High Risk Of Recurrence Research Articles

Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial

The phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial met its primary endpoint. Niraparib first-line maintenance significantly prolonged progression-free survival (PFS) among patients with newly diagnosed advanced ovarian cancer (aOC) that responded to first-line platinum-based chemotherapy, regardless of homologous recombination deficiency (HRD) status. Final overall survival (OS) results are reported. Patients were randomized 2:1 to niraparib or placebo, stratified by response to first-line treatment, receipt of neoadjuvant chemotherapy, and tumor HRD status. After reaching 60% target maturity, OS was evaluated via a stratified log-rank test using randomization stratification factors and summarized using Kaplan-Meier methodology. OS testing was hierarchical (overall population first, then the homologous recombination-deficient [HRd] population). Other secondary outcomes and long-term safety were assessed; an updated, ad hoc analysis of investigator-assessed PFS was also conducted (cutoff date, 08Apr2024). Median follow-up was 73.9 months. In the overall population, the OS hazard ratio (HR) was 1.01 (95% CI, 0.84-1.23; P= 0.8834) for niraparib (n= 487) versus placebo (n;= 246). In the HRd (n= 373) and homologous recombination-proficient (n= 249) populations, the OS HRs were 0.95 (95% CI, 0.71-1.29) and 0.93 (95% CI 0.69-1.26), respectively. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 11.7% and 15.8% of niraparib patients and 37.8% and 48.4% of placebo patients in the overall and HRd populations, respectively. The 5-year PFS rate numerically favored niraparib in the overall (niraparib, 22%; placebo, 12%) and HRd populations (niraparib, 35%; placebo, 16%). Myelodysplastic syndromes/acute myeloid leukemia incidence was <2.5% (niraparib, 2.3%; placebo, 1.6%). No new safety signals were observed. In patients with newly diagnosed aOC at high risk of recurrence, there was no difference in OS between treatment arms. In the HRd population, patients alive at 5 years were twice as likely to be progression free with niraparib treatment than placebo. Long-term safety remained consistent with the established niraparib safety profile.

Urinary incontinence due to pregnancy – the impact of hormones and biofeedback therapy

Abstract In this article, attention is drawn to the serious problem of the occurrence of urinary incontinence because of pregnancy. The condition is problematic mainly in the elderly, as well because of the first and each subsequent pregnancy. Urinary incontinence can be a reason for social and professional exclusion, psychological problems and rising medical costs worldwide. Pregnancy as a complex process is a major factor in the occurrence of urinary incontinence in women at a younger age, consisting of hormones and all the procedures associated with childbirth. The physiotherapist has many tools that clearly affect how quickly the patient will recover, and one of them is biofeedback therapy. The process of treating incontinence needs further research and improved guidelines, as the condition is one of the most common complications of pregnancy, with a high risk of recurrence.

Les cancers thyroïdiens : diagnostic et suivi

AbstractThyroid cancers are often diagnosed during the exploration of a thyroid nodule. They are developed at the expense of follicular cells mainly differentiated of papillary or vesicular types and associated with a good prognosis, more rarely of oncocytic type and exceptionally of anaplastic type, associated with a poor prognosis. Medullary thyroid carcinomas are developed at the expense of C cells and are part of a MEN 2, associated with a proto-oncogene RET mutation in 25% of cases. Thyroid function is generally conserved. Diagnosis is based on ultrasound, which will characterize the thyroid nodule(s) and the cervical adenopathies to be punctured. The cyto-histological examination establishes the definitive diagnosis and the classification of the tumor determining the management and follow-up. A total or partial thyroidectomy is performed, possibly associated with lymph node removal. Hypothyroidism is quasi-systematic after surgery requiring a supplementation by L-thyroxine. In thyroid differentiated carcinomas, a high L-thyroxine dosage to suppress TSH and an adjuvant iratherapy (1131) are recommended in the forms with high risk of recurrence. Biological follow-up relies on serum thyroglobulin, indetectable in the absence of relapse. In the case of medullary carcinoma, biological follow-up relies on serum calcitonin, indetectable in the absence of persistence or recurrence and carcinoembryonic antigen (CEA). The search for a RET mutation is always recommended.

949P Update results of ALTER-H006: A phase II study of TQB2450 plus anlotinib as adjuvant therapy in hepatocellular carcinoma (HCC) with high risk of recurrence after surgical resection

949P Update results of ALTER-H006: A phase II study of TQB2450 plus anlotinib as adjuvant therapy in hepatocellular carcinoma (HCC) with high risk of recurrence after surgical resection

Diagnosis and treatment of venous thrombosis - part 2

The subject of this guideline from the Institute of Family Medicine at the University of Zurich (IHAMZ) is the management of venous thrombosis. The review summarizes the current evidence and recommendations from international guidelines (1-6). The IHAMZ-guidelines focus on primary care, they also provide guidance on the coordination of general and specialist medical care as well as on the transition between outpatient and hospital care taking into account the special features of the Swiss healthcare system. The guideline is devided in two parts. Part 1 discusses the diagnosis and treatment of deep vein thrombosis (DVT). A validated algorithm is recommended for the diagnostic process, which begins with the assessment of the clinical probability. With the inclusion of the D-dimer test, the need for subsequent imaging diagnostics can be reduced. The differences between the evaluation of an initial and recurrent DVT are shown and the indications and scope of evidence-based environmental diagnostics (thrombophilia and tumor search) are presented. All patients with DVT should receive anticoagulation (AC) for 3-6 months, as there is a high risk of recurrence with AC 3 months. The duration of the subsequent secondary prophylaxis depends on the presumed risk of recurrence on the one hand and the risk of bleeding on the other. Part 2 is dedicated to special thrombosis situations such as isolated distal thrombosis of the deep and muscle veins (idDVT, iMVT), shoulder-arm vein thrombosis (SAVT), cancer-associated thrombosis (CAT) and superficial vein thrombosis (SVT). The article on hormone- and pregnancy-associated DVT, developed together with the Department of Gynecology at the University Hospital of Zurich, discusses the importance of hormonal contraception and menopausal hormone replacement therapy (HRT) as thrombogenic risk factor as well as special features in the diagnosis and treatment of thrombosis in pregnancy.

The surgical, histopathological characteristics, and survival outcome of ovarian clear cell carcinoma: a retrospective case series sharing the experience of a tertiary cancer centre.

Ovarian clear cell carcinoma (OCCC) is a rare and distinct subtype of epithelial ovarian cancer (EOC). It is unique in several biological aspects. This study analyzes the clinicopathological features and survival outcome of patients with OCCC, aiming to identify factors affecting recurrence, progression-free survival (PFS) and overall survival (OS). A retrospective study included 49 women with OCCC between January 2009 and December 2021 at Oxford Cancer Center. All demographic and pathological characteristics, pre-operative biomarkers, surgical procedure, complications, hospital stay, chemotherapy regimen, and disease status on follow-up, were collected from electronic medical records. No residual disease (R0) was achieved in 39 out of 49 women who underwent cytoreductive surgery. The follow-up time had a mean of 8.75 years. The 3-year OS was 73.4%, and the 3-year PFS was 81.3% [95% confidence interval (CI): 84.63-118.93]. Women with stage 1 disease had the best outcome. There was a marked difference (P<0.001) in OS in the presence of residual disease. No residual disease conferred a 3-year OS of 88.6% (95% CI: 108.6-141.8), compared to only 12.5% in the presence of residual disease (95% CI: 4.48-32.11). In multivariant analysis, the International Federation of Gynecology and Obstetrics (FIGO) stage was the only independent prognostic indicator of OS with (P<0.05), including carbohydrate antigen (CA) 125, hemoglobin, albumin, associated endometriosis, ascites, residual disease and FIGO staging. Surgery to achieve no residual disease is necessary to improve the prognosis in advanced OCCC. The true challenge is to predict which patients with early-stage disease at higher risk of recurrence and would most benefit from adjuvant treatments.

324. A RETROSPECTIVE SINGLE CENTRE PROPENSITY-MATCHED ANALYSIS OF TRANSTHORACIC VERSUS TRANSABDOMINAL PROCEDURES FOR GIANT HIATAL HERNIAS

Abstract Background Transthoracic open procedure (TTO) was historically the preferred approach for treatment of giant hiatal hernias. However, the last decades transabdominal laparoscopic procedures (TAL) became the standard approach in many centres. The aim of the study was to compare short-term and midterm outcomes, as well as patient-reported outcome measures (PROMs, between TTO and TAL for giant hiatal hernias. Methods A retrospective analysis was conducted on all primary surgeries performed for giant hiatal hernias between 2008 and 2022. Patients who underwent TAL were propensity-matched (n= 36) to those who underwent TTO based on: age, gender, Charlson Comorbidity Score and hernia type. The two groups were compared in terms of surgery duration, length of stay (LOS), Clavien-Dindo score, intrahospital reoperation, hernia recurrence and need for reinterventions. PROMswere compared between total of TTO (n= 187) and TAL (n= 48): for symptom score, QoL-score, overall satisfaction and wound pain. Median clinical follow-up was 365.5 days. Median PROMsfollow-up was 55.3 months. Results Surgery duration (224 vs 177min, P&amp;lt;0.001) and LOS (11 vs 4days, P&amp;lt;0.001) were longer in TTO. Clavien-Dindo scores were alike (P= 0.260). Intrahospital reoperation was not statistically different (8.3% vs 0%, P= 0.239). Midterm recurrence rates suggested a non-significant trend towards lower recurrence in TTO (2.8% vs 16.7%, P= 0.107). Reintervention rates were alike (16.7% vs 11.1%, P= 0.735). QoL-score was inferior for TTO (0.705 vs 0.355, P= 0.036). Wound pain scores were higher in TTO (1 vs 0, P &amp;lt;0.001). Symptom score and satisfaction scores were alike, respectively 0.685 vs 0.760, P= 0.688 and 9 vs 9, P= 0.421. Conclusions TAL for giant hiatal hernias showed superior results compared to TTO for duration of surgery, length of hospital stay, QoL-score and wound pain scores. However, midterm results showed a noticeable trend towards higher recurrence rates for TAL. TAL should be considered when proceeding with surgery for giant hiatal hernias but a possible higher risk of recurrence must be taken into account. Further long-term clinical follow-up and comparison to PROMscould guide future decision-making.

Outcomes of Atrial Fibrillation Ablation in Heart Failure Subtypes.

Catheter ablation (CA) improves clinical outcomes in patients with atrial fibrillation (AF) and heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to evaluate the impact of CA on clinical and quality-of-life outcomes across HF subtypes. All patients undergoing AF ablation at a tertiary center were enrolled in a prospective registry and included in this study (2013-2021). The primary end point was AF recurrence. Secondary end points included AF-related hospitalizations and quality-of-life outcomes. Patients were categorized according to their HF status: no HF, HFrEF, HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). A total of 7020 patients were included (80% no HF, 8% HFrEF, 7% HFmrEF, and 5% HFpEF). Over 3 years, the cumulative incidence of AF recurrence after ablation was as follows: HFpEF (53%), HFmrEF (41%), HFrEF (41%), and no HF (34%); P<0.01. Multivariable Cox analyses confirmed these findings using no HF group as reference (HFpEF: hazard ratio, 1.47 [95% CI, 1.21-1.78]; HFmrEF: hazard ratio, 1.23 [95% CI, 1.04-1.45]; and HFrEF: hazard ratio, 1.17 [95% CI, 1.01-1.37]; P<0.05 for all). In all groups, CA resulted in a significant reduction of AF-related hospitalization (mean rate per 1 patient-years [before and after CA]; HFpEF [1.8 versus 0.3], HFmrEF [1.1 versus 0.2], HFrEF [1.1 versus 0.2], and no HF [1 versus 0.1]; P<0.01 for each comparison) and significant improvement in quality of life as measured by both the AF symptom severity score and the AF burden score (P<0.01 for the comparison between baseline and follow-up for each score when tested separately). AF recurrence rates after CA were higher in patients with HF compared with those without HF, with patients with HFpEF being at the highest risk of recurrence. Nonetheless, CA was associated with a significant reduction in AF symptoms, AF-related hospitalization, and HF symptoms in most patients irrespective of HF subtypes.

Rheumatoid Arthritis Exacerbates Eosinophilic Inflammation Contributing to Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps.

To assess the impact of rheumatoid arthritis (RA) on histopathological features and the risk of postoperative recurrence in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. A retrospective cohort study of CRSwNP patients who underwent functional endoscopic sinus surgery was performed. Patients were followed up for more than two years, and classified into RA and Non-RA groups, recurrent and non-recurrent groups. The influence of RA on histopathological features and the risk of CRSwNP recurrence was explored. A total of 517 CRSwNP patients were finally recruited, including 78 RA patients. The RA group exhibited a higher recurrence rate, tissue eosinophil counts and percentages compared to the non-RA group (P < 0.05). Tissue eosinophil count and percentage, and the prevalence of allergic rhinitis were significantly higher in the recurrent group in compared to the non-recurrent group (P < 0.05). Multivariate logistic regression analysis identified tissue eosinophil count and percentage, RA, and allergic rhinitis as significant predictors of increased recurrence risk (P < 0.05). Both adjusted and unadjusted models affirmed RA as an independent risk factor for CRSwNP postoperative recurrence (P < 0.05). Kaplan-Meier curves further indicated a higher recurrence risk in CRSwNP patients with RA than those without (P < 0.05). Our findings suggest that RA significantly exacerbates tissue eosinophilic inflammation and independently heightens the risk of postoperative recurrence in CRSwNP patients. These insights underscore the need for tailored therapeutic strategies addressing the complex interplay between CRSwNP and RA to mitigate recurrence risks and improve clinical outcomes.

Tumor Apparent Diffusion Coefficient is Associated with Early Recurrence of Intrahepatic Cholangiocarcinoma

Rationale and ObjectivesIdentifying intrahepatic cholangiocarcinoma (iCCA) patients who are at high risk for early recurrence (ER) can guide personalized treatment strategy and improve survival. This study aimed to investigate the value of preoperative MRI, especially diffusion-weighted imaging, in predicting ER, including in patients receiving neoadjuvant therapy. Materials and methodsThis study included 175 pathologically-confirmed iCCA patients who underwent curative resection (114 men, 61 women; mean age 59.0±9.56 years). MRI features, particularly apparent diffusion coefficient (ADC), were analyzed and compared between ER and non-ER cases. Survival analyses of ER were evaluated using Cox regression and Kaplan-Meier analysis. ResultsER occurred in 54.3% (95/175) of patients. Multivariate logistic regression analysis identified tumor ADC as the only independent predictor of ER (odds ratio=0.034, P<0.001), with AUCs of 0.758 (95%CI 0.664, 0.836) in the testing cohort and 0.779 (95%CI 0.622, 0.893) in the validation cohort. The optimal ADC threshold was 1.273×10-3mm2/s. Tumor ADC was comparable to the AJCC 8th staging system in predicting ER (AUC 0.758 vs 0.650 in testing cohort and 0.779 vs 0.661 in validation cohort). Multivariate Cox analysis identified high tumor burden score (HR=1.109, P=0.009), non-smooth margin (HR=2.265, P=0.008) and tumor ADC (HR=0.111, P<0.001) as independent risk factors for ER. Lower ADC values were linked to shorter RFS in both testing and validation cohorts (P<0.001 and 0.0219), as well as in patients receiving neoadjuvant therapy (P=0.003). ConclusionPreoperative MRI, particularly ADC, can help predict ER in iCCA, regardless of the application of neoadjuvant therapy, comparable to the AJCC 8th staging system.

795. REVIEW OF CLINICAL CHARACTERISTICS AND PROGNOSIS OF MULTIPLE PRIMARY ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Multiple Primary Esophageal Squamous Cell Carcinoma (MPESCC) is a rare and highly aggressive type of tumor, classified into Synchronous Multiple Primary Esophageal Squamous Cell Carcinoma (S-MPESCC) and Metachronous Multiple Primary Esophageal Squamous Cell Carcinoma (M-MPESCC). MPESCC has garnered increasing attention in recent years due to its complex pathogenesis, poor prognosis, and unclear treatment protocols. Compared to solitary esophageal squamous cell carcinoma (SESCC), patients with MPESCC typically show higher rates of lymph node and distant metastasis, leading to a poorer prognosis. This review aims to summarize the clinical characteristics, common treatment methods, and prognosis of MPESCC by analyzing existing literature, providing references for clinical practice. Methods The clinical characteristics of MPESCC patients differ significantly from those of SESCC patients, relevant literature was collected for meta-analysis of the following data of the patients: Gender and Age, Medical History, Pathological Features, Lymph Node and Distant Metastasis, Tumor Distribution. Treatment Methods include Surgical Treatment, Radiotherapy and Chemotherapy. Postoperative recurrence and metastasis are also included in the statistics. Results Tumors in MPESCC patients exhibit significant differences in pathological staging and grading, which makes treatment more challenging. Patients with MPESCC have significantly higher rates of lymph node and distant metastasis compared to those with SESCC. MPESCC tumors can appear in multiple locations within the esophagus, with pathological characteristics that may vary between sites. Surgery remains the primary treatment method for MPESCC. Due to the high risk of recurrence and metastasis in MPESCC patients, regular endoscopic and imaging examinations are necessary postoperatively to detect and address any recurrent or new tumors early. Conclusion MPESCC is a complex type of esophageal cancer with a poor prognosis. It’s clinical characteristics and treatment strategies differ significantly from those of SESCC. Multidisciplinary comprehensive treatment and close postoperative follow-up are crucial for improving the prognosis of patients with MPESCC. Further research is needed to optimize treatment protocols and enhance patient survival rates.

948P Drug type and duration of adjuvant immune checkpoint inhibitors in hepatocellular carcinoma with high-risk recurrence factors (PREVENT): An update analysis of a prospective, multicentric cohort study

948P Drug type and duration of adjuvant immune checkpoint inhibitors in hepatocellular carcinoma with high-risk recurrence factors (PREVENT): An update analysis of a prospective, multicentric cohort study

P.392: Combining transarterial chemoembolization with simultaneous thermal ablation for solitary hepatocellular carcinomas in high-risk recurrence areas.

P.392: Combining transarterial chemoembolization with simultaneous thermal ablation for solitary hepatocellular carcinomas in high-risk recurrence areas.

Safety and efficacy of hepaticoduodenostomy for biliary reconstruction after extrahepatic mid-bile duct cancer surgery.

Bile duct resection and reconstruction for bile duct cancer (BDC) is a complex surgical and oncologic procedure that requires extensive resection and reconstruction of the biliary tract. Hepaticojejunostomy is commonly performed for biliary reconstruction after extrahepatic mid-bile duct resection, while hepaticoduodenostomy (HD) is performed only rarely due to the risk of ascending cholangitis. However, the efficacy of HD has not been well-established in extrahepatic mid-BDC surgery. In this study, we aimed to analyze the outcomes of HD in patients who underwent bile duct resection for extrahepatic mid-BDC. We retrospectively analyzed 38 extrahepatic mid-BDC patients who underwent bile duct resection in our center between January 2018 and June 2023. We compared postoperative outcomes, cancer recurrence, and patient survival between hepaticojejunostomy (n=20) and HD (n=18) groups. Operation time for the HD group was significantly shorter than that of the hepaticojejunostomy group (188 vs. 206 min, P=0.044) with no significant differences in postoperative outcomes. Regression analysis showed that a HD was not associated with a significantly high risk of cancer recurrence or decrease in patient survival. HD appears to have comparable operative benefits, postoperative complications, and oncologic outcomes to hepaticojejunostomy in extrahepatic mid-BDC patients.

Mutant P53 modulation by cryptolepine through cell cycle arrest and apoptosis in triple negative breast cancer

BackgroundTriple Negative Breast cancer is an aggressive breast cancer subtype. It has a more aggressive clinical course, an earlier age of onset, a larger propensity for metastasis, and worse clinical outcomes as evidenced by a higher risk of recurrence and a shorter survival rate. Currently, the primary options for TNBC treatment are surgery, radiation, and chemotherapy. These treatments however remain ineffective due to recurrence. However, given that p53 mutations have been identified in more than 60–88 % of TNBC, translating p53 into the clinical situation is particularly important in TNBC. In this study, we screened and evaluated the therapeutic potential of cryptolepine (CRP) in TNBC in-vitro models being an anti-malarial drug it could be repurposed as an anti-cancer therapeutic targeting TNBC. Moreover, the cytotoxicity activity of cryptolepine to TNBC cells and a detailed anti-tumor mechanism in mutant P53 has not been reported before. MethodsMTT assays were used to examine the cytotoxicity and cell viability activity of Cryptolepine in TNBC, non-TNBC T47D and MCF-7 and non-malignant MCF10A cells. Scratch wound and clonogenic assay was used to evaluate the cryptolepine’s effect on migration and colony forming ability of TNBC cells. Flow cytometry, MMP and DAPI was used to assess cell cycle arrest and cell apoptosis mechanism. The expression of proteins was detected by western blots. The differential expression of RNAs was evaluated by RT-PCR and the interaction between P53 and drug was evaluated computationally using in-silico approach and in-vitro using ChIP assay. ResultsIn this study, we found that cryptolepine has more preferential cytotoxicity in TNBC than non-TNBC cells. Notably, our studies revealed the mechanism by which cryptolepine induces intrinsic apoptosis and inhibit migration, colony formation ability, induce cell cycle arrest by inducing conformational change in the mutant P53 thereby increasing its DNA binding ability, hence activating its tumor suppressing potential significantly. ConclusionOur study revealed that CRP significantly reduced the proliferation, migration and colony forming ability of TNBC cells lines. Moreover, it was revealed that CRP induces cell cycle arrest and apoptosis by activating mutant P53 and enhancing its DNA binding ability to induce its tumor suppressing ability.

Evidence for Radiation Therapy in Stage III Locoregionally Advanced Cutaneous Melanoma in the Post-Immunotherapy Era: A Literature Review.

In the landscape of Stage III locoregionally advanced cutaneous melanoma treatment, the post-immunotherapy era has sparked a number of questions on the management of the nodal basin. However, much of the available literature is not focused on radiation therapy as an adjuvant therapy. This literature review aims to illuminate the evidence surrounding radiation therapy's potential to mitigate regional recurrences in the adjuvant setting for melanoma. Additionally, it seeks to identify adjunct systemic therapy options and explore the synergy between systemic therapy and radiation. Despite strides in surgical techniques and systemic therapies, controlling regional Stage III melanoma remains a formidable clinical hurdle. While historical data strongly suggest the efficacy of adjuvant radiation therapy in reducing regional recurrence risk, its evaluation predates the advent of MAPK pathway inhibitors and robust immunotherapy options. Notably, clinical trials have yet to definitively demonstrate a survival advantage with adjuvant radiation therapy. Additional research should focus on refining the definition of high risk for regional recurrence through gene expression profiling or tumor immune profiling scores and elucidate the optimal role of adjuvant radiation therapy in patients treated with neoadjuvant systemic therapy.

Integrating the melanoma 31-gene expression profile test with clinical and pathologic features can provide personalized precision estimates for sentinel lymph node positivity: an independent performance cohort.

Up to 88% of sentinel lymph node biopsies (SLNBs) are negative. The 31-gene expression profile (31-GEP) test can help identify patients with a low risk of SLN metastasis who can safely forego SLNB. The 31-GEP classifies patients as low (Class 1A), intermediate (Class 1B/2A), or high risk (Class 2B) for recurrence, metastasis, and SLN positivity. The integrated 31-GEP (i31-GEP) combines the 31-GEP risk score with clinicopathologic features using a neural network algorithm to personalize SLN risk prediction. Patients from a single surgical center with 31-GEP results were included (n = 156). An i31-GEP risk prediction < 5% was considered low risk of SLN positivity. Chi-square was used to compare SLN positivity rates between groups. Patients considered low risk by the i31-GEP had a 0% (0/30) SLN positivity rate compared to a 31.9% (30/94, p < 0.001) positivity rate in those with > 10% risk. Using the i31-GEP to guide SLNB decisions could have significantly reduced the number of unnecessary SLNBs by 19.2% (30/156, p < 0.001) for all patients and 33.0% (30/91, p < 0.001) for T1-T2 tumors. Patients with T1-T2 tumors and an i31-GEP-predicted SLN positivity risk > 10% had a similar SLN positivity rate (33.3%) as patients with T3-T4 tumors (31.3%). The i31-GEP identified patients with < 5% risk of SLN positivity who could safely forego SLNB. Combining the 31-GEP with clinicopathologic features for a precise risk estimate can help guide risk-aligned patient care decisions for SLNB to reduce the number of unnecessary SLNBs and increase the SLNB positivity yield if the procedure is performed.

Drug-Free "Triboelectric Immunotherapy" Activating Immunity for Osteomyelitis Treatment and Recurrence Prevention.

Treatment of osteomyelitis is clinically challenging with low therapeutic efficacy and high risk of recurrence owing to the immunosuppressive microenvironment. Existing therapies are limited by drug concentration and single regulatory effect on the immune network, and emphasize the role of anti-inflammatory effects in reducing osteoclast rather than the role of proinflammatory effects in accelerating infection clearance, which is not conducive to complete bacteria elimination and recurrence prevention. Herein, a direct-current triboelectric nanogenerator (DC-TENG) is established to perform antibacterial effects and modulate immunological properties of infectious microenvironments of osteomyelitis through electrical stimulation, namely triboelectric immunotherapy. Seeing from the results, the triboelectric immunotherapy successfully activates polarization to proinflammatory (M1) macrophages in vitro, accompanied by satisfying direct antibacterial effects. The antibacterial and osteogenic abilities of triboelectric immunotherapy are verified in rat cranial osteomyelitis models. The effects on the polarization and differentiation of immune-related cells in vivo are investigated by establishing in situ tibial osteomyelitis models and immunosurveillance models in C57 mice respectively, indicating the ability of activating immunity and producing immunological memory for in situ infection and secondary recurrence, thus accelerating healing and preventing relapse. This study provides an efficient, long-acting, multifunctional, and wearable triboelectric immunotherapy strategy for drug-free osteomyelitis treatment systems.

Risk stratification of surveillance for low-grade appendiceal mucinous neoplasms

BackgroundLow-grade appendiceal mucinous neoplasms (LAMNs) can progress to pseudomyxoma peritonei (PMP). The incidence and risk factors for recurrence are unclear, and there is a lack of consensus on the need and duration of surveillance imaging. MethodsPatients at the Mayo Clinic in Rochester, Minnesota, with a histologic diagnosis of LAMNs confined to the appendix and limited involvement of the right lower quadrant from 1992 to 2023 were included. Associations between recurrence and risk factors were assessed using Kaplan-Meier curves and Cox proportional hazards regression. ResultsA total of 125 patients with LAMNs underwent abdominal imaging surveillance for a median of 51.2 months (IQR, 26–92). Of note, 5 patients (4%) recurred, all of which were PMP. Overall, the 5- and 10-year cumulative recurrence incidence rates were 3% and 6%, respectively. The median time to recurrence was 24 months (IQR, 23–87). Only LAMNs limited to the right lower quadrant and LAMN tumor size of <2 cm were associated with recurrence (P < .05). The 5- and 10-year cumulative recurrence risks were 12% and 30%, respectively, for the 21 patients with either risk factor. Only 1% of patients without these 2 risk factors developed a recurrence at 10 years. ConclusionThe overall recurrence risk of LAMN after resection is low. Appendectomy is sufficient for LAMN. Select patients with acellular mucin confined to the right lower quadrant and a tumor size of <2 cm are at higher risk of recurrence. Thus, long-term surveillance is recommended for high-risk individuals. Conversely, LAMNs without risk factors can be safely observed expectantly.

Oncofetal IGF2BP3-mediated control of microRNA structural diversity in the malignancy of early-stage lung adenocarcinoma

The nature of microRNA (miRNA) dysfunction in carcinogenesis remains controversial because of the complex connection between miRNA structural diversity and biological processes. Here, we found that oncofetal IGF2BP3 regulates the selective production of a subset of 3'-isoforms (3'-isomiRs), including miR-21-5p and Let-7 family, which induces significant changes in their cellular seed occupancy and structural components, establishing a cancer-specific gene expression profile. The D-score, reflecting dominant production of a representative miR-21-5p+C (a 3'-isomiR), discriminated between clinical early-stage lung adenocarcinoma (LUAD) cases with low and high recurrence risks, and was associated with molecular features of cell cycle progression, epithelial-mesenchymal transition pressure, and immune evasion. We found that IGF2BP3 controls the production of miR-21-5p+C by directing the nuclear Drosha complex to select the cleavage site. IGF2BP3 was also involved in the production of 3'-isomiRs of miR-425-5p and miR-454-3p. IGF2BP3-regulated these three miRNAs are suggested to be associated with the regulation of p53, TGF-β, and TNF pathways in LUAD. Knockdown of IGF2BP3 also induced a selective upregulation of Let-7 3'-isomiRs, leading to increased cellular Let-7 seed occupancy and broad repression of its target genes encoding cell cycle regulators. The D-score is an index that reflects this cellular situation. Our results suggest that the aberrant regulation of miRNA structural diversity is a critical component for controlling cellular networks, thus supporting the establishment of a malignant gene expression profile in early stage LUAD.