Challenge of gastro-intestinal stromal tumor management in low-income countries: example of Benin

GISTs are rare digestive tumors [1]. Fifteen cases were identified during the study period. Similar trends were seen in other African series. Only 19 cases of gastric GIST were identified in Cairo, Egypt, over a 6-year period at the National Cancer Institute; and 10 cases of GIST (all localizations included) over a 8-year period at the main hospital of Dakar, Senegal [6, 7].

The median age at diagnosis was 52 years. Similar data are reported by other series from Africa [6, 7]. The median age in the western series seems higher than ours, ranging from 65,8 to 69 years [12,13,14]. This could be explained by the higher age of the western population as well as their better life expectancy.

We noted in our series a male preponderance. However, GISTs usually affect both genders without predilection [3]. Other studies from Africa with a small sample size reported similar results [3, 7, 15].

Delay in care seeking after the onset of symptoms ranged from 24 h to 15 years. In case of non-emergency, patients seek health care late, probably because of their low-income status. This leads to late diagnosis which involve a higher risk of recurrence.

All patients were symptomatic, and the most frequent symptoms were abdominal pain and abdominal mass. Other African series studies have reported similar symptoms [6, 7]. Most GISTs remain silent until reaching a large size. Symptoms vary according to location and size. The main symptoms are pain and gastrointestinal bleeding [2, 3]. The delay in diagnosis in Africa has probably caused the tumors to become larger and palpable, and the patients to become symptomatic.

The stomach was the most common site for GISTs with 8 cases followed by the large bowel. Given the size of our sample, the interpretation of the frequency of locations could be biased. For instance, the second most frequent location in many studies is the small intestine [2, 3, 12, 14].

In our series, endoscopy contributed to diagnosis in few cases (n=5). The typical endoscopic appearance of GIST is usually a nonspecific smooth bulge covered by normal mucosa [16]. The endoscopic lesions (ulcerating and ulcerative-budding lesions) in our series were probably due to tumor size. But the intraluminal lesion isn’t always correlated with tumor size. Figure 4A is an example of large gastric GIST associated with a small intraluminal lesion.

Fig. 4figure 4

A Gastric mucosa with a slight nonspecific (black arrow) smooth bulge due to a large gastric GIST (blue arrow) in a 66-year-old patient. B Complex resection of the gastric tumor involving the spleen (yellow arrow) and the tail of the pancreas (green arrow)

In our study, all endoscopic biopsies were conclusive. In contrast, according to many authors, the endoscopic biopsy used to be negative because it does not often reach the submucosa where the tumor is located [3, 17]. Our biopsies were conclusive probably because of endoscopic appearance of the tumors which were large with a relatively large intraluminal portion.

Laparoscopy was performed on two patients for diagnostic purposes. This allowed for adequate neoadjuvant treatment to be put in place. However, in western studies, it is most often performed for therapeutic purposes [18, 19]. In our series, the size of the tumors did not allow laparoscopic resection.

Most of the tumors resected in the study were larger than 10 cm (n = 6) with a median size of 11 cm. The large size of the tumors was due to the fact that patients, because of their low income, sought medical management late. Therefore, the treatment strategy was neoadjuvant imatinib therapy for at least 6 to 12 months before resection. This results in a reduction in the size of the tumor, making it easier to remove. Similar data with large tumor sizes have been reported from other low-income countries of Africa and South America [6, 20, 21]. On the contrary, studies in Iceland, Korea, and Japan have found a median tumor size of about 4 cm [14, 22]. The large tumor size is the evidence of the impact of delayed diagnosis in low-income countries like Benin. Such locally advanced tumors led to complex resection in our setting. For example, in this case, depicted in Fig. 4, a 66 years old and had gastric GIST infiltrating the abdominal wall. He received neoadjuvant imatinib with a good response. At laparotomy, a tumor invading the spleen and pancreas remained. He underwent Complex resection of the gastric tumor involving the spleen and the tail of the pancreas. Unfortunately, this is a frequent case in our practice.

We noted a strong predominance of the fusiform cell type and the expression of KIT. In fact, GISTs are often spindle-shaped types and almost always express the KIT [2, 3, 16, 23]. Almost half of the tumors (n = 7) expressed DOG1. DOG1 is a sensitive and specific biomarker that can contribute to the diagnosis of GIST [24]. It is important to point out that the low income of patients contributes to diagnosis delay due to the high cost of immunohistochemistry in our country. The cost of an immunohistochemistry test is 157 dollars while the guaranteed minimum wage in Benin is 70 dollars. In addition, the CNHU HKM did not have a pathology laboratory equipped for immunohistochemistry during the study period. Therefore, immunohistochemistry was performed on specimens sent abroad (mainly in France). Moreover, exams such as molecular biology are required to improve treatment. Unfortunately, these diagnostic methods are not available in most sub-Saharan African countries such as Benin.

Most of our patients were at high risk of recurrence according to Joensuu’s modified NIH scoring system. Our data are similar to those of Egypt [6]. In Iceland, Korea, and Japan, few patients presented a high risk of recurrence [14, 22]. This could be explained by the large size of the tumors in the African series due to delay in diagnosis. However, other scores such as the peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), Onodera’s prognostic nutritional index (OPNI) and the Naples prognostic score (NPS) have recently been shown to be good predictors of outcome in GISTs preoperatively [25, 26].

The only potentially curative treatment of GISTs is a complete surgical resection [2, 3]. In situations where the tumor is locally advanced, resection is eligible if it is complete. Patients may receive adjuvant therapy (primarily imatinib in the first line and sunitinib in the second line) for up to three years, depending on their risk of recurrence. The alternative of a neoadjuvant therapy makes sense when the resection appears too complex or uncertain preoperatively. Surgery is considered when the maximum response is observed (after 6 to 12 months of treatment) [3]. Although imatinib treatment has not yet been standardized, this preoperative therapy is very effective. For example, in our study and others, it leads to a reduction in tumor size and facilitates surgical resection [27, 28].

Access to imatinib was difficult in Africa especially in Benin [7, 10]. The high cost of targeted therapies for GIST creates a significant barrier to providing cancer patients in low- and middle-income countries [11]. Until 2010 imatinib was not available in Benin [10]. A high risk of recurrence was associated to poor outcomes. But for the past five years, the GIPAP program has enabled patients with GIST to obtain imatinib free of charge. This has greatly improved the outcome of GIST in our country. However, an effort must be made to make second-line treatment, such as sunitinib and sorafenib, financially accessible. In fact, even if sorafenib is actually available in Benin, its cost (279 dollars) is prohibitive.

This study highlights the difficulty of managing GIST in low-income countries such as Benin. Its particularity lies in the diagnostic methods including histology but also immunohistochemistry. Its weaknesses are essentially the small sample size and the retrospective data collection.

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