coil was fully embedded within the transducer head, resulting in one indivisible device. Comparison of integrated versus external coils was performed on a clinical 1.5T scanner. RESULTS: The integrated coils showed higher sensitivity compared with the standard extracorporeal coil with factors of up to 7.5 (rectal applicator) and 3.3 (esophageal applicator). High-resolution MR images for both anatomy (voxel 0.4 × 0.4 × 5 mm(3)) and thermometry (voxel 0.75 × 0.75 × 8 mm(3), 2 s/image) were acquired in vivo with the rectal endoscopic device. The temperature feedback loop accurately controlled multiple control points over the region of interest. CONCLUSION: This study showed significant improvement of MR data quality using endoluminal integrated coils versus standard external coil. Inframillimeter spatial resolution and accurate feedback control of MR-guided HICU thermotherapy were achieved.

Routine follow-up imaging of kidney injuries may not be justified.

BACKGROUND: The purpose of this investigation was to determine the yield of repeat follow-up imaging in patients sustaining renal trauma. METHODS: The Los Angeles County+University of Southern California Medical Center trauma registry was reviewed to identify all patients with a diagnosis of kidney injury from 2005 to 2008. All final attending radiologist interpretations and the dates of the initial and follow-up computerized tomography (CT) scans were also reviewed. Grades I, II, and III were grouped as low-grade injuries and grades IV and V as high-grade injuries. RESULTS: During the 4-year study period, 120 (1.2% of all trauma admissions) patients had a total of 121 kidney injuries: 85.8% were male, and the mean age±SD was 31.1 years±14.5 years. Overall, 22.6% of blunt and 35.6% of penetrating kidney injuries were high grade (IV-V; p=0.148). These high-grade injuries were managed operatively in 35.7% and 76.2% of blunt and penetrating injuries, respectively, (p=0.022). Overall, 31.7% underwent at least one follow-up CT; 24.2% of patients with blunt and 39.7% of patients with penetrating kidney injury, respectively. None of the patients with a low-grade injury managed nonoperatively developed a complication, independent of the injury mechanism. High-grade blunt and penetrating kidney injuries managed nonoperatively were associated with 11.1% and 20.0% complication rate identified on follow-up CT, respectively. For patients who underwent surgical interventions for penetrating kidney injuries, the diagnosis of the complication was made at 9.8 days±7.0 days (range, 1-24 days), with 83.3% of them diagnosed within 8 days postoperatively. The most frequent complication identified was an abscess in the renal fossa (50.0% of all complications). Other complications included urinoma, ureteral stricture, and pseudoaneurysm. All patients who developed complications were symptomatic, prompting the imaging that led to the diagnosis. All patients who developed a complication after a penetrating injury required intervention for the management of the complication. CONCLUSION: Selective reimaging of renal injuries based on clinical and laboratory criteria seems to be safe regardless of injury mechanism or management. High-grade penetrating injuries undergoing operative intervention should carry the highest degree of vigilance and lowest threshold for repeat imaging.

Automatic temperature control for MR-guided interstitial ultrasound ablation in liver using a percutaneous applicator: ex vivo and in vivo initial studies.

Image-guided thermal ablation offers minimally invasive options for treating hepatocellular carcinoma and colorectal metastases in liver. Here, the feasibility and the potential benefit of active temperature control for MR-guided percutaneous ultrasound ablation was investigated in pig liver. An MR-compatible interstitial ultrasound applicator (flat transducer), a positioning system with rotation-translation guiding frame, and an orbital ring holder were developed. Step-by-step rotated elementary lesions were produced, each being formed by directive heating of a flame-shaped volume of tissue. In vivo feasibility of automatic temperature control was investigated on two pigs. Proton Resonance Frequency Shift (PRFS)-based MR thermometry was performed on a 1.5-T clinical scanner, using SENSE acceleration and respiratory gating. MR follow-up of animals and macroscopic analysis were performed at 3 and, respectively, 4 days postprocedure. No sonication-related radiofrequency artifacts were detected on MR images. The temperature controller converged to the target elevation within +/-2 degrees C unless the requested power level exceeded the authorized limit. Large variability of the controller's applied powers from one sonication to another was found both ex vivo and in vivo, indicating highly anisotropic acoustic coupling and/or tissue response to identical beam pattern along different radial directions. The automatic control of the temperature enabled reproducible shape of lesions (15 +/- 2 mm radial depth).

In vivo evaluation of a mechanically oscillating dual-mode applicator for ultrasound imaging and thermal ablation.

Unresectable liver tumors are often treated with interstitial probes that modify tissue temperature, and efficacious treatment relies on image guidance for tissue targeting and assessment. Here, we report the in vivo evaluation of an interstitial applicator with a mechanically oscillating five-element dual-mode transducer. After thoroughly characterizing the transducer, tissue response to high-intensity ultrasound was numerically calculated to select parameters for experimentation in vivo. Using perfused porcine liver, B-mode sector images were formed before and after a 120-s therapy period, and M-mode imaging monitored the therapy axis during therapy. The time-averaged transducer surface intensity was 21 or 27 W/cm (2). Electroacoustic conversion efficiency was maximally 72 +/- 3% and impulse response length was 295 +/- 1.0 ns at -6 dB. The depth of thermal damage measured by gross histology ranged from 10 to 25 mm for 13 insertion sites. For six sites, M-mode data exhibited a reduction in gray-scale intensity that was interpreted as the temporal variation of coagulation necrosis. Contrast ratio analysis indicated that the gray-scale intensity dropped by 7.8 +/- 3.3 dB, and estimated the final lesion depth to an accuracy of 2.3 +/- 2.4 mm. This paper verified that the applicator could induce coagulation necrosis in perfused liver and demonstrated the feasibility of real-time monitoring.

Developing an interstitial ultrasound applicator for thermal ablation in liver: results of animal experiments.

BACKGROUND: In this project, an interstitial ultrasound applicator was developed for the treatment of primary and secondary cancers of the liver. Experiments on animals were used to check the destructive capabilities of this probe within the hepatic parenchyma of the pig in vivo, with a study of the physical parameters of the ultrasound treatment. In parallel, the possibility of visualizing the lesions induced by means of ultrasound imaging was also studied. MATERIALS AND METHODS: Thirteen pigs were used in this project, which had received the prior approval of the ethics committee of Lyon Veterinary School. Ultrasound lesions were performed by varying the physical parameters of the treatment (acoustic intensity and shot time) with the aim of obtaining larger and larger areas of destruction. An operative device was developed to ensure precision in treatments. Two types of lesions were performed: elementary lesions corresponding to single shots at 40 degrees to 50 degrees rotation intervals, and cylindrical lesions obtained by a continuous rotary deployment of the probe. The effect of hepatic pedicle clamping on the size of ultrasound lesions was studied. The aspect and dimension of the lesions were analyzed by means of operative ultrasound imaging and macroscopic examination. Histological analysis showed the impact of the treatment on the hepatic parenchyma. RESULTS: This work made it possible to study the elementary ultrasound lesions produced by our probe. Seventy elementary ultrasound lesions were analyzed. Treatments could be performed on all pigs without any difficulty. There were no operative incidents. The ultrasound-induced elementary lesions showed complete necrosis, with lesion length of up to 37 mm obtained without resort to pedicle clamping; this must be considered as a radius of the final lesion obtained over a complete rotary deployment (360 degrees ), then a diameter of 7 cm of thermal ablation can theoretically be obtained. The effect of pedicle clamping was studied and showed improvement of the lesion length. Results of continuous rotary deployment of the probe were encouraging. Operative ultrasound imaging proved to be a simple tool for directing and positioning the applicator in the target zone on the one hand and which, on the other hand, enabled accurate, real-time visualization of the ultrasound lesions. On histological analysis, the ultrasound-induced necrosis was complete and well defined. CONCLUSION: This work shows that it is feasible to treat cancers of the liver using interstitial ultrasound probe. Thermal damage obtained on the hepatic parenchyma of pigs in vivo is complete and can be monitored using simple diagnostic ultrasound. The ultrasound parameters can be adapted to obtain destruction of variable size.

Liver regeneration and hemodynamics in pigs with mesocaval shunt.

BACKGROUND: A surgical technique using a mesocaval shunt and downstream ligation of the superior mesenteric vein has been recently proposed to overcome the size limitations that restrict the use of partial liver grafts. We designed an experimental study in pigs to evaluate the capacities of liver regeneration and hemodynamic changes after completion of this procedure. MATERIAL AND METHODS: Liver regeneration after left hepatectomy was compared between two groups of five pigs, with or without mesocaval shunt, sacrificed 11 to 14 days after surgery. A third group of five animals was used for hemodynamic studies. RESULTS: Liver regeneration in study animals was 45.3% of controls. This was obtained despite a reduction of the venous inflow to 15.6% of the control, resulting in a net decrease of the total blood inflow to 56% of the control, despite a compensatory increase in the arterial inflow. There was no significant difference in mitotic index, hepatocellular size, and glycogen content between study and control animals. CONCLUSION: Our experimental study confirms that the regenerative capacities of the pig liver are largely preserved despite the dramatic reduction of the venous blood inflow, reduced to its gastroduodenosplenopancreatic component. This lends further support to the hypothesis that the gastroduodenosplenopancreatic blood is enriched in hepatotrophic factors, likely to originate from the pancreas and duodenum.