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1.
BMJ Open ; 14(5): e080976, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38692724

RESUMEN

INTRODUCTION: Symptoms due to chemotherapy are common in patients with cancer. Cancer-related symptoms are closely associated with the deterioration of physical function which can be associated with decreased quality of life and increased mortality. Thus, timely symptom identification is critical for improving cancer prognosis and survival. Recently, remote symptom monitoring system using digital technology has demonstrated its effects on symptom control or survival. However, few studies examined whether remote monitoring would contribute to retaining physical function among patients with cancer. Therefore, this study aimed to evaluate the effectiveness of mobile-based symptom monitoring in improving physical function among patients with cancer under chemotherapy. METHODS AND ANALYSIS: This study is a multicentre, open-label, parallel-group, randomised controlled trial. We will recruit 372 patients at three tertiary hospitals located in Seoul, South Korea. Study participants will be randomly assigned to either an intervention group receiving the ePRO-CTCAE app and a control group receiving routine clinical practice only. The primary outcome is changes in physical function from commencement to completion of planned chemotherapy. A linear mixed model will be performed under the intention-to-treat principle. The secondary outcomes include physical activity level; changes in pain interference; changes in depressive symptom; unplanned clinical visits; additional medical expenditure for symptom management; completion rate of planned chemotherapy; changes in symptom burden and health-related quality of life; and 1-year overall mortality. ETHICS AND DISSEMINATION: The study has been approved by the institutional review board and ethics committee at the three university hospitals involved in this trial. Written informed consent will be obtained from all the participants. The results of the trial will be submitted for publication in peer-reviewed academic journals and disseminated through relevant literatures. TRIAL REGISTRATION NUMBER: KCT0007220.


Asunto(s)
Aplicaciones Móviles , Neoplasias , Calidad de Vida , Humanos , Neoplasias/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Masculino , Femenino , República de Corea , Adulto , Telemedicina/métodos
2.
Nature ; 628(8006): 162-170, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38538791

RESUMEN

Ageing of the immune system is characterized by decreased lymphopoiesis and adaptive immunity, and increased inflammation and myeloid pathologies1,2. Age-related changes in populations of self-renewing haematopoietic stem cells (HSCs) are thought to underlie these phenomena3. During youth, HSCs with balanced output of lymphoid and myeloid cells (bal-HSCs) predominate over HSCs with myeloid-biased output (my-HSCs), thereby promoting the lymphopoiesis required for initiating adaptive immune responses, while limiting the production of myeloid cells, which can be pro-inflammatory4. Ageing is associated with increased proportions of my-HSCs, resulting in decreased lymphopoiesis and increased myelopoiesis3,5,6. Transfer of bal-HSCs results in abundant lymphoid and myeloid cells, a stable phenotype that is retained after secondary transfer; my-HSCs also retain their patterns of production after secondary transfer5. The origin and potential interconversion of these two subsets is still unclear. If they are separate subsets postnatally, it might be possible to reverse the ageing phenotype by eliminating my-HSCs in aged mice. Here we demonstrate that antibody-mediated depletion of my-HSCs in aged mice restores characteristic features of a more youthful immune system, including increasing common lymphocyte progenitors, naive T cells and B cells, while decreasing age-related markers of immune decline. Depletion of my-HSCs in aged mice improves primary and secondary adaptive immune responses to viral infection. These findings may have relevance to the understanding and intervention of diseases exacerbated or caused by dominance of the haematopoietic system by my-HSCs.


Asunto(s)
Inmunidad Adaptativa , Envejecimiento , Linaje de la Célula , Células Madre Hematopoyéticas , Linfocitos , Células Mieloides , Rejuvenecimiento , Animales , Femenino , Masculino , Ratones , Inmunidad Adaptativa/inmunología , Envejecimiento/inmunología , Linfocitos B/citología , Linfocitos B/inmunología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/inmunología , Inflamación/inmunología , Inflamación/patología , Linfocitos/citología , Linfocitos/inmunología , Linfopoyesis , Células Mieloides/citología , Células Mieloides/inmunología , Mielopoyesis , Fenotipo , Linfocitos T/citología , Linfocitos T/inmunología , Virus/inmunología
3.
Cancer Med ; 13(5): e7096, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38466031

RESUMEN

OBJECTIVE: To evaluate a psychometric validation of the endometrial cancer subscales (EnCS) in the Functional Assessment of Cancer Therapy-Endometrial (FACT-EN) among patients with endometrial cancer. METHODS: This cross-sectional study was conducted at a tertiary university-based hospital in South Korea between April and October 2022. Participants completed a survey questionnaire that included the FACT-EN. Exploratory and confirmatory factor analyses (EFA, CFA) and the reliability were measured using the intraclass correlation coefficient (ICC) under a two-way mixed model. Pearson's correlations were used to evaluate the validity. We also tested known-group validity. RESULTS: In total, 240 patients with endometrial cancer participated in the survey. In EFA, we found EnCS included four domains. In CFA, four-factor solution model was good: CFI = 0.659; SRMR = 0.066, and RMSEA = 0.073. The mean (SD) of total score of FACT-EN was 122.84 (23.58). The floor and ceiling effects were 0.4% and 0.4%, respectively. Cronbach's α coefficients for the five scales of the EnCS ranged from 0.78 to 0.91. The ICC of EnCS was 0.76. The convergent and discriminant validity of EnCS was acceptable. In the group analysis, older age and lower ECOG performance scores were associated with higher EnCS scores. The stomach and vaginal domains in EnCS were higher in patients who had completed treatment for more than 1 year compared to those who were still undergoing treatment. CONCLUSIONS: FACT-EN has demonstrated its validity as an assessment tool with significant implications for capturing various symptoms in patients with endometrial cancer.


Asunto(s)
Neoplasias Endometriales , Femenino , Humanos , Estudios Transversales , Psicometría , Reproducibilidad de los Resultados , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/terapia , Análisis Factorial
4.
Front Genet ; 15: 1342021, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38463169

RESUMEN

Gene expression profiling using RNA-sequencing (RNA-seq) and microarray technologies is widely used in cancer research to identify biomarkers for clinical endpoint prediction. We compared the performance of these two methods in predicting protein expression and clinical endpoints using The Cancer Genome Atlas (TCGA) datasets of lung cancer, colorectal cancer, renal cancer, breast cancer, endometrial cancer, and ovarian cancer. We calculated the correlation coefficients between gene expression measured by RNA-seq or microarray and protein expression measured by reverse phase protein array (RPPA). In addition, after selecting the top 103 survival-related genes, we compared the random forest survival prediction model performance across test platforms and cancer types. Both RNA-seq and microarray data were retrieved from TCGA dataset. Most genes showed similar correlation coefficients between RNA-seq and microarray, but 16 genes exhibited significant differences between the two methods. The BAX gene was recurrently found in colorectal cancer, renal cancer, and ovarian cancer, and the PIK3CA gene belonged to renal cancer and breast cancer. Furthermore, the survival prediction model using microarray was better than the RNA-seq model in colorectal cancer, renal cancer, and lung cancer, but the RNA-seq model was better in ovarian and endometrial cancer. Our results showed good correlation between mRNA levels and protein measured by RPPA. While RNA-seq and microarray performance were similar, some genes showed differences, and further clinical significance should be evaluated. Additionally, our survival prediction model results were controversial.

5.
Gland Surg ; 13(1): 19-31, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38323228

RESUMEN

Background: The enhanced recovery after surgery (ERAS) protocols have been consistently associated with improved patient experience and surgical outcomes. Despite the release of ERAS Society guidelines specific to gynecologic oncology, the adoption of ERAS in gynecology on global level has been disappointingly low and some centers have shown minimal improvement in clinical outcomes after adopting ERAS. The aim of this study is to describe the development and early experience of ERAS protocols in gynecologic surgery at an urban academic tertiary medical center. Methods: This was an observational prospective cohort study. The target patient population included those with low comorbidities who were scheduled to undergo various types of gynecologic surgeries for both benign and malignant diseases between October 2020 and February 2021. Two attending surgeons implemented the protocols for their patients (ERAS cohort) while three attending surgeons maintained the conventional perioperative care for their patients (non-ERAS cohort). Baseline characteristics, surgical outcomes and patients' answers to a 12-question survey were compared. A case-matched comparative analysis was also performed between the ERAS cohort and the historical non-ERAS cohort (those who received the same types of surgical procedures from the two ERAS attending surgeons prior to the implementation of the protocols). Results: A total of 244 patients were evaluated (122 in the ERAS cohort vs. 122 in the non-ERAS cohort). The number of vials of opioid analgesia used during the first two postoperative days was significantly lower whereas the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen was more frequent in the ERAS cohort group. The patients in the ERAS group reported less postoperative pain, feelings of hunger and thirst, and greater amount of exercise postoperatively. These benefits of the ERAS cohort were more pronounced in the patients who underwent laparotomic surgeries than those who underwent laparoscopic surgeries. The case-matched comparative analysis also showed similar results. The length of hospital stay did not differ between those who underwent the ERAS protocols and those who did not. Conclusions: The results of the study demonstrated the safety, clinical feasibility and benefits of the ERAS protocols for patients undergoing gynecologic surgeries for both benign and malignant indications.

6.
Front Oncol ; 14: 1341228, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38327741

RESUMEN

Introduction: We aimed to predict platinum sensitivity using routine baseline multimodal magnetic resonance imaging (MRI) and established clinical data in a radiomics framework. Methods: We evaluated 96 patients with ovarian cancer who underwent multimodal MRI and routine laboratory tests between January 2016 and December 2020. The patients underwent diffusion-weighted, contrast-enhanced T1-weighted, and T2-weighted MRI. Subsequently, 293 radiomic features were extracted by manually identifying tumor regions of interest. The features were subjected to the least absolute shrinkage and selection operators, leaving only a few selected features. We built the first prediction model with a tree-based classifier using selected radiomics features. A second prediction model was built by combining the selected radiomic features with four established clinical factors: age, disease stage, initial tumor marker level, and treatment course. Both models were built and tested using a five-fold cross-validation. Results: Our radiomics model predicted platinum sensitivity with an AUC of 0.65 using a few radiomics features related to heterogeneity. The second combined model had an AUC of 0.77, confirming the incremental benefits of the radiomics model in addition to models using established clinical factors. Conclusion: Our combined radiomics-clinical data model was effective in predicting platinum sensitivity in patients with advanced ovarian cancer.

7.
J Gynecol Oncol ; 35(2): e66, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38330382

RESUMEN

In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.


Asunto(s)
Neoplasias Endometriales , Neoplasias de los Genitales Femeninos , Neoplasias Ováricas , Neoplasias del Cuello Uterino , Femenino , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Endometriales/tratamiento farmacológico
8.
J Gynecol Oncol ; 35(2): e45, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38216137

RESUMEN

The Korean Society of Gynecologic Oncology (KSGO) had been making an effort to standardize and enhance the quality of domestic uterine corpus cancer treatment by developing updated clinical practice guidelines in 2021. The KSGO revised the guidelines based on a literature search using 4 key elements: Population, Intervention, Comparison, and Outcome framework. These elements include the evaluation of the efficacy and safety of immune checkpoint inhibitor treatment in recurrent/advanced endometrial cancer patients who have failed platinum-based chemotherapy, as well as the effect of combined treatment with trastuzumab in patients with HER2/neu-positive endometrial cancer. Additionally, the guideline assessed the efficacy and safety of omitting lymph node dissection in low-risk endometrial cancer patients, investigated the effect of sentinel lymph node mapping in early-stage endometrial cancer surgery, addressed the outcome of chemoradiation therapy as a postoperative treatment in patients with advanced (stage III-IVA) endometrial cancer, and explored the impact of initial treatment with immune checkpoint inhibitors on survival in patients with advanced or recurrent endometrial cancer patients.


Asunto(s)
Neoplasias Endometriales , Ganglio Linfático Centinela , Neoplasias Uterinas , Femenino , Humanos , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Neoplasias Uterinas/patología , Neoplasias Endometriales/patología , Escisión del Ganglio Linfático , República de Corea , Biopsia del Ganglio Linfático Centinela , Ganglio Linfático Centinela/patología , Ganglios Linfáticos/patología
9.
Elife ; 122023 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-38131311

RESUMEN

Computational prediction of protein structure has been pursued intensely for decades, motivated largely by the goal of using structural models for drug discovery. Recently developed machine-learning methods such as AlphaFold 2 (AF2) have dramatically improved protein structure prediction, with reported accuracy approaching that of experimentally determined structures. To what extent do these advances translate to an ability to predict more accurately how drugs and drug candidates bind to their target proteins? Here, we carefully examine the utility of AF2 protein structure models for predicting binding poses of drug-like molecules at the largest class of drug targets, the G-protein-coupled receptors. We find that AF2 models capture binding pocket structures much more accurately than traditional homology models, with errors nearly as small as differences between structures of the same protein determined experimentally with different ligands bound. Strikingly, however, the accuracy of ligand-binding poses predicted by computational docking to AF2 models is not significantly higher than when docking to traditional homology models and is much lower than when docking to structures determined experimentally without these ligands bound. These results have important implications for all those who might use predicted protein structures for drug discovery.


Asunto(s)
Furilfuramida , Receptores Acoplados a Proteínas G , Simulación del Acoplamiento Molecular , Unión Proteica , Receptores Acoplados a Proteínas G/metabolismo , Descubrimiento de Drogas , Ligandos , Sitios de Unión , Conformación Proteica
10.
J Pers Med ; 13(10)2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37888044

RESUMEN

Laparoscopic surgery has evolved with technological advances in many aspects and increasing demand for its benefits in cosmetics, fast recovery, reduced complication rates and pain. However, it still possesses drawbacks such as limited surgical movement due to the nature of rigid laparoscopic instruments. In order to overcome such limitations, several laparoscopic jointed instruments have been developed. In this prospective multicenter, single-arm cohort study, we investigated the short-term safety and feasibility of the new articulating laparoscopic instruments in benign gynecologic surgery. A total of 113 patients who were diagnosed with benign gynecologic adnexal diseases underwent laparoscopic surgery with articulating laparoscopic instruments. Surgical outcomes, including intra/postoperative complication rates, operation time and estimated blood loss, as well as surgeon's subjective evaluation of the usage of the instruments, were evaluated. The results demonstrated that the articulating laparoscopic instruments had comparable usability and produced similar surgical outcomes to conventional laparoscopic surgery. The objective parameters, such as the operative time and complication rates, as well as the subjective parameters, such as the surgeon's own evaluation of the surgical instruments' usability, demonstrated potential benefits of the instruments in benign gynecological diseases. Overall, the study demonstrated that the use of this novel articulating device is feasible in gynecologic laparoscopic surgery.

11.
J Pers Med ; 13(7)2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37511791

RESUMEN

We compared surgical outcomes between single-port access total laparoscopic hysterectomy (SPA-TLH) and hybrid robotic single-site hysterectomy (RSSH), a new technique of combining the benefits of SPA-TLH with RSSH in this study. A total of 64 patients were retrospectively analyzed. They underwent either hybrid RSSH or SPA-TLH for benign gynecologic disease between December 2018 and August 2021. To assess the feasibility of hybrid RSSH, the clinical characteristics and surgical outcomes were compared between the hybrid RSSH group (n = 29) and the SPA-TLH group (n = 35). All of the surgeries were completed without requiring additional ports or conversion to laparotomy. The surgical outcomes including total operative time, uterine weight, estimated blood loss, hemoglobin changes, length of hospital stay, and postoperative pain scores were not significantly different between the two groups. The colpotomy time, including the detachment of the uterosacral and cardinal ligaments, was shorter in the hybrid RSSH group than in the SPA-TLH group (8.0 min vs. 14.0 min; p = 0.029). However, the vaginal cuff closure time was longer in the hybrid RSSH group than in the SPA-TLH group (15.0 min vs.10.0 min; p = 0.001). No difference was observed with regards to intraoperative and postoperative complications. Hybrid RSSH appears to be a feasible procedure for hysterectomy in patients with benign gynecologic diseases.

12.
J Clin Med ; 12(14)2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37510787

RESUMEN

The purpose of this study was to compare single-port access (SPA) laparoscopy and SPA robot assisted laparoscopy (RAL) for endometriosis with respect to ovarian reserve preservation and surgical outcomes. Clinical factors affecting any reduction in ovarian function after surgery were also evaluated. Patients with endometriosis who underwent SPA laparoscopy (n = 87) or RAL (n = 78) were retrospectively reviewed. Patients' baseline characteristics, including the severity of endometriosis and surgical outcomes including surgical complexity, were collected. To assess the preservation of ovarian reserve after surgery, serum anti-Müllerian hormone (AMH) levels before surgery, at two weeks, and at three months after surgery were collected. Age, ovarian cyst size, location of cyst, complexity of surgery, and the severity of endometriosis were associated with the reduction in AMH levels after surgery. The severity of endometriosis was higher in the RAL group than in the SPA group. There were no significant differences in other clinical baseline characteristics, including preoperative AMH levels. For surgical outcomes, radical surgery was more frequently performed in the RAL group. In univariate and multivariate linear regression analyses, age, ovarian cyst size, location of cyst, complexity of surgery, and the severity of endometriosis were associated with the reduction in AMH levels after surgery. Incorporating surgical approaches and risk factors for postoperative ovarian function decrease, RAL was more beneficial than SPA laparoscopy for the preservation of ovarian reserve in patients with mild endometriosis (stage I/II) (postoperative 3 month AMH reduction rate (%), SPA laparoscopy vs. RAL, 33.51 ± 19.98 vs. 23.58 ± 14.98, p = 0.04) and in patients who underwent non-complex surgery (postoperative 3 month AMH reduction rate (%), SPA laparoscopy vs. RAL, 37.89 ± 22.37 vs. 22.37 ± 17.49, p = 0.022). SPA RAL may have advantages over SPA laparoscopy in ovarian function preservation, especially in patients with mild endometriosis and patients who have undergone a non-complex surgery.

13.
J Gynecol Oncol ; 34(5): e58, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37170725

RESUMEN

OBJECTIVE: Fenbendazole (FZ) has potential anti-cancer effects, but its poor water solubility limits its use for cancer therapy. In this study, we investigated the anti-cancer effect of FZ with different drug delivery methods on epithelial ovarian cancer (EOC) in both in vitro and in vivo models. METHODS: EOC cell lines were treated with FZ and cell proliferation was assessed. The effect of FZ on tumor growth in cell line xenograft mouse model of EOC was examined according to the delivery route, including oral and intraperitoneal administration. To improve the systemic delivery of FZ by converting fat-soluble drugs to hydrophilic, we prepared FZ-encapsulated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (FZ-PLGA-NPs). We investigated the preclinical efficacy of FZ-PLGA-NPs by analyzing cell proliferation, apoptosis, and in vivo models including cell lines and patient-derived xenograft (PDX) of EOC. RESULTS: FZ significantly decreased cell proliferation of both chemosensitive and chemoresistant EOC cells. However, in cell line xenograft mouse models, there was no effect of oral FZ treatment on tumor reduction. When administered intraperitoneally, FZ was not absorbed but aggregated in the intraperitoneal space. We synthesized FZ-PLGA-NPs to obtain water solubility and enhance drug absorption. FZ-PLGA-NPs significantly decreased cell proliferation in EOC cell lines. Intravenous injection of FZ-PLGA-NP in xenograft mouse models with HeyA8 and HeyA8-MDR significantly reduced tumor weight compared to the control group. FZ-PLGA-NPs showed anti-cancer effects in PDX model as well. CONCLUSION: FZ-incorporated PLGA nanoparticles exerted significant anti-cancer effects in EOC cells and xenograft models including PDX. These results warrant further investigation in clinical trials.


Asunto(s)
Nanopartículas , Neoplasias Ováricas , Humanos , Animales , Ratones , Femenino , Fenbendazol/uso terapéutico , Neoplasias Ováricas/patología , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Línea Celular Tumoral , Agua
14.
PLoS One ; 18(4): e0283780, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37097995

RESUMEN

BACKGROUND: Preoperative anxiety is an unpleasant experience that can adversely affect perioperative outcomes. Although clinical benefits of preoperative oral carbohydrate is well reported, the effect of adding chewing gum to carbohydrate loading has never been studied. We aimed to investigate the effect of adding gum-chewing to oral carbohydrates on preoperative anxiety and gastric volume in patients undergoing gynecologic surgery. METHODS: One hundred and four patients were enrolled and randomized either into a carbohydrate drink group (CHD group) or CHD with gum group. The CHD group was instructed to drink 400 mL of oral carbohydrate the evening before and 200-400 mL 3 hours before surgery. The CHD with gum group was encouraged to chew gum freely during preanesthetic fasting in addition to consuming oral carbohydrates in the same manner. The primary endpoint was preoperative anxiety assessed using the Amsterdam preoperative anxiety and information scale (APAIS). The degree of patient-reported quality of recovery after surgery and gastric volume prior to general anesthesia were also compared as secondary outcomes. RESULTS: Preoperative APAIS was lower in the CHD with gum group compared with the CHD group (16 [11.5, 20] vs. 20 [16.5, 23], p = 0.008). Patient-rated quality of recovery after surgery was also higher in the CHD with gum group and showed a significant negative correlation with preoperative APAIS score (correlation coefficient: -0.950, p = 0.001). Gastric volume were not different between the groups (0 [0-0.45] vs. 0 [0-0.22], p = 0.158). CONCLUSION: The addition of gum chewing to oral carbohydrate loading during preoperative fasting was more effective in relieving preoperative anxiety than oral carbohydrate alone in women patients undergoing elective gynecologic surgery. TRIAL REGISTRATION: Clinical Research Information Services, CRIS identifier: KCT0005714, https://cris.nih.go.kr/cris/index.jsp.


Asunto(s)
Carbohidratos , Goma de Mascar , Humanos , Femenino , Procedimientos Quirúrgicos Ginecológicos , Estómago , Ansiedad , Cuidados Preoperatorios
15.
Biomaterials ; 296: 122087, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36924663

RESUMEN

The development of organoid culture technologies has triggered industrial interest in ex vivo drug test-guided clinical response prediction for precision cancer therapy. The three-dimensional culture encapsulated with basement membrane (BM) components is extremely important in establishing ex vivo organoids and drug sensitivity tests because the BM components confer essential structures resembling tumor histopathology. Although numerous studies have demonstrated three-dimensional culture-based drug screening methods, establishing a large-scale drug-screening platform with matrix-encapsulated tumor cells is challenging because the arrangement of microspots of a matrix-cell droplet onto each well of a microwell plate is inconsistent and difficult to standardize. In addition, relatively low scales and lack of reproducibility discourage the application of three-dimensional organoid-based drug screening data for precision treatment or drug discovery. To overcome these limitations, we manufactured an automated organospotter-integrated high-throughput organo-on-pillar (high-TOP) drug-screening platform. Our system is compatible with various extracellular matrices, including BM extract, Matrigel, collagen, and hydrogel. In addition, it can be readily utilized for high-content analyses by simply exchanging the bottom plates without disrupting the domes. Our system demonstrated considerable robustness, consistency, reproducibility, and biological relevancy in three-dimensional drug sensitivity analyses using Matrigel-encapsulated ovarian cancer cell lines. We also demonstrated proof-of-concept cases representing the clinical feasibility of high-TOP-assisted ex vivo drug tests linked to clinical chemo-response in ovarian cancer patients. In conclusion, our platform provides an automated and standardized method for ex vivo drug-sensitivity-guided clinical response prediction, suggesting effective chemotherapy regimens for patients with cancer.


Asunto(s)
Técnicas de Cultivo de Célula , Neoplasias Ováricas , Femenino , Humanos , Técnicas de Cultivo de Célula/métodos , Reproducibilidad de los Resultados , Evaluación Preclínica de Medicamentos/métodos , Descubrimiento de Drogas , Organoides , Neoplasias Ováricas/patología , Ensayos Analíticos de Alto Rendimiento/métodos
16.
Anesth Analg ; 137(3): 525-533, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36727850

RESUMEN

BACKGROUND: Surgery for gynecologic malignancy via midline-laparotomy leads to severe postoperative pain. Adequate pain control while sparing opioid consumption does offer benefits in postoperative complications and recovery. Intrathecal morphine (ITM) provides simple and effective analgesia. In this randomized trial, we compared postoperative opioid consumption in patients who received either ITM or a sham procedure. METHODS: We enrolled 68 adult patients undergoing open gynecologic oncology surgery from June 2021 to November 2021. They were randomly allocated to the ITM group (ITM; 200 µg injection) or sham group (sham procedure) to achieve a final 1:1 ratio between groups. We compared opioid consumption and pain severity during 72 hours after surgery. The variables regarding postoperative recovery and patient-centered outcomes were collected. The primary outcome is cumulative intravenous (IV) opioid consumption 24 hours after surgery. RESULTS: The median (interquartile range) cumulative IV opioid consumption during 24 hours after surgery was 18 mg (12-29) in the ITM group and 36 mg (27-42) in the sham group (median difference, 13; 95% confidence interval, 7.2-20.7; P < .001). Patient satisfaction regarding pain control was statistically significantly higher in the ITM group than in the sham group at postoperative 24 and 48 hours ( P < .001 and P = .005, respectively). There were no significant differences in the variables associated with postoperative recovery and frequency of complications requiring treatment. CONCLUSIONS: ITM is a safe and effective analgesic method after curative intent laparotomy for gynecologic malignancy. ITM provides better pain relief, reduces opioid consumption, and improves patient satisfaction without additional evident adverse events.


Asunto(s)
Analgésicos Opioides , Neoplasias de los Genitales Femeninos , Adulto , Humanos , Femenino , Morfina , Neoplasias de los Genitales Femeninos/cirugía , Neoplasias de los Genitales Femeninos/inducido químicamente , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Inyecciones Espinales , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología
17.
Clin Nucl Med ; 48(2): e51-e59, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36607373

RESUMEN

PURPOSE: The aim of this study was to develop an 18F-FDG PET/CT-based model to predict complete cytoreduction during primary cytoreductive surgery (CRS) for ovarian cancer (OC). PATIENTS AND METHODS: We retrospectively identified patients with stage III-IV OC who underwent primary CRS between June 2013 and February 2020 at 2 tertiary centers. Patients from each hospital were assigned to training and test sets. The abdominal cavity was divided into 3 sections, and data for the PET/CT-derived parameters were collected through image analysis. Various prediction models were constructed by combining clinicopathologic characteristics and PET/CT-derived parameters. The performance of the model with the highest area under the receiver operating characteristic curve (AUC) was externally validated. RESULTS: The training and test sets included 159 and 166 patients, respectively. The median age of patients in the test set was 55 years; 72.3% of them had stage III tumors, and 65.4% underwent complete cytoreduction. Metabolic tumor volume, total lesion glycolysis, and the number of metastatic lesions above the upper margin of the renal vein (area A) were selected among the PET/CT parameters. The best predictive multivariable model consisted of CA-125 (<750 or ≥750 IU/mL), number of metastatic lesions (<2 or ≥2), and metabolic tumor volume of area A, predicting complete cytoreduction with an AUC of 0.768. The model was validated using a test set. Its predictive performance yielded an AUC of 0.771. CONCLUSIONS: We successfully developed and validated a preoperative model to predict complete cytoreduction in advanced OC. This model can facilitate patient selection for primary CRS in clinical practice.


Asunto(s)
Neoplasias Ováricas , Femenino , Humanos , Persona de Mediana Edad , Carcinoma Epitelial de Ovario/patología , Procedimientos Quirúrgicos de Citorreducción , Fluorodesoxiglucosa F18 , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos
18.
J Pers Med ; 12(12)2022 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-36556217

RESUMEN

The objective of the present pilot study is to compare operative outcomes between vaginal natural orifice transluminal endoscopic surgery (vNOTES) and single-port access (SPA) adnexectomy. Subjects were patients who underwent adnexectomy for benign adnexal disease, from November 2019 to May 2021. A total of 12 patients underwent vNOTES adnexectomy, and 55 patients received SPA laparoscopic adnexectomy. All surgeries were performed by one surgeon. In order to balance the baseline characteristics of the patients, 1:2 matching was performed. The vNOTES group demonstrated a low postoperative pain score within 12 h after surgery. They also required less use of analgesic medications postoperatively. Other surgical outcomes were comparable between the two groups. This study showed that vNOTES adnexectomy has comparable surgical outcomes to SPA.

19.
Front Oncol ; 12: 926878, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36158646

RESUMEN

We investigated the incidence of reactive thrombocytosis after maximal cytoreductive surgery in advanced epithelial ovarian cancer (EOC) and its role in patient survival. We retrospectively reviewed the electronic medical records of patients who underwent primary cytoreductive surgery for advanced EOC from 1 January 2012 to 31 December 2017. We analyzed the serum platelet counts at various time points from before surgery, during the peri-operative period, and after each cycle of adjuvant chemotherapy. A total of 474 patients were eligible for the analysis. Among them, 401 patients (84.6%) had FIGO stage III disease status. The most common histology type was serous adenocarcinoma (405 patients, 85.4%). Seventy-nine patients (22.6%) received splenectomy, and optimal cytoreduction was achieved in 326 patients (68.8%). A week after surgery, thrombocytosis was observed in 165 patients (34.8%) in the entire cohort. Higher platelet counts were observed in patients with splenectomy compared with patients without splenectomy. In particular, thrombocytosis on the fifth cycle of adjuvant chemotherapy showed the most significant effects on overall survival in multivariate analysis. In a logistic regression model, splenectomy was significantly attributed to thrombocytosis on the fifth cycle of chemotherapy. Reactive thrombocytosis after primary cytoreductive surgery is associated with poor survival in advanced EOC, particularly when thrombocytosis is observed during adjuvant chemotherapy.

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