Intragastric balloon insertion and pancreatitis: Case series

Highlights • Intra-Gastric Balloon use as non-operative strategy for bariatric patients.• Rise of adverse life-threatening outcomes of Intra-Gastric Balloon.• Pancreatitis could be secondary to pancreas compression by the Intra-Gastric Balloon.• Need for the recognition of balloon pancreatitis as a complication of Intra-Gastric Balloon insertion.


Introduction
Obesity is recognized as major public health problem and has reached epidemic proportions worldwide [1]. In the State of Kuwait, the prevalence of obesity is alarmingly high, affecting 40% of adults [2]. The rising prevalence of obesity and its associated health related comorbidities highlight the need for effective treatment strategies to manage and reduce the burden of disease [3]. Bariatric surgery is considered the most effective treatment for morbid obesity, and is found to positively ameliorate related comorbidities, compared to conventional strategies [4]. However, although, bariatric surgery is primarily restricted to morbidly obese patients that meet a preoperative criteria (BMI > 35 with comorbidities, or BMI > 40), an intermediate group of patients that are not bariatric candidates that are also found to not respond well to medical therapy may benefit from surgery [5,6].
To address this intermediary group, in 1985 the Garren-Edwards Gastric Bubble (GEGB ® ) was introduced in the United States [7]. Initially, however, it was recommended that the intra-gastric balloons (IGB) are utilized only in clinical trials due to safety issues [8]. However, since then, several IGB were developed to meet pre-set standards for safety [9]. The uses of IGB vary, ranging from primary weight loss, weight loss solutions in high risk patients and as a bridge to bariatric surgery [10]. Table 1 summarizes the most popular types in used.
The safety of IGB has been evaluated in multiple studies and is considered generally safe [11,12]. However, several lifethreatening complications have been reported including gastric perforation, intestinal obstruction secondary to migration, and rarely acute pancreatitis [13][14][15]. In this case series, we shed light on the latter complication and present five patients who developed acute pancreatitis secondary to IGB insertion. Our aim is to investigate this emerging complication and propose that it is better recognized and listed as a possible post-procedure adverse event. The present case series is compliant with the PROCESS guidelines for case series [16].

Cases overview
Five cases of patients are described; three female and two males with a mean age of 23.6 years (SD ± 6.17), and a mean BMI of 34 kg/m 2 (SD ± 6.17). As presented in Table 2 there were no critical past medical histories and no other apparent risk factors for pancreatitis. One patient (20%) was morbidly obese and four (80%) were actively practicing lifestyle modification. All patients consented prior to inclusion in this case series.
All IGB were inserted by General Surgeons across several centers in Kuwait with an exception of the Spatz balloon which was inserted in the United Arab Emirates. There were no reported occurrences of intra-operative complications. The average volume injected into the IGB was 558 ml (range: 500-600, SD ± 39.6) of methylene blue with normal saline.

Post IGB complications
All the cases presented to clinical care from the emergency department across two centers in Kuwait. The clinical course of balloon pancreatitis is detailed in Table 3.
On biochemical investigation, the mean levels of serum amylase and lipase were 422 U/L (SD ± 185) and 429 U/L (SD ± 448), respectively. Elevated amylase and lipase were observed in 100% and 60% of cases, respectively. All five cases were diagnosed and treated for acute pancreatitis. The mean duration from IGB insertion to the development of acute pancreatitis was 154 days (SD ± 170).

Management
The average length of stay under clinical care was 2 days. Two cases responded to conservative medical treatment while three cases required additional medical treatment and IGB removal. All five cases were kept nil per os (NPO) and received intravenous fluids, antiemetics, and analgesia. Three cases additionally received intravenous proton pump inhibitors. The chemical and biochemical details of cases are illustrated in Table 3.

Statistical analysis
To investigate whether factors can significantly influence the management outcome (IGB removal versus conservative medical treatment) in the management of balloon pancreatitis. Statistical analysis was carried out using SPSS (IBM SPSS statistics version 20). Descriptive statistics were carried out, mean and standard deviation was calculated for continuous variables, and frequencies and numbers for categorical variables.
The case series is registered with research registry, unique identifier number: researchregistry5842.

Discussion
The benefits of IGB in weight reduction are well documented in the literature. However, the present case series demonstrates  that although rare, balloon pancreatitis is a significant complication among patients undergoing IGB insertion. A diagnostic triad was developed as a useful aid to diagnose the condition, and aid clinicians in recognizing the complication. The diagnostic criterion included: 1) recent gastric balloon insertion; 2) symptoms consistent with pancreatitis; 3) biochemical or radiological evidence of pancreatitis.
The removal of the balloon provided significant symptomatic relief in most patients, whereas two patients were managed conservatively without removing the IGB. Similar to previous case reports, patients in the present case series were found to present with mild pancreatitis [24,25,35]. Nevertheless, since severe course of pancreatitis has been described in the literature, it should be cautioned that not all balloon pancreatitis remain mild [23].
As summarized in Table 4, balloon pancreatitis remains to be a disease limited to case reports observed in centers that use IGB to aid weight reduction among bariatric patients. Although it has been suggested that an abdominal ultrasound should be performed to rule out the presence of gallstones, in most reports, the IGB is frequently removed. As such, in one case study, the presence of a distended gallbladder confounded the diagnosis of pancreatitis, which was believed to be secondary to an acute cholecystitis [34]. Despite performing a laparoscopic cholecystectomy, the patient did not improve symptomatically and eventually had the IGB removed. In another case series Alsohaibani et al. (2019), reported that of the 10 patients with balloon pancreatitis, five were treated conservatively [40]. Moreover, patients were found to present with a mild course of pancreatitis, and the greatest severity reported as a Bedside Index for Severity in Acute Pancreatitis (BISAP) score was 2 [40]. The authors also reported that patients who developed this condition was found to be following Heliosphere air-filled balloon insertion [40]. However, due to the limited number of reports on balloon pancreatitis due to an air-filled balloon system, it could be suggested that the underlying cause was related to direct physical pressure.
These findings led to the proposition that the pathogenesis for balloon pancreatitis is secondary to the compression of the pancreas by the IGB, as observed during computed tomography (CT) imaging of the abdomen [25]. This aforementioned compression is likely to affect both the stomach and the pancreas. Compression of blood flow to the area of the stomach may even lead to localized ischemia resulting in ulcer formation and eventually perforation [29][30][31]. Giardello et al. suggested that the pathology is more obvious among patients with previous gastric surgery due to the alteration of the abdominal anatomy and blood supply to the stomach. Thus, some investigators recommend that previous gastric surgeries are an absolute contraindication for the insertion of IGB [32].
In this series, patients were considered healthy and did not undergo gastric surgery prior to the insertion of IGB. In Patient 1, imaging obtained demonstrated IGB compressing an acutely inflamed pancreas (Fig. 1). This highlights the accuracy of using CT scans to diagnose and stratify the severity of the condition in cases where no improvement is observed.
Several studies have shown the safety and efficacy profile for the use of IGB in bariatric patients [26][27][28]. These studies vary with regards to sample size, therefore may not detect the incidence of balloon pancreatitis. Although severe complications resulting from IGB have been reported [26], the incidence of balloon pancreatitis remains to be underreported. As more IGB are utilized in the management of bariatric patients globally, it is likely that the incidence of balloon pancreatitis will increase.

Limitations
Limitations of the case series include the small sample size which may have limited statistical analysis, and thus the standard error value could not be added to the mean value, as such only descriptive analysis was carried out. In addition to the small sample size, the retrospective nature of this paper limits the scope of our findings to a descriptive analysis, which cannot confer causation.

Conclusion
As previously discussed, the proposed pathogenesis for balloon pancreatitis may possibly be due to the compression of the pancreas by the IGB. Following the review of the literature, and clinical experience of the authors, the case series demonstrated that there appears to be a bias towards endoscopic removal of IGB. Nevertheless, in line with recommendations of other case reports, some patients may benefit from a more conservative approach. Given the rarity of the condition, it may be difficult to perform a randomized control trial in order to establish an evidence-based standard of care. Further research is needed to better understand the implications of the balloon shape, size, volume and location of insertion, in order to potentially prevent this fatal complication. Authors of the case series suggest that balloon pancreatitis is recognized as a complication of IGB insertion and that both patients and treating physicians are aware of this during the course of follow-up.

Declaration of Competing Interest
No conflict of interest.

Sources of funding
None.

Ethical approval
Retrospective case series are exempt from ethical approval by the Ethical Committee at the Ministry of Health Kuwait.

Consent
Written informed consent was obtained from the publication of the case series.

Author contribution
All authors contributed equally to the data collection, analysis and write-up of this case series.

Registration of research studies
The case series is registered with research registry, unique identifier number: researchregistry5842.

Provenance and peer review
Not commissioned, externally peer-reviewed.