Meckel's diverticulum (MD) is the most frequent congenital malformation of the small intestines due to incomplete degeneration of an omphalomesenteric duct or a vitelline duct, which takes place around 5-7 weeks of the fetal period [1,2]. Complications of the MD have been reported to include hemorrhage, perforation, inflammation, intestinal obstruction, stone formation, and hemia [3]. MD can be diagnosed when symptoms appear due to complications or can be detected accidentally without any symptoms. The former case is often accompanied by hemorrhage, intestinal obstruction and acute abdominal pain [4,5]. Bani-Hani and Shatnawi [6] reported that symptoms occurred more frequently in younger patients, when MD was 2 cm or more in length, when ectopic tissue existed, and in male patients.

There are many methods for diagnosis of MD. Among these, Meckel's scan is an important and non-invasive test with a low radiation burden and it is easy to perform. In particular, it has a high accuracy for detection of MD with ectopic gastric mucosa [7].

Until recently in South Korea, there have been a few reports of clinical study on MD [8,9]. In addition, no study on comparison and analysis of clinical features of MD that are attributable to difference in diagnostic methods has been reported.

Against this background, this study targeted pediatric patients who were diagnosed with symptomatic MD in order to compare and analyze clinical symptoms, examination findings, histological findings, and therapies depending on performance of Meckel's scan. This study is intended to provide useful information for selection of a diagnostic method based on clinical features of patients with MD, and, consequently, for early diagnosis and treatment.

This study targeted 34 patients whose diagnosis of symptomatic MD was confirmed during the period from January 2000 to December 2012 at three university hospitals that located in Incheon city. Regarding the number of patients for each hospital, the Gachon University Gil Medical Center had 14 cases, the Inha University Hospital had 11 cases, and the Incheon St. Mary's Hospital had nine cases. Medical records were examined retrospectively for comparison and analysis of clinical symptoms (gastrointestinal [GI] bleeding, abdominal pain, vomiting, abdominal distension, irritability, etc), complete blood count (CBC) profiles, diagnostic methods, pre-operative diagnoses, operation methods, and pathologic findings after the patients were divided in the group of patients diagnosed by Meckel's scan (group 1) and the group of patients diagnosed using methods other than Meckel's scan (group 2). MD which were accidentally found during other operations, were excluded.

Mann-Whitney test with a MedCalc (MedCalc Software, Acacialaan 22, B-8400 Ostend, Belgium) program was performed for calculation p-value of the CBC profile, and the length and diameter of MD between two groups while p-value less than 0.05 was considered significant.

In the initial fetal period, the vitelline duct connects the yolk sac with the midgut. The vitelline duct shrinks and becomes closed within 7-8 weeks when the yolk sac is replaced by the placenta as a source of nutrition for the fetus. In this case, if the vitelline duct remains, this may cause MD, intestinal umbilical fistula, vitelline cyst, fibrous cord, or intestinal umbilical sinus depending on the degree of closure. Among these, MD is the most common [10].

Incidence rate of MD is 2-3%. In most cases, MD shows no symptoms but causes complications such as hemorrhage, intestinal obstruction, inflammation, and perforation in less than 5% of cases [11].

In regard to incidence rate based on sex ratio, more male than female were reported to have MD at a ratio of 2.4 : 1 in the study for adults and children by Yamaguchi et al. [12], and a ratio of 2.3 : 1 in the study for only children by Lee et al. [8]. In this study, which targeted only children, the ratio was 7.5 : 1, the results were weighted towards male. However, Mackey and Dineen [13] reported that no difference in sex ratio was found when MD showed no symptoms (when MD was found accidentally in the middle of an autopsy). They reported that incidence rate of complications was higher by 3-4 times in male than in female. With respect to incidence frequency by age, Lee et al. [14] stated that MD was found in 60% of patients aged 6 years or younger. Lee et al. [9] also stated that patients in the less than 5 years showed the highest frequency of incidence. In this study that targeted children, patients younger than 10 years took up 66.5% of the total patients.

Depending on complications, clinical symptoms include lower GI hemorrhage, abdominal pain, nausea, vomiting, and fever. Among these systems, abdominal pain is the most common. However, this study found that indolent lower GI hemorrhage was the most common symptom. Regarding complications among adults and children, Mackey and Dineen [13] reported intestinal obstruction of 33.8%, inflammation of 30.9%, and rectal hemorrhage of 25%. In the study for only children by Lee et al. [9] reported that the GI bleeding was the most frequent (76%). In addition, in this study, lower GI bleeding (47.0%) was the most common, followed by intestinal obstruction (32.4%), which showed the second highest percentage. In particular, the main symptom of lower GI bleeding was found in 91.7% of cases in group 1, where Meckel's scan was performed. In group 2, where Meckel's scan was not performed, abdominal pain was the most common, as it was found in 45.6% of cases in the group. Group 1 did not show any clinical features other than GI bleeding. Regarding pre-operative diagnosis, Yamaguchi et al. [12] reported intestinal obstruction of 42.5%, acute appendicitis 24.7%, and MD 11.8%. In this study, however, in 73.5% of cases, an operation was performed due to diagnosis with or suspicion of MD, which was the highest percentage, followed by intussusceptions that were not cured by air reduction at 14.7%, omphalitis at 8.9%, and neonatal enterocolitis at 2.9%.

Lower GI bleeding is a major symptom of MD. Amount of bleeding may vary in diverse cases, ranging from a positive reaction to stool occult blood test to active massive bleeding that leads to failure in circulatory function. In particular, if the case is the latter one (massive bleeding) or continuous bleeding (even though the amount is small), this causes anemia due to loss of blood [15,16]. In this study, group 1 showed statistically significant differences in values of RBC count, Hb, Hct, MCV, and MCH, greater than those of group 2. Platelet count showed that one patient in group 1 had idiopathic thrombocytopenic purpura. Consequently, if a patient who visits the hospital due to lower GI bleeding, abdominal distension, or abdominal pain shows severe anemia or unexplained anemia, it is desirable to perform Meckel's scan in consideration of the possibility of MD as the first priority.

For diagnosis of MD, Meckel's scan (^99mTc-pertechnetate) is mainly performed, as an isotope is used to find ectopic gastric mucosa. This is the best non-invasive method for pre-operative diagnosis of MD with ectopic gastric mucosa, which is used for patients with lower GI hemorrhage. Among children, detection rate using Meckel's scan was reported to be 90% [17], while sensitivity and specificity were reported to be 0.6-0.75, positive predictive value 1.0, and negative predictive value 0.77 [15]. Using Meckel's scan, non-specific false positive findings are not common while potential causes include intestinal obstructive disease, intussusception, inflammatory disease, arteriovenous malformation, ulcer, GI tumor, angioma, and anomaly of the urinary system (hydronephrosis, ectopic kidney, vesicoureteral reflex, and bladder diverticulum). False negative diagnosis is attributable to the case where ulcer and hemorrhage are found without ectopic gastric mucosa, the case where ectopic gastric mucosa is insufficient or its function is insufficient according to reading of a scanned image (abnormality in blood supply), the case where radioactivity is diluted or washed away due to hemorrhage or intestinal hypersecretion, or the case where increased echogenisity is concealed due to lack of skill or duplication of organs (bladder or duodenum) [18]. Pentagastrin, glucagon, and H₂ blocker are injected in order to increase sensitivity of Meckel's scan. Cimetidine, a commonly used antagonist of histamine receptor (H₂), suppresses secretion of pertechnetate inside the intestine. Intravenous injection of cimetidine one hour before isotope scan can increase accuracy of diagnosis [19]. In this study, premedication was administered only for 41.7% of patients in the group where Meckel's scan was performed. One case was shown to be a false negative on the first scan, whereas it was positive on the second scan.

When a child with lower GI bleeding, the cause of which is not known, does not show any indication or ectopic gastric mucosa, Meckel's scan is negative. Therefore, many methods, including high-resolution ultrasound scan, laparoscopy, and CT have been tried for diagnosis of MD at an early stage [20]. In this study, Meckel's scan was performed for 36.4% of patients, while diagnostic laparoscopy was performed for 42.4% of patients, as was the most used diagnostic method.

Treatment of MD with symptoms is surgical resection. State of lesions and anatomical differences must be considered before a proper operation method is chosen, such as diverticulectomy or end-to-end anastomosis after ileal resection. Ileal resection is performed for a patient with hemorrhage who has a broad-based diverticulum in order to avoid a situation in which ectopic mucosa remains after surgery. However, Piñero et al. [20] reported that ileal resection showed a higher frequency of post-operative complications, such as infection or intestinal obstruction (stenosis or band) in junction than diverticulectomy. In particular, if the diameter of the diverticulum base is larger than that of the intestine, a child is likely to have stenosis of the ileum after diverticulectomy. Therefore, ileal resection has been known to be safer [10]. In this study, the numbers of diverticulectomy and of ileal resection were almost similar, whereas a simple diverticulectomy took up the higher percentage in group 1.

According to Yamaguchi et al. [12] ectopic tissue in MD was found together with gastric mucosa (62.4%), pancreatic tissue (16.1%) or small intestine mucosa (2.1%). According to Lee et al. [9] tissue was found along with small intestine mucosa (43%), gastric mucosa (48%), or both gastric and pancreatic mucosa (9%), while there was no case of pancreatic mucosa alone. In this study, however, ectopic tissue was found along with small intestine mucosa tissue (58.1%), gastric mucosa tissue (25.8%), or both gastric and pancreatic tissue (9.7%). Out of the 11 cases where gastric mucosa tissue was found, five cases (45.5%) showed lower GI bleeding. Reason for the GI bleeding is that as around 80% of MD mucosa is attributable to gastric mucosa, gastric acid is secreted in ectopic gastric mucosa inside diverticulum, causing damage to the intestine. However, gastric mucosa tissue was found only in 50% of cases in group 1.

Yahchouchy et al. [21] reported that as the length of the diverticulum and diameter of its base were factors causing complications of MD, a narrow-and-long-based diverticulum was more likely to cause intestinal obstruction and inflammation, whereas foreign bodies were likely to slide into a broad-and-short-based diverticulum. According to the report by Lee et al. [8], diverticulum was located primarily in the distance of 35-70 cm in the proximal part from the ileocecal valve, and the length of the diverticulum was less than 5 cm in 80% of cases. Lee et al. [9] also reported that diverticulum was located at a mean distance of 45.9 cm from the ileocecal valve, while the mean length of the diverticulum was 3.2 cm with a mean diameter of 1.8 cm. In addition, in this study, diverticulum was located at a mean distance of 47.0 cm (7-85 cm) toward the proximal part from the ileocecal valve, while the mean length of the diverticulum was 3.7 cm (1.5-7 cm) with a mean diameter of 1.8 cm (1-7 cm).

In this study, which was conducted retrospectively, there were some limitations, namely that negative scan data and insufficient premedication cases for the scan were excluded. Finding clinical features and hematological characteristics for selection of diagnostic methods including Meckel's scan is essential, because a quick and accurate diagnosis is important in order to minimize complications that may be caused by late diagnosis of MD and to ensure a quick recovery. It is desirable to perform Meckel's scan in consideration of the possibility of MD as the first priority if patients suffer from GI bleeding or unexplained anemia as well as GI symptoms.

It is believed that prospective studies on comparison of scintigraphic and non-scintigraphic diagnosis of MD are required henceforward.