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BACKGROUND: This retrospective study aims to provide a comprehensive analysis of the demographics, survival rates, and therapeutic approaches of small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) while highlighting key differences compared to common urinary bladder cancers. METHODS: Our analysis utilized the Surveillance, Epidemiology, and End Results database (SEER), and data was collected from 2000-2020. RESULTS: A total of 1040 cases of urinary bladder SCNEC and LCNEC were identified. Most patients were over the age of 80 years (33.2%), male (78.9%), and Caucasian (83.6%). Most tumors were over 4.1cm (47.4%) and in the lateral wall of the bladder (37.8%). The overall 5-year survival was 22.1% (95% confidence interval (95% CI):20.7-23.5). The 5-year survival by sex was greatest for the female population (28.0%; (95% CI: 24.5-35.0). For treatment modality, the 5-year survival for each was as follows: surgery, 12.5% (95% CI: 10.5-14.5) multimodality therapy (surgery and chemotherapy), 31.1% (95% CI: 28.5-33.7) and combination (surgery, chemotherapy, and radiation) 32.8% (95% CI: 29.1-36.5). On multivariable analysis, positive nodal status hazar ratio (HR)(HR3.65 [95% CI: 2.34-5.71], P < .001) was identified as a negative predictor for survival, and increasing age was nearly significant for a worse prognosis (P = .052). The prognostic nomogram that was created to predict patient survivability mirrored the findings from the statistical analysis, with a statistically significant difference found in race, treatment modality, and tumor stage. CONCLUSIONS: SCNEC and LCNEC are rare yet highly intrusive subtypes of bladder cancer that usually affect Caucasian males over the age of 80 years old. The study identifies older age and positive nodal status as adverse prognostic indicators. Our findings offer crucial insights that can inform future clinical guidelines and serve as a basis for more tailored treatment strategies for these aggressive subtypes of bladder cancer.
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Pediatric arteriovenous malformations (AVMs) are rare but carry a risk of devastating neurological morbidity and mortality. Rupture of a cerebral AVM is the most common cause of spontaneous intracranial hemorrhage in children, with an unruptured AVM having an approximate hemorrhage risk of 2%-4% per year. The complex etiology of pediatric AVMs persists as an impediment to a comprehensive understanding of pathogenesis and subsequent targeted gene therapies. While AVMs secondary to vascular malformation syndromes have a clearer pathogenesis, a variety of gene mutations have been identified within sporadic AVM cases. The Ephrin B2/EphB4 (RASA-1, KRAS, and MEK) signaling axis, hemorrhagic telangiectasia, NOTCH, and TIE2 receptor complexes (PIK3CA and mTOR), in addition to other isolated gene variants, have been implicated in AVM pathogenesis. Furthering the understanding of the molecular mechanisms of AVM pathogenesis will lead to future novel therapies and treatment paradigms. Given the expected lifespan of a child, pediatric patients have an unacceptably high cumulative lifetime risk of hemorrhage. AVM treatment strategies are dependent on AVM grade, provider preference, and institutional resources. While open microsurgery is the mainstay of treatment for some AVMs, radiosurgery for definitive treatment and adjunctive endovascular embolization are also used extensively. There is increasing evidence indicating that all three modalities play important and potentially synergistic roles in the armamentarium for pediatric AVM treatment. This review serves to report current understanding in the genetic and molecular mechanisms of pediatric AVMs, review clinical diagnostic and classification criteria, and detail treatment options and subsequent outcomes of pediatric AVM patients.
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OBJECTIVE: To explore the effect of dietary modification-assisted multimodal therapy in the prevention and treatment of chronic prostatitis. METHODS: A total of 132 cases of chronic prostatitis treated in the Outpatient Department of our hospital were randomly divided into an observation group (n = 68) and a control group (n = 64), the former following the Mediterranean dietary pattern, the latter adhering to their own dietary habits, and meanwhile both receiving lifestyle guidance, psychological counseling, symptomatic medication and physiotherapy according to their specific symptoms. The patients were followed up for 4 weeks, therapeutic effects were observed and comparisons were made between the two groups in the NIH-CPSI scores before and after treatment. RESULTS: Compared with the baseline, the quality of life (QOL) scores, pain and urination discomfort scores and total NIH-CPSI scores were significantly decreased in both the observation and the control groups after treatment (P < 0.05), even more decreased in the former than in the latter, but with no statistically significant difference between the two (P > 0.05). The rate of therapeutic effectiveness was higher in the observation group than in the control (87.1% vs 79.7%, but showed no statistically significant difference between the two groups (P > 0.05). CONCLUSION: Multimodal therapy is suitable for the management of different clinical manifestations of individual patients, while dietary habits vary from person to person as well as from region to region. Therefore, scientific dietary modification for the prevention and treatment of CP/CPPS needs further exploration.
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Prostatitis , Calidad de Vida , Humanos , Masculino , Prostatitis/terapia , Terapia Combinada , Enfermedad Crónica , Resultado del Tratamiento , Dieta Mediterránea , Estilo de Vida , AdultoRESUMEN
Rheumatoid arthritis (RA) is an autoimmune disease with multifactorial etiology and intricate pathogenesis. In RA, repeated monotherapy is frequently associated with inadequate efficacy, drug resistance, and severe side effects. Therefore, a shift has occurred in clinical practice toward combination therapy. However, conventional combination therapy encounters several hindrances, including low selectivity to arthritic joints, short half-lives, and varying pharmacokinetics among coupled drugs. Emerging nanotechnology offers an incomparable opportunity for developing advanced combination therapy against RA. First, it allows for co-delivering multiple drugs with augmented physicochemical properties, targeted delivery capabilities, and controlled release profiles. Second, it enables therapeutic nanomaterials development, thereby expanding combination regimens to include multifunctional nanomedicines. Lastly, it facilitates the construction of all-in-one nanoplatforms assembled with multiple modalities, such as phototherapy, sonodynamic therapy, and imaging. Thus, nanotechnology offers a promising solution to the current bottleneck in both RA treatment and diagnosis. This review summarizes the rationale, advantages, and recent advances in nano-empowered combination therapy for RA. It also discusses safety considerations, drug-drug interactions, and the potential for clinical translation. Additionally, it provides design tips and an outlook on future developments in nano-empowered combination therapy. The objective of this review is to achieve a comprehensive understanding of the mechanisms underlying combination therapy for RA and unlock the maximum potential of nanotechnology, thereby facilitating the smooth transition of research findings from the laboratory to clinical practice.
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Artritis Reumatoide , Humanos , Artritis Reumatoide/tratamiento farmacológico , Animales , Nanomedicina/métodos , Nanotecnología/métodos , Terapia Combinada , Antirreumáticos/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Nanopartículas/químicaRESUMEN
Ferroptosis-mediated multimodal therapy has emerged as a promising strategy for tumor elimination, with lipid peroxide (LPO) playing a pivotal role. However, the therapeutic efficiency is limited due to insufficient intracellular levels of free fatty acids (FFA), which severely hinder the production of LPO. To address this limitation, we proposed a lipophagy strategy aimed at degrading lipid droplets (LDs) to release FFA, serving as the essential "fuel" for LPO production. In this study, the lipophagy inducer epigallocatechin gallate (EGCG) was self-assembled with reactive oxygen species (ROS)-producer phenethyl isothiocyanate (PEITC) mediated by Fe2+ to form EFP nanocapsules, which were further integrated into microneedle patches to form a "all-in-one" EFP@MNs. The metal-polyphenol network structure of EFP endow it with photothermal therapy capacity. Upon insertion into tumors, the released EFP nanocapsules were demonstrated to induce lipophagy through metabolic disturbance, thereby promoting LPO production and facilitating ferroptosis. When combined with photothermal therapy, this approach significantly remolded the tumor immune microenvironment by driving tumor-associated macrophages toward M1 phenotype and enhancing dendritic cell maturation. Encouragingly, in conjunction with αPD-L1 treatment, the proposed EFP@MNs exhibited remarkable efficacy in tumor ablation. Our study presents a versatile framework for utilizing microneedle patches to power ferroptosis-mediated multimodal therapy.
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Selective mutism (SM) is an anxiety disorder that is characterized by a child's persistent inability to communicate verbally in some or all contexts of social life. It is often associated with other cognitive-affective disorders. Performing cognitive-behavioral assessments and psychological interventions can be challenging due to the difficulty in administering standardized neuropsychological tests and involving family and teachers in the intervention program. In a single case study, a young Filipina girl with SM underwent a comprehensive neuropsychological assessment and received multimodal therapeutic intervention between the ages of 7 and 11. The psychological intervention included cognitive-behavioral psychotherapy to improve social-cognitive skills and learning abilities, reduce anxiety, and provide speech therapy. The parents and teachers were actively involved in the therapeutic process and a underwent a psycho-education program. Following this treatment, at the age of 11, the girl started verbalizing in therapy and school contexts, although she still used non-verbal strategies. There was also a gradual improvement in her communicative-linguistic skills and school learning. In conclusion, this report emphasizes the importance of applying an integrated and multimodal intervention to treat SM in children, including psychoeducation for parents and teachers.
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In order to improve the effectiveness of tumor treatment and reduce the toxic side effects of drugs, we formed carrier-free multifunctional nanoparticles (BI NPs) by noncovalent interaction of berberine hydrochloride and IR780. BI NPs possessed the synergistic effects of promoting apoptosis, inhibiting proliferation and metastasis of tumors, and phototherapeutic treatment. Dispersive and passive targeting ability retention (EPR) effects of BI NPs on tumor sites in vivo could be monitored by fluorescence imaging. In addition, BI NPs exhibited effective reactive oxygen species (ROS) generation and photothermal conversion capabilities, photodynamic therapy (PDT), and photothermal therapy (PTT). Importantly, BI NPs inhibit tumor suppression through the AMPK/PI3K/AKT signaling pathway to inhibit tumor proliferation and metastasis. BI NPs not only have efficient in vivo multimodal therapeutic effects but also have good biosafety and potential clinical applications.
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Apoptosis , Carcinoma Hepatocelular , Proliferación Celular , Neoplasias Hepáticas , Nanomedicina , Nanopartículas , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Humanos , Proliferación Celular/efectos de los fármacos , Animales , Nanopartículas/química , Nanopartículas/uso terapéutico , Nanomedicina/métodos , Ratones , Especies Reactivas de Oxígeno/metabolismo , Fotoquimioterapia/métodos , Berberina/farmacología , Berberina/química , Berberina/uso terapéutico , Terapia Fototérmica , Ratones Endogámicos BALB C , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND/AIM: There is limited evidence regarding the systemic treatment of retroperitoneal soft-tissue sarcoma, and the current Japanese guidelines fail to make definitive suggestions. Here, we report our experience with combination chemotherapy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in this population. PATIENTS AND METHODS: We retrospectively reviewed the records of eight patients (three male and five female) who received MAID for pathologically diagnosed metastatic unresectable retroperitoneal sarcoma (either leiomyosarcoma or pleomorphic sarcoma) between October 2019 and January 2022. Treatment efficacy, tolerability (need for dose reduction), and safety profiles were evaluated and summarized. RESULTS: At initiation, the median age was 56.0 years, and the body mass index was 20.0 kg/cm2 Six patients had Eastern Cooperative Oncology Group performance status scores of 0. The net clinical benefit was a partial response in three (37.5%) patients, stable disease in four (50.0%), and progressive disease in one (12.5%). During the median 90.8 weeks of follow-up, disease in five patients progressed, resulting in a median progression-free survival of 48.4 weeks, and five deaths occurred, resulting in an overall survival of 95.1 weeks. Commonly observed adverse events were neutropenia (eight patients), anemia (eight patients), and decreased platelet count (seven patients), which led to dose reduction (60-80%) in six patients. CONCLUSION: MAID combination therapy may be an acceptable option for advanced retroperitoneal sarcoma; however, its benefits must be carefully assessed owing to its not insignificant toxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica , Dacarbazina , Doxorrubicina , Ifosfamida , Mesna , Neoplasias Retroperitoneales , Sarcoma , Humanos , Masculino , Femenino , Persona de Mediana Edad , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Retroperitoneales/tratamiento farmacológico , Neoplasias Retroperitoneales/patología , Sarcoma/tratamiento farmacológico , Sarcoma/patología , Mesna/administración & dosificación , Mesna/uso terapéutico , Anciano , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Dacarbazina/uso terapéutico , Estudios Retrospectivos , AdultoRESUMEN
Smart drug platforms based on spatiotemporally controlled release and integration of tumor imaging are expected to overcome the inefficiency and uncertainty of traditional theranostic modes. In this study, a composite consisting of a thermosensitive hydrogel (polyvinyl alcohol-carboxylic acid hydrogel (PCF)) and a multifunctional nanoparticle (Fe3O4@Au/Mn(Zn)-4-carboxyphenyl porphyrin/polydopamine (FAMxP)) is developed to combine tumor immunogenic cell death (ICD)/immune checkpoint blockade (ICB) therapy under the guidance of magnetic resonance imaging (MRI) and fluorescence imaging (FI). It can not only further recognize the target cells through the folate receptor of tumor cells, but also produce thermal dissolution after exposure to near-infrared light to slowly release FAMxP in situ, thereby prolonging the treatment time and avoiding tumor recurrence. As FAMxP entered the tumor cells, it released FAMx in a pH-dependent manner. Chemodynamic, photothermal and photodynamic therapy can cause significant ICD in cancer cells. ICB can thus be further enhanced by injecting anti-programmed cell death ligand 1, improving the effectiveness of tumor treatment. The developed PCF-FAMxP composite hydrogel may represent an updated drug design approach with simple compositions for cooperative MRI/FI-guided targeted therapeutic pathways for tumors.
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Hidrogeles , Hidrogeles/química , Animales , Ratones , Humanos , Imagen por Resonancia Magnética/métodos , Modelos Animales de Enfermedad , Nanopartículas Multifuncionales/química , Línea Celular Tumoral , Indoles/química , Indoles/farmacología , Sistemas de Liberación de Medicamentos/métodos , Polímeros/química , Imagen Óptica/métodosRESUMEN
PURPOSE: Endometrial cancer (EC) is one of the most common malignancies among women in western countries. This study aimed to assess data on patient treatment in Germany throughout two decades to evaluate the development and effect of surgery, radiation, and chemotherapy. METHODS: This retrospective registry study included 34,349 EC patients diagnosed between 2000 and 2020. Patients were classified into five risk groups. Overall survival was analyzed by Kaplan-Meier method as well as univariable and multivariable Cox regression to evaluate risk factors and treatment options. RESULTS: Over the study period, minimal invasive surgery was used more often compared to open surgery and was associated with better overall survival. Patients with advanced EC were more likely to receive multimodal therapy. Patients with intermediate risk EC had a good prognosis upon surgery, which further improved when radiotherapy was added. High-risk patients showed poorer prognosis but clearly benefited from additional radiotherapy. Survival of elderly high-risk patients with a non-endometrioid histology was improved when chemotherapy was added to surgery and radiotherapy. CONCLUSION: Our study includes a large analysis of data from German clinical cancer registries on the care of endometrial cancer during two decades. We observed an increase of minimal invasive surgery. There is evidence that minimal invasive surgery is not inferior to open surgery. Adjuvant radio- and chemotherapy further improves survival depending on risk group and age.
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Neoplasias Endometriales , Humanos , Femenino , Neoplasias Endometriales/terapia , Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/patología , Neoplasias Endometriales/mortalidad , Estudios Retrospectivos , Alemania/epidemiología , Anciano , Persona de Mediana Edad , Sistema de Registros , Anciano de 80 o más Años , Terapia Combinada , Adulto , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Pelvic malignancies consistently pose significant global health challenges, adversely affecting the well-being of the male population. It is anticipated that clinicians will continue to confront these cancers in their practice. Nanomedicine offers promising strategies that revolutionize the treatment of male pelvic malignancies by providing precise delivery methods that aim to improve the efficacy of therapeutic outcomes while minimizing side effects. Nanoparticles are designed to encapsulate therapeutic agents and selectively target cancer cells. They can also be loaded with theragnostic agents, enabling multifunctional capabilities. OBJECTIVE: This review aims to summarize the latest nanomedicine research into clinical applications, focusing on nanotechnology-based treatment strategies for male pelvic malignancies, encompassing chemotherapy, radiotherapy, immunotherapy, and other cutting-edge therapies. The review is structured to assist physicians, particularly those with limited knowledge of biochemistry and bioengineering, in comprehending the functionalities and applications of nanomaterials. METHODS: Multiple databases, including PubMed, the National Library of Medicine, and Embase, were utilized to locate and review recently published articles on advancements in nano-drug delivery for prostate and colorectal cancers. CONCLUSION: Nanomedicine possesses considerable potential in improving therapeutic outcomes and reducing adverse effects for male pelvic malignancies. Through precision delivery methods, this emerging field presents innovative treatment modalities to address these challenging diseases. Nevertheless, the majority of current studies are in the preclinical phase, with a lack of sufficient evidence to fully understand the precise mechanisms of action, absence of comprehensive pharmacotoxicity profiles, and uncertainty surrounding long-term consequences.
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Neoplasias Colorrectales , Sistemas de Liberación de Medicamentos , Nanomedicina , Neoplasias de la Próstata , Humanos , Masculino , Nanomedicina/métodos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/patología , Sistemas de Liberación de Medicamentos/métodos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/patología , Nanopartículas/química , Neoplasias Pélvicas/patología , Neoplasias Pélvicas/tratamiento farmacológico , Neoplasias Pélvicas/terapia , Medicina de Precisión/métodos , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , AnimalesRESUMEN
OBJECTIVE: To determine the effectiveness and adverse effects of urethrectomy alone or as part of multimodal therapy (MMT). METHODS: A comprehensive search was conducted across MEDLINE (OVID), EMBASE, LILACS and the Cochrane Central Register of Controlled Trials (CENTRAL) databases, from their inception to the present date. The study cohort comprised individuals aged 16 years and older diagnosed with urethral tumours at any stage who underwent either isolated urethrectomy or urethrectomy as an integral component of MMT. RESULTS: Ninety-two studies comprising 25 480 patients met the inclusion criteria. Surgical outcomes for urethral cancer vary considerably, with 5-year overall survival (OS) ranging from 10% to 68% based on disease extent, approach, and gender. Radiotherapy (RT) alone provides 5-year OS of approximately 40%. Combined regimens provide better outcomes compared to single modalities, including reduced recurrence and enhanced survival. However, trimodal therapy showed survival benefits only for urothelial subtypes, indicating the need to tailor management according to cancer type. MMT with neoadjuvant chemotherapy prior to surgery demonstrated the most consistent survival gains. CONCLUSIONS: The management of urethral cancer demands a nuanced, personalised approach, accounting for factors such as tumour location, sex, and tumour stage. MMT combining surgery, chemotherapy and RT has shown the ability to enhance outcomes in advanced disease. More extensive collaborative studies through specialised centres are imperative to advance evidence-based protocols and refine treatment in order to improve survival.
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Neoplasias Uretrales , Humanos , Neoplasias Uretrales/terapia , Masculino , Terapia Combinada , FemeninoRESUMEN
Cancer immunotherapy recently transforms the traditional approaches against various cancer malignancies. Immunotherapy includes systemic and local treatments to enhance immune responses against cancer and involves strategies such as immune checkpoints, cancer vaccines, immune modulatory agents, mimetic antigen-presenting cells, and adoptive cell therapy. Despite promising results, these approaches still suffer from several limitations including lack of precise delivery of immune-modulatory agents to the target cells and off-target toxicity, among others, that can be overcome using nanotechnology. Mesoporous silica nanoparticles (MSNs) are investigated to improve various aspects of cancer immunotherapy attributed to the advantageous structural features of this nanomaterial. MSNs can be engineered to alter their properties such as size, shape, porosity, surface functionality, and adjuvanticity. This review explores the immunological properties of MSNs and the use of MSNs as delivery vehicles for immune-adjuvants, vaccines, and mimetic antigen-presenting cells (APCs). The review also details the current strategies to remodel the tumor microenvironment to positively reciprocate toward the anti-tumor immune cells and the use of MSNs for immunotherapy in combination with other anti-tumor therapies including photodynamic/thermal therapies to enhance the therapeutic effect against cancer. Last, the present demands and future scenarios for the use of MSNs for cancer immunotherapy are discussed.
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Inmunoterapia , Nanopartículas , Neoplasias , Dióxido de Silicio , Dióxido de Silicio/química , Humanos , Nanopartículas/química , Nanopartículas/uso terapéutico , Inmunoterapia/métodos , Neoplasias/terapia , Neoplasias/inmunología , Porosidad , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos , Animales , Vacunas contra el Cáncer/química , Células Presentadoras de Antígenos/inmunologíaRESUMEN
Triple-negative breast cancer (TNBC) is a highly aggressive and uncommon subtype of breast cancer with a poor prognosis. It is crucial to prioritise the creation of a nanotherapeutic method that is highly selective and actively targeting TNBC. This study explores a new nanosystem, Cu9S8-SNAP@PM (C-S@P), composed of Cu9S8-SNAP coated with a platelet membrane (PM). The purpose of this nanosystem is to cure TNBC using multimodal therapy. The utilisation of PM-coated nanoparticles (NPs) enables active targeting, leading to the efficient accumulation of C-S@P within the tumour. The Cu9S8 component within these NPs serves the potential to exert photothermal therapy (PTT) and chemodynamic therapy (CDT). Simultaneously, the S-Nitroso-N-Acetylvanicillamine (SNAP) component enables nitric oxide (NO) gas therapy (GT). Furthermore, when exposed to NIR-II laser light, Cu9S8 not only increases the temperature of the tumour area for PTT, but also boosts CDT and stimulates the release of NO through thermal reactions to improve the effectiveness of GT. Both in vitro and in vivo experimental results validate that C-S@P exhibits minimal side effects and represents a multifunctional nano-drug targeted at tumors for efficient treatment. This approach promises significant potential for TNBC therapy and broader applications in oncology.
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Plaquetas , Neoplasias de la Mama Triple Negativas , Animales , Femenino , Humanos , Ratones , Plaquetas/metabolismo , Línea Celular Tumoral , Cobre/química , Cobre/farmacología , Nanopartículas/química , Óxido Nítrico/metabolismo , Óxido Nítrico/química , Fototerapia , Terapia Fototérmica , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/terapiaRESUMEN
BACKGROUND: The detection rates of early gastric cancer (GC) in China are approximately 20%; upon diagnosis, the majority of patients with GC are identified as having advanced stage disease, and in some cases, even metastatic advanced GC. Currently, the optimal treatment strategy for peritoneal metastasis (PM) in GC remains uncertain, and pathological complete response (pCR) is rare following conversion therapy. CASE PRESENTATION: This case report details the management of a 66-year-old patient diagnosed with advanced stage IVB (T4N2M1c) adenocarcinomas of the gastric cardia with PM who received multimodal therapy comprised of hyperthermic intraperitoneal chemotherapy (HIPEC), XELOX chemotherapy, and anti-programmed cell death-1 (PD-1) therapy followed by radical gastrectomy. Through the multimodal management, the patient attained PCR and experienced long-term survival. CONCLUSION: The conversion therapy protocol combined with HIPEC, XELOX chemotherapy, and anti-PD-1 therapy and our scientific, accurate, full-course management strategy may be propagable for potentially curing patients with advanced GC with PM.
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Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Quimioterapia Intraperitoneal Hipertérmica , Oxaloacetatos , Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/terapia , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/tratamiento farmacológico , Anciano , Capecitabina/uso terapéutico , Capecitabina/administración & dosificación , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/terapia , Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Fluorouracilo/uso terapéutico , Fluorouracilo/administración & dosificación , Estadificación de Neoplasias , Gastrectomía , Terapia Combinada , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Resultado del TratamientoRESUMEN
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy about 50% of PDAC are metastatic at presentation. In this study, we evaluated PDAC demographics, annual trend analysis, racial disparities, survival rate, and the role of different treatment modalities in localized and metastatic disease. METHODS: A total of 144,824 cases of PDAC were obtained from the SEER database from 2000 to 2018. RESULTS: The median age was 69 years, with a slightly higher incidence in males (52%) and 80% of all cases were white. Among cases with available data, 43% were grade III tumors and 57% were metastatic. The most common site of metastasis was the liver (15.7%). The annual incidence has increased steadily from 2000 to 2018. The overall observed (OS) 5-year survival rate was 4.4% (95% CI 4.3-4.6%), and 5 years cause-specific survival (CSS) was 5% (95% CI 5.1-5.4%). The 5-year survival with multimodal therapy (chemotherapy, surgery, and radiation) was 22% (95% CI 20.5-22.8%). 5-year CSS for the blacks was lower at 4.7% (95% CI 4.2-5.1%) compared to the whites at 5.3% (95% CI 5.1-5.4%). Multivariate analysis found male gender and black race associated with worse prognosis. Kaplan-Meier survival analysis found multimodal therapy to have the best outcomes in all three stages. CONCLUSION: PDAC is an aggressive malignancy with male gender and black race are associated with a poor prognosis. Surgery with chemoradiation was associated with the best overall survival. With steadily increasing rates of PDAC, improved treatment modalities are paramount to improving survival in these patients.
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OBJECTIVES: Postoperative empyema is a severe, potentially lethal complication also present, but poorly studied in patients undergoing surgery for pleural mesothelioma. We aimed to analyse which perioperative characteristics might be associated with an increased risk for postoperative empyema. METHODS: From September 1999 to February 2023 a retrospective analysis of consecutive patients undergoing surgery for pleural mesothelioma at the University Hospital of Zurich was performed. Uni- and multivariable logistic regression was used to identify associated risk factors of postoperative empyema after surgery. RESULTS: A total of 400 PM patients were included in the analysis, of which n = 50 patients developed empyema after surgery (12.5%). Baseline demographics were comparable between patients with (Eyes) and without empyema (Eno). 39% (n = 156) patients underwent extrapleural pneumonectomy (EPP), of whom 22% (n = 35) developed postoperative pleural empyema; 6% (n = 15) of the remaining 244 patients undergoing pleurectomy and decortication (n = 46), extended pleurectomy and decortication (n = 114), partial pleurectomy (n = 54) or explorative thoracotomy (n = 30) resulted in postoperative empyema. In multivariable logistic regression analysis, EPP (odds ratio 2.8, 95% confidence interval 1.5-5.4, P = 0.002) emerged as the only risk factor associated with postoperative empyema when controlled for smoking status. Median overall survival was significantly worse for Eyes (16 months, interquartile range 5-27 months) than for Eno (18 months, interquartile range 8-35 months). CONCLUSIONS: Patients undergoing EPP had a significantly higher risk of developing postoperative pleural empyema compared to patients undergoing other surgery types. Survival of patients with empyema was significantly shorter.
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Empiema Pleural , Neoplasias Pleurales , Complicaciones Posoperatorias , Humanos , Masculino , Estudios Retrospectivos , Femenino , Empiema Pleural/epidemiología , Empiema Pleural/cirugía , Empiema Pleural/etiología , Factores de Riesgo , Anciano , Neoplasias Pleurales/cirugía , Neoplasias Pleurales/mortalidad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Persona de Mediana Edad , Neumonectomía/efectos adversos , Mesotelioma/cirugía , Mesotelioma/mortalidad , Mesotelioma Maligno/cirugía , Neoplasias Pulmonares/cirugíaRESUMEN
This case report describes a 32-year-old Pakistani male patient with an Ewing sarcoma (ES) of the adrenal gland. Presenting complaints were abdominal distention, pain, low-grade fever, and weight loss. Initial studies, including imaging and tumor markers, ruled out any other possible origins of the mass. A percutaneous biopsy verified the tumor's neuroendocrine origin. Extensive involvement of nearby anatomical structures was discovered through exploratory laparotomy, rendering total resection difficult. Based on the presence of malignant, round, blue cells that were positive for specific immunostaining markers, the histopathology report supported the diagnosis of an ES with a staging of T3N0M0. Chemotherapy, in accordance with the VAC-IE protocol, was administered after debulking surgery. Subsequent imaging and close monitoring revealed no metastatic or residual tumors. Adrenal ES is an uncommon, aggressive tumor that mandates prompt diagnosis and management. This case report highlights the value of early detection and multimodal therapy in enhancing patient outcomes for this rare malignancy.
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Although immunotherapy has revolutionized cancer care, there is still an urgent need to enhance its efficacy and ensure its safety. A correct cancer theory and proper scientific method empower pertinent cancer research and enable effective and efficient drug versus therapy development for patient care. In this perspective, we revisit the concept of immune privilege in a cancer cell versus normal cell, as well as in a cancer stem cell versus normal stem cell. We re-examine whether effective immunotherapies are efficacious due to their anti-cancer and/or immune modulatory mechanisms. We reassess why checkpoint inhibitors (CPIs) are not equal. We reconsider whether one can attribute the utility of immunotherapy to specific cancer subtypes and its futility to certain tumor/immune compartments, components, and microenvironments. We propose ways and means to advance immunotherapy beyond CPIs by combining anti-PD1/L1 with various other treatment modalities according to an appropriate scientific theory, e.g., stem cell origin of cancer, and based on available clinical evidence, e.g., randomized clinical trials. We predict that a stem cell theory of cancer will facilitate the design of better and safer immunotherapy with improved selection of its use for the right patient with the right cancer type at the right time to optimize clinical benefits and minimize potential toxic effects and complications.