Citations

4235 Background: Malignant portal vein tumor thrombus (PVTT) arising from hepatic metastases is associated with poor prognosis, rapid hepatic decompensation, and limited effective local treatment options despite systemic therapy. In real-world practice, local treatment intensity is frequently adapted to disease burden and treatment response. We evaluated outcomes of a risk-adapted, step-up local treatment strategy using microwave ablation (MWA) alone or in combination with iodine-125 (I-125) seed implantation for patients with malignant PVTT. Methods: We retrospectively reviewed patients with hepatic metastases treated with MWA with or without I-125 seed implantation between 2023 and July 2025. In clinical practice, MWA alone was preferentially used for patients with relatively limited disease burden, while MWA plus I-125 was employed as an escalation strategy for patients with more advanced PVTT or disease progression following MWA alone. The primary endpoint was PVTT-directed local outcome, defined as portal vein patency and/or local control of tumor thrombus on follow-up imaging. Secondary endpoints included progression-free survival (PFS), overall survival (OS), hepatic function changes, and treatment-related toxicity. Survival analyses were considered exploratory. Results: A total of 73 patients were included, of whom 50 were treated with MWA alone and 23 with MWA plus I-125 seed implantation. Patients receiving MWA plus I-125 demonstrated more advanced disease characteristics, including universal presence of PVTT and higher disease stage, consistent with treatment escalation by disease severity. Among patients with PVTT, MWA plus I-125 achieved portal vein patency and/or local control in 65% at first follow-up imaging. Treatment-related toxicities were manageable, with no unexpected grade ≥3 adverse events attributable to I-125 implantation. Median PFS was 11.5 months in patients treated with MWA alone and 9.9 months in patients treated with MWA plus I-125, consistent with greater baseline disease burden in the latter group. Conclusions: MWA alone and MWA plus I-125 function as complementary components of a risk-adapted, step-up local treatment strategy for malignant PVTT from hepatic metastases. Escalation to MWA plus I-125 appears feasible in patients with advanced or refractory PVTT and demonstrates a potential signal for improved PVTT-directed local control and portal vein patency. Prospective studies focused on PVTT-specific endpoints are warranted.

OBJECTIVE Intramedullary spinal cord tumors (IMSCTs) are typically treated with maximal safe resection, during which neurosurgeons often monitor for neurological injury using muscle motor evoked potential (mMEP) and direct wave (D-wave) neuromonitoring. The predictive value of changes in D-waves for identifying motor outcomes is underexplored. This study evaluated the utility of D-waves for predicting postoperative motor deficits. METHODS Patients who underwent resection of a primary IMSCT with mMEP neuromonitoring from 2003 to 2023 at a tertiary care hospital were identified. Patients who underwent D-wave monitoring in addition to mMEP monitoring were compared to those who underwent mMEP monitoring alone using the Mann-Whitney U-test, chi-square test, and Fisher’s exact test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of D-wave and mMEP monitoring for identifying new neurological deficits immediately postoperatively and at 1 month, 6 months, and last follow-up were calculated. RESULTS After matching, 125 patients were included (median age 42.0 years; 57.6% male; median follow-up 34.0 months), of whom 88 had both mMEP and D-wave data. The most common pathologies were ependymoma (64.0%) and astrocytoma (17.6%). Patients who did and did not undergo D-wave neuromonitoring had similar preoperative neurological function, primary pathology, tumor grade, and tumor location. D-wave use was associated with increased gross-total resection (88.6% vs 64.9%, p = 0.002) and reduced mortality (5.7% vs 24.3%, p = 0.007), length of stay (5.0 vs 6.0 days, p = 0.033), and 30-day readmission (2.3% vs 13.5%, p = 0.013) and reoperation (1.1% vs 10.8%, p = 0.012). At the 6-month follow-up, D-wave monitoring alone was superior to mMEP and combination monitoring for detecting new motor deficits. D-wave monitoring had peak sensitivity (77.8%) and NPV (96.5%) at 6 months and peak specificity (95.8%) and PPV (76.9%) in the immediate postoperative period. CONCLUSIONS D-wave monitoring was associated with reduced mortality and was more accurate than mMEP monitoring alone or combination monitoring for detecting new postoperative neurological deficits. Further prospective studies are needed to validate these results.

Objectives To compare patients’ perception of their degree of subglottic stenosis to their endoscopic exam findings, Clinical Dyspnea Questionnaire, and peak flow results. Study Design Prospective Multi-Institutional. Setting Tertiary Care Clinic. Methods A study of 50 patients comparing patients’ perception of their degree of subglottic stenosis to their endoscopic exam findings. All patients filled out a Clinical Dyspnea Questionnaire and a 10-point scale reflecting their perceived degree of stenosis in 10% intervals. Surgeons filled out the same scale based on measurements from the patients’ exam. Accuracy was defined as +/-1 on a 10-point scale. Pulmonary function testing, number of dilation procedures undergone, cause of stenosis, and demographic information were collected. Results Data complete for 49/50 patients. 48 (98%) were female, 47 (97.9%) Caucasian, 44 (89.8%) had idiopathic subglottic stenosis, and 28 (58.3%) had Grade I subglottic stenosis on the Cotton-Meyer scale. Spearman correlation coefficient was 0.67 indicating moderate correlation overall but 0.88, or high correlation, for those with normal Body Mass Index. Increased Dyspnea Index scores and higher Body Mass Index were correlated with decreased accuracy. Number of previous procedures was not correlated with accuracy. Higher Body Mass Index was correlated with increased dyspnea and lower peak flow volume. Conclusion Patients with normal Body Mass Index have strong predictive accuracy regarding their degree of subglottic stenosis. Better dyspnea scores were correlated with improved accuracy. There is no standard consensus on subglottic stenosis patient follow up. Prior studies have looked at using peak flow meters and validated questionnaires to monitor symptoms.

Introduction Historic series have demonstrated the importance of construct rigidity in the treatment of pelvic discontinuities, but there remains limited data comparing different constructs, especially contemporary cup-cages and custom triflange components. The aim of this study was to evaluate reconstructive constructs with emphasis on implant survivorship, radiographic results, complications, and clinical outcomes. Methods We reviewed 184 revision THAs with unilateral pelvic discontinuity at a single institution between 1998–2022. Mean age was 66 years, 83% were female, and mean BMI was 29 kg/m2. Constructs included uncemented cup and plating (n=66, 36%), cup-cages (n=59, 32%), jumbo uncemented acetabular components (n=30, 16%), conventional antiprotrusio cages (n=16, 9%), and custom triflanges (n=13, 7%). Since 2013, 73% of cases were treated with either a cup-cage or custom triflange. Acetabular distraction (n=36, 20%) and porous augments (n=33, 18%) were used as adjuncts. Mean follow-up was 8 years. Results The 5-year survivorships free of revision for aseptic loosening, any revision, and any reoperation were 92%, 79%, and 75%. Of 43 revisions, the most common indications were aseptic loosening (n=15) and dislocation (n=15). For each construct, the 5-year survivorships free of revision for aseptic loosening were 100% (triflange), 94% (cup-cage), 92% (uncemented jumbo acetabular component), 90% (plating), and 86% (conventional anti-protrusio cage). Radiographic analysis demonstrated discontinuity healing in 85% of unrevised patients. Of the 15 re-revisions for aseptic loosening, 92% involved loss of fixation from inferior hemipelvis. There were 63 complications with dislocation (n=32), nerve palsy (n=10), and wound problems (n=9) most common. Mean Harris hip scores improved from 51 to 70 at 5 years. Conclusion In this series, the 5-year survivorship free from aseptic loosening was very good (92%), especially with contemporary techniques like custom triflange (100%) and cup-cage constructs (94%). Survivorship free from any revision (79%) and reoperation (75%) remain lower due to dislocation and infection.

Background: Contemporary rotating-hinge total knee arthroplasties (RH-TKAs) have shown reasonable short-term survivorship in smaller series, but concerns remain regarding risks of aseptic and septic failure. The purpose of this study was to assess outcomes of contemporary RH-TKAs in one of the largest series to date. Methods: We retrospectively identified 575 RH-TKAs (60% used for aseptic etiologies and 40% used during reimplantation in 2-stage treatment of periprosthetic joint infection [PJI]) from 2002 to 2021 at a single institution. The mean age was 67 years, 58% were female, and the mean body mass index was 33 kg/m 2 . Sixty-five percent had Anderson Orthopaedic Research Institute (AORI) type-2B or 3 bone loss. Kaplan-Meier survivorship analyses were performed. The mean follow-up was 6 years (range, 2 to 19 years). Results: Survivorship free from any revision was 76% at 5 years and 64% at 10 years. The most common revision indications were PJI (54%) and aseptic loosening (20%). RH-TKA used in the primary setting showed better survivorship compared with RH-TKA used during reimplantation after PJI (79% versus 60% at 10 years). Survivorship free from revision for aseptic loosening was 96% at 5 years and 90% at 10 years. Survivorship free from revision for PJI was 84% at 5 years and 81% at 10 years. Survivorship free from revision for PJI was even lower for RH-TKAs used during reimplantation, 74% at 5 years and 73% at 10 years. RH-TKA used during reimplantation in the treatment of PJI was associated with an increased risk of any revision (HR = 2, p < 0.001). Radiographic analysis of 425 knees that were not revised and had radiographs available for review showed that 6% of femoral components and 8% of tibial components had evidence of loosening at the time of final follow-up. The mean Knee Society Score improved from 33 to 69 at 2 years (p < 0.001). Conclusions: The 10-year survivorship free from aseptic loosening was 90% in this large series of RH-TKAs. This represents one of the best survivorships free from aseptic loosening published to date. Knees with prior PJI had markedly poorer survivorship than knees treated for aseptic etiologies, with double the risk of revision. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Abstract Background: Early-onset gastrointestinal (GI) cancers are increasing globally, yet the genomic basis for age-related differences across multiple tumor types remains poorly defined. We leveraged AACR Project GENIE v18.0 (N≈34,000 GI tumors) to characterize molecular distinctions by age in colorectal, pancreatic, small bowel, and anal cancers with sufficient early-onset representation. Methods: Clinical and genomic data were extracted and tumors classified into early-onset (&lt;50 years) and late-onset (≥50 years). Mutation frequencies were compared by cancer type and age group, focusing on recurrent drivers, DNA repair, Wnt signaling, RAS/MAPK, chromatin remodeling genes, and targetable alterations. Results: Early-onset colorectal cancer (N=5,724) showed increased Wnt/β-catenin pathway alterations: APC (+4.9%), TCF7L2 (+4.1%), and TP53 (+5.0%), while late-onset tumors (N=15,807) were enriched for BRAF (−5.4%), RNF43 (−1.9%), and GNAS (−1.1%), indicating divergent tumorigenic pathways. Early-onset pancreatic cancer (N=890) exhibited significantly lower frequencies of canonical drivers—KRAS (−24.7%), TP53 (−15.6%), CDKN2A (−6.9%), SMAD4 (−6.0%)—with enrichment of MEN1 (+3.5%), TSC2 (+3.0%), ATRX (+2.0%), DAXX (+1.9%), and CTNNB1 (+2.4%), consistent with fusion-driven, hereditary, and chromatin remodeling biology. Small bowel cancer (N=99) in early-onset patients demonstrated enrichment in DNA damage response and MAPK/RAS genes including BRCA2 (+7.2%), NF1 (+7.4%), FBXW7 (+8.8%), FLT4 (+6.5%), ARAF (+6.4%), and ALK (+5.1%), whereas late-onset tumors (N=538) were enriched for KDR (−5.1%) and MGA (−5.2%). Early-onset anal cancer (N=62) showed elevated MGA (+7.8%), WHSC1/NSD2 (+6.9%), PBRM1 (+6.2%), FANCA (+5.2%), ERCC5 (+6.2%), and MSH6 (+5.9%), highlighting chromatin remodeling and DNA repair pathways potentially related to HPV biology; late-onset tumors (N=464) had enrichment in ATM (−5.6%), PTEN (−5.5%), STK11 (−5.2%), APC (−5.2%), and KMT2C (−5.0%), reflecting age-associated genomic instability. Conclusions: This pan-GI age-stratified analysis reveals distinctive oncogenic programs in early-onset GI cancers characterized by Wnt/TP53-driven colorectal, fusion- and chromatin remodeling-driven pancreatic, DNA damage response/MAPK-driven small bowel, and chromatin-immune DDR signatures in anal cancers. These findings underscore the need for age-tailored precision oncology and support routine genomic profiling in early-onset GI malignancies to identify targetable alterations enriched in younger patients. Citation: AACR Project GENIE Consortium. AACR Project GENIE: Powering Precision Medicine Through an International Consortium. Cancer Discov. 2017;7(8):818-831. (Data: GENIE Release 18.0-public)Acknowledgement: AACR and Project GENIE registry Citation Format: Ahmed Abdelhakeem, Nency Ganatra, Dina Elantably, Tayo Adeoye, Nayef H. Abdel-Razeq, Mosalem M. Osama, Hani M. Babiker. Distinct age associated genomic landscapes in colorectal, pancreatic, small bowel, and anal cancers: A pan gastrointestinal analysis of 34,000 tumors from AACR Project GENIE v18.0 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4105.

Abstract Background: PARP inhibitors are restricted to a subset of BRCA-associated cancers, but homologous recombination repair (HRR) deficiency signifies a broader genomic vulnerability that may extend therapeutic opportunities across diverse malignancies. We utilized AACR Project GENIE v18.0-public to define the pan-cancer prevalence of HRR gene alterations. Methods: Somatic mutation and clinical sample data from GENIE v18.0-public were analyzed. HRR genes included BRCA1, BRCA2, ATM, CHEK2, PALB2, RAD51B/C/D, RAD51L1, BARD1, BRIP1, and core FANC genes. HRR alteration rates were calculated by tumor type using unique samples; only de-identified aggregate results are reported. Results: Among 101,240 tumors, HRR gene alterations were frequent in multiple non-BRCA-associated cancers. Highest rates were seen in sialoblastoma (100%), large cell medulloblastoma (50%), malignant glomus tumor (50%), lung cancer (46.0%), infantile fibrosarcoma (42.9%), liver (40%), kidney (40%), non-melanoma skin (36.9%), colorectal (36.6%), melanocytoma (34.2%), biliary tract (33.3%), bladder (31.5%), and ovarian/fallopian tube (30.2%). Notably, lung, bladder, hepatobiliary, renal, gastrointestinal, and some sarcoma subtypes showed HRR mutation prevalence equal or higher than current PARP indications, yet lack FDA approval. Conclusions: HRR alterations are widespread across solid tumors, often surpassing rates in cancers eligible for PARP treatment. These findings support expanding tumor-agnostic HRR genomic testing beyond BRCA-linked malignancies and warrant prospective trials of PARP inhibitors in HRR-enriched tumor types such as lung, bladder, hepatobiliary, renal, gastrointestinal, and pediatric/rare cancers. Impact: Large-scale genomic profiling from AACR Project GENIE demonstrates that HRR gene alterations are common across diverse solid tumors, with prevalence in multiple cancer types surpassing those currently eligible for PARP inhibitor therapy. These findings support broad implementation of HRR genomic testing in routine molecular diagnostics and provide a rationale for expanding PARP inhibitor use beyond BRCA-associated malignancies. The data justify prospective tumor-agnostic clinical trials of PARP inhibitors in HRR-enriched cancers such as lung, bladder, hepatobiliary, renal, gastrointestinal, and select pediatric and rare tumors; this could transform therapeutic decision-making and accelerate development of synthetic lethality-based targeted therapies Citation: AACR Project GENIE Consortium. Cancer Discov. 2017;7(8):818-831 Acknowledgement: AACR and Project GENIE Citation Format: Ahmed Abdelhakeem, Nency Ganatra, Dina Elantably, Tayo Adeoye, Nayef H. Abdel-Razeq, Osama M. Mosalem, Hani M. Babiker. Pan cancer enrichment of homologous recombination repair (HRR) gene alterations in 101,240 tumor samples from AACR Project GENIE: Implications for tumor-agnostic PARP inhibitor expansion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4106.

Background: Revision total hip arthroplasty (THA) rates are increasing, with instability, aseptic loosening, and infection identified as primary indications for surgery. Managing significant acetabular and femoral bone loss remains a complex challenge, requiring standardized classification systems to guide reconstruction strategies. Objective: This article reviews current surgical protocols and clinical outcomes for complex THA revisions, specifically focusing on the management of bone defects and periprosthetic fractures using techniques employed at the Mayo Clinic. Key Points: Preoperative evaluation must prioritize the exclusion of infection via inflammatory markers and joint aspiration. Acetabular reconstructions are categorized by the Paprosky classification; Type 3 defects often necessitate jumbo cups, porous tantalum augments, or custom triflange implants to achieve stability. In cases of pelvic discontinuity, tantalum cup-cage constructs or distraction techniques are utilized, showing high short-term survival despite risks of stress fractures or reduced bone stock. Femoral revisions utilize modular fluted tapered stems (TMFT) for Paprosky Type 3 and 4 defects, providing superior axial and longitudinal stability compared to cemented options. Extended lateral femoral osteotomy is frequently employed to facilitate component removal. Periprosthetic fractures are managed according to the Vancouver classification, with stable stems treated via internal fixation and loose stems requiring TMFT or proximal femoral replacement. Conclusion: Successful THA revision relies on meticulous preoperative planning and the selection of implants that ensure osseointegration and mechanical stability. The shift toward porous metal technology and modular femoral components has improved outcomes in cases of severe bone deficiency.

Aims Total knee arthroplasty (TKA) for end-stage osteonecrosis has historically been associated with concerns regarding aseptic loosening, and long-term data are limited. The purpose of this study was to update and expand our previous series with long-term follow-up, with specific emphasis on implant survivorship, risk factors for failure, complications, and clinical outcomes in a consecutive cohort of TKAs performed for primary and secondary osteonecrosis. Methods We retrospectively identified 295 consecutive TKAs in 266 patients for osteonecrosis performed at a single tertiary care academic institution from January 2002 to July 2022. Of these, 207 TKAs (70%) were performed for primary osteonecrosis, and 88 (30%) for secondary osteonecrosis. The predominant cause of secondary osteonecrosis was steroid use (59%; n = 52), followed by post-traumatic (25%; n = 22), radiation-induced (9%; n = 8), and alcohol-induced (7%; n = 6) osteonecrosis. Implant survivorship was analyzed as a time-to-event outcome using Kaplan-Meier estimation. The mean age was 61 years (18 to 93), with 67% being female (n = 197). The mean follow-up was nine years (2 to 20). Results The 15-year survivorship free of any revision for the entire cohort was 92% (95% CI 87 to 97), with similar rates between primary and secondary osteonecrosis (92% (95% CI 87 to 98) vs 93% (95% CI 87 to 100), respectively; p = 0.459). Varus-valgus constraint implant designs (HR 10.8 (95% CI 2.7 to 43.4); p < 0.001) and tibial stem use (HR 12.0 (95% CI 4.1 to 35.1); p < 0.001) were associated with an increased risk of any revision. The 15-year survivorship free of aseptic loosening was 97% (95% CI 93 to 100) for the entire cohort. Age under 65 years (HR 2.7 (95% CI 1.4 to 5.4); p = 0.005) and secondary osteonecrosis (HR 1.9 (95% CI 1.0 to 3.4); p = 0.044) were associated with an increased risk of any reoperation at 15 years. Conclusion TKA is a durable and reliable option for primary osteonecrosis at long-term follow-up. However, TKAs performed for secondary osteonecrosis carry a higher reoperation risk. Cite this article: Bone Joint J 2026;108-B(4):455–462.

Background: Rheumatic heart disease (RHD) remains a prevalent cause of valvular heart pathology worldwide, especially in younger populations of low- and middle-income countries. Tricuspid valve (TV) involvement in RHD is usually secondary to left-sided valvular lesions and is often underdiagnosed, since two-dimensional echocardiography (2DE) has limited ability to visualize the complex tricuspid anatomy. Compared with 2DE, three-dimensional echocardiography (3DE) provides an en face visualization of the tricuspid valve, enabling direct planimetric measurements and detailed commissural assessment, and offers advantages for evaluating complex valvular heart disease (VHD). Thus, this study aimed to assess baseline characteristics and valvular morphology in patients with rheumatic tricuspid valve disease using 3DE. Methods: A prospective cohort single-center study conducted between April 2022 and April 2023 included 34 patients with rheumatic TV involvement. Baseline demographics, morphological features, and hemodynamic parameters were assessed using transthoracic 3DE. Results: The mean age of included patients was 45.5 ± 9.1 years, and 88.2% were female. Most patients had associated left-sided valvular involvement (mitral or combined mitral and aortic). Commissural fusion (50%), leaflet thickening (82.4%), restricted mobility (85.3%), and coaptation loss (58.8%) were predominantly noted. The mean diastolic TV gradient was 3.9 ± 3.4 mmHg, planimetry area 3.3 ± 1.7 cm2, and estimated pulmonary artery systolic pressure 43.3 ± 19.5 mmHg. Mean right ventricular (RV) global longitudinal strain was –23.6 ± 6.1%. Conclusion: Rheumatic TV involvement is characterized by commissural fusion, leaflet thickening, and coaptation loss, highlighting the diagnostic value of 3DE in identifying morphological patterns that may guide intervention planning.