()Anatomy: A Cost-Effective Intelligent Decision Support
System in Surgery for More Effective Treatment of
Gastrointestinal Diseases through Optimal Surgical
Procedures
Collaborating Principal Investigator
1 Overall Objectives
Crohn’s disease is a clinically challenging inflammatory condition capable of afflicting the entire gastro-intestinal tract. Surgically, Crohn’s disease with multiple narrow strictures is treated not by resection but by changing the intestinal geometry using a procedure called the Heineke-Mikulicz (HM) strictureplasty. There is growing appreciation that mechanical stresses influence the development and progression of pathology. I hypothesize that the wall mechanical strain and stress fields generated by the strictureplasty geometry as well as certain types of anastomosis (end-to-end, side-to-side, end-to-side) may predispose the intestinal wall to mechanical instability states, and this can lead to intestinal maladaptation and subsequent surgical failure, e.g. anastomotic leak or recurrence of disease. The overall goal of this proposal is to design and implement an intelligent decision support system (IDSS) in surgery that will be able to identify those points of mechanical instability and will provide the surgeon with alternative optimal surgical procedures that could alleviate the risk of surgical failure, thus improving the quality of life of children and adults affected by this disease and reducing the re-operative rates that are known to be associated with significant patient morbidity in inflammatory bowel diseases (IBD). The IDSS will model the strain and stress fields in the segment of the patient-specific intestinal wall around the suture line and far-field from it under varied loading conditions and with given anastomotic geometries.
∗Address: Department of Bioengineering, Center for Vascular Remodeling and Regeneration, McGowan
Institute for Regenerative Medicine, University of Pittsburgh, 300 Technology Drive, Pittsburgh, PA 15213,
United States; phone: 650-796-8846; fax: 412-383-8788; e-mail: alt83@pitt.edu †Address: Department of Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Pitts-
burgh, PA 15213, United States, e-mail: pocivavsekl@upmc.edu
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2 Specific Aims
I have formulated the following hypotheses and designed the associated specific aims to test them: Hypothesis #1: The intestinal wall response to the surgical geometry depends on its material properties. Specific Aim #1: Measure either ex-vivo or intra-operatively the intestinal wall material properties in different locations such as duodenum, jejunum, ileum, appendix, colon, and rectum, and correlate the measured material properties with known patient-specific clinical factors, e.g. smoking, malnutrition, chemo-radiation treatment, lead- ing to increased risks of surgical anastomoses failure. Hypothesis #2: The location of multiple strictureplasties and the intraluminal pressure and flow can make the intestinal wall susceptible to recurrence of Crohn’s disease. Specific Aim #2: Improve the current model of single HM strictureplasty to account for the effect of multiple strictureplasties and the pressure and flow profiles on mechanical instability states in a patient-specific geomet- rical setting. Hypothesis #3: Side-to-side anastomosis can serve as a point of reversible obstruction and lead to increased symptoms in Crohn’s patients. Specific Aim #3: Model the strain and stress fields in different geometries of anastomosis, i.e. end-to-end, side-to- side, and end-to-side, to reveal states of mechanical instability that would predispose the initiation of surgical failure. Hypothesis #4: Patient anatomic factors, such as length of sigmoid colon, length of inferior mesenteric artery and vein, can play a role in the mechanical stability of low colorectal anastomosis. Specific Aim #4: Integrate the specific mechanical constraints that far-field patient anatomy, such as length of sigmoid colon and mesentery, imposes on the local anastomotic mechanical fields.
3 Background
Crohn’s disease is a clinically challenging inflammatory condition capable of afflicting the entire gastro-intestinal (GI) tract [1]. The pathology is part of a wider set of conditions termed inflammatory bowel disease (IBD). Due to the multi-focal nature of Crohn’s in- flammation, multiple non-adjoining areas of localized luminal narrowing are commonly en- countered upon surgical exploration [2]. Surgically, Crohn’s disease with multiple narrow strictures (Figure 1) is treated not by resection but by changing the intestinal geometry using a procedure called the Heineke-Mikulicz (HM) strictureplasty, in hopes of preserving the intestinal length in a patient population at high risk for short-gut syndrome [2, 3]. Tech- nically, the procedure involves making a longitudinal incision on the anti-mesenteric side (top side, opposite from where the blood vessels enter the intestinal wall) across the stric- tured portion of intestine (Figure 2A), then juxtaposing the two vertices of the incision (Figure 2B-C), and closing the incision transversely (Figure 2D).
Mechanical forces play an intricate role in biological systems from the tissue and organ level down to individual cells and even proteins [4, 5, 6]. There is growing appreciation that mechanical stresses influence the development and progression of pathology. For example, in the much studied cardiovascular system, arteries are known to be sensitive to the local mechanical environment to which they are exposed, and it is well established in the literature that variation in the mechanical stresses can cause growth and remodeling in the arterial wall [7, 8, 9]. Less work has been done in the GI system [10, 11, 12]. However, small animal
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studies have shown that intestinal tissue also undergoes active remodeling as a function of increased mechanical stress [10, 12, 13]. Surgeons empirically understand that mechanical forces play an important role in healing. In GI surgery, tension on an anastomosis plays an important role and is strongly linked to poor anastomotic healing and tissue breakdown [14]. Likewise, plastic surgeons strive to decrease the degree of tension (in-plane stretching) in skin flaps to avoid tissue death [15]. Surgery by definition leads to reconstruction of tissues in non-native geometries that alter the mechanical environment of those tissues.
Figure 1: Multiple small bowel strictures. Figure taken from [3].
Figure 2: Heineke-Mikulicz (HM) strictureplasty procedure performed in a patient with focal stricturing. (A.) Linear incision is made along the anti-mesenteric border, extending proximally (a) and distally (a’) across the stricture into healthy bowel. (B. and C.) The incision is closed transversely with the approximation of vertex points a and a’, which initially were separated by the length of the incision. (D.) Completed HM strictureplasty. Figure taken from [16].
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3.1 Previous work in the area by others
Bowel preserving Crohn’s colitis surgery in the form of HM strictureplasties introduces new anatomy (geometry) to a local part of the intestine. This new anatomy can be indicative of buckling modes which can undergo limit point instability states [17]. Buckling of thin plates with through cracks has been studied in compressive loading [18, 19, 20, 21], bending loading [22], and tensile loading [20, 21, 22]. Of note, buckling in tensile loading, which is not directly evident, can occur in compressed regions especially around cracks or holes [20]. It has been reported that, if a thin plate is bent in one direction and deformed in the other direction, similar to the combined loading conditions generated by the strictureplasty, this may generate limit point instabilities or singularities [23].
3.2 Previous work by Pocivavsek et al. [16]
Prior work by Pocivavsek et al [16] focused on the purely geometric components of the HM strictureplasty procedure, concluding that the transverse closure generates a saddle-like ge- ometry with a central point carrying −2π Gaussian curvature condensation (Figure 3A, black circle) flanked by +π cones (Figure 3A, red circles). Simple elastic modeling of the anti-mesenteric surface showed that these purely geometric factors could account for the overall strictureplasty shape. A key conclusion of this work was a connection between the saddle-like geometry and its effect on luminal cross-sectional area (Figure 3B), a parameter closely tied to Crohn’s pathology. Immediately underneath the transverse suture line there was pronounced dilation (Figure 3B, green shaded area, top image), as expected from the highly successful clinical application of strictureplasty to alleviate obstructions. How- ever, just proximal and distal to this dilation, there were areas of contracture (Figure 3B, green shaded area, bottom left and right images). Pocivavsek et al [16] hypothesized that the geometry-induced luminal narrowing proximal and distal to the strictureplasty may serve to promote disease recurrence: first, increased propensity for bowel content stasis prox- imal to the strictureplasty leading to potential overgrowth and inflammation, and secondly, given an already compromised lumen, the need for less disease-specific narrowing prior to clinical re-presentation of obstruction. In summary, the geometric analysis of HM stricture- plasties argues for altered luminal flow (fluid mechanics) as a potential explanation of disease recurrence patterns after successful strictureplasty.
3.3 Previous work by Tsamis et al. [24, 25]
With Crohn’s disease, surgeons have noted that pathology tends to recur not at the site of transverse closure but at some distance proximal or distal to it [26, 27], and recurrence rates are higher in the inter-plasty regions [28]. I hypothesize that the stress distributions generated by the non-linear HM strictureplasty geometry may serve as the nidus of disease recurrence. In particular, the recurrence of Crohn’s disease can be associated with remodeling of the mesenteric wall (bottom side, where the blood vessels enter the intestine) which can be driven by stress-induced alteration in blood perfusion or in interstitial pressure [7]. To test the hypothesis, I used finite element simulations to reproduce the highly non-linear geometries of the HM strictureplasty and at the same time calculate mechanical stress fields
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around the suture line and far-field from it. My aim is to study and understand the mechanics of these non-linear geometries in idealized materials, and to formulate a general framework upon which further layers of complexity can subsequently be added.
Figure 3: Models of single enterotomy Heineke-Mikulicz (HM) strictureplasties of varying length. (A.) CT derived three-dimensional reconstructions of final Heineke-Mikulicz geome- tries generated from 2, 3, and 4cm linear enterotomies. (B.) Shows the relative cross-sectional areas of the three models from distal to proximal ends and across the HM strictureplasty sites as a function of arc length. Figure taken from [16].
I designed the HM strictureplasty finite element models in Abaqus (Version 6.12-3, c© Dassault Systemes, 2012) to simulate the above-mentioned surgical procedure which is displacement-driven. I modeled the intestine as a 3D deformable extruded cylindrical shell of diameter 2cm and length 10cm [16] (Figure 4A). The surgical cut (enterotomy) was gen- erated by an extruded linear cut on the anti-mesenteric side (Figure 4A, inset). The linear cut length varied from 0.5-2 times the diameter, with a gap width of 2µm in the middle of the cut length. The two edges of the cut were formed by 2 spline curves as shown in Figure 4B. For all simulations tube diameter was fixed to 2cm, while enterotomy length was varied. The wall material was assumed linearly elastic, isotropic and incompressible. The enterotomy was closed transversely in twenty consecutive steps. The governing dimensionless parameters in the problem were α=cylinder thickness/cut length and φ=tube diameter/cut length.
I tested the above-mentioned hypothesis by analyzing the variation of the wall stress across the wall thickness on both the anti-mesenteric and mesenteric surfaces, knowing that bending stresses in the middle surface of the thickness (neutral surface) are close to zero. The measure of stress that I used in the model is the equivalent tensile stress or von Mises stress
σMises =
xy + σ2 yz + σ2
Alkiviadis Tsamis
which is frequently used to describe the stress field of materials under multiaxial loading conditions. The σxx, σyy , and σzz are the normal components, and the σxy, σyz , and σzx are the shear components, of the Cauchy stress tensor
σ =
X
Y
Z
X
Z
Figure 4: (A.) The intestinal wall was modeled as a 3D deformable extruded cylindrical shell of diameter 2cm and length 10cm [16]. The surgical cut (enterotomy) was simulated as an extruded linear cut (0.5-2 times diameter) on the anti-mesenteric side that was formed by 2 spline curves separated by a small gap of 2µm in the middle of the length of the model cylinder (A., inset). (A.) also shows 1 partition on the X-Z plane, 1 partition on the Y-Z plane, and 41 equi-distanced circular partitions on the X-Y plane along the length of the linear cut to provide locations for displacement boundary conditions. (B.) Shows the 2 spline curves that are used to form the two edges of the cut.
Stress distributions on the inner, middle, and outer shell surfaces are shown for φ = 1.3 with α = 0.033 (Figure 5A) and α = 0.067 (Figure 5B), and for φ = 0.5 with α = 0.013 (Figure 6A) and α = 0.025 (Figure 6B). By setting the middle surface as the origin (z = 0) allows us to define the outer shell surface as z = +t/2 and inner shell surface as z = −t/2, where t is shell thickness. On the anti-mesenteric half, the pattern of stress distribution is similar for all cases, with a high stress middle plane core σij |z=0 around the HM strictureplasty vertex, while outside this core σij |z=0 ∼ 0. The core size is most sensitive to shell thickness and relatively insensitive to enterotomy length as seen by comparing Figure 5 and Figure 6. Moving onto the inner and outer shell planes, the stress magnitude increases and the distribution encompasses a larger area of the anti-mesenteric surface: σij |z=±t/2 >> σij |z=0. These stresses are distributed in a floret pattern along the peaks and valleys of the hyperbolic saddle generated by the HM strictureplasty and, again, their magnitude is most sensitive to shell thickness.
On the mesenteric half a very different pattern of stress distribution is seen compared to the anti-mesentery. First, the stress magnitudes are highly sensitive to enterotomy length.
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For φ = 1.3, the mesenteric surface in nearly stress-free across shell thickness (see Figure 5). However, as the enterotomy length is quadrupled (φ = 0.5 and Figure 6), a semi-elliptical ring of stress around a stress-free central zone located underneath the transverse closure appears. In contrast to the nodal distribution of stress magnitude observed on the anti- mesentery, the mesenteric stresses are more uniformly distributed throughout shell thickness: σij |z=−t/2 ∼ σij |z=0 ∼ σij |z=+t/2. It should be noted that the mesenteric stresses are highest at points distal and proximal to the HM strictureplasty suture line.
INNER MIDDLE OUTER
A.
B.
stress
Figure 5: Stress distributions on the inner, middle, and outer shell surfaces for φ = 1.3 with α = 0.033 (A.) and α = 0.067 (B.). On the anti-mesenteric half, both shells showed the same pattern of high stress focused only at the vertex core for the middle surface but high stress regions distributed along the peaks and valleys of the hyperbolic saddle on the inner and outer surfaces (floret type distribution). On the mesenteric half, there was trace stress only along the middle surface.
Furthermore, the luminal area distal and proximal to the transverse closure collapsed for φ=0.5 and underwent a phase transition as the strictureplasty was formed. The model suggests that under long enterotomy lengths, the stresses on the mesenteric wall may lead to focal areas of hypo-perfusion and may trigger the initiation of tissue adaptation and possi- ble recurrence of Crohn’s disease distal and proximal to the HM strictureplasty suture line. Bending modes of deformation in the anti-mesentery and stretching modes of deformation in the mesentery suggest that, ideally, an optimal combination of bending, tensile and compres-
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sive loads might provide an anatomy in which the developed strains and stresses could be minimal. Finally, based on our analysis, the stitch connecting the enterotomy vertices seems to be the controlling stitch, which sets not only the global geometry but also the overall energy of the deformation. Furthermore, the force in this stitch becomes minimal after a critical value of enterotomy length (Figure 7, diameter/cut length∼0.8).
INNER MIDDLE OUTER
A.
B.
stress
Figure 6: Stress distributions on the inner, middle, and outer shell surfaces for φ = 0.5 with α = 0.013 (A.) and α = 0.025 (B.). On the anti-mesenteric half, the stress distribution again showed a pattern of stress-focusing at the vertex core for the middle surface, with high stress regions covering nearly the whole half on the inner and outer surfaces. On the mesenteric half, stresses were present throughout the thickness of the shell and distributed in a semi-elliptical ring around a stress-free central zone located underneath the transverse closure.
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0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 0
0.05
0.1
0.15
0.2
0.25
0.3
displacement
F z
Φ = 2.00
Φ = 1.30
Φ = 1.00
Φ = 0.80
Φ = 0.66
Φ = 0.57
Φ = 0.50
Figure 7: Force (z − component) versus displacement curves for vertex point closure with different values of enterotomy length φ and thickness 0.06. For small enterotomy length (φ > 1.3), the curves were indicative of Euler buckling. However, with increasing enterotomy length (φ ≤ 1.3), the force-displacement curves were indicative of limit point instability. It is interesting that the maximum force did not change for φ ≤ 0.8 and remained lower than the maximum force corresponding to smaller enterotomy lengths (φ > 0.8).
4 Detailed Research Plan
The overall goal of this proposal is to design and implement an intelligent decision support system (IDSS) in surgery that will provide the surgeon with patient-specific optimal surgi- cal geometries for more effective treatment of GI disease. Our approach initially focuses on Crohn’s surgeries such as the strictureplasty, however the tools developed will easily be broad- ened to other common GI surgical procedures. The methodology is based on the hypothesis that the wall mechanical strain and stress distributions generated by the non-linear geom- etry of the strictureplasty as well as certain types of anastomosis (end-to-end, side-to-side, end-to-side) may serve as the nidus of surgical failure, e.g. anastomotic leak or recurrence of GI disease. More specifically, the anatomy of a surgical geometry can predispose the GI wall to mechanical instability states under varied loading conditions, and this can lead to GI mal- adaptation and subsequent surgical failure. The personalized IDSS will be able to identify points of mechanical instability that can be caused by the intended surgical intervention, and will provide the surgeon with alternative optimal surgical procedures that would alleviate the risk of surgical failure within the patient-specific tissue properties and anatomy, thus
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improving the treatment of Crohn’s disease and the quality of life of children and adults affected by this disease, and reducing the re-operative rates that are known to be associated with significant patient morbidity in IBD. The IDSS will be finite element-based to reproduce the highly non-linear geometries of the strictureplasty and anastomosis. It will model the strain and stress fields in the segment of the patient-specific GI wall around the suture line and far-field from it under varied loading conditions and with given anastomotic geometries, eventually incorporating realistic material properties to give a true biomechanics picture. The IDSS will be formulated on a general framework upon which further layers of complexity can subsequently be added, such as material heterogeneity, the effect of splenic mobilization, the effect of mesenteric attachments (inferior mesenteric artery and vein ligation), intra-luminal intestinal fluid mechanical stresses (effect of diverting loop ileostomy), and the contact of the GI wall with surrounding abdominal tissue.
4.1 Hypothesis #1
The GI wall response to the non-linear surgical geometry is dependent on its anisotropic non- linear material properties. Specific Aim #1a: Measure either ex-vivo or intra-operatively the GI wall anisotropic non-linear material properties in different locations of the GI tract such as duodenum, jejunum, ileum, appendix, colon, and rectum. Specific Aim #1b: Correlate measured material properties with known patient-specific clinical factors, e.g. smoking, mal- nutrition, chemo-radiation treatment, leading to increased risks of surgical anastomoses fail- ure. The GI wall anisotropic non-linear material properties will be measured either ex-vivo, using fresh (non-fixed) tissue samples obtained from surgical resections under IRB-approved protocols, or intra-operatively. The ex-vivo characterization of elastic moduli will be done using biaxial testing machine, as well as compressional tensiometer to obtain bulk moduli. The clinical control parameters could be: albumin, pre-albumin, age, sex, smoking status, immuno-modulatory medications, cancer status, history of chemotherapy, history of radi- ation, and history of IBD, as well as nutritional status of patients. The intra-operative characterization of tissue properties could be done using optical methods such as elastogra- phy.
4.2 Hypothesis #2
The location of multiple strictureplasties and the dynamics of pressure and flow in the lumen of the GI tract can make the GI wall susceptible to recurrence of Crohn’s disease. Specific Aim #2: Improve the current model of single HM strictureplasty [24, 25] to account for the effect of multiple strictureplasties and the pressure and flow profiles on mechanical in- stability states in a patient-specific geometrical setting. Strains and stresses in the surgical GI anatomy will be obtained using finite element analysis in ABAQUS (Version 6.12-3, c© Dassault Systemes, 2012). The current model of single HM strictureplasty will be improved to include realistic wall thickness, anisotropic non-linear material properties, multiple HM strictureplasties within one model tube, effect of internal pressure (positive or negative) on HM strictureplasty geometry and stresses, and flow profiles through one or multiple HM strictureplasties to couple the elasticity-derived geometry with flow of fluid or solid material in the intestinal lumen. Simulations will be repeated using patient-specific intestinal geome-
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tries obtained from CT images under IRB-approved protocols. The 3D geometries will then be reconstructed using commercially available software (IDL, MATLAB, RHINOCEROS, TRUEGRID) and be input in ABAQUS.
4.3 Hypothesis #3
Side-to-side anastomosis can serve as a point of reversible obstruction (un-published clinical data provided by Dr. David Binion, Department of Medicine, GI Section, UPMC) and lead to increased symptoms in Crohn’s patients. Specific Aim #3: Model the strain and stress fields in different geometries of anastomosis, i.e. end-to-end, side-to-side, and end-to-side, to reveal states of mechanical instability that would predispose the initiation of surgical failure. Depending on the anatomy of Crohn’s disease, surgeons often perform anastomosis instead of HM strictureplasty. Anastomosis can be end-to-end, side-to-side, or end-to-side. Side-to-side geometry can create a high resistance zone along the length of the intestine. This may serve as a point of reversible obstruction and lead to increased symptoms in Crohn’s patients. The strain and stress fields in different anastomotic geometries would be very important in this regard, and therefore should be studied and modeled separately. I will model the three cases of anastomosis in ABAQUS using two cylinders with radii r1 = r2 and r1 6= r2. A multitude of ratios ζ = r1/r2 can be studied (0.8 ≤ ζ ≤ 1.2). The integrity of all cases of anastomosis will then be tested under different loading conditions: (A) tension, (B) twist, (C) pressure, (D) fluid flow and shear, (E) coupling of elastic loads and flow. The tests will be repeated using patient-specific intestinal geometries as described in Specific Aim #2.
4.4 Hypothesis #4
Patient-derived anatomic factors, such as length of sigmoid colon, length of inferior mesen- teric artery and vein, can play a role in the mechanical stability of low colorectal anastomosis. Specific Aim #4: Integrate the specific mechanical constraints that far-field patient anatomy, such as length of sigmoid colon and mesentery, imposes on the local anastomotic mechan- ical fields. All above simulations will be integrated to explore the effect of patient-specific anatomic factors, such as length of sigmoid colon, length of inferior mesenteric artery and vein, on the mechanical field of low colorectal anastomosis. The far-field patient anatomy will be obtained from CT images under IRB-approved protocols. The 3D geometry will then be reconstructed using commercially available software (IDL, MATLAB, RHINOCEROS, TRUEGRID) and be input in ABAQUS to be in assembly with the introduced patient- specific intestinal geometries.
5 Significance and Relevance of the Proposed Research
to Crohn’s Disease
Crohn’s disease is marked by its chronic and at times highly morbid nature. The past decades have seen wonderful progress in the medical management of Crohn’s, however, surgical inter- vention remains a mainstay even at a time when the majority of patients continue to receive disease modifying treatment post-primary resection. Certain subsets of highly aggressive
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Crohn’s such as the diffusely stricturing disease often require multiple re-operative interven- tions. It is well appreciated that every re-hospitalization and especially re-operation carries with it great morbidity and increasing risk of life-long disability for the patient. Thirty years ago, pioneering work was done by IBD surgeons in the United States in using the classic Heineke-Mikulicz strictureplasty (commonly used for pyloric stenosis in children and post- vegotomy procedures) to treat Crohn’s strictures in the small intestine. This bowel sparing procedure decreased the incidence of short gut syndrome, a dreaded complication in patients with diffuse Crohn’s. However, disease recurrence remains a problem post-strictureplasty particularly in tissue distal or proximal to the prior operation. The challenge of mod- ern surgery and especially complex gastro-intestinal re-construction is understanding the inherent biomechanical environment that the new surgically altered anatomy imposes on surrounding tissue. However, such understanding necessitates advanced modeling and study using engineering tools. The primary focus of this grant is building such a tool set, with a particular focus on Crohn’s re-constructive surgeries. Imagine the surgeon having at his/her fingertips in the pre-operative setting a detailed set of simulations among different possi- ble re-constructions derived using patient-specific anatomic and physiologic data (CT scans, upper GI studies, pre-albumin level, existing treatment, etc.). Using these simulations, the surgeon in discussion with the patient and other members of their healthcare team could plan out the most appropriate, safest, and optimal procedure.
6 Facilities Available and Important Collaborations to
Carry Out the Proposed Studies
I strongly believe that the University of Pittsburgh, Department of Bioengineering, will be an ideal place for me to carry out the proposed research plan, because it affords me the valuable experience of interfacing directly with strong clinical collaborators, yet it demonstrates what it takes to navigate the barriers that come with multi-disciplinary research. Dr. David Vorp (Vascular Bioengineering Laboratory) will provide me with laboratory resources to support the work outlined in the proposed research plan. In this work I will make use solely of human intestinal tissue and CT images collected under IRB-approved protocols. All tissue samples and CT images will be de-identified through an established process using an honest broker. The human intestinal tissue and CT images will be provided to me by Dr. Luka Pocivavsek from the University of Pittsburgh Medical Center, with whom I have established strong interdisciplinary collaboration within the frame of the proposed research project. Dr. Pocivavsek is my Collaborating Principal Investigator. He will provide me with valuable clinical data, his experience and expertise in IBD research, and through him I will interact directly with his strong clinical collaborators, including Dr. Anthony Bauer and Dr. Kenneth Lee. Further, my current affiliation with the McGowan Institute for Regenerative Medicine has developed collaboration with Dr. Antonio D’Amore and Dr. William Wagner. Within the frame of this collaboration, I will be able to use the biaxial tensile testing device in Dr. Wagner’s laboratory to measure the material properties of the human intestinal tissue with Crohn’s disease and under multiple loading and geometrical constraints.
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[27] Munoz-Juarez, M., Yamamoto, T., Wolff, B. G., and Keighley, M. R., 2001, “Wide- lumen stapled anastomosis vs. conventional end-to-end anastomosis in the treatment of crohn’s disease,” Diseases of the Colon & Rectum, 44(1), pp. 20–26.
[28] Greenstein, A. J., Zhang, L. P., Miller, A. T., Yung, E., Branco, B. C., Sachar, D. B., and Greenstein, A. J., 2009, “Relationship of the number of crohn’s strictures and stric- tureplasties to postoperative recurrence,” Journal of the American College of Surgeons, 208(6), pp. 1065–1070.
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Previous work by Tsamis et al. tsamis2013strictureplasty, tsamis2012bmes
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