Intussusception is one of the most common causes of an acute abdomen in the pediatric emergency clinic and is the leading cause of acute bowel obstruction in infants and young children (1–3). In general, most intussusceptions can be categorized as primary or idiopathic, with thickened bowel wall lymphoid tissue (Peyer patches) acting as the lead point. Approximately 5–12% of intussusceptions are pathological, which usually present with different symptoms and are caused by conditions such as Meckel’s diverticula (4), intestinal polyps (5, 6), intestinal duplication (7), allergic purpura (8) and some rare digestive tract malignant tumors (9, 10).

Although diagnosing an intussusception is relatively easy, an expanded differential diagnosis in the setting of a pathological intussusception remains a challenge for most pediatricians, radiologists and pediatric surgeons. The initial management of an intussusception in most cases is non-surgical reduction via air or barium enema. Operative reduction is only needed when there is suspicion of bowel necrosis and perforation or non-surgical reduction fails. When a pathological intussusception is caused by pathologic lead points (PLPs), surgical treatment is ultimately required. Surgery should not be delayed in children in the setting of a difficult or doubtful pneumatic reduction, especially in older children. Timely diagnosis and treatment of intussusception avoids serious complications such as bowel necrosis, perforation, and death (11, 12).

Doctors usually order an ultrasound or CT scan when PLPs are suspected in patients with intussusceptions, but these have low sensitivity and specificity (13, 14). If a pathological intussusception could be diagnosed and treated earlier using advanced diagnostic capabilities, discomfort caused by repeated enemas would be avoided and prognosis would improve (15, 16). There exists a need to establish a more accurate, non-invasive and reusable diagnostic model for diagnosing pathological intussusceptions. Several models that have already been established are not perfect, and few focus specifically on the risk factors for a pathological intussusception. The aim of this study was to develop and validate a diagnostic nomogram based on the clinical and pathologic risk factors for individual pre-operative risk prediction.

Here we developed and validated an effective preoperative nomogram that used clinicopathologic risk factors to predict a pathological intussusception in children. Episode time, mass length and the infection history were incorporated into the nomogram based on data from a relatively large database derived from two different hospitals. The novel nomogram is a non-invasive, easy-to-use preoperative tool to predict a pathological intussusception in children with intussusceptions that may reduce the need for air enemas or the need for additional radiological examinations. Though some of the cases underwent diagnostic CT scans in our study, we strongly recommend that a diagnostic air enema would have been a better choice due to higher risk of the radiation from the CT scan.

Our results suggest that episode time was an independent risk factor for pathological intussusceptions in children. Prior studies have reported a relationship between pathological intussusceptions and recurrent intussusceptions, as more than 3 recurrences makes a pathological intussusception highly likely (22, 23). Intussusception secondary to PLPs tended to recur frequently. The overall recurrence rate of all intussusception cases was extremely variable and depended on the series, ranging from 2 to 20% (23–26). Lin et al. (15) reported that 78.5% (51/65) of patients with intussusceptions secondary to PLPs recurred after their first episode. Among the 65 pathological intussusception patients in their work, 51 recurred after a successful reduction (21 with one recurrence, 14 with two, 10 with three, and 6 with more than three). Chen et al. (22) reported an overall recurrence rate of 20.0%, and the proportion of PLPs in recurrence group was higher than in the non-recurrence group (2.2% and 1.2%, P = 0.005). Univariate and multiple logistic regression analyses confirmed that PLPs were predictive of the intussusception recurrence in children (27), which was similar to our results. Furthermore, multiple authors (12, 28) emphasized that the presence of PLPs should always be considered in children with recurrent intussusceptions.

Zhang et al. (13) in their analysis of 37 cases of pathological intussusception reported that the length of the intussusception was significantly longer in pathological intussusceptions than in primary intussusceptions (P = 0.042), which could be explained by the existence of PLPs in pathological intussusceptions. Due to the presence of PLPs, the proximal retracted small bowel (intussusceptum) carries the mesentery into the distal bowel tract (sheath), so pathological intussusceptions would involve a longer length of bowel. We found in the present work that patients with pathological intussusceptions more commonly had intussusception lengths ≥ 8 cm compared with those with primary intussusceptions.

Multiple logistic regression analysis in our study confirmed that a history of infection, defined as symptoms and signs of fever, coughing, rhinorrhea, and diarrhea, was significantly less common in patients with pathological intussusceptions than primary intussusceptions. A history of infection was found to be an independent negative predictor of a pathological intussusception in children. Lee et al. (29) reported that a history of infection was significantly more common in non-recurrent (72/114, 63.2%) than recurrent (5/23, 21.7%) intussusceptions (P < 0.001). Park et al. (30) found that the incidence of pediatric intussusceptions decreased after the COVID-19 pandemic. That decreased incidence may be related to the reduced circulation of communicable diseases. However, the proportion of patients with more severe intussusceptions and PLPs rose (2/87 and 4/27). All of those findings are consistent with ours, fewer incidences of history of infection in pathological intussusception than in primary.

Our multivariate analysis showed that age was not a strong independent predictor of a pathological intussusception, which makes the exclusion of this variable a common strategy for model development. However, the rejection of potentially important predictors may be the result of nuances in the data set or confounding by other predictors (17). A non-significant statistical association with pathological intussusception therefore does not definitively imply that age is not predictive of this pathology. Zhang et al. (13) reported that the age of patients with pathological intussusceptions was older than those with primary intussusception. Lin et al. (15) further found that those patients older than 2 years of age, especially between 2 and 5 years of age, were more likely to have a pathological intussusception. Blakelock and Beasley (31) reported that 60% of PLPs occurred in children aged 5–14 years. Our nomogram that excluded age as a clinical risk factor demonstrated adequate discrimination in the primary cohort (C-index, 0.922), although it deteriorated in the validation cohort (C-index, 0.886). Given that the incidence of pathological intussusceptions was comparable between the two cohorts, even the reduced discrimination suggests that our nomogram is highly predictive and could be applied directly to validation cohorts.

Pathological intussusception with malignant tumors as their pathologic lead points are rare and mostly caused by Burkitt’s lymphoma (32, 33) in children. Only 6 out of 368 patients in our study had lymphoma. Their disease was limited to the area of the intussusception and was completely resected. However, prior works noted that some patients with stage III or IV disease could only undergo an incomplete surgical resection of their intussusception followed by additional chemotherapy, and had poor prognoses (33). Early diagnosis and treatment are therefore of great importance. We hope that the nomogram developed in the present study may allow these patients to have better outcomes.

Decision curve analysis was used to justify the clinical usefulness of our nomogram. Clinical impact curves showed that if the threshold probability of the is > 7%, there is good agreement between the number of positive patients by the nomogram and that of actually positive patients.

There are several limitations to this study. First, the nomogram was established based on data obtained from a single institution in China. Second, all data were collected retrospectively and bias therefore could not be avoided. Further prospective studies are needed to validate our model. Lastly, the universality of the nomogram for all intussusception patients remains unknown because some of the patients who had successful air enema reductions were excluded from this study. Further prospective analyses are required to validate our model in all patients with intussusceptions.

In conclusion, we developed a nomogram based on clinical risk factors for a pathological intussusception. This nomogram can be conveniently used to facilitate pre-operative decision-making for children with intussusceptions.

The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by the Ethics Committee of Shanghai Children’s Hospital (2018R055). Written informed consent to participate in this study was provided by the participants’ legal guardian.

YG and LZ: conception and design. XT and DX: administrative support and collection and assembly of data. XT, DX, and XW: provision of study materials. XT, YG, and LJ: data analysis and interpretation. All authors listed have made a substantial, direct, and intellectual contribution to the work, approved it for publication, and wrote the manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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