Hepatic Metastatic GIST: Diagnostic and Therapeutic Difficulties in Souro Sanou Teaching Hospital in Bobo Dioulasso, Burkina Faso

Introduction: Gastrointestinal stromal tumor (GIST) is the most common non-epithelial, mesenchymal tumor of the digestive tract. Targeted therapy has improved the prognosis but the diagnosis must be accurate before using the existing drugs. Aim: To report the diagnostic difficulty in our context through the clinical polymorphism and define the position of targeted therapy in the management of GIST metastatic stomach. Casuistry: We report 3 cases of gastric GIST with liver metastasis in different circumstances of discovery. Patients were 21, 45, and 73 years old. Discovery circumstances were respectively digestive hemorrhage, severe clinical anemia, abdominal tumor and gastric tumor. There was hepatic metastasis in the three cases. The three patients received Imatinib treatment, adjuvant treatment for the first two cases, and neo-adjuvant treatment for the third case, with a very good clinical response and CT response on metastases. Conclusion: Because of their rarity, GISTs are often difficult to diagnose, and necessarily require immunohistochemistry which is not available in our work context. The effectiveness of targeted therapy even on metastasis needs a rigorous diagnostic approach to improve patient survival.

Gastric location is the most common site, followed by the small intestine, colon, rectum, and esophagus [2] [3] [5]. Gastric GISTs have variable clinical expression [2] [3] [4]. From non-painful form with low metastatic risk, some may remain stable for years whereas others, very symptomatic, progress rapidly and already metastasized at the time of the diagnosis [2] [6]. Local forms treatment is essentially based on surgery R0 [2] [5], however advanced gist (metastatic and/or unresectable from the outset) has an improved prognosis by the addition of the Imatinib, and treatment target of the CD117 receptor expressed by these tumors We report three cases of gastric GIST metastasized to the liver to show the importance of the rigorous diagnostic procedure and the contribution of the targeted treatment to tumors whose prognosis is often considered pejorative from the beginning in our context.

Case 1
A21-year-oldfemale student, consulted in cancer unit in October 2015, referred by the gastroenterology department for Gastric Tumor. She had history of gastric ulcer diagnosed three months before consultation by upper GIT endoscopy and was receiving a treatment. No malignant cells or helicobacter Pylori were found on histology. Because of persistency of symptoms, a second endoscopy was requested and described a bombing tumor with a central crater in the lumen of the small gastric curvature (Figure 1(a)). A histology of a biopsy taken from this indurated lesion was not contributing. Further investigations revealed hepatic localization of secondary metastasis on segment II and IV. Due to the severity of anemia at 5 g/dl, 4/5 gastrectomy was performed on 19/10/2015 and took out a tumor of the small curvature with parietal development in the gastric lumen without breaking the mucosa (Figure 1(b)). The Post-operative evolution was non-complicated and the patient was discharged after 6 days. Weight gain and disappearance of anemia were noted after the surgery. The histology of the operative specimen was compatible with a gastrointestinal stromal tumor ( Figure   1(c), Figure 1(d)). The immunohistochemistry investigation performed confirms the diagnosis with CD34 labeling and CD117. An abdominopelvic CT scan of 29/01/2016 before the start of the treatment found a new hepatic location of segment IV (Figure 1(e)). An adjuvant palliative treatment by Imatinib was instituted since February 2016. After 21 months of treatment, a good clinical evolution was noted and a CT scan showed a near complete resolution of hepaticlesions (Figure 1(f)).

Case 2
A 72 years old, housewife, was received in cancer consulting unit in September

Discussion
GISTs are rare pathologies since they represent 0.1% to 3% digestive cancers and We reported three cases of hepatic metastasis from GIST in the same year.
That demonstrates that the pathology is relatively rare in our working context.
Actually, the frequency may be underestimated due to the diagnostic difficulties [7]. One of the causes of this difficulty is the delay in consultation, related to the variability of symptoms. Dyspepsia is found in almost all cases at the beginning.
In advanced forms, anaemia or bulky mass are the most common manifestations found in other series [1] [2] [3] [4]. Nevertheless, the incidental diagnosis was reported in 18.7% of cases [2]. In our context the delay diagnosis can be explained by unavailability of endoscopy (poorly equipped centres), available only in the two major cities of the country and also the lack of compliance of patients who have the fear of the procedure.
Sometimes, the lesion has an exotic luminal development and can spare the gastric mucosa, and then biopsies may not be contributory. However, the typical endoscopic picture can strongly suspect the diagnosis and requires the indication of atypical partial gastrostomy for diagnostic and therapeutic purpose in some cases, after multidisciplinary consultations [2]. Indeed in one of our cases, endoscopic biopsy performed twice did not allow the diagnosis. The typical image was not enough for the diagnosis in the absence of a concerted opinion. The surgery was needed before repeated severe anaemia despite multiple blood transfusions.
The diagnosis delay can be also connected with the misdiagnosis in front of the big size of the mass suggestive of retro-peritoneal sarcoma or lymphoma.
Echo-guided biopsy that we carried out for this case did not allow to make the diagnosis because it found a benign fibrous lesion; endoscopy was not requested due to lack of gastric symptoms.  [4]. Therefore the addition of the molecule (Imatinib, monoclonal antibody) inhibiting this pathway signal, has radically changed the prognosis, even for metastatic GISTs [10]. Indeed overall survival goes from 41% without Imatinib to 72% with Imatinib or 85% for the Imatinib arm and resection R0 [2].  [11]. The necessity of metastasectomy is still being discussed, without a consensus [2] [12]. While waiting for conclusive randomized studies, some studies seem to point prolonged survival associated with resection R0 coupled with intake of Imatinib [4].
Because of high risk of secondary resistance to Imatinib due to second mutations described by some authors [10] [11] resection of a persistent metastasis would be indicated as well as the tumour residue of more than 2 cm after neoadjuvant treatment.

Conclusion
Gastric Gist is the most common digestive mesenchymal tumour. It has to be kept in mind before any gastrointestinal bleeding and gastric mass or bulky meso-colic with non-contributory endoscopic biopsy. The diagnosis of certainty by Immunohistochemistry is necessary in view of the interest of Imatinib in taking metastatic forms or unresectable from the outset.

Patients Consent
The patients have given their consent for the Case reports to be published.