Tech Coloproctol DOI 10.1007/s10151-013-1097-5

ORIGINAL ARTICLE

A novel anchoring system for colonic stents: a pilot in vivo study in a porcine model A. Nevler • U. Willantz • O. Doron J. Sandbank • Y. Ziv



Received: 3 October 2013 / Accepted: 14 November 2013 Ó Springer-Verlag Italia 2013

Abstract Background Colorectal stents have a proven role in colorectal cancer as palliative care or a bridge to surgery. However, their efficacy and anchoring to the tissue varies according to stent design with stent migration rates up to 50 %. We present preliminary in vivo results of a new endluminal anchoring system for stent fixation to the rectal canal. The aim was to assess the efficacy and safety of the stent using the anchoring system while subjecting the device to daily abdominal pressures related to daily activities in a porcine animal model. Methods Ex vivo anatomical and physical studies were performed to improve the system’s structure and safety. Four female pigs were followed for the acute and chronic (16 weeks) period. Two animals were euthanized and Chaim Sheba Medical Center is affiliated with Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Assaf Harofeh Medical Center is affiliated with Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

underwent en-bloc pelvic visceral excision and histopathological examination. Device fixation time, animal behavior, device patency, anoscopic examination and histopathological features were assessed. Results Mean anchoring time was 13.83 weeks (standard error ± 1.38 weeks). One of the animals experienced early device expulsion with no complications. No obstruction was noted in any of the animals. Macroscopic examination revealed mild focal submucosal scarring in one animal and a normal examination in the other. Hematoxylin and eosin staining revealed mucosal ulceration and mixed inflammatory cell infiltrate, with no signs of granulomata, foreign body giant cell reaction or microabscess formation. Conclusions A novel fixation device designed for longterm intrarectal implantation was well tolerated and maintained anal canal patency without migration. Larger studies are needed before its implementation in humans. Keywords Self-expanding metallic stent  Colonic stent  Stent migration

Dr. Avinoam Nevler and Dr. Yehiel Ziv have contributed equally to this work.

Introduction A. Nevler Department of Surgery and Transplantation, Chaim Sheba Medical Center, 52621 Tel-Hashomer, Israel U. Willantz  O. Doron Lahav Research Institute, Kibbutz Lahav, Israel J. Sandbank Department of Pathology, Assaf Harofeh Medical Center, Zerifin, Israel Y. Ziv (&) Coloproctology Unit, Division of Surgery, Assaf Harofeh Medical Center, 70300 Zerifin, Israel e-mail: [email protected]

In colorectal cancer, obstruction may occur in 7–29 % of cases. Such patients tend to have more advanced disease and represent a higher perioperative risk with higher morbidity and mortality than in patients who undergo elective surgery [1]. Since the first deployment of a flexible colonic stent by Dohmoto in 1991 [2], comparative studies assessing urgent surgery with initial colonic stenting as a bridge to elective resection have shown that stented patients tend to have a higher primary anastomosis rate as well as better outcomes in terms of hospital and intensive care unit stay [3, 4]. This effect extends to higher risk

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Tech Coloproctol Fig. 1 Curved anchoring pin. Curved titanium pin profile (a), curved titanium pin (profile) (b), inverse cutting pin profile (c)

elderly patients [5] and appears in some studies to be more cost-effective than emergent surgery, resulting in fewer operative procedures per patient, lower procedure-related mortality [6] and equivalent long-term survival [7]. Equally, the definitive placement of a colonic stent in patients with advanced metastatic or inoperable disease may be effective in selected cases, avoiding a palliative colostomy, [8] without any effect on cancer-specific survival [9]. A systematic review of the literature showed both a high technical and clinical success rate for emergent stent deployment, although there are significant problems including early and delayed perforation, stent migration and tumor ingrowth with stent occlusion [10]. Stent migration in particular occurs in 3–22 % of cases [11] developing early (within days) in up to one-quarter of cases, necessitating stent removal, stent reinsertion or urgent surgery in up to half the patients. The likelihood of stent migration is greater if it is associated with endoscopic laser pretreatment, neoadjuvant chemotherapy use, deployment for a benign tumor or the use of a covered stent [10, 12, 13]. Most studies have used uncovered stents, which may lead to a greater risk of tumor ingrowth. However, comparative data have shown a low migration rate with the UltraflexTM precision colonic stent (Boston Scientific, Natick MA, USA) when compared with the Colonic Enteral WallstentTM (Boston Scientific, Natick MA, USA), with a lower rate of delayed complications, the need for re-intervention or re-occlusion [14, 15]. Recent data confirm, however, that differences in stent type or manufacturer do not cause significant differences in stent migration and occlusion rates [16]. We hereby describe a covered metal stent with a novel anchoring system specifically designed to prevent migration in a porcine model.

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Materials and methods The Sphinx-Tech system and ex vivo data The Sphinx-Tech colorectal anchoring system (SphinxTech Ltd, Singer Instruments Ltd, Tirat Carmel, Israel) underwent extensive ex vivo testing throughout 2010 in order to determine the optimal anchoring pin shape, size, width and diameter as well as to assess basic tissue fixation strength, the resistance to expulsion forces, the technical efficiency of the locking mechanism and the overall safety and tissue reactivity of the device. The system includes the assist device (made of titanium with an external diameter of 40 mm, an internal diameter of 28 mm and a length of 52 mm) and the fixation element (made of titanium with an external diameter of 40 mm and a length of 40.5 mm—the internal diameter is not relevant). The fixation testing was performed on a larger bovine model with larger pins and devices, showing that the straight fixation pins could withstand up to 4.7 kgf in fresh tissue with no benefit in fixation force of using longer or thicker pins. Extensive studies in the porcine model showed that the specific curvature of the pins permitted fixation of the device for a mean of 10 weeks, withstanding shearing forces of over 4.3 kgf. Similar tests were performed for the accompanying insertion assist device. The system contains a fixation mechanism that anchors the device housing to the rectal wall. It is composed of 18 built-in fixation points that comprise rows of curved, rotatable, inverse cutting, titanium pins with an external diameter of 5 mm (Fig. 1). These have been fitted onto a 50 mm long 9 25 mm wide titanium cylinder (Fig. 2) with a titanium internal locking element for internal insertion into the device after pin deployment. This is supplemented by a design of a dedicated titanium insertion assist device permitting device

Tech Coloproctol Fig. 2 Stent with fixation elements. Fixation device; pins undeployed (a). Fixation device; pins deployed (b). Fixation device; locking element inserted (c). Locking element (d)

mounting (Fig. 3). The physical characteristics of the device are shown in Table 1. Animal procedure Animal care and all experiments were conducted in accordance with the research protocol approved by the Animal Bioethics Committee and the local Institutional Review Board. All devices were cleaned and disinfected with 70 % ethanol–chlorhexidine solution prior to insertion. The cylinder with the anchoring pins was mounted on the insertion assist device, and deployment of the pins was tested prior to each insertion procedure. A total of 4 female pigs of domestic breed (Large white 9 Landrace, Sus scrofa domestica) were obtained from the Lahav Research Institute (LRI) with a mean body weight of 87.9 kg (standard error (SE) ± 3.6 kg). Animals were fed a daily, balanced, swine diet with the exception of the day of surgery, with free water access at all times. Feeding was withheld 6 h prior to operation. A preoperative enema was administered 30 min before operation. Animals were placed in the lithotomy position and sedated with intramuscular ketamine hydrochloric acid (HCl) (10 mg/kg), xylazine (1–2 mg/kg) and intravenous diazepam (5–10 mg/ animal). The pigs were intubated and artificially ventilated. A manual and an anoscopic examination was performed assessing the anatomy (location of dentate line and pelvic shelf) determining the optimal location for insertion. The assist device with the readied cylinder was transrectally inserted to the determined depth (tip at 8–12 cm from the anal verge). Deployment of the rotatable pins was

performed using the assist device (Fig. 4) with further assessment of the deployment by means of digital vaginal examination. After positioning the device, the assist device was detached and an internal locking element was inserted. After locking of the pins, an anoscopic evaluation was performed to verify the exact device placement and ensure full locking. A 14Fr Foley catheter was inserted into the lumen of the cylinder and secured at its distal end by a tape and to the animal’s tail at its proximal end. Animals were routinely assessed for appetite, behavior and bowel movements, including a daily search of the enclosures for expelled devices. All animals were given stool softeners (Paraffin oil 30 cc 9 2/day) with their regular swine diet. Using a modification of the balloon expulsion test described for the assessment of evacuatory difficulty [17], intermittent obstruction periods were artificially created to assess the efficacy of the anchoring system. The usual protocol after 2 weeks follow-up was to inflate and deflate the catheter intermittently with 15 ml of water on a daily basis, thereby permitting 24 h of open anal passage and 24 h of obstructed passage. In cases of balloon dislodgment or rupture, the balloon was replaced under sedation with intramuscular ketamine HCl (10 mg/kg). Due to repeated events of balloon pulling by other animals or catheter dislodgement, the last 2 animals in the series (LRI 3413 and 3255) had the balloon secured to their tail using a thin 1-mm metallic wire. Device patency was assessed by observation of unobstructed defection and by visual inspection when replacing ruptured or dislodged balloons. The animals were followed for 48 h after device expulsion and euthanized at that time. In 2 animals, the

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Tech Coloproctol

Fig. 3 Fixation device with internal locking element. Internal locking element (a), titanium casing of the fixation device (b), curved rotatable titanium pins (c)

treated successfully with oral antibiotics (ofloxacin). Two animals underwent metal wire securing of their balloon— LRI 3,255 on postoperative day 73 and LRI 3,413 on its operative day after device insertion and deployment. Both animals experienced device expulsion 2 weeks after the use of the metal wire. Device expulsion was not associated with any overt signs of bleeding or infection. Details of animal outcome are shown in Table 1. The mean anchoring time of the device was 13.83 weeks (SE ± 1.38 weeks). Figure 5 shows the macroscopic appearance of one the sacrificed animals subjected to an en-bloc pelvic visceral excision, showing minimal fibrosis and scarring 86 days after device implantation. After formalin fixation, specimens were gross cut longitudinally assessing tissue cores around the site of implantation. Hematoxylin and eosin (H&E) staining showed an ulcerated mucosa with a mixture of inflammatory cell infiltrate, submucosal and serosal fibrosis and foci of fibrosis within the muscularis propria. Numerous blood vessel thrombi were found both in the sub-mucosa and in the thickened serosa. Granulomas, foreign body giant cell reaction or microabscess formation were not found in any of the cases.

Discussion anorectal and vaginal area was resected en-bloc and sent for histopathological examination.

Results A total of 4 female pigs underwent insertion of the device using the Sphinx-Tech anchoring system. All devices were anchored at the level of the pelvic shelf. Rectal patency was maintained throughout the entire follow-up period. No intraoperative complications were observed except for slight mucosal tearing during insertion of the device, evident on visual anoscopic inspection in all cases. Animal LRI 3,255 presented with lethargy and loss of appetite by week 4 postinsertion. Examination by a veterinarian (U.W.) showed signs of infection, and the animal was

This preliminary animal study showed that our novel fixation device designed for long-term intrarectal implantation was well tolerated without early expulsion in 3 of 4 cases while maintaining anal canal patency without migration. Macroscopic and microscopic examination of the area of implantation showed minimal inflammation reactivity and scarring. We suggest that this specialized anchoring device may be a useful adjunct to colonic stent design in an attempt to prevent device migration when used as a bridge to resection during neoadjuvant therapy and also as definitive treatment in stage IV colonic cancer cases. Colonic stent migration poses a significant problem following stent deployment and is observed in about 7–29 % of patients [10, 18]. These patients will require repeat stent placement or surgery [19]. Some selected cases

Table 1 Short-term and longer-term outcome of 4 female pigs undergoing Sphinx-Tech device insertion Animal code

Intraoperative complications

Early complications

Late complications

LRI 3255



Suspected infection

Device expulsion after 12.5 weeks

LRI 3413



Device expulsion POD 15

None

LRI 3500





Device expulsion after 12 weeks

LRI 3501





Device expulsion after 16.5 weeks

POD Postoperative day

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Tech Coloproctol Fig. 4 Insertion system containing assist device and attached fixation device. Assist device (a), fixation device (b)

Fig. 5 Macroscopic specimen of en-bloc resection of anorectal and vaginal canals, showing minor scarring (pointed to), normal mucosal folds with no macroscopic signs of inflammation or ulceration

may be replaced endoscopically [20]. Such migration typically occurs early after stent insertion, and the factors involved in stent migration are both technical and pathology related. In the first instance, migration is more commonly reported when the stent diameter is too small [21], where there is excessive colonic angulation and where there is an insufficient length of colonic narrowing to permit stent flaring. Migration is more likely to occur later after a response to chemotherapy, if the area of stenosis is readily passed endoscopically, in benign colonic stricture or if the cause of the obstruction is extra-colonic [22–24]. Long-term success in the maintenance of stent placement is more likely with shorter stents (\10 cm in length) and in those patients with more distal colonic (as opposed to proximal colonic) obstruction [25], although this is still a matter of debate [26]. Our device functions as a covered,

anchored stent, which prevents the delayed phenomenon of stent migration. The second late complication of stent re-occlusion, mainly due to tumor ingrowth, is partially obviated by the use of a covered device. Re-obstruction occurs in about 10 % of cases, most commonly in those patients with palliative stents [10]. The obstruction, which usually results from tumor overgrowth, may also develop with stent migration, stent fracture and/or disintegration, and also due to fecal impaction. Careful sizing to permit a 2-cm overlap of the ends of the stent into non-diseased colonic segments is likely to reduce tumor overgrowth. However, this is dependent upon the inherent tumor pathology and may be unachievable with very lower cancers. The use of a covered stent is also more likely to palliate symptoms in those patients with more extensive cancers where fistulous tracks arise directly from the tumor [27]. Other approaches to these delayed stent-related complications have required complex novel technologies such as the use of a double-layered covered stent (NiTi-S enteral colonic stent Comvi type) to prevent these problems, where slightly reduced rates of stent re-occlusion with composite stents have shown a trade-off with higher reported migration rates when compared with double-wire woven uncovered stents [28].

Conclusions Our preliminary data in a porcine model show that a novel anchoring system for the deployment of a stent is safe and well tolerated, maintaining patency without early expulsion. The anchoring design has the potential to prevent delayed stent migration or repeat occlusion. The SphinxTech colorectal anchoring system requires further study with modified designs so that it may be potentially applicable for longer, more extensive and more proximal colonic tumors. Conflict of interest The authors Dr. Avinoam Nevler and Dr. Yehiel Ziv are the founders and researchers of the Sphinx-Tech System.

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A novel anchoring system for colonic stents: a pilot in vivo study in a porcine model.

Colorectal stents have a proven role in colorectal cancer as palliative care or a bridge to surgery. However, their efficacy and anchoring to the tiss...
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