Introduction: Insulinoma during pregnancy is exceedingly rare, with fewer than 30 cases reported worldwide. Diagnosis is often delayed due to overlapping physiological and gestational symptoms, posing significant risks to both mother and fetus. Case: We report a case of a 36-year-old G4P2 + 1 female presenting at 7 weeks’ gestation with recurrent symptomatic hypoglycemia initially suspected due to poor oral intake. She returned at 12 weeks with persistent neuroglycopenic symptoms and weight loss. Biochemical evaluation demonstrated inappropriately non-suppressed insulin and C-peptide levels during hypoglycemia, raising suspicion for endogenous hyperinsulinemia. Imaging with magnetic resonance imaging identified a 2.3 × 2.5 cm pancreatic lesion consistent with insulinoma. A multidisciplinary team (MDT) approach involving Internal Medicine, Endocrinology, Obstetrics and Gynecology (Maternal-Fetal Medicine), Hepatobiliary Surgery, and Radiology guided management. Due to concerns regarding surgical and ablative risks during pregnancy, medical therapy with octreotide was initiated, achieving partial glycemic control. The pregnancy was complicated by fetal growth restriction, necessitating delivery at 34 weeks. Postpartum, the patient underwent endoscopic ultrasoundguided radiofrequency ablation (EUS-RFA), requiring two sessions before achieving glycemic stabilization. Conclusion This case highlights the diagnostic challenges of insulinoma in pregnancy and underscores the importance of MDTguided individualized management. It also illustrates the limitations of EUS-RFA and medical therapy, particularly in larger tumors, and raises important considerations regarding fetal outcomes.
Female ; Pregnancy ; Insulinoma ; Hypoglycemia

Introduction: A negative computed tomography (CT) scan does not preclude an insulinoma, as small lesions frequently remain undetected on conventional imaging. This case highlights the indispensable role of endoscopic ultrasound (EUS)— not just for localizing occult tumors, but as a definitive, minimally invasive therapeutic alternative to high-risk surgical resection. Case: A 39-year-old female with underlying hypertension presented with a 5-month history of predominantly fasting hypoglycemia (glucose <3.0 mmol/L) and neuroglycopenic symptoms, fulfilling Whipple’s triad. A supervised 72-hour fast confirmed endogenous hyperinsulinemic hypoglycemia at 31 hours, with a nadir glucose of 1.4 mmol/L, insulin 116 pmol/L, and C-peptide 821 pmol/L. Notably, contrastenhanced CT of the pancreas was reported as normal. To overcome this, EUS was performed, successfully identifying a hidden 19 × 18 mm lesion in the head of the pancreas, intimately abutting the main pancreatic duct. Despite medical therapy with diazoxide and strict dietary modifications, her hypoglycemia remained refractory. Given the tumor’s proximity to the main pancreatic duct, surgical enucleation carried a prohibitively high risk of complications. Consequently, she underwent EUS-guided radiofrequency ablation (RFA). Immediate post-procedure outcomes demonstrated near-complete resolution of the hypoglycemic episodes. Diazoxide was subsequently stopped. Outpatient continuous glucose monitoring confirmed sustained normoglycemia and marked symptom resolution, with no procedure-related complications. Conclusion The absence of a pancreatic lesion on CT demands persistent clinical suspicion in cases of biochemically proven hypoglycemia. EUS remains paramount for detecting occult lesions missed by standard imaging. Importantly, EUSRFA serves as a highly effective, tissue-sparing alternative to surgical resection for insulinomas, especially when conventional surgery poses prohibitive anatomical risks.
Insulinoma ; Tomography, X-Ray Computed

Introduction: Pancreatic neuroendocrine tumors (PNETs) are rare, comprising less than 3% of all pancreatic neoplasms. These tumors are broadly classified as functioning or nonfunctioning. Insulinoma is the most common functioning PNET. Non-functioning PNETs often present significant diagnostic issues and may be misdiagnosed as pancreatic adenocarcinoma, especially when immunohistochemical evaluation is omitted during histological examination. We describe a case of metastatic insulinoma that was misdiagnosed as a poorly differentiated pancreatic adenocarcinoma. Case: A 65-year-old female first presented to a private hospital in 2023 with obstructive jaundice and was found to have a pancreatic head lesion that was causing biliary obstruction. As a result, a biliary stent was placed. She underwent aortocaval lymph node biopsy, and the result showed poorly differentiated pancreatic adenocarcinoma. Nonetheless, she refused surgical and oncological intervention. Even so, she remained clinically stable and maintained good functional status for 2 years. In 2025, she presented to Hospital Canselor Tuanku Muhriz with recurrent hypoglycemia fulfilling Whipple’s triad. The unexpectedly indolent clinical course prompted reassessment of the initial diagnosis. Biochemical evaluation confirmed endogenous hyperinsulinemic hypoglycemia, with inappropriately elevated insulin (11.03 µIU/mL) and C-peptide levels (1,089 pmol/L). Computer tomography of the abdomen revealed multiple hepatic lesions and progressive lymphadenopathy, suggestive of metastatic disease. Re-evaluation of the initial histopathological specimen showed a well-differentiated neuroendocrine tumor (Grade 1, Ki-67 ~2%). Hence, the diagnosis was revised to metastatic insulinoma. She was referred to the hepatobiliary surgical team for surgical debulking, but the procedure was deemed highrisk and likely to have high mortality due to the extent of the disease. She was managed with diazoxide and longacting somatostatin analogues for glycemic control. Conclusion This case highlights the critical importance of diagnostic vigilance when evaluating pancreatic neoplasms. Persistent or unexplained clinical courses, especially when endocrine symptoms arise, should prompt thorough reassessment. Immunohistochemical confirmation is essential to avoid misdiagnosis and ensure optimal patient management.
Adenocarcinoma ; Insulinoma ; Pancreatic Neoplasms

Introduction: Insulinoma is a rare functioning pancreatic neuroendocrine tumor and the most common cause of endogenous hyperinsulinemic hypoglycemia. Although biochemical confirmation is usually straightforward, tumor localization may be difficult when lesions are small and not detected on conventional cross-sectional imaging. In such cases, endoscopic ultrasound (EUS) plays an important role in identifying occult lesions and facilitating definitive treatment. Case: A 52-year-old female was admitted in April 2025 with recurrent seizures secondary to hypoglycemia for 3 years, with increasing frequency over time. She fulfilled Whipple’s triad, with documented capillary glucose of 1.8 mmol/L during an episode and symptom resolution following glucose administration. A supervised prolonged fasting test confirmed endogenous hyperinsulinemic hypoglycemia, with plasma glucose 1.4 mmol/L, insulin 122 pmol/L, and C-peptide 1,010 pmol/L. Short Synacthen test demonstrated adequate adrenal reserve. Due to persistent hypoglycemia, she required high-dose diazoxide. Contrast-enhanced computed tomography abdomen did not reveal a pancreatic lesion but incidentally detected a right ovarian teratoma. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy in June 2025, with histopathology confirming a mature cystic teratoma without malignancy. However, hypoglycemic episodes persisted. Further evaluation with EUS in July 2025 identified a highly vascular isoechoic 8 × 8 mm lesion in the pancreatic body. Fine-needle biopsy confirmed a well-differentiated neuroendocrine tumor (WHO grade 1) with Ki-67 index of 2%. She subsequently underwent EUSguided radiofrequency ablation in August 2025. Follow-up EUS in December 2025 showed post-ablation change, and her hypoglycemic episodes resolved completely, allowing diazoxide to be discontinued. Conclusion This case highlights the diagnostic challenge of occult insulinoma in the presence of negative conventional imaging. EUS was pivotal for tumor localization and tissue diagnosis, while EUS-guided radiofrequency ablation provided effective minimally invasive treatment in a carefully selected patient.
Insulinoma ; Tomography, X-Ray Computed

Objective The aim of this study was to investigate the effect of p38 on stem cell maintenance of pancreatic cancer. Methods Human pancreatic cancer cells PANC-1 were treated with different concentrations of 5-fluorouracil(5-FU)(0.5×IC₅₀, IC₅₀, and 2×IC₅₀) for 24 hours, and VX-702 (p38 phosphorylation inhibitor) was added, and the cells were inoculated in 6-well culture dishes with ultra-low adhesion to observe the changes of sphere tumors. The expression levels of cyclin-dependent kinase 2(CDK2), cyclin B1 and D1, Octamer-binding transcription factor 4(OCT4), SRY-box transcription factor 2(SOX2), Nanog and p38 were measured by Western blot. The mRNA expression levels of p38, OCT4, Nanog and SOX2 were tested by RT-PCR. Cell cycle, apoptosis, and the proportion of CD44⁺CD133⁺PANC-1 cells were evaluated by flow cytometry. Results The results showed that 5-FU inhibited the formation of tumor spheres in PANC-1 cells, increased CD44⁺CD133⁺cell fragments, down-regulated the expression of OCT4, Nanog and SOX2, and inhibited the stemness maintenance of PANC-1 tumor stem cells. Phosphorylation of PANC-1 cells was inhibited by a highly selective p38 MAPK inhibitor, VX-702(p38 mitogen-activated protein kinase inhibitor), which had the same effect as 5-FU treatment. When VX-702 combined with 5-FU was used to treat PANC-1 cells, the therapeutic effect was enhanced. Conclusion p38 inhibitors decreased PANC-1 cell activity and increased cell apoptosis. p38 inhibitors inhibit the stemness maintenance of pancreatic cancer stem cells.
Humans ; Phosphorylation/drug effects* ; Cell Line, Tumor ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors* ; Neoplastic Stem Cells/metabolism* ; Drug Resistance, Neoplasm/drug effects* ; Fluorouracil/pharmacology* ; Pancreatic Neoplasms/pathology* ; Apoptosis/drug effects* ; SOXB1 Transcription Factors/genetics* ; Octamer Transcription Factor-3/genetics*

OBJECTIVES: In recent years, the incidence and detection rate of pancreatic cystic lesions (PCLs) have increased significantly. Endoscopic ultrasound (EUS) plays an indispensable role in the diagnosis and differential diagnosis of PCLs. However, evidence comparing the diagnostic performance of EUS-guided fine-needle aspiration (EUS-FNA) and fine-needle biopsy (FNB) remains limited. This study aims to compare the diagnostic yield, adequacy of tissue acquisition, and safety between EUS-FNA and EUS-FNB in evaluating PCLs to inform clinical practice. METHODS: A retrospective review was conducted on patients with PCLs who underwent either EUS-FNA or EUS-FNB between January 2014 and August 2021. The diagnostic yield, tissue acquisition adequacy, and incidence of adverse events were compared between the 2 groups. RESULTS: A total of 90 patients with PCLs were included (52 in the FNA group and 38 in the FNB group). The diagnostic yield was similar between the FNA and FNB groups (94.2% vs 94.7%, P>0.05). The adequacy of tissue acquisition was 71.2% in the FNA group and 81.6% in the FNB group (P>0.05). No statistically significant difference was observed in the incidence of adverse events between the 2 groups (P>0.05). CONCLUSIONS Both EUS-FNA and EUS-FNB demonstrate equally high diagnostic yields and tissue adequacy in PCLs, with excellent safety profiles. Both methods are safe and effective diagnostic tools for evaluating PCLs.
Humans ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/adverse effects* ; Retrospective Studies ; Female ; Male ; Pancreatic Cyst/diagnostic imaging* ; Middle Aged ; Biopsy, Fine-Needle/adverse effects* ; Aged ; Pancreatic Neoplasms/diagnosis* ; Adult ; Endosonography/methods* ; Pancreas/pathology* ; Diagnosis, Differential

OBJECTIVES: To evaluate the value of ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/CT imaging in staging and treatment decision for gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). METHODS: This retrospective analysis was conducted in 49 patients with GEP-NEN undergoing ¹⁸F-FDG and ⁶⁸Ga-DOTATATE PET/CT imaging at our hospital from August, 2020 to March, 2023, including 34 newly diagnosed patients and 15 patients with recurrence or metastasis after treatment. GEP-NEN were classified into G1, G2, and G3 neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC) based on pathological typing. The detection efficiency were classified into 4 patterns based on the number of positive tumor lesions detected by the two tracers: ⁶⁸Ga-DOTATATE>¹⁸F-FDG (A); ⁶⁸Ga-DOTATATE=¹⁸F-FDG (B); ⁶⁸Ga-DOTATATE<¹⁸F-FDG (C); and complementation (D). The value of dual-modality imaging in staging and treatment decision were evaluated by visual analysis. RESULTS: In the 49 patients with GEP-NEN, ⁶⁸Ga-DOTATATE PET/CT was superior to ¹⁸F-FDG PET/CT for detecting systemic tumor lesions (P<0.001) and more sensitive for detecting primary/recurrent lesions, lymph node metastasis, liver metastasis, and bone metastasis (P<0.05), while ¹⁸F-FDG PET/CT had higher detection rates for lung metastasis and peritoneal metastasis (P<0.05). In terms of the detection efficiency, Pattern A was found in 46.9% (23/49) patients, Pattern B in 38.8% (19/49), Pattern C in 12.2% (6/49), and Pattern D in 2.0% (1/49). The complementary value of ¹⁸F-FDG PET/CT to ⁶⁸Ga-DOTATATE PET/CT was 0% in G1 NET patients (0/13), 8.3% in G2 NET patients (2/24), 50% in G3 NET patients (3/6), and 33.3% in NEC patients (2/6). 12.2% (6/49) of the patients had their staging confirmed or changed due to additional lesions detected by ¹⁸F-FDG PET/CT imaging, resulting subsequently in establishment or adjustment of their treatment plans. CONCLUSIONS ⁶⁸Ga-DOTATATE PET/CT imaging should be the primary choice for GEP-NEN patients. Additional ¹⁸F-FDG PET/CT imaging can potentially improve precision of staging and treatment decision-making for G2, G3 and NEC patients but provides virtually no clinical benefits for G1 NET patients.
Humans ; Positron Emission Tomography Computed Tomography/methods* ; Neuroendocrine Tumors/therapy* ; Pancreatic Neoplasms/therapy* ; Retrospective Studies ; Organometallic Compounds ; Stomach Neoplasms/therapy* ; Neoplasm Staging ; Fluorodeoxyglucose F18 ; Intestinal Neoplasms/therapy* ; Female ; Male ; Middle Aged ; Aged ; Adult

OBJECTIVES: To evaluate the inhibitory effect of oridonin against proliferation of pancreatic cancer cells and the mechanism underlying the synergistic effect of low-intensity pulsed ultrasound (LIPUS). METHODS: PANC-1 cells treated with different concentrations of oridonin were examined for changes in cell proliferation using CCK-8 assay and in MDA, GSH and ATP levels using flow cytometry. The protein expressions of GPX4, Nrf2 and HO-1 in the treated cells were detected with Western blotting. The effect of Fer-1, a ferroptosis inhibitor, on proliferation of oridonin-treated cells were assessed, and the effects of oridonin combined with LIPUS on PIEZO1 protein expression was evalauted using Western blotting. A C57BL/6J mouse model bearing pancreatic cancer cell xenograft was established and treated with oridonin, LIPUS, or both, and the histological changes in the tumor tissues and tumor cell proliferation were examined with HE staining and immunohistochemistry for Ki67; the changes in GPX4 expression in the tumor tissues were detected using Western blotting and immunofluorescence staining. RESULTS: In PANC-1 cells, oridonin treatment significantly inhibited cell proliferation, increased intracellular Fe²⁺, ROS, and MDA levels, and decreased GSH and ATP levels. Oridonin also resulted in lowered GPX4 and increased HO-1 and Nrf2 protein expression levels in the cells. The combined treatment with LIPUS signficiantly enhanced the inhibitory effect of oridonin on PANC-1 cell viability in vitro and on xenograft growth in the mouse models, resulting also in more obvious reduction of the intensity of Ki67 staining and GPX4 protein expression and more pronounced increase of PIEZO1 protein expression in the tumor tissues in the mouse models. CONCLUSIONS LIPUS enhances the effect of oridonin to promote ferroptosis of pancreatic cancer cells by activating PIEZO1 through the Nrf2/HO-1/GPX4 pathway.
Ferroptosis/drug effects* ; Animals ; Pancreatic Neoplasms/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Humans ; Cell Line, Tumor ; Mice ; Heme Oxygenase-1/metabolism* ; Diterpenes, Kaurane/pharmacology* ; Cell Proliferation/drug effects* ; Mice, Inbred C57BL ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Ion Channels/metabolism* ; Ultrasonic Waves ; Signal Transduction

OBJECTIVES: To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer. METHODS: PBK expression levels were investigated in 33 cancer types based on data from TCGA, GEO and CPTAC databases. RT-PCR and Western blotting were employed to examine PBK expression in clinical pancreatic cancer specimens and cell lines. The diagnostic and prognostic value of PBK in pancreatic cancer was evaluated using survival analysis, Cox regression analysis, ROC curve analysis, and clinical correlation studies. Gene enrichment and immune correlation analyses were conducted to explore the potential role of PBK in tumor microenvironment, and its correlation with drug sensitivity was investigated using GDSC and CTRP datasets. In pancreatic cancer BXPC-3 cells, the effects of lentivirus-mediated PBK knockdown on cell proliferation, migration, and invasion were examined using CCK-8, colony formation, and Transwell assays. The interaction between PBK and non-SMC condensin II complex subunit G2 (NCAPG2) was analyzed using co-immunoprecipitation and Western blotting. RESULTS: PBK was overexpressed in multiple cancer types, including pancreatic cancer. A high PBK expression was associated with a poor prognosis of the patients and correlated with immune infiltration and alterations in the tumor microenvironment. Elevated PBK expression was positively correlated with the sensitivity to MEK inhibitors (Trametinib) and EGFR inhibitors (Afatinib) but negatively with the sensitivity to Bcl-2 inhibitors (TW37) and niclosamide. In BXPC-3 cells, PBK knockdown significantly suppressed NCAPG2 expression and inhibited cell proliferation, migration, and invasion. Co-immunoprecipitation confirmed a direct binding between PBK and NCAPG2. CONCLUSIONS PBK is a key regulator of pancreatic cancer and interacts with NCAPG2 to promote tumor progression, suggesting its value as a potential biomarker and therapeutic target for pancreatic cancer.
Humans ; Pancreatic Neoplasms/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Adenocarcinoma/metabolism* ; Tumor Microenvironment ; Cell Movement ; Mitogen-Activated Protein Kinase Kinases

Pregnancy after undergoing major gastrointestinal surgeries like the Whipple’s procedure (pancreaticoduodenectomy) for pancreatic neoplasm is rare. This case report describes a 24-year-old woman who conceived and delivered a healthy baby after undergoing a Whipple’s procedure 5 months earlier for a pancreatic tumor. Her pregnancy was managed by a multidisciplinary team, and she delivered at 37 weeks of gestation through cesarean section without any complications. This case highlights the potential for successful pregnancy following a Whipple’s procedure, with proper counseling, coordinated care, and close monitoring during pregnancy.
Pancreatic Neoplasms ; Pancreaticoduodenectomy ; Pregnancy