Preoperative imatinib and laparoscopic intersphincteric resection for large rectal gastrointestinal stromal tumor: A case report

Highlights • Rectal GIST is a rare disease, and have often grown by the time of discovery due to lack of initially subjective symptoms.• A large rectal GIST often require extensive surgery which may lead to postoperative bowel dysfunction.• Preoperative chemotherapy with imatinib mesylate is effective for reducing the rectal GIST.• Laparoscopic intersphincteric resection may be a useful technique for giant rectal GIST, which enables anal preservation.


Introduction
Surgical resection is the preferred treatment for gastrointestinal stromal tumors (GISTs). Due to lack of initially subjective symptoms, rectal GISTs have often grown by the time of discovery, and therefore, anus preservation during surgery is often difficult [1]. Recently, the effectiveness of preoperative chemotherapy with imatinib mesylate (IM) has been shown, resulting in some cases where anal-preserving surgery was possible after tumor reduction. However, there have been few reports of laparoscopic anal-preserving surgery for giant rectal GIST. We present the case Abbreviations: GIST, gastrointestinal stromal tumor; IM, imatinib mesylate; ISR, intersphincteric resection.
of a patient with a 10 cm rectal GIST who was successfully treated with IM and laparoscopic intersphincteric resection (ISR) to preserve the anus. We also review prior cases of rectal GIST where patients had undergone anal-preserving surgery following preoperative chemotherapy with IM. Our case represented the largest tumor size in that review witch was operated laparoscopically. The work has been reported in line with the SCARE criteria [2].

Presentation of case
A 55-year-old man, with a history of abnormal bowel movements, visited local clinics over a 5-month period. Lower gastrointestinal endoscopy showed no abnormality in the rectal mucosa. An abdominal computed tomography (CT) found a huge mass in the Ra (rectum/above the peritoneal reflection) -Rb (rectum/below the peritoneal reflection) section of the rectum, and the patient was referred to the hospital for thorough examination.  Pelvic magnetic resonance imaging (MRI) showed a mass measuring 10 cm on the left side of the lower rectum (Fig. 1). The tumor extended to the left side of the prostate and the left levator ani muscle. Endoscopic ultrasound-fine needle aspiration revealed bundles of spindle cells with positive immunohistochemical staining for c-Kit and DOG-1 but negative for S-100 protein, leading to a diagnosis of rectal GIST. Since it would be difficult to excise the tumor without pseudo-capsule damage, neoadjuvant imatinib (400 mg/day) was initiated. In a CT scan 2 months later, the tumor diameter had shrunk to 9.5 cm and the contrast effects inside the tumor had disappeared ( Fig. 1). Eight months after chemotherapy was initiated, the tumor showed marked shrinkage to 7.8 cm, an almost maximum tumor response. It was decided that surgical treatment was possible at this point.
The patient indicated a strong desire to preserve the anus, and therefore, we chose laparoscopic ISR and temporary transverse colostomy (Fig. 2). Surgery was started from mobilizing the descending colon and sigmoid colon. The origin of the inferior mesenteric artery was exposed and dissected. Next, mesorectal excision was performed as much as possible. Around the left side of the rectum, we dissected the tumor without damaging the pseudo-capsule (Fig. 2a). When the tumor location was confirmed by intraoperative rectal examination, we judged that it was difficult to dissect the rectum from the intraperitoneal with a enough anal margin (Fig. 2b), so got started anal-side approach under the microscope. A transanal access platform (GelPOINT Path; Applied Medical) and AirSeal (CONMED) platform was introduced. Mucosal dissection was performed at the height of dentate line. The tumor was extended to the left levator ani muscle, so the mass was dissected with some muscles attached to it. The abdominal cavity and anal side was opened all around (Fig. 2c). The anal side of rectum and oral side of colon was resected, and we removed the specimen. The rectosigmoid colon and anal canal was anastomosed by handsewn suture and a temporary transverse colostomy was performed. The operation time was 608 min, and the blood loss was 130 ml.
The patient recovered with no postoperative complications and left the hospital on postoperative day 10. In histopathological tissue, most of the tumor disappeared by vitrification and fibrosis (Fig. 3). One year after postoperative chemotherapy with IM, the patient exhibits no evidence of recurrence.

Discussion
Primary rectal GIST is a relatively rare disease, accounting for approximately 5% of all GIST [3]. The current report presents the case of a patient who had a large rectal GIST that had progressed to other organs and was successfully treated with preoperative IM and anus-preserving anus ISR [1]. The primary treatment for a rectal GIST is complete surgical resection with negative microscopic margins, but this procedure is challenging for surgeons because of the confined pelvic space and the nature of the GIST to densely adhere to the pelvic floor [4]. Therefore, rectal GIST might require extensive surgery, such as abdominoperineal resection or pelvic exenteration, which may lead to postoperative bowel dysfunction [3]. Recently, there have been some reported cases where anal preservation surgery was possible for large tumors following preoperative chemotherapy with IM [1,[5][6][7][8][9].
Preoperative chemotherapy with IM is useful for the treatment of rectal GIST. Cvanar et al. studied 83 patients with rectal GIST who underwent preoperative chemotherapy and found a high tumor shrinkage rate. Sixty patients (72.3%) had a partial response (PR), 18 (21.7%) had stable disease (SD), 3 (4.8%) had a complete response (CR), and 1 (1.2%) had progressive disease (PD) according to RECIST guidelines [5]. In addition, in their retrospective series examining surgical margins, 46 of 51 patients (90%) who underwent neoadjuvant Imatinib and surgery had negative margins compared to 33 of 63 (52%) patients who did not [5]. Jakob et al. reviewed 39 patients and reported that preoperative chemotherapy led to improved surgical margins and increased local disease-free and overall survivals [6]. Wilkinson et al. examined 19 patients who underwent extended surgery for rectal GIST and reported that reducing the tumor size with preoperative chemotherapy resulted in an increased likelihood of sphincter-sparing surgery [7]. Thus, preoperative chemotherapy with IM for rectal GIST can be expected to have a tumor shrinking effect, ensure surgical margins that avoid  A goal of surgery for GIST is to ensure a surgically safe margin without pseudo-capsule damage [8]. For small tumors, local excision, such as transanal, transsacral, and transperineal approaches, may be selected since they are minimally invasive and preserve defecation function. On the other hand, local excision may experience a poor surgical field of view, and therefore, it may be difficult to ensure the surgical margin. Jakob et al. examined 36 patients who underwent surgical treatment for rectal GIST and reported that all cases with local recurrence had undergone local excision with positive margins and with no preoperative Imatinib [6]. They concluded that local resection should only be performed when microscopically clear margins can be safely achieved [6].
Laparoscopic ISR may, therefore, be a useful technique for giant rectal GIST. The advantages of this procedure are: 1. it may preserve anal function for tumors located in a lower position of the rectum and 2. it may ensure a safe surgical margin by extending to the intersphincteric plane through the abdomen and in resection of distal margins under a direct view through the anus [9]. However, few reports have studied the benefits of laparoscopic ISR for rectal GIST. Fuimoto et al. performed laparoscopic ISR for 5 patients with a rectal GIST after preoperative chemotherapy. All cases achieved curative resection and recurrence did not occur for any patient during the 1-to 4-year postoperative period [10].