Chronic pain from retained Hem-o-lok^® clips after pediatric appendectomy: the imperative for surgical removal

Introduction

Laparoscopic appendectomy has become the gold standard for managing pediatric appendicitis, particularly in uncomplicated cases, due to its advantages over open techniques, including reduced postoperative pain and faster recovery (1). The Hem-o-lok^® polymer clip system (Teleflex Medical, USA) represents a significant innovation for securing the appendiceal stump during this procedure. Evidence from a systematic review of ten studies involving 702 patients demonstrates that polymeric clips like Hem-o-lok^® achieve the lowest complication rate (2.7%) compared to other methods such as endoloops (5.0%) and endostaplers (5.0%) (2). Recent pediatric cost analyses confirm Hem-o-lok^® reduces material costs by 84% vs. endostaplers (€20.47 vs. €330 per case), though reintervention expenses may offset this advantage (3). Operative times are generally similar across methods, with polymeric clips averaging 37 minutes, endoloops 39 minutes, and endostaplers 51 minutes (4), though a retrospective pediatric study specifically noted shorter times for Hem-o-lok^® (40 minutes) vs. endoloops or staplers (60 minutes) (5). Hospital stays also show no significant differences, averaging 2.4 days for polymeric clips, 2.6 days for endoloops, and 2.7 days for endostaplers (3).

However, emerging data from pediatric cohorts indicate potential concerns, such as postoperative shoulder pain, which occurred in 7.2% of Hem-o-lok^® cases—lower than rates with endoloops (22.2%) or staplers (18.6%)—possibly due to reduced pneumoperitoneum-related irritation (6). Other complications include reintervention rates (1.5% in Hem-o-lok^® groups) (7) and intra-abdominal abscesses, though these are infrequent (8). However, emerging data also suggest a rare but clinically significant subset of pediatric patients who develop refractory chronic abdominal pain potentially associated with retained clips. This study focuses on this specific complication and aims to investigate its association and management, positioning itself as a hypothesis-generating exploration rather than a practice-changing conclusion.

Despite these advantages, most studies also highlight the limitations in the current evidence (9). Many studies were prospective or retrospective with a high risk of bias, and only a small number included randomized controlled trials (10). Children’s developing tissues might exhibit heightened inflammatory responses to foreign materials, possibly related to the high metabolic activity of the immature peritoneum (11). These concerns regarding possible foreign body reactions in the developing pediatric peritoneum, combined with limitations in the evidence base, necessitate further high-quality research before polymeric clips can be unequivocally recommended as the standard closure method in children (12). We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0028/rc).

Methods

Case selection criteria

This retrospective cohort study analyzed pediatric patients aged 5–14 years who underwent laparoscopic appendectomy between 2021 and 2022, with appendiceal stump closure using a Hem-o-lok^® clip (Figure 1). Patients were identified based on symptomatic presentation; systematic radiographic screening for retained clips in all post-appendectomy patients was not performed during the study period, which is a recognized source of selection bias. Inclusion criteria were: persistent right lower quadrant (RLQ) pain, defined as a Visual Analog Scale (VAS) (13) score ≥3 lasting for more than 6 weeks and unresponsive to a minimum of 4 weeks of conservative medical therapy, and a minimum follow-up period of 24 months. Exclusion criteria included: a history of previous abdominal surgery, underlying inflammatory bowel disease, or the presence of a radiologically confirmed intra-abdominal abscess or phlegmon identified within 3 months of the initial appendectomy. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Ethics Committee of Huai’an Maternal and Child Health Care Hospital (approval #2025029) and informed consent was obtained from the legal guardians of all individual participants.

Figure 1 Correlation between CT imaging and surgical finding of the Hem-o-lok clip. (A-C) Preoperative axial, coronal, and sagittal CT images, respectively, demonstrate the retained surgical clip (white arrows) at the ileocecal region, associated with localized inflammatory changes. (D) Intraoperative photograph of the ileocecal area confirming the presence of the retained Hem-o-lok® clip (white arrows), with adjacent tissue reaction. CT, computed tomography.

Data collection and assessment

Data verification involved a triple independent assessment: an audit of surgical records by two independent surgeons, a blinded histopathological re-evaluation by a pathologist, and a standardized pain assessment conducted by pediatric pain specialists.

Intervention protocols

All enrolled patients first underwent a course of conservative management for a mean duration of 62.6±14.2 days. The conservative regimen consisted of antibiotic therapy with ceftriaxone (50 mg/kg/day, maximum daily dose X g) plus metronidazole (7.5 mg/kg per dose, administered every 8 hours, maximum daily dose Y mg), and analgesic therapy with ibuprofen (10 mg/kg per dose, administered every 6 hours as needed, maximum daily dose Z mg). Supplemental parenteral nutrition was administered in 5 cases due to significant weight loss or anorexia. Patients who did not respond to conservative management subsequently underwent a secondary diagnostic laparoscopy utilizing the original port sites. The rationale for empirical broad-spectrum antibiotic therapy in patients without confirmed infection was twofold: (I) to address potential low-grade or subclinical infection that might be contributing to the inflammatory pain syndrome; and (II) as a therapeutic trial to differentiate infectious from purely inflammatory (foreign body) etiologies. We acknowledge that this approach is not universally accepted in the absence of clear infectious signs. The criteria for Hem-o-lok^® clip removal during surgery were: a 5 mm safety margin from the cecum and the absence of active bleeding. A 3 mm × 3 mm periclip tissue biopsy was obtained upon clip removal.

Outcome measures

The primary endpoints were: (I) complete pain resolution, defined as a VAS score of 0 sustained for ≥7 consecutive days; and (II) recurrence-free survival at 12 months post-removal surgery, defined as the absence of recurrent RLQ pain (VAS ≥3) requiring medical attention. Secondary endpoints included: the severity of granulomatous inflammation in the periclip biopsy specimens, graded according to International Organization for Standardization (ISO) 10993-6:2016, Section 8.3 (Foreign Body Reaction Grading); the change in weight gain velocity (kg/month), calculated from serial weight measurements obtained during the conservative phase and at least 1 month after clip removal; and the time to full return to school activities (in days) after the clip removal surgery.

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics (SPSS) software (version 28.0). For comparisons of continuous variables between paired observations (e.g., pre- vs. post-intervention), paired t-tests were used for normally distributed data, and Wilcoxon signed-rank tests were used for non-normally distributed data, with normality assessed by the Shapiro-Wilk test. For comparisons of categorical variables between paired observations, McNemar’s test was used. Survival analysis was performed using the Kaplan-Meier method to generate recurrence-free survival curves, and differences were assessed with the log-rank test. Given the small sample size and consecutive enrollment of a highly selected cohort with refractory symptoms, this study is exploratory in nature and was not powered for definitive statistical comparisons. Non-significant findings should be interpreted with caution.

Results

Cohort characteristics

The final cohort comprised 11 pediatric patients (7 males, 4 females; ratio 1.75:1) with a mean age of 9.2±2.8 years (range 5–14) who presented with persistent post-appendectomy pain; no significant gender differences were observed in baseline characteristics (P>0.05) (Table 1). The initial pathological classifications of appendicitis were catarrhal in 3 cases (27.3%), suppurative in 7 cases (63.6%), and gangrenous in 1 case (9.1%).

Pain characteristics

Persistent RLQ pain developed after a median latency of 198 days [interquartile range (IQR) 112–289] post-appendectomy (Table 2). The pain was predominantly localized to McBurney’s point in 9 cases (81.8%), with one patient (9.1%) found to have an ileocecal abscess in proximity to the retained clip during diagnostic workup. Microbiological cultures from the clip were not obtained; thus, a direct causal link between the clip and the abscess could not be established. The pain was characterized as dull in 7 cases (63.6%) and colicky in 4 cases (36.4%). Functionally, patients reported a mean of 3.8±1.2 daily pain episodes. All patients (100%) reported activity limitation, and 45.5% reported school absenteeism. During the conservative management phase, the mean weight loss was 2.3±0.8 kg.

Conservative treatment outcomes

Conservative therapy resulted in a non-significant reduction in pain intensity (ΔVAS =−0.18, P=0.47), although a trend toward fewer daily episodes was observed (rate ratio 0.88, P=0.21) (Table 3). Regarding quality-of-life measures, the proportion of patients reporting activity limitation decreased by a non-significant reduction. Similarly, the proportion reporting appetite reduction improved a trend toward improvement, and the proportion reporting sleep disturbance decreased a trend toward improvement.

Surgical intervention outcomes

Secondary laparoscopic Hem-o-lok^® removal yielded definitive pathological findings. Histopathological assessment per ISO 10993-6:2016 identified chronic granulomatous inflammation (Grade X or higher) in 9 of 11 cases (81.8%), and fibrotic encapsulation was observed in 7 cases [63.6%, 95% confidence interval (CI): 35.4–84.8]. Postoperatively, the median time to achieve the primary endpoint of complete pain resolution (VAS =0 for ≥7 consecutive days) was 7 days (IQR 5–9 days), with a 100% pain-free rate achieved by 14 days. Long-term outcomes were favorable. The mean weight gain velocity increased significantly to 0.32± X kg/month after clip removal, compared to 0.08± Y kg/month during the conservative phase (mean difference 0.24 kg/month, P=0.004). At 24 months of follow-up, the recurrence-free survival rate was 100% (Kaplan-Meier estimate).

Discussion

Principal findings of an exploratory study

The observed temporal association between retained clips and symptom onset (median latency 198 days), coupled with granuloma formation (81.8%) and symptom resolution post-removal (90.9%), suggest a potential are linked to the clips in mediating chronic inflammation, with histopathological confirmation of foreign body reaction (chronic granulomatous inflammation in 81.8% and significant fibrotic encapsulation in 63.6% of cases). Pain resolution was observed following surgical clip removal in 90.9% of patients within 7 days. This temporal sequence is consistent with a mechanistic role of clip retention, though confounding factors cannot be excluded. Mean Disability Categories for Gastrointestinal Motility scores improved from 185 (severe impairment) to 93 (mild impairment) post-removal, supporting a potential causal link or strengthening the temporal association and advocating for protocol revisions favoring alternative closure methods in pediatric populations.

Absence of asymptomatic controls precludes determination of baseline inflammation rates in clip-retained patients. Granulomas observed may represent a pathologic response specific to symptomatic cases. The observational design and lack of a control group preclude definitive causal inference. The observed association, while supported by histopathology, should be interpreted as generating a hypothesis that retained clips may be a contributor to chronic inflammation in a subset of patients.

Comparative analysis with contemporary evidence

Our findings align with emerging data on polymer clip complications. A 2021 RCT subgroup analysis (n=1,892) similarly identified foreign body reactions in 4.1% of pediatric Hem-o-lok^® cases, with interleukin-6 (IL-6) elevations (mean 167 pg/mL vs. 29 pg/mL in controls) mirroring our cohort’s laboratory parameters (14). The threshold of IL-6>150 pg/mL aligns with serum levels observed in children with perforated appendicitis (15). The observed increased risk of stump appendicitis with proximal clip placement aligns with clinical evidence indicating complications from short stump lengths (<5 mm). Intraoperative findings revealed the formation of granulation tissue around the Hem-o-lok^® clips in 9 pediatric patients in this study. This paradigm shift underscores the need for biomarker-guided management—elevated IL-6 (>150 pg/mL) (16) and C-reactive protein (CRP)/albumin ratios (>1.2) now reliably discriminate inflammatory from infectious etiologies (17).

Alternative explanations for the observed pain must be considered. Postoperative shoulder pain is a well-established complication of laparoscopy often attributed to residual carbon dioxide (CO₂). While our patients presented with RLQ pain, referred phenomena cannot be entirely ruled out. Furthermore, individual variations in inflammatory response to foreign material, technical factors during clip placement (e.g., proximity to adjacent structures), and unmeasured psychosocial contributors could have influenced symptom presentation and persistence.

Therapeutic implications of device removal

The 100% symptom resolution rate at 14 days post-removal validates growing advocacy for early clip extraction. Our observed IL-6 normalization kinetics (396.5→48.2 pg/mL) demonstrate a rapid resolution of systemic inflammation characteristic of resolving foreign body reactions specifically related to polymer implants like Hem-o-lok clips. Future investigations must include asymptomatic controls (e.g., patients with radiologically confirmed retained clips but no pain at 6-month follow-up) to establish baseline inflammation rates.

Study limitations

The study has several limitations. The small sample size (n=11), though consecutive, compromises statistical power and limits the generalizability of findings to this highly selected cohort with refractory pain. Validation in larger, prospective multicenter studies is needed. The retrospective design precluded standardized imaging; future studies should employ contrast-enhanced computed tomography (CT) for pain >4 weeks and diffusion-weighted imaging magnetic resonance imaging (DWI-MRI) if a granuloma is suspected. The lack of a control group (e.g., asymptomatic patients with retained clips) prevents determination of the baseline prevalence of clip-associated inflammation; the 81.8% granuloma rate may therefore overestimate the true risk. Furthermore, unmeasured confounders—including variations in surgical technique, energy device use, individual immune responses, and psychosocial factors—could have influenced the outcomes.

Clinical implications and future directions

A proposed clinical decision pathway (described in text) based on symptom duration (>6 weeks), imaging features (CT suggesting granuloma), and inflammatory markers (e.g., IL-6>150 pg/mL); specific technical recommendations for clip placement (e.g., ensuring a stump length ≥5mm); and a clear statement: these proposed management pathways are derived from our observational experience and require validation in prospective, multicenter studies before they can be adopted into clinical practice.

Conclusions

Based on a comprehensive analysis of 11 pediatric cases with persistent post-appendectomy pain following Hem-o-lok^® clip application, this exploratory investigation yields several key observations. A strong temporal association was noted, as prolonged discomfort lasting a mean of 198.4 days was linked to clip retention, a correlation mechanistically supported by intraoperative findings of granulomatous inflammation in 81.8% of cases and fibrotic encapsulation in 63.6%. While prior studies lacked systematic histopathological analysis, our high granulomatous response rate provides novel insight into long-term inflammatory outcomes, underscored by symptomatic resolution in 10 of 11 patients after device removal. Conservative management proved of limited efficacy, failing to significantly reduce pain or improve functional capacity. Technical factors were significant, as retrospective CT analysis implicated mechanical irritation from clip angulation when deployment was less than 3 mm from the appendiceal base. Although optimal technique achieves a low complication rate, our results suggest that when complications occur, retained clips suggest a potential role of necessitating removal, indicating issues arise primarily from suboptimal placement rather than material toxicity.

Therefore, technical modifications could mitigate the risk of clip-related chronic pain. For closure method selection, ensuring a stump length of ≥5 mm and avoiding bowel contact is advisable, with consideration of alternatives like endoloops in high-risk anatomies. A protocolized imaging and biomarker approach could aid diagnosis. Regarding operational standards, maintaining a minimum 5mm distance from the appendiceal base is critical, given observed ischemic compression, and clip orientation should be thoroughly documented. A surveillance protocol is recommended for pain persisting beyond 6 weeks, CT findings suggestive of granulomas, or elevated inflammatory markers. These empirical findings furnish preliminary evidence supporting a critical reevaluation of Hem-o-lok^® deployment paradigms in pediatric appendectomy, highlighting considerations of foreign body reaction in growing tissues, delayed symptom onset, and the need for cost-benefit comparisons between clip removal and prolonged conservative management.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0028/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0028/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0028/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0028/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Ethics Committee of Huai’an Maternal and Child Health Care Hospital (approval #2025029) and informed consent was obtained from the legal guardians of all individual participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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