Nemtabrutinib is a Bruton's tyrosine kinase (BTK) inhibitor under clinical investigation in patients with hematologic malignancies, including chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL). Nemtabrutinib plasma concentration data from 578 patients enrolled in phase 1 and 2 clinical studies, treated with doses from 5 to 80 mg daily were used to develop a preliminary population pharmacokinetic (PK) model. A two-compartment model with first-order absorption with time delay, and first-order elimination described the data accurately. A full covariate modeling approach was adopted to evaluate prespecified clinically meaningful covariates. The final model included the impact of body weight, sex, race, and disease indication on clearance (CL) and central volume of distribution; age, albumin, moderate CYP3A4 inducers, strong CYP3A4 inhibitors, mild hepatic and moderate renal impairment on CL; and acid reducing agents (ARAs) (i.e., proton pump inhibitors, H2 antagonists, and antacids) on bioavailability. The effect of CYP3A4 modulators and ARAs was estimated to be very low (< 4%) and none of the intrinsic factors were found to have a clinically significant impact on nemtabrutinib PK. Preliminary exposure-efficacy analysis in patients with CLL/SLL showed a significant trend of increased probability of best overall response with increased exposure to nemtabrutinib, while preliminary exposure-safety in patients with hematologic malignancies showed a significant trend between increased exposure and increased probability of any-grade drug-related adverse events (as assessed by investigator) and any-grade hypertension events. Taken together, these exposure-response analyses suggest that 65 mg daily is an appropriate dose for nemtabrutinib monotherapy treatment of patients with CLL/SLL.

Pancreatic cystic lesions (PCLs) range from benign to malignant, creating diagnostic and therapeutic challenges. While most PCLs are serous or mucinous neoplasms, rare entities such as acinar cell cystadenoma (ACC) remain poorly characterized. This study reports a tertiary center cohort and a systematic literature review.

We retrospectively analyzed 23 ACC patients at Karolinska University Hospital. A systematic review was performed following PRISMA guidelines.

In our cohort (median age 67.0 years; 73.9% male), ACCs were most often incidentally detected, with abdominal pain being the most frequent indication for imaging. No patients underwent surgery, and no malignant transformation was observed during a median follow-up of 10.4 months. Most patients (87%) underwent both CT and MR imaging, and 65.2% fulfilled proposed imaging diagnostic criteria.The systematic review included 41 studies with 165 patients. Abdominal pain was the most common indication for imaging, and most patients underwent pancreatic surgery. Median follow-up was 1.3 years, with no malignant transformation observed. Imaging typically showed well-circumscribed cystic lesions, usually non-communicating with the main pancreatic duct and mimicking other cystic neoplasms. Histopathology consistently demonstrated an acinar phenotype with low proliferative activity.

ACC appears to be an asymptomatic, incidentally discovered lesion, with imaging playing a central diagnostic role. Neither endocrine nor exocrine pancreatic insufficiency nor malignant transformation was observed. However, the relatively short overall follow-up limits conclusions regarding long-term outcomes.

Nearly 20% of patients with neuroendocrine tumors (NET) develop carcinoid syndrome (CS), and 20-25% of those with CS develop carcinoid heart disease (CHD). Contemporary risk factors for CHD and prognostic variables in NET management remain limited. This study aimed to characterize the clinical and imaging factors associated with the development, and prognostic impact of carcinoid heart disease in patients with neuroendocrine neoplasms.

A single-institution, retrospective analysis of well-differentiated NET patients from January 2010 to December 2024 was conducted. Cox proportional hazards regression assessed associations between baseline covariates and CHD development (primary endpoint) and overall survival (OS; secondary endpoint). CHD was defined as moderate or severe tricuspid regurgitation on echocardiogram with echocardiographic features consistent with carcinoid valvulopathy. Survival curves were estimated using Kaplan-Meier methods. A p-value < 0.05 was considered significant.

We identified 270 patients with NET. Median age was 64.5 years; 52% were male; 5.6% developed CHD. CS was present in 10% (n = 27), and 41% of those with CS developed CHD. Fifteen patients (5.6%) developed carcinoid heart disease. Common primary sites were lung (26%), pancreas (17.4%), and small intestine (16.2%). CHD was associated with more hospitalizations and greater use of systemic or multimodal therapies. For OS, median OS for CHD patients was 90.8 months, while median OS was not reached for the full NET cohort. CHD independently predicted worse OS (HR 7.09; 95% CI: 1.84-27.40; p = 0.004). Systemic therapy use (HR 8.97; p = 0.0101) and high-grade tumors (HR 6.92; p < 0.001) were also associated with worse OS.

In NET patients, CHD and high-grade tumors were associated with worse OS. Systemic therapy use was associated with worse overall survival, likely reflecting more advanced disease rather than a causal treatment effect. Although CHD incidence is low, early detection and close monitoring remain essential.

This study aimed to systematically compare robot-assisted nipple-sparing mastectomy (R-NSM) with conventional nipple-sparing mastectomy (C-NSM) in terms of perioperative safety and oncological outcomes through a meta-analysis.

A comprehensive literature search was conducted in PubMed/MEDLINE, Web of Science Core Collection, Embase, and the Cochrane Central Register of Controlled Trials from database inception to February 27, 2026. Controlled studies comparing robotic nipple-sparing mastectomy (R-NSM) and conventional nipple-sparing mastectomy (C-NSM) in women with early-stage breast cancer (stage 0-II, including a small proportion of risk-reducing mastectomy cases) were included. Study selection and data extraction were independently performed by two reviewers, with discrepancies resolved by consensus. Statistical analyses were conducted using Review Manager (RevMan) version 5.4. The primary outcomes were overall postoperative complications, major complications (Clavien-Dindo grade ≥ III), positive surgical margin, and local recurrence. Secondary outcomes included operative time, estimated intraoperative blood loss, length of hospital stay, reoperation rate, and individual postoperative complications (including nipple-areolar complex necrosis, skin-flap necrosis, surgical-site infection, hematoma, seroma, delayed wound healing, and implant loss). Perioperative mortality was not reported in the included studies.

A total of 12 studies involving 2,312 patients (1 RCT and 11 non-randomized studies) were included in the quantitative synthesis. The reported follow-up duration across included studies ranged from 3 to approximately 51 months, with most studies reporting a median or mean follow-up of around 18-30 months. Compared with C-NSM, R-NSM was associated with a lower incidence of overall postoperative complications (RR = 0.82, 95% CI: 0.68-0.99, P = 0.04) and major complications defined as Clavien-Dindo grade ≥ III (RR = 0.44, 95% CI: 0.22-0.86, P = 0.02). R-NSM was also associated with a reduced risk of delayed wound healing (RR = 0.51, 95% CI: 0.26-0.98, P = 0.04). However, no statistically significant differences were observed between the two approaches with respect to nipple-areolar complex necrosis, skin flap necrosis, postoperative infection, hematoma, seroma, implant loss, reoperation rate, positive surgical margin, or local recurrence. R-NSM was associated with longer operative time and a modest reduction in intraoperative blood loss. However, TSA suggested that the cumulative evidence remains insufficient.

Current evidence suggests that, under strict patient selection, R-NSM does not appear to compromise short-term perioperative safety or oncological outcomes when compared with the conventional approach. Although a reduction in composite postoperative complications was observed, no significant differences were identified in most individual major complications, and operative time remains longer. Given the predominance of retrospective studies, limited information size, and relatively short follow-up, further high-quality prospective research is required to more definitively establish the role of R-NSM in clinical practice.

Serous cystadenoma (SCA) of the pancreas is typically a benign neoplasm, and variants are exceptionally rare. While tumors in the pancreatic head often cause upstream ductal dilatation and parenchymal atrophy due to obstruction, the concurrent presentation of SCA with congenital distal pancreatic duct atresia and complete acinar cell loss is unique. We report this case to highlight a potential congenital pathogenesis linking ductal developmental defects to the formation of these lesions.

A 56-year-old woman presented with persistent right upper abdominal distension and discomfort lasting over one year. She had a 20-year history of an abdominal mass and had undergone two previous unsuccessful surgical interventions, including a palliative bypass and an aborted resection. Preoperative imaging revealed a large cystic-solid mass in the pancreatic head. Intraoperative exploration identified a 12-cm lesion replacing the pancreatic head and neck, accompanied by complete fatty replacement of the pancreatic body and tail. The patient underwent en bloc pancreaticoduodenectomy with partial portal vein resection and synthetic vascular graft reconstruction. Histopathological examination confirmed the diagnosis of SCA. Notably, the distal pancreatic tissue exhibited a complete absence of acini and visible ductal structures, while islet cells were preserved. Postoperative recovery was uneventful, and at the 12-month follow-up, the patient remained disease-free with preserved endocrine function despite the loss of exocrine function.

This case illustrates the rare coexistence of a SCA with congenital distal pancreatic duct atresia and acinar cell depletion. The preservation of islet function amidst complete exocrine loss supports a developmental anomaly rather than obstruction-induced atrophy. This association suggests that congenital ductal defects may predispose patients to SCA formation. Surgical resection remains the optimal strategy for the diagnosis and management of atypical cystic pancreatic lesions with uncertain biological behavior.

This study aimed to investigate the clinical characteristics and imaging features of walled-off pancreatic necrosis (WOPNs) involving the pancreatic parenchyma in patients with no documented pancreatitis, and to establish a diagnostic prediction nomogram using Lasso regression to differentiate WOPNs from mucinous cystic neoplasms (MCNs).

A total of 247 cases were retrospectively collected from three independent hospitals, including surgically confirmed post-inflammatory necrotic collections meeting imaging criteria for WOPNs and pathologically confirmed MCNs. Clinical and imaging features were analyzed, and independent predictors were identified using Lasso regression. Clinical, imaging, and combined diagnostic models were constructed and assessed using ROC, calibration, and decision curve analyses (DCA). A diagnostic nomogram was developed from the best model.

Univariate analysis revealed significant differences between WOPNs and MCNs in the training cohort for age, sex, clinical symptoms, lesion location, shape, lesion margin, cyst category, incomplete septation, peripancreatic fat space, density/signal, cyst wall and/or septal thickness, mural nodule, lesion calcification, peripancreatic inflammatory changes, MPD morphology, location of ductal dilation, vascular involvement, and organ involvement (p < 0.05). Lasso regression identified three clinical features, eight imaging features, and five combined clinical and imaging features as independent risk factors, which were subsequently used to construct clinical, imaging, and combined models. The combined model achieved the highest diagnostic performance, with AUC values of 0.880 in the training cohort and 0.858 and 0.856 in the two external validation cohorts, respectively, demonstrating good sensitivity, specificity, and overall accuracy.

We established a reliable, non-invasive diagnostic prediction nomogram based on Lasso regression to differentiate WOPNs with no documented pancreatitis from MCNs.

Duodenal tumors constitute 35%-55% of small bowel neoplasms, yet the misdiagnosis rate remains substantial. This study investigated the clinical features of duodenal tumors missed during endoscopic examination.

This retrospective cohort analysis included patients who were diagnosed with duodenal tumors between 2019 and 2023 at West China Hospital. Demographic data, tumor characteristics, endoscopic findings, and missed diagnosis records were extracted from electronic medical records and telephone follow-ups. The exploratory analysis identified the reasons for the missed diagnosis during endoscopy.

Among the 307 enrolled patients with duodenal tumors, 36 patients (34 with adenocarcinomas and 2 with neuroendocrine tumors) had undergone previous endoscopic examinations without a definitive diagnosis, yielding a missed detection rate of 11.7%. In all missed cases, the mean number of endoscopic procedures performed prior to definitive diagnosis was 2 (range: 1-8), with an average interval of 11.1 months (range: 3-36 months). The anatomical distribution of missed lesions included the duodenal papilla (44.4%, 16/36), duodenal bulb (25.0%, 9/36), bulb-descending junction (5.6%, 2/36), descending (13.9%, 5/36) and horizontal (5.6%, 2/36) parts. The causes of missed diagnoses included exposure errors (n = 20), judgment errors (n = 5), biopsy errors (n = 8), and unclassified errors (n = 3). The difference in the pattern of missed duodenal tumors between tertiary hospitals and non-tertiary hospitals was not statistically significant (P > 0.05).

The missed diagnosis rate of duodenal tumors is high during endoscopic examination. Comprehensive endoscopic observation and improved detection awareness of duodenal tumors are essential in both tertiary and nontertiary hospitals.

Gastric cancer (GC), a highly aggressive and heterogeneous malignancy, remains challenging in immunotherapy despite recent advancements. This study aims to identify novel biomarkers and construct a prognostic model to improve outcome prediction and therapeutic strategies. Mendelian randomization (MR) analysis identified immune cell subtypes linked to GC using FinnGen and GWAS cohorts. CIBERSORT and WGCNA algorithms were applied to define M2 tumor-associated macrophage (TAM)-related gene modules. Key prognostic genes were selected via Lasso-Cox regression to establish a risk model, validated using GEO datasets. Biological function disparities, tumor microenvironment heterogeneity, and therapeutic sensitivities were assessed via GSEA and immune infiltration analysis. Protein-level validation was performed using TCGA, HPA, and Western blot. MR analysis revealed 26 immune cell subtypes associated with GC. WGCNA identified 20 gene modules, with the most M2 TAM-correlated module prioritized. A prognostic signature incorporating SEC61G, BGN, and STC1 was developed, stratifying patients into distinct risk groups with divergent survival outcomes (1-/3-/5-year, all P < 0.05). High-risk patients exhibited enriched calcium signaling pathways, reduced immunotherapy responsiveness, and increased sensitivity to veriparib and palbociclib. Protein overexpression of key genes was validated in GC tissues. This integrated bioinformatics-MR framework establishes a TAM-driven prognostic model for GC, demonstrating clinical utility in survival prediction, immunotherapy efficacy evaluation, and personalized therapeutic targeting. The findings provide actionable insights for advancing precision immunotherapy in GC.

Myelodysplastic syndromes (MDS) and Acute Myeloid Leukemia (AML) are increasingly recognized to exhibit immune dysregulation, which can occasionally present with autoinflammatory manifestations. We describe four patients with MDS/AML harboring p53 mutations and a complex karyotype who developed inflammatory serositis without infectious correlation. All patients showed clinical improvement following corticosteroid therapy.

BCL-2 has been implicated in prostate cancer (PCa) progression and development of castration-resistant disease (CRPC); however, it remains unclear how the BCL-2- and AR-expressing PCa cell populations evolve across the PCa continuum, how AR molecularly regulates BCL-2 and whether BCL-2 represents a common therapeutic target in heterogeneous CRPC. Here we first show the selective induction of BCL-2 by AR pathway inhibitors (ARPIs). Vectra-based quantitative multiplex immunofluorescence (qmIF) and image mass cytometry (IMC) analyses with single-cell resolution in patient PCa and xenograft models reveal markedly increased BCL-2⁺ (AR⁺ or AR^-) PCa cells in CRPC. Mechanistically, AR represses BCL-2 transcription through several AR binding sites and ARPIs relieve this repression. Therapeutic studies in cells, organoids and xenografts support BCL-2 as a shared vulnerability across diverse CRPC subtypes. A Phase Ib clinical trial (NCT03751436) combining enzalutamide and BCL-2 inhibitor venetoclax demonstrated reduced circulating tumor cells in responding patients. In summary, by integrating high-content single-cell level imaging analyses with mechanistic studies, extensive preclinical therapeutic experiments and a Phase Ib clinical trial, our studies herein elucidate the AR^+/-BCL-2^+/- PCa cell subpopulation dynamics and credentials BCL-2 as a vital therapeutic target in heterogeneous CRPC.