Gastrointestinal stromal tumours are the most common mesenchymal neoplasms of the gastrointestinal tract. They are characterized predominantly by activating alterations involving the KIT or PDGFRA tyrosine kinase pathways and demonstrate a wide spectrum of biological behaviour, ranging from indolent lesions to highly aggressive tumours with metastatic potential. Although GISTs can occur anywhere along the gastrointestinal tract, the stomach is the most frequent site, followed by the small intestine. Small bowel GISTs represent a relatively uncommon subgroup but are clinically important because they tend to have a less favourable prognosis than gastric GISTs of comparable size and mitotic activity. Tumour size, mitotic activity, anatomical site and tumour rupture are established determinants of recurrence risk. For localized disease, complete surgical resection remains the standard treatment. The objectives of surgery are complete removal of the tumour, preservation of the tumour pseudocapsule, avoidance of tumour rupture and achievement of an R0 resection whenever feasible. Routine lymphadenectomy is generally unnecessary because clinically significant nodal metastases are uncommon. However, the management of larger tumours presents a therapeutic dilemma. Neoadjuvant imatinib has therefore emerged as an important treatment strategy in selected patients. Current NCCN recommendations recognize neoadjuvant therapy for resectable GISTs in which surgery would otherwise result in significant morbidity (1). ESMO similarly considers preoperative treatment with imatinib appropriate when R0 surgery is not feasible without major sequelae and the tumour carries an imatinib-sensitive mutation (2). The 2023 GEIS guidelines recommend consideration of neoadjuvant imatinib for locally advanced GIST where tumour shrinkage may facilitate surgery (3). They emphasize multidisciplinary assessment, molecular profiling before treatment and early response assessment. Importantly, however, these guidelines do not establish 5 cm as a specific threshold for neoadjuvant treatment. The Japanese Clinical Practice Guidelines for GIST provide a weak recommendation for neoadjuvant imatinib in tumours measuring ≥10 cm or where incomplete resection is suspected, but acknowledge the low quality of evidence and absence of randomized trials demonstrating an overall survival or recurrence-free survival advantage for neoadjuvant treatment (4). This creates an important clinical question: Could a lower tumour-size threshold identify patients with small bowel GIST who may benefit from neoadjuvant therapy before they undergo potentially morbid upfront surgery? At our centre, 14 patients underwent surgery for small bowel GIST between December 2023 and August 2026. Of these, 4 had tumours larger than 5 cm. All four underwent upfront surgery. Despite R0 resection and pathologically clear margins, two patients subsequently developed recurrence. One patient developed an anastomotic leak and another died from postoperative complications. These observations prompted us to propose that tumour size >5 cm in small bowel GIST should be regarded as a trigger for multidisciplinary assessment and consideration of neoadjuvant therapy, rather than proceeding automatically to upfront surgery. The present study therefore aims to describe our institutional experience and generate a clinically relevant hypothesis for future prospective investigation. AIM To evaluate the surgical outcomes of patients with small bowel gastrointestinal stromal tumours treated at a single centre and to propose a role for neoadjuvant therapy in tumours measuring more than 5 cm. OBJECTIVES Primary Objective To assess the postoperative and oncological outcomes of patients undergoing surgery for small bowel GIST, with particular emphasis on tumours measuring >5 cm. Secondary Objectives 1. To determine the proportion of patients with tumours >5 cm. 2. To evaluate recurrence following surgical resection. 3. To assess postoperative complications, particularly anastomotic leak and postoperative mortality. 4. To examine outcomes following R0 resection in tumours >5 cm. 5. To compare the observed outcomes with contemporary guideline recommendations. 6. To propose a practical algorithm for consideration of neoadjuvant therapy in small bowel GIST >5 cm.

This was a single-centre observational case series of patients undergoing surgical treatment for small bowel GIST. The study included patients operated between: December 2023 and August 2026. A total of 14 patients with small bowel GIST underwent surgical treatment during the study period. Inclusion Criteria Patients were included if they: • Had a GIST originating from the small intestine. • Underwent surgical treatment at the study centre. • Had sufficient clinical and pathological information for assessment. • Had a confirmed or subsequently confirmed diagnosis of GIST. Exclusion Criteria Patients were excluded if: • The primary tumour originated from the stomach, colon, oesophagus or rectum. • The final diagnosis was not GIST. • Adequate clinical or pathological information was unavailable. DATA COLLECTION The following variables were assessed: Demographic variables, Tumour-related variables, Treatment-related variables, Outcome variables Tumor size classification For the purpose of the present analysis, tumours were categorized into two groups: The >5-cm threshold was selected as the principal focus of the present study because of the observed recurrence and postoperative outcomes in this subgroup. This threshold is proposed by the investigators as a potential clinical trigger for multidisciplinary consideration of neoadjuvant therapy and is not presented as an established guideline-defined indication. Surgical Management All patients underwent surgical treatment according to the anatomical location and extent of the tumour. The fundamental surgical objectives were: Complete tumour excision, preservation of the tumour pseudocapsule, avoidance of tumour rupture, achievement of R0 resection where feasible, appropriate bowel reconstruction and avoidance of unnecessary lymphadenectomy. Current international guidelines similarly regard complete surgical resection as the standard treatment for localized GIST. Pathological assesment Pathological assessment included: Tumour size, Tumour site, Histological pattern, Mitotic activity, Necrosis, Tumour rupture, Resection margins, Immunohistochemistry, Risk stratification. Where available, molecular analysis of KIT and PDGFRA mutations was considered. Risk assessment should incorporate tumour size, mitotic activity, anatomical site and tumour rupture rather than relying on margin status alone. The NIH-modified and AFIP/Miettinen systems are established approaches for risk assessment. OUTCOME DEFINITIONS R0 Resection: No macroscopic or microscopic residual tumour following resection. Recurrence: Radiological or pathological evidence of recurrent disease following definitive treatment. Anastomotic Leak: Evidence of leakage from the bowel anastomosis requiring conservative, interventional or operative management. Postoperative Mortality: Death occurring as a consequence of postoperative complications (Clavein-Dindo - 5). STATISTICAL ANALYSIS Continuous variables were summarized using appropriate descriptive statistics. Categorical variables were expressed as frequencies and percentages. Given the small sample size of 14 patients, the analysis was primarily descriptive. No attempt was made to draw definitive causal conclusions regarding tumour size, recurrence or the benefit of neoadjuvant therapy. The subgroup of patients with tumours >5 cm was specifically described because it formed the basis of the study hypothesis.

Table1: Distribution into groups according to size Group-A Tumor <5cm Group-B Tumor >5cm Overall Cohort A total of 14 patients underwent surgery for small bowel GIST between December 2023 and August 2026. Distribution according to tumor size Ten patients had tumours measuring less than 5 cm, while four patients had tumours measuring more than 5 cm. OUTCOMES IN PATIENTS WITH TUMOURS >5 CM All four patients with tumours >5 cm underwent upfront surgery. Despite achieving R0 resection with pathologically clear margins: 2 of 4 patients developed recurrence, 1 patient developed an anastomotic leak, 1 patient died due to postoperative complications. Thus, the recurrence rate in the >5-cm subgroup was 50%. The postoperative mortality rate in this subgroup was 25% and the anastomotic leak rate was 25%. OBSERVATION: The most important observation from this series was that R0 resection did not eliminate the risk of recurrence in patients with tumours >5 cm. Two of the four patients with tumours >5 cm developed recurrence despite apparently complete resection with clear pathological margins. This observation reinforces an important principle in GIST surgery: An R0 margin is a surgical endpoint, but it does not necessarily equate to low biological risk. Tumour size, anatomical site, mitotic activity and tumour rupture contribute to recurrence risk independently of margin status. This is consistent with established GIST risk-stratification systems.

The present study represents the surgical experience of a single centre involving 14 patients with small bowel GIST over a period of approximately 33 months. Although the cohort is small, the findings raise an important question regarding the management of small bowel GISTs measuring more than 5 cm. The central observation was that all four patients with tumours >5 cm underwent upfront surgery. Despite R0 resection and pathologically clear margins, two patients developed recurrence. In addition, one patient developed an anastomotic leak and another died from postoperative complications. The findings therefore suggest that the clinical problem associated with large small bowel GIST may extend beyond the ability to obtain a clear pathological margin. The reason small bowel GISTs need special consideration is that the biological behaviour of GIST varies according to anatomical site. Small bowel GISTs generally carry a less favourable prognosis than gastric GISTs. Established risk models incorporate anatomical location along with tumour size and mitotic activity because these factors influence recurrence risk(5). Previous studies of small intestinal GIST have reported substantial recurrence following apparently curative surgery. In one large historical series, 44 of 85 patients undergoing curative resection developed recurrence, with the liver being the most common site. High mitotic activity and other pathological features were associated with inferior disease-free survival(6). These data support the concept that small bowel GIST should not simply be considered equivalent to gastric GIST in terms of biological behaviour(7). For a small, mobile small bowel GIST, segmental bowel resection with primary anastomosis is usually straightforward. The situation changes as the tumour becomes larger(8). A bulky tumour may: occupy a large portion of the abdominal cavity; involve multiple bowel loops; become closely adherent to adjacent structures; compromise the mesentery; requires a larger bowel resection; make bowel reconstruction more difficult; increase the risk of anastomotic complications; becomes friable and susceptible to rupture during manipulation. The objective of surgery is not merely to achieve a microscopic negative margin. The surgeon must also achieve safe oncological resection without tumour rupture and without unnecessary loss of normal bowel or adjacent organs. This is where neoadjuvant therapy may provide a potential advantage. WHAT CURRENT GUIDELINES RECOMMEND Current guidelines already recognize the concept of preoperative treatment, although they do not establish >5 cm as an independent indication. The NCCN guideline framework includes neoadjuvant imatinib among treatment options for resectable GISTs where surgery would otherwise result in significant morbidity. The ESMO-EURACAN-GENTURIS guideline states that when R0 surgery is not feasible or would result in major sequelae, preoperative imatinib is standard for a tumour harbouring a sensitive mutation. The GEIS guideline similarly recommends considering neoadjuvant imatinib for locally advanced GIST when tumour shrinkage can facilitate surgery. It emphasizes multidisciplinary decision-making and molecular profiling before initiation of therapy. The Japanese guideline provides a weak recommendation for neoadjuvant imatinib in GIST ≥10 cm or when incomplete resection is suspected, while acknowledging that the evidence quality is low and randomized evidence demonstrating an OS or RFS benefit is lacking. Thus, the existing guidelines support the principle of neoadjuvant therapy but do not currently establish a 5-cm threshold. Our rationale is based on three considerations: 1. Small bowel GISTs have a relatively unfavourable biological profile compared with gastric GISTs. 2. Larger tumours may be associated with greater surgical complexity and potential morbidity. 3. In our series, half of the patients with tumours >5 cm developed recurrence despite R0 resection and clear pathological margins. Therefore, we propose that the identification of a small bowel GIST >5 cm should prompt a deliberate question: “Would neoadjuvant treatment improve the quality and safety of the subsequent surgical procedure?” rather than proceeding automatically to upfront surgery. Imatinib is generally used at a dose of 400 mg/day for sensitive GISTs. NCCN, ESMO and GEIS all recognize imatinib-sensitive GIST as the principal setting for neoadjuvant treatment. Early radiological response assessment is important. GEIS recommends assessment as early as approximately 4 weeks because an ineffective treatment should not unnecessarily delay potentially curative surgery. Surgery is generally considered after maximal useful response rather than after an arbitrarily fixed duration(9). Neoadjuvant treatment should not be used simply to delay surgery. If imaging demonstrates progression on imatinib, or if the tumour is not responding appropriately, the treatment strategy should be reconsidered promptly. Similarly, if the tumour is already easily resectable with minimal morbidity, neoadjuvant treatment may provide little additional surgical benefit. Therefore, The objective of neoadjuvant treatment is to improve surgery — not to replace surgery. STRENGTHS: The strengths of this study include: 1. It represents real-world institutional experience. 2. It specifically evaluates small bowel GIST rather than combining gastric and small bowel tumours. 3. It identifies a clinically important subgroup based on tumour size. 4. It demonstrates recurrence despite R0 resection in the >5-cm subgroup. 5. It generates a specific and testable hypothesis regarding a >5-cm threshold for consideration of neoadjuvant therapy. LIMITATIONS: The study has several important limitations. 1. Small sample size. Only 14 patients were included, with only four patients in the >5-cm subgroup. 2. Single-centre design. The findings may reflect institutional surgical practice and patient selection. 3. No control group. There was no comparison between upfront surgery and neoadjuvant therapy. 4. No neoadjuvant cohort. Because all four patients with tumours >5 cm underwent upfront surgery, the study cannot demonstrate that neoadjuvant therapy would have prevented recurrence or postoperative complications. Potential confounding Important pathological and molecular variables such as mitotic rate, KIT/PDGFRA mutation status, tumour rupture and risk category are not yet incorporated into the current dataset. Follow-up duration Because the study extends only to August 2026, the follow-up duration varies between patients and may be insufficient to capture all late recurrences. Causality The study cannot establish that tumour size directly caused recurrence, anastomotic leak or mortality. Therefore, the recommendation should be considered hypothesis-generating.

Small bowel GISTs are uncommon gastrointestinal malignancies but represent a clinically important subgroup because of their potential for aggressive behaviour and recurrence. In this single-centre series of 14 patients operated between December 2023 and August 2026, 10 patients had tumours <5 cm and 4 had tumours >5 cm. All four patients with tumours >5 cm underwent upfront surgery. Despite R0 resection and pathologically clear margins, two patients subsequently developed recurrence. One patient developed an anastomotic leak and another died due to postoperative complications. Although these observations cannot establish a causal relationship between tumour size and adverse outcomes, they raise a clinically important question regarding the optimal management of larger small bowel GISTs. Based on our institutional experience, we therefore propose that small bowel GISTs measuring >5 cm should trigger multidisciplinary evaluation for neoadjuvant therapy, rather than proceeding automatically to upfront surgery. The proposed threshold should not be interpreted as an absolute indication for treatment. Patients with >5-cm tumours that are readily resectable with low morbidity may still appropriately undergo primary surgery. Neoadjuvant imatinib should particularly be considered when tumour reduction is expected to: facilitate R0 resection; reduce the risk of tumour rupture; avoid extensive bowel or multivisceral resection; preserve bowel function; or reduce operative morbidity. The present study therefore proposes a new hypothesis rather than a new standard of care: In small bowel GIST, a tumour size >5 cm may represent a clinically useful threshold for considering neoadjuvant imatinib, particularly when upfront surgery is expected to carry significant oncological or operative morbidity. Prospective multicentre studies comparing upfront surgery with neoadjuvant therapy in small bowel GISTs >5 cm are required before this threshold can be incorporated into formal treatment guidelines(10). RECOMMENDATIONS Based on the present experience, we propose the following: 1. All patients with small bowel GIST should undergo multidisciplinary evaluation. 2. Tumour size should be documented accurately on baseline imaging. 3. Tumours measuring >5 cm should trigger consideration of neoadjuvant therapy, rather than automatically proceeding to upfront surgery. 4. Biopsy and molecular characterization should be obtained when neoadjuvant treatment is being considered. 5. Response should be evaluated radiologically during treatment. 6. Surgery should be undertaken once adequate tumour response has been achieved and the optimal surgical window has been reached.

1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Gastrointestinal Stromal Tumors (GISTs). NCCN. 2. Casali PG, Abecassis N, Aro HT, et al. Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2022. 3. Serrano C, Mariño-Enríquez A, Tao DL, et al. 2023 GEIS Guidelines for gastrointestinal stromal tumors. Ther Adv Med Oncol. 2023. 4. Japanese Society of Clinical Oncology. English version of Japanese Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST). 5. DeMatteo RP, Lewis JJ, Leung D, et al. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. 6. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 7. Miettinen M, Makhlouf H, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol. 8. Rutkowski P, Hompes D. Combined therapy of gastrointestinal stromal tumors. Chirurgia. 9. Eisenberg BL, Judson I. Surgery and imatinib in the management of GIST: emerging approaches to adjuvant and neoadjuvant therapy. Ann Surg Oncol. 10. National Cancer Institute. Gastrointestinal Stromal Tumors Treatment (PDQ). 11. Indian Council of Medical Research. Consensus document for the management of gastrointestinal stromal tumors. The ICMR document recognizes individualized preoperative imatinib for very large localized tumours, tumours at risk of bleeding/rupture, and cases where R0 resection is unlikely.