Determination of differential diagnostic criteria in pediatric hematology-oncology patients with acute abdomen in terms of tphylitis – appendicitis

Introduction and aim: Typhlitis (neutropenic enterocolitis) is a necrotizing inflammatory process in the intestinal mucosal wall, often involving the cecum, and seen in pediatric malignancy patients with high mortality. Although the survival rate is high with treatment, delay in diagnosis increases the risk of mortality, as symptoms can be confused with appendicitis. Medical imaging methods are useful for the diagnosis of typhilitis but there is no definitive algorithm for the definitive diagnosis and for the differential diagnosis from appendicitis. The difference in treatment approaches of typhlitis and appendicitis increases the importance of early diagnosis to avoid morbidity or mortality. In this study, we aimed to compile the results of patients who were followed-up with the diagnosis of typhlitis and who underwent surgical interventions with the diagnosis of appendicitis and to investigate the possible factors in the differential diagnosis with typhlitis. Material and method: Records of the patients who were followed up in our department and who were consulted to Pediatric Surgery with a preliminary diagnosis of typhlitis/appendicitis from the Pediatric Hematology and Oncology clinics between January 2010 and December 2019 were reviewed retrospectively. Demographic characteristics, main symptoms, physical examination findings, laboratory findings, medical imaging results, treatment results of the patients were compiled. Four groups were formed according to the patients who met/did not meet the diagnosis criteria of typhlitis and who underwent surgery: 1. Typhlitis present group (n = 34): Comprised of typhilitis patients who met diagnostic criteria for typhilitis. 2. Typhlitis absent group (n = 37): Comprised of non-typhilitis patients who did not meet diagnostic criteria for typhilitis. 3. Malignancy appendicitis group (n = 11): Comprised of patients diagnosed as appendicitis and underwent surgery thus surgically confirmed cases. 4. Appendicitis in the absence of malignancy group (n = 10): Comprised of acute appendicitis cases with no underlying malignant pathology and who were operated with the definitive diagnosis of acute appendicitis. Abdominopelvic CT of the patients were re-evaluated by the expert radiologist and ileum, cecum, ascendig, transverse, descending colon wall thickness were measured, periapendiceal fluid, pericecal fluid, intraabdominal free fluid were searched. Data are expressed as mean ± standard error of the mean (SEM). The data obtained from the groups were statistically evaluated using the SPSS-22 (IBM, Chicago, IL) program. Since the data did not conform to normal distribution, Kruskal- Wallis variance analysis was used for the comparison of parameters between multiple groups. Mann-Whitney U test was used for comparisons in paired groups and evaluated using Bonferroni correction. Categorical data were compared with Chi-square and Fisher's exact tests. Statistical significance level was accepted as p <0.05. Results: Data of a total of 358 malignancy patients who were consulted to Pediatric Surgery for acute abdominal symptoms (abdominal pain, nausea, vomiting, diarrhea) out of 940 malignancy patients treated by Pediatric Hematology and Pediatric Oncology services between January 2010 and December 2019 were compiled. The number of patients followed up with preliminary diagnosis of typhlitis was. A total 43 of the patients were girls, 39 were boys, and the mean age of the patients was 9.15 ± 0.57 years (2- 18 years). Underlying primary malignancies were AML, ALL and neuroblastoma in 61.8% of cases in the typhlitis present group, 56.7% in the typhlitis absent group and 72.9% in the malignancy appendicitis group. Duration of symptoms was 60.71 ± 7.82 hours (24-240 hours) in the typhlitis present group and it was significantly higher than the typhlitis absent group (37.14 ± 5.03 hours) (3-168 hours). Fever was present in 79.4% (p = 0.003) and diarrhea was present in 82.4% (p = 0.000) in typhlitis present group, which were significantly higher than typhlitis absent and appendicitis in the absence of malignancy groups. Abdominal guarding was present in 80% of the cases in appendicitis in the absence of malignancy group. Abdominal guarding was positive in 11.7% of cases in typhilis positive group, 5.4% in typhilitis absent group and 18.2 in the malignancy appendicitis group (p = 0.000). US showed periapendiceal fluid in 90% of the cases in appendicitis in the absence of malignancy group, in 81.8%of the cases in malignancy appendicitis group, which are significantly higher compared to typhlitis present (0%) and typhlitis absent (0%) groups (p = 0,000). Abdominal CT showed pericecal fluid in 72.7% of the cases in malignancy appendicitis group and in 90% of the cases in appendicitisin the absence of malignancy group, which were significantly higher compared to typhlitis present (2.9%) and typhlitis absent (0%) groups (p = 0.000). Abdominal CT showed periapendiceal fluid in 27.3% of the cases in malignancy appendicitis group and 80% in appendicitis in the absence of malignancy groups which were significantly higher compared to typhlitis present (0%) and typhlitis absent (0%) groups (p = 0.001). Cecal wall thickness was 6.40 ± 0.71 mm in typhlitis present group which was higher compared to typhlitis absent (1.50 ± 0.22 mm) and appendicitis in the absence of malignancy (2.09 ± 0.32 mm) groups. Ascending colon wall thickness was found to be significantly higher in typhlitis present group (5.28 ± 0.46 mm) compared to typhlitis absent (1.26 ± 0.17 mm) and appendicitis in the absence of malignancy (1.14 ± 0.10 mm) groups (p = 0.002). Conclusion: Medical imaging modalities are useful in the differential diagnosis of typhlitis and appendicitis in the uncertainty of symptoms and physical examination findings. The presence of increased intestinal wall thickening on US or CT, especially wall thickness in the cecum and ascending colon supports the diagnosis of typhlitis. Intestinal wall thickness of more than 3 mm in the cecum, ascending colon and/or other colon segments can be evaluated as typhilitis, and the presence of periapendiceal and pericecal fluid can be considered as a criterion in favor of appendicitis. The measured values of the intestinal wall thicknesses by US are similar to the results obtained by CT, thus we suggest that US is sufficient for the diagnosis of typhlitis. As a minimally invasive approach, diagnostic laparoscopy can be performed in patients for whom differential diagnosis cannot be made by medical imaging and suspicion of appendicitis cannot be eliminated.