Gastrointestinal Seed Bezoars: A Systematic Review of Case Reports and Case Series

Seed bezoars are a distinct subcategory of phytobezoars, caused by indigestible vegetable or fruit seeds. The aim of our study was to present a comprehensive review on seed bezoars, focusing on epidemiology, symptomatology, diagnosis and treatment options. A systematic review of the English literature (1980-2018) was conducted, using PubMed, Embase and Google Scholar databases. Fifty-two studies fulfilled the inclusion criteria, with a total of 153 patients, the majority of whom (72%) came from countries around the Eastern Mediterranean and the Middle East. Patients complained primarily about constipation (63%), abdominal/rectal pain (19%) or intestinal obstruction (17%). Most seed bezoars were found in the rectum (78%) and the terminal ileum (16%). Risk factors were recognised in 12% of cases. Manual disimpaction under general anaesthesia was the procedure of choice in 69%, while surgery was required in 22% of cases. Seed bezoars appear to represent a different pathophysiological process compared to fibre bezoars. Seeds usually pass through the pylorus and ileocaecal valve, due to their small size, and accumulate gradually in the colon. Seed bezoars are usually found in the rectum of patients without predisposing factors, causing constipation and pain. History and digital rectal examination are the mainstay of diagnosis, with manual extraction under general anaesthesia being the procedure of choice.


Introduction And Background
Bezoars are retained aggregates of indigestible material that accumulate and conglomerate in the gastrointestinal tract. They can occur anywhere from the oesophagus to the rectum, however, they are most commonly found in the stomach. Recognised risk factors are prior gastric surgery, neuropsychiatric disease, endocrinopathies impairing gastrointestinal motility and poor mastication [1,2].
Based on their component, they are classified into four main types: phytobezoar (fruit and vegetable fibres), trichobezoar (hair), lactobezoar (undigested milk concretions) and pharmacobezoar (medications) [1,2]. Seed bezoars are a distinct subtype of phytobezoars, caused by undigested vegetable seeds or fruit pits. In contrast to other bezoar categories, the majority is found in the rectum of patients with no predisposing factors, a fact suggesting a different pathophysiological process [3,4].
We hereby present a systematic, up-to-date review of case reports and case series of gastrointestinal seed bezoars, with emphasis on epidemiology, diagnosis and treatment options.

Review Methods
We performed a systematic review of the literature, following the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, in order to identify all studies of patients with gastrointestinal seed bezoars [5]. Literature searches were conducted in PubMed/MEDLINE, EMBASE and Google Scholar bibliographic databases, spanning years 1980 to 2018. The keywords "bezoar", "phytobezoar", "seed", "grain" and "pit" were used in all possible combinations. Moreover, the reference lists of all eligible studies were assessed for additional articles.
All study designs (case series and case reports) were eligible for inclusion in the final analysis. Patient age was not an exclusion criterion, and both adult and paediatric cases were included in the review. Articles without full text availability were excluded.
Titles and abstracts of all articles from the initial search were independently screened by two authors, to determine those articles for full text review. Any discrepancies concerning the evaluation of the studies were arbitrated by all authors. A flow chart of study selection is shown in Figure 1.

FIGURE 1: Flowchart of literature search
For each eligible study, data were extracted about demographic (number of patients, age, sex, and country of origin) and clinical characteristics (seed type, predisposing factors, bezoar location, clinical presentation, diagnostic and therapeutic management).
Statistical analysis was performed on SPSS, version 20.0 (IBM Corp, Armonk, NY). All data were tabulated and outcomes were cumulatively analysed. Continuous variables were expressed as mean ± standard deviation, while categorical variables were expressed as frequencies or percentages. Additionally, adult and paediatric subgroups were compared, using Student's ttest for continuous variables and chi-square or Fisher's exact test for categorical variables. Statistical significance was set to p < 0.05.

Results
Fifty-two studies were included in the final analysis (two retrospective case series and 50 case reports), with a total of 153 patients (Appendix). Demographic characteristics of patients are presented in Table 1.

TABLE 1: Demographic characteristics of seed bezoar cases
The vast majority of cases (110/153, 71.9%) came from countries of the eastern Mediterranean basin and the Middle East, whereas 29 patients (19.0%) came from Western countries and 14 (9.1%) from Asia.

TABLE 3: Comparison of paediatric versus adult cases
In both groups, the rectum was the most common location of the seed bezoar and constipation was the prevailing symptom. Intestinal obstruction was more frequent in adults than in children (24.3% vs 10.8%), however it marginally did not reach statistical significance (p = 0.07). Manual disimpaction was the procedure of choice in the majority of both children (78.3%) and adults (58.6%). Surgical exploration was required more commonly in adults (30% vs 14.5%, p = 0.03). Finally, predisposing factors were more frequently reported in adult than in paediatric cases (24.3% vs 1.2%, p < 0.0001).
The word "bezoar" derives its etymology from the Persian word "padzahr" or the Arabic "badizahr", which both mean "antidote" [1]. Indeed, bezoars had been ascribed mystical powers and were popular through the Middle Ages as remedies against a variety of poisons [1,6]. It was not until the 19th century that they were recognised as potentially serious medical conditions, being the cause of 3-7% of small intestinal obstructions [7,8].
Seed bezoars are a distinct subgroup of phytobezoars, caused by the accumulation of indigestible vegetable or fruit seeds in the intestinal lumen. Grains and seeds usually pass through the pylorus and the ileocaecal valve, due to their small size, and accumulate gradually in the colon [3,4,9]. Reaching the rectum, the faecal mass is further dehydrated and forms a hard bezoar, commonly presenting as faecal impaction. This pathophysiological process of seed bezoars appears to be different from fibre bezoars, which are usually found in the stomach. Fibres contained in fruits and vegetables (cellulose, lignin, tannins) polymerise and agglutinate in the acidic environment of the stomach, and form a glue-like coagulum which affixes to other material and only rarely overcomes the pyloric sphincter [8,10].
This hypothesis of different pathophysiology is further supported by the fact that seed bezoars seem to arise in patients without predisposing factors [3,4]. In our review, previous gastric surgery, neuropsychiatric disease and endocrinopathies (diabetes, hypothyroidism) were recognised only in 12% of cases. On the contrary, retrospective series of gastric and intestinal fibre bezoar cases reported rates of risk factors exceeding 85% [7,8,11]. As expected, we observed these predisposing conditions significantly more frequently in adult patients compared to children (24.3% vs 1.2%, p < 0.0001).
Another interesting observation is the geographical distribution of cases, which may reflect the dietary habits across the Mediterranean basin and the Middle East, a diet still including fresh fruits and vegetables, as opposed to the "typical" western diet, based on processed carbohydrates and saturated fats [7]. Watermelons and prickly pears are common delicacies consumed during summer months, while dried sunflower and pumpkin seeds are a favourite snack among all ages and seasons.
As far as the clinical presentation is concerned, the pooled analysis found that seed bezoars occurred most frequently in the rectum, in both children and adults (84% and 70%, respectively). The primary complain was therefore constipation (69% of children, 56% of adults), followed by non-specific abdominal or rectal pain (19% of children, 17% of adults).
Intestinal obstruction was relatively rare (17%) and mainly affected those patients with seed bezoars in the terminal ileum. While bowel perforation is the most feared complication, peritonitis was reported only in one case. On the contrary, fibre bezoars in the stomach may run asymptomatic for years or present with vague, non-specific symptoms including epigastric discomfort, abdominal bloating, nausea and vomiting, early satiety, post-prandial fullness, halitosis and weight loss [1].
Diagnosis of seed bezoars should be fairly straightforward, suggested by a careful history. Digital per rectum examination is the sine-qua-non of the diagnostic workup, aided by rectoscopy in selected cases. A full colonoscopy may be advisable in adult patients, to exclude malignant pathology, following bezoar extraction.
On the other hand, seed bezoars in the small intestine and colon are trickier to diagnose and require further investigations. Plain abdominal radiographs may show a solid stool mass, but generally they are within normal limits. Computerised tomography scans are considered the gold standard of diagnosis, offering information about the type, location and degree of obstruction, as well as potential bowel wall ischemia [12,13]. Of the 20 patients who required supplementary imaging studies, 70% had bezoars proximal to the rectum.
In children with ambiguous right lower quadrant or hypogastric pain, negative imaging studies and suspicion of acute appendicitis, a digital rectal examination should not be omitted. Of 83 children diagnosed with seed bezoars, five had been admitted in hospital with an initial working diagnosis of appendicitis and in three of them a rectal bezoar was revealed, thus eliminating the need for surgery.
Manual evacuation under general anaesthesia is the procedure of choice for rectal seed bezoars, to minimise patient discomfort, while surgery is practically inevitable for small bowel seed bezoars presenting as intestinal obstruction [7]. Indeed, among the 33 cases of operative management in this review, 31 cases concerned seed bezoars of the stomach, duodenum, small and large bowel, proximal to the rectum. Depending on the intraoperative findings, the surgeon may choose between enterotomy and removal of the obstructing bezoar, fragmentation and milking of the bezoar through the ileocaecal valve, and segmental enterectomy.
Although conservative treatment (endoscopy or chemical dissolution) works well for fibre bezoars, it does not appear to be efficient in patients with seed bezoars [7,14,15]. Our review showed that only 6% of seed bezoars were amenable to conservative measures (fleet enemas, stool softeners). Moreover, endoscopy alone usually failed to extract the bezoar, since the endoscope could not pass beyond the seed mass without risking perforation of the rectum, being successful only in 3% of cases.

Conclusions
In conclusion, seed bezoars should be considered as a distinct subgroup of phytobezoars, with different pathophysiology compared to bezoars caused by fibre accumulation. They are usually found in the rectum of children and adults without predisposing factors, causing constipation and pain. History and digital rectal examination are the cornerstones of diagnosis. In most patients rectal seed bezoars can be manually extracted under general anaesthesia, whereas intestinal seed bezoars are usually found in the terminal ileum causing intestinal obstruction and therefore mandate operative intervention.