Characteristics and Clinical Outcomes Associated with Appendix Location in Children with Acute Appendicitis

doi:10.21203/rs.3.rs-4203268/v1

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Characteristics and Clinical Outcomes Associated with Appendix Location in Children with Acute Appendicitis

https://doi.org/10.21203/rs.3.rs-4203268/v1

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PURPOSE

To categorize appendix location with a modified classification and describe the outcomes associated to each location.

METHODS

Prospective observational cohort study of children who underwent laparoscopic appendectomy in a reference children’s hospital; the diagnosis of acute appendicitis (AA) was confirmed by the pathology department and clinical history data were taken. The location of the appendix was classified as retrocecal (RA), pelvic (PEA), right Iliac fossa (RIF) and an intraoperative photograph was taken for confirmation.

RESULTS

The location of the appendix was divided in three groups (RIF 42%, PEA 33%, RA 25%). Significant differences were found in time of symptom onset (RA > 48 hours in 54.5% of patients p: 0.001) and in the ultrasound diagnosis of appendicitis (RIF 49.3%, RA 25.9%, PEA 24.6% p: 0.01). The primary outcome assessed was appendix perforation, also with significant differences between appendix locations (average 37.8%, PEA 46% p: 0.001).

CONCLUSION

The classification of the location of the appendix in RIF, PEA and RA is clear, simple, and reproducible, being RIF the most frequent location. The pelvic localization was associated with the presence of perforation, possibly because signs of peritoneal irritation are less common in these children, and it was less visualized on ultrasound.

Appendix location

Acute appendicitis

Children

Appendix position

Acute appendicitis (AA) is the most common abdominal surgical pathology in the pediatric population [1, 2]. The clinical manifestations and imaging findings may vary according to age, gender, underlying pathological conditions, and the development of complications, including perforation [3–6]. It has been suggested that the appendix location may affect the disease’s overall behavior, although no studies confirm this.

There are many classifications in the literature regarding the location of the cecal appendix, but they lack defined anatomical limits. Studies conducted on cadavers and open surgery report wide variability in the location of the vermiform appendix in the abdominal cavity [7, 8], being considered the organ with the widest anatomical variability concerning its location [9] without a clear relationship with a particular clinical outcome [10]. Classically, the retrocecal location (RA) is described as the most frequent (approximately 65%), followed by the pelvic position (PEA) (~ 25–45%), with the rest of the locations as a whole not exceeding 20% [11]. The current classifications are impractical since they are not easily replicable in surgery.

Consequently, we intend to create an easy-to-implement classification with defined limits and to evaluate the clinical outcomes associated with the appendix location.

This observational, analytical, longitudinal, prospective cohort study included patients under 18 years of age with AA undergoing urgent appendectomy by laparoscopy in a referral hospital in Bogotá, Colombia (HOMI-Fundación Hospital Pediátrico La Misericordia) from November 1, 2019, to March 31, 2020. Children whose appendicitis was confirmed by histopathological study were included. Patients with no parental consent, medical records with incomplete data, pathology not confirming appendicitis, interval appendectomies, open surgeries, and patients with malrotation of the colon were excluded.

Authorization was obtained from the institutional review board of HOMI’s ethics committee, as stated in Minute CEI 237 − 19. The present study followed the protocol, good clinical practices, and other relevant confidentiality regulations derived from the Declaration of Helsinki.

After signing informed consent, personal data was collected and handled under strict confidentiality. During the laparoscopic surgery, we took a photographic record of the location of the appendix and subsequently reviewed the medical records of patients whose care had already been completed. Only the group of researchers had access to the database, and additionally, only one researcher had access to the patient’s affiliation data for data collection. No individual results or information that would identify a specific subject were reported. There are no conflicts of interest derived from the research.

At the beginning of the surgery, after the pneumoperitoneum was insufflated and before surgical manipulation, we took a photographic record of the location of the tip of the appendix and saved the file assigned to the medical history number of each patient. Two researchers evaluated the photographs and compared them with the findings recorded in the surgical description. Initially, the appendices whose location coincided with the three assessments were immediately included in the study. The surgeon’s opinion was added to the surgical description in cases of discrepancy or doubts in the photograph.

The appendix location was defined by the location of the distal third (tip) of the appendix, as follows: appendices located lateral to the anterior teniae coli of the cecum/right colon were classified as Retrocecal Appendix (RA); those situated inferior to the iliac vessels were classified as Pelvic Appendix (PEA); those in the right lower quadrant that did not belong to the two previous locations were classified as an appendix in the right iliac fossa (RIF) (Fig. 1). During surgery, appendicitis was classified as perforated or non-perforated [4, 12, 13] and within the perforated ones, those with pus in three or four quadrants of the abdomen were considered to have generalized peritonitis.

Upon obtaining the pathology report and confirming the diagnosis of AA, the medical record was reviewed to collect the variables. The data obtained were analyzed using SPSS software. A descriptive analysis was performed for the quantitative variables, estimating central tendency and dispersion measures according to their distribution. For the qualitative variables, absolute and relative frequencies were calculated. The distribution of results was evaluated according to the appendix location. Bivariate analyses assessed the relationship of the different outcomes. The difference was considered statistically significant if p < 0.05. A multivariate analysis was performed with the variables that were most prevalent or with substantial differences.

During the study period, 571 patients underwent appendectomy; the diagnosis of AA was confirmed by pathology in 522. Seventy-three patients had at least one exclusion criterion, leaving 449 as subjects of analysis of the present study.

The demographic variables, most frequent symptoms, pediatric AA scale, and percentage of perforation are described in Table 1. The average evolution time of symptoms was 1.8 days (SD 1.3). Overweight was documented in 22.4% of patients. The most common symptom associated with pain was vomiting, followed by fever. Percussion pain at 74.6% in the RIF was the most frequently recorded sign of peritoneal irritation.

Table 1

Characteristics of the Population and Variables Studied
Variable	Description (N = 449)
Demographics
Age	Mean 10 years (SD 3.5 years) 2–4: 22 (4.9%) 5–9: 143 (31.85%) 10–14: 219 (48.7%) 15–17: 65 (14.48%)
Sex	Male: 252 (56.1%)
Overweight	101 (22.49%)
Clinical Manifestation
Evolution time	Median 1 day (IQR 1) Mean 1.85 days (SD 1.3) > 48 hours: 206 (45.88%)
Pain migration	198 (44.1%)
Vomiting/Nausea	401 (89.3%)
Fever	239 (53.2%)
Diarrhea	121 (26.9%)
Anorexia	204 (45.3%)
Painful cough	254 (56.7%)
Percussion pain	335 (74.6%)
Hypersensitivity	259 (57.6%)
Paraclinical Tests
Leukocytes (cell/mm3)	Mean 16,189 (SD 5,359)
Leukocytosis	322 (71.7%)
Neutrophilia	427 (95.1%)
Neutrophils (% of total leukocytes)	Median 82% (IQR 11)
Deviation to the left	428 (95.3%)
154 (34.3%)
Ultrasound diagnosis of appendicitis	152 (33.8%)
PAS*	Median 7 (IQR 3) Low: 46 (10.2%) Intermediate: 138 (30.7%) High: 265 (59%)
Surgical Findings
Perforation	170 (37.8%)
Generalized peritonitis	69 (15.3%)
Location	RIF 188 (41.8%) PEA 149 (33.1%) RA 112 (24.9%)
PAS = Pediatric Appendicitis Score, RIF = Right Iliac Fossa appendix, PEA = Pelvic Appendix, RA = Retrocecal Appendix

Pre-surgical ultrasound was performed on 218 patients; the appendix was visualized in 74%, 73% had findings suggestive of AA, and two cases were reported as normal (Table 1).

In surgery, the most frequent location of the appendix was RIF in 41.8% of patients, followed by PEA in 33.1% and RA in 24.9% (Fig. 2). Perforation occurred in 37.8% of patients, of which 15.3% had generalized peritonitis.

The bivariate analysis found that 45.88% of the patients had an evolution time of more than 48 hours from the onset of symptoms to the time of surgery; however, 54.5% of RA appendixes had an evolution time of more than 48 hours (p 0.001).

Of the patients evaluated by ultrasound, the appendix was visualized mostly in the RIF location (49.3%) compared to RA (26%) and PEA (25%) (p 0.01) (Table 2).

Table 2

Bivariate Analysis of Variables by Appendix Location
Variable	p
Variable	p	RIF	PEA	RA
Evolution time > 48h
Yes	67 (32.5%)	78 (37.8%)	61 (29.6%)	0.001*
No	121 (49.7%)	71 (29.2%)	51 (20.9%)	0.001*
Symptoms
Vomiting/Nausea	164 (40.9%)	138 (34.4%)	99 (24.6%)	0.265
Fever	96 (40.1%)	81 (33.8%)	62 (25.9%)	0.727
Diarrhea	49 (40.5%)	49 (40.5%)	23 (19%)	0.079

Yes	76 (49.3%)	38 (24.6%)	40 (25.9%)	0.017*
No	19 (28.3%)	30 (44.7%)	18 (26.8%)	0.017*
Ultrasound Diagnosis
Yes	76 (50%)	37 (24.3%)	39 (25.6%)	0.010*
No	18 (27.2%)	29 (43.9%)	19 (28.7%)	0.010*
Perforation
Yes	57 (33.5%)	69 (40.5%)	44 (25.8%)	0.010*
No	131 (46.9%)	80 (28.6%)	68 (24.3%)	0.010*
Generalized Peritonitis
Yes	26 (37.6%)	31 (44.9%)	12 (17.3%)	0.066
No	162 (42.6%)	118 (31%)	100 (26.3%)	0.066
RIF = Right Iliac Fossa appendix, PEA = Pelvic Appendix, RA = Retrocecal Appendix
*p < 0.05 statistically significant

Perforation was documented in 37.8% of patients: 46% PEA vs. 39% RIF and 30% RA (p 0.01). In the group of patients with perforated appendicitis, generalized peritonitis was more frequent in patients with PEA (45% vs 37.7% RIF vs 17.4% RA) (p 0.06) (Table 2).

The most representative variables were considered in the multivariate analysis (Table 3). The RIF location was used as a comparison standard because it is the most frequent. For an evolution time of more than 48 hours, RA location is 2.24 times more frequent (CI: 1.38–3.63); that is to say, in clinical conditions with a longer duration of evolution, the appendix is more likely to have an RA location.The most representative variables were considered in the multivariate analysis (Table 3). The RIF location was used as a comparison standard because it is the most frequent. For an evolution time of more than 48 hours, RA location is 2.24 times more frequent (CI: 1.38–3.63); that is to say, in clinical conditions with a longer duration of evolution, the appendix is more likely to have an RA location.

Regarding the risk of perforation adjusted for all variables, an evolution time greater than 48 hours increases the risk 1.73 times, fever increases the risk 2.54 times, and the PEA location increases it twice (OR: 2.04 CI: 1.23–3.38). The rest of the multivariate model’s associations are insignificant (Table 3).

Table 3

Multivariate Analysis for Appendix Location and Perforation
Variable	Analysis
Variable	RR	95% CI	p
Location = RIF	(Base outcome)
PEA
• Time > 48 hours	1.93	(1.24–3)	0.03*
• Diarrhea	1.28	(0.79–2)	0.312
• Percussion	0.99	(0.61–1.61)	0.986
RA
• Time > 48 hours	2.24	(1.38–3.63)	0.001*
• Diarrhea	0.67	(0.38–1.2)	0.183
• Percussion	1.75	(0.97–3.16)	0.059
Perforation	OR
Location
• PEA	2.03	(1.23–3.38)	0.006*
• RA	1.48	(0.85–2.57)	0.162
Time > 48 hours	1.73	(1.11–2.67)	0.014*
Fever	2.54	(1.59–4.06)	0.000*
Diarrhea	1.29	(0.80–2.09)	0.287
Vomiting	1.63	(0.73–3.62)	0.227
Percussion	1.23	(0.57–2.64)	0.589
RIF = Right Iliac Fossa appendix, PEA = Pelvic Appendix, RA = Retrocecal Appendix
*p < 0.05 statistically significant

AA is children’s most common intra-abdominal surgical pathology [1]; its clinical behavior can vary widely between patients and regions [3–5]. One of the factors that has been speculated to impact this aspect is the location of the distal end of the cecal appendix, with no clear association with clinical outcomes [10, 14]. As previously reviewed, this is the first study that evaluates the location of the appendix in children with AA confirmed by pathology who underwent laparoscopic appendectomy, associating the location with clinical outcomes.

Cadaver and open surgery studies have found RA as the most frequent location, with reports of up to 65%, followed by PEA [7, 11, 15]. Still, differences in the appendix location have been found between healthy patients and those with AA [16]. In adults taken to laparoscopy for different causes, a higher prevalence of the PEA location has been reported [17], while in children with AA undergoing laparoscopic and open appendectomy, the RA location was the most prevalent [8]. Given the confusion caused by the variability in the definitions of the location and the non-unification of terms, we propose a simplified and easily replicable classification that involves the two most frequently described in the literature (RA and PEA) and describes easily identifiable anatomical references during a laparoscopic procedure, so that the classification can be reproduced in other studies. In our research, RA was the least frequent location (24.9%), being almost a third of the frequency reported globally, and the locations associated with the RIF classification exceeded 40% of the cases, being the most frequent in children with AA. The differences found in the present work regarding the frequency of the appendix location and the published literature may be due to geographical aspects, as has already been documented [10]; another hypothesis to take into account is that the method used in the present study (laparoscopy with photographic records) is unlike all those previously published and possibly more precise.

Although studies confirm no data, it is speculated that RA location has a longer evolution time due to difficulties in diagnosis, masking of pain, and signs of peritoneal irritation, which agrees with the significant increase in time to diagnosis noted in our study (54% >48h). However, the increase in the evolution time in RA was not correlated with the rise in the perforation frequency for this group of patients. The distribution of symptoms is similar to that reported in the literature [18].

Regarding intraoperative findings, perforation was more frequent in the PEA location (p 0.01; OR 2.04; CI: 1.23–3.38), without this finding being previously reported in the literature. The RA location presented with less generalized peritonitis (17.4% vs. 37.7% RIF vs 44.9% PE) without reaching statistically significant differences (p 0.06).

In conclusion, the appendix location in children with AA differs from that reported in the literature for the global population in cadaver studies. The classification of the location of the appendix in RIF, PEA, and RA is clear, simple, and reproducible, with RIF being the most frequent location in the present study.

Longer time of symptoms (> 48h) was associated with the RA location. Pelvic localization was associated with perforation, possibly because signs of peritoneal irritation are less common in these children and were less visualized in ultrasound.

Multicentric studies must be performed using this new classification to corroborate the present findings in this study.

This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

The authors did not receive support from any organization for the submitted work.

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Figures: own elaboration (word and paint)

Compliance with Ethical Standards

All authors have no conflicts of interest to declare.

Informed consent

was obtained from legal guardians.

Ethics approval

Approval was obtained from HOMI’s ethics committee, as stated in Minute CEI 237 − 19. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

Author Contribution

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by J. M. E. E., N. G. A. and J. J. V. The first draft of the manuscript was written by J. M. E. E., N. G. A. and J. J. V. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Acknowledgement

Leila Tatiana Daza Ladino

Data Availability

Data is provided within the manuscript

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No competing interests reported.

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Characteristics and Clinical Outcomes Associated with Appendix Location in Children with Acute Appendicitis

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Abstract

PURPOSE

METHODS

RESULTS

CONCLUSION

Figures

Introduction

MATERIALS AND METHODS

RESULTS

DISCUSSION

Declarations

Author Contribution

Acknowledgement

Data Availability

References

Additional Declarations

Status:

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