RESUMEN

PURPOSE: To describe the frequency, findings, and interventions of patients' emergency department visits after all types of glaucoma surgery DESIGN: Retrospective cohort study SUBJECTS: All surgical glaucoma patients between 2013 and 2021 METHODS: This single institution study collected demographics, surgery type, and surgical parameters for each patient. Subsequently, for those visiting the emergency department within 50 days of surgery, data was collected on reason for visit, findings, and ophthalmic intervention. Logistic regression models were used to determine the odds of ED visits based on multiple risk factors. MAIN OUTCOME: Postoperative presentation to ED RESULTS: Among 9155 surgeries in 5505 patients, 5.7% had ED visits within 50 days, with 46.3% having ocular complaints. Patients with ocular diagnoses presented earlier than those without (p < 0.001). Patients who presented to the ED with an ocular diagnosis were found to be significantly younger than those who did not present (62.2 ± 18.6 vs 65.4 ± 18.0 years old, p < 0.028). Furthermore, white patients were more likely than black patients to present with an ocular diagnosis compared to a non-ocular diagnosis (OR 2.64, 95% CI 1.67-4.18, p<0.001). Patients undergoing their first glaucoma surgery had a much higher chance of presenting to the ED compared to patients who had undergone more than one surgery (OR: 3.75, 95%CI 2.74 - 5.14, p < 0.001). Those who underwent traditional surgeries were more likely than patients with trabecular meshwork bypass stent (TMBS) to present to the ED with an ocular diagnosis (OR: 3.02, 95% CI 1.29 - 7.08, p = 0.011). Filtering surgeries and glaucoma drainage device (GDD) revisions exhibited more vision-threatening conditions than glaucoma drainage devices (p = 0.037 and p = 0.010 respectively). Ophthalmology consultation was sought for 88.0% of ocular diagnoses. Most received medical therapy (71.0%), primarily IOP-lowering drops. CONCLUSION: ED visits after glaucoma surgery are infrequent, yet more often seen in younger patients or those undergoing their first glaucoma surgery. TMBS, but not trabecular meshwork excision and/or Schlemm's canal dilation (TME/SCD), were less likely to present to the ED than traditional surgeries. Filtering surgeries and tube revisions presented more often with visual threatening conditions.

RESUMEN

Background: To report the surgical safety of reinforced bio-interventional cyclodialysis with scleral allograft reinforcement. Methods: This was a consecutive case series of 243 eyes with open-angle glaucoma who underwent a bio-scaffolded cyclodialysis (BSC) procedure for uveoscleral outflow enhancement using allogeneic bio-spacers to maintain patency of the internal filtration conduit. Results: 79% of the eyes underwent concomitant phacoemulsification cataract surgery prior to BSC intervention, while the remaining eyes underwent stand-alone BSC surgery. All patients had a postoperative surgical safety period of at least 30 days. There were no sight-threatening or serious ocular adverse events. There was one case of prolonged iritis beyond 30 days, which resolved with topical treatment. Two cases (0.8%) of intraoperative and five (2%) of postoperative non-sight-threatening hyphema were without clinical sequelae, which resolved with conservative management. There were 11 cases of IOP elevation and one case of numeric hypotony without maculopathy, which resolved within the study period. The rate of secondary surgical intervention for IOP control was low, and overall, IOP for the cohort improved in the postoperative period, with 78.6% of eyes achieving IOP ≤ 18 mmHg without an increase in medications. Conclusions: Allogeneic biotissue for cyclodialysis intervention demonstrates a biocompatible ocular profile as an implantable material for internal scleral reinforcement during uveoscleral outflow enhancement surgery.

RESUMEN

BACKGROUND: For distal forearm fractures in children, it has been shown that a below-elbow cast is an adequate treatment that overcomes the discomfort of an above-elbow cast and unnecessary immobilization of the elbow. For reduced diaphyseal both-bone forearm fractures, our previous randomized controlled trial (RCT)-which compared an above-elbow cast with early conversion to a below-elbow cast-revealed no differences in the risk of redisplacement or functional outcomes at short-term follow-up. Although studies with a longer follow-up after diaphyseal both-bone forearm fractures in children are scarce, they are essential, as growth might affect the outcome. QUESTIONS/PURPOSES: In this secondary analysis of an earlier RCT, we asked: (1) Does early conversion from an above-elbow to a below-elbow cast in children with reduced, stable diaphyseal forearm fractures result in worse clinical and radiological outcome? (2) Does a malunion result in inferior clinical outcomes at 7.5 years of follow-up? METHODS: In this study, we evaluated children at a minimum of 5 years of follow-up who were included in a previous RCT. The median (range) duration of follow-up was 7.5 years (5.2 to 9.9). The patients for this RCT were included from the emergency departments of four different urban hospitals. Between January 2006 and August 2010, we treated 128 patients for reduced diaphyseal both-bone forearm fractures. All 128 patients were eligible; 24% (31) were excluded because they were lost before the minimum study follow-up or had incomplete datasets, leaving 76% (97) for secondary analysis. The loss in the follow-up group was comparable to the included population. Eligible patients were invited for secondary functional and radiographic assessment. The primary outcome was the difference in forearm rotation compared with the uninjured contralateral arm. Secondary outcomes were the ABILHAND-kids and QuickDASH questionnaire, loss of flexion and extension of the elbow and wrist compared with the contralateral forearm, JAMAR grip strength ratio, and radiological assessment of residual deformity. The study was not blinded regarding the children, parents, and clinicians. RESULTS: At 7.5-year follow-up, there were no differences in ABILHAND-kids questionnaire score (above-elbow cast: 41 ± 2.4 versus above/below-elbow cast: 41.7 ± 0.7, mean difference -0.7 [95% confidence interval (CI) -1.4 to 0.04]; p = 0.06), QuickDASH (above-elbow cast: 5.8 ± 9.6 versus 2.9 ± 6.0 for above-/below-elbow cast, mean difference 2.9 [95% CI -0.5 to 6.2]; p = 0.92), and grip strength (0.9 ± 0.2 for above-elbow cast versus 1 ± 0.2 for above/below-elbow cast, mean difference -0.04 [95% CI -1 to 0.03]; p = 0.24). Functional outcomes showed no difference (loss of forearm rotation: above-elbow cast 7.9 ± 17.7 versus 4.1 ± 6.9 for above-/below-elbow cast, mean difference 3.8 [95% CI -1.7 to 9.4]; p = 0.47; arc of motion: above-elbow cast 152° ± 21° versus 155° ± 11° for the above/below-elbow cast group, mean difference -2.5 [95% CI -9.3 to -4.4]; p = 0.17; loss of wrist flexion-extension: above-elbow cast group 1.0° ± 5.0° versus 0.6° ± 4.2° for above/below-elbow cast, mean difference 0.4° [95% CI -1.5° to 2.2°]; p = 0.69). The secondary follow-up showed improvement in forearm rotation in both groups compared with the rotation at 7 months. For radiographical analysis, the only difference was in AP ulna (above-elbow cast: 6° ± 3° versus above/below-elbow cast: 5° ± 2°, mean difference 1.8° [0.7° to 3°]; p = 0.003), although this is likely not clinically relevant. There were no differences in the other parameters. Thirteen patients with persistent malunion at 7-month follow-up showed no clinically relevant differences in functional outcomes at 7.5-year follow-up compared with children without malunion. The loss of forearm rotation was 5.5ׄ° ± 9.1° for the malunion group compared with 6.0° ± 13.9° in the no malunion group, with a mean difference of 0.4 (95% CI of -7.5 to 8.4; p = 0.92). CONCLUSION: In light of these results, we suggest that surgeons perform an early conversion to a below-elbow cast for reduced diaphyseal both-bone forearm fractures in children. This study shows that even in patients with secondary fracture displacement, remodeling occurred. And even in persistent malunion, these patients mostly showed good-to-excellent final results. Future studies, such as a meta-analysis or a large, prospective observational study, would help to establish the influence of skeletal age, sex, and the severity and direction of malunion angulation of both the radius and ulna on clinical result. Furthermore, a similar systematic review could prove beneficial in clarifying the acceptable angulation for pediatric lower extremity fractures. LEVEL OF EVIDENCE: Level I, therapeutic study.

RESUMEN

In prostate cancer (PCa), cancer-associated fibroblasts (CAFs) promote tumor progression, drug resistance, and metastasis. Although circulating tumor cells are studied as prognostic and diagnostic markers, little is known about other circulating cells and their association with PCa metastasis. Here, we explored the presence of circulating CAFs (cCAFs) in metastatic castration-naïve prostate cancer (mCNPC) patients. cCAFs were stained with fibroblast activation protein (FAP), epithelial cell adhesion molecule (EpCAM), and receptor-type tyrosine-protein phosphatase C (CD45), then FAP+EpCAM- cCAFs were enumerated and sorted using fluorescence-activated cell sorting. FAP+EpCAM- cCAFs ranged from 60 to 776 (389 mean ± 229 SD) per 2 × 108 mononuclear cells, whereas, in healthy donors, FAP+ EpCAM- cCAFs ranged from 0 to 71 (28 mean ± 22 SD). The mCNPC-derived cCAFs showed positivity for vimentin and intracellular collagen-I. They were viable and functional after sorting, as confirmed by single-cell collagen-I secretion after 48 h of culturing. Two cCAF subpopulations, FAP+CD45- and FAP+CD45+, were identified, both expressing collagen-I and vimentin, but with distinctly different morphologies. Collectively, this study demonstrates the presence of functional and viable circulating CAFs in mCNPC patients, suggesting the role of these cells in prostate cancer.

RESUMEN

Increased use of therapeutic monoclonal antibodies and the relatively high manufacturing costs fuel the need for more efficient production methods. Here we introduce a novel, fast, robust, and safe isolation platform for screening and isolating antibody-producing cell lines using a nanowell chip and an innovative single-cell isolation method. An anti-Her2 antibody producing CHO cell pool was used as a model. The platform; (1) Assures the single-cell origin of the production clone, (2) Detects the antibody production of individual cells and (3) Isolates and expands the individual cells based on their antibody production. Using the nanowell platform we demonstrated an 1.8-4.5 increase in anti-Her2 production by CHO cells that were screened and isolated with the nanowell platform compared to CHO cells that were not screened. This increase was also shown in Fed-Batch cultures where selected high production clones showed titers of 19-100 mg/L on harvest day, while the low producer cells did not show any detectable anti-Her2 IgG production. The screening of thousands of single cells is performed under sterile conditions and the individual cells were cultured in buffers and reagents without animal components. The time required from seeding a single cell and measuring the antibody production to fully expanded clones with increased Her-2 production was 4-6 weeks.

Asunto(s)

RESUMEN

PRCIS: In this retrospective study of glaucoma patients receiving the bimatoprost implant at Duke Eye Center, the number of topical intraocular pressure-lowering medications was significantly reduced through 12 months after the implant. PURPOSE: To study the effects of the bimatoprost implant on intraocular pressure (IOP) and the need for topical IOP-lowering medications in glaucoma patients in the clinical practice setting. PATIENTS AND METHODS: Patients who received the bimatoprost implant at Duke Eye Center from November 2020 to October 2021 were identified. Exclusion criteria included addition of other IOP-lowering medications concurrent with the implant and <1 month of follow-up. The change in IOP and number of topical IOP-lowering medications from baseline to months 1, 3, 6, 9, and 12 after the implant was calculated. Subgroup analysis was performed for different glaucoma severities. RESULTS: A total of 63 patients and 92 eyes were included (mean age 77.8 ± 10.1 years). Glaucoma severity ranged from mild (11%), moderate (30%), to severe (54%). There was a nonsignificant decrease in IOP at all timepoints. The mean number of topical IOP-lowering medications significantly decreased by 0.81, 0.75, 0.63, 0.70, and 0.67 at month 1, 3, 6, 9, and 12, respectively (all P < 0.001). There was no significant change in the total number of medications, including the bimatoprost implant. When divided by glaucoma severity, the reduction in the number of topical medications was significant at 1, 3, and 6 months for mild/moderate disease and at 1 month for severe disease. During the follow-up period, 19 eyes underwent additional laser or surgical procedures, 68% of which had a history of prior incisional glaucoma surgery. CONCLUSIONS: The bimatoprost implant may reduce the need for topical IOP-lowering agents over a 1-year period, especially in mild to moderate-stage glaucoma. The efficacy of the implant may be more limited in severe glaucoma, and further work is needed to characterize its long-term effects.

Asunto(s)

RESUMEN

Circulating tumor cell (CTC) and tumor-derived extracellular vesicle (tdEV) loads are prognostic factors of survival in patients with carcinoma. The current method of CTC enumeration relies on operator review and, unfortunately, has moderate interoperator agreement (Fleiss' kappa 0.60) due to difficulties in classifying CTC-like events. We compared operator review, ACCEPT automated image processing, and refined the output of a deep-learning algorithm to identify CTC and tdEV for the prediction of survival in patients with metastatic and nonmetastatic cancers. Operator review is only defined for CTC. Refinement was performed using automatic contrast maximization CM-CTC of events detected in cancer and in benign samples (CM-CTC). We used 418 samples from benign diseases, 6,293 from nonmetastatic breast, 2,408 from metastatic breast, and 698 from metastatic prostate cancer to train, test, optimize, and evaluate CTC and tdEV enumeration. For CTC identification, the CM-CTC performed best on metastatic/nonmetastatic breast cancer, respectively, with a hazard ratio (HR) for overall survival of 2.6/2.1 vs. 2.4/1.4 for operator CTC and 1.2/0.8 for ACCEPT-CTC. For tdEV identification, CM-tdEV performed best with an HR of 1.6/2.9 vs. 1.5/1.0 with ACCEPT-tdEV. In conclusion, contrast maximization is effective even though it does not utilize domain knowledge.

RESUMEN

Immunomagnetic enrichment of cell populations from bodily fluids followed by immunofluorescent labeling is an established sample preparation method often used for the detection and enumeration of rare cells such as circulating tumor cells. For a detailed analysis of the heterogeneous characteristics of these cells, the cells need to be retrieved individually. Although several technologies are available to obtain 100% pure cells either individually or in bulk, these are often expensive, have low specificity, or suffer from high cell losses, either inherent to the technology or caused by sample transfer into special chips. To solve this issue, we introduce the magnetic micro-needle approach, which allows for the isolation of immunomagnetically labeled target cells by the use of a magnetized microneedle directly from glass slides. The magnetic microneedle approach makes use of the already present magnetic labeling used for enrichment, while the glass-slide-based open sample container allows for easy and loss-free sample loading. Additionally, the system facilitates not only the isolation but also the precise placement of cells. As the used parts are low cost, the technology provides researchers with an affordable and efficient method to pick up and isolate, as well as specifically place magnetically labeled cells from enriched fractions, thereby enabling the researchers to isolate or analyze these rare cells in more detail.

Asunto(s)

RESUMEN

The clinical utility of circulating tumor cells (CTCs) is hampered by the low number of cells detected. Diagnostic leukapheresis (DLA) offers a solution but, due to the observed non-specific binding and clumping, processing of DLA samples using the CellSearch system only allows for the processing of aliquots consisting of ~ 2% of the total DLA sample per test. Here, we introduce a flow enrichment target capture Halbach-array (FETCH)-based separation method in combination with a DNase preprocessing step to capture CTCs from larger fractions of DLA products without clumping. To evaluate the FETCH method, we processed peripheral blood samples from 19 metastatic castration-naïve prostate cancer (mCNPC) patients with CellSearch, and processed 2% aliquots of leukapheresis samples from the same patients with CellSearch as well as FETCH with or without DNase preprocessing. Using 2% aliquots from six patients, the use of FETCH with fewer immunomagnetic epithelial cellular adhesion molecule (EpCAM) conjugated ferrofluids was tested, whereas 20% aliquots from four patients were used to evaluate the processing of 10-fold larger DLA samples using FETCH. Results show that the cell clumping normally seen after immunomagnetic enrichment of DLA material was greatly reduced with the use of DNase pretreatment, while the number of CTCs detected was not affected. The number of CTCs detected in 2% aliquots of DLA using FETCH was unchanged compared to CellSearch and did not decrease when using down to 10% of the volume of immunomagnetic anti-EpCAM ferrofluids normally used in a CellSearch test, whereas the number of co-enriched white blood cells reduced a median 3.2-fold. Processing of a 20% aliquot of DLA with FETCH resulted in a 14-fold increase in CTCs compared to the processing of 2% aliquots of DLA using CellSearch and a total 42-fold median increase in CTCs compared to peripheral-blood CellSearch.

RESUMEN

BACKGROUND AND PURPOSE: previous RCT compared short-term results of above-elbow cast (AEC) with early conversion to below-elbow cast (BEC) in children with non-reduced diaphyseal both-bone forearm fractures. After 7 months both groups had comparable function. Our primary aim was to investigate whether forearm rotation improves or worsens over time. Secondary aims were loss of flexion and extension of the elbow and wrist, patient-reported outcomes measures, grip strength ratio, and radiographic assessment. PATIENTS AND METHODS: We performed long-term follow-up (FU) of a previous RCT. All patients were invited again for the long-term FU measurements. Primary outcome was limitation of forearm rotation. Secondary outcomes were loss of flexion and extension of the elbow and wrist compared with the contralateral forearm, the ABILHAND-Kids questionnaire and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, grip strength ratio, and radiographic assessment. RESULTS: The mean FU was 7.5 (4.4-9.6) years. Of the initial 47 children, 38 (81%) participated. Rotation improved in both groups over time, with no significant difference in the final forearm rotation: 8° (SD 22) for the AEC group and 8° (SD 15) for the BEC group with a mean difference of 0° (95% confidence interval -13 to 12). Secondary outcomes showed no statistically significant differences. Finally, children < 9 years almost all have full recovery of function. CONCLUSION: Long-term follow-up showed that loss of forearm rotation after a non-reduced diaphyseal both-bone forearm fracture improved significantly compared with that at 7 months, independent of the initial treatment and children aged < 9 will have almost full recovery of function. This substantiates that the remaining growth behaves like a "friend" at long-term follow-up.

Asunto(s)

RESUMEN

Hepatocyte damage during liver injury instigates activation of macrophages and hepatic stellate cells (HSCs) resulting in liver inflammation and fibrosis respectively. Improving hepatocyte survival and proliferation thereby ameliorating inflammation and fibrosis represents a promising approach for the treatment of liver injury. In the liver, fibroblast growth factors (FGFs) play a crucial role in promoting hepatocyte proliferation and tissue regeneration. Among 22 FGFs, FGF7 induces hepatocyte survival and liver regeneration as shown previously in mouse models of cholestatic liver injury and partial hepatectomy. We hypothesized that FGF7 promotes hepatocyte survival and proliferation by interacting with FGFR2b, expressed on hepatocytes, and ameliorates liver injury (inflammation and early fibrogenesis) via paracrine mechanisms. To prove this hypothesis and to study the effect of FGF7 on hepatocytes and liver injury, we administered FGF7 exogenously to mice with acute carbon tetrachloride (CCl4)-induced liver injury. We thereafter studied the underlying mechanisms and the effect of exogenous FGF7 on hepatocyte survival and proliferation, and the consequent paracrine effects on macrophage-induced inflammation, and HSCs activation in vitro and in vivo. We observed that the expression of FGF7 as well as FGFR2 is upregulated during acute liver injury. Co-immunostaining of FGF7 and collagen-I confirmed that FGF7 is expressed by HSCs and is possibly captured by the secreted ECM. Immunohistochemical analysis of liver sections showed increased hepatocyte proliferation upon exogenous FGF7 treatment as determined by Ki67 expression. Mechanistically, exogenous FGF7 improved hepatocyte survival (and increased drug detoxification) via AKT and ERK pathways while maintaining hepatocyte quiescence restricting hepatocarcinogenesis via P27 pathways. Flow cytometry analysis revealed that improved hepatocyte survival and proliferation leads to a decrease in infiltrated monocytes-derived macrophages, as a result of reduced CCL2 (and CXCL8) expression by hepatocytes. Moreover, conditioned medium studies showed reduced collagen-I secretion by HSCs (indicative of HSCs activation) upon treatment with FGF7-treated hepatocytes conditioned medium. Altogether, we show that exogenous administration of FGF7 induces hepatocyte survival and proliferation and leads to amelioration of inflammatory response and fibrosis in acute liver injury via paracrine mechanisms. Our study further demonstrates that FGF7, FGF7 derivatives, or nano-engineered FGF7 may benefit patients with hepatic dysfunction.

Asunto(s)

RESUMEN

The median number of circulating tumor cells (CTCs) detected in 7.5 mL of peripheral blood by CellSearch (PB-CS) in patients with metastatic prostate cancer is in the order of 1-10, which means many samples have insufficient tumor cells for comprehensive characterization. A significant increase is obtained through diagnostic leukapheresis (DLA), however, only 2%-3% of the DLA product can be processed per CellSearch test, limiting the gain. We processed aliquots from 30 DLA products of metastatic prostate cancer patients consisting of 0.2 × 109 leukocytes using CellSearch (DLA-CS) as well as the newly introduced reduced enrichment reagent protocol (RER), which uses 10-fold less enrichment reagents than DLA-CS. The number of tumor cells and the total number of captured cells were determined using the CellTracks Analyzer. Additionally, for six DLA samples, a 1.0 × 109 leukocyte aliquot was processed (RER+), using twofold less enrichment reagents than DLA-CS. A median 2.7-fold reduction in leukocyte co-enrichment was found between DLA-CS and RER methods without any loss in tumor cell recovery (Wilcoxon Signed Ranks Test, p = 0.953). Using 1.0 × 109 leukocyte aliquots a fourfold increase in tumor cells was found compared to DLA-CS and a 19-fold increase compared to PB-CS was obtained. The here-introduced RER protocol results in a higher final sample purity without any loss in tumor cell recovery while using 10-fold less CellSearch capture reagent. With this improved method, 26% of the leukapheresis sample can now be processed using reagents from a single CellSearch test, enabling the obtainment of a sufficient number of CTCs for comprehensive characterization in most metastatic prostate cancer patients.

Asunto(s)

RESUMEN

Virtual reality (VR) allows visuotactile interaction in a virtual environment. VR has several potential applications such as surgical training, phobia treatments, and gait rehabilitation. However, further interface development is required. Therefore, the objective of this study was to develop a noninvasive wearable device control to a VR gait training program. It consists of custom-made insoles with vibratory actuators, and plantar pressure sensor-based wireless interface with a VR game. System usability testing involved a habituation period and three gaming sessions. Significant gait improvement was associated with game scores (P < 0.05). This VR gait training system allowed real-time virtual immersive interaction with anticipatory stimulus and feedback during gait.

Asunto(s)

RESUMEN

When evaluating EpCAM-based enrichment technologies for circulating tumour cells (CTCs), the cell lines used should closely resemble real CTCs, meaning the EpCAM expression of CTCs needs to be known, but also the EpCAM expression of cell lines at different institutions and times is important. As the number of CTCs in the blood is low, we enriched CTCs through the depletion of leukocytes from diagnostic leukapheresis products of 13 prostate cancer patients and measured EpCAM expression using quantitative flow cytometry. Antigen expression was compared between multiple institutions by measuring cultures from each institution. Capture efficiency was also measured for one of the used cell lines. Results show CTCs derived from castration-sensitive prostate cancer patients have varying but relatively low EpCAM expression, with median expression per patient ranging from 35 to 89,534 (mean 24,993) molecules per cell. A large variation in the antigen expression of identical cell lines cultured at different institutions was found, resulting in recoveries when using the CellSearch system ranging from 12 up to 83% for the same cell line. We conclude that large differences in capture efficiency can occur while using the same cell line. To closely resemble real CTCs from castration-sensitive prostate cancer patients, a cell line with a relatively low EpCAM expression should be used, and its expression should be monitored frequently.

Asunto(s)

RESUMEN

Cancer-associated fibroblasts (CAFs) are important drivers in the tumor microenvironment and facilitate the growth and survival of tumor cells, as well as metastasis formation. They may travel together with tumor cells to support their survival and aid in the formation of a metastatic niche. In this study, we aimed to study circulating CAFs (cCAFs) and circulating tumor cells (CTCs) in a preclinical breast tumor model in mice in order to understand the effect of chemotherapy on cCAFs and CTC formation. Tumors with MDA-MB-231 human breast tumor cells with/without primary human mammary fibroblasts (representing CAFs) were coinjected in SCID mice to develop tumors. We found that the tumors with CAFs grew faster than tumors without CAFs. To study the effect of the stroma on CTCs and cCAFs, we isolated cells using microsieve filtration technology and established ITGA5 as a new cCAF biomarker, which showed good agreement with the CAF markers FAP and α-SMA. We found that ITGA5+ cCAFs shed in the blood of mice bearing stroma-rich coinjection-based tumors, while there was no difference in CTC formation. Although treatment with liposomal doxorubicin reduced tumor growth, it increased the numbers of both cCAFs and CTCs in blood. Moreover, cCAFs and CTCs were found to form clusters in the chemotherapy-treated mice. Altogether, these findings indicate that the tumor stroma supports tumor growth and the formation of cCAFs. Furthermore, chemotherapy may exacerbate the formation of cCAFs and CTCs, which may eventually support the formation of a metastasis niche in breast cancer.

RESUMEN

PURPOSE: Circulating tumor cells (CTCs) are strongly prognostic for overall survival (OS) in metastatic breast cancer although additional prognostic biomarkers are needed. We evaluated the complementary prognostic value of tumor-derived extracellular vesicles (tdEVs) next to CTCs. METHODS: We applied the open-source ACCEPT software to archived CellSearch images from the prospective clinical trial SWOG0500 to enumerate CTCs and tumor-derived extracellular vesicles (tdEVs) before and after one cycle of chemotherapy. RESULTS: CTCs enumerated by ACCEPT were strongly correlated with classical ocular enumeration (correlation r = 0.98). OS was worse with elevated tdEVs (median OS for high/medium/low groups: 17.1 v 29.0 v 43.3 months; P < .0001). In patients with longer OS by CTC counts (< 5 CTC/7.5 mL blood), elevated tdEV levels were independently associated with poorer OS (multivariable analysis P < .001). OS was also longer for patients with low tdEVs after one cycle of chemotherapy (median OS for high/medium/low group: 10.8 v 17.8 v 26.7; P < .0001). CONCLUSION: This study highlights the complementary prognostic significance of tdEVs in metastatic breast cancer before and after one cycle of chemotherapy.

Asunto(s)

RESUMEN

This narrative review aims to provide a comprehensive overview of the current state of circulating tumor cell (CTC) analysis and its clinical significance in patients with epithelial cancers. The review explores the advancements in CTC detection methods, their clinical applications, and the challenges that lie ahead. By examining the important research findings in this field, this review offers the reader a solid foundation to understand the evolving landscape of CTC analysis and its potential implications for clinical practice. The comprehensive analysis of CTCs provides valuable insights into tumor biology, treatment response, minimal residual disease detection, and prognostic evaluation. Furthermore, the review highlights the potential of CTCs as a non-invasive biomarker for personalized medicine and the monitoring of treatment efficacy. Despite the progress made in CTC research, several challenges such as standardization, validation, and integration into routine clinical practice remain. The review concludes by discussing future directions and the potential impact of CTC analysis on improving patient outcomes and guiding therapeutic decision-making in epithelial cancers.

RESUMEN

Circulating tumor cell (CTC)- and/or tumor-derived extracellular vesicle (tdEV) loads in the blood of metastatic castration-resistant prostate cancer (CRPC) patients are associated with worse overall survival and can be used as predictive markers of treatment response. In this study, we investigated the quantity/quality of CTCs and tdEVs in metastatic castration-naive prostate cancer (CNPC) and CRPC patients, and whether androgen deprivation therapy (ADT) affects CTCs and tdEVs. We included 104 CNPC patients before ADT initiation and 66 CRPC patients. Blood samples from 31/104 CNPC patients were obtained 6 months after ADT. CTCs and tdEVs were identified using ACCEPT software. Based on the morphology, CTCs of metastatic CNPC and CRPC patients were subdivided by manual reviewing into six subclasses. The numbers of CTCs and tdEVs were correlated in both CNPC and CRPC patients, and both CTCs (p = 0.013) and tdEVs (p = 0.005) were significantly lower in CNPC compared to CRPC patients. Qualitative differences in CTCs were observed: CTC clusters (p = 0.006) and heterogeneously CK expressing CTCs (p = 0.041) were significantly lower in CNPC patients. CTC/tdEV numbers declined 6 months after ADT. Our study showed that next to CTC-load, qualitative CTC analysis and tdEV-load may be useful in CNPC patients.

RESUMEN

Prostate cancer is the most dominant male malignancy worldwide. The clinical presentation of prostate cancer ranges from localized indolent to rapidly progressing lethal metastatic disease. Despite a decline in death rate over the past years, with the advent of early diagnosis and new treatment options, challenges remain towards the management of metastatic prostate cancer, particularly metastatic castration sensitive prostate cancer (mCSPC) and castration resistant prostate cancer (mCRPC). Current treatments involve a combination of chemotherapy with androgen deprivation therapy and/or androgen receptor signalling inhibitors. However, treatment outcomes are heterogeneous due to significant tumor heterogeneity indicating a need for better prognostic biomarkers to identify patients with poor outcomes. Liquid biopsy has opened a plethora of opportunities from early diagnosis to (personalized) therapeutic disease interventions. In this review, we first provide recent insights about (metastatic) prostate cancer and its current treatment landscape. We highlight recent studies involving various circulating biomarkers such as circulating tumor cells, genetic markers, circulating nucleic acids, extracellular vesicles, tumor-educated platelets, and the secretome from (circulating) tumor cells and tumor microenvironment in metastatic prostate cancer. The comprehensive array of biomarkers can provide a powerful approach to understanding the spectrum of prostate cancer disease and guide in developing improved and personalized treatments for patients.

RESUMEN

After a CellSearch-processed circulating tumor cell (CTC) sample is imaged, a segmentation algorithm selects nucleic acid positive (DAPI+), cytokeratin-phycoerythrin expressing (CK-PE+) events for further review by an operator. Failures in this segmentation can result in missed CTCs. The CellSearch segmentation algorithm was not designed to handle samples with high cell density, such as diagnostic leukapheresis (DLA) samples. Here, we evaluate deep-learning-based segmentation method StarDist as an alternative to the CellSearch segmentation. CellSearch image archives from 533 whole blood samples and 601 DLA samples were segmented using CellSearch and StarDist and inspected visually. In 442 blood samples from cancer patients, StarDist segmented 99.95% of CTC segmented by CellSearch, produced good outlines for 98.3% of these CTC, and segmented 10% more CTC than CellSearch. Visual inspection of the segmentations of DLA images showed that StarDist continues to perform well when the cell density is very high, whereas CellSearch failed and generated extremely large segmentations (up to 52% of the sample surface). Moreover, in a detailed examination of seven DLA samples, StarDist segmented 20% more CTC than CellSearch. Segmentation is a critical first step for CTC enumeration in dense samples and StarDist segmentation convincingly outperformed CellSearch segmentation.