The synchronous occurrence of a gastrointestinal stromal tumor (GIST) and pancreatic ductal adenocarcinoma (PDAC) is exceptionally rare and poses significant diagnostic and therapeutic challenges. We report a 67-year-old female presenting with biliary obstruction, right upper quadrant pain, and dyspeptic symptoms. CT imaging revealed a pancreatic head mass, while a submucosal gastric lesion was identified only intraoperatively. Laparotomy enabled excision of a pedunculated gastric GIST, whereas the unresectable pancreatic tumor involved critical vascular structures, necessitating a palliative double bypass comprising cholecystectomy, hepaticojejunostomy, gastrojejunostomy, and enteroenterostomy. Histopathology confirmed a low-risk GIST and a moderately differentiated PDAC with distinct immunohistochemical profiles, supporting the presence of two independent primary tumors.

This case underscores the critical importance of meticulous intraoperative exploration, particularly in the presence of atypical or incidentally discovered lesions, and demonstrates the durable palliation afforded by surgical bypass in unresectable PDAC. Beyond the clinical context, potential molecular overlaps—activation of MAPK/ERK and PI3K/AKT/mTOR pathways, VEGF-mediated angiogenesis, and defects in DNA repair—provide a plausible biological basis for the synchronous occurrence of these otherwise unrelated neoplasms, informing potential strategies for personalized therapy

Background: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A), represents an important component of systemic therapy for metastatic colorectal cancer (mCRC). By inhibiting angiogenesis and promoting vascular normalization, bevacizumab enhances the efficacy of cytotoxic drugs. However, despite proven benefits, some uncertainties remain regarding its safety profile, particularly the risk of gastrointestinal perforation and other vascular toxicities. Materials and Methods: This retrospective, single-center, observational study included patients with histologically confirmed mCRC treated with combination chemotherapy and bevacizumab (FOLFOX/FOLFIRI + bevacizumab) at the Oncology Department of Zemun Clinical Hospital Center between July 2022 and July 2025. Efficacy was assessed according to RECIST 1.1 criteria, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and duration of response (DoR). Adverse events were classified according to CTCAE v6.0. Results: A total of 74 patients were analyzed (56.8% male; mean age 67 ± 9 years). The median PFS was 6.5 months (IQR 3–9.8), and DoR 7.3 months (95% CI 5.2–9.5). ORR was 35.1%, and DCR 82.4%. The most common toxicities were hypertension (12.2%) and proteinuria (10.9%), while gastrointestinal perforation was observed in 4.1% of patients—slightly higher than in larger real-world series, which may be related to locally advanced disease, peritoneal carcinomatosis, or an intact primary tumor. Conclusion: Bevacizumab-based therapy demonstrated consistent efficacy and an acceptable safety profile in patients with mCRC. Although the incidence of perforation and fistula formation was somewhat higher, the therapy remained safe with careful patient selection and monitoring.