|Year : 2022 | Volume
| Issue : 4 | Page : 432-438
Clinicopathological features, risk profile assessment, and the surgical outcome of gastrointestinal stromal tumors in Lagos, Nigeria
Olanrewaju Samuel Balogun1, Adedapo Olumide Osinowo1, Fatimah Biade Abdulkareem2, Olugbenga O Ajayi2, Oluwole Ayoola Atoyebi1, John Taiwo Da Rocha-Afodu1
1 Department of Surgery, General Surgery Unit, Lagos University Teaching Hospital, Lagos, Nigeria
2 Department of Anatomic and Molecular Pathology, Lagos University Teaching Hospital, Lagos, Nigeria
|Date of Submission||23-Aug-2021|
|Date of Decision||29-Dec-2021|
|Date of Acceptance||21-Jan-2022|
|Date of Web Publication||16-Nov-2022|
Olanrewaju Samuel Balogun
Department of Surgery, College of Medicine, Lagos University Teaching Hospital, University of Lagos
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs originate from the interstitial cells of Cajal and are most commonly found in the stomach. Most available reports on GISTs in the Sub-Sahara Africa were in case reports and case series. Aim: To report our local experience and challenges in the management of GISTs in 33 patients in Lagos, Nigeria. Methodology: This is a descriptive study of adult patients of 16 years and above managed for GISTs at the Lagos University Teaching Hospital and some Lagos private hospital facilities between January 2015 and March 2021. Information on the patients' demographic characteristics, clinicopathological features, surgery performed, and postoperative complications were retrieved from the hospital's medical records for analysis. Data analysis was carried out using IBM SPSS Statistics for Windows, Version 23.0., Armonk, NY, USA: IBM Corp. Results: Thirty-three patients comprising 19 males and 14 females with a male: female ratio of 1.4:1 were included in the study. The mean age at presentation was 52.5 years. Abdominal pain (69.7%) and anemic symptoms (45.4%) were the principal modes of presentation. Abdominal computed tomography (CT) scan revealed stomach as the primary source of GISTs in 75.8% of patients. Forty-five percent of the patients had CT features of local organ invasion and 27.2% had features of metastasis. Surgical resection was feasible in 28 (84.8%) patients. Postoperative mortality was recorded in two patients with recurrent GISTs. Histological cell types were spindle cell (57.6%), mixed spindle and epithelioid (24.2%), and epithelioid (18.2%). Joensuu high-risk tumors (64. 3%) were the most prevalent in our series. Conclusion: Advanced-stage disease and features of anemia were hallmarks of GISTs among patients in this series. Surgical resection of GIST may be possible in some cases of advanced disease. Spindle cell types and high-risk GISTs were the most common pathological varieties in our patients.
| Abstract in French|| |
Contexte: Les tumeurs stromales gastro-intestinales (GIST) sont les tumeurs mésenchymateuses les plus courantes du tractus gastro-intestinal. Les GIST proviennent des cellules interstitielles de Cajal et se trouvent le plus souvent dans l'estomac. La plupart des rapports disponibles sur les GIST en Afrique subsaharienne étaient des rapports de cas et des séries de cas. Objectif: rendre compte de notre expérience locale et des défis dans la gestion des GIST chez 33 patients à Lagos, au Nigeria. Méthodologie: Il s'agit d'une étude descriptive de patients adultes de 16 ans et plus pris en charge pour des GIST à l'hôpital universitaire de Lagos et dans certains établissements hospitaliers privés de Lagos entre janvier 2015 et mars 2021. Informations sur les caractéristiques démographiques des patients, les caractéristiques clinicopathologiques, la chirurgie effectuée, et les complications postopératoires ont été extraites des dossiers médicaux de l'hôpital pour analyse. L'analyse des données a été effectuée à l'aide d'IBM SPSS Statistics pour Windows, version 23.0., Armonk, NY, États-Unis: IBM Corp. l'étude. L'âge moyen à la présentation était de 52,5 ans. Les douleurs abdominales (69,7 %) et les symptômes anémiques (45,4 %) étaient les principaux modes de présentation. La tomodensitométrie abdominale (TDM) a révélé que l'estomac était la principale source de GIST chez 75,8 % des patients. Quarante-cinq pour cent des patients présentaient des caractéristiques CT d'invasion d'organes locaux et 27,2 % présentaient des caractéristiques de métastases. La résection chirurgicale était réalisable chez 28 (84,8 %) patients. La mortalité postopératoire a été enregistrée chez deux patients avec des GIST récurrents. Les types de cellules histologiques étaient les cellules fusiformes (57,6 %), les cellules mixtes fusiformes et épithélioïdes (24,2 %) et les épithélioïdes (18,2 %). Les tumeurs à haut risque de Joensuu (64,3 %) étaient les plus répandues dans notre série. Conclusion: La maladie à un stade avancé et les caractéristiques de l'anémie étaient les caractéristiques des GIST chez les patients de cette série. La résection chirurgicale des GIST peut être possible dans certains cas de maladie avancée. Les types de cellules fusiformes et les GIST à haut risque étaient les variétés pathologiques les plus fréquentes chez nos patients.
Mots clés: Bilan, tumeurs stromales gastro-intestinales, pathologie, risque, gestes chirurgicaux
Keywords: Assessment, gastrointestinal stromal tumors, pathology, risk, surgical procedures
|How to cite this article:|
Balogun OS, Osinowo AO, Abdulkareem FB, Ajayi OO, Atoyebi OA, Rocha-Afodu JT. Clinicopathological features, risk profile assessment, and the surgical outcome of gastrointestinal stromal tumors in Lagos, Nigeria. Ann Afr Med 2022;21:432-8
|How to cite this URL:|
Balogun OS, Osinowo AO, Abdulkareem FB, Ajayi OO, Atoyebi OA, Rocha-Afodu JT. Clinicopathological features, risk profile assessment, and the surgical outcome of gastrointestinal stromal tumors in Lagos, Nigeria. Ann Afr Med [serial online] 2022 [cited 2022 Dec 7];21:432-8. Available from: https://www.annalsafrmed.org/text.asp?2022/21/4/432/361259
| Introduction|| |
Gastrointestinal stromal tumors (GISTs) are clinically heterogeneous and the most common type of mesenchymal tumors of the gastrointestinal tract., GISTs are nonepithelial and they constitute about 1% of all gastrointestinal cancers. GISTs have variable biological behavior. About 20%–25% of gastric and 40%–50% of small intestinal GISTs are clinically malignant. GISTs occur mostly in the stomach and the proximal small bowel; less commonly GISTs can be found in the omentum, the mesentery, and the peritoneum.,,
GISTs arise from the interstitial cells of Cajal found in the muscle layer of the gastrointestinal tract. GIST cells are classified into spindle cell, epithelioid cell, and mixed types (spindle and epithelioid cells) [Figure 1] on hematoxylin and eosin (H and E) stains. GISTs cell types and size have prognostic significance., Immunohistochemical studies for the expression of GIST tumor receptors CD117 and DOG1 are useful in confirming the diagnosis of GISTs and excluding other close histological differential diagnosis.
|Figure 1: Histological types (H and E stains) of gastrointestinal intestinal stromal tumor. (a) Spindle cell, (b) Epithelioid cells,(c)Mixed (spindle + epithelioid) cells|
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GISTs are asymptomatic in most cases until the tumor attains a larger size. Several GISTs have been discovered during the investigation of other abdominal pathologies. Gastric GIST, in particular, constitutes an important differential diagnosis of upper gastrointestinal bleeding with an estimated prevalence of 50%–100%. Abdominal ultrasound can be used for diagnosing GIST >5 cm. Computed tomography (CT) and magnetic resonance imaging(MRI) scans are invaluable in determining the size of the tumor, presence of necrosis, tumour vascularity, invasion of adjacent structures and presence of metastasis. Endoscopic diagnosis of GISTs requires endoscopic ultrasound scan and fine needle aspiration. The regular endoscopic forceps biopsy has poor diagnostic yield as the tumor originates from the muscularis propria.
Surgery is the cornerstone for treatment of GISTs. Complete surgical resection with adjuvant imatinib resection may offer hope for a cure. Neoadjuvant imatinib helps downsize the tumor and permit organ-preserving surgery., Prognostic factors after resection of GISTs depends on the tumor, the size, location, mitotic index, intraoperative tumor spillage, age and gender., These factors are components of Joensuu National Institute of Health (NIH) risk criteria and armed forces institute of pathology scores which are used in risk stratification and prognosis in GISTs. The focus of this paper is to examine the clinicopathological characteristics, management outcome, and challenges in the treatment of GISTs in our center. This is needed to document our local experience and compare our outcome with other published series.
| Methodology|| |
This is a descriptive retrospective study of cohorts of 33 adult patients aged 16 years and above and managed at the General Surgery Unit of the Lagos University Teaching Hospital and some private hospital facilities in Lagos between January 2015 and March 2021. Approval for this study was obtained from the Ethics Research Committee of the Lagos University Teaching Hospital. Data for the study were retrieved from the medical records and the histopathological reports of the patients. Our inclusion criteria were adult patients aged 16 years and above with radiological and pathological diagnosis of gastrointestinal stromal tumor on H and E staining procedure [Figure 1]. All pathological specimen slides were reviewed by the pathologists (3rd and 4th authors) for the confirmation of histological diagnosis and prognostic risk stratification. Relevant information recorded in the study pro forma for analysis were patients' demographic characteristics, onset of symptoms, clinicopathological features, surgery performed, postoperative morbidity and mortality, histology, and immunohistochemistry results.
Using the NIH consensus criteria (the Joensuu risk-stratification criteria), which comprises 4 prognostic factors, namely, tumor size, tumor site, mitotic count, and tumor rupture, the risk of recurrence and hence the need for adjuvant therapy tumor specimen was classified as high risk, intermediate risk, and low risk.
Data analysis was carried out using IBM SPSS Statistics for Windows, Version 23.0., Armonk, NY, USA: IBM Corp. Categorical data were presented in simple proportion. Continuous data were expressed in median and interquartile range for nonparametric data and ranges.
| Results|| |
There were 33 patients comprising 19 males and 14 females in this study giving a male-to-female ratio of 1.4:1. The age range of the patients was between 31 and 75 years. The modal age was within the 5th decade of life with 9 (27.3%) patients [Table 1]. The mean age at presentation was 52.5 ± 12.7 years. Onset of clinical symptoms to presentation ranged from 2 days to 8 years. The major presenting symptoms were abdominal pain in 23 patients (69.7%), anemic symptoms (dizziness, fainting attacks, and palpitation) in 15 patients (45.4%), abdominal mass in 15 patients (45.4%), and weight loss in nine patients (27.3%) [Table 2]. Essential hypertension, the most common comorbidity in the study, was recorded in six patients [Table 2].
CT identified the primary site of GIST in 30 out of 33 patients in this series. Primary GISTs found in multiple sites constituted the remaining 3 cases and were classified as nonspecific [Table 3]. The most common CT-reported location of GIST was in the stomach in 25 patients (75. 8%). Local invasion of GISTs to adjacent organs was documented in the abdominal CT scan of 15 patients (45.5%). Nine patients (27.2%) had abdominal CT features of metastasis (peritoneal and small bowel seedlings, liver, and small bowel) at presentation [Table 3]. Fifteen patients in this series were evaluated with upper gastrointestinal endoscopy; of these, ulcerated bleeding gastric tumor [Figure 2] was found in 6 patients and a gastric mass in the remaining nine patients.
|Figure 2: Bleeding gastric fundal gastrointestinal stromal tumors seen with a retroflexed maneuver at endoscopy|
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|Table 3: Location and complications of the primary tumor on computed tomography features (n=33)|
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Surgical resection of GISTs was carried out in 28 (84.8%) out of 33 patients. The remaining 5 patients had advanced or unresectable tumors and were commenced on neoadjuvant imatinib therapy after histological confirmation of the tumor via ultrasound-guided biopsy. Even though many of the patients required multivisceral resection (en bloc excision of locally infiltrated tissues) procedures, the surgical procedures performed for the primary GISTs were open wedge (sleeve) gastric resection (16 patients), open distal gastrectomy (two patients), laparoscopic wedge excision (two patients), segmental small bowel resection (three patients), left hemicolectomy (one patient), and transverse colectomy (one patient). In three patients, procedures done were not specified [Figure 3] and [Table 4]. Eight (28.6%) out of 28 patients who had surgery developed complications in the post-operative period. Wound dehiscence from surgical site infection and tumour recurrence were the most frequent complications [Table 4]. There were 2 mortalities in the review, one of which was due to postoperative enterocutaneous fistula following surgery for obstructing recurrent GIST [Table 4].
|Figure 3: Huge gastric fundal gastrointestinal stromal tumors with local infiltration of the adjacent anterolateral abdominal wall and multiple liver metastasis|
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|Table 4: Surgery performed according to the site of the tumour(n = 28) and post-operative complications(n = 8)|
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The size of the primary tumor was estimated by the maximum dimension of the tumor as reported by the CT scan and histology of the excised specimen. The primary tumor size as recorded in this series ranged from 6 to 27 cm. Reported histologic cell types were spindle cell (57.6%), mixed spindle and epithelioid (24.2%), and epithelioid (18.2%) [Table 5]. One patient in this series had metastatic GISTs in lymph nodes harvested at surgery. Immunohistochemistry for CD117 and DOG antigens were carried out in 9 patients. Immunohistochemical staining was positive for CD117 and DOG tumor antigens in 7 tumor specimens. The remaining 2 specimens showed CD117 positivity in one and DOG positivity in the other. According to the Joensuu criteria, tumor specimens were evaluated in 28 patients who had surgery. High-risk tumors were the most prevalent (64. 3%). Intermediate-risk and low-risk categories accounted for 21.4% and 14.2%, respectively [Table 5].
|Table 5: Pathologic characteristics of the tumor specimen and Joensuu risk-stratification of tumor specimens|
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| Discussion|| |
The finding of a slightly higher proportion of GISTs in male patients in this study is in concordance with the pattern of sex distribution reported by Abdulkareem et al. However, no gender disparity was noted in a systematic review on GIST in Nigeria by Ogun et al. There appears to be no universal agreement in the sex distribution of GISTs. While some large-scale studies have reported a higher prevalence of GIST in males,, a recent systematic global review of the epidemiology of GIST reported equal distribution of GISTs in most studies. The peak age of presentation of GISTs between the 5th and 6th decade of life was in keeping with findings of a local systemic review on GISTs. The mean age of 52 years in this study was slightly lower than those reported by Ogun. Manrique et al. in Peru reported the mean age of 64 years. Søreide et al. reported that the median age of GISTs in the mid-60s was documented in most studies. The mean age of our patients may suggest that GISTs in our environment probably occur in relatively younger patients when compared to the global average.
Clinical presentation of GISTs is influenced by the tumor size and location. GISTs have also been diagnosed as an incidental finding in otherwise asymptomatic patients undergoing screening investigations in a population based studies by Nilsson et al. Similar to the findings in some hospital-based studies,, there was no asymptomatic patient in our series and none of the patients was diagnosed as an incidental finding.
Gastrointestinal symptoms in GISTs are variable with no pathognomonic features. The predominant symptoms in our patients were abdominal pain, anemic symptoms, and weight loss. Anemic symptoms were deduced from histories of dizziness, fainting spells, or blood transfusion within the duration of abdominal symptoms. Some studies and reviews reported abdominal pain as the most common symptoms,,, gastrointestinal bleeding constituted the most prevalent symptoms in some series with predominance of gastric GISTs., Gastrointestinal bleeding in GISTs may occur as an acute presentation and should be considered a differential diagnosis of massive gastrointestinal bleeding in middle-aged patients in our environment. Chronic gastrointestinal bleeding in GISTs has a more insidious course with occult blood positive stool or recurrent melena. Melena in this study occurred at a higher frequency than hematemesis. Gastrointestinal bleeding in GISTs has been identified as an independent predictor of poor prognosis. Rare symptoms of GISTs such as intestinal obstruction, dyspepsia and dysphagia, and bowel perforation were found in a minority of patients in this study. Regardless of the presenting symptoms, an abdominal CT finding of local invasion of adjacent structures [Figure 3] in 45.5% of our patients and features of metastasis in 27.2% were indicative of delayed presentation in many of our patients.
The principal aim of surgery in GISTs is to achieve a negative tumor resection margin. For a local disease, this can be accomplished by wedge resection for gastric fundal GISTs [Figure 4]a or segmental bowel resection for intestinal GISTs. Lymph node dissection is not indicated as GISTs rarely spread to lymph nodes. Only one patient in this series had lymph node metastasis. Current evidence suggest that patients with advanced, metastatic, and recurrent GISTs should be managed with neoadjuvant imatinib chemotherapy before considering surgery.,,, This is because GISTs are known to be highly sensitive to imatinib mesylate, but resistance of about 10% has been reported within 3–6 months of neoadjuvant treatment and this may rise to additional 40%–50% within 2 years even despite an initial partial response or disease stabilization. Neoadjuvant imatinib mesylate chemotherapy is believed to offer good symptom control by reduction in the tumor mass and risk of intraoperative tumor rupture. Moreover, neoadjuvant imatinib therapy facilitates safer tumor resection and organ preservation.,, Our experience with neoadjuvant imatinib is limited as only three patients in this study were on this regimen. Obtaining samples for preoperative diagnosis of GISTs was challenging in most of our patients. Ultrasound-guided percutaneous procedures for tissue biopsy were not readily available in our institution. Endoscopic ultrasound/fine needle biopsy and mucosal incision-assisted biopsy facilities for GISTs diagnosis are also lacking in our practice. Our principal considerations for selecting patient with resectable GISTs for surgery were radiological evidence of resectability, worsening abdominal pain, and constitutional symptoms like weight loss. Among 25 patients with gastric GISTs, 2 selected patients with an exophytic “hanging” GIST had laparoscopic wedge resection [Figure 4]b. Open distal gastrectomy was performed in two patients, but one of them had to be reoperated for efferent loop obstruction. Wound dehiscence from superficial surgical site infection after surgery was the most common complication in this study. One of the two mortalities in our series was in a patient who had surgery for recurrent multiple GISTs causing intestinal obstruction. The patient had poor compliance to imatinib mesylate therapy after the primary surgery.
|Figure 4: (a) A large gastric fundal gastrointestinal stromal tumors during open surgical wedge excision. (b) Laparoscopic stapled wedge resection of a pedunculated gastric gastrointestinal stromal tumors|
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The proportion of histologic cell types in our study was similar to the experience in some series., Spindle cell type was the most common in our patients. However, immunohistochemistry which is confirmatory for GISTs was not readily available in our center. Only 9 patients had immunohistochemical confirmation of GISTs. Tumor grading according to the Joensuu's risk-stratification criteria showed that high-risk GISTs with characteristic features of increased mitosis and large size predominated in our series. High-risk GISTs have high tendency for relapse and tumor progression. The majority of high-risk GISTs in this study provided an insight into the delayed pattern of presentation, aggressive biological behavior of the majority of GISTs occurring in our patients. Overall post-operative complication rate of 28.6% in this study is a reflection of the advanced stage of presentation of GISTs in the majority of our patients. Neo-adjuvant and adjuvant therapies for GISTs may improve surgical outcomes in most of our patients.
GISTs are considered to be rare tumors, hence a reflection of the small sample size in this study. GISTs are considered to be rare tumors, hence a reflection of the small sample size in this study. This limits the extent of our statistical analysis. A local future prospective longitudinal study on the biology of GISTs, response to imatinib therapy and surgical outcome will provide more insight on the prognosis of GISTs in our patients.
| Conclusion|| |
GIST in this study had peak of occurrence in the 5th decade of life with slight male preponderance. Advanced-stage disease, features of anemia, and delayed presentation were hallmarks of GISTs in our center. Resection of GIST may be possible in many cases of locally advanced disease. Histologic pattern of GIST and the risk profile in our patients is similar to other published series. A local study on the sensitivity of GISTs to imatinib in neoadjuvant and adjuvant settings may give more insight on the biology of GISTs in our patients.
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Conflicts of interest
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]