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. 2023 Sep 8;18(9):e0290430. doi: 10.1371/journal.pone.0290430

Prognostic factors for persistent obstructive symptoms in patients with Hirschsprung disease following pull-through

Naisya Balela 1, Aditya Rifqi Fauzi 1, Ninditya Nugroho 1, Andi Dwihantoro 1, Gunadi 1,*
Editor: Paul Kwong-Hang Tam2
PMCID: PMC10490837  PMID: 37682877

Abstract

Background

Although most patients with Hirschsprung disease (HSCR) improve after pull-through, some patients still have persistent obstructive symptoms. Most previous studies reported persistent obstructive symptoms after pull-through in HSCR patients from developed countries. Our study determined the prognostic factors of persistent obstructive symptoms in patients with HSCR following pull-through from a particular developing country.

Methods

A cross-sectional study was conducted using medical records of patients with HSCR at our institution from January 2017 to January 2022.

Results

We ascertained 114 patients with HSCR: 79 males and 35 females. Most of them (90.4%) showed a short aganglionosis and underwent transanal endorectal pull-through (55.3%). Twenty-two percent of patients showed persistent obstructive symptoms following pull-through. Operative technique and age at definitive surgery were significantly associated with the persistent obstructive symptoms after pull-through (p = 0.011 and 0.019, respectively), while sex, aganglionic segment length, presence of global developmental delay, and Down syndrome were not (p = 0.873, 0.525, 0.647, and 0.301, respectively). Multivariate analysis revealed that age at pull-through was a significant independent factor for persistent obstructive symptoms after pull-through, with an odds ratio of 3.41 (95% CI = 1.18–9.91; p = 0.02).

Conclusions

Our study shows a moderate frequency of persistent obstructive symptoms after pull-through in our institution. In addition, patients who underwent pull-throughs at a younger age might have persistent obstructive symptoms following a definitive surgery. Our study provides new data on persistent obstructive symptoms after pull-through from a particular population that might be beneficial for pediatric surgeons’ consideration before performing definitive surgery on patients with HSCR.

Introduction

Hirschsprung disease (HSCR) is a complex hereditary disorder characterized by the lack of an enteric ganglion in the submucosa and a myenteric plexus that varies along the distal intestine. HSCR affects 1 in every 5,000 live births, with the Asian population having the most significant incidence, 2.8 out of 10,000 live births. HSCR shows a male: female ratio of 4:1 [1]. Its incidence in Indonesia is approximately 1:3,250 [2].

Although most HSCR patients improved after surgery, some patients suffered from the possibility of postoperative complications [3], including persistent obstructive symptoms following pull-through [3,4]. Postoperative persistent obstructive symptoms were defined as abdominal distension, bloating, borborygmi, vomiting, or severe constipation following pull-through [3]. The incidence of postoperative persistent obstructive symptoms is approximately 8–30% [1]. Moreover, persistent obstructive symptoms after pull-through can lead to chronic enterocolitis, resulting in failure to thrive in children [5]. Most previous studies reported persistent obstructive symptoms after pull-through in HSCR patients from developed countries [35]. Here, we aimed to determine the prognostic factors of persistent obstructive symptoms in patients with HSCR from a particular developing country.

Material and methods

Patients

A cross-sectional study was conducted using medical records of patients with HSCR at Dr. Sardjito Hospital, Yogyakarta, Indonesia, from January 2017 to January 2022. Diagnosis of HSCR in our hospital was established according to histopathological findings. HSCR patients were classified as short-segment (aganglionosis affects the rectosigmoid colon), long-segment (aganglionosis extending proximal to the splenic flexure), and total colon aganglionosis (TCA, aganglionosis of the entire colon). The aganglionic segment length was determined using intraoperative histopathological evaluations (frozen sections) [6]. Intraoperative frozen sections were compared with permanent sections to ensure the segment length was appropriately diagnosed. All frozen sections samples, except two cases, correlated with the permanent sections.

The inclusion criterion was all HSCR patients <18 years old and underwent pull-through in our institution. The exclusion criteria were deceased patients and incomplete medical records. We included 114 HSCR patients with persistent obstructive symptoms after the transanal endorectal (TEPT), Swenson-like, and Duhamel pull-through. The data were retrospectively collected from March to April 2022, while the data were accessed for research purposes from April to May 2022. Authors had access to identifying information during or after data collection. The patients were taken care of at the ward at least five days after the pull-through. Subsequently, the patients were routinely follow-up at the outpatient clinic at least every two weeks until at least six months after the pull-through.

The Ethical Committee of the Faculty of Medicine, Universitas Gadjah Mada/Dr. Sardjito Hospital, Indonesia, approved the study (KE/FK/0135/EC/2022). Written informed consent was obtained from all parents for participating in this study. The research has been performed following the Declaration of Helsinki.

Prognostic factors

Postoperative persistent obstructive symptoms were defined as abdominal distension, bloating, borborygmi, vomiting, or severe constipation following pull-through [3]. After admission, the patients with persistent obstructive symptoms were managed with antibiotics, irrigations, and nothing per oral. They were evaluated using the following diagnostic approach: history, abdominal X-ray, contrast enema, and examination under anesthesia [3,4]. Treatment of patients was determined according to the etiology of the obstructive symptoms, anatomic, pathological, or functional [3,4].

Next, we evaluated prognostic factors for postoperative persistent obstructive symptoms: sex, aganglionic segment length, operative technique, age at definitive surgery, presence of global developmental delay, and Down syndrome. The operative technique consisted of TEPT, transanal Swenson-like, and Duhamel pull-through. The pull-through methods were chosen according to the attending pediatric surgeon’s discretion. To minimize bias, the authors did not know who performed the pull-through during data analysis. According to a previous study, the age at definitive surgery was classified into <1 year and ≥1 year [7].

Definitive surgery

Prior to definitive surgery, the children were managed by rectal irrigation. If the rectal irrigation was ineffective in keeping the colon decompressed, the children underwent colostomy.

TEPT

We put the everting sutures throughout the anus to show the mucosa. Subsequently, we incised the mucosa circumferentially about 0.5 cm above the dentate line by a needle tip cautery. We conducted a submucosal dissection proximally for about 1 cm and converted it to the full thickness of the rectal wall until the transition zone was reached. Once we confirmed the ganglion cells in the colon by frozen section, we removed at least an additional 5 cm of the colon to ensure that we resected the transition zone as well. Finally, we conducted coloanal anastomosis [8].

Duhamel pull-through

We performed a two-staged Duhamel pull-through for our patients in our hospital, i.e., all patients received stoma first. We made a hockey-stick incision incorporation colostomy. We mobilized the colon proximal to the prior colostomy. We then created a retrorectal space and preserved around 4 cm of the original rectum. We closed the rectal stump from the abdomen using interrupted sutures. After the posterior rectal wall was exposed, we made a full-thickness incision 0.5 cm above the dentate line. Subsequently, we pulled the mobilized colon through this incision. We performed the coloanal anastomosis using interrupted sutures. Eventually, we used an automatic stapling device to obliterate the septum between the original rectum and the pulled colon [9].

All TCA patients have been managed with a diverting ileostomy first. They underwent definitive surgery using the Duhamel approach at the age of at least one-year-old (Table 1).

Table 1. Baseline characteristics of patients with HSCR involved in this study.
Characteristics N (%)
Sex
◾ Male
◾ Female

79 (69.3)
35 (30.7)
Aganglionosis type and definitive surgery
◾ Short
    √ TEPT
    √ Duhamel
    √ Transanal Swenson-like
◾ Long
    √ TEPT
    √ Duhamel
    √ Transanal Swenson-like
◾ Total colon aganglionosis
    √ TEPT
    √ Duhamel
    √ Transanal Swenson-like

103 (90.4)
60
30
13
9 (7.9)
3
6
0
2 (1.7)
0
2
0
Definitive surgery and age at pull-through (year)
◾ TEPT
    √ <1
    √ ≥1
◾ Duhamel
    √ <1
    √ ≥1
◾ Transanal Swenson-like
    √ <1
    √ ≥1

63 (55.3)
54
9
38 (33.3)
4
34
13 (11.4)
10
3
Age at pull-through (year)
◾ <1
◾ ≥1

68 (59.6)
46 (40.4)
Global developmental delay
◾ Yes
◾ No

7 (6.1)
107 (93.9)
Down syndrome
◾ Yes
◾ No

5 (4.4)
109 (9.6)
Persistent obstructive symptoms
◾ Yes
◾ No

25 (22)
89 (78)

TEPT, transanal endorectal pull-through.

Transanal Swenson-like pull-through

We put the lone star retractor hooks just above the dentate line to hide and protect the dentate line during the dissection. We placed interrupted sutures circumferentially 1.0 cm above the dentate line. Subsequently, we conducted a full-thickness dissection using a needle-tip cautery until reaching the peritoneal cavity. We then pulled through the colon to the appropriate level. After we confirmed the ganglion cells in the colon by intraoperative histopathological findings, we resected a minimum of an additional 5 cm of the colon to ensure we resected the transition zone too. Ultimately, we performed coloanal anastomosis [10].

Post pull-through management

The nasogastric tube was removed soon after surgery finished, while the feedings were given once the bowel sound was normal. The Foley catheter was removed on postoperative day (POD) 2 after Duhamel and TEPT, and POD4 after transanal Swenson-like pull-through. Antibiotics were given for five days after surgery. Most patients were discharged on POD5.

Statistical analysis

The Chi-square or Fisher Exact test was utilized to assess the association between prognostic variables and persistent obstructive symptoms after pull-through. The multivariate analysis was conducted using the backward stepwise logistic regression to identify significant prognostic factors for persistent obstructive symptoms after pull-through. A p-value of <0.05 was considered to be significant. IBM SPSS Statistics version 20 (SPSS Chicago, USA) was used for all statistical analyses.

Results

Baseline characteristics

We involved 114 HSCR patients. Most of them had short aganglionosis (90.4%), underwent TEPT (55.3%), and had age at surgery < 1-year-old (59.6%) (Table 1). Twenty-five (22%) patients showed persistent obstructive symptoms following pull-through. Time to the incidence of obstructive symptoms varied among patients from 10 days to 16 months following pull-through (S1 Table).

Association between prognostic factors and persistent obstruction of children with HSCR

Operative technique and age at definitive surgery were significantly associated with persistent obstructive symptoms after pull-through (p = 0.011 and 0.019, respectively). At the same time, sex, aganglionic segment length, presence of global developmental delay, and Down syndrome were not (Table 2).

Table 2. Association between prognostic factors and persistent obstructive symptoms following pull-through in HSCR patients.

Persistent obstructive symptoms p-value OR (95% CI)
Factor Prognostics Yes (N, %) No (N, %)
Sex
◾ Male
◾ Female

17 (14.9)
8 (7)

62 (54.4)
27 (23.7)

0.862

0.93 (0.36–2.40)
Aganglionosis type
◾ Short
◾ Long
◾ Total colon aganglionosis

24 (21.1)
1 (0.9)
0

79 (69.3)
8 (7)
2 (1.8)

0.469
1

0.41 (0.05–3.46)
N/A
Definitive surgery
◾ TEPT
◾ Duhamel
◾ Transanal Swenson-like

19 (16.7)
3 (2.6)
3 (2.6)

44 (38.6)
35 (30.7)
10 (8.8)

0.011*
0.745

0.20 (0.05–0.73)
0.69 (0.17–2.81)
Age at pull-through (year)
◾ <1
◾ ≥1

20 (17.5)
5 (4.4)

48 (42.1)
41 (36)

0.019

3.42 (1.18–9.91)
Global developmental delay
◾ Yes
◾ No

2 (1.8)
23 (20.2)

5 (4.4)
84 (73.7)

0.647

1.46 (0.27–8.02)
Down syndrome
◾ Yes
◾ No

2 (1.8)
23 (20.2)

3 (2.6)
86 (75.4)

0.584

2.49 (0.39–15.81)

*, p<0.05; CI, confidence interval; OR, odds ratio; HSCR, Hirschsprung disease; N/A, not applicable; TEPT, transanal endorectal pull-through.

Multivariate analysis of prognostic factors for persistent obstruction of children with HSCR

Next, we performed a multivariate analysis. Age at pull-through was a significant independent factor for persistent obstructive symptoms after pull-through, with an odds ratio ((OR) of 3.41 (95% CI = 1.18–9.91; p = 0.02) (Table 3).

Table 3. Multivariate analysis of prognostic factors for persistent obstructive symptoms.

Factor Prognostics p-value OR (95% CI)
Definitive surgery (TEPT) 0.54 0.75 (0.29–1.87)
Sex (Male) 0.82 1.12 (0.41–3.09)
Age at surgery (<1 year) 0.02* 3.41 (1.18–9.91)
Aganglionosis type (Short) 0.50 1.99 (0.26–14.96)
Global developmental delay 0.60 1.60 (0.27–9.51)
Down syndrome 0.32 2.63 (0.38–18.08)

*, p<0.05; CI, confidence interval; OR, odds ratio; TEPT, transanal endorectal pull-through.

Discussion

Our study shows that age at definitive surgery is a significant independent prognostic factor for the persistent obstructive symptoms after pull-through, with an OR of ~ 3.4-fold for children who underwent pull-through at <1 year of age. Our study provides new data on prognostic factors associated with persistent obstructive symptoms following pull-through from a particular developing country. Most previous studies reported persistent obstructive symptoms after pull-through in HSCR patients from developed countries [35,7].

The best time to perform definitive surgery is still being debated [1114]. Prior studies mentioned that surgery at an early age could help prevent poor bowel decompression, which happens in 25% of preoperative patients and can lead to chronic colorectal obstruction [11,12]. Contrary, surgery at a non-neonatal age provides the advantage of a more developed anal canal and sphincter complex [13]. A current meta-analysis concluded that infants under 2.5 months old show worse functional outcomes after TEPT [15]. Several possible hypotheses why younger infants have worse outcomes after pull-through have been proposed, including the pelvic floor or nerve plexus and anal sphincter prone to injury during pull-through and difficulty in identifying the normal ganglion cells in younger HSCR patients [15]. Additionally, technical approaches have been proposed as contributing factors for the outcomes [16]. Notably, the pull-through technique in our study was determined according to attending pediatric surgeons.

In this study, 21.9% of HSCR patients experienced postoperative persistent obstructive symptoms. It is similar to a previous report showing an 8–30% incidence [3]. There are three classifications of etiologies of persistent obstructive symptoms after pull-through: 1) anatomic, 2) pathological, and 3) functional (4) [3,4]. Unfortunately, we did not classify the cause of persistent obstructive symptoms in our patients. Our study focused on the prognostic factors associated with persistent obstructive symptoms following pull-through. Moreover, we did not determine the postoperative complications that might affect the persistent obstructive symptoms in our patients.

Our study also included disorders associated with HSCR, particularly global developmental delay and Down syndrome, as prognostic factors for persistent obstructive symptoms. Previous studies reported that HSCR patients with Down syndrome had worse outcomes after pull-through than those without, including persistent obstructive symptoms [1719]. It should be noted that the number of HSCR patients with global developmental delay (6.1%) dan Down syndrome (4.4%) in our study is minimal. These facts might cause an insignificant association between those variables and persistent obstructive symptoms.

Interestingly, our HSCR patients who underwent TEPT had a ~5-fold higher possibility of having persistent obstructive symptoms than those who underwent the Duhamel procedure (p = 0.011). A previous study reported that among HSCR patients who suffered from persistent obstructive symptoms, 52.4%, 28.6%, and 19% underwent TEPT, transabdominal Soave, and Duhamel procedures, respectively [20]. Another report showed that 49 HSCR patients suffered from persistent obstructive symptoms, with the original pull-through of Soave (51%), Duhamel (30.6%), and Swenson (18.4%) pull-through [21]. Persistent obstructive symptom after initial definitive surgery is usually associated with anatomic problems, with the most common etiology of anastomotic stricture [4]. Soave (endorectal) pull-through purposely leaves a muscular cuff that might develop scar tissue or roll down, causing a constricting ring and leading to mechanical obstruction [22]. These facts might be associated with the high frequency of persistent obstructive symptoms in the TEPT group in our study and other reports [20,21].

Our study noted several limitations, including 1) a retrospective design; therefore, we noted the variables, such as abdominal distension, bloating, borborygmi, vomiting, or severe constipation, relied on the medical record. Moreover, our study’s retrospective nature may introduce inherent biases and limitations in data collection and analysis; 2) a single-center report, implying that more multicenter research is required to corroborate our findings. In addition, our study focuses on a single institution, which may limit the generalizability of the findings to other healthcare settings or populations; 3) our study had more patients with short segment aganglionosis and underwent TEPT; 4) the follow-up period was short, and variable among patients after the pull-through; 5) we did not use anorectal manometry as a standard tool for clinical assessment after pull-through due to tool unavailability in our hospital; and 6) we did not determine the severity of persistent obstructive symptoms experienced by our patients. Performing neonatal pull-through would be different from performing a pull-through at 3 months old (mo) vs. 6 mo vs. 9 mo of age, and simply defining age as <1 or ≥1 year old can eliminate possible differences, notably when our multivariate analysis determined that age was a significant independent factor. These aspects should be considered while interpreting our findings. In addition, we have not included enterocolitis as persistent obstructive symptoms since we have already specifically determined the prognostic factors for enterocolitis in our previous studies [23,24].

Conclusions

Our study shows that the frequency of persistent obstructive symptoms after pull-through in our institution is considered moderate. In addition, patients who underwent pull-throughs at a younger age might have persistent obstructive symptoms following a definitive surgery. Our study provides new data on persistent obstructive symptoms after pull-through from a particular population that might be beneficial for pediatric surgeons’ consideration before performing definitive surgery on patients with HSCR.

Supporting information

S1 Table

(XLSX)

Acknowledgments

We thank those who provided excellent technical support and assistance during the study. We also thank the English editing service staff at the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, for checking the manuscript’s grammar. Some results for the manuscript are from Naisya Balela’s thesis.

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Tam PK. Hirschsprung’s disease: A bridge for science and surgery. J Pediatr Surg. 2016;51(1):18–22. doi: 10.1016/j.jpedsurg.2015.10.021 [DOI] [PubMed] [Google Scholar]
  • 2.Gunadi, Kalim AS, Iskandar K, Marcellus, Puspitarani DA, Diposarosa R, et al., Exome sequencing identifies novel genes and variants in patients with Hirschsprung disease. J Pediatr Surg. 2023;58(4):723–728. doi: 10.1016/j.jpedsurg.2022.11.011 [DOI] [PubMed] [Google Scholar]
  • 3.Langer JC, Rollins MD, Levitt M, Gosain A, Torre L, Kapur RP, et al. Guidelines for the management of postoperative obstructive symptoms in children with Hirschsprung disease. Pediatr Surg Int. 2017;33(5):523–526. doi: 10.1007/s00383-017-4066-7 [DOI] [PubMed] [Google Scholar]
  • 4.Ahmad H, Yacob D, Halleran DR, Gasior AC, Lorenzo CD, Wood RJ, et al. Evaluation and treatment of the post pull-through Hirschsprung patient who is not doing well; Update for 2022. Semin Pediatr Surg. 202231(2):151164. [DOI] [PubMed] [Google Scholar]
  • 5.Levitt MA, Dickie B, Peña A. Evaluation and treatment of the patient with Hirschsprung disease who is not doing well after a pull-through procedure. Semin Pediatr Surg. 2010;19(2):146–53. doi: 10.1053/j.sempedsurg.2009.11.013 [DOI] [PubMed] [Google Scholar]
  • 6.Haikal Z, Dwihantoro A, Gunarti H, Gunadi. Accuracy of transition zone in contrast enema to predict intraoperative aganglionosis level in patients with Hirschsprung disease. BMC Res Notes. 2020;13(1):104. doi: 10.1186/s13104-020-04945-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Kapur RP, Smith C, Ambartsumyan L. Postoperative Pullthrough Obstruction in Hirschsprung Disease: Etiologies and Diagnosis. Pediatr Dev Pathol. 2020;23(1):40–59. doi: 10.1177/1093526619890735 [DOI] [PubMed] [Google Scholar]
  • 8.Gunadi, Ivana G, Mursalin DA, Pitaka RT, Zain MW, Puspitarani DA, et al. Functional outcomes of patients with short-segment Hirschsprung disease after transanal endorectal pull-through. BMC Gastroenterol. 2021. Feb 23;21(1):85. doi: 10.1186/s12876-021-01668-x [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Widyasari A, Pavitasari WA, Dwihantoro A, Gunadi. Functional outcomes in Hirschsprung disease patients after transabdominal Soave and Duhamel procedures. BMC Gastroenterol. 2018;18(1):56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Levitt MA, Hamrick MC, Eradi B, Bischoff A, Hall J, Peña A. Transanal, full-thickness, Swenson-like approach for Hirschsprung disease. J Pediatr Surg. 2013;48(11):2289–95. doi: 10.1016/j.jpedsurg.2013.03.002 [DOI] [PubMed] [Google Scholar]
  • 11.Demehri FR, Halaweish IF, Coran AG, Teitelbaum DH. Hirschsprung-associated enterocolitis: pathogenesis, treatment and prevention. Pediatr Surg Int. 2013;29(9):873–81. doi: 10.1007/s00383-013-3353-1 [DOI] [PubMed] [Google Scholar]
  • 12.Beltman L, Labib H, Oosterlaan J, van Heurn E, Derikx J. Risk factors for complications in patients with Hirschsprung disease while awaiting surgery: Beware of bowel perforation. J Pediatr Surg. 2022;57(11):561–568. doi: 10.1016/j.jpedsurg.2022.02.022 [DOI] [PubMed] [Google Scholar]
  • 13.Zani A, Eaton S, Morini F, Puri P, Rintala R, Heurn EV, et al. European Paediatric Surgeons’ Association Survey on the Management of Hirschsprung Disease. Eur J Pediatr Surg. 2017;27(1):96–101. doi: 10.1055/s-0036-1593991 [DOI] [PubMed] [Google Scholar]
  • 14.Bradnock TJ, Walker GM. Evolution in the management of Hirschsprung’s disease in the UK and Ireland: a national survey of practice revisited. Ann R Coll Surg Engl. 2011;93(1):34–8. doi: 10.1308/003588410X12771863936846 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Westfal ML, Okiemy O, Chung PHY, Feng J, Lu C, Miyano G, Tam PKH, et al. Optimal timing for Soave primary pull-through in short-segment Hirschsprung disease: A meta-analysis. J Pediatr Surg. 2022;57(4):719–725. doi: 10.1016/j.jpedsurg.2021.07.007 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Miyano G, Takeda M, Koga H, Okawada M, Nakazawa-Tanaka N, Ishii J, et al. Hirschsprung’s disease in the laparoscopic transanal pull-through era: implications of age at surgery and technical aspects. Pediatr Surg Int. 2018;34:183–8. doi: 10.1007/s00383-017-4187-z [DOI] [PubMed] [Google Scholar]
  • 17.Saberi RA, Gilna GP, Slavin BV, Huerta CT, Ramsey WA, O’Neil CF Jr, et al. Hirschsprung disease in Down syndrome: An opportunity for improvement. J Pediatr Surg. 2022;57(6):1040–1044. doi: 10.1016/j.jpedsurg.2022.01.065 [DOI] [PubMed] [Google Scholar]
  • 18.Friedmacher F, Puri P. Hirschsprung’s disease associated with Down syndrome: a meta-analysis of incidence, functional outcomes and mortality. Pediatr Surg Int. 2013;29(9):937–46. doi: 10.1007/s00383-013-3361-1 [DOI] [PubMed] [Google Scholar]
  • 19.Travassos D, van Herwaarden-Lindeboom M, van der Zee DC. Hirschsprung’s disease in children with Down syndrome: a comparative study. Eur J Pediatr Surg. 2011;21(4):220–3. doi: 10.1055/s-0031-1271735 [DOI] [PubMed] [Google Scholar]
  • 20.Elsherbeny M, Abdelhay S. Obstructive complications after pull-through for Hirschsprung’s disease: different causes and tailored management. Annals of Pediatric Surgery. 2019;15(1):1–5. [Google Scholar]
  • 21.Langer JC. Persistent obstructive symptoms after surgery for Hirschsprung’s disease: development of a diagnostic and therapeutic algorithm. Journal of pediatric surgery. 2004;39(10):1458–62. doi: 10.1016/j.jpedsurg.2004.06.008 [DOI] [PubMed] [Google Scholar]
  • 22.Dickie BH, Webb KM, Eradi B, Levitt MA. The problematic Soave cuff in Hirschsprung disease: manifestations and treatment. J Pediatr Surg. 2014;49:77–81. doi: 10.1016/j.jpedsurg.2013.09.034 [DOI] [PubMed] [Google Scholar]
  • 23.Gunadi Luzman RA, Kencana SMS Arthana BD, Ahmad F, Sulaksmono G, et al. Comparison of Two Different Cut-Off Values of Scoring System for Diagnosis of Hirschsprung-Associated Enterocolitis After Transanal Endorectal Pull-Through. Front Pediatr. 2021;9:705663. doi: 10.3389/fped.2021.705663 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Gunadi, Sukarelawanto AVR, Ritana A, Balela N, Putri WJK, Sirait DN, et al. Postoperative enterocolitis assessment using two different cut-off values in the HAEC score in Hirschsprung patients undergoing Duhamel and Soave pull-through. BMC Pediatr. 2020;20(1):457. doi: 10.1186/s12887-020-02360-x [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Paul Kwong-Hang Tam

18 Jun 2023

PONE-D-23-13236Prognostic factors for persistent obstructive symptoms in patients with Hirschsprung disease following pull-throughPLOS ONE

Dear Dr. Gunadi,

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Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This study examined prognostic factors for persistent obstructive symptoms in Hirschsprung disease patients following pull-through surgery in a specific developing country. The results revealed that younger age at pull-through surgery was significantly associated with a higher risk of persistent obstructive symptoms, while other factors such as operative technique and patient demographics did not show significant associations.

Strengths of the Study:

The study fills a research gap by investigating the prognostic factors for persistent obstructive symptoms in HSCR patients from a developing country, broadening our understanding of the condition in diverse populations.

The use of a cross-sectional study design and a comprehensive analysis of various factors enhance the reliability and validity of the findings.

The large sample size and inclusion of both males and females contribute to the generalizability of the results within the specific population under study.

Limitations/Issues of the Study:

The study's retrospective nature may introduce inherent biases and limitations in data collection and analysis.

The study focuses on a single institution, which may limit the generalizability of the findings to other healthcare settings or populations.

The study does not provide detailed information on the specific nature and severity of persistent obstructive symptoms experienced by the patients.

How the obstructive symptoms were handled is not demonstrated

How are the patients managed postoperatively - not demonstrated

A time to incidence of obstructive symptoms is needed

Overall, this study provides valuable insights into prognostic factors for persistent obstructive symptoms after pull-through surgery in HSCR patients from a developing country. The findings emphasize the importance of considering operative technique and age at definitive surgery when assessing the risk of persistent obstruct

Reviewer #2: Your article's goal is laudable - risk factors for Hirschsprung's associated enterocolitis and other postoperative complications after surgery are not well understood from developed countries, and data from a developing country is valuable. There are, however, a few revisions that your paper can benefit from.

1. Define "persistent obstructive symptoms" in the Introduction. This is a vague term that would benefit from clear definition as it can vary within institutions.

2. Were intraoperative frozen sections compared with permanent sections to ensure that the segment length was appropriately diagnosed? If so, how many frozen sections correlated with the permanent sections?

3. How are the postoperative persistent obstructive symptoms treated in your institution? Admission into the hospital, NPO, antibiotics, irrigations? How do these symptoms affect your patient population specifically as it may be different in developed countries?

4. While you mention that surgeon preference defined which procedures were performed, what information was used to decide when to perform a 2-stage Duhamel? Were all procedures done as 2-stage (all patients received colostomy first)?

5. What criteria was used to define short vs long segment? For total colonics, how were these reconstructed and at what age?

6. Table 1 should list how many short, long, total colonics underwent TEPT, Duhamel, or Transanal Swenson, and at what age distribution. It should also define age <1 yo better. Performing neonatal pullthrough would be different from performing a pullthrough at 3mo vs 6 mo vs. 9 mo of age, and simply defining age as less than 1 yo or greater than 1 yo can eliminate possible differences, especially when your multivariate analysis determined that age was a significant independent factor.

7. If age >1yo is associated with less obstructive symptoms, do you advocate for later pullthroughs? How are children managed prior to definitive pullthrough - colostomy vs irrigations vs other?

8. In your discussion, you mention that anorectal manometry was not used. However, were other adjuncts used to define cause of postoperative obstruction such as abdominal x-ray, contrast enema, or anorectal exam under anesthesia?

Overall, your data can be more granular to better understand potential prognostic factors, and you need to describe how persistent obstructive symptoms are treated in your institution, and what part of your practice, if any, will change based on your findings.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2023 Sep 8;18(9):e0290430. doi: 10.1371/journal.pone.0290430.r002

Author response to Decision Letter 0


27 Jun 2023

RESPONSES TO REVIEWER AND EDITOR:

The editor and reviewer comments are in italics in the material below, and our responses are regular.

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

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We have ensured that our manuscript meets PLOS ONE's style requirements, including file naming.

2. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

We have uploaded our study's minimal underlying data set as Supplement File 1 (S1_File).

3. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

We have removed our ethics statement written in the section beside the Methods.

Reviewers' comments:

Reviewer 1

Reviewer #1: This study examined prognostic factors for persistent obstructive symptoms in Hirschsprung disease patients following pull-through surgery in a specific developing country. The results revealed that younger age at pull-through surgery was significantly associated with a higher risk of persistent obstructive symptoms, while other factors such as operative technique and patient demographics did not show significant associations.

Thank you very much for these encouraging comments from this reviewer.

Strengths of the Study:

The study fills a research gap by investigating the prognostic factors for persistent obstructive symptoms in HSCR patients from a developing country, broadening our understanding of the condition in diverse populations.

The use of a cross-sectional study design and a comprehensive analysis of various factors enhance the reliability and validity of the findings.

The large sample size and inclusion of both males and females contribute to the generalizability of the results within the specific population under study.

Thank you very much for these encouraging comments from this reviewer.

Limitations/Issues of the Study:

The study's retrospective nature may introduce inherent biases and limitations in data collection and analysis.

We have added the following sentences in the Discussion section: "Our study's retrospective nature may introduce inherent biases and limitations in data collection and analysis.”

The study focuses on a single institution, which may limit the generalizability of the findings to other healthcare settings or populations.

We have added the following sentences in the Discussion section: “In addition, our study focuses on a single institution, which may limit the generalizability of the findings to other healthcare settings or populations.”

The study does not provide detailed information on the specific nature and severity of persistent obstructive symptoms experienced by the patients.

We have added the following sentences in the Discussion section: "We did not determine the severity of persistent obstructive symptoms experienced by our patients."

How the obstructive symptoms were handled is not demonstrated.

We have now added the following sentences in the Methods section: “We managed the patients with persistent obstructive symptoms as follows: first, patients were admitted into the hospital, nothing per oral, given antibiotics, and irrigations; second, defined the cause of postoperative obstructive symptoms using abdominal X-ray, contrast enema, and examination under anesthesia.3,4 Treatment of our patients depends on the cause of postoperative obstructive symptoms, whether anatomic, pathological, or functional.3,4”

How are the patients managed postoperatively - not demonstrated.

We have now added the following section in the Methods:

Post pull-through management

The nasogastric tube was removed on postoperative day (POD) one after pull-through, while the feedings were given once the bowel sound was normal. The Foley catheter was removed on POD2 after Duhamel and TEPT, and POD4 after transanal Swenson-like pull-through. Antibiotics were given for five days after surgery. Most patients were discharged on POD5.

A time to incidence of obstructive symptoms is needed.

We have now added Supplementary File 1, including a time to incidence of obstructive symptoms. We have now also added the following sentences in the Results section: “The time to the incidence of obstructive symptoms varied among patients from 10 days to 16 months following pull-through (S1_File)”.

Overall, this study provides valuable insights into prognostic factors for persistent obstructive symptoms after pull-through surgery in HSCR patients from a developing country. The findings emphasize the importance of considering operative technique and age at definitive surgery when assessing the risk of persistent obstructive symptoms.

Thank you very much for these encouraging comments from this reviewer.

Reviewer #2: Your article's goal is laudable - risk factors for Hirschsprung's associated enterocolitis and other postoperative complications after surgery are not well understood from developed countries, and data from a developing country is valuable.

Thank you very much for these encouraging comments from this reviewer.

There are, however, a few revisions that your paper can benefit from.

1. Define "persistent obstructive symptoms" in the Introduction. This is a vague term that would benefit from clear definition as it can vary within institutions.

In the Introduction section, we have defined persistent obstructive symptoms: "Postoperative persistent obstructive symptoms were defined as abdominal distension, bloating, borborygmi, vomiting, or severe constipation following pull-through.3”

2. Were intraoperative frozen sections compared with permanent sections to ensure that the segment length was appropriately diagnosed? If so, how many frozen sections correlated with the permanent sections?

We added the following sentences in the Methods section: “Intraoperative frozen sections were compared with permanent sections to ensure that the segment length was appropriately diagnosed. All frozen sections samples, except two cases, correlated with the permanent sections.”

3. How are the postoperative persistent obstructive symptoms treated in your institution? Admission into the hospital, NPO, antibiotics, irrigations? How do these symptoms affect your patient population specifically as it may be different in developed countries?

We have now added the following sentences in the Methods section: “We managed the patients with persistent obstructive symptoms as follows: first, patients were admitted into the hospital, nothing per oral, given antibiotics, and irrigations; second, defined the cause of postoperative obstructive symptoms using abdominal X-ray, contrast enema, and examination under anesthesia.3,4 Treatment of our patients depends on the cause of postoperative obstructive symptoms, whether anatomic, pathological, or functional.3,4”

4. While you mention that surgeon preference defined which procedures were performed, what information was used to decide when to perform a 2-stage Duhamel? Were all procedures done as 2-stage (all patients received colostomy first)?

We have added the following sentences in the Duhamel pull-through section: "We performed a two-staged Duhamel pull-through for our patients in our hospital, i.e., all patients received stoma first.”

5. What criteria was used to define short vs long segment? For total colonics, how were these reconstructed and at what age?

We have now added the following sentences in the Methods section: “HSCR patients were classified as short-segment (aganglionosis affects the rectosigmoid colon), long-segment (aganglionosis extending proximal to the splenic flexure), and total colon aganglionosis (TCA, aganglionosis of the entire colon).”

“All TCA patients have been managed with a diverting ileostomy first. They underwent definitive surgery using the Duhamel approach at the age of at least one-year-old (Table 1).”

6. Table 1 should list how many short, long, total colonics underwent TEPT, Duhamel, or transanal Swenson, and at what age distribution. It should also define age <1 yo better. Performing neonatal pullthrough would be different from performing a pullthrough at 3mo vs 6 mo vs. 9 mo of age, and simply defining age as less than 1 yo or greater than 1 yo can eliminate possible differences, especially when your multivariate analysis determined that age was a significant independent factor.

We have now revised Table 1 as suggested by this reviewer. Moreover, we have now added the following sentences in the Discussion section: "Performing neonatal pull-through would be different from performing a pull-through at 3 months old (mo) vs. 6 mo vs. 9 mo of age, and simply defining age as <1 or �1 year old can eliminate possible differences, particularly when our multivariate analysis determined that age was a significant independent factor.”

7. If age >1yo is associated with less obstructive symptoms, do you advocate for later pull-throughs? How are children managed prior to definitive pull-through - colostomy vs irrigations vs other?

We have now added the following sentences in the Discussion section: “Performing neonatal pull-through would be different from performing a pull-through at 3 months old (mo) vs. 6 mo vs. 9 mo of age, and simply defining age as <1 or �1 year old can eliminate possible differences, particularly when our multivariate analysis determined that age was a significant independent factor. These aspects should be considered while interpreting our findings.”

We have added the following sentences in the Methods section: "Prior to definitive surgery, the children were managed by rectal irrigation. If the rectal irrigation was ineffective in keeping the colon decompressed, the children underwent colostomy.”

8. In your discussion, you mention that anorectal manometry was not used. However, were other adjuncts used to define cause of postoperative obstruction such as abdominal x-ray, contrast enema, or anorectal exam under anesthesia?

We have now added the following sentences in the Methods section: “We managed the patients with persistent obstructive symptoms as follows: first, patients were admitted into the hospital, nothing per oral, given antibiotics, and irrigations; second, defined the cause of postoperative obstructive symptoms using abdominal X-ray, contrast enema, and examination under anesthesia.3,4 Treatment of our patients depends on the cause of postoperative obstructive symptoms, whether anatomic, pathological, or functional.3,4”

Overall, your data can be more granular to better understand potential prognostic factors, and you need to describe how persistent obstructive symptoms are treated in your institution, and what part of your practice, if any, will change based on your findings.

We have made our data more granular to understand potential prognostic factors better. We have also described how persistent obstructive symptoms are treated in our institution.

Attachment

Submitted filename: ResponseToReviewer_Naisya.edited.docx

Decision Letter 1

Paul Kwong-Hang Tam

17 Jul 2023

PONE-D-23-13236R1Prognostic factors for persistent obstructive symptoms in patients with Hirschsprung disease following pull-throughPLOS ONE

Dear Dr. Gunadi,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Aug 31 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Paul Kwong-Hang Tam

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors present their single institution experience between 2017-2022 of patients post pull through dealing with obstructive symptoms in a developing country. They evaluated 25 patients (or 22% of the 114) to determine factors for obstructive symptoms.

The authors need to rewrite the number of patients so that there is consistent way of # of patients and percentage in all parts of the manuscript.

I still do not understand how obstructive symptoms were evaluated or why an NGT tube is required postoperatively.

They have overall provided answers to the reviewers criticisms.

Reviewer #2: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2023 Sep 8;18(9):e0290430. doi: 10.1371/journal.pone.0290430.r004

Author response to Decision Letter 1


18 Jul 2023

RESPONSES TO REVIEWER AND EDITOR:

The editor and reviewer comments are in italics in the material below, and our responses are regular.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Thank you very much for these encouraging comments from these reviewers.

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Thank you very much for these encouraging comments from these reviewers.

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Thank you very much for these encouraging comments from these reviewers.

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Thank you very much for these encouraging comments from these reviewers.

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Thank you very much for these encouraging comments from these reviewers.

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors present their single institution experience between 2017-2022 of patients post pull through dealing with obstructive symptoms in a developing country. They evaluated 25 patients (or 22% of the 114) to determine factors for obstructive symptoms.

The authors need to rewrite the number of patients so that there is consistent way of # of patients and percentage in all parts of the manuscript.

We have now rewritten the number of patients so that there is a consistent way of # of patients and percentage in all parts of the manuscript.

I still do not understand how obstructive symptoms were evaluated or why an NGT tube is required postoperatively.

We have now revised the Methods section: “After admission, the patients with persistent obstructive symptoms were managed with antibiotics, irrigations, and nothing per oral. They were evaluated using the following diagnostic approach: history, abdominal X-ray, contrast enema, and examination under anesthesia.3,4 Treatment of patients was determined according to the etiology of the obstructive symptoms, anatomic, pathological, or functional.3,4”

The placement of NGT was our protocol from the anesthesiologist during the surgery. The NGT was removed soon after the surgery.

We have now revised the Methods section:

“Post pull-through management

The nasogastric tube was removed soon after surgery finished.”

They have overall provided answers to the reviewers criticisms.

Thank you very much for these encouraging comments from this reviewer.

Reviewer #2: (No Response)

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Attachment

Submitted filename: ResponseToReviewer2_Naisya.edited.docx

Decision Letter 2

Paul Kwong-Hang Tam

9 Aug 2023

Prognostic factors for persistent obstructive symptoms in patients with Hirschsprung disease following pull-through

PONE-D-23-13236R2

Dear Dr. Gunadi

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Paul Kwong-Hang Tam

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Revision is satisfactory

Acceptance letter

Paul Kwong-Hang Tam

30 Aug 2023

PONE-D-23-13236R2

Prognostic factors for persistent obstructive symptoms in patients with Hirschsprung disease following pull-through

Dear Dr. Gunadi:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Paul Kwong-Hang Tam

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table

    (XLSX)

    Attachment

    Submitted filename: ResponseToReviewer_Naisya.edited.docx

    Attachment

    Submitted filename: ResponseToReviewer2_Naisya.edited.docx

    Data Availability Statement

    All relevant data are within the paper and its Supporting Information files.


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