Ischemic etiopathogenesis as the possible origin of post-double baloon enteroscopy pancreatitis. A porcine model study.

The aim is to evaluate the pancreatic vascular-ischemic effects related to double balloon enteroscopy in the porcine model as a possible etiopathogenesis of post-enteroscopic pancreatitis. For this reason we carry out two independent experiments in a porcine animal model. In the first arm protocol (group I), 10 animals underwent 90 minutes of oral enteroscopy with 7 days follow-up.The levels of amylase, lipase and C-reactive protein were measured at T0 basal-T1 -90 min, T2-24, T3-7 days. Also we perform upper gastrointestinal endoscopy in a control group. At 7 days, the animals of experimental protocol-I had their pancreases removed for a pathological and immunohistochemical study to evaluate vascular epithelial growth factor (VEGF) expression.The second experimental protocol in this study aims to evaluate possible changes in vascular topography due to the double balloon enteroscopy (DBE). Group-II (10 animals) underwent oral enteroscopy and selective angiography of the cranial mesenteric artery and celiac trunk. None of the group I or control group animals presented pancreatitis, although the biochemical results for group-I showed increases in the levels of amylase, lipase and C reactive protein at 24 hours. The microscopic study for group-I showed pancreatic necrotic foci and positive VEGF expression, though these changes were not expressed in the control group.These foci were found in 50% of the group I animals and in relation to the total of the parenchyma were quantified at 6% of the pancreas. The results for group-II showed that the enteroscopy caused mobilization of the mesenteric vascular axis, with signs of both intestinal and pancreatic hypoperfusion. The conclusions of this study are that, after enteroscopy in the porcine model, pancreatic necrotic foci are produced, in addition to ischemic phenomena causing VEGF expression. This could be related to episodes of visceral hypoperfusion caused by vascular alterations on a topographic level. This can be related to the possible ischemic etiopathogenesis described for post-enteroscopic pancreatitis.

Validation of a realistic simulator for veterinary gastrointestinal endoscopy training.

This article reports on the face, content, and construct validity of a new realistic composite simulator (Simuldog) used to provide training in canine gastrointestinal flexible endoscopy. The basic endoscopic procedures performed on the simulator were esophagogastroduodenoscopy (EGD), gastric biopsy (GB), and gastric foreign body removal (FBR). Construct validity was assessed by comparing the performance of novices (final-year veterinary students and recent graduates without endoscopic experience, n=30) versus experienced subjects (doctors in veterinary medicine who had performed more than 50 clinical upper gastrointestinal endoscopic procedures as a surgeon, n=15). Tasks were scored based on completion time, and specific rating scales were developed to assess performance. Internal consistency and inter-rater agreement were assessed. Face and content validity were determined using a 5-point Likert-type scale questionnaire. The novices needed considerably more time than the experts to perform EGD, GB, and FBR, and their performance scores were significantly lower (p<.010). Inter-rater agreement and the internal validity of the rating scales were good. Face validity was excellent, and both groups agreed that the endoscopy scenarios were very realistic. The experts highly valued the usefulness of Simuldog for veterinary training and as a tool for assessing endoscopic skills. Simuldog is the first validated model specifically developed to be used as a training tool for endoscopy techniques in small animals.

Carbon dioxide insufflation safety in double-balloon enteroscopy: an experimental animal study.

AIM: The aim of the present study was to assess the safety and efficacy of CO(2) during double-balloon enteroscopy (DBE) in an experimental animal model study. In this study, insufflation with room air and with CO(2) was compared. METHODS: Twenty healthy swines were used. The animals were randomly allocated to two groups. The room air-DBE group was insufflated with room air, whereas the CO(2)-DBE group was insufflated with CO(2). Endoscopy duration was 90 min. The following parameters were measured during the study (basal, 30 min, 60 min, 90 min): invasive hemodynamic parameters, ventilatory parameters, arterial blood gases, exploration depth, as well as biochemical tests. Residual gas was evaluated at the end of DBE, at 180 min and 24 h after DBE. RESULTS: During the endoscopic exploration none of the animals showed hemodynamic, ventilatory or arterial blood gas alterations in the normal reference range for the swine species. The CO(2) group showed statistically significant differences over the room air group with lower post-procedure residual gas and greater depth of the small bowel explored. CONCLUSION: The use of CO(2) for insufflation during DBE was safe and no complications associated with CO(2) were observed. In addition, the use of CO(2) offers benefits over the use of room air for insufflation during DBE.

New combined approach in metallic ureteral stenting to avoid urothelial hyperplasia: study in swine model.

PURPOSE: We assessed the therapeutic value of a new treatment option for ureteral strictures that may avoid urothelial hyperplasia, which is the main cause of metallic stent failure. MATERIALS AND METHODS: We used 24 pigs in this study. An experimental model of ureteral stricture was induced in all animals. Obstruction was confirmed by ultrasound and retrograde ureteropyelogram 6 weeks after model creation. The pigs were then randomly allocated to 2 experimental groups. Therapy involved placement of a 6 × 30 mm metallic ureteral covered stent in the ureteral stricture in group 1 and subsequent endoureterotomy at the ureteral segments adjacent to the 2 ends of the stent in group 2. A double pigtail stent was then deployed for 3 weeks. Completion studies 6 months after therapy included retrograde ureteropyelogram, endoluminal ultrasound and ureteroscopy to assess urothelial hyperplasia formation. RESULTS: At the end of the study evidence of urothelial hyperplasia was seen in 50% of the pigs in group 1 and in 29% in group 2. Four and 2 cases of cranial stent migration in groups 1 and 2, respectively, were seen at 6 months. Hyperplasia and renal involvement were statistically significantly different between the groups with more damage in group 1 than in group 2. CONCLUSIONS: Hyperplasia was markedly reduced when ureteral peristalsis was inhibited by endoureterotomy at the area of interaction between the stent and the ureter.

Evaluation of a New Design of Antireflux-biodegradable Ureteral Stent in Animal Model.

OBJECTIVE: To determine the effects in urinary tract of a new antireflux-biodegradable ureteral stent. MATERIALS AND METHODS: Thirty six ureters belonging to 24 pigs were used. The study began with endoscopic, nephrosonographic, and fluoroscopic assessments. Three study groups of ureters (n = 12) were then specified. In group I, a biodegradable antireflux ureteral stent (BDG-ARS) was inserted in the right ureter of 12 pigs. Group II comprised the left ureter of the same animals, in which a double-pigtail stent was placed for 6 weeks. Group III ureters, belonging to 12 additional animals, were subjected to a ureteropelvic junction obstruction model that was then treated by endopyelotomy and stenting with BDG-ARS. Follow-ups were performed at 3-6 weeks and at 5 months. RESULTS: None of the ureters receiving the BDG-ARS showed any evidence of vesicoureteral reflux (VUR). BDG-ARS degradation took place in a controlled and predictable fashion from the third to the sixth weeks, and no obstructive fragments appeared. No differences were found between groups I and II regarding passive ureteral dilation, but significant differences were found regarding VUR and ureteral orifice damage. BDG-ARS always maintained distal ureteral peristalsis. BDG-ARS in group III showed a 50% positive urine culture rate and a 16.6% migration rate in both BDG-ARS groups. CONCLUSION: BDG-ARS avoided VUR and bladder trigone irritation. In addition, this polymer combination and stent-braided design achieved a consistent biodegradation rate with no obstructive fragments and with uniform degradation between the third and the sixth weeks. Consequently, morbidity associated with ureteral stents might be reduced.

Antireflux ureteral stent proof of concept assessment after minimally invasive treatment of obstructive uropathy in animal model.

OBJECTIVES: To assess the efficacy of a new anti-reflux intraureteral stent design in a swine model after minimally invasive treatment of ureteral stricture to reduce ureteral stent morbidity, previous to manufacture this design in a biodegradable fashion. METHODS: Twenty-eight female pigs were included. The study began with a cystoscopic, nephrosonographic and contrast fluoroscopic assessment. Afterwards, obstructive uropathy model in right ureter was created. Obstruction was confirmed 6 weeks later and animals were randomly distributed into 2 groups. Group I underwent laser endopyelotomy and Group-II laparoscopic pyeloplasty A 3Fr anti-reflux intraureteral stent was placed 6 weeks. Follow-up evaluations were performed at 3-6 weeks. The final follow-up was completed at 5 months and included the aforementioned diagnostic methods and pathological study. RESULTS: None of the study animals showed any vesicoureteral reflux signs or ureteral orifice injury. There were no urinomas or ureteric fistulas. The dislodgement rate was 10.7%. After 6 weeks of stenting, 71.4% of ureters showed ureteral peristalsis below the stent, and 100% at the final follow-up. After pathological assessment, no differences were shown at UPJ and healing in the incised area was correct in both groups. CONCLUSIONS: The new stent design avoids vesicoureteral reflux and bladder trigone irritation, consequently might reduce morbidity associated with double pigtail ureteral stents. This study also shows that it is only necessary temporary scaffolding the incised ureteral segment and not the entire length of the ureter after minimally invasive surgery. It is also necessary to manufacture this design in a biodegradable material, thus avoiding its removal.

Evidences supporting the vascular etiology of post-double balloon enteroscopy pancreatitis: Study in porcine model.

Double balloon enteroscopy (DBE) is an endoscopic technique broadly used to diagnose and treat small bowel diseases. Among the associated complications of the oral DBE, post-procedure pancreatitis has taken the most attention due to its gravity and the thought that it might be associated to the technique itself and anatomical features of the pancreas. However, as the etiology has not been clarified yet, this paper aims to review the published literature and adds new results from a porcine animal model. Biochemical markers, histological sections and the vascular perfusion of the pancreas were monitored in the pig during DBE practice. A reduced perfusion of the pancreas and bowel, the presence of defined hypoxic areas and disseminated necrotic zones were found in the pancreatic tissue of pigs. All these evidences contribute to support a vascular distress as the most likely etiology of the post-DBE pancreatitis.

Laparoscopic Partial Nephrectomy With Potassium-titanyl-phosphate Laser Versus Conventional Laparoscopic Partial Nephrectomy: An Animal Randomized Controlled Trial.

OBJECTIVE: To explore the feasibility, safety, and short-term results of potassium-titanyl-phosphate (KTP) laser laparoscopic partial nephrectomy (KTP-LPN) vs conventional laparoscopic partial nephrectomy (C-LPN). MATERIALS AND METHODS: Thirty large white female pigs were randomized to KTP-LPN or C-LPN. Laparoscopic radical right nephrectomy was performed, and an artificial renal tumor was placed in the left kidney in 3 locations. A week later, 15 pigs underwent C-LPN and 15 underwent KTP-LPN. All C-LPNs were performed with renal ischemia. A 120-W setting was used, without arterial clamping in the KTP-LPN group. Follow-up was done at day 1, week 3, and week 6. Retrograde pyelography was performed at 6 weeks, followed by animal sacrifice and necropsy. RESULTS: All KTP-LPNs were performed without hilar clamping. C-LPNs were performed with hilar clamping, closing of the collecting system, and renorraphy. In the KTP laser group, 2 pigs died due to urinary fistula in the first week after surgery. In the C-LPN group, 1 pig died due to myocardial infarction and another due to malignant hyperthermia. Hemoglobin and hematocrit recovery were lower at 6 weeks in the KTP-LPN group. Renal function 24 hours after surgery was worse in the KTP-LPN group but recovered at 3 weeks and 6 weeks. No differences were observed in surgical margins. The necropsy showed no differences. Limitations of the study are the impossibility to analyze the collecting tissue sealing by the KTP, and the potential renal toxicity of the KTP laser. CONCLUSION: Although KTP-LPN is feasible and safe in the animal model, further studies are needed.

[Effects of preventive double-J stent placement in ureteral obstruction treatment with metal stents on animal model]. / EFECTOS DE LA COLOCACIÓN PREVENTIVA DE UN CATÉTER URETERAL JJ DURANTE EL TRATAMIENTO DE LA OBSTRUCCIÓN URETERAL CON STENTS METÁLICOS EN MODELO ANIMAL.

OBJECTIVES: The purpose of this experimental study is to assess the additive effects of temporary JJ stent placement together with metal stents (MS) in the treatment obstructive uropathy, in order to reduce urothelial hyperplasia formation. METHODS: Twenty-four pigs were included, and an experimental model of obstructive uropathy was created. Six weeks after obstructive uropathy model induction, ureteral obstruction was confirmed using ultrasonography, ureteropyelography and endoluminal ultrasound. Afterwards, animals were randomly distributed into 2 groups. Group I underwent covered MS placement and JJ ureteral stenting for 3 weeks. Animals in Group II received the same MS without simultaneous JJ stenting. The follow-up was at 3 weeks and at 6 months. RESULTS: Incidence of urothelial hyperplasia was higher in Group I than Group II, but without statically significant differences. On the other hand, Group II showed a significantly higher degree of obstruction severity due to hyperplasia. The migration rate in both groups was 33.3% at the end of the study. Significant differences were shown on animals showing urinary tract infection (UTI) and hyperplasia against those with hyperplasia but no infection. There was a high rate of correlation between UTI and obstructive urothelial hyperplasia. CONCLUSIONS: Placement of JJ ureteral catheter does not inhibit urothelial hyperplasia associated with placement of metal mesh stents, although it significantly reduces its obstructive severity in long-term follow-up. Urinary tract infection is directly related to the development and magnitude of the urothelial hyperplasia.

Preliminary Assessment of a New Antireflux Ureteral Stent Design in Swine Model.

OBJECTIVE: To assess a new antireflux ureteral stent in animal model. The design expects to reduce morbidity associated with JJ ureteral stents. MATERIALS AND METHODS: Twelve pigs were used in this study. The study began with a nephrosonographic assessment and excretory urography. Afterward, measurement of the internal diameter of both ureteropelvic junctions (UPJ) by retrograde ureteropyelography was performed. A 3 Fr (ARS group) antireflux ureteral stent was placed in the right kidney and a JJ 4 Fr (JJ group) stent was placed in the left. Follow-ups were performed at 3-6 weeks; both stents were removed at 6 weeks. The final follow-up was completed at 5 months. This includes the above-mentioned diagnostic methods and an anatomopathological study. RESULTS: There were no significant differences in UPJ diameter evolution between groups. During renal damage assessment, significant differences at 3 and 6 weeks were found, renal dilation being larger in JJ group. The JJ group shows a higher degree of vesicoureteral reflux at 3 and 6 weeks. After assessment of ureteral orifice, significant differences between groups were found at 3 weeks, 6 weeks, and 5 months, damage being more severe in the JJ group. After anatomopathological assessment, no statistical significance at UPJ was observed. However, statistical significance was found at ureterovesical junction, damage being more severe in the JJ group. CONCLUSION: The antireflux ureteral stent design dilates the upper urinary tract without affecting ureterovesical junction, and consequently reduces morbidity associated with JJ ureteral stents. Therefore, its patient tolerance will possibly be better than that to existent designs.

Development and Validation of a Novel Skills Training Model for Retrograde Intrarenal Surgery.

PURPOSE: The aim of this study is to validate a training model that combines the use of nonbiologic and biologic simulators as well as live porcine animal model in endoscopic retrograde intrarenal surgery (RIRS). MATERIALS AND METHODS: A total of 60 urologists took part in this study, and the activity lasted for 2 days. The training model was divided into three modules: Module-I, related to the acquisition of basic theoretical knowledge; Module-II, consisting of an internship with bench models; and Module III, in which animal models were used. First, trainees practiced with animals without using a lesion model (placement of an ureteral access sheath under fluoroscopic guidance and flexible ureterorenoscopy). Afterward, they practiced on a porcine animal model of bilateral renal lithiasis. Performance was measured using a validated global rating score and RIRS checklist score. Face and content validation as well as constructive validation provided by trainees in front of 15 experts were performed during the practice. RESULTS: Face and content validations were satisfactory. "Individual" constructive validity showed statistical significance between the first and the last time that trainees practiced on an animal model. Statistical significance was also found between trainees and expert scores. There were 73.4% of trainees who increased their skills by more than 40%. CONCLUSION: This RIRS training model allows for the acquisition of technical knowledge and skills as face, content, and constructive validation show. A structured use of nonbiologic, biologic, and animal model simulators allows the increase of RIRS skills.

Description and validation of realistic and structured endourology training model.

PURPOSE: The aim of the present study was to validate a model of training, which combines the use of non-biological and ex vivo biological bench models, as well as the modelling of urological injuries for endourological treatment in a porcine animal model. MATERIAL AND METHODS: A total of 40 participants took part in this study. The duration of the activity was 16 hours. The model of training was divided into 3 levels: level I, concerning the acquisition of basic theoretical knowledge; level II, involving practice with the bench models and level III, concerning practice in the porcine animal model. First, trainees practiced with animals without using a model of injured (ureteroscopy, management of guide wires and catheters under fluoroscopic control) and later practiced in lithiasic animal model. During the activity, an evaluation of the face and content validity was conducted, as well as constructive validation provided by the trainees versus experts. Evolution of the variables during the course within each group was analysed using the Student's t test for paired samples, while comparisons between groups, were performed using the Student's t test for unpaired samples. RESULTS: The assessments of face and content validity were satisfactory. The constructive validation, "within one trainee" shows that were statistical significant differences between the first time the trainees performed the tasks in the animal model and the last time, mainly in the knowledge of procedure and Holmium laser lithotripsy cathegories. At the beginning of level III, there are also statistical significant differences between trainee's scores and the expert's scores. CONCLUSIONS: This realistic Endourology training model allows the acquisition of knowledge and technical and non-technical skills as evidenced by the face, content and constructive validity. Structured use of bench models (biological and non biological) and animal model simulators increase the endourological basic skills.

Evaluation in an animal model of a hybrid covered metallic ureteral stent: a new design.

OBJECTIVE: To evaluate a new design for a hybrid, dynamic, metallic ureteral stent that might avoid the formation of urothelial hyperplasia after ureteral metallic stenting in an experimental study. MATERIALS AND METHODS: A total of 30 healthy female pigs were included in the present study, and an experimental obstructive uropathy in the right lumbar ureter was created in each pig. Obstruction was confirmed using percutaneous ultrasonography and retrograde ureteral pyelography and endoluminal ultrasonography 6 weeks after obstructive uropathy model creation. Then, the pigs were randomly distributed into 2 groups. Group 1 underwent standard metallic ureteral self-expanding internally covered stent deployment. Group 2 received a new hybrid metallic ureteral self-expanding internally covered stent. The follow-up period was 6 months. RESULTS: The hybrid metallic ureteral self-expanding internally covered stent group had a lower rate of urothelial hyperplasia (21% vs 70%), reduced stent migration (6.6% vs 33.3%), and a greater success rate after 6 months of follow-up (86.6% vs 47%) compared with the standard metallic ureteral self-expanding internally covered stent deployment group, with statically significant differences between the 2 groups. CONCLUSION: Our experimental results have indicated that the use of the hybrid metallic ureteral self-expanding internally covered stent in ureteral strictures is feasible, safe, and effective and reduces the formation of urothelial hyperplasia without secondary interventions to maintain ureteral patency.