Pharmaprojects No. 3498

No pollutant acts alone: environmental co-exposure and the cardiovascular exposome.

Münzel Thomas T, Daiber Andreas A, Landrigan Philip J PJ

Endoscopic "Two-Step Method" for resection of a large tumor at the major duodenal papilla: A case report (with video).

Wu Dan D, Sun DaYong D, Niu ChaoHui C, Wei Hong H

Endoscopic papillectomy is the standard treatment for noninvasive tumors of the ampulla of Vater. However, reports on the endoscopic resection of large tumors at the major duodenal papilla are rare. The "two-step" endoscopic approach described herein represents the first such report for a giant lesion. A 75-year-old female patient was admitted to the hospital with a 6-month history of abdominal distension. Gastroscopy revealed a giant tumor in the descending duodenum that prevented clear visualization of its full extent. Duodenoscopy revealed a laterally spreading tumor, granular homogeneous type (LST-P, Paris 0-IIa), measuring approximately 60 × 50 mm, surrounding the major duodenal papilla. Contrast-enhanced computed tomography showed a 65 × 35 mm intraluminal lesion with no lymphadenopathy. Endoscopic ultrasonography confirmed mucosal and submucosal origin without biliary or pancreatic duct invasion. Biopsy revealed low-grade intraepithelial neoplasia. The final diagnosis was a giant laterally spreading tumor of the major duodenal papilla. Endoscopic resection was performed using a novel "Two-Step Method." In the first session, the bulk of the tumor was resected piecemeal to improve the operative field. Five days later, the residual lesion was resected by endoscopic mucosal resection after submucosal injection. Prophylactic biliary and pancreatic duct stents were placed upon completion of the second session. The patient commenced a cold liquid diet on the second postoperative day. She experienced no abdominal pain, hematochezia, or fever. Histopathology revealed a villous-tubular adenoma with low-grade intraepithelial neoplasia. No adenomatous tissue was identified at the cauterized margins of the submitted specimens. No complications occurred, and no recurrence was observed during the 12-month follow-up. Few reports describe the endoscopic treatment of large duodenal tumors. This case demonstrates that the two-step method is a safe and effective alternative for giant duodenal mucosal lesions when single-session resection is precluded by limited operative space. Further experience is needed to establish consensus on the optimal management of such lesions.

Psychiatric disorders and gynecologic tumors: A 2-sample Mendelian randomization study of 20 exposure-outcome pairs.

Zheng Ping P, Chen Wenjuan W, Jiang Meiying M

Previous epidemiological evidence has suggested associations between psychiatric disorders and gynecologic tumors, but the causal relationships have not been fully characterized. This study aims to investigate the potential causal relationships using genetic instrumental variables. A 2-sample Mendelian randomization (MR) analysis was conducted utilizing 3 large-scale genome-wide association study databases: FinnGen, UK Biobank, and the Integrative Epidemiology Unit. The exposures included anxiety disorder, obsessive-compulsive disorder, schizophrenia, major depressive disorder, and bipolar disorder. The outcomes comprised cervical cancer (CC), ovarian cancer (OC), endometrial cancer, and uterine fibroids. Causal estimates were primarily derived using inverse variance weighting, with robustness assessed via MR-Egger regression, weighted median, and pleiotropy-robust methods. Heterogeneity and horizontal pleiotropy were evaluated using Cochran's Q statistic, MR-Egger intercept test, and sensitivity analyses. False discovery rate (FDR) correction was applied for multiple testing across 20 exposure-outcome pairs. The data included CC (909 cases and 2,38,249 controls), OC (2188 cases and 2,37,839 controls), endometrial cancer (1218 cases and 1,98,523 controls), and uterine fibroids (21,024 cases and 2,37,694 controls). No data loss occurred. Among 20 exposure-outcome pairs, only schizophrenia showed a statistically significant and robust association with OC after FDR correction (OR = 1.0464, 95% CI: 1.0136-1.0801, P = .0052; FDR-adjusted P = .0258). Sensitivity analyses confirmed no significant heterogeneity (inverse variance weighting Q P = .068) or horizontal pleiotropy (MR-Egger intercept P = .116). Mendelian Randomization-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) was performed with 5000 permutations; the global test revealed no evidence of horizontal pleiotropy (RSSobs = 328.65, P = .058) and no outlier Single nucleotide polymorphisms were detected. Although major depressive disorder was nominally associated with CC (P = .0056, FDR = 0.0258), leave-one-out sensitivity analysis revealed this association was highly unstable and not robust. No other causal associations were observed. The suggestive genetic association between schizophrenia and OC merits attention in future etiological research. The null findings for anxiety disorder, bipolar disorder, and obsessive-compulsive disorder with gynecologic tumors may help alleviate unnecessary clinical concerns.

Primary breast diffuse large B-cell lymphoma mimicking breast carcinoma: A case report and literature review.

Li Longquan L, Yao Hongxi H, Liu Siyu S, Yin Jieting J et al.

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal manifestation of non-Hodgkin lymphoma (NHL) that can closely resemble breast carcinoma clinically and radiologically. This overlap may delay accurate diagnosis and appropriate treatment. We report a case of PB-DLBCL in a postmenopausal woman whose initial multimodal imaging findings were suspicious for breast carcinoma, but whose final diagnosis was established by core needle biopsy with immunohistochemical and molecular evaluation. A 59-year-old postmenopausal woman presented with a painless, palpable mass in the right breast that had been present for approximately 3 weeks. Breast ultrasonography, mammography, magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) demonstrated a suspicious right breast mass with ipsilateral axillary lymphadenopathy, initially raising concern for breast carcinoma. Ultrasound-guided core needle biopsy showed diffuse infiltration by atypical lymphoid cells. Immunohistochemistry confirmed a B-cell phenotype, and fluorescence in situ hybridization (FISH) showed no MYC, BCL2, or BCL6 rearrangements. Bone marrow biopsy showed no evidence of marrow involvement. The final diagnosis was PB-DLBCL, non-germinal center B-cell-like (non-GCB) subtype, Ann Arbor stage IIE. The patient received 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemoimmunotherapy. No breast-directed surgery, consolidative radiotherapy, or central nervous system prophylaxis was administered. At 6 weeks after completion of R-CHOP therapy, PET/CT showed complete metabolic resolution of the right breast lesion, with only a residual punctate calcified focus measuring approximately 0.4 × 0.4 × 0.3 cm. The Deauville score decreased from 5 at baseline to 1 after treatment, meeting Lugano criteria for complete response. No clinically significant treatment-related adverse events were documented. PB-DLBCL can closely mimic breast carcinoma on multimodal imaging. Suspicious breast imaging findings do not exclude lymphoma. Tissue diagnosis with adequate immunophenotypic and molecular evaluation is essential before definitive treatment planning to avoid misdiagnosis and unnecessary surgery.