Citations

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent and aggressive subtype of non-Hodgkin lymphoma comprising 30% to 40% of cases. While DLBCL frequently arises in the lymph nodes, up to 40% of cases originate in extranodal tissues. Primary splenic DLBCL is extremely rare comprising only ~1% of DLBCL cases and can be complicated by rare entities including gastrosplenic fistula (GSF). In contrast to DLBCL, polycythemia vera (PV) is a myeloproliferative malignancy. Polycythemia vera can transform into other hematologic malignancies including post-polycythemia myelofibrosis, but associations with DLBCL are uncommon. We present the first case of PV with concomitant primary splenic DLBCL complicated by GSF. While the majority of splenic lesions are benign, they have a broad differential diagnosis including malignant etiologies. Cystic or solid morphology, the number of lesions, and vascularity on imaging heavily guide further management. Due to concern for imminent massive upper gastrointestinal bleeding in the setting of GSF, our patient was diagnosed and managed with prompt splenectomy and gastrectomy. Percutaneous splenic biopsy is also a safe and effective diagnostic modality, but was deferred in our case given increased bleeding risk with PV. In conclusion, primary splenic lymphoma should be in the differential for a splenic mass regardless of whether the patient has a prior hematologic malignancy, and management should be prompt especially if complicated by a GSF.

Background: Total knee arthroplasty (TKA) and hindfoot reconstruction (HFR) are often used to treat osteoarthritis and deformities of the knee and hindfoot. Despite the proven clinical effectiveness of these treatments, postoperative patient dissatisfaction is high. The knee and ankle are adjacent joints in the lower extremity, and angular deformity of either joint is known to affect positioning of the anatomical and mechanical axes of the entire limb. Although it is understood this relationship exists, there are limited studies evaluating outcomes of ipsilateral procedures on patients with pathologies of both knee and hindfoot. This article aims to evaluate whether TKA or TAA/HFR sequencing influences postoperative outcome. The study hypothesis is that TKA prior to TAA/HFR results in lower reoperation. Methods: A retrospective chart review using Current Procedural Terminology ( CPT ) codes was performed encompassing all patients who underwent TKA in conjunction with a variety of hindfoot procedures. All procedures were performed at a single academic medical site between 2000 and 2022. Exclusion criteria included those patients not having both ipsilateral TKA and hindfoot procedures or those lacking conclusive postoperative data. The primary outcome of this study was to identify significant reoperations such as adjacent joint arthrodeses, hardware removal, or unrelated ipsilateral limb surgery. Secondary outcomes included identification of revision procedures including revision TKA or revision HFR and other postoperative complication data. Results: This study included 158 patients, with 79 patients in each group. In the TKA-first group, the mean follow-up time was 10.24 years (range, 1.10-22.42 years) and the mean time to HFR was 5.94 years. In the HFR-first group, the mean follow-up time was 9.01 years (range, 1.01-23.55 years) and the mean time to TKA was 5.51 years. In patients who underwent TKA first, the mean reoperation rate was not significantly different from those who underwent HFR/TAA first, 30.4% vs 19.0% ( P = .12). In patients who underwent TKA first, the rate of HFR reoperations (22.78%) was greater than TKA reoperations (7.59%) ( P < .01). The revision rate was higher in the TKA-first group (17.7%) when compared to the HFR-first group (6.3%) ( P = .03). Additionally, there were more revision HFR procedures in the TKA-first group (9/79) compared with the HFR-first group (1/79) ( P = .009). Conclusion: In contrast to the study hypothesis that TKA first would result in less reoperation, our study found that TAA or HFR performed before TKA had an overall lower complication rate. However, these findings should be interpreted cautiously as the sample size was limited. Level of Evidence: Level III, retrospective cohort study.

The gastrointestinal tract is made up of specialized organs that work in tandem to facilitate digestion. The colon regulates the final steps in this process where complex motor patterns in proximal regions facilitate the formation of fecal pellets that are propelled along the distal colon via self-sustaining neural peristalsis and temporarily stored before defecation. Historically, our understanding of colonic motility has focused primarily on distal regions, and the intrinsic reflex circuits of the enteric nervous system involved in neural peristalsis have been defined, but we do not yet have a clear grasp on the mechanisms orchestrating motor function in proximal regions. New approaches have brought to the forefront the unique structural, neurochemical, and functional characteristics that exist in distinct regions of the mouse and human colon. In this mini-review, we highlight key differences along the proximal-distal colonic axis and discuss how these differences relate to region-specific motor function.

Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterised by multiorgan pathological histiocytic infiltration. Cardiac involvement occurs in 40–75% of patients and increases mortality. A 55-year-old woman with chest pain and dyspnoea was found to have an interatrial septal mass and aortitis suspicious for ECD without other organ involvement. After two inadequate transcatheter interatrial biopsies were obtained using ultrasound guidance alone, diagnostic samples were successfully obtained using intraprocedural frozen section examination. The patient started genotype-targeted treatment with good response. Biopsy confirmation of ECD is required to guide treatment; however, cardiac biopsies are uncommonly performed when other organs are affected. Our unique case of isolated cardiovascular involvement highlights how frozen sectioning with multimodal intraprocedural imaging guidance can improve diagnostic yield of endomyocardial biopsies. It also highlights how diagnosis of rare conditions requires careful multidisciplinary evaluation of affected organs, procedural risk and diagnostic yield. The use of frozen sectioning can improve diagnostic yield of endomyocardial biopsies.

Abstract Biliary tract cancer (BTC) remains among the most challenging malignancies with a poor prognosis and limited treatment options, particularly in pretreated patients. As most patients experience disease progression after first-line treatment, effective second-line and subsequent treatments are required. Although the addition of modified FOLFOX (fluorouracil, leucovorin, and oxaliplatin) to active symptom control improved the overall survival of patients with progressing advanced BTC despite gemcitabine plus cisplatin treatment, its efficacy was modest. Moreover, most clinical trials demonstrated modest efficacy of molecular-targeted agents for molecularly unselected pretreated advanced BTC. Patients with advanced BTC carry a relatively high druggable genetic alteration rate and have shown promising responses to molecular-matched therapies targeting gene alterations such as FGFR2 fusions/rearrangements, IDH1 mutation, and HER2 overexpression/amplification. Additionally, tumor-agnostic approaches, including BRAF V600E, NTRK fusion, and RET fusion, have expanded the treatment options for some patients. Immune checkpoint inhibitors have shown limited efficacy as mono- or combination therapy in patients with pretreated advanced BTC. Therefore, developmental efforts have shifted to immune checkpoint inhibitor and other combinations such as vascular endothelial growth factor receptor inhibitors or radiation. In addition to refining combination strategies to enhance the therapeutic potential of immune checkpoint inhibitor, future research should focus on elucidating the tumor microenvironment. This review delineates the evolution of systemic therapies in patients with pretreated advanced BTC. By examining past developments and recent advances through prospective trials, it highlights novel approaches that may improve outcomes in this challenging disease.

Importance Completion of the Human Genome Project prompted predictions that genomics would transform medicine, including through genomic screening that identifies potentially medically actionable findings that could prevent disease, detect it earlier, or treat it better. However, genomic screening remains anchored in research and largely unavailable as part of routine care. Objective To summarize 11 years of experience with genomic screening and explore the landscape of genomic screening efforts. Design, Setting, and Participants This cohort study was based in Geisinger’s MyCode Community Health Initiative, a genomic screening program in a rural Pennsylvania health care system in which patient-participants exomes are analyzed. Main Outcomes and Measures Genomic screen-positive rates were evaluated and stratified by condition type (cancer, cardiovascular, other) and US Centers for Disease Control and Prevention (CDC) Tier 1 designation. The proportion of participants previously unaware of their genomic result was assessed. Other large-scale population-based genomic screening efforts with genomic results disclosure were compiled from public resources. Results A total of 354 957 patients participated in Geisinger’s genomic screening program (median [IQR] age, 54 [36-69] years; 194 037 [59.7%] assigned female sex at birth). As of June 2024, 175 500 participants had exome sequencing available for analysis, and 5934 participants (3.4%) had a pathogenic variant in 81 genes known to increase risk for disease. Between 2013 and July 2024, 5119 results were disclosed to 5052 eligible participants, with 2267 (44.2%) associated with risk for cardiovascular disease, 2031 (39.7%) with risk for cancer, and 821 (16.0%) with risk for other conditions. Most results (3040 [59.4%]) were in genes outside of those with a CDC Tier 1 designation. Nearly 90% of participants (4425 [87.6%]) were unaware of their genomic risk prior to disclosure. In a survey of large-scale biobanks with genomic and electronic health record (EHR) data, only 25.0% (6 of 24) disclosed potentially actionable genomic results. Conclusions and Relevance In this large, genomics-informed cohort study from a single health system, 1 in 30 participants had a potentially actionable genomic finding. However, nearly 90% were unaware of their risk prior to screening, demonstrating the utility of genomic screening in identifying at-risk individuals. Most large-scale biobanks with genomic and EHR data did not return genomic results with potential medical relevance, missing opportunities to significantly improve genomic risk ascertainment for these individuals and to perform longitudinal studies of clinical and implementation outcomes in diverse settings.