Gokce Belge Bilgin

Background: Hyperkinetic biliary dyskinesia, defined as a gallbladder ejection fraction (EF) ≥80% on cholecystokinin (CCK)-stimulated hepatobiliary iminodiacetic acid scans in the setting of biliary-type pain, has been increasingly recognized as a potential functional gallbladder disorder. The clinical significance of this entity and the role of cholecystectomy remain uncertain. Patients and Methods: We conducted a systematic review and meta-analysis of studies reporting outcomes in patients with CCK-hepatobiliary iminodiacetic acid EF ≥80% who underwent cholecystectomy due to non-acute biliary-type pain. Primary outcomes included mean EF, rates of symptom resolution and improvement following cholecystectomy, and prevalence of chronic cholecystitis on pathology. Secondary outcomes included normal histology rates and symptom reproduction with CCK stimulation. All statistical analyses were conducted in R (version 4.5.0) using a random-effects model to obtain pooled estimates. Results: A total of 14 retrospective studies, including 686 patients, were analyzed. The pooled mean gallbladder EF was 90.27% (95% CI: 88.73–91.80, I ² = 86.6%). Symptom resolution occurred in 83.1% (95% CI: 76.7–89.4, I ² = 76.8%), and symptom improvement in 91.6% (95% CI: 89.0–94.2, I ² = 29.7%) of patients following cholecystectomy. Histopathologic analysis revealed chronic cholecystitis in 85.1% (95% CI: 76.9–93.4, I ² = 90.6%) of surgical specimens, while normal gallbladder histology was rare, observed in only 9.9% (95% CI: 4.6–15.2, I ² = 83.7%). The pooled risk ratio indicated a 6.70-fold higher likelihood of chronic cholecystitis compared with normal histology (95% CI: 3.69–12.17, I ² = 65.2%, P = 0.0022). Functional reproduction of symptoms during CCK stimulation was frequent, with a pooled rate of 78.3% (95% CI: 70.4–86.3, I ² = 35.6%). Egger regression test suggested potential publication bias for the normal histology outcome ( P = 0.0223), but not for symptom resolution ( P = 0.1589). Conclusions: This meta-analysis suggests that a high gallbladder EF in the setting of biliary-type pain could represent clinically relevant hyperkinetic biliary dyskinesia rather than normal physiology. Cholecystectomy appears to provide meaningful symptom relief in appropriately selected patients, and pathologic findings frequently indicate underlying chronic inflammation. Further studies are needed to establish clear diagnostic cutoffs and guide management.

Long-established prostate cancer cell lines provide limited insight into how contemporary early prostate cancer evolves into drug-resistant and neuroendocrine-like refractory disease. Patient-derived three-dimensional (3D) ex vivo models may better preserve this transition. Here, we found that 8 of 10 magnetic resonance imaging-guided biopsy specimens from patients with early-stage prostate cancer generated sustained 3D tumor spheroid cultures. After 12 weeks of enzalutamide selection, only one patient-derived culture acquired a resistant phenotype with treatment-emergent neuroendocrine prostate cancer (t-NEPC)-like features, including increased chromogranin A (CgA) and synaptophysin (SYP); reduced androgen receptor (AR), prostate-specific antigen (PSA), and prostate-specific membrane antigen (PSMA); and conversion from compact spheroids into irregular resistant aggregates. During this transition, WD repeat and SOCS box-containing protein 1 (WSB1) increased, whereas PSMA progressively decreased. WSB1 silencing restored PSMA, AR, and PSA expression and reduced neuroendocrine-associated features. A similar WSB1 dependency was observed in enzalutamide-resistant LNCaP cells, the castration-resistant prostate cancer model 22Rv1, and the neuroendocrine/small-cell prostate cancer model NCI-H660. Mechanistically, WSB1 functioned as a SOCS box-dependent E3 ubiquitin ligase adaptor that promoted PSMA ubiquitination and degradation. SOCS box deletion or T380A mutation impaired this process, while Aurora kinase A (AURKA) inhibition reduced WSB1-dependent PSMA ubiquitination. WSB1 depletion, AURKA inhibition with alisertib, and combined AURKA inhibition with EZH2 suppression reduced resistant aggregate growth and increased apoptosis-associated markers in patient-derived enzalutamide-resistant neuroendocrine-like spheroids and related models. These findings nominate the AURKA–WSB1–PSMA axis as a therapeutic vulnerability in refractory prostate cancer.

Peptide receptor radionuclide therapy (PRRT) has emerged as a promising treatment for metastatic pheochromocytoma and paraganglioma (mPPGL). This study aimed to evaluate PRRT outcomes in patients with mPPGL in a single institution. Methods: Records of patients with mPPGL who received PRRT were retrospectively reviewed. The outcomes of interest were objective response rate (ORR), disease control rate (DCR), symptomatic benefit, hypertension control, and treatment-related toxicity. ORR included complete response and partial response, whereas DCR encompassed complete response, partial response, and stable disease, determined using RECIST 1.1. Symptomatic benefit was defined as patient-reported symptom improvement relative to baseline. Hypertension control was assessed on the basis of adjustments in antihypertensive medication requirements. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 5.0. Overall survival and progression-free survival were also evaluated. Results: Of the 15 patients included in our study, 7 (47%) had paraganglioma and 8 (53%) had pheochromocytoma. The mean follow-up duration was 28.4 ± 19.3 mo. PRRT was the initial systemic therapy in 2 patients (13%), and 2 treated with PRRT (13%) underwent retreatment, receiving 8 cycles. Two patients (13%) discontinued PRRT because of disease progression, and the remaining 13 patients (87%) completed all 4 cycles. The ORR was 27%, and the DCR was 73%, including 7 patients with stable disease and 4 with a partial response. The mean PRRT response duration was 16.2 ± 14.2 mo. A reduction in dose or no escalation of antihypertensive therapy was observed in 13 patients (87%). Ten patients (67%) reported symptom improvement. The most common toxicities were grade 1 or 2 anemia and leukopenia (40%). Grade 3 or 4 hematologic toxicities occurred in 2 patients (13%), including 1 with thrombocytopenia (7%) and 1 with myelodysplastic syndrome (7%). No moderate or severe nephrotoxicity was observed. Hypertensive crises occurred in 2 patients (13%), 1 with a prior history of such events. The median overall survival was 54.8 mo (95% CI, 6.8–102.8 mo), and the median progression-free survival was 26.9 mo (95% CI, 13.3–40.5 mo). Conclusion: Our findings suggest that PRRT remains a therapeutic strategy for mPPGL, is well-tolerated, and may improve cancer-related symptoms. Large-scale prospective studies are needed to validate structural responses and durability.

Background Central nervous system (CNS) metastases in prostate cancer are rare but pose a significant treatment challenge and are linked to poor prognosis. Data on the outcomes of this specific patient subgroup treated with radioligand therapy (RLT) remain scarce. In this study, we aim to leverage real-world clinical data to evaluate the outcomes of RLT with [¹⁷⁷Lu] Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC) and CNS metastases. Methods Clinical and imaging data of patients who received their initial dose of [¹⁷⁷Lu] Lu-PSMA-617 between March 2022 and April 2024 were retrospectively reviewed. All patients who were known to have at least one parenchymal CNS metastasis confirmed radiologically through dedicated neuroimaging, with or without histopathological confirmation, were included in the study. Central nervous system metastases (CNS) were defined as metastatic lesions involving the cerebrum, cerebellum, or spinal cord. The mCRPC patients with dural metastases but without parenchymal CNS disease were excluded. Results A total of 589 patients underwent RLT with [¹⁷⁷Lu] Lu-PSMA-617 for mCRPC, of whom 12 (2%, 12/589) had CNS metastases. Among these, eight patients (67%, 8/12) had pre-existing CNS lesions, while the remaining four patients (33%, 4/12) were diagnosed with CNS metastases after initiating RLT. Patients received no additional systemic or focal therapies concurrently with RLT. The mean follow-up period was 5.7 ± 6.9 months. The median overall survival from the initial dose of RLT was 4.5 months (range: 1.1–29.87 months). Among eight patients with pre-existing CNS metastases, CNS lesions resolved completely or nearly completely in three patients (37.5%, 3/8), while two patients (25%, 2/8) exhibited a mixed response, and three patients (37.5%, 3/8) experienced CNS disease progression following RLT. Among four patients diagnosed with CNS metastases after initiating therapy, three patients (75%, 3/4) experienced a rapid clinical decline necessitating urgent intervention, while the remaining patient (25%, 1/4) responded well to the therapy without developing new or worsening neurological symptoms. None of the patients were able to complete the full six cycles of RLT, with discontinuation mainly due to overall disease progression or infection-related complications. Conclusions Our study suggests that patients with CNS metastases, whether diagnosed before or after therapy, exhibited a poor prognosis, with a median survival of 4.5 months after initiation of RLT. Although a complete/near-complete radiologic response in the CNS lesions was observed in 25% of the patients, only two patients were able to complete more than three cycles of therapy. Given the small sample size, larger multicenter studies are needed to validate these findings.

Tumor thrombus arising from osteosarcoma is rare, with only a few cases documented in the literature. Herein, we report a case of locally recurrent osteosarcoma complicated by tumor thrombus in a patient who had undergone prior neoadjuvant chemotherapy, surgical resection, and rotationplasty for a distal left femoral osteosarcoma. An [¹⁸F] FDG PET/CT scan revealed an FDG-avid locally recurrent tumor in the soft tissues of the left thigh contiguous with FDG-avid tumor thrombus extending from the mid-left femoral vein to the left external iliac vein. This case illustrates that, although rare, osteosarcoma can cause tumor thrombus, and [¹⁸F] FDG PET/CT can be a useful diagnostic tool in such cases.

Hidradenocarcinoma is a rare and aggressive malignant cutaneous adnexal tumor that originates from the intradermal ducts of eccrine sweat glands. Herein, we report a case of hidradenocarcinoma that had transformed from a previously excised benign hidradenoma. [¹⁸F] FDG PET/CT revealed an FDG-avid mass in the left calf, and extensive metastatic disease, including soft tissue, pulmonary, osseous, and extensive nodal metastases. This case underscores the potential for malignant transformation of hidradenoma and highlights the utility of [¹⁸F] FDG PET/CT in staging hidradenocarcinoma.

Background: The impact of certain comorbidities on mechanical thrombectomy (MT) outcomes remains largely unexplored. Diabetes mellitus (DM) and admission hyperglycemia have been associated with poor clinical outcomes for patients treated with MT. In this study, we sought to investigate the effects of DM and admission hyperglycemia on MT outcomes. Methods: Following PRISMA guidelines, a systematic literature search was conducted in Medline, Embase, Scopus, and Web of Science databases. Data regarding successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] ≥2b), functional independence (modified Rankin Scale [mRS] 0–2), excellent outcomes (mRS 0–1), symptomatic intracranial hemorrhage (sICH), and mortality were extracted from the included studies. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using random effects model. Results: Twenty-one studies comprising 9708 patients were included. A total of 2311 patients (24%) had a history of DM, and 2026 patients (21%) had admission hyperglycemia. Admission hyperglycemia was associated with significantly lower odds of mTICI ≥2b (OR = 0.7, 95% CI = 0.55–0.89), mRS 0–2 (OR = 0.47, 95% CI = 0.41–0.53), and mRS 0–1 (OR = 0.43, 95% CI = 0.34–0.55) as compared to normoglycemic state. Patients with hyperglycemia had significantly higher rates of sICH (OR = 2.05, 95% CI = 1.66–2.54) and mortality (OR = 1.99, 95% CI = 1.58–2.52) than normoglycemic patients. Diabetes mellitus was associated with significantly high rates of mortality (OR = 1.74, 95% CI = 1.31–2.3) and lower rates of mRS 0–2 (OR = 0.60, 95% CI = 0.48–0.76) in sensitivity analyses. Conclusion: Our results indicate that admission blood glucose levels and DM can negatively affect MT outcomes. Further research should focus on optimizing MT outcomes for these patients.

Radioligand therapies such as [¹⁷⁷Lu] Lu-PSMA-617 have gained significant momentum in cancer treatment after clinical trials and multicenter studies demonstrated their safety and efficacy. As these innovative treatments become more widespread, rare and unique clinical manifestations are expected to be observed. In this report, we describe a case with metastatic castration-resistant prostate cancer (mCRPC) and peripancreatic lymph node metastases who developed acute pancreatitis following [¹⁷⁷Lu] Lu-PSMA-617 therapy.