Journal of Indian Association of Pediatric Surgeons
Journal of Indian Association of Pediatric Surgeons
                                                   Official journal of the Indian Association of Pediatric Surgeons                           
Year : 2011  |  Volume : 16  |  Issue : 4  |  Page : 137--141

Nissen fundoplication for gastroesophageal reflux: No deterioration of gastric emptying measured by 13C-acetate breath test

Tadao Okada, Shohei Honda, Hisayuki Miyagi, Masashi Minato 
 Department of Pediatric Surgery, Hokkaido University Hospital, Sapporo, Japan

Correspondence Address:
Tadao Okada
Department of Pediatric Surgery, Hokkaido University Hospital, Kita-ku, Kita 14, Nishi 5, Sapporo 060-8648


Aim: To study the gastric emptying 30 days after laparoscopic Nissen fundoplication (NF) in gastroesophageal reflux. Materials and Methods: Three patients were evaluated with 13 C-acetate breath test (ABT) performed pre and post-NF. The liquid test meal consisted of Racol TM mixed with 13 C-acetate. Results: In the patient without neurological impairment (NI), the preoperative t 1/2 ex and t lag were 0.900 and 0.510 hours, respectively. The postoperative t 1/2 ex and t lag were 0.959 and 0.586 hours, respectively. In one patient with NI, the preoperative t 1/2 ex and t lag were 1.828 and 1.092 hours, respectively. The postoperative t 1/2 ex and t lag were 2.081 and 1.025 hours, respectively. In the other patient with NI, the preoperative t 1/2 ex and t lag were 2.110 and 0.980 hours, respectively. The postoperative t 1/2 ex and t lag were 1.118 and 0.415 hours, respectively. Conclusions: Our findings suggest that 13 C-ABT parameters did not worsen in any of the children after laparoscopic NF.

How to cite this article:
Okada T, Honda S, Miyagi H, Minato M. Nissen fundoplication for gastroesophageal reflux: No deterioration of gastric emptying measured by 13C-acetate breath test.J Indian Assoc Pediatr Surg 2011;16:137-141

How to cite this URL:
Okada T, Honda S, Miyagi H, Minato M. Nissen fundoplication for gastroesophageal reflux: No deterioration of gastric emptying measured by 13C-acetate breath test. J Indian Assoc Pediatr Surg [serial online] 2011 [cited 2021 Oct 16 ];16:137-141
Available from:

Full Text


Laparoscopic Nissen fundoplication (NF) is the most commonly used operation for the treatment of gastroesophageal reflux in children. Despite the success of NF in controlling reflux, patients occasionally experience postoperative symptoms of bloating, retching and even recurrent reflux. [1],[2],[3],[4] Although clinical reports suggest that these complications may be related to a delay in gastric emptying (GE) in some patients, [5],[6],[7],[8] the usefulness of performing a concomitant gastric drainage procedure such as pyloroplasty for such patients at the time of NF remains controversial. Furthermore, quantitative data on the necessity for pyloroplasty in conjunction with laparoscopic NF are not available in the literature.

Recently, 13 C has been used as an alternative tool for measuring the GE rates of both solids and liquids. [9],[10],[11],[12] 13 C is a stable, naturally occurring, nonradioactive isotope that can easily be detected by mass spectrometry. [9],[10] An ingested 13 C-containing test meal is converted to 13 CO 2 , which is absorbed quantitatively from the intestinal tract and then exhaled rapidly by the lungs. [10],[11] 13 C-octanoate is hydrophobic and has been used to evaluate the GE of solids in test meals. [12],[13],[14] More recently, based on its hydrophilicity, 13 C-acetate was developed for use in measuring the GE of liquids in test meals used in clinical diagnosis. [9] The rate of 13 CO 2 expiration following 13 C-acetate ingestion is an indirect indicator of GE that can be used as an alternative to radioisotope scintigraphy. [11],[15]

Recent studies by our laboratory have shown that a delay of GE is often observed in children with neurological impairment (NI) and gastroesophageal reflux employing the 13 C-acetate breath test (ABT). [9] Our hypothesis in this study was that GE in children who underwent laparoscopic NF for gastroesophageal reflux would markedly differ between pre- and postlaparoscopic NF. Furthermore, it is unknown whether children require pyloroplasty on laparoscopic NF. The aim of this study was to preliminarily evaluate GE of liquids in children with gastroesophageal reflux using the ABT, [11],[15] and to compare the results of GE pre- and postlaparoscopic NF.

 Materials and Methods

Patients: Between April 2002 and March 2011, three patients with gastroesophageal reflux were admitted to our institution, and gastroesophageal reflux was documented based on upper gastrointestinal studies and 24-hour pH monitoring. No patients were premature or had pulmonary diseases. The operative indications of laparoscopic NF are failure of conservative treatments such as gastric kinetic drugs, H 2 blockers, and nasogastric tube feeding. Patients underwent laparoscopic NF and gastrostomy without pyloroplasty for feeding if they had NI. All three patients underwent 13 C-ABT pre- and postlaparoscopic NF. There was one patient without NI aged 3-years old and two patients with NI aged 13 and 16-years old. The fraction of the time the pH was below 4.0 was 63.7% in the patient without NI and 32.8 and 81.4% in the patients with NI. None of the patients received any medication that could potentially influence gastrointestinal motility during this study.

Laparoscopic NF procedure: Laparoscopically, a 2-cm long and 360΀ wrap was thus constructed. The anterior and posterior vagus nerves were carefully protected and preserved. Stamm gastrostomy for feeding was performed.

Diagnostic methods

Test meal of 13 C-ABT: Informed consent to perform 13 C-ABT was obtained from the parents. All children fasted for 2 hours for liquids and 6 hours for solids prior to 13 C-ABT. Racol TM (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan) was used as the test meal and was administered at 5 ml/kg (maximum dose: 200 ml). The nutrient composition of 100 ml of Racol TM (100 kcal) is 4.4 g of protein, 15.6 g of carbohydrate, and 2.2 g of fat. 13 C was used to label acetate (99%; Cambridge Isotope Laboratories, Woburn, MA, USA), which is absorbed in the duodenum but not in the stomach. Racol TM was mixed with 13 C-acetate (50 mg for infants, 100 mg for children, and 150 mg for adolescents). [15] In all children, the meal was consumed within a few minutes or administered by nasogastric tube.

13 C-ABT: Breath samples were collected for 13 CO 2 measurement before the intake of the meal, every 15 minutes during the first 2 hours after the meal, and every 30 minutes thereafter. During each expiration phase, exhaled air was collected into a bag using a modified face mask or tracheostomy tube 11 times in total. It took about 1 minute to collect the exhaled air into one bag. 13 CO 2 was measured using a gas chromatograph-isotope ratio mass spectrometer (UBiT-IR300, Ootsuka Electronic Corp). For 13 C-ABT values, the concentration of 13 CO 2 (the final product in exhaled air) was measured. The results were expressed as % of 13 C expired per hour and % 13 CO 2 cumulative excretion over a 3-hour period. GE studies using 13 C-ABT were repeated 30 days after the laparoscopic NF.

Statistical analysis: The % 13 CO 2 cumulative excretion in the breath was assessed using a nonlinear regression formula: y=m (1-e -kt )b to fit the curve of the cumulative 13 C-recovery. [15],[16] The % 13 CO 2 excretion per hour was fitted to the formula: mkbe -kt (1-e -kt )b-1 . [15],[16] T is time and m, k, and % are constants. The value of m represents the total cumulative 13 CO 2 recovery when the time is infinite. The half excretion time of 13 C-ABT (t 1/2 ex) was calculated using the formula: t 1/2 ex= -1/k ln(1-e -1/b). [15],[16] The lag time (t lag), which reflects the initial delay of GE, was expressed as lnb/k. [15],[16] We compared the half excretion time and lag time of 13 C-ABT between pre- and postlaparoscopic NF.


13 C-ABT findings in the patient without NI

[Figure 1] shows the findings of pre- and postlaparoscopic NF 13 C-ABT in case 1. The preoperative t 1/2 ex and t lag were 0.900 and 0.510 hours, respectively. The postoperative t 1/2 ex and t lag were 0.959 and 0.586 hours, respectively.{Figure 1}

13 C-ABT findings in the patients with NI

[Figure 2] shows the findings of pre- and postlaparoscopic NF 13 C-ABT in case 2. The preoperative t 1/2 ex and t lag were 1.828 and 1.092 hours, respectively. The postoperative t 1/2 ex and t lag were 2.081 and 1.025 hours, respectively.{Figure 2}

[Figure 3] shows the findings of pre- and postlaparoscopic NF 13 C-ABT in case 3. The preoperative t 1/2 ex and t lag were 2.110 and 0.980 hours, respectively. The postoperative t 1/2 ex and t lag were 1.118 and 0.415 hours, respectively.{Figure 3}


Patients with NI have a high incidence (up to 15%) of gastroesophageal reflux. [17] It is known that the probability of gastroesophageal reflux and rate of such episodes are related to delayed GE. [17] In children with severe NI, the incidence of delayed GE is higher than 50%. Sparse information is available concerning the actual pathophysiology of delayed GE in children with symptomatic reflux, although recent studies suggest that there may be a defect of global gastric motility rather than gastric outflow obstruction. [18],[19] After NF, persistent delay of GE is believed to cause gastric distention, which may, in turn, exert chronic stress on the gastroesophageal junction, and thus increase the risk of wrap disruption and recurrent reflux. [1]

Our findings suggest that 13 C-ABT parameters such as t 1/2 ex and t lag did not worsen after laparoscopic NF in any of the children, including those with NI. On the contrary, laparoscopic NF was found to promote postoperative improvement in GE in one child (case 3) with NI. The process of GE is affected by a number of factors, such as gastrointestinal electrical activity, neural regulation, hormones, and meal composition. [20] In patients with severe NI, several mechanisms combine to determine the GE process depending on the balance between propulsive forces and resistance to outflow: these mechanisms include gastric accommodation and tone, antral contractivity, antroduodenal coordination, pyloric function, and entero-enteric reflux. [10] The gastric pacemaker is located in the fundus; therefore, GE may be delayed as a result of abnormalities of the cardiohiatal sector. [20]

The development of a prospective, randomized study to investigate pre- and postoperative GE in children undergoing laparoscopic NF with or without an associated GE procedure is limited further by costs and ethical issues. [1] In the literature, it is reported that pyloroplasty remains useful in infants and children as an operative technique to solve problems of gastric outlet obstruction or as a drainage procedure. Cambell et al. performed pyloroplasty if necessary as a secondary procedure. [21] Bustorff-Silva et al. showed that adding pyloroplasty to NF leads to a long-term improvement of GE with no late return to preoperative values in animal models using radioisotope scintigraphy. [1] However, it is unclear whether these observations are relevant to the clinical setting. Furthermore, designing a well-controlled, randomized, long-term study to investigate the role of pyloroplasty in preventing recurrent reflux is difficult because of the low incidence of recurrent reflux after laparoscopic NF in children. [1]

Previously reported clinical and experimental data have shown that NF induces an acceleration of GE. [1],[22] In our study, one patient (case 3) with NI showed a postoperative improvement in GE. Maddern reported that five of six patients with delayed GE before NF showed normal emptying after NF, using radionuclide solid meals before and after NF. [22] The improvement in GE is believed to be associated with changes in the degree of gastric relaxation and compliance. [23] NF has been shown to cause only a transient improvement in GE. [1] However, data on GE before and after laparoscopic NF have not been provided hitherto as quantitative values, to our knowledge.

Clinical and experimental studies have shown that NF decreases the gastric volume, which may enhance GE. [1],[18],[19],[22],[23] Wilbur et al. previously showed that reducing the radius of the proximal stomach by fundectomy in dogs resulted in increased GE of liquids. [24] Within 30 days after NF, the GE returned to preoperative values, which was associated with the return of the gastric volume to the same levels measured before surgery. Therefore, we measured the half excretion time (t 1/2 ex) and lag time (t lag) by employing 13 C-ABT at 1 month after laparoscopic NF in our study.

Our findings suggest 13 C-ABT parameters preliminarily did not worsen after laparoscopic NF in any of the children, including those with NI. On the contrary, NF was found to promote a postoperative improvement in GE of one child with NI. Larger studies are required to determine the accuracy of GE rate measurements before and after laparoscopic NF. However, our analysis does not indicate any advantage of adding pyloroplasty to the treatment of children with severe neurological disorders who are undergoing antireflux surgery.


The authors thank Yumiko Tsuda for her excellent technical assistance.


1Bustorff-Silva J, Fonkalsrud EW, Perez CA, Hoh C, Raybonld HE, Atkinson JB. Pyloroplasty improves long-term gastric emptying in rats undergoing fundoplication. J Pediatr Surg 2000;35:1087-90.
2Rothenberg SS. The first decade's experience with laparoscopic Nissen fundoplication in infants and children. J Pediatr Surg 2005;40:142-6, discussion 147.
3Masqusi S, Velanovich V. Pyloroplasty with fundoplication in the treatment of combined gastroesophageal reflux disease and bloating. World J Surg 2007;31:332-6.
4Tovar JA, Luis AL, Encinas JL, Burgos L, Pederiva F, Martinez L, et al. Pediatric surgeons and gastroesophageal reflux. J Pediatr Surg 2007;42:277-83.
5Hinder RA, Stein HJ, Bremner CG, DeMeester TR. Relationship of a satisfactory outcome to normalization of delayed gastric emptying after Nissen fundoplication. Ann Surg 1989;210:458-64, discussion 464-5.
6Jolley SG, Tunell WP, Leonard JC, Hoelzer DJ, Smith EI. Gastric emptying in children with gastroesophageal reflux. II. The relationship to retching symptoms following antireflux surgery. J Pediatr Surg 1987;22:927-30.
7Khajanchee YS, Dunst CM, Swanstrom LL. Outcomes of Nissen fundoplication in patients with gastroesophageal reflux disease and delayed gastric emptying. Arch Surg 2009;144:823-8.
8Caldaro T, Garganese MC, Torroni F, Ciofetta G, De Angelis P, di Abriola GF, et al. Delayed gastric emptying and typical scintigraphic gastric curves in children with gastroesophageal reflux disease: Could pyloromyotomy improve this condition? J Pediatr Surg 2011;46:863-9.
9Okada T, Sasaki F, Asaka M, Kato M, Nakagawa M, Todo S. Delay of gastric emptying measured by 13 C-acetate breath test in neurologically impaired children with gastroesophageal reflux. Eur J Pediatr Surg 2005;15:77-81.
10Bjorkman DJ, Moore JG, Klein PD, Graham DY. 13 C-bicarbonate breath test as a measure of gastric emptying. Am J Gastroenterol 1991;86:821-3.
11Braden B, Adams S, Duan LP, Orth KH, Manl FD, Lembcke B, et al. The [ 13 C] acetate breath test accurately reflects gastric emptying of liquids in both liquid and semisolid test meals. Gastroenterology 1995;108:1048-55.
12Choi MG, Camilleri M, Burton D, Zinsmeister AR, Forstrom LA, Nair KS. 13 C octanoic acid breath test for gastric emptying of solids: Accuracy, reproducibility, and comparison with scintigraphy. Gastroenterology 1997;112:1155-62.
13Veereman-Wauters G, Ghoos YF, Schoor S, Maes B, Hebbalkar N, Devileger H, et al. The 13 C-octanoic acid breath test: A non invasive technique to assess gastric emptying in preterm infants. J Pediatr Gastroenterol Nur 1996;26:111-7.
14Galmiche JP, Delbeude B, Perri E, Andriulli A. 13 C octanoic acid breath test. Gut 1998;43:S28-30.
15Gatti C, Abrola FD, Dall'Ogalio L, Villa M, Franchini F, Amarri S. Is the 13 C-accetate breath test a valid procedure to analyse gastric emptying in children? J Pediatr Surg 2000;35:62-5.
16González A, Mugueta C, Parra D, Labayen I, Martinez A, Varo N, et al. Characterisation with stable isotopes of the presence of a lag phase in the gastric emptying of liquids. Eur J Nutr 2000;39:224-8.
17Boix-Ochoa J, Rowe MI. Chapter in a book. Gastroesophageal reflux. In: O'Neill JA, Rowe MI, Grosfeld JL, Fonkalsrud EW, Coran AG, editors. Pediatric Surgery. Missouri: Mosby-Year Book; 1998. p. 1007-28.
18Cucchiara S, Salvia G, Borrelli O, Ciccimarra E, Az-Zeqeh N, Rapagiolo S, et al. Gastric electrical dysrhythmias and delayed gastric emptying in gastroesophageal reflux disease. Am J Gastroenterol 1997;92:1103-8.
19Ravelli AM, Milla PJ. Vomiting and gastroesophageal motor activity in children with disorders of the central nervous system. J Pediatr Gastroenterol Nutr 1998;26:56-63.
20Montgomery M, Escobar-Billing R, Hellström PM, Karlsson KA, Frenckner B. Impaired gastric emptying in children with repaired esophageal atresia: A controlled study. J Pediatr Surg 1988;33:476-80.
21Campbell JR, Gilchrist BF, Harrison MW. Pyloroplasty in association with Nissen fundoplication in children with neurologic disorders. J Pediatr Surg 1989;24:375-7.
22Maddern GJ, Jamieson GG. Fundoplication enhances gastric emptying. Ann Surg 1985;201:296-9.
23Wijnhoven BP, Salet GA, Roelofs JM, Smout AJ, Akkermans LM, Gooszen HG. Function of the proximal stomach after Nissen fundoplication. Br J Surg 1998;85:267-71.
24Wilbur BG, Kelley KA, Code CF. Effect of gastric fundectomy on canine gastric electrical and motor activity. Am J Physiol 1974;226:1445-9.