P-OGC67 Gastric GISTs: Can presentation, Location and Radiological Features predict behaviour? – Experience in a UK cohort

Background Gastrointestinal stromal tumours (GISTs) most commonly arise in the stomach, vary significantly in behaviour and can be difficult to risk stratify accurately pre-operatively. They are increasingly being identified incidentally during endoscopies or cross-sectional imaging. They have malignant potential and but vary from very low to high-risk. Pre-operatively, histological diagnosis can be achieved by performing endoscopic ultrasound (EUS) guided fine-needle aspirate or biopsy, but samples often contain insufficient material. This study aims to assess other features help identify aggressiveness of GISTs pre-operatively to help guide management decisions. Methods This is a retrospective cohort study analysing patients treated surgically for GIST from 2011-2020 at a UK tertiary centre. Exclusion criteria were non-gastric GISTs and patients who received a different diagnosis post-operatively. Hospital electronic patient record and e-noting systems were used to collect data. Risk groups were stratified according to the NCCN risk classification for GIST. ‘Very low risk’ and ‘low risk’ groups were combined in the analysis to form the ‘lower risk’ group; ‘moderate risk’ and ‘high risk’ categories combined to form the ‘higher risk’ group. Statistical analyses were conducted using STATA version 15. Results 171 patients were included in total. OGD diagnosed gist on histology if ulcerated in 14.7% of cases. EUS biopsy was performed in 39% of cases pre-operatively – 84.6% of these were diagnostic. There was a higher proportion of higher risk GISTs in the GOJ/cardia region than lower risk GISTs (16.2% versus 6.7%), though this did not reach statistically significance (p = 0.32). A greater proportion of higher risk tumours were irregular in outline (p=.26), heterogenous (p = 0.003) and necrotic (p = 0.001) than lower risk tumours. In addition, higher risk tumours were significantly more likely to be exophytic than lower risk tumours, which were significantly more endophytic (p = 0.05). A ROC curve including all the variables had an AUC of 0.8971. Conclusions This is the largest analysis of gastric GISTs in a UK population. This study found that a higher proportion of higher risk tumours were irregular, heterogenous and necrotic than lower risk tumours. In this study, a greater proportion of higher risk tumours arose in the GOJ/cardia. In keeping with muscularis origin, endoscopic biopsy was found to be a poor diagnostic tool unless ulcerated. EUS and FNA biopsies had a much higher rate of histological confirmation. This knowledge might help facilitate a more individualised approach with non-operative surveillance in lower risk tumours or expedited surgery in higher risk lesions.

Surgical Resection Is Still Better Than Endoscopic Resection for Patients With 2-5 cm Gastric Gastrointestinal Stromal Tumours: A Propensity Score Matching Analysis

BackgroundThe management of 2-5 cm gastric gastrointestinal stromal tumours (GISTs) is still debated between surgeons and endoscopists. We aimed to investigate short-term and long-term outcomes between surgical resection (SR) and endoscopic resection (ER).MethodsThis study included 67 and 215 patients between 2010 and 2020 who underwent ER and SR, respectively. After propensity score matching, the clinical outcomes were compared. Individual patient information that requires special instructions is also summarized.ResultsAfter matching, the operation time (P=0.005) and postoperative hospital stay (P=0.005) were significantly longer in the SR group than in the ER group. However, there were no significant differences in blood loss (P=0.741), resection margin (P=1.000) or time to liquid diet (P=0.055). Statistical differences were also seen in en bloc resection (P<0.001) and adverse events (P=0.027). The recurrence rate did not differ significantly between the two techniques, and the mitotic index and ulceration were identified as independent prognostic factors of progression-free survival.ConclusionsER might be comparable to SR for the treatment of 2-3 cm gastric GISTs. SR is still considered the standard treatment for 3-5 cm gastric GISTs, while the intraoperative and postoperative information of ER should be recorded in detail and closely evaluated. Surgical resection is recommended if the tumour has a high mitotic index or mucosal ulceration.

Minimally Invasive Approach to Gastric GISTs: Analysis of a Multicenter Robotic and Laparoscopic Experience with Literature Review

Background: Gastrointestinal stromal tumors (GISTs) are most frequently located in the stomach. In the setting of a multidisciplinary approach, surgery represents the best therapeutic option, consisting mainly in a wedge gastric resection. (1) Materials and methods: Between January 2010 to September 2020, 105 patients with a primary gastrointestinal stromal tumor (GISTs) located in the stomach, underwent surgery at three surgical units. (2) Results: A multi-institutional analysis of minimally invasive series including 81 cases (36 laparoscopic and 45 robotic) from 3 referral centers was performed. Males were 35 (43.2%), the average age was 66.64 years old. ASA score ≥3 was 6 (13.3%) in the RS and 4 (11.1%) in the LS and the average tumor size was 4.4 cm. Most of the procedures were wedge resections (N = 76; 93.8%) and the main operative time was 151 min in the RS and 97 min in the LS. Conversion was necessary in five cases (6.2%). (3) Conclusions: Minimal invasive approaches for gastric GISTs performed in selected patients and experienced centers are safe. A robotic approach represents a useful option, especially for GISTs that are more than 5 cm, even located in unfavorable places.

GIST and Ghrelin: To Be or Not to Be?

Background: Ghrelin is the orexigenic hormone secreted mainly by the stomach. Its involvement in neoplastic development has been studied in gastrointestinal adenocarcinomas. Our paper aims to evaluate the influence of the ghrelin axis in gastrointestinal stromal tumors (GISTs). Materials and Methods: The study design included two groups of patients, 46 with gastric GISTs and 30 with obesity. Archived tissue samples were evaluated for the presence of gastritis and H. pylori. Immunohistochemical expression of ghrelin and its receptor (GHS-R) was assessed. Results: All GISTs showed absent immunohistochemical expression for ghrelin, while GHS-R displayed a particular pattern, with notable differences in intensity (p = 0.0256) and percentage of stained cells (p < 0.00001) in the periphery vs. core of tumors. Positive ghrelin expression was lower in the gastric mucosa of the first group compared to the second group (p < 0.001). Conclusion: The ghrelin axis can influence GISTs carcinogenesis through activation of GHS-R. A previously described direct autocrine/paracrine mechanism is not supported by our findings.

On the Track of New Endoscopic Alternatives for the Treatment of Selected Gastric GISTs—A Pilot Study

Background and Objectives: GISTs (Gastrointestinal stromal tumors) are the most common mesenchymal gastrointestinal tract tumours and are mainly located in the stomach. Their malignant potential depends on size, location, and type. Endoscopic techniques are a less invasive modality for patients not eligible for surgery. ESD (endoscopic submucosal dissection) is mainly used for the removal of smaller GISTs, with intraluminal growth and a more superficial location. Thus, R0 resection capability in some cases may be not sufficient, limited by tumour size, location in the gastric wall, and its connection level with the muscularis propria. In such cases, an endoscopic full-thickness resection can become a new alternative. In this retrospective pilot study, we evaluated ESD and hybrid resection techniques in terms of safety, efficacy, and disease recurrence for selected types of gastric GISTs. Materials and Methods: A retrospective comparison was conducted in a group of patients who underwent ESD or a hybrid technique combining endoscopic resection with endoscopic suturing using the OverStitch system (HT) for type II or III gastric GISTs. A total of 21 patients aged 70 ± 8 years underwent endoscopic resection. Seventeen lesions were treated with ESD and four with the HT. Results: R0 resection was achieved in all patients treated using HT (type III lesions) and in 53% of those treated with ESD (p = 0.08). None of the type III lesions treated with ESD were excised with R0. Lesions treated with R0 ESD resections were significantly smaller (1.76 ± 0.35 cm) than those with R1 ESD resections (2.39 ± 0.40 cm) (p < 0.01). The mean lesion size treated with the HT was 2.88 ± 0.85 cm. Conclusions: HT may be a new resection modality for large gastric GISTs with high muscularis propria connection grades. Further studies are required to evaluate its safety and efficacy and to form precise inclusion criteria for endoscopic resection techniques.

Laparoscopic Partial Gastrectomy for Large Gastric GISTs

Background: Gastrointestinal stromal tumors (GISTs) are considered the most common mesenchymal tumors in the gastrointestinal tract and the stomach is the most frequently site affected (50–60%). The safety and feasibility of laparoscopic surgery for gastric GISTs of sizes larger than 5 cm remains unclear. It depends on the surgical skills, tumor location and the learning curve of the surgeons. Methods: Between December 2013 and January 2021, thirty patients diagnosed with gastric GISTs underwent laparoscopic partial gastrectomy. This is a retrospective study done in surgical oncology unit, Oncology Center, Mansoura University, Egypt. Results: The most common tumor location was in the greater curvature in (46.7%). The mean tumor size was 7.2 cm (the largest was 13 cm). All of the patients underwent laparoscopic partial gastrectomy. Splenectomy was done for one patient only. The mean operative time was 152.67 minutes and the estimated blood loss (EBL) was 139.33 ml. The mean hospital stay was 3.53 days. The mean follows up period was 32.4 months. Conclusion: Laparoscopic resection for gastric GISTs has become a feasible method. Patients with large tumors have the same favorable outcomes as small tumors. Large-sized GISTs may receive neoadjuvant therapy to downstage the disease and make it amenable for laparoscopic resection.

Differential Expression of CADM1 in Gastrointestinal Stromal Tumors of Different Sites and with Different Gene Abnormalities

Gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor of the human gastrointestinal tract, differentiating toward the interstitial cell of Cajal (ICC), arises predominantly in the stomach and small intestine. Small intestinal GISTs appear to have worse prognosis than gastric GISTs. In a pilot study of a cDNA expression chip using several GISTs, we found that Cell Adhesion Molecule 1 (CADM1), which could contribute to tumor growth and infiltration, is expressed more strongly in small intestinal GISTs than gastric GISTs. In the present study, we examined CADM1 expression in GISTs of different sites and with different gene abnormalities using a large number of gastric and small intestinal GISTs. First, immunoblotting confirmed significantly higher CADM1 expression in small intestinal GISTs with exon 11 c-kit mutation than gastric GISTs with exon 11 c-kit mutation. Real-time PCR also revealed that small intestinal GISTs with exon 11 c-kit mutation showed significantly higher CADM1 mRNA than gastric GISTs with exon 11 c-kit mutation. Although most small intestinal GISTs showed high CADM1 mRNA expression regardless of gene abnormality types, different CADM1 expression was detected between gastric GISTs with c-kit mutation and those with PDGFRA mutation. Immunohistochemistry showed that many small intestinal GISTs were CADM1-positive but most gastric GISTs CADM1-negative or -indefinite. In the normal gastric and small intestinal walls, immunoreactivity of CADM1 was detected only in nerves, but neither in gastric ICCs nor small intestinal ICCs, indicating that the high CADM1expression in small intestinal GISTs might be acquired during tumorigenesis. Different CADM1 expression between gastric and small intestinal GISTs might be related to different prognoses between them. Further functional experiments are needed to elucidate the role of CADM1 on GIST biology, and there is a possibility that targeting therapy against CADM1 has a preventive effect for tumor spreading in small intestinal GISTs.

Correlation of endoscopic ultrasonography features with mitotic index in 2–5 cm gastric gastrointestinal stromal tumors

Background: Predicting the malignancy potential of gastrointestinal stromal tumor (GIST) before resection could improve patient management strategies, as gastric GISTs with a low malignancy potential can be safely treated endoscopically, but surgical resection is required for those tumors with a high malignancy potential. This study aimed to evaluate endoscopic ultrasound (EUS) features of 2–5 cm gastric GISTs that might be used to predict their mitotic index using surgical specimens as the gold standard. Patients and Methods: Forty-nine patients (30 females and 19 males; mean age 55.1 ± 12.7 years) who underwent EUS examinations, followed by surgical resections of 2–5 cm gastric GISTs were retrospectively reviewed. Results: The mean tumor size was 3.44 ± 0.97 cm (range 2.1–5.0 cm). A univariate analysis revealed no significant differences in age, sex, and tumor location in the low mitotic index and high mitotic index groups (all P > 0.05). In terms of EUS features, there were no significant differences in the mitotic indexes with respect to the shape, surface lobulation, border regularity, echogenicity, homogeneity, growth patterns, presence of mucosal ulceration, hyperechogenic foci, anechoic spaces, and hypoechoic halos (all P > 0.05). However, the tumor size was larger in the high mitotic index group than in the low mitotic index group (3.97 ± 1.05 vs. 3.27 ± 0.9 cm, P = 0.03). Conclusion: Conventional EUS features are not reliable for predicting the mitotic index of 2–5 cm gastric GISTs. Further modalities for predicting the mitotic index are needed to prevent unnecessary surgical resections in patients with a low risk of malignancy.