Cyclodextrin Polymer Preserves Sirolimus Activity and Local Persistence for Antifibrotic Delivery over the Time Course of Wound Healing.

Fibrosis and dysphagic stricture of the esophagus is a major unaddressed problem often accompanying endoscopic removal of esophageal cancers and precancerous lesions. While weekly injections of antiproliferative agents show potential for improved healing, repeated injections are unlikely clinically and may alternatively be replaced by creating an esophageal drug delivery system. Affinity-based polymers have previously shown success for continuous delivery of small molecules for weeks to months. Herein, we explored the potential of an affinity-based microparticle to provide long-term release of an antiproliferative drug, sirolimus. In molecular docking simulations and surface plasmon resonance experiments, sirolimus was found to have suitable affinity for beta-cyclodextrin, while dextran, as a low affinity control, was validated. Polymerized beta-cyclodextrin microparticles exhibited 30 consecutive days of delivery of sirolimus during in vitro release studies. In total, the polymerized beta-cyclodextrin microparticles released 36.9 mg of sirolimus per milligram of polymer after one month of incubation in vitro. Taking daily drug release aliquots and applying them to PT-K75 porcine mucosal fibroblasts, we observed that cyclodextrin microparticle delivery preserved bioactivity of sirolimus inhibiting proliferation by 27-67% and migration of fibroblasts by 28-100% of buffer treated controls in vitro. Testing for esophageal injection site losses, no significant loss was incurred under simulated saliva flow for 10 min, and 16.7% of fluorescently labeled polymerized cyclodextrin microparticle signal was retained at 28 days after submucosal injection in esophageal tissue ex vivo versus only 4% of the initial amount remaining for free dye molecules injected alone. By combining affinity-based drug delivery for continuous long-term release with a microparticle platform that is injectable yet remains localized in tissue interstitium, this combination platform demonstrates promise for preventing esophageal fibrosis and stricture.

Magnetic compression anastomosis (magnamosis) in a porcine esophagus: Proof of concept for potential application in esophageal atresia.

BACKGROUND: Magnetic compression anastomosis (magnamosis) is the process of forming a sutureless anastomosis of the gastrointestinal tract using two magnetic Harrison rings. It has been shown to be effective in stomach, small bowel and colon, but has not been implemented in the esophagus. A pure esophageal atresia porcine model was developed to test the concept. METHODS: Five pigs weighing between 35 and 65 kg were used. In all pigs, a percutaneous endoscopic gastrostomy (PEG) tube was placed, and a right thoracotomy was performed. Esophageal atresia was simulated by transecting the esophagus with a cutting stapler, and magnets were placed endoscopically to approximate the two ends of the esophagus. In the first pig, the tissue within the magnetic ring was excised endoscopically to achieve immediate patency. In the second pig, approximation of the blind esophageal ends was reinforced with 3-4 externally-placed sutures but immediate patency was not performed. In the last three pigs, both external suture reinforcement and immediate patency were performed. The pigs survived for 10-14 days and received nutrition through PEG tube. At necropsy, an esophagram was performed, the specimen was explanted and a leak test was performed. RESULTS: The first pig died in the early postoperative period from a leak owing to separation of the magnets. The second pig died from aspiration before the anastomosis formed. The last three pigs survived until the study endpoint. The third pig had a contained leak owing to the staple line being placed between the magnets; this was not clinically significant. The last two pigs had well-formed anastomoses. Burst tests showed no leak when injecting saline up to 30 mmHg. CONCLUSION: Magnamosis is technically feasible for esophagoesophageal anastomoses. A survival model for pure esophageal atresia was developed and refined in pigs. Further work in this area may lead to clinical use in humans.

Creation of an Esophageal Atresia Animal Model Using a Bifurcated Esophagus to Maintain Digestive Tract Continuity.

INTRODUCTION: We previously developed a porcine model of long gap pure esophageal atresia (EA) to aid in the creation of novel devices and techniques for treatment of EA. Shortcomings of the model included difficulty decompressing the proximal esophageal pouch (leading to recurrent aspiration) and a requirement for gastrostomy tube (G-tube) feeds. Therefore, we sought to create a porcine model with a bifurcated esophagus wherein one portion of the esophageal lumen retained patency and the other part mimicked EA. METHODS: After G-tube placement, thoracotomy was performed with subsequent partial stapled transection of the esophagus in a transverse manner, followed by longitudinal, partial stapled transection of the esophagus proximally and distally. Magnets were placed in the esophageal pouches. RESULTS: Proximal and distal esophageal pouches were created while preserving a parallel, narrower segment of continuous esophagus. G-tube feeds were used initially, but the animal ultimately tolerated full nutrition by mouth. The magnets successfully restored esophageal continuity. The animal regained much of the initial weight lost and survived to planned euthanasia. Necropsy revealed anastomosis formation without evidence of leak. CONCLUSIONS: A bifurcated porcine esophagus model was successfully devised, simulating EA while allowing the animal to receive oral feeds and clear oral secretions. This model is anticipated to promote animal well-being and ease of care during future investigations, as well as a platform for the safe development of new therapies for EA.

Assessing the Adequacy of Absorbable Braided Suture for Laparoscopic High Ligation in Rabbits.

PURPOSE: Our previous work demonstrated that intentional peritoneal injury reduces the incidence of recurrence of a patent processus vaginalis even after removal of the suture. Therefore, the necessity of permanent suture has been brought into question because of the risk of suture granuloma formation. The purpose of this study was to evaluate the efficacy of absorbable, braided versus permanent, braided suture in a rabbit survival model of laparoscopic percutaneous ligation of the processus vaginalis with intentional peritoneal injury. MATERIALS AND METHODS: Eighteen New Zealand White rabbits underwent bilateral subcutaneous endoscopically assisted ligation (SEAL) of the internal ring. Before SEAL, peritoneal injury was caused with endoscopic shears. Each animal was randomized to receive absorbable braided suture on one side and permanent braided suture on the contralateral side. The rabbits were survived for 8 weeks to allow for complete hydrolysis of the absorbable suture. Necropsy was performed during which the integrity of the repair was assessed with insufflation of carbon dioxide up to 30 mm Hg. McNemar's test for paired data was performed for statistical analysis. RESULTS: Seventeen rabbits survived 8 weeks. One rabbit died in the early postoperative period because of urinary tract obstruction. After insufflation, four (24%) recurrences were present in the absorbable group and two (12%) recurrences were present in the permanent group. This difference was not statistically significant (P = .50). Both rabbits with a recurrence on the side with permanent suture also had a recurrence with absorbable suture on the contralateral side. In all rabbits, the permanent suture was identified, whereas there was no visual evidence of absorbable suture. CONCLUSIONS: A trend toward a higher recurrence rate with the use of absorbable braided suture was present, although, in this study, the finding was not statistically significant. Caution should be used when considering implementation of absorbable suture for laparoscopic inguinal hernia repair.

Creation of an animal model for long gap pure esophageal atresia.

INTRODUCTION: Long gap pure esophageal atresia (LGPEA) is a congenital disorder in which the esophagus is in discontinuity, and the proximal and distal ends cannot be anastomosed in a primary fashion. No animal model for pure esophageal atresia exists. Here we describe a survival animal model for LGPEA, which will ultimately serve to test novel devices and techniques to restore continuity. METHODS: A non-survival study was first conducted in six rabbits to refine a protocol for the survival model. An open gastrostomy tube was placed, followed by a partial esophagectomy. Next, a survival study was performed with seven rabbits in which the same procedures were performed. Finally, the procedure was optimized in domestic swine. RESULTS: Despite developing the techniques and gaining valuable information in the non-survival study, none of the rabbits in the survival portion of the study lived beyond post-operative day four. Due to this complication with the rabbit, the LGPEA model was attempted in a porcine model. The pig survived to post-operative day ten, and was healthy enough to be used for further study. CONCLUSION: A porcine model of long gap pure esophageal atresia was developed which is effective and feasible to be used for testing new methods of treatment of LGPEA.

Porcine Abdominal Wall Simulator for Laparotomy Incision and Closure.

We describe an economical and simple abdominal wall model that provides a realistic experience for trainees as they develop the skills of creating an abdominal incision through the midline, followed by closure of the fascia and skin.

Preliminary results of antiscarring therapy in the prevention of postendoscopic esophageal mucosectomy strictures.

BACKGROUND: Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C (MMC), halofuginone (Hal), and transforming growth factor ß3 (TGF-ß3) exhibits antiscarring effects that may prevent post-ESD stricture formation. METHODS: Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n = 6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5 mg (n = 2), 0.5 mg (n = 2); Hal 5 mg (n = 2), 1.5 mg (n = 2), 0.5 mg (n = 2); TGF-ß3 2 µg (n = 2), 0.5 µg (n = 2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80 % or the animals were unable to maintain weight. RESULTS: The control group had a luminal diameter reduction of 78.2 ± 10.9 % by 2 weeks and were euthanized by week 3. Compared at 2 weeks, the Hal group showed a decrease in mean stricture formation (68.4 % low dose, 57.7 % high dose), while both TGF-ß3 dosage groups showed no significant change (65.3 % low dose, 76.2 % high dose). MMC was most effective in stricture prevention (53.6 % low dose, 35 % high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-ß3 and Hal treated areas appeared re-epithelialized and healthy. CONCLUSIONS: Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formation after EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy.

Commercially available biological mesh does not prevent stricture after esophageal mucosectomy.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) offers a minimally invasive therapy for advanced esophageal dysplasia and early cancers but stricture formation limits its applicability. We aimed at assessing the efficacy of placement of a commercially available biological mesh for preventing stricture formation following esophageal EMR. METHODS: 25 swine were submitted to circumferential esophageal EMR with 10-cm extent and divided in five groups: one group with EMR only (control); one receiving an uncovered stent (stent-only group); and three groups receiving a stent covered with one of three extracellular matrices, namely small intestine submucosa (SIS group), acellular dermal matrix (ADM group), or urinary bladder matrix (UBM group). Stricture formation was evaluated with weekly esophagograms. RESULTS: The stent-only group had significantly less stricture formation and survival was extended compared with controls (4.8 vs. 2.4 weeks). Compared with stenting only, the addition of a biological mesh did not reduce stricture formation: percent reductions in esophageal diameter for the groups were SIS 86 %, ADM 94 %, and UBM 94 %, compared with 82 % in the stent-only group. CONCLUSIONS: Placement of commercially available biological meshes did not alter remodeling sufficiently to prevent stricture formation after esophageal EMR.

Laparoscopic mechanical fixation devices: does firing angle matter?

BACKGROUND: A variety of permanent and absorbable tacks are available for mesh fixation during laparoscopic hernia repairs. Although manufacturers recommend deploying tacks perpendicular to the tissue, achieving this can sometimes be challenging. This study aimed to analyze comparatively the effects of angled deployment among commonly used tacks. METHODS: A piece of composite mesh was fixed to the peritoneal surface of a pig with a single tack fired at either a perpendicular (90°) or acute (30°) angle. A lap-shear test was performed to determine fixation strength. Two permanent tacks (a titanium spiral tack: Protack [PT]; and a hollow screw fastener: PermaFix [PF]) and three absorbable tackers (a solid screw: Absorbatack [AT]; a hollow screw fastener: SorbaFix [SF]; and a strap: SecurStrap [SS]) were challenged. A total of 16 samples were performed for each device at each angle. A nonabsorbable transfascial suture was used as a control condition. RESULTS: Transabdominal sutures had the maximum acute tensile strength (ATS) (29.9 ± 5.5 N). Protack at both 90° and 30° performed significantly better than absorbable tacks (p < 0.01). No significant difference was found among absorbable tacks at 90°. When the same construct was compared at different angles, SS and SF performance was not affected (p = 0.07 and 0.2, respectively). In contrast, PT and AT had significantly reduced fixation strength (p = 0.003 and 0.004, respectively). However, PT fired at an acute angle had fixation equal to that of absorbable tacks fired perpendicularly. CONCLUSION: Transabdominal sutures performed better than tacks in the acute setting. No absorbable fixation device demonstrated superior efficacy within its class. Spiral titanium tacks provided better fixation than absorbable tacks at both perpendicular and acute angles. Moreover, titanium spiral tacks deployed at 30° performed equal to or better than absorbable tacks fired perpendicularly to the tissue. It appears that spiral titanium tacks should be strongly considered for cases in which perpendicular tack deployment cannot be achieved.

A novel over-the-scope deployment method for enteral stent placement.

BACKGROUND: Over the last two decades, self-expanding enteral stents have gained popularity and shown therapeutic potential for strictures, obstructions, fistulae, and perforations of the gastrointestinal (GI) tract. Currently available stent delivery systems make deployment in many locations in the GI tract difficult due to the inability to traverse curves or impossible due to the size requirements of the deployment systems. METHODS: A 67-year-old male presented to our hospital with severe gallstone pancreatitis, requiring a prolonged intensive care unit course. Two days after discharge to a rehabilitation facility he developed acute abdominal pain and pneumoperitoneum. Operative exploration failed to identify a perforation. Subsequently, a left-upper-quadrant abscess developed that was drained percutaneously, yielding coliform bacteria. The drain produced several hundred milliliters of stool a day. A barium enema demonstrated a perforation in the descending colon from an old colo-colic anastomosis site. We proposed a novel over-the-scope (OTS) stent deployment method. Utilizing a heat-activated polymer sheath, the stent was affixed to the endoscope. A modified speed-banding attachment was created to permit release of the polymer sheath once endoscopic and fluoroscopic confirmation of the correct position was obtained. RESULTS: Utilizing this method of OTS stent deployment, a fully covered 23 × 155 mm self-expanding metal stent (WallFlex, Boston Scientific, Natick, MA) was placed in the colon. Endoscopic and fluoroscopic evaluation following stent placement confirmed stent coverage of the perforation with no ongoing evidence of leak. The patient was discharged to his home state 2 weeks after stent placement in stable condition. CONCLUSION: We have developed a novel method of OTS stent placement that permits deployment of a variety of enteral stents on any available endoscope. This method permits placement of fully covered stents in locations in the GI tract not reachable with currently available delivery systems.

Biodegradable esophageal stent placement does not prevent high-grade stricture formation after circumferential mucosal resection in a porcine model.

BACKGROUND: Advanced esophageal dysplasia and early cancers have been treated traditionally with esophagectomy. Endoscopic esophageal mucosectomy (EEM) offers less-invasive therapy, but high-degree stricture formation limits its applicability. We hypothesized that placement of a biodegradable stent (BD-stent) immediately after circumferential EEM would prevent stricturing. METHODS: Ten pigs (five unstented controls, five BD-stent) were utilized. Under anesthesia, a flexible endoscope with a band ligator and snare was used to incise the mucosa approximately 20 cm proximal to the lower esophageal sphincter. A 10-cm, circumferential, mucosal segment was dissected and excised by using snare electrocautery. In the stented group, an 18-×120-mm, self-expanding, woven polydioxanone stent (ELLA-CS, Hradec-Kralove) was deployed. Weekly esophagograms evaluated for percent reduction in esophageal diameter, stricture length, and proximal esophageal dilation. Animals were euthanized when the stricture exceeded 80% and were unable to gain weight (despite high-calorie liquid diet) or at 14 weeks. RESULTS: The control group rapidly developed esophageal strictures; no animal survived beyond the third week of evaluation. At 2 weeks post-EEM, the BD-stent group had a significant reduction in esophageal diameter (77.7 vs. 26.6%, p < 0.001) and degree of proximal dilation (175 vs. 131%, p = 0.04) compared with controls. Survival in the BD-stent group was significantly longer than in the control group (9.2 vs. 2.4 weeks, p = 0.01). However, all BD-stent animals ultimately developed clinically significant strictures (range, 4-14 weeks). Comparison between the maximum reduction in esophageal diameter and stricture length (immediately before euthanasia) demonstrated no differences between the groups. CONCLUSIONS: Circumferential EEM results in severe stricture formation and clinical deterioration within 3 weeks. BD-stent placement significantly delays the time of clinical deterioration from 2.4 to 9.2 weeks, but does not affect the maximum reduction in esophageal diameter or proximal esophageal dilatation. The timing of stricture formation in the BD-stent group correlated with the loss radial force and stent disintegration.

Comparison of anterior transgastric access techniques for natural orifice translumenal endoscopic surgery.

BACKGROUND: The advancement of natural orifice translumenal endoscopic surgery (NOTES) into clinical practice is dependent on its safety, efficacy, and efficiency. Access is the obligatory first step in NOTES and serves as a surrogate to technical difficulties associated with this novel surgical approach. This study aimed to compare endoscopic transgastric access techniques in terms of safety, reproducibility, and efficiency. METHODS: Seven variations for anterior transgastric NOTES access were evaluated with female domestic swine. After marking of an anterior site, electrocautery was used to create a small gastrotomy, followed by balloon dilation and entry into the peritoneal cavity. Methodologic variations incorporated the use of guidewires, electrocautery and dilation combined within a single device, support tubes, and dilation without electrocautery. Access times were recorded, and tissue injury was evaluated. RESULTS: In 70 access attempts, the most serious complication was bleeding from the gastroepiploic vessel, controlled with electrocautery. High variability in access times was prevalent with almost all the access techniques. CONCLUSIONS: This study supports the presumption that an anterior transgastric access technique for NOTES procedures is safe. The use of a wire to mark the site and another wire to retain the gastrotomy provided safe, efficient, and reproducible transgastric access. Comparison with laparoscopy exposed the disparity in technical challenges facing NOTES, suggesting that new technology and further refinement in methodology are required for NOTES to be clinically relevant.

Endoscopic access to and exploration of the lesser sac in a human cadaver model: opportunity for transgastric endoscopic pancreatic surgery (with video).

BACKGROUND: Transgastric endoscopy may represent a viable platform for diagnostic and therapeutic pancreatic interventions with reduced morbidity. In a human cadaver model, we aimed to determine the feasibility of transgastric endoscopic access to the lesser sac, creation of an adequate working space within the lesser sac, and reliable identification of lesser sac anatomic structures. METHODS: In six human cadavers, endoscopic guidance was used to determine an appropriate access site to the lesser sac. Subsequently, endosonographic guidance was used to introduce an aspiration needle into the potential space between the stomach and the pancreas. After creating a fluid cushion and dilating the needle tract, an endoscope was advanced through the gastrotomy into the lesser sac and air insufflation was used to create a working space. Predetermined anatomic structures were systematically sought and marked when recognized. In the final two cadavers, endoscopic closure of the access site was performed. RESULTS: All six procedures were successful in achieving access to the lesser sac and establishing an adequate working space. The access sites appeared amenable to endoscopic closure. Reliable organ identification, however, was not achieved in all cases, representing one of the immediate barriers to clinical application. CONCLUSIONS: Transgastric endoscopic access to the lesser sac can be achieved reliably and an adequate working space can be established. Additional research addressing endoscopic orientation and organ recognition within the lesser sac is necessary. The immediate potential applications of this approach include differentiating benign from malignant pancreatic pathology.

Initial evaluation of a novel, prototype, forward-viewing echoendoscope in a porcine arterial bleeding model (with video).

BACKGROUND: Real-time visualization of submucosal arterial flow at the base of an ulcer might improve endoscopic hemostasis by permitting more accurate assessment of the artery, precise targeting of therapy, and confirmation of vessel ablation. OBJECTIVE: To evaluate the utility of a novel, forward-viewing echoendoscope in identifying bleeding submucosal arteries, guiding hemostatic therapy, and confirming cessation of flow through treated vessels. DESIGN: In 7 pigs, a previously described porcine model for peptic ulcer hemorrhage was created by isolating the gastroepiploic and/or short gastric artery and tunneling it into the subserosal space at laparotomy. SETTING: Animal research facility. INTERVENTION: The prototype endoscope was used to image submucosal arterial flow. EUS guidance was then used to deliver endoscopic hemostatic therapy and assess treatment adequacy. MAIN OUTCOME MEASUREMENTS: Identification of the target submucosal artery and successful delivery of EUS-guided endoscopic therapy, evidenced by cessation of Doppler flow through the target vessel. RESULTS: Tunneled arteries were visualized endosonographically in all 7 cases. EUS-guided submucosal injection of epinephrine was successful in 2 of 2 cases. EUS-guided delivery of thermal hemostatic therapy was successful in 2 of 4 cases. Absence of flow through treated vessels was confirmed in cases in which EUS-guided therapy was successfully delivered. LIMITATIONS: Acute animal model. CONCLUSION: Proof of principle experiments in a porcine peptic ulcer hemorrhage model suggest that real-time sonographic imaging of submucosal arteries is feasible with a forward-viewing echoendoscope, and guided hemostatic therapy can be delivered.

Hydroperitoneum-facilitated EUS-guided peritoneal entry and closure of alternate access sites for NOTES.

BACKGROUND: Access sites other than the anterior gastric wall may provide improved ergonomics for natural orifice transluminal endoscopic surgery (NOTES). Endoscopic ultrasound (EUS) guidance significantly reduces, but does not eliminate, risk of access through these alternate sites. This study evaluates the utility of hydroperitoneum as an adjunct to EUS-guided access and closure of alternate access sites for NOTES. METHODS: Access and closure procedures were initially performed with EUS guidance alone, and subsequently, because of complications resulting from this technique, the procedures were performed with the aid of a transabdominal hydroperitoneum. RESULTS: In this nonrandomized study, 6 access and closure procedures performed with EUS guidance alone resulted in 4 complications. After modifying the technique to incorporate pre-access hydroperitoneum, 7 EUS-guided access and closure procedures were performed without significant complications. CONCLUSIONS: Hydroperitoneum appears to be an effective adjunct to ensure the safety of EUS-guided peritoneal entry and closure of alternate access sites for NOTES.

The diagnostic efficacy of natural orifice transluminal endoscopic surgery: is there a role in the intensive care unit?

BACKGROUND: Evaluation of a potential source for abdominal sepsis in a critically ill patient can be challenging. With flexible endoscopy readily available in this setting, we sought to evaluate the diagnostic efficacy of a transgastric natural orifice transluminal endoscopic surgery (NOTES) peritoneoscopy vs. laparoscopic exploration in the identification of intra-abdominal pathology in a porcine model. METHODS: In this acute study, 15 pigs were randomized to demonstrate 0 to 4 pathologic lesions: small bowel ischemia (SBI), small bowel perforation (SBP), colon perforation (CP), and gangrenous cholecystitis (GC). Two blinded surgical endoscopists were allowed 60 min to perform NOTES or laparoscopy (LAP) to correctly identify or exclude each lesion. A prototype endoscope (R-scope, Olympus, Inc), which enables independent instrument mobility, was used in the NOTES arm. RESULTS: When considering all lesions, LAP was more sensitive diagnostically than NOTES (77.4% vs. 61.3%) overall. LAP also displayed a slightly higher NPV compared with NOTES (79.4% vs. 70.7%). However, NOTES was 100% specific with 100% positive predictive value (PPV) compared with 93.1% and 92.3% with LAP, respectively. Individually, NOTES was found most sensitive with CP identification (87.5%) and least sensitive with SBP (37.5%). The sensitivity of NOTES for SBI and GC was 62.5% and 57.1%, respectively. CONCLUSIONS: The utilization of NOTES as a diagnostic tool may have an important role in the critically ill patient when operative intervention is highly morbid. Although it may be overall inferior diagnostically compared with laparoscopy, a positive identification was highly specific with a strong predictive value. Further investigation addressing an improved small bowel evaluation technique would be beneficial. A human trial of NOTES in the ICU utilizing the current technology would still initially mandate laparoscopic or open surgical confirmation and treatment.

Peritoneal inflammatory response of natural orifice translumenal endoscopic surgery (NOTES) versus laparoscopy with carbon dioxide and air pneumoperitoneum.

BACKGROUND: The immunologic and physiologic effects of natural orifice translumenal endoscopic surgery (NOTES) versus traditional surgical approaches are poorly understood. Previous investigations have shown that NOTES and laparoscopy share similar inflammatory cytokine profiles except for a possible late-phase tissue necrosis factor-alpha (TNF-alpha) depression with NOTES. The local peritoneal reaction and immunomodulatory influence of pneumoperitoneum agents in NOTES also are not known and may play an important role in altering the physiologic insult induced by NOTES. METHODS: In this study, 51 animals were divided into four study groups, which respectively underwent abdominal exploration via transgastric NOTES using room air (AIR) or carbon dioxide (CO(2)) or via laparoscopy (LX) using AIR or CO(2) for pneumoperitoneum. Laparotomy and sham surgeries were additionally performed as control conditions. Measurements of TNF-alpha, interleukin-1beta (IL-1beta), and IL-6 were performed for peritoneal fluid collected after 0, 2, 4, and 6 h and on postoperative days (PODs) 1, 2, and 7. RESULTS: Of the 45 animals assessed, 6 were excluded because of technical operative complications. The findings showed that LX-CO(2) generated the most pronounced response with all three inflammatory markers. However, no significant differences were detected between LX-CO(2) and either NOTES group at these peak points. No differences were encountered between NOTES-CO(2) and NOTES-AIR. Subgroup comparisons showed significantly higher levels of TNF-alpha and IL-6 with NOTES-CO(2) than with LX-AIR on POD 1 (p = 0.022) and POD 2 (p = 0.002). The LX-CO(2) subgroup had significantly higher levels of TNF-alpha than the LX-AIR subgroup at 4 h (p = 0.013) and on POD 1 (p = 0.021). No late-phase TNF-alpha depression occurred in the NOTES animals. CONCLUSION: The local inflammatory reaction to NOTES was similar to that with traditional laparoscopy, and the previously described late-phase systemic TNF-alpha depression in serum was not reproduced. At the peritoneal level, NOTES is no more physiologically stressful than laparoscopy. Furthermore, regardless of which gas was used, the role of the pneumoperitoneum agent did not affect the cytokine profile after NOTES, suggesting that air pneumoperitoneum is adequate for NOTES.

Pure natural orifice translumenal endoscopic surgery partial cystectomy: intravesical transurethral and extravesical transgastric techniques in a porcine model.

OBJECTIVES: To describe 2 pure natural orifice translumenal endoscopic surgery (NOTES) techniques for partial cystectomy in a porcine model. NOTES is a new minimally invasive modality for performing abdominal surgery without transcutaneous incision. METHODS: Transurethral-A rigid cystoscope is inserted into the porcine bladder with CO(2) insufflation. With an endoscopic loop device and a grasping device, the targeted area of the bladder is manipulated into the loop. The bladder segment is excised with electrocautery. Transgastric-A gastrotomy is made with a dual channel endoscope in the porcine stomach. The endoscope is inserted and pneumoperitoneum is established by insufflation through a channel. After identifying bladder, 2 endoscopic loops are placed at the intended area of resection. An incision is made between the loops to excise the specimen. In both cases, full-thickness specimen is removed en bloc with the scope and the defect is reapproximated with endoscopic clips. RESULTS: Transurethral and transgastric NOTES approaches were achieved using standard endoscopic equipment in a porcine model. Transurethral NOTES partial cystectomy was successful in acute (n = 2) and chronic (n = 2) models. The transgastric NOTES approach was successfully performed in an acute animal. CONCLUSIONS: NOTES partial cystectomy could potentially reduce morbidity of conventional methods of partial cystectomy. Transurethral NOTES may be the least invasive method possible for partial cystectomy. Potential advantages of a transgastric NOTES approach include visualization of adjacent structures, access to sites difficult to reach transurethrally, and lymph node sampling. However, a gastrotomy could be a source of morbidity. Further investigation is required to assess safety, efficacy, and adequate bladder healing.

Human peritoneal membrane controls adhesion formation and host tissue response following intra-abdominal placement in a porcine model.

BACKGROUND: Even with the advent of bioresorbable barriers, complications due to visceral adhesions following surgery continue to occur. The use of a homologous adhesive barrier such as human peritoneal membrane (HPM) could prevent adhesions formation and enhance wound healing. This study evaluates HPM as an effective adhesive barrier in a porcine model simulating a ventral hernia procedure. MATERIALS AND METHODS: Through a midline laparotomy, meshes (10 cmx10 cm) were sewn onto the intact peritoneum of a pig, on each side of a midline incision in superior and inferior positions (4 randomized meshes/pig, n=9 pigs). The pigs were survived for 90 d. The meshes used were: HPM, compressed polytetrafluoro-ethylene (cPTFE), cPTFE+HPM, and polyester-collagen composite (PX). Exploratory laparoscopy was performed at 30 and 90 d to evaluate the extent of visceral adhesions. At necropsy, the extent and tenacity of visceral adhesions as well as material-abdominal wall integration were evaluated. Finally, host tissue response was assessed through scoring of inflammation, foreign body reaction, and mesothelialization. RESULTS: HPM and PX led to the least extent and tenacity of visceral adhesions compared to cPTFE and cPTFE+HPM, but integrated less strongly within the adjacent abdominal wall. PX displayed the most robust foreign body reaction among all prosthetic materials, while HPM scored similarly to the native peritoneum. The extent of mesothelialization was similar throughout the materials tested. CONCLUSIONS: The HPM barrier which promotes long-term peritoneal remodeling could diminish postsurgical intraperitoneal adhesions following hernia repair.

In vitro evaluation of the permeability of prosthetic meshes as the possible cause of postoperative seroma formation.

INTRODUCTION: Seroma formation is one of the most common post operative complications related to abdominal wall hernia repairs with mesh. We hypothesized that the different biomaterials used to construct commonly used prosthetic mesh may influence permeability to fluid and affect seroma formation rates. METHODS: We designed an in vitro study where a 5 cm piece of mesh was placed in a closed system where normal saline was forced across the mesh and the pressure (mmHg) required for a constant stream of fluid was recorded. Eight prosthetic materials were studied: polyester/oxidized collagen (PC), expanded PTFE (DM), polypropylene/ePTFE (BC), polypropylene/oxidized cellulose (PR), light weight polypropylene/omega 3 fatty acid (CQ), compressed PTFE (MM), polypropylene (PP) and polyester (P) mesh. RESULTS: Each mesh was tested five times and the results averaged. The 3 meshes without anti-adhesive barriers (MM, PP, P) had fluid move across with minimal pressure (<1 mmHg). For the intraperitoneal mesh, there was a significant difference in pressure necessary for fluid movement (PR = 3.6, CQ = 36, PC = 56.6, DM > 350, BC > 350 mmHg, p = <0.001). However, the fenestrations at the suture lines necessary to combine the PP and DM in the BC mesh permitted fluid transport at low pressures (<1 mmHg). CONCLUSION: Based on our in vitro study, each mesh exhibited different fluid permeability, especially in the case of meshes with anti-adhesive barriers. This study also infers that methods to create pressure gradients across mesh, such as an abdominal binder, may reduce seroma formation of certain meshes.