1 Introduction

Gastrointestinal stromal tumors (GISTs) are the most commonly occurring mesenchymal tumors within the gastrointestinal (GI) tract and arise from the interstitial cells of Cajal [1]. GISTs can involve almost any segment of the GI tract, with the majority occurring within the stomach, and the rarest occurring within the gastroesophageal junction (GEJ) or esophagus [2, 3]. GISTs are more common in males, peak in incidence in older adults with the median age being between 60 and 65 and rarely occur in those under the age of 40 [4]. Common signs and symptoms include blood in stool or vomit, abdominal pain, fatigue, dysphagia, or early satiety [5].

GISTs can be identified with upper endoscopy (EGD), endoscopic ultrasound (EUS), or computed tomography (CT) with a definitive diagnosis made only with immunohistochemical examination via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsy [3]. Three morphologic subtypes exist, with spindle cell morphology being the most common and approximately 85%–90% containing KIT or PDGFRA mutations [2]. Overall prognosis is based on tumor size, mitotic activity, and location. The risk of metastasis is based more exclusively on tumor size and the amount of mitosis per 50 high-power fields [3, 6].

Tumors less than 5 cm are considered candidates for a minimally invasive surgical resection, and there are several accepted surgical approaches [7, 8]. Increased survival is associated with surgery and imatinib therapy for resectable GISTs [2, 3, 9]. Although treatment success ultimately varies with tumor spread, location, and size, those undergoing surgical resection for GEJ GISTs have a more favorable prognosis when compared with those in the small intestine [9]. It is estimated that 60% of GEJ GISTs are curable if present with localized disease [3, 10, 11].

This case details the successful resection of a GEJ GIST in a high body mass index (BMI 70.7 kg/m²) patient and is unique amongst the reviewed literature for patient age and BMI [1, 12]. Although obesity has not been directly correlated with the incidence of GISTs, there does appear to be a higher risk of GISTs in obese patients [1, 11, 13]. Increasingly, the surgical community may find the need for innovative surgical strategies to decrease morbidity and accomplish therapeutic resection in obese patients with GISTs.

2 Case Description

A thirty-one-year-old female with a past medical history significant for gastroesophageal reflux disease and morbid obesity (BMI 69.5 kg/m²) first presented to her local hospital with fatigue, shortness of breath, and melena. She was found to have a microcytic anemia and required multiple blood transfusions, after which she started iron supplementation and protonix. An abdominal CT scan depicted a 4.9-cm polypoid mass arising in the proximal stomach adjacent to the GEJ. Follow-up EGD/EUS demonstrated non-ulcerating external compression of the gastric wall at the fundus with an associated 5-cm mass. FNA was then performed revealing spindle cell proliferation with no mitotic figures or necrosis. The initial facility could not offer the patient surgery due to her high BMI and she was referred to our center.

Repeat EUS with FNA was performed, which again revealed a discrete 4.4 cm by 4.0 cm GIST (DOG1+ and CD117+) arising from the muscularis propria. The patient's case was reviewed at our multidisciplinary GI tumor board with multiple management approaches considered. These options included the initiation of neoadjuvant imatinib for three-to-six months prior to surgery with the goal of minimizing the tumor burden. Another management option proposed by our medical oncology team included proceeding with surgical resection first and then reviewing the final pathology to determine the need for adjuvant imatinib. After an extensive discussion with the patient, which included the risks and benefits of each approach, the patient ultimately elected to proceed with surgery first.

Given the patient's obesity and associated large abdominal wall, the surgical plan was a laparoscopic transgastric GIST resection with possible gastric bypass. Pre-operatively, she followed a liver-shrinking, low-carbohydrate, low-fat diet for 3 weeks. Her perioperative risk was assessed and optimized. Her American Society of Anesthesiologists (ASA) class was III. The risk of myocardial infarction or cardiac arrest intraoperatively or up to 30 days postoperatively was 0.6% per the Gupta MICA calculator. The risk of in-hospital post-operative pulmonary complications was 13.3% per her ARISCAT/CANET score. She was noted to be prediabetic with an A1C of 5.8%. Her weight was 438 pounds (height 167.6 cm, BMI 70.7 kg/m²) on the day of surgery.

The patient underwent the planned surgery with general anesthesia and endotracheal intubation. She was prepped and draped in sterile fashion. Pneumoperitoneum was established with Veress needle introduction at Palmer's point. Ports were placed with a right sided 5 mm port for liver retraction, a 12 and 5 mm port in the right mid-clavicular line, a supraumbilical 12 mm port, and a left mid-abdomen 5 mm port (Figure 1a). The stomach was identified, and simultaneous intraoperative EGD was performed. EGD revealed a large GIST near the GEJ. The tumor was deemed too close to the GEJ for possible wedge resection. Instead, a transgastric approach was undertaken. A proximal gastrotomy was performed, and the tumor was delivered into the peritoneal cavity. A laparoscopic stapler was used to staple across the base of the tumor with three serial purple loads. A frozen section was sent to pathology, and the initial staple line margin was noted to be positive for GIST cells. Therefore, an additional cuff of tissue was subsequently taken, which was benign. The gastrotomy was then closed by reapproximating the gastric edges and firing serial purple loads across the defect. These purple loads were reinforced with peri-strips to reduce the risk of postoperative leakage at the staple line. The specimen was removed via an endocatch specimen bag through the LUQ port site (Figure 1b). Repeat endoscopy was conducted to confirm an intact stomach and no leakage. The fascial defect from the specimen extraction site was closed using the Crossbow Fascial Closure System and 0 ethibond sutures. Excellent hemostasis was obtained, and the remainder of laparoscopic port sites were closed. The patient tolerated the procedure well and was transferred to the post-anesthesia care unit in stable condition. On postoperative day 1, she was tolerating a diet, voiding, ambulating, and pain was controlled on oral medications. She was deemed appropriate for discharge and was prescribed a 4-week course of Lovenox as an outpatient. The final surgical pathology of the obtained specimen can be found in Table 1.

During her 1-week post-operative follow-up visit, a same-day CT esophagram with oral contrast was performed and showed no evidence of leakage from the esophagus or stomach. The patient reported that she was doing well, complaining only of mild left-sided soreness. She was tolerating her full liquid diet and denied nausea, vomiting, diarrhea, heartburn, or dysphagia. At this clinic visit, she was advanced to a soft food diet and normal diet shortly thereafter. The patient was then seen by medical oncology 1 month after surgery. Based on the tumor grade, size, and mitotic rate, the patient was noted to have a recurrence rate of 55% and was therefore initiated on adjuvant imatinib (400 mg PO daily) with plans to complete a 3-year course. She has also had subsequent cross-sectional imaging every two-to-three months since surgery that is without disease recurrence or metastasis.

Given her morbid obesity, the patient has also closely followed our bariatric surgery team. After a required pre-surgical psychosocial and nutritional evaluation, the patient underwent a robotic biliopancreatic duodenal switch and gastric sleeve. When she presented for her 1-year follow-up visit, her weight was 283 lb (BMI 46.7 kg/m²), indicating that she had lost 53% of her original excess weight. At this visit, she reported feeling more energetic, had been exercising regularly, and was tolerating her post-operative bariatric diet.

3 Discussion

Obesity intuitively requires longer operative times, and recent data demonstrate additional associations to increased blood loss, higher rates of infections, renal complications, and venous thromboembolism [14]. Perhaps less intuitively, the recent SPLENDID study demonstrated that bariatric surgery compared to no surgery resulted in significantly lower incidences of cancer-related mortality and obesity-associated cancer [15]. As obesity becomes more prevalent in our society, it is important to recognize its wide-reaching effects not only on perioperative outcomes but also on the incidence of pathologies and cancers that require surgical resection for cure.

Specific to primary and localized GISTs, surgical resection is a therapeutic option for cure with complete tumor resection [16]. Wedge resection is considered the standard approach for GISTs due to the tumor's low risk of lymph node metastasis [17]. Here we describe a rare transgastric approach to overcome the excessive torque and force of the patient's large abdominal wall secondary to her morbid obesity. This approach requires additional manipulation of the tumor and luminal exposure to the peritoneum, which has an associated risk of peritoneal recurrence. However, we ultimately felt that the transgastric approach was best for improved laparoscopic ergonomics, increased visualization of the tumor margins, and preserved an appropriate amount of remnant gastric volume while allowing for complete resection and cure for this patient.

In addition to surgical resection, the antineoplastic drug imatinib has become a standard adjunct in the management of GISTs. In the last 20 years, investigators have noted therapeutic success with imatinib even in the treatment of metastatic GISTs. Using this potent tyrosine-kinase inhibitor was a viable secondary option if complete surgical resection was unable to be achieved. One phase III trial compared 400 mg imatinib daily versus placebo in the treatment of GISTs, and the trial was prematurely stopped due to its significant prolongation of disease-free survival (DFS) [18]. At the median follow up (19.7 months), the recurrence rate for the imatinib arm was 8% compared to the 20% in the placebo group [18]. In a separate study, DFS was compared at 1, 2, and 3 years between a treatment group (imatinib 400 mg daily) and a placebo group. DFS in these two groups (treatment vs. placebo) was 100% versus 90%, 96% versus 57%, and 89% versus 48% respectively [19]. Therefore, imatinib was included in the management of our patient; combining surgical resection with imatinib may lead to optimal outcomes and length of DFS in patients with GISTs.

Future studies may focus on continued innovations in the surgical approach to these tumors, and ways to optimize a morbidly obese patient for successful oncologic surgery. We encourage further work in comparing neoadjuvant versus adjuvant imatinib therapy durations in patients with GISTs and are particularly interested in the addition of bariatric surgical techniques (e.g., sleeve gastrectomy, gastric bypass, biliopancreatic duodenal switch in loop fashion or with single anastomosis) in the treatment of GISTs in patients with morbid obesity.

4 Conclusion

This case study demonstrates a safe and innovative resection of a GIST in a patient with an exceedingly high BMI. Given the increasing prevalence of obesity, understanding and improving surgical approaches in these patients becomes paramount in preventing surgical morbidity. By using a multidisciplinary and inventive approach, a high-grade GIST in an uncommon location (i.e. GEJ) in a patient with morbid obesity can be successfully resected with optimal postoperative outcomes.

Author Contributions

Felipe Quistian: conceptualization (equal), investigation (equal), methodology (equal), writing – original draft (equal). Kristen M. Quinn: conceptualization (equal), data curation (equal), formal analysis (equal), investigation (equal), methodology (equal), project administration (equal), resources (equal), supervision (equal), writing – original draft (equal), writing – review and editing (equal). Michael A. Deal: data curation (equal), project administration (equal), validation (equal), writing – review and editing (equal). Rana Pullatt: conceptualization (equal), resources (equal), supervision (equal), validation (equal), writing – review and editing (equal).

Ethics Statement

In accordance with institutional policy, this single case report was exempt from IRB review as all non-essential and identifying details have been omitted to ensure patient anonymity.

Consent

No written consent has been obtained from the patients as there is no patient identifiable data included.

Conflicts of Interest

The authors declare no conflicts of interest.