High-throughput viable circulating tumor cell isolation using tapered-slit membrane filter-based chipsets in the differential diagnosis of ovarian tumors.

OBJECTIVE: To evaluate the diagnostic performance of circulating tumor cells (CTCs) using tapered-slit membrane filter (TSF)-based chipsets for the differential diagnosis of adnexal tumors. METHODS: A total of 230 women with indeterminate adnexal tumors were prospectively enrolled. The sensitivity, specificity, and accuracy of the CTC-detecting chipsets were analyzed according to postoperative pathological results and compared with those of cancer antigen (CA)-125 and imaging tests. RESULTS: Eighty-one (40.3%) benign tumors, 31 (15.4%) borderline tumors, and 89 (44.3%) ovarian cancers were pathologically confirmed. The sensitivity, specificity, and accuracy of CTC-detecting chipsets (75.3%, 58.0%, and 67.1%) for differentiating ovarian cancer from benign tumors were similar to CA-125 (78.7%, 53.1%, and 66.5%), but lower than CT/MRI (94.2%, 77.9%, and 86.5%). "CTC or CA125" showed increased sensitivity (91.0%) and "CTC and CA-125" revealed increased specificity (77.8%), comparable to CT/MRI. CTC detection rates in stage I/II and stage III/IV ovarian cancers were 69.6% and 81.4%, respectively. The sensitivity to detect high-grade serous (HGS) cancer from benign tumors (84.6%) was higher than that to detect non-HGS cancers (68.0%). CONCLUSION: Although the diagnostic performance of the TSF platform to differentiate between ovarian cancer and benign tumors did not yield significant results, the combination of CTC and CA-125 showed promising potential in the diagnostic accuracy of ovarian cancer.

Fixation of femoral neck fracture with femoral neck system: a retrospective cohort study of 43 patients.

BACKGROUNDS: This study aimed to analyze the clinical outcomes of femoral neck fractures (FNF) in patients treated with a femoral neck system (FNS, DePuy Synthes), which is a recently introduced device. METHODS: This retrospective cohort study of 43 patients who underwent osteosynthesis using FNS for FNF between July 2019 and June 2021 with a minimum follow-up of 6 months. The researchers examined the patients' demographic factors and radiologically evaluated the fracture type and fixation status, bone union, and postoperative complications. RESULTS: Of 43 patients, 25 were female, and the patients' mean age and body mass index were 62.1 years and 22.5 kg/m2, respectively. According to the Association of Osteosynthesis/Orthopaedic Trauma Association (AO/OTA) classification, the most common fracture types were 31B1.1 and B1.2 (13 cases each), followed by B2.3, B2.1, and B2.2 (seven, five, and four cases, respectively). Radiological bone union was confirmed in 39 patients (90.7%), and the mean time to union was 3.6 months. Two cases of nonunion, one case of lag screw cut-out, and one case of osteonecrosis were confirmed; all four cases later underwent arthroplasty. The mean time to reoperation was 4.5 months. Meanwhile, five patients underwent implant removal after the bone union, and distal locking screw stripping was noted in three patients. All three patients required metal plate cutting to remove the implants. CONCLUSIONS: Osteosynthesis of FNF using the newly introduced FNS showed favorable clinical outcomes and no specific hardware-related complications were reported during the follow-up. However, attention must be paid to the issue regarding distal locking screw failure during hardware removal.

Failure after intramedullary nailing for geriatric trochanteric fracture: does quality of fracture reduction on the AP and lateral planes show the same results?

PURPOSE: This study aimed to investigate the failure of trochanteric fracture fixation according to the quality of fracture reduction on the anteroposterior (AP) and lateral views. METHODS: Data from 340 female and 152 male patients ≥ 60 years of age who underwent intramedullary nailing for a trochanteric fracture between 2016 and 2020 were analysed retrospectively. The quality of fracture reduction was classified as type A, type E, and type I on the AP view and type N, type A, and type P on the lateral view according to the relative position of the proximal and distal fragments. The failure rate was evaluated and compared according to the quality of fracture reduction. The risk factors of the fixation failure were investigated by comparison of variables between patients with and without failure and by regression analysis. RESULTS: Patients with poor reduction, type I and type P had higher failure rates. However, a statistically significant difference was found only for patients with poor reduction (type P) on the lateral view (p < 0.001). Patients with failure showed significantly higher rates of poor reduction on the lateral view and AO/OTA type A3 fractures. The regression analysis also showed that poor reduction on the lateral view (odds ratio [OR] 12.70; 95% confidence interval [CI] 4.0-40.6; p < 0.001) and AO/OTA type A3 fractures (OR 5.40; 95% CI 1.24-23.49, p = 0.025) were risk factors for failure. CONCLUSION: Poor reduction such as type P reduction was associated with failure after intramedullary nailing for trochanteric fractures. Surgeons should check the quality of fracture reduction carefully with the proper fluoroscopic view to prevent failure in geriatric patients with trochanteric fractures.

Reusable and Porous Skin Patches with Thermopneumatic Adhesion Control Capability and High Water Vapor Permeability.

We present a reusable and porous skin patch (RPS patch) capable of controlling adhesion force with a thermal-pneumatic method for repetitive use as well as improving moisture permeability for long-term use without skin troubles. Previous skin patches cause skin troubles due to high adhesion force (∼30 kPa) and low moisture permeability (∼382 g/m2/day), hindering them from repeatable and long-term use. We control the skin adhesion force of the RPS patch using thermopneumatic pressure generated by an embedded heater on multiple chamber arrays. The RPS patch controls the adhesion force ranging from 8 to 29 kPa on both dry and wet skin while keeping the stable adhesion force for 48 h. It shows repeatable adhesion up to 100 times, and the adhesion force is restored after the RPS patch is washed with water, thus enabling repetitive skin adhesion. We improve the moisture permeability of the RPS patch to 733 g/m2/day while maintaining the adhesion force by making the RPS patch with porous materials. The RPS patch shows no skin troubles for 7 days of attachment, thereby being available for long-term skin attachment. The RPS patch, having adhesion control capability and high moisture permeability, shows potential for use in daily life in biomedical applications, including wearable sensors, medical adhesives, and rehabilitation robots.

A Comprehensive Review on Ensemble Solar Power Forecasting Algorithms.

With increasing demand for energy, the penetration of alternative sources such as renewable energy in power grids has increased. Solar energy is one of the most common and well-known sources of energy in existing networks. But because of its non-stationary and non-linear characteristics, it needs to predict solar irradiance to provide more reliable Photovoltaic (PV) plants and manage the power of supply and demand. Although there are various methods to predict the solar irradiance. This paper gives the overview of recent studies with focus on solar irradiance forecasting with ensemble methods which are divided into two main categories: competitive and cooperative ensemble forecasting. In addition, parameter diversity and data diversity are considered as competitive ensemble forecasting and also preprocessing and post-processing are as cooperative ensemble forecasting. All these ensemble forecasting methods are investigated in this study. In the end, the conclusion has been drawn and the recommendations for future studies have been discussed.

The Influence of Tyrosol-Enriched Rhodiola sachalinensis Extracts Bioconverted by the Mycelium of Bovista plumbe on Scopolamine-Induced Cognitive, Behavioral, and Physiological Responses in Mice.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits, which are accompanied by memory loss and cognitive disruption. Rhodiola sachalinensis (RSE) is a medicinal plant that has been used in northeastern Asia for various pharmacological activities. We attempted to carry out the bioconversion of RSE (Bio-RSE) using the mycelium of Bovista plumbe to obtain tyrosol-enriched Bio-RSE. The objective of this study was to investigate the effects of Bio-RSE on the activation of the cholinergic system and the inhibition of oxidative stress in mice with scopolamine (Sco)-induced memory impairment. Sco (1 mg/kg body weight, i.p.) impaired the mice's performance on the Y-maze test, passive avoidance test, and water maze test. However, the number of abnormal behaviors was reduced in the groups supplemented with Bio-RSE. Bio-RSE treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. Bio-RSE dramatically improved the cholinergic system by decreasing acetylcholinesterase activity and regulated oxidative stress by increasing antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)). The reduction in nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling in the brain tissue due to scopolamine was restored by the administration of Bio-RSE. Bio-RSE also significantly decreased amyloid-beta 1-42 (Aß1-42) and amyloid precursor protein (APP) expression. Moreover, the increased malondialdehyde (MDA) level and low total antioxidant capacity in Sco-treated mouse brains were reversed by Bio-RSE, and an increase in Nrf2 and HO-1 was also observed. In conclusion, Bio-RSE protected against Sco-induced cognitive impairment by activating Nrf2/HO-1 signaling and may be developed as a potential beneficial material for AD.

Mid-term outcomes after the surgical treatment of atypical femoral fractures : minimum three-year follow-up.

AIMS: The incidence of atypical femoral fractures (AFFs) continues to increase. However, there are currently few long-term studies on the complications of AFFs and factors affecting them. Therefore, we attempted to investigate the outcomes, complications, and risk factors for complication through mid-term follow-up of more than three years. METHODS: From January 2003 to January 2016, 305 patients who underwent surgery for AFFs at six hospitals were enrolled. After exclusion, a total of 147 patients were included with a mean age of 71.6 years (48 to 89) and 146 of whom were female. We retrospectively evaluated medical records, and reviewed radiographs to investigate the fracture site, femur bowing angle, presence of delayed union or nonunion, contralateral AFFs, and peri-implant fracture. A statistical analysis was performed to identify the significance of associated factors. RESULTS: The mean follow-up period was 70.2 months (36 to 191). There were 146 AFFs (99.3%) in female patients and the mean age was 71.6 years (48 to 89). The AFFs were located in the subtrochanter and shaft in 52 cases (35.4%) and 95 (64.6%), respectively. The preoperative mean anterior/lateral femoral bowing angles were 10.5° (SD 5.7°)/6.1° (SD 6.2°). The postoperative mean anterior/lateral bowing values were changed by 8.7° (SD 5.4°)/4.6° (SD 5.9°). Bisphosphonates had been used contemporarily in 115 AFFs (78.2%) for a mean of 52.4 months (1 to 204; SD 45.5) preoperatively. Nailing was performed in 133 AFFs (90.5%), and union was obtained at a mean of 23.6 weeks (7 to 85). Delayed union occurred in 41 (27.9%), and nonunion occurred in 13 (8.8%). Contralateral AFF occurred in 79 patients (53.7%), and the use of a bisphosphonate significantly influenced the occurrence of contralateral AFFs (p = 0.019). Peri-implant fractures occurred in a total of 13 patients (8.8%), and a significant increase was observed in cases with plating (p = 0.021) and high grade of postoperative anterolateral bowing (p = 0.044). CONCLUSION: The use of a bisphosphonate was found to be a risk factor for contralateral AFF, and high-grade postoperative anterolateral bowing and plate fixation significantly increased the occurrence of peri-implant fractures. Long-term follow-up studies on the bilaterality of AFFs and peri-implant fractures are warranted. Cite this article: Bone Joint J 2021;103-B(11):1648-1655.

Secondary Subtrochanteric Fracture After Atypical Femoral Shaft Fracture Treated With Intramedullary Nail.

Intramedullary (IM) nail fixation is widely used for the treatment of atypical fractures of the femoral shaft. The configuration and location of proximal interlocking screws are unique to each nailing system and maybe transverse or oblique in direction. The authors experienced two cases of incomplete secondary fractures at the subtrochanteric region after IM nail fixation for atypical femoral shaft fractures. The proximal screw fixation of the two cases was different from one another. One was fixed with a spiral blade plus transverse screw and the other was fixed using an oblique direction screw from the greater trochanter to the femoral neck base. Based on our experience, we recommend only using a proximal locking screw toward the head when using an IM nail for the treatment of atypical femoral diaphyseal fractures. An 82-year-old female patient who had been fixed with an IM nail for the treatment of atypical femoral shaft fracture 13 months ago visited the outpatient clinic with pain in the right hip joint for one month. Local hot uptake was observed at the proximal interlocking screw insertion site around the subtrochanteric region on bone scan. A simple removal of the proximal locking screw was enough to treat the incomplete fracture. A 79-year-old woman visited the emergency room for pain in the right hip joint. On the radiograph, the right femur was found to be fixed with an IM nail, and an incomplete fracture line around the lower border of the lesser trochanter was observed. This patient was treated by replacing the IM nail with a reconstruction nail. When using an IM nail for the treatment of atypical femoral shaft fractures, it is appropriate to insert only the screw toward the femoral head for proximal fixation to prevent secondary subtrochanteric fracture.

Straight nail insertion through a laterally shifted entry for diaphyseal atypical femoral fractures with bowing: good indications and limitations of this technique.

PURPOSE: Inserting a straight (piriformis fossa entry) nail through the tip of the greater trochanter has been used for treating atypical femoral fractures (AFFs) with bowing. This study aimed to determine what degree of bowing can be successfully treated using a laterally shifted entry technique. METHODS: Twenty-three complete and six incomplete diaphyseal AFFs treated using the shifted entry technique were retrospectively analysed. Radiologic parameters and complications were evaluated. The complete AFFs were divided into two groups based on the severity of preoperative bowing: grade 0-II bowing and < 20° lateral bowing (minimal/moderate) and grade III bowing or ≥ 20° lateral bowing (severe). Comparison according to postoperative malalignment, a change of lateral or anterior bowing ≥ 5° was also performed. RESULTS: Three complete AFFs in the minimal/moderate group showed malalignment, as did all in the severe group (p < 0.001). The change of bowing was greater for the severe group in lateral and anterior bowing (p = 0.004 and 0.001, respectively). A greater fracture gap was found on AP and lateral radiographs in the severe group (p = 0.044 and 0.026, respectively). In the comparison according to postoperative malalignment, a significant difference was found for the percentage of severe deformity (p < 0.001). All incomplete AFFs were united without complication. CONCLUSION: Diaphyseal AFFs with grade 0-II bowing and < 20° anterior bowing were treated successfully by the shifted entry technique. However, postoperative malalignment was found in all cases of AFFs with severe bowing. Therefore, other techniques should be considered for AFFs with grade III bowing or ≥ 20° anterior bowing.

The Development and Optimization of Hot-Melt Extruded Amorphous Solid Dispersions Containing Rivaroxaban in Combination with Polymers.

Rivaroxaban (RXB), a novel oral anticoagulant that directly inhibits factor Xa, is a poorly soluble drug belonging to Biopharmaceutics Classification System (BCS) class II. In this study, a hot-melt extruded amorphous solid dispersion (HME-ASD) containing RXB is prepared by changing the drug:polymer ratio (Polyvinylpyrrolidione-vinyl acetate 64, 1:1-1:4) and barrel temperature (200-240 °C), fixed at 20% of Cremophor® RH 40 and 15 rpm of the screw speed, using the hot-melt extruding technique. This study evaluates the solubility, dissolution behavior, and bioavailability for application to oral drug delivery and optimizes the formulation of rivaroxaban amorphous solid dispersion (RXB-ASD). Based on a central composite design, optimized RXB-ASD (PVP VA 64 ratio 1:4.1, barrel temperature 216.1 °C, Cremophor® RH 40 20%, screw speed 15 rpm) showed satisfactory results for dependent variables. An in vitro drug dissolution study exhibited relatively high dissolution in four media and achieved around an 80% cumulative drug release in 120 min. Optimized RXB-ASD was stable under the accelerated condition for three months without a change in crystallinity and the dissolution rate. A pharmacokinetic study of RXB-ASD in rats showed that the absorption was markedly increased in terms of rate and amount, i.e., the systemic exposure values, compared to raw RXB powder. These results showed the application of quality by design (QbD) in the formulation development of hot-melt extruded RXB-ASD, which can be used as an oral drug delivery system by increasing the dissolution rate and bioavailability.

Wearable porous PDMS layer of high moisture permeability for skin trouble reduction.

The present research proposes the present porous polydimethylsiloxane (PDMS) layer for the skin trouble reduced daily life skin attachable devices. The present research proposes the new pores forming method in the PDMS by crystallization and dissolution of the citric acid in the PDMS for fabricating high uniform and small size pores. The present porous PDMS layer (i) decreases the pore size 93.2%p and increases the pore size uniformity 425%p compared to the conventional porous PDMS layer of mixing sugars and PDMS; (ii) is able to be fabricated in the thickness of 21-101 µm by spin-coating; (iii) has the 2.2 times higher water vapor transmission rate (947 ± 10.8 g/day•m2) compared to the human skin water vapor transmission rate. The present porous PDMS layer reduces the skin trouble effectively by having the high water vapor permeability, therefore is applicable to the human daily-life skin attachable devices.

A porous PDMS pulsewave sensor with haircell structures for water vapor transmission rate and signal-to-noise ratio enhancement.

We present a porous polydimethylsiloxane (PDMS) pulsewave sensor with haircell structures that improves both water vapor transmission rate (WVTR) and signal-to-noise ratio (SNR). The conventional planar PDMS pulsewave sensors have the problems of low WVTR and low SNR for real-time and long-term pulsewave monitoring. In order to improve WVTR, we fabricated a porous PDMS layer with the thickness of 40 µm and high porosity of 45% by crystallizing and dissolving citric acid powders in PDMS. On the porous PDMS layer, we form haircell structures to increase the skin contact area, thus enhancing SNR. The porous PDMS pulsewave sensor with haircell structures achieved an enhanced WVTR of 486.17 g-1 d-1 m-2 and an SNR of 22.89, respectively, 72% and 757% higher than those of the conventional PDMS pulsewave sensors without haircell structures. Furthermore, the enhanced WVTR is 13% higher than the human skin sweat rate of 432 g-1 d-1 m-2. The present pulsewave sensor shows strong potential for applications in real-time and long-term pulsewave monitoring with the lower skin irritation and the enhanced SNR.

Circulating Tumor Marker Isolation with the Chemically Stable and Instantly Degradable (CSID) Hydrogel ImmunoSpheres.

Here, we present chemically stable and instantly degradable (CSID) hydrogel immunospheres for the isolation of circulating tumor cells (CTCs) and circulating tumor exosomes (CTXs). The CSID hydrogels, which are prepared by the hybridization of alginate and poly(vinyl alcohol), show an equilibrium swelling ratio (ESR) of at pH 7, with a highly stable pH-responsive property. The present hybrid hydrogel is not easily disassociated in the biological buffers, thus being suitable for use in "liquid biopsy", requiring a multistep, long-term incubation process with biological samples. Also, it is gradually degraded by the action of chelating agents; effortless retrieval of the circulating markers has been achieved. Then, we modified the CSID hydrogel spheres with the anti-EpCAM antibody ("C-CSID ImmunoSpheres") and the anti-CD63 antibody ("E-CSID ImmunoSpheres") to isolate two promising circulating markers in liquid biopsy: CTCs and CTXs. The immunospheres' capabilities for marker isolation and retrieval were confirmed by a fluorescence image, where the spheres successfully isolate and effortlessly retrieve the target circulating markers. Lastly, we applied the CSID hydrogel immunospheres to five blood samples from colorectal cancer patients and retrieved average 10.8 ± 5.9 CTCs/mL and average 96.5 × 106 CTXs/mL. The present CSID hydrogel immunospheres represent a simple, versatile, and time-efficient assay platform for liquid biopsy in the practical setting, enabling us to gain a better understanding of disease-related circulating markers.

Automated White Blood Cell Counting in Nailfold Capillary Using Deep Learning Segmentation and Video Stabilization.

White blood cells (WBCs) are essential components of the immune system in the human body. Various invasive and noninvasive methods to monitor the condition of the WBCs have been developed. Among them, a noninvasive method exploits an optical characteristic of WBCs in a nailfold capillary image, as they appear as visual gaps. This method is inexpensive and could possibly be implemented on a portable device. However, recent studies on this method use a manual or semimanual image segmentation, which depends on recognizable features and the intervention of experts, hindering its scalability and applicability. We address and solve this problem with proposing an automated method for detecting and counting WBCs that appear as visual gaps on nailfold capillary images. The proposed method consists of an automatic capillary segmentation method using deep learning, video stabilization, and WBC event detection algorithms. Performances of the three segmentation algorithms (manual, conventional, and deep learning) with/without video stabilization were benchmarks. Experimental results demonstrate that the proposed method improves the performance of the WBC event counting and outperforms conventional approaches.

Multi-modal liquid biopsy platform for cancer screening: screening both cancer-associated rare cells and cancer cell-derived vesicles on the fabric filters for a reliable liquid biopsy analysis.

Circulating tumor cells (CTCs) are receiving a great amount of scientific interest as a diagnostic biomarker for various types of cancer. Despite the recent progress in the development of highly sensitive CTC isolation devices, post-capture analysis of CTCs is still hindered by technical challenges associated with their rarity. Herein, we present a multi-modal CTC screening platform which is capable to analyze CTCs and CTC-derived extracellular vesicles (EVs), simultaneously from a single sample. Cytochalasin B (CB) treatment promotes cells to release large number of EVs from their surface, as demonstrated by CB-treated cells (5 µg/mL for 3 h) secreting 3.5-fold more EVs, compared to the non-treated cells. CB further generates 1.7-fold more EVs from the cells captured on our CTC filtration device (the fabric filter), compared to those from the cell culture flasks, owing to its multiple pore structure design which reduces the non-specific binding of EVs. Both CB-treated cancer cells and CB-induced EVs are found to overexpress tumor-associated markers, demonstrating a potential for the development of CTC dual-screening platform. Collectively, the results presented in this study reveal that our multi-modal cancer screening platform can synergistically improve the reliability and efficacy of the current CTC analysis systems.

Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway.

Atherosclerosis is one of the most reported diseases worldwide, and extensive research and trials are focused on the discovery and utilizing for novel therapeutics. Nitric oxide (NO) is produced mainly by endothelial nitric oxide synthase (eNOS) and it plays a key role in regulating vascular function including systemic blood pressure and vascular inflammation in vascular endothelium. In this study hypothesized that Impressic acid (IPA), a component isolated from Acanthopanax koreanum, acts as an enhancer of eNOS activity and NO production. IPA treatment induced eNOS phosphorylation and NO production, which was correlated with eNOS phosphorylation via the activation of JNK1/2, p38 MAPK, AMPK, and CaMKII. In addition, the induction of eNOS phosphorylation by IPA was attenuated by pharmacological inhibitor of MAPKs, AMPK, and CaMKII. Finally, IPA treatment prevented the adhesion of TNF-α-induced monocytes to endothelial cells and suppressed the TNF-α-stimulated ICAM-1 expression via activation of NF-κB, while treatment with L-NAME, the NOS inhibitor, reversed the inhibitory effect of IPA on TNF-α-induced ICAM-1 expression via activation of NF-κB. Taken together, these findings show that IPA protects against TNF-α-induced vascular endothelium dysfunction through attenuation of the NF-κB pathway by activating eNOS/NO pathway in endothelial cells.

Gamma Irradiated Rhodiola sachalinensis Extract Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia by Downregulating 5-Alpha Reductase and Restoring Testosterone in Rats.

The effect of Rhodiola sachalinensis Boriss extract irradiated with 50 kGy gamma rays (HKC) on benign prostatic hyperplasia (BPH) was investigated. Seven-week-old male SD rats received a subcutaneous injection of 20 mg/kg of testosterone propionate (TP) to induce BPH. Then, the testosterone only group received testosterone, the testosterone + finasteride group received testosterone and finasteride (5 mg/kg), the testosterone + HKC group received testosterone and HKC extract (500 mg/kg). Prostate weight and the dihydrotestosterone (DHT) levels in serum or prostate tissue were determined. The mRNA expressions of 5-alpha reductase (AR) in prostate tissue were also measured. Compared to the control group, prostate weight was significantly improved in the TP group and decreased in the HKC and finasteride-treated groups. Furthermore, the mRNA expression of 5-AR in the prostate was significantly reduced in the HKC and finasteride-treated groups. Similarly, the expression levels of α-smooth muscle actin (α-SMA) and cytokeratin, which are associated with prostatic enlargement in the HKC and finasteride groups, were much lower than in the TP group. HKC treatment showed similar efficacy to finasteride treatment on rats with testosterone-induced BPH. HKC may be explored as a potential new drug for BPH treatment.

Circulating tumor cells are associated with poor outcomes in early-stage hepatocellular carcinoma: a prospective study.

BACKGROUND: Previous studies evaluating association between circulating tumor cells (CTCs) and clinical outcomes in hepatocellular carcinoma (HCC) have shown inconsistent results due to suboptimal detection methods and patient heterogeneity. METHODS: Patients undergoing surgery for early-stage HCC were prospectively enrolled. The CTC numbers were determined using a tapered slit platform, which detects CTCs based on the cell size and morphology. Survival and recurrence were evaluated, and Cox proportional hazards models were used to demonstrate the prognostic significance of CTC. RESULTS: Of 105 patients, 25 had increased CTC numbers after surgery (ΔCTC > 0, defined as positive) and a significantly higher level of recurrence (p = 0.042). A positive ΔCTC was seen to be an independent predictor of recurrence (hazard ratio 2.28), along with hepatitis B virus infection, alanine aminotransferase level, and the presence of satellite nodules (all p < 0.05). Subgroup analyses showed that a positive ΔCTC was associated with lower survival and higher recurrence among patients with low alpha-fetoprotein levels and cirrhosis (all p < 0.05). CONCLUSION: Calculation of ΔCTC based on the physical properties of the cells is predictive of recurrence in patients with early HCC undergoing surgery.

Post-debulking circulating tumor cell as a poor prognostic marker in advanced stage ovarian cancer: A prospective observational study.

Circulating tumor cells (CTCs) have received enormous attention as a novel biomarker in various malignant diseases. We investigated the clinical association between the presence of perioperative CTCs and survival outcomes in women with ovarian cancer. In a total of 30 women who were scheduled to undergo a surgical treatment for ovarian cancer, peripheral blood samples were obtained before and after surgery. CTCs were isolated and counted using the optimized tapered-slit filter (TSF) platform. The association between the presence of perioperative CTCs and tumor features was evaluated. The impact of the presence of perioperative CTCs on progression-free survival (PFS) and overall survival (OS) rates were analyzed using a Kaplan-Meier method. The median age was 58 (range, 24-77) years, and the median follow-up period was 31.5 (range, 1-41) months. Overall, the CTC detection rate was not significantly different before and after surgery (76.7% vs 57.1%, P = .673). The presence of postoperative CTCs was not significantly associated with 3-year PFS (29.1% vs 58.3%, P = .130) and OS (84.4% vs 80.0%, P = .559) rates in the whole study population. In advanced stage, PFS rate in patients with postoperative CTCs had lower PFS rates than those without postoperative CTCs, although there was no statistical significance (18.8% vs 57.1%, P = .077). Postoperative CTC was more frequently detected in women who had lymph node involvement than those who did not (7/7 [100%] vs 3/10 [30.0%], P = .010). The presence of postoperative CTCs as detected using the TSF platform seems to be associated with poorer PFS rates in women with ovarian cancer of advanced stage. Further study with a larger population is warranted to validate our study findings.

Detection of circulating tumour cells and their potential use as a biomarker for advanced renal cell carcinoma.

INTRODUCTION: The aim of this study was to detect circulating tumour cells (CTCs) in patients with advanced renal cell carcinoma (RCC) using a novel CTC detection platform. Furthermore, we evaluated the clinical outcomes associated with a CTC-positive status. METHODS: A total of 34 patients with advanced RCC (stage III or IV) were prospectively enrolled, and 104 peripheral blood samples were analyzed for the presence of CTCs at various time points. CTCs were isolated using a tapered-slit filter, which captures CTCs based on size and deformability. The presence of CTCs was confirmed using both staining and morphological criteria. CTC status was then correlated with clinical characteristics and survival outcomes. RESULTS: CTCs were detected in 62% of patients during the pre-treatment period, and the median CTC count was 2 (interquartile range 1-3). During the followup period, CTCs were detected in 56% (18/32), 65% (20/31), and 41% (7/17) of patients at one week, one month, and three months after treatment, respectively. Overall, CTCs were found in 57.9% (66/114) of blood samples in the range of 1-7 cells. Although no statistical significance was found, CTC detection in patients with stage IV disease was more common than in patients with stage III disease (68.4% vs. 53.3%). Two-year progression-free survival and cancer-specific survival tended to be lower in CTC-positive patients compared with CTC-negative patients. CONCLUSIONS: The tapered-slit filter is an efficient technique to detect CTCs in advanced RCC.