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Preservation of intestinal motility after the serial transverse enteroplasty procedure in a large animal model of short bowel syndrome
Journal of Pediatric Surgery (2009) 44, 229–235
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Preservation of intestinal motility after the serial transverse enteroplasty procedure in a large animal model of short bowel syndrome Biren P. Modi a,b,⁎, Y. Avery Ching a,b , Monica Langer a,b , Kate Donovan c , Dario O. Fauza b , Heung Bae Kim a,b,d , Tom Jaksic a,b , Samuel Nurko c a
Center for Advanced Intestinal Rehabilitation (CAIR), Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA b Department of Surgery, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA c Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology and Nutrition, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA d Pediatric Transplant Center, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA Received 4 October 2008; accepted 7 October 2008
Key words: Short bowel syndrome; Serial transverse enteroplasty; Intestinal lengthening; Intestinal failure; Motility
Abstract Introduction: Serial transverse enteroplasty (STEP) has been shown to improve bowel function in short bowel syndrome. The effect of the STEP procedure on intestinal motility is not known, but some have hypothesized that it could disrupt bowel innervation and thus impair intestinal motility. Methods: Growing Yorkshire pigs (n = 7) underwent 3 operations at 6-week intervals: (1) reversal of 50 cm of jejunum, (2) 90% bowel resection ± STEP to the proximal dilated bowel (4 STEP, 3 control), and (3) implantation of serosal strain gauges. At each operation, baseline and post-octreotide small intestinal motility was studied with continuously perfused manometry catheters using non-anticholinergic anesthesia. In addition, awake monitoring was performed using strain gauge analysis 1 week after the third operation. Characteristics of phase III of the migrating motor complex (MMC) were compared between and within groups using t test, χ2, and analysis of variance, with significance set at P b .05. Results: Manometry data from the third surgery revealed no differences between groups or compared with baseline within groups for the presence and characteristics of phase III of the MMC. Specifically, the mean amplitude and frequency of phase III after octreotide, and both the mean baseline and mean octreotide-stimulated motility indices were equivalent. The duration of phase III after octreotide stimulation was significantly increased in the STEP animals, suggesting a potential benefit of the STEP procedure. Strain gauge analysis, performed in awake animals, confirmed no differences between the groups for basal and octreotide-stimulated characteristics of phase III of the MMC. Conclusions: These preliminary data suggest that the STEP procedure in a porcine model of short bowel syndrome does not interfere with baseline or hormonally stimulated motility within the small bowel.
Presented at the 39th annual meeting of the American Pediatric Surgical Association, Phoenix, AZ, May 27-June 1, 2008. ⁎ Corresponding author. Department of Surgery, Children's Hospital Boston, Boston, MA 02115, USA. Tel.: +1 617 355 9600; fax: +1 617 730 0477. E-mail address: [email protected] (B.P. Modi). 0022-3468/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2008.10.045
230
B.P. Modi et al. These findings further support the STEP procedure as a safe option for the surgical management of short bowel syndrome. © 2009 Elsevier Inc. All rights reserved.
Short bowel syndrome, with resulting intestinal failure, can be a devastating pediatric disease with a prolonged recovery and a high expected mortality. The fundamental problem of inadequate intestinal absorptive capacity fosters further difficulties: bacterial overgrowth and its related complications [1], parenteral nutrition–associated liver disease with cholestasis and eventual liver failure [2], and dysfunctional intestinal motility because of inherent abnormalities in the bowel (eg, gastroschisis) or chronic intestinal dilatation through the adaptation response [3-5]. Surgical methods of treating short bowel syndrome most notably include the Bianchi longitudinal intestinal lengthening and tapering procedure and the serial transverse enteroplasty (STEP) procedure [6,7]. The STEP procedure has gained increasing interest since its introduction in 2003 because of its ease of use and good early outcomes. Multiple reports have suggested that the STEP procedure is effective at increasing tolerance to enteral feeding with a low complication rate [8-11]. The pattern of intestinal motility after the STEP procedure for short bowel syndrome is not known. One could postulate that tapering of the dilated bowel would provide for a more contoured channel that would be able to undergo more effective peristalsis. Alternatively, one could postulate that the transverse application of the stapling device in the STEP procedure might interrupt the neuroenteric system, thus negatively impacting the orderly progression of peristalsis along the length of the bowel. Although improved and more orderly peristalsis could certainly be one mechanism to explain the improvement in overall intestinal function experienced after the STEP procedure, it is possible that the procedure might actually have a negative impact on intestinal motility. The purpose of this study was to evaluate the pattern of intestinal motility after the STEP procedure in an established large animal model of short bowel syndrome. We hypothesized that small bowel motility in STEP animals, characterized by the presence and motility index of phase III of the migrating motor complex (MMC), is comparable to non-STEP short bowel animals.
Briefly, 7 growing female Yorkshire pigs underwent 3 operations at 6-week intervals. During the first operation, a laparotomy was performed and 50 cm of jejunum beginning 125 cm distal to the ligament of Treitz was reversed in situ. Six weeks later, a second laparotomy was performed and a 90% enterectomy was performed, including the reversed segment and all distal small bowel except 25 cm of terminal ileum. During this second surgery, the pigs were randomized to undergo simple reanastomosis (control, n = 3) or to undergo reanastomosis and a STEP procedure to the proximal dilated segment (approximately 125 cm) of small intestine (STEP, n = 4). For the study group, the STEP procedure was performed in the standard fashion using serial incomplete transverse applications of a linear cutting stapling device (GIA stapler, Autosuture, Norwalk, Conn) from alternating sides of the intestine [7,12]. At the third operation, after another period of 6 weeks, a repeat laparotomy was performed and all animals underwent implantation of 6 strain gauge catheters. Six gauges were placed in each animal in following locations, using 4 corner seromuscular stitches of nonabsorbable suture for each gauge: gastric antrum, second portion of duodenum, 3 gauges at equal distances along the length of the small intestine proximal to the anastomosis, and a last gauge 5 cm distal to the intestinal anastomosis. In all cases, the gauges were oriented to detect contraction of the longitudinal muscle layer of the intestine. After implantation, the gauges were tunneled externally to the midscapular region and the animals fitted with a pocketed jacket (Kent Scientific, Torrington, Conn) to prevent unintentional displacement of or damage to the gauges. Animals were fasted overnight before each operation. Before all operations, a single dose of preoperative first-generation cephalosporin was administered intravenously. All intestinal anastomoses were performed using a single layer of nonabsorbable suture. Animal weights were recorded before each operation. All intestinal lengths were measured intraoperatively along the antimesenteric border of the intestine.
1.2. Manometric monitoring
1. Methods All studies were performed under protocol approval by the Institutional Animal Care and Use Committee at the Animal Research facility at Children's Hospital (ARCH).
1.1. Operative model A previously reported porcine model of short bowel syndrome was modified for the purposes of this study [12].
Motility testing was performed using 2 independent methods. The first consisted of manometric monitoring intraoperatively during each of the 3 operations in all animals. To diminish the effect of general anesthesia on intestinal motility, gas anesthesia was not used until motility studies were completed. Anesthesia was induced using intramuscular ketamine at a dose of 25 mg/kg, then maintained with a bolus dose of 25 mg/kg pentobarbital intravenously followed by intermittent administration of additional pentobarbital as needed. This method of
STEP procedure in a porcine model of short bowel syndrome anesthesia has been shown to not interfere with motility events [13]. Once manometry studies were completed, anesthesia was switched to inhalational isoflurane until completion of the operative procedure. In this way, the first manometric measurement was accomplished before any bowel manipulation, the second measurement before any bowel resection or STEP, and the last measurement 6 weeks after STEP. Manometric studies were performed with a multilumen polyvinyl catheter continuously perfused by a low-compliance pneumohydraulic pump (Model ARM2, Arndorfer Medical Specialties Inc, Greendale, Wis). The catheter contained 8 ports placed at 15-cm intervals and radially oriented at 45° angles from one another. The most distal port was situated 1 cm from the tip of the catheter. Pressure readings were transmitted to the Polygraf ID multiparametric recorder, stored in a personal computer and analyzed using Polygramnet software (Medtronic Inc, Minneapolis, Minn). Baseline measurements were set at atmospheric pressure. At each operation, after laparotomy and before performance of the procedure, a sterilized manometry catheter was advanced retrograde via an enterotomy into the bowel lumen until the tip was located at the ligament of Treitz. Given the infrequent occurrence of phase III of the MMC, octreotide, a somatostatin analogue that has been shown to reliably produce phase III, was administered at a dose of 5 μg/kg subcutaneously after a baseline observation period of 30 minutes [14-16]. Further monitoring was performed for another 30 minutes before completion of manometry monitoring. At this point, the catheter was withdrawn, the enterotomy closed or resected, depending on the procedure, and the remainder of the operation completed.
1.3. Strain gauge monitoring The second method of monitoring motility was adapted from the method of Bass using implanted strain gauge force transducers [17]. This method has been established for assessing bowel motility in other animal models [18,19]. As described above, 6 custom-made strain gauges (13 × 9 mm with 36-in connecting wire, RB Products, Stillwater, Minn) were implanted (n = 3 in each group) at the third operation and tunneled externally. After recovery for 1 week, the animals were again fasted overnight and strain gauge monitoring was undertaken without sedation while the animals were awake in their pens. The leading wire from each gauge was attached to a connecting cable relaying the signal to an amplifier system (15LT Amplifier System, Astro-Med, Inc, West Warwick, RI) with a dedicated channel for each gauge. The signals obtained from the amplifiers were then relayed to a computerized data acquisition software system on a personal computer (Polyview/XL, Astro-Med Inc) for recording and subsequent review. Strain gauges were calibrated before insertion using a standardized weight. Monitoring was performed for a period of 4 hours at baseline. Octreotide
231 was then administered at a dose of 5 μg/kg subcutaneously, and the animals were monitored for an additional 30 minutes.
1.4. Analysis Recordings from both the manometric and strain gauge monitoring were analyzed for the presence and characteristics of phase III of the MMC. One blinded reviewer (SN) reviewed and analyzed all recordings. The motility index was defined as the percentage of activity × the mean amplitude of contraction waves [20]. Amplitude was measured in millimeters of mercury and frequency as contractions per minute. Phase III activity of the MMC was defined as regular contractions of at least 1 minute duration at a frequency of 10 to 12 contractions per minute occurring in at least 3 recording sites and followed by a period of relative quiescence (phase I) [14]. Qualitative values were expressed in percentage and quantitative values as mean ± SD. Comparisons between groups were made with the t test and χ2 test, as appropriate. Comparisons among the 3 surgeries were made with analysis of variance. The Statistical Package for Social Sciences (SPSS for Windows version 14.0, SPSS, Chicago, Ill) was used. Significance was set at P b .05.
2. Results Mean intestinal length after resection was 99 ± 16 cm in the STEP animals (n = 4) and 117 ± 8 cm in the control animals (n = 3, P = not significant [NS]). Mean intestinal length in STEP animals increased to 124 ± 19 cm from 99 ± 16 cm after the STEP procedure (P = NS). Mean weights at each operation were 28.4 ± 2.2, 34.0 ± 3.7, and 31.1 ± 4.8 kg in the STEP animals and 26.6 ± 3.0, 33.4 ± 2.1, 34.2 ± 4.3 kg in the control animals (all P = NS).
2.1. Manometric monitoring Manometry data revealed that the 2 groups had similar motility indices and characteristics at baseline and after octreotide administration during all 3 surgeries (Table 1). Phase III of the MMC was present in post-STEP animals. When comparing the 2 groups at the third surgery, there were no differences in the motility index, presence or absence of phase III of the MMC, or phase III characteristics. There was a tendency for the basal contraction amplitude to be higher in the STEP group, as compared with the control group, but this did not reach statistical significance in this small series. Both groups showed nonspecific abnormalities of phase III of the MMC; the most common was abnormal migration throughout all segments, including simultaneous contractions or contractions present in only proximal or distal segments. Tonic contractions were also noted. There were, however, no
232 Table 1
B.P. Modi et al. Summary of results from manometric monitoring
Variable
Baseline presence of contractions Basal max amplitude of contractions (mm Hg) Basal mean amplitude (mm Hg) Basal motility index Post-octreotide presence of phase III Post-octreotide normal migration Post-octreotide tonic component Post-octreotide retrograde migration Post-octreotide max amplitude (mm Hg) Post-octreotide mean amplitude (mm Hg) Post-octreotide motility index Post-octreotide duration (s) Post-octreotide frequency (contractions/min)
Control
STEP
Initial surgery
Second surgery
Final surgery
Initial surgery
Second surgery
Final surgery
0/3 33.9 ± 16.8
1/3 17.4 ± 6.5
2/3 22.6 ± 11.6
2/4 21.4 ± 10.0
2/4 49.4 ± 70.6
1/4 39.4 ± 14.5 ⁎
8.5 ± 7.0 5.3 ± 1.6 3/3 1/3 1/3 0/3 96.5 ± 113.0 8.7 ± 3.2 5.7 ± 0.6 350.7 ± 357.6 11.3 ± 3.1
3.9 ± 7.5 5.0 ± 1.5 3/3 1/3 1/3 0/3 31.7 ± 18.0 1.2 ± 3.3 † 5.4 ± 0.8 324.0 ± 343.6 12.3 ± 3.1
8.6 ± 8.1 5.0 ± 2.2 3/3 0/3 0/3 1/4 32.3 ± 16.0 9.2 ± 8.2 5.3 ± 2.3 209.9 ± 62.5 11.7 ± 0.6
4.8 ± 8.7 4.4 ± 1.7 4/4 1/4 1/4 0/4 80.8 ± 44.9 6.5 ± 8.0 5.2 ± 1.5 742.0 ± 716.8 13.0 ± 1.4
4.4 ± 7.3 5.0 ± 1.8 2/4 1/2 0/2 0/2 89.2 ± 44.1 13.4 ± 7.4 5.2 ± 1.5 275.0 ± 70.0 12.5 ± 11.3
9.5 ± 13.4 5.6 ± 1.3 3/4 1/3 1/3 2/3 42.6 ± 28.3 9.0 ± 12.2 5.3 ± 1.7 625.3 ± 131.5 ‡, § 11.3 ± 2.1
All comparisons between groups and within groups were nonsignificant except as indicated. ⁎ P b .08, final vs initial. † P b .05, initial vs second. ‡ P b .05, final vs second. § P b .05, STEP final vs control final.
differences in the frequency or types of abnormalities when comparing the 2 groups. Notably, during the final measurement, the mean duration of phase III of the MMC after administration of octreotide was significantly longer in the STEP group as compared with that in the control group
(625.3 ± 131.5 vs 209.9 ± 62.5 seconds, P b .05). In addition, as depicted in Table 1, the duration of phase III was longer at the third surgery as compared with the second surgery for STEP animals (625.3 ± 131.5 vs 275.0 ± 70.0 seconds, P b .05). When comparing within groups, no
Fig. 1 Manometric readings demonstrating octreotide-stimulated phase III of the MMC in STEP (A) and control (B) animals. In these examples, both animals demonstrated phase III activity that started proximally and migrated distally. In the STEP animal, the progression of phase III showed some simultaneous activity in the distal channels. In the control animal, the lower segments showed abnormal contractions with a tonic component.
STEP procedure in a porcine model of short bowel syndrome Table 2
233
Summary of results from strain gauge monitoring Control (n = 3)
STEP (n = 3)
Characteristics of phase III of the MMC at baseline Presence of phase III complexes Number of phase III complexes Number of normal phase III complexes Percent normal phase III complexes Percent of phase III with normal amplitude (mm Hg) Percent of phase III with tonic component Percent of phase III with normal propagation Mean frequency of contractions (contractions/min) Mean amplitude (mm Hg) Mean duration (s) Mean speed (cm/s)
3/3 5.0 ± 1.0 3.0 ± 1.7 57.2 ± 28.7 58.9 ± 41.7 66.7 ± 57.7 43.3 ± 40.4 16.1 ± 0.7 16.0 ± 2.6 360.0 ± 87.5 0.3 ± 0.2
3/3 5.3 ± 0.6 3.7 ± 2.5 66.7 ± 41.6 73.3 ± 46.2 31.1 ± 30.1 54.4 ± 32.0 15.2 ± 0.9 10.7 ± 7.3 339.5 ± 160.2 0.4 ± 0.3
Characteristics of phase III of the MMC post-octreotide Presence of phase III complexes Number of phase III complexes Number of normal phase III complexes Percent normal phase III complexes Percent of phase III with normal amplitude (mm Hg) Percent of phase III with tonic component Percent of phase III with normal propagation Mean frequency of contractions (contractions/min) Mean amplitude (mm Hg) Mean duration (s) Mean speed (cm/s)
3/3 1.5 ± 0.7 0.5 ± 0.7 50.0 ± 70.7 0.0 ± 0.0 50.0 ± 70.7 75.0 ± 35.4 18.5 ± 2.1 14.6 ± 5.3 338.7 ± 130.7 0.40 ± 0.01
3/3 1.0 ± 0.0 1.0 ± 0.0 100.0 ± 0.0 50.0 ± 70.7 100.0 ± 0.0 50.0 ± 70.7 15.0 ± 1.4 10.5 ± 0.8 183.2 ± 57.2 0.1 ± 0.0
All comparisons between groups were nonsignificant (P = NS).
differences existed between measurements at baseline and at the final surgery. Fig. 1 shows examples of phase III of the MMC obtained during the last surgery in both STEP and control animals.
2.2. Strain gauge monitoring Strain gauge monitoring revealed that both the STEP animals and control animals had normal, physiologic MMCs within the small intestine (Table 2). The mean number of phase III contractions seen during the 4-hour baseline monitoring was 5.0 ± 1.0 in the control group and 5.3 ± 0.6 in the STEP group (P = NS). Both groups demonstrated the presence of normal MMCs at baseline and after octreotide, without significant differences when comparing results in both groups. Nonspecific abnormalities similar to those seen with manometric monitoring were again noted, without significant differences between the groups. The transduced data from the strain gauge monitoring are similar to phase III activity visualized with manometry. A representative example from each group is given in Fig. 2.
3. Discussion These data represent an initial attempt to study the motility of the small intestine after the STEP procedure. The
strain gauge data suggest that the motility of the small intestine after the STEP procedure is intact, with presence of phase III of the MMC in a fasting state. This finding is further bolstered by the ability to provoke phase III of the MMC using the somatostatin analogue, octreotide, in both strain gauge monitoring and manometric monitoring. The ramifications of these findings are important in the setting of the improvement seen in tolerance of enteral nutrition after the STEP procedure [8-11]. The postulated mechanisms by which the STEP procedure might elicit these beneficial results include (1) improvement in the absorption of enteral nutrients, perhaps by increasing overall intestinal absorptive surface area, (2) decreased bacterial overgrowth, via tapering and reduction in stasis, and (3) more ordered intestinal motility allowing for better handling of enteral intake and perhaps contributing to the other 2 mechanisms. Early animal studies of the STEP procedure have demonstrated that the first 2 hypothetical mechanisms do indeed seem to be true. These studies demonstrated improved absorption of enteric markers of intestinal nutrient absorption in STEP animals compared with controls and a near elimination of bacterial overgrowth in STEP animals [12]. No prior studies have evaluated the effect of the STEP procedure on motility within the small intestine. The presence of both spontaneous phase III activity in awake animals and phase III activity after octreotide administration demonstrates the integrity of the myenteric plexus and
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Fig. 2 Phase III of the MMC progresses from the duodenum (top panel) through the small bowel (middle and bottom panels) in both STEP (A) and control (B) animals during awake strain gauge transducer monitoring.
indicates that the STEP procedure does not seem to alter its organization. Previous studies have demonstrated that the presence of phase III of the MMC has been associated with the ability to tolerate enteral feedings in children. The preservation of motility may be a factor in the improvement observed after the STEP procedure [21]. It has also been shown that a lack of phase III of the MMC is associated with bacterial overgrowth, suggesting that one mechanism leading to the decreased bacterial overgrowth seen post-STEP may be related to the preservation of phase III complexes [22]. Some nonspecific abnormalities in MMC characteristics were noted in both groups. Propagation of phase III was abnormal at times throughout the whole length of measured bowel, whereas some complexes also had a tonic component. The clinical significance of these abnormalities is not known because nonspecific abnormal manometric patterns do not necessarily correlate with abnormal transit [15]. More objective studies to specifically evaluate intestinal transit through post-STEP bowel are needed to understand the clinical significance of the abnormalities seen in this study.
Although it is still possible that some areas of the myenteric plexus may be altered by the STEP procedure, the presence of the abnormalities in the recordings of both groups indicates that this effect on motility is probably a result of small bowel dilatation, measurement conditions, or intestinal surgery rather than the STEP procedure itself. Although the data are limited to a small number of animals, there was a longer duration of the post-octreotide phase III contractions in STEP animals and a trend toward higher amplitude of the contractions, pointing to a possible beneficial effect of the STEP procedure. Studies with larger numbers, perhaps including experiments in patients who have undergone the STEP procedure, are needed to determine if these trends are true differences between the groups. It is unclear how the process of adaptation might relate to the preserved, and potentially improved, motility seen after the STEP procedure. Intestinal dilation as a consequence of adaptation after significant bowel shortening likely results in some part to the disordered motility seen in short bowel syndrome. Tapering of the “adapted” intestine, without obvious
STEP procedure in a porcine model of short bowel syndrome detriment to the processes of bowel motility, may partially be the source of the success of the STEP procedure. It is unlikely, however, that adaptation played a large role in the outcomes of these experiments, given the short periods involved. A potential weakness of the present study is the inability to study the pigs under natural conditions. Manometric monitoring was performed under anesthesia and after laparotomy, although the anesthetic agents used have been demonstrated to have minimal impact on intestinal motility [13]. In addition, although the strain gauge monitoring was performed in awake animals, it required implantation of the gauges onto the intestine, perhaps therefore affecting the ordered motility of the intestine. Previous animal studies, however, have shown that motility is preserved in this setting [23]. Using the 2 modalities in conjunction arguably allows their findings to corroborate each other. Finally, the effect of the STEP procedure on human motility cannot necessarily be extrapolated from these experiments. Studies in which small bowel motility is monitored in patients undergoing the STEP procedure would be useful. In conclusion, in this large animal model, manometric monitoring and strain gauge transduction of small intestinal motility demonstrate no negative impact from the STEP procedure in the presence of or the characteristics of the MMC. In addition, the presence of normal MMC patterns in awake animals during a fast indicates that the inherent mechanisms of small intestinal motility are intact after the STEP procedure.
Acknowledgments Support for this work was provided by the Children's Hospital Boston Surgical Foundation and the Joshua Ryan Rappaport Fellowship in Pediatric Surgical Research (BPM). The authors would also like to thank Dr Arthur Nedder, Mark Kelly, and the rest of the staff at ARCH for their excellent animal care and assistance.
References [1] O'Keefe SJ, Buchman AL, Fishbein TM, et al. Short bowel syndrome and intestinal failure: consensus definitions and overview. Clin Gastroenterol Hepatol 2006;4:6-10. [2] Kelly DA. Intestinal failure-associated liver disease: what do we know today? Gastroenterology 2006;130:S70-7. [3] Ching YA, Gura K, Modi B, et al. Pediatric intestinal failure: nutrition, pharmacologic, and surgical approaches. Nutr Clin Pract 2007;22:653-63. [4] Buchman AL. Etiology and initial management of short bowel syndrome. Gastroenterology 2006;130:S5-S15. [5] Goulet O, Ruemmele F, Lacaille F, et al. Irreversible intestinal failure. J Pediatr Gastroenterol Nutr 2004;38:250-69. [6] Bianchi A. Intestinal loop lengthening—a technique for increasing small intestinal length. J Pediatr Surg 1980;15:145-51. [7] Kim HB, Fauza D, Garza J, et al. Serial transverse enteroplasty (STEP): a novel bowel lengthening procedure. J Pediatr Surg 2003;38:425-9.
235 [8] Javid PJ, Kim HB, Duggan CP, Jaksic T. Serial transverse enteroplasty is associated with successful short-term outcomes in infants with short bowel syndrome. J Pediatr Surg 2005;40:1019-23 [discussion 10231024]. [9] Modi BP, Javid PJ, Jaksic T, et al. First report of the International Serial Transverse Enteroplasty Data Registry: Indications, efficacy, and complications. J Am Coll Surg 2007;204:365-71. [10] Sudan D, Thompson J, Botha J, et al. Comparison of intestinal lengthening procedures for patients with short bowel syndrome. Ann Surg 2007;246:593-601 [discussion 601-604]. [11] Wales PW, de Silva N, Langer JC, et al. Intermediate outcomes after serial transverse enteroplasty in children with short bowel syndrome. J Pediatr Surg 2007;42:1804-10. [12] Chang RW, Javid PJ, Oh JT, et al. Serial transverse enteroplasty enhances intestinal function in a model of short bowel syndrome. Ann Surg 2006;243:223-8. [13] Nurko S, Rattan S. Role of vasoactive intestinal polypeptide in the internal anal sphincter relaxation of the opossum. J Clin Invest 1988; 81:1146-53. [14] Savoye G, Bouin M, Labbe L, et al. Concomitant variations of gastric tone and duodenal motility in humans: results of a placebo-controlled study assessing octreotide and sumatriptan. Scand J Gastroenterol 2006;41:536-43. [15] Nurko S. Gastrointestinal manometry: methodology and indications. In: Walker WA, Kleinman RE, Sherman PM, editors. Pediatric gastrointestinal disease. Philadelphia (Pa): B.C. Decker Inc.; 2004. p. 1786-808. [16] Di Lorenzo C, Lucanto C, Flores AF, et al. Effect of octreotide on gastrointestinal motility in children with functional gastrointestinal symptoms. J Pediatr Gastroenterol Nutr 1998;27:508-12. [17] Bass P, Wiley JN. Contractile force transducer for recording muscle activity in unanesthetized animals. J Appl Physiol 1972;32:567-70. [18] Kaji T, Takamatsu H, Kajiya H. Motility of the gastrointestinal tract and gallbladder during long-term total parenteral nutrition in dogs. JPEN JPEM J Parenter Enteral Nutr 2002;26:198-204. [19] Nishimoto Y, Taguchi T, Masumoto K, et al. Real-time monitoring for detecting rejection using strain gauge force transducers in porcine small bowel transplantation. Transplant Proc 2004;36:343-4. [20] Camilleri M, Hasler WL, Parkman HP, et al. Measurement of gastrointestinal motility in the GI laboratory. Gastroenterology 1998; 115:747-62. [21] Di Lorenzo C, Flores AF, Buie T, et al. Intestinal motility and jejunal feeding in children with chronic intestinal pseudo-obstruction. Gastroenterology 1995;108:1379-85. [22] Vantrappen G, Janssens J, Hellemans J, et al. The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J Clin Invest 1977;59:1158-66. [23] Nakada K, Ikoma A, Suzuki T, et al. Amelioration of intestinal dysmotility and stasis by octreotide early after small-bowel autotransplantation in dogs. Am J Surg 1995;169:294-9.
Discussion Speaker: Thank you very much for the presentation. I have a question. These data are fasting period, so do you have some other difference in the postprandial phase? Dr Modi: We have done some studies using markers of transit which have not yet elucidated the specifics of postprandial motility. In the fasting state, however, looking truly at the migrating motor complex, it seems to be similar between control and STEP groups.
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Preservation of intestinal motility after the serial transverse enteroplasty procedure in a large animal model of short bowel syndrome Biren P. Modi a,b,⁎, Y. Avery Ching a,b , Monica Langer a,b , Kate Donovan c , Dario O. Fauza b , Heung Bae Kim a,b,d , Tom Jaksic a,b , Samuel Nurko c a
Center for Advanced Intestinal Rehabilitation (CAIR), Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA b Department of Surgery, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA c Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology and Nutrition, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA d Pediatric Transplant Center, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA Received 4 October 2008; accepted 7 October 2008
Key words: Short bowel syndrome; Serial transverse enteroplasty; Intestinal lengthening; Intestinal failure; Motility
Abstract Introduction: Serial transverse enteroplasty (STEP) has been shown to improve bowel function in short bowel syndrome. The effect of the STEP procedure on intestinal motility is not known, but some have hypothesized that it could disrupt bowel innervation and thus impair intestinal motility. Methods: Growing Yorkshire pigs (n = 7) underwent 3 operations at 6-week intervals: (1) reversal of 50 cm of jejunum, (2) 90% bowel resection ± STEP to the proximal dilated bowel (4 STEP, 3 control), and (3) implantation of serosal strain gauges. At each operation, baseline and post-octreotide small intestinal motility was studied with continuously perfused manometry catheters using non-anticholinergic anesthesia. In addition, awake monitoring was performed using strain gauge analysis 1 week after the third operation. Characteristics of phase III of the migrating motor complex (MMC) were compared between and within groups using t test, χ2, and analysis of variance, with significance set at P b .05. Results: Manometry data from the third surgery revealed no differences between groups or compared with baseline within groups for the presence and characteristics of phase III of the MMC. Specifically, the mean amplitude and frequency of phase III after octreotide, and both the mean baseline and mean octreotide-stimulated motility indices were equivalent. The duration of phase III after octreotide stimulation was significantly increased in the STEP animals, suggesting a potential benefit of the STEP procedure. Strain gauge analysis, performed in awake animals, confirmed no differences between the groups for basal and octreotide-stimulated characteristics of phase III of the MMC. Conclusions: These preliminary data suggest that the STEP procedure in a porcine model of short bowel syndrome does not interfere with baseline or hormonally stimulated motility within the small bowel.
Presented at the 39th annual meeting of the American Pediatric Surgical Association, Phoenix, AZ, May 27-June 1, 2008. ⁎ Corresponding author. Department of Surgery, Children's Hospital Boston, Boston, MA 02115, USA. Tel.: +1 617 355 9600; fax: +1 617 730 0477. E-mail address: [email protected] (B.P. Modi). 0022-3468/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2008.10.045
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B.P. Modi et al. These findings further support the STEP procedure as a safe option for the surgical management of short bowel syndrome. © 2009 Elsevier Inc. All rights reserved.
Short bowel syndrome, with resulting intestinal failure, can be a devastating pediatric disease with a prolonged recovery and a high expected mortality. The fundamental problem of inadequate intestinal absorptive capacity fosters further difficulties: bacterial overgrowth and its related complications [1], parenteral nutrition–associated liver disease with cholestasis and eventual liver failure [2], and dysfunctional intestinal motility because of inherent abnormalities in the bowel (eg, gastroschisis) or chronic intestinal dilatation through the adaptation response [3-5]. Surgical methods of treating short bowel syndrome most notably include the Bianchi longitudinal intestinal lengthening and tapering procedure and the serial transverse enteroplasty (STEP) procedure [6,7]. The STEP procedure has gained increasing interest since its introduction in 2003 because of its ease of use and good early outcomes. Multiple reports have suggested that the STEP procedure is effective at increasing tolerance to enteral feeding with a low complication rate [8-11]. The pattern of intestinal motility after the STEP procedure for short bowel syndrome is not known. One could postulate that tapering of the dilated bowel would provide for a more contoured channel that would be able to undergo more effective peristalsis. Alternatively, one could postulate that the transverse application of the stapling device in the STEP procedure might interrupt the neuroenteric system, thus negatively impacting the orderly progression of peristalsis along the length of the bowel. Although improved and more orderly peristalsis could certainly be one mechanism to explain the improvement in overall intestinal function experienced after the STEP procedure, it is possible that the procedure might actually have a negative impact on intestinal motility. The purpose of this study was to evaluate the pattern of intestinal motility after the STEP procedure in an established large animal model of short bowel syndrome. We hypothesized that small bowel motility in STEP animals, characterized by the presence and motility index of phase III of the migrating motor complex (MMC), is comparable to non-STEP short bowel animals.
Briefly, 7 growing female Yorkshire pigs underwent 3 operations at 6-week intervals. During the first operation, a laparotomy was performed and 50 cm of jejunum beginning 125 cm distal to the ligament of Treitz was reversed in situ. Six weeks later, a second laparotomy was performed and a 90% enterectomy was performed, including the reversed segment and all distal small bowel except 25 cm of terminal ileum. During this second surgery, the pigs were randomized to undergo simple reanastomosis (control, n = 3) or to undergo reanastomosis and a STEP procedure to the proximal dilated segment (approximately 125 cm) of small intestine (STEP, n = 4). For the study group, the STEP procedure was performed in the standard fashion using serial incomplete transverse applications of a linear cutting stapling device (GIA stapler, Autosuture, Norwalk, Conn) from alternating sides of the intestine [7,12]. At the third operation, after another period of 6 weeks, a repeat laparotomy was performed and all animals underwent implantation of 6 strain gauge catheters. Six gauges were placed in each animal in following locations, using 4 corner seromuscular stitches of nonabsorbable suture for each gauge: gastric antrum, second portion of duodenum, 3 gauges at equal distances along the length of the small intestine proximal to the anastomosis, and a last gauge 5 cm distal to the intestinal anastomosis. In all cases, the gauges were oriented to detect contraction of the longitudinal muscle layer of the intestine. After implantation, the gauges were tunneled externally to the midscapular region and the animals fitted with a pocketed jacket (Kent Scientific, Torrington, Conn) to prevent unintentional displacement of or damage to the gauges. Animals were fasted overnight before each operation. Before all operations, a single dose of preoperative first-generation cephalosporin was administered intravenously. All intestinal anastomoses were performed using a single layer of nonabsorbable suture. Animal weights were recorded before each operation. All intestinal lengths were measured intraoperatively along the antimesenteric border of the intestine.
1.2. Manometric monitoring
1. Methods All studies were performed under protocol approval by the Institutional Animal Care and Use Committee at the Animal Research facility at Children's Hospital (ARCH).
1.1. Operative model A previously reported porcine model of short bowel syndrome was modified for the purposes of this study [12].
Motility testing was performed using 2 independent methods. The first consisted of manometric monitoring intraoperatively during each of the 3 operations in all animals. To diminish the effect of general anesthesia on intestinal motility, gas anesthesia was not used until motility studies were completed. Anesthesia was induced using intramuscular ketamine at a dose of 25 mg/kg, then maintained with a bolus dose of 25 mg/kg pentobarbital intravenously followed by intermittent administration of additional pentobarbital as needed. This method of
STEP procedure in a porcine model of short bowel syndrome anesthesia has been shown to not interfere with motility events [13]. Once manometry studies were completed, anesthesia was switched to inhalational isoflurane until completion of the operative procedure. In this way, the first manometric measurement was accomplished before any bowel manipulation, the second measurement before any bowel resection or STEP, and the last measurement 6 weeks after STEP. Manometric studies were performed with a multilumen polyvinyl catheter continuously perfused by a low-compliance pneumohydraulic pump (Model ARM2, Arndorfer Medical Specialties Inc, Greendale, Wis). The catheter contained 8 ports placed at 15-cm intervals and radially oriented at 45° angles from one another. The most distal port was situated 1 cm from the tip of the catheter. Pressure readings were transmitted to the Polygraf ID multiparametric recorder, stored in a personal computer and analyzed using Polygramnet software (Medtronic Inc, Minneapolis, Minn). Baseline measurements were set at atmospheric pressure. At each operation, after laparotomy and before performance of the procedure, a sterilized manometry catheter was advanced retrograde via an enterotomy into the bowel lumen until the tip was located at the ligament of Treitz. Given the infrequent occurrence of phase III of the MMC, octreotide, a somatostatin analogue that has been shown to reliably produce phase III, was administered at a dose of 5 μg/kg subcutaneously after a baseline observation period of 30 minutes [14-16]. Further monitoring was performed for another 30 minutes before completion of manometry monitoring. At this point, the catheter was withdrawn, the enterotomy closed or resected, depending on the procedure, and the remainder of the operation completed.
1.3. Strain gauge monitoring The second method of monitoring motility was adapted from the method of Bass using implanted strain gauge force transducers [17]. This method has been established for assessing bowel motility in other animal models [18,19]. As described above, 6 custom-made strain gauges (13 × 9 mm with 36-in connecting wire, RB Products, Stillwater, Minn) were implanted (n = 3 in each group) at the third operation and tunneled externally. After recovery for 1 week, the animals were again fasted overnight and strain gauge monitoring was undertaken without sedation while the animals were awake in their pens. The leading wire from each gauge was attached to a connecting cable relaying the signal to an amplifier system (15LT Amplifier System, Astro-Med, Inc, West Warwick, RI) with a dedicated channel for each gauge. The signals obtained from the amplifiers were then relayed to a computerized data acquisition software system on a personal computer (Polyview/XL, Astro-Med Inc) for recording and subsequent review. Strain gauges were calibrated before insertion using a standardized weight. Monitoring was performed for a period of 4 hours at baseline. Octreotide
231 was then administered at a dose of 5 μg/kg subcutaneously, and the animals were monitored for an additional 30 minutes.
1.4. Analysis Recordings from both the manometric and strain gauge monitoring were analyzed for the presence and characteristics of phase III of the MMC. One blinded reviewer (SN) reviewed and analyzed all recordings. The motility index was defined as the percentage of activity × the mean amplitude of contraction waves [20]. Amplitude was measured in millimeters of mercury and frequency as contractions per minute. Phase III activity of the MMC was defined as regular contractions of at least 1 minute duration at a frequency of 10 to 12 contractions per minute occurring in at least 3 recording sites and followed by a period of relative quiescence (phase I) [14]. Qualitative values were expressed in percentage and quantitative values as mean ± SD. Comparisons between groups were made with the t test and χ2 test, as appropriate. Comparisons among the 3 surgeries were made with analysis of variance. The Statistical Package for Social Sciences (SPSS for Windows version 14.0, SPSS, Chicago, Ill) was used. Significance was set at P b .05.
2. Results Mean intestinal length after resection was 99 ± 16 cm in the STEP animals (n = 4) and 117 ± 8 cm in the control animals (n = 3, P = not significant [NS]). Mean intestinal length in STEP animals increased to 124 ± 19 cm from 99 ± 16 cm after the STEP procedure (P = NS). Mean weights at each operation were 28.4 ± 2.2, 34.0 ± 3.7, and 31.1 ± 4.8 kg in the STEP animals and 26.6 ± 3.0, 33.4 ± 2.1, 34.2 ± 4.3 kg in the control animals (all P = NS).
2.1. Manometric monitoring Manometry data revealed that the 2 groups had similar motility indices and characteristics at baseline and after octreotide administration during all 3 surgeries (Table 1). Phase III of the MMC was present in post-STEP animals. When comparing the 2 groups at the third surgery, there were no differences in the motility index, presence or absence of phase III of the MMC, or phase III characteristics. There was a tendency for the basal contraction amplitude to be higher in the STEP group, as compared with the control group, but this did not reach statistical significance in this small series. Both groups showed nonspecific abnormalities of phase III of the MMC; the most common was abnormal migration throughout all segments, including simultaneous contractions or contractions present in only proximal or distal segments. Tonic contractions were also noted. There were, however, no
232 Table 1
B.P. Modi et al. Summary of results from manometric monitoring
Variable
Baseline presence of contractions Basal max amplitude of contractions (mm Hg) Basal mean amplitude (mm Hg) Basal motility index Post-octreotide presence of phase III Post-octreotide normal migration Post-octreotide tonic component Post-octreotide retrograde migration Post-octreotide max amplitude (mm Hg) Post-octreotide mean amplitude (mm Hg) Post-octreotide motility index Post-octreotide duration (s) Post-octreotide frequency (contractions/min)
Control
STEP
Initial surgery
Second surgery
Final surgery
Initial surgery
Second surgery
Final surgery
0/3 33.9 ± 16.8
1/3 17.4 ± 6.5
2/3 22.6 ± 11.6
2/4 21.4 ± 10.0
2/4 49.4 ± 70.6
1/4 39.4 ± 14.5 ⁎
8.5 ± 7.0 5.3 ± 1.6 3/3 1/3 1/3 0/3 96.5 ± 113.0 8.7 ± 3.2 5.7 ± 0.6 350.7 ± 357.6 11.3 ± 3.1
3.9 ± 7.5 5.0 ± 1.5 3/3 1/3 1/3 0/3 31.7 ± 18.0 1.2 ± 3.3 † 5.4 ± 0.8 324.0 ± 343.6 12.3 ± 3.1
8.6 ± 8.1 5.0 ± 2.2 3/3 0/3 0/3 1/4 32.3 ± 16.0 9.2 ± 8.2 5.3 ± 2.3 209.9 ± 62.5 11.7 ± 0.6
4.8 ± 8.7 4.4 ± 1.7 4/4 1/4 1/4 0/4 80.8 ± 44.9 6.5 ± 8.0 5.2 ± 1.5 742.0 ± 716.8 13.0 ± 1.4
4.4 ± 7.3 5.0 ± 1.8 2/4 1/2 0/2 0/2 89.2 ± 44.1 13.4 ± 7.4 5.2 ± 1.5 275.0 ± 70.0 12.5 ± 11.3
9.5 ± 13.4 5.6 ± 1.3 3/4 1/3 1/3 2/3 42.6 ± 28.3 9.0 ± 12.2 5.3 ± 1.7 625.3 ± 131.5 ‡, § 11.3 ± 2.1
All comparisons between groups and within groups were nonsignificant except as indicated. ⁎ P b .08, final vs initial. † P b .05, initial vs second. ‡ P b .05, final vs second. § P b .05, STEP final vs control final.
differences in the frequency or types of abnormalities when comparing the 2 groups. Notably, during the final measurement, the mean duration of phase III of the MMC after administration of octreotide was significantly longer in the STEP group as compared with that in the control group
(625.3 ± 131.5 vs 209.9 ± 62.5 seconds, P b .05). In addition, as depicted in Table 1, the duration of phase III was longer at the third surgery as compared with the second surgery for STEP animals (625.3 ± 131.5 vs 275.0 ± 70.0 seconds, P b .05). When comparing within groups, no
Fig. 1 Manometric readings demonstrating octreotide-stimulated phase III of the MMC in STEP (A) and control (B) animals. In these examples, both animals demonstrated phase III activity that started proximally and migrated distally. In the STEP animal, the progression of phase III showed some simultaneous activity in the distal channels. In the control animal, the lower segments showed abnormal contractions with a tonic component.
STEP procedure in a porcine model of short bowel syndrome Table 2
233
Summary of results from strain gauge monitoring Control (n = 3)
STEP (n = 3)
Characteristics of phase III of the MMC at baseline Presence of phase III complexes Number of phase III complexes Number of normal phase III complexes Percent normal phase III complexes Percent of phase III with normal amplitude (mm Hg) Percent of phase III with tonic component Percent of phase III with normal propagation Mean frequency of contractions (contractions/min) Mean amplitude (mm Hg) Mean duration (s) Mean speed (cm/s)
3/3 5.0 ± 1.0 3.0 ± 1.7 57.2 ± 28.7 58.9 ± 41.7 66.7 ± 57.7 43.3 ± 40.4 16.1 ± 0.7 16.0 ± 2.6 360.0 ± 87.5 0.3 ± 0.2
3/3 5.3 ± 0.6 3.7 ± 2.5 66.7 ± 41.6 73.3 ± 46.2 31.1 ± 30.1 54.4 ± 32.0 15.2 ± 0.9 10.7 ± 7.3 339.5 ± 160.2 0.4 ± 0.3
Characteristics of phase III of the MMC post-octreotide Presence of phase III complexes Number of phase III complexes Number of normal phase III complexes Percent normal phase III complexes Percent of phase III with normal amplitude (mm Hg) Percent of phase III with tonic component Percent of phase III with normal propagation Mean frequency of contractions (contractions/min) Mean amplitude (mm Hg) Mean duration (s) Mean speed (cm/s)
3/3 1.5 ± 0.7 0.5 ± 0.7 50.0 ± 70.7 0.0 ± 0.0 50.0 ± 70.7 75.0 ± 35.4 18.5 ± 2.1 14.6 ± 5.3 338.7 ± 130.7 0.40 ± 0.01
3/3 1.0 ± 0.0 1.0 ± 0.0 100.0 ± 0.0 50.0 ± 70.7 100.0 ± 0.0 50.0 ± 70.7 15.0 ± 1.4 10.5 ± 0.8 183.2 ± 57.2 0.1 ± 0.0
All comparisons between groups were nonsignificant (P = NS).
differences existed between measurements at baseline and at the final surgery. Fig. 1 shows examples of phase III of the MMC obtained during the last surgery in both STEP and control animals.
2.2. Strain gauge monitoring Strain gauge monitoring revealed that both the STEP animals and control animals had normal, physiologic MMCs within the small intestine (Table 2). The mean number of phase III contractions seen during the 4-hour baseline monitoring was 5.0 ± 1.0 in the control group and 5.3 ± 0.6 in the STEP group (P = NS). Both groups demonstrated the presence of normal MMCs at baseline and after octreotide, without significant differences when comparing results in both groups. Nonspecific abnormalities similar to those seen with manometric monitoring were again noted, without significant differences between the groups. The transduced data from the strain gauge monitoring are similar to phase III activity visualized with manometry. A representative example from each group is given in Fig. 2.
3. Discussion These data represent an initial attempt to study the motility of the small intestine after the STEP procedure. The
strain gauge data suggest that the motility of the small intestine after the STEP procedure is intact, with presence of phase III of the MMC in a fasting state. This finding is further bolstered by the ability to provoke phase III of the MMC using the somatostatin analogue, octreotide, in both strain gauge monitoring and manometric monitoring. The ramifications of these findings are important in the setting of the improvement seen in tolerance of enteral nutrition after the STEP procedure [8-11]. The postulated mechanisms by which the STEP procedure might elicit these beneficial results include (1) improvement in the absorption of enteral nutrients, perhaps by increasing overall intestinal absorptive surface area, (2) decreased bacterial overgrowth, via tapering and reduction in stasis, and (3) more ordered intestinal motility allowing for better handling of enteral intake and perhaps contributing to the other 2 mechanisms. Early animal studies of the STEP procedure have demonstrated that the first 2 hypothetical mechanisms do indeed seem to be true. These studies demonstrated improved absorption of enteric markers of intestinal nutrient absorption in STEP animals compared with controls and a near elimination of bacterial overgrowth in STEP animals [12]. No prior studies have evaluated the effect of the STEP procedure on motility within the small intestine. The presence of both spontaneous phase III activity in awake animals and phase III activity after octreotide administration demonstrates the integrity of the myenteric plexus and
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Fig. 2 Phase III of the MMC progresses from the duodenum (top panel) through the small bowel (middle and bottom panels) in both STEP (A) and control (B) animals during awake strain gauge transducer monitoring.
indicates that the STEP procedure does not seem to alter its organization. Previous studies have demonstrated that the presence of phase III of the MMC has been associated with the ability to tolerate enteral feedings in children. The preservation of motility may be a factor in the improvement observed after the STEP procedure [21]. It has also been shown that a lack of phase III of the MMC is associated with bacterial overgrowth, suggesting that one mechanism leading to the decreased bacterial overgrowth seen post-STEP may be related to the preservation of phase III complexes [22]. Some nonspecific abnormalities in MMC characteristics were noted in both groups. Propagation of phase III was abnormal at times throughout the whole length of measured bowel, whereas some complexes also had a tonic component. The clinical significance of these abnormalities is not known because nonspecific abnormal manometric patterns do not necessarily correlate with abnormal transit [15]. More objective studies to specifically evaluate intestinal transit through post-STEP bowel are needed to understand the clinical significance of the abnormalities seen in this study.
Although it is still possible that some areas of the myenteric plexus may be altered by the STEP procedure, the presence of the abnormalities in the recordings of both groups indicates that this effect on motility is probably a result of small bowel dilatation, measurement conditions, or intestinal surgery rather than the STEP procedure itself. Although the data are limited to a small number of animals, there was a longer duration of the post-octreotide phase III contractions in STEP animals and a trend toward higher amplitude of the contractions, pointing to a possible beneficial effect of the STEP procedure. Studies with larger numbers, perhaps including experiments in patients who have undergone the STEP procedure, are needed to determine if these trends are true differences between the groups. It is unclear how the process of adaptation might relate to the preserved, and potentially improved, motility seen after the STEP procedure. Intestinal dilation as a consequence of adaptation after significant bowel shortening likely results in some part to the disordered motility seen in short bowel syndrome. Tapering of the “adapted” intestine, without obvious
STEP procedure in a porcine model of short bowel syndrome detriment to the processes of bowel motility, may partially be the source of the success of the STEP procedure. It is unlikely, however, that adaptation played a large role in the outcomes of these experiments, given the short periods involved. A potential weakness of the present study is the inability to study the pigs under natural conditions. Manometric monitoring was performed under anesthesia and after laparotomy, although the anesthetic agents used have been demonstrated to have minimal impact on intestinal motility [13]. In addition, although the strain gauge monitoring was performed in awake animals, it required implantation of the gauges onto the intestine, perhaps therefore affecting the ordered motility of the intestine. Previous animal studies, however, have shown that motility is preserved in this setting [23]. Using the 2 modalities in conjunction arguably allows their findings to corroborate each other. Finally, the effect of the STEP procedure on human motility cannot necessarily be extrapolated from these experiments. Studies in which small bowel motility is monitored in patients undergoing the STEP procedure would be useful. In conclusion, in this large animal model, manometric monitoring and strain gauge transduction of small intestinal motility demonstrate no negative impact from the STEP procedure in the presence of or the characteristics of the MMC. In addition, the presence of normal MMC patterns in awake animals during a fast indicates that the inherent mechanisms of small intestinal motility are intact after the STEP procedure.
Acknowledgments Support for this work was provided by the Children's Hospital Boston Surgical Foundation and the Joshua Ryan Rappaport Fellowship in Pediatric Surgical Research (BPM). The authors would also like to thank Dr Arthur Nedder, Mark Kelly, and the rest of the staff at ARCH for their excellent animal care and assistance.
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235 [8] Javid PJ, Kim HB, Duggan CP, Jaksic T. Serial transverse enteroplasty is associated with successful short-term outcomes in infants with short bowel syndrome. J Pediatr Surg 2005;40:1019-23 [discussion 10231024]. [9] Modi BP, Javid PJ, Jaksic T, et al. First report of the International Serial Transverse Enteroplasty Data Registry: Indications, efficacy, and complications. J Am Coll Surg 2007;204:365-71. [10] Sudan D, Thompson J, Botha J, et al. Comparison of intestinal lengthening procedures for patients with short bowel syndrome. Ann Surg 2007;246:593-601 [discussion 601-604]. [11] Wales PW, de Silva N, Langer JC, et al. Intermediate outcomes after serial transverse enteroplasty in children with short bowel syndrome. J Pediatr Surg 2007;42:1804-10. [12] Chang RW, Javid PJ, Oh JT, et al. Serial transverse enteroplasty enhances intestinal function in a model of short bowel syndrome. Ann Surg 2006;243:223-8. [13] Nurko S, Rattan S. Role of vasoactive intestinal polypeptide in the internal anal sphincter relaxation of the opossum. J Clin Invest 1988; 81:1146-53. [14] Savoye G, Bouin M, Labbe L, et al. Concomitant variations of gastric tone and duodenal motility in humans: results of a placebo-controlled study assessing octreotide and sumatriptan. Scand J Gastroenterol 2006;41:536-43. [15] Nurko S. Gastrointestinal manometry: methodology and indications. In: Walker WA, Kleinman RE, Sherman PM, editors. Pediatric gastrointestinal disease. Philadelphia (Pa): B.C. Decker Inc.; 2004. p. 1786-808. [16] Di Lorenzo C, Lucanto C, Flores AF, et al. Effect of octreotide on gastrointestinal motility in children with functional gastrointestinal symptoms. J Pediatr Gastroenterol Nutr 1998;27:508-12. [17] Bass P, Wiley JN. Contractile force transducer for recording muscle activity in unanesthetized animals. J Appl Physiol 1972;32:567-70. [18] Kaji T, Takamatsu H, Kajiya H. Motility of the gastrointestinal tract and gallbladder during long-term total parenteral nutrition in dogs. JPEN JPEM J Parenter Enteral Nutr 2002;26:198-204. [19] Nishimoto Y, Taguchi T, Masumoto K, et al. Real-time monitoring for detecting rejection using strain gauge force transducers in porcine small bowel transplantation. Transplant Proc 2004;36:343-4. [20] Camilleri M, Hasler WL, Parkman HP, et al. Measurement of gastrointestinal motility in the GI laboratory. Gastroenterology 1998; 115:747-62. [21] Di Lorenzo C, Flores AF, Buie T, et al. Intestinal motility and jejunal feeding in children with chronic intestinal pseudo-obstruction. Gastroenterology 1995;108:1379-85. [22] Vantrappen G, Janssens J, Hellemans J, et al. The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J Clin Invest 1977;59:1158-66. [23] Nakada K, Ikoma A, Suzuki T, et al. Amelioration of intestinal dysmotility and stasis by octreotide early after small-bowel autotransplantation in dogs. Am J Surg 1995;169:294-9.
Discussion Speaker: Thank you very much for the presentation. I have a question. These data are fasting period, so do you have some other difference in the postprandial phase? Dr Modi: We have done some studies using markers of transit which have not yet elucidated the specifics of postprandial motility. In the fasting state, however, looking truly at the migrating motor complex, it seems to be similar between control and STEP groups.