Esophagectomy remains the standard therapy for localized esophageal cancer, but postoperative function depends heavily on effective gastric conduit emptying. The aperistaltic conduit located in the negative pressure thoracic cavity is at risk of delayed gastric emptying leading to aspiration and pulmonary complications. This article summarizes historical and contemporary evidence evaluating pyloroplasty and alternative pyloric drainage strategies during esophagectomy. While earlier trials produced mixed results, recent level I evidence supports pyloroplasty as a safe adjunct that reduces gastric outlet obstruction and postoperative interventions. Meticulous conduit construction and vigilant postoperative assessment remain essential. There continues to be controversy, and an ongoing randomized trial, The PYNI-GAREREO Phase III Trial of Pyloroplasty Vs. No Pyloroplasty will be completed in the near future. (Trials.2023 Jun 19;24:412) and will add further level 1 evidence to this controversy.

The low response rate to immunotherapy in patients with lung adenocarcinoma is primarily due to tumor immune evasion. The tumor immunosuppressive microenvironment orchestrates this evasion, yet the underlying mechanisms remain elusive. Here we identify non-specific cytotoxic cell receptor protein 1 (NCCRP1) as a critical and previously uncharacterized regulator of this process.

We first analyzed publicly accessible patient-derived single-cell RNA sequencing and RNA sequencing data to investigate the expression of NCCRP1 in lung adenocarcinoma and its impact on the tumor immune microenvironment. Subsequently, the Nccrp1 gene was knocked out in mouse lung adenocarcinoma cells using CRISPR-Cas9. The effect of NCCRP1 deletion on tumor growth was then evaluated using subcutaneous transplantation models in both NSG and C57BL/6 mice. Single-cell RNA sequencing, flow cytometry and multiple targeted in vivo interventions were employed to assess the influence of NCCRP1 on the tumor immune microenvironment. To explore the underlying mechanisms by which NCCRP1 regulates the tumor immune microenvironment, we conducted co-immunoprecipitation, RNA pull-down, ubiquitination assay, mass spectrometry, isobaric tags for relative and absolute quantitation proteomics, dual-luciferase reporter gene assay, and ELISA.

Loss of NCCRP1 inhibits lung tumor growth and prolongs survival in immunocompetent C57BL/6 mouse models. NCCRP1 deficiency upregulates CX3CL1 to recruit CX3CR1⁺ antitumoral macrophages. These macrophages subsequently secrete CXCL9 and CXCL10, enhancing the infiltration of CD8⁺ T cells and NK cells into the tumor microenvironment. Mechanistically, NCCRP1 and STAU1 competitively bind to NEDD4. NCCRP1 deficiency enhances the STAU1-NEDD4 interaction, promoting ubiquitination and proteasomal degradation of STAU1, thereby increasing CX3CL1 messenger RNA stability. Remarkably, ablating NCCRP1 synergized with anti-programmed cell death protein 1 or interferon-γ therapy, leading to complete tumor eradication.

Our findings highlight NCCRP1 targeting as a promising therapeutic strategy to reprogram the immunosuppressive microenvironment and overcome the "cold tumor" phenotype in lung adenocarcinoma.

To characterize functional network alterations associated with aphasia and preserved language function in patients with left-hemispheric brain tumors using resting-state fMRI graph-theoretical analysis, with secondary evaluation of whether whole-brain network metrics are associated with aphasia status within the tumor cohort.

This retrospective IRB-approved study included 120 participants: 40 aphasic patients, 40 non-aphasic patients with left-hemispheric intra-axial tumors, and 40 matched healthy controls. ROI-to-ROI rs-fMRI connectivity across seven canonical networks yielded graph metrics (global/local efficiency, clustering, path length, centrality) at whole-brain, hemispheric, and network levels with FDR-corrected comparisons. Multinomial logistic regression compared healthy controls, non-aphasic patients, and aphasic patients. A secondary exploratory patient-only binary logistic regression examined aphasia status using whole-brain graph metrics and demographic covariates, including age, sex, and handedness.

The whole-brain multinomial model did not significantly distinguish healthy controls, non-aphasic patients, and aphasic patients (χ²=21.622, df=18, p=0.249; classification accuracy=57.5%). Therefore, individual graph-metric coefficients from this model were treated as exploratory rather than confirmatory. In a secondary exploratory patient-only regression, the model did not significantly distinguish aphasic from non-aphasic tumor patients after adjustment for age, sex, and handedness (Omnibus χ²=7.147, df=10, p=0.712; Nagelkerke R²=0.114; Hosmer-Lemeshow p=0.508; accuracy=62.5%). Whole-brain graph metrics were not independently associated with aphasia after demographic adjustment. ROI-level analyses showed focal differences in non-aphasic patients, including greater left IFG closeness, posterior parietal centrality, and anterior cerebellar connectivity, but these findings were interpreted as exploratory network correlates rather than definitive evidence of compensation.

Rs-fMRI graph-theoretical measures characterized network-level differences among aphasic patients, non-aphasic patients, and healthy controls, but the three-group multinomial model did not significantly distinguish the groups and the secondary patient-only regression did not independently distinguish aphasic from non-aphasic tumor patients after demographic adjustment. These findings suggest that graph metrics should be interpreted as exploratory system-level correlates of aphasia status and preserved language rather than stand-alone predictors or definitive markers of compensation.

Inhibitors of the KRAS protein have recently been reported to significantly improve the survival of patients with pancreatic cancer, bringing hope where once there was none. It is therefore timely, at this remarkable inflection point, that we review the long history of discoveries, many of them made by pathologists, that constructed this hope. Looking back, almost 20 years passed between Kirsten and Mayer's 1967 report of a transforming "murine sarcoma virus" and the first reports, in the mid-1980s, of somatic KRAS gene mutations in human pancreatic ductal adenocarcinomas (pancreatic cancers). The decades that followed saw confirmation of the remarkably high prevalence of these mutations in pancreatic cancer and the characterization of the timing of these mutations in precursor lesions, pancreatic intraepithelial neoplasms (PanINs) and intraductal papillary mucinous neoplasms (IPMNs). The demonstration in 2003 by Tuveson and colleagues that the introduction of mutant Kras^G12D into the mouse pancreas leads to the development of pancreatic cancer and its precursor lesions helped solidify the causal role for KRAS as an early driver of pancreatic tumorigenesis. In the years that followed, the high prevalence of somatic KRAS mutations in precursor lesions and in pancreatic cancer was used as a foundation for the development of new approaches to classify cyst type in the pancreas and to detect pancreatic cancer earlier. In 2013, Shokat and colleagues reported the successful direct chemical inhibition of mutant (KRAS^G12C) KRAS. The undruggable, became druggable. There are now over 50 agents, small molecules and vaccines, targeting mutant KRAS in clinical trials, and early reports include a near doubling of survival for patients with advanced disease. This story highlights the long arc of science: while decades may separate a fundamental discovery from improvements inpatient care, research saves lives.

Differentiating atypical Spitz tumors (AST) from true Spitz melanomas (SM) and conventional melanomas with spitzoid features (MSF) remains a formidable diagnostic challenge. Because current molecular epidemiological data are overwhelmingly derived from Caucasian cohorts, the genomic landscape of Asian populations remains largely unexplored. To elucidate the molecular progression landscape and refine diagnostic criteria, we performed a comprehensive multimodal analysis-integrating histomorphology, immunohistochemistry (IHC), multi-probe fluorescence in situ hybridization (FISH), and targeted RNA/DNA-based next-generation sequencing (NGS)-on a cohort of 140 spitzoid neoplasms. This cohort, comprising 126 ASTs, 8 SMs, and 6 MSFs, represents the largest Asian cohort to date. Malignant phenotype strongly correlated with lesional asymmetry, deep atypical mitoses, a sheet-like growth pattern, diffuse PRAME positivity, and significant loss of p16 expression (64.3% in SM/MSF vs. 9.5% in ASTs; P<0.0001). Building upon established melanoma FISH criteria, we optimized a prognostic threshold of ≥2 FISH abnormalities specifically tailored for spitzoid neoplasms. We demonstrated that isolated single chromosomal aberrations (particularly MYB loss) are relatively stable events frequent in indolent ASTs, whereas our refined ≥2 threshold yielded 100% sensitivity and 91.7% specificity for predicting regional lymph node metastasis/local recurrence. Molecularly, NGS identified mutually exclusive initiating driver alterations (comprising kinase fusions and HRAS mutations) in 89.9% of true Spitz neoplasms, a remarkably high prevalence suggesting a distinct genetic background in Asian populations. We also characterized five entirely novel kinase fusions (ZNF24::ROS1, PCBP1::ROS1, NUMA1::RET, CBWD1::ALK, and TPR::NTRK1). Furthermore, NGS definitively segregated true Spitz neoplasms from morphologic mimics (MSF), which lacked fusions and were driven by canonical genomic alterations of the conventional melanoma pathway. Integrating these genomic landscapes validated a stepwise progression model. While isolated kinase fusions drove indolent ASTs, malignant SM invariably harbored concurrent pathogenic secondary alterations, demonstrating a profound reliance on CDKN2A/B, TP53, and CDK4 aberrations. Ultimately, we propose an integrated diagnostic algorithm combining morphologic evaluation, the refined FISH threshold, and comprehensive NGS profiling, providing a precise, evidence-based framework for pathway classification and clinical management of spitzoid neoplasms.

Accurate pathology classification of lung neuroendocrine neoplasms (LNENs) can be challenging, particularly in small biopsies, resulting in substantial interobserver variability. To overcome this issue, central pathology review is frequently used in clinical and translational studies to improve diagnostic accuracy, but its methodology and impact remain poorly characterized. This systematic review was conducted in accordance with the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD42022354131). A comprehensive literature search of Embase, MEDLINE, Web of Science, Cochrane Central, and Google Scholar was performed (August 2022; updated January 2025). Eligible studies included original research involving ≥20 patients with pulmonary carcinoid and/or large cell neuroendocrine carcinoma that applied central pathology review. Two reviewers independently screened studies and extracted data on study characteristics, central pathology review methodology, and diagnostic concordance. Due to anticipated heterogeneity, results were synthesized descriptively without meta-analysis. A total of 8892 records was identified, of which 359 studies met the inclusion criteria. A central pathology review was described in 106 studies (29.5%). Methodology varied widely, including the number of pathologists (median 2 pathologists, ranging from 1 to 19), or not reported (12.3%)), definition of the consensus, and procedures to resolve disagreement. Diagnostic concordance measures were reported in only 21 studies (19.8%): unanimous diagnoses had a median of 59.3% (range 11.8-100%), while consensus rates had a median of 63.8% (range 22.3-100%), and disagreement rates had a median of 17.3% (range 6.3-36.7%. Interobserver variability, most often assessed using Cohen's kappa, ranged from 0.21 to 0.98. Overall, both implementation and reporting of central pathology review showed substantial heterogeneity. Central pathology review is applied in fewer than one-third of studies on LNENs and is characterized by marked heterogeneity in methodology, reporting, and assessment of diagnostic agreement. The frequent absence of standardized consensus criteria and concordance measures limits comparability and interpretability across studies. Greater transparency and standardization of central pathology review procedures, such as the structured reporting form proposed in this study, are needed to improve diagnostic reliability and reproducibility in pathology-driven translational and clinical research.

Atrial fibrillation (AF) and obesity are increasingly prevalent and interrelated, but how body mass index (BMI) influences cardiovascular outcomes and mortality in AF patients at a population level remains uncertain.

This study aimed to assess cardiovascular hospitalizations and mortality among AF patients by BMI.

Using linked Clinical Practice Research Datalink, Hospital Episodes Statistic, and Office for National Statistics data, we identified 71,519 adults with newly diagnosed AF (1998-2016) and a BMI measure within 12 months of diagnosis. Patients were grouped by World Health Organization BMI categories: underweight, normal weight, overweight, and obese. Primary outcome was all-cause mortality; secondary outcomes were hospitalizations for heart failure (HF), myocardial infarction, ischemic stroke, and bleeding.

The mean age was 74.9 ± 11.3 years; 44.9% were females. Over the median follow-up 5.72 years, 32,198 patients (45.0%) died. After multivariable adjustment, underweight was associated with higher all-cause mortality (HR: 1.87; 95% CI: 1.77-1.96), whereas overweight (HR: 0.72; 95% CI: 0.70-0.74) and obese (HR: 0.69; 95% CI: 0.67-0.71) categories had lower mortality vs normal weight. Obesity was independently associated with increased HF hospitalization risk, whereas overweight was modestly protective. Obesity was associated with lower adjusted myocardial infarction and bleeding hospitalization and showed no significant adjusted association with ischemic stroke. Cause-specific mortality analysis showed higher circulatory and neoplasm deaths among obese patients and higher respiratory deaths in underweight patients.

In this large, nationwide AF cohort, being underweight at the time of AF diagnosis was associated with higher mortality, whereas being overweight and obese were paradoxically associated with lower all-cause mortality despite increased HF hospitalizations in obese patients.

Lymph node metastasis (LNM) is frequent in patients with thymic neuroendocrine neoplasms (T-NENs), but detailed studies on metastatic patterns remain limited. This study integrates surgical, imaging, and pathologic data to characterize nodal spread, providing reference data to optimize lymph node dissection (LND) and radiotherapy planning.

Patients with pathologically confirmed T-NENs at our institution were included. Medical records were reviewed to obtain patient characteristics, treatment modalities, failure patterns, and survival outcomes. These data were subsequently analyzed.

Between September 2008 and December 2022, 72 patients (55 males, 17 females; median age 55 years, range 25-70 years) were included. Pathologic subtypes comprised typical carcinoid (TC, n = 9), atypical carcinoid (AC) (n = 50), and neuroendocrine carcinomas (NEC) (n = 13). During a median follow-up of 53 months, cumulative lifetime nodal involvement (including baseline and recurrence) was observed in 67 patients (93.06%). Cumulatively, the most frequently involved stations were right lower paratracheal (51.39%), left perijugular (47.22%), and subcarinal (43.06%), with additional, less frequent involvement at other stations. The cumulative LNM rate was 100% in TC, 92.00% (46/50) in AC, and 92.31% (12/13) in NEC. The median progression-free survival was 23 months, and the 5-year overall survival was 63.31%.

This study summarizes detailed patterns of LNM and highlights the importance of locoregional treatment. The findings provide a reference for defining the extent of surgical dissection and designing radiotherapy clinical target volumes (CTV), and a basis for future prospective studies.

Chemotherapy-induced neutropenia is a frequent complication in patients with cancer that can lead to severe outcomes like sepsis, hospitalizations, and treatment delays. A neutropenic sepsis care bundle was implemented in an.

At diagnosis and throughout treatment of acute myeloid leukemia, oral leukemic infiltrates from malignant blast cell invasion and mucosal ulcerations (i.e., mucositis as a side effect of antineoplastic therapy) are common. Ma.