Search Results (380)

Background: Conservative mastectomy with prepectoral breast reconstruction is becoming increasingly widespread and validated in recent years. Today, while aesthetic advantages and improvement in quality-of-life outcomes are widely acknowledged, oncological safety remains subject of debate. There is limited evidence on residual breast tissue after conservative mastectomy, and it still represents an unknown risk for local recurrence. The recent spread of this surgical technique precludes a standardized surgical approach in case of local recurrence of ipsilateral breast cancer, and the lack of evidence in the literature complicates the decision-making process. The objective of this study is to describe the surgical treatment of local relapses for breast cancer patients following conservative mastectomy and prepectoral implant-based reconstruction. Methods: Between January 2018 and May 2024 at a single institution, 648 consecutive patients underwent conservative mastectomy and prepectoral reconstruction as their primary treatment. We identified 12 patients with T1-2 breast cancer who subsequently had histologically confirmed ipsilateral breast cancer recurrence and a local wide excision or radical mastectomy were performed. Each clinical case was discussed in a multidisciplinary meeting to define the most appropriate surgical treatment. At time of diagnosis of recurrence, patients with lymph node metastasis or systemic involvement were excluded from the study. Results: Among 648 consecutive patients who underwent conservative mastectomy, 12 with histologically confirmed ipsilateral breast cancer recurrence were included. The mean interval to recurrence was 43 months (range 10–76 months) from the primary operation. Recurrence sites were as follows: upper outer quadrant in four patients (33.4%), upper inner quadrant in three (25.0%), lower inner quadrant in two (16.6%), lower outer quadrant in one (8.4%), and central quadrant with nipple involvement in two (16.6%). Of the 12 patients, 9 (75%) underwent wide local excision, including 2 who also received partial capsulectomy, while 3 (25%) required radical mastectomy with implant removal. Adjuvant radiation therapy was administered to 6 patients (50%)—5/6 (83.3%) in the excision group and 1/6 (16.7%) in the mastectomy group. No significant differences were observed in distant disease–free survival or overall survival between the two groups. Conclusions: Currently, surgical treatment of ipsilateral breast tumor recurrence following conservative mastectomy and prepectoral breast reconstruction is not reported in the literature, and this study represents the first instance where wide local excision is described. The management of ipsilateral recurrence should be discussed in multidisciplinary meetings and could be performed safely in selected cases, sparing the prosthesis and avoiding radical mastectomy. Full article

Background: Soft tissue sarcomas (STSs) are rare and heterogeneous malignancies requiring a multidisciplinary approach to diagnosis and treatment. Advances in surgical techniques, chemotherapy, and radiotherapy have improved survival rates but often result in significant functional impairments, particularly in patients undergoing limb-sparing procedures. Rehabilitation is crucial for restoring mobility and independence, with recent studies emphasizing the importance of personalized rehabilitation protocols tailored to specific surgical interventions. Quantitative assessments, such as 3D motion capture and surface electromyography, provide objective insights into gait performance and motor function, enabling more precise rehabilitation strategies to optimize recovery. Methods: This study evaluated gait performance in 21 patients with lower-limb impairment following limb-sparing surgery for STS. Patients underwent two instrumented gait assessments using marker-based 3D motion capture and surface electromyography to measure spatiotemporal gait parameters, joint kinematics, and muscle activity. Independence in the activity of daily living was assessed with the modified Barthel Index in both timepoints. Results: Following rehabilitation, patients demonstrated significant improvements in functional independence, as reflected by an increase in the modified Barthel Index (p < 0.001). Gait analysis revealed increased walking speed, stride length, cadence, and improved joint range of motion at the hip, knee, and ankle, though electromyographic analysis showed no statistically significant differences in muscle activation patterns or co-contraction indices. Conclusions: These findings underscore the importance of a rehabilitation programs personalized on gait strategies. A deeper understanding of motor adaptations based on sarcoma location and surgical approach could further refine rehabilitation protocols, ultimately enhancing patient outcomes and quality of life. Full article

Background and Clinical Significance: Cervical ectopic pregnancy (CEP) is a rare and potentially serious condition, in which the embryo implants within the cervical canal rather than the uterine cavity and is present in less than 1% of all ectopic pregnancies. There are different treatment options depending on the particular situation and the woman’s reproductive desire but conservative approaches as the first line of treatment is preferred in all cases and hysteroscopic resection of the fetus is one of these options. Several types of laser systems are available for use in hysteroscopic surgery, including neodymium:YAG (Nd:YAG) lasers, KTP and Argon lasers, as well as diode lasers. The holmium:YAG (Ho:YAG) laser, although more commonly used in urology due to its ability to cut, coagulate, and vaporize tissue, has gained interest in gynecologic procedures because of its precision and favorable safety profile. Case Presentation: We present the case of a 32-year-old woman, pregnant for the first time, who was diagnosed with CEP and successfully treated using a Ho:YAG laser during an outpatient hysteroscopic procedure. As far as we know, this is the first published case using this approach. Conclusions: The Ho:YAG laser is a proven tool for outpatient hysteroscopic procedures like septum and adhesion removal. Its ability to both cut and coagulate offers a minimally invasive, fertility-sparing option for managing cervical ectopic pregnancy. With the right patient and proper backup plans in place, this approach could be a promising alternative to more aggressive treatments. Full article

Ultrahigh dose rate (UHDR) radiotherapy, also known as FLASH radiotherapy (FLASH-RT), has shown potential for increasing tumor control while sparing normal tissue. In parallel, gold nanoparticles (GNPs) have been extensively explored as radiosensitizers due to their high atomic number and ability to enhance the generation of reactive oxygen species (ROS) through water radiolysis. In this study, we investigate the synergistic effects of UHDR electron beams and GNP-mediated radiosensitization using Monte Carlo (MC) simulations based on the Geant4-DNA code. A spherical water phantom with embedded GNPs of varying sizes (5–100 nm) was irradiated using pulsed electron beams (100 keV and 1 MeV) at dose rates of 60, 100, and 150 Gy/s. The chemical yield of ROS near the GNPs was quantified and compared to an equivalent water nanoparticle model, and the yield enhancement factor (YEF) was used to evaluate radiosensitization. Results demonstrated that YEF increased with smaller GNP sizes and at lower UHDR, particularly for 1 MeV electrons. A maximum YEF of 1.25 was observed at 30 nm from the GNP surface for 5 nm particles at 60 Gy/s. The elevated ROS concentration near GNPs under FLASH conditions is expected to intensify DNA damage, especially double-strand breaks, due to increased hydroxyl radical interactions within nanometric distances of critical biomolecular targets. These findings highlight the significance of nanoparticle size and beam parameters in optimizing ROS production for FLASH-RT. The results provide a computational basis for future experimental investigations into the combined use of GNPs and UHDR beams in nanoparticle-enhanced radiotherapy. Full article

Reactive oxygen species (ROS) act as double-edged swords in cancer biology—facilitating tumor growth, survival, and metastasis at moderate levels while inducing oxidative damage and cell death when exceeding cellular buffering capacity. To survive under chronic oxidative stress, cancer cells rely on robust antioxidant systems such as the glutathione (GSH) and thioredoxin (Trx), and superoxide dismutases (SODs). These systems maintain redox homeostasis and sustain ROS-sensitive signaling pathways including MAPK/ERK, PI3K/Akt/mTOR, NF-κB, STAT3, and HIF-1α. Targeting the antioxidant defense mechanisms of cancer cells has emerged as a promising therapeutic strategy. Inhibiting the glutathione system induces ferroptosis, a non-apoptotic form of cell death driven by lipid peroxidation, with compounds like withaferin A and altretamine showing strong preclinical activity. Disruption of the Trx system by agents such as PX-12 and dimethyl fumarate (DMF) impairs redox-sensitive survival signaling. Trx reductase inhibition by auranofin or mitomycin C further destabilizes redox balance, promoting mitochondrial dysfunction and apoptosis. SOD1 inhibitors, including ATN-224 and disulfiram, selectively enhance oxidative stress in tumor cells and are currently being tested in clinical trials. Mounting preclinical and clinical evidence supports redox modulation as a cancer-selective vulnerability. Pharmacologically tipping the redox balance beyond the threshold of cellular tolerance offers a rational and potentially powerful approach to eliminate malignant cells while sparing healthy tissue, highlighting novel strategies for targeted cancer therapy at the interface of redox biology and oncology. Full article

Cancer remains one of the most pressing global health challenges, driving the need for innovative treatment strategies. Boron neutron capture therapy (BNCT) offers a highly selective approach to destroying cancer cells while sparing healthy tissues. To improve boron delivery, Fe₃O₄@Au nanoparticles were developed and functionalized with a boron-containing carborane compound. Fe₃O₄ nanoparticles were synthesized and covered by gold, followed by (3-Aminopropyl)triethoxysilane (APTES) modification to introduce amino groups for carborane immobilization. Comprehensive characterization using SEM, DLS, FTIR, EDX, Brunauer–Emmett–Teller (BET), and XRD confirmed successful functionalization at each stage. TEM confirmed the final structure and elemental composition of the nanoparticles. BET analysis revealed a surface area of 94.69 m²/g and a pore volume of 0.51 cm³/g after carborane loading. Initial release studies in PBS demonstrated the removal of only loosely bound carborane within 48 h, with FTIR confirming stable retention of the compound on the nanoparticle surface. The modified nanoparticles achieved a stable zeta potential of −20 mV. The particles showed low toxicity within a range of concentrations (0–300 μg Fe/mL) and were efficiently accumulated by U251MG cells. These results demonstrate the potential of the obtained nanoparticles to carry boron and gold for their possible application as a theranostic agent. Full article

Overexpression of growth factor receptors and immunosuppressive molecules is a hallmark of many tumour cells, distinguishing them from normal tissue. This co-expression enables tumours both to exploit proliferative signalling and to evade immune surveillance. Here, we propose a strategy that employs a combination of monoclonal antibodies (mAbs) targeting two distinct antigens (Ags) at sub-cytotoxic doses. This approach aims to achieve a threshold cytotoxic density of immune complexes selectively on malignant cells expressing both target Ags, while sparing normal cells that express only one. Typically, the first target Ag may be a growth factor receptor, such as epidermal growth factor receptor (EGFR and HER1), epidermal growth factor receptor 2 (HER2), or vascular endothelial growth factor receptor 2 (VEGFR2), and the second, an immunoinhibitory molecule, such as programmed death-ligand 1 (PD-L1). Selective mAb-mediated tumour destruction is expected to enhance neoantigen (NeoAg) presentation to the immune system, while the blockade of PD-1/PD-L1 interactions should further stimulate anti-tumour immune responses. Notably, this strategy can be implemented using clinically approved therapeutic mAbs, potentially enabling rapid translation into clinical practice without extensive regulatory hurdles. Full article

Endometriosis, a chronic estrogen-dependent disorder defined by ectopic endometrial-like tissue growth, causes pelvic pain and infertility in reproductive-age women. Despite its prevalence, the underlying mechanisms driving lesion persistence and reproductive impairment remain unclear. This review synthesizes recent pathophysiological advances, highlighting how hormonal dysregulation, immune dysfunction, epigenetic alterations, and oxidative stress collectively foster lesion persistence and treatment resistance. Critically, these molecular disturbances disrupt critical reproductive functions—including oocyte quality, endometrial receptivity, and embryo implantation. We further explore emerging non-hormonal therapeutic strategies, including MAPK and PI3K/AKT inhibitors as well as epigenetic agents targeting HOXA10 methylation and microRNA modulation, which offer fertility-sparing alternatives to conventional hormonal suppression. To enhance clinical translation, we propose a multi-level prevention framework—encompassing at the primary level, risk reduction; at the secondary level, biomarker-guided intervention; and at the tertiary level, fertility preservation—to anticipate disease progression and personalize reproductive care. By delineating shared pathways between endometriosis and infertility, this work advances precision medicine approaches for affected patients. Full article

Histotripsy is a novel, noninvasive, non-thermal technology invented in 2004 for the precise destruction of biologic tissue. It offers a powerful alternative to more conventional thermal or surgical interventions. Using short-pulse, low-duty cycle ultrasonic waves, histotripsy creates cavitation bubble clouds that selectively and precisely destroy targeted tissue in a predefined volume while sparing critical structures like bile ducts, ureters, and blood vessels. Such precision is of value when treating tumors near vital structures. The FDA has cleared histotripsy for the treatment of all liver tumors. Major medical centers are currently spearheading clinical trials, and some institutions have already integrated the technology into patient care. Histotripsy is now being studied for a host of other cancers, including primary kidney and pancreatic tumors. Preclinical murine and porcine models have already revealed promising outcomes. One of histotripsy’s primary advantages is its non-thermal mechanical actuation. This feature allows it to circumvent the limitations of heat-based techniques, including the heat sink effect and unpredictable treatment margins near sensitive tissues. In addition to its non-invasive ablative capacities, it is being preliminarily explored for its potential to induce immunomodulation and promote abscopal inhibition of distant, untreated tumors through CD8+ T cell responses. Thus, it may provide a multilayered therapeutic effect in the treatment of cancer. Histotripsy has the potential to improve precision and outcomes across a multitude of specialties, from oncology to cardiovascular medicine. Continued trials are crucial to further expand its applications and validate its long-term efficacy. Due to the speed of recent developments, the goal of this review is to provide a comprehensive and updated overview of histotripsy. It will explore its physics-based mechanisms, differentiating it from similar technologies, discuss its clinical applications, and examine its advantages, limitations, and future. Full article

By 2030, millions of new cancer cases will be diagnosed, as well as millions of cancer-related deaths. Traditional drug delivery methods have limitations, so developing smart drug delivery systems (SDDs) has emerged as a promising avenue for more effective and precise cancer treatment. Nanotechnology, particularly nanomedicine, provides innovative approaches to enhance drug delivery, including the use of nanoparticles. One such type of SDD is thermosensitive nanoparticles, which respond to internal and external stimuli, such as temperature changes, to release drugs precisely at tumor sites and minimize off-target effects. On the other hand, hyperthermia is a cancer treatment mode that goes back centuries and has become popular because it can target cancer cells while sparing healthy tissue. This paper presents a comprehensive review of smart thermosensitive nanoparticles for cancer treatment, with a primary focus on organic nanoparticles. The integration of hyperthermia with temperature-sensitive nanocarriers, such as micelles, hydrogels, dendrimers, liposomes, and solid lipid nanoparticles, offers a promising approach to improving the precision and efficacy of cancer therapy. By leveraging temperature as a controlled drug release mechanism, this review highlights the potential of these innovative systems to enhance treatment outcomes while minimizing adverse side effects. Full article

Proton therapy has emerged as a highly precise and tissue-sparing radiotherapy technique, capitalizing on the unique energy deposition pattern of protons characterized by the Bragg peak. Ensuring treatment accuracy relies on calibration phantoms, often composed of tissue-equivalent polymeric materials. This study investigates the dosimetric behavior of four commonly used polymers—Parylene, Epoxy, Lexan, and Mylar—by analyzing their linear energy transfer (LET) values and Bragg curve characteristics across various proton energies. Experimental LET data were collected and used to train and evaluate the predictive power for Bragg peak of multiple artificial intelligence models, including kNN, SVR, MLP, RF, LWRF, XGBoost, 1D-CNN, LSTM, and BiLSTM. These algorithms were optimized using 10-fold cross-validation and assessed through statistical error and performance metrics including MAE, RAE, RMSE, RRSE, CC, and R². Results demonstrate that certain AI models, particularly RF and LWRF, accurately (in terms of all evaluation metrics) predict Bragg peaks in Epoxy polymers, reducing the reliance on costly and time-consuming simulations. In terms of CC and R² metrics, the LWRF model demonstrated superior performance, achieving scores of 0.9969 and 0.9938, respectively. However, when evaluated against MAE, RMSE, RAE, and RRSE metrics, the RF model emerged as the top performer, yielding values of 12.3161, 15.8223, 10.3536, and 11.4389, in the same order. Additionally, the SVR model achieved the highest number of statistically significant differences when compared pairwise with the other eight models, showing significance against six of them. The findings support the use of AI as a robust tool for designing reliable calibration phantoms and optimizing proton therapy planning. This integrative approach enhances the synergy between materials science, medical physics, and data-driven modeling in advanced radiotherapy systems. Full article

Colorectal liver metastasis (CRLM) poses a significant challenge in oncology due to its high incidence and poor prognosis in unresectable cases. Current treatments, including surgical resection, systemic chemotherapy, and liver-directed therapies, often fail to effectively target hypoxic tumor regions, which are inherently more resistant to these interventions. This review examines the potential of a novel therapeutic strategy combining irreversible electroporation (IRE) ablation and Clostridium novyi-nontoxic (C. novyi-NT) bacterial therapy. IRE is a non-thermal tumor ablation technique that uses high-voltage electric pulses to create permanent nanopores in cell membranes, leading to cell death while preserving surrounding structures, and is often associated with temporary tumor hypoxia due to disrupted perfusion. C. novyi-NT is an attenuated, anaerobic bacterium engineered to selectively germinate and proliferate in hypoxic tumor regions, resulting in localized tumor cell lysis while sparing healthy, oxygenated tissue. The synergy between IRE-induced hypoxia and hypoxia-sensitive C. novyi-NT may enhance tumor destruction and stimulate systemic antitumor immunity. Furthermore, the integration of advanced imaging and artificial intelligence can support precise treatment planning and real-time monitoring. This integrated approach holds promise for improving outcomes in patients with CRLM, though further preclinical and clinical validation is needed. Full article

Background: Pulsed field ablation (PFA) is a novel non-thermal modality for pulmonary vein isolation (PVI) in atrial fibrillation (AF), offering myocardial selectivity through irreversible electroporation while sparing surrounding structures. However, concerns have emerged regarding potential subclinical hemolysis, reflected by alterations in biochemical markers such as lactate dehydrogenase (LDH). Methods: We conducted a retrospective, single-center study involving 249 patients undergoing PVI: 121 treated with PFA (PulseSelect or FARAPULSE) and 128 with radiofrequency (RF) ablation (PVAC catheter). Laboratory parameters were assessed at baseline, post-procedure, and at discharge, including hemoglobin, hematocrit, red blood cell (RBC) count, platelet count, creatinine, and LDH. The primary endpoint was the variation in blood cell indices; the secondary endpoint was the evaluation of LDH and hematocrit changes. Statistical analysis included t-tests and chi-square tests. Results: Baseline characteristics and pre-procedural labs did not differ significantly between groups. No significant changes in hemoglobin, hematocrit, RBC count, platelet count, or creatinine were observed post-ablation or at discharge. However, LDH levels significantly increased in the PFA group both post-procedurally and at discharge (p < 0.001), without concurrent changes in other blood cell parameters. Conclusions: PFA and RF ablation yield comparable hematological profiles after PVI, with no significant impact on key blood cell parameters. Nonetheless, the consistent rise in LDH levels in the PFA group suggests mild, subclinical hemolysis or tissue injury due to more extensive lesions. While supporting the hematologic safety of PFA, these findings underscore the need for further studies to assess the clinical significance of these biochemical alterations, particularly in high-risk patients or extensive ablation settings. Full article

Background and Clinical Significance: Breast reconstruction following mastectomy is a critical aspect of treatment for many patients, offering both physical and psychological benefits. Traditional methods include autologous tissue flaps and implants, with implant-based techniques being the most prevalent in the Western world. However, complications such as capsular contracture remain a concern. Acellular dermal matrices (ADM) have emerged as a valuable alternative, improving outcomes by reducing capsular contracture rates and enhancing tissue integration. Case Presentation: This case report presents the first use of a novel ADM, biocade^® (biotrics bioimplants AG, Berlin, Germany) in breast reconstruction following a mastectomy. A 55-year-old female patient underwent a left-sided nipple-sparing mastectomy, followed by prepectoral direct-to-implant reconstruction using an ADM-wrapped implant. The patient tolerated the procedure well, with no immediate complications observed. Postoperative monitoring focused on wound healing and assessing for signs of complications related to the implant. The use of the ADM resulted into satisfactory aesthetic and functional outcomes. Conclusions: The successful outcome of this case highlights the potential benefits of using collagen matrices in breast reconstruction, particularly in preserving mastectomy scenarios. The immediate results and improved aesthetics offered by prepectoral direct-to-implant reconstruction with ADM align well with patient expectations for a more natural appearance and faster recovery. However, this case report also highlights the need for ongoing research to fully explore the potential of these biomaterials and address associated challenges. Full article

Ultra-high dose rate radiotherapy known as Flash radiotherapy (FLASH-RT) offers tremendous opportunities to improve the therapeutic ratio of radiotherapy by sparing the normal tissue while maintaining similar tumoricidal efficacy. However, the underlying biophysical basis of the FLASH effect remains under active investigation with several proposed mechanisms involving oxygen depletion, altered free-radical chemistry, and differential biological responses. This article provides an overview of available experimental and computational tools that can be utilized to probe the tumor and normal tissue microenvironment. We analyze in vitro, ex vivo, and in vivo systems used to study FLASH responses. We describe various computational and imaging technologies that can potentially aid in understanding the biophysics of FLASH-RT and lead to safer clinical translational. Full article