Selective Binding of Tannic Acid-Conjugated Lipid Nanovesicles to Proline-Rich Proteins Enhances Transdermal Lipophilic-Antioxidant Delivery.

Tannic acid (TA) possesses a notable ability to adhere to proline-rich proteins that make up skin cells and the extracellular matrix (ECM) in the skin tissue. Drug carriers with this specific adhesion ability exhibit improved drug delivery efficiency on the skin. Taking advantage of this, this study presents skin-adhesive TA-conjugated lipid nanovesicles (TANVs) for enhanced transdermal antioxidant delivery. We found that TANVs exhibited selective intermolecular interactions with keratinocyte proline-rich proteins (KPRPs) and collagen that makes up skin cells by hydrogen bonding and van der Waals interactions, further enabling the strong bonding to macroscopic skin itself and ECM. We used vitamin E (α-tocopherol), which is known to effectively reduce oxidative stress but has limited skin penetration, as a drug to verify improved in vitro delivery and therapeutic efficacy. The evaluation revealed that the antioxidant-loaded TANVs exerted excellent scavenging effects against reactive oxygen species induced by ultraviolet light or peroxides in the skin, thereby enabling the development of an active drug delivery system for dermal therapy.

Differential diagnosis of thyroid nodules using heterogeneity quantification software on ultrasound images: correlation with the Bethesda system and surgical pathology.

Ultrasonography (US)-guided fine-needle aspiration cytology (FNAC) is the primary modality for evaluating thyroid nodules. However, in cases of atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), supplemental tests are necessary for a definitive diagnosis. Accordingly, we aimed to develop a non-invasive quantification software using the heterogeneity scores of thyroid nodules. This cross-sectional study retrospectively enrolled 188 patients who were categorized into four groups according to their diagnostic classification in the Bethesda system and surgical pathology [II-benign (B) (n = 24); III-B (n = 52); III-malignant (M) (n = 54); V/VI-M (n = 58)]. Heterogeneity scores were derived using an image pixel-based heterogeneity index, utilized as a coefficient of variation (CV) value, and analyzed across all US images. Differences in heterogeneity scores were compared using one-way analysis of variance with Tukey's test. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristic (AUROC) curve. The results of this study indicated significant differences in mean heterogeneity scores between benign and malignant thyroid nodules, except in the comparison between III-M and V/VI-M nodules. Among malignant nodules, the Bethesda classification was not observed to be associated with mean heterogeneity scores. Moreover, there was a positive correlation between heterogeneity scores and the combined diagnostic category, which was based on the Bethesda system and surgical cytology grades (R = 0.639, p < 0.001). AUROC for heterogeneity scores showed the highest diagnostic performance (0.818; cut-off: 30.22% CV value) for differentiating the benign group (normal/II-B/III-B) from the malignant group (III-M/V&VI-M), with a diagnostic accuracy of 72.5% (161/122). Quantitative heterogeneity measurement of US images is a valuable non-invasive diagnostic tool for predicting the likelihood of malignancy in thyroid nodules, including AUS or FLUS.

Comprehensive CT Imaging Analysis of Primary Colorectal Squamous Cell Carcinoma: A Retrospective Study.

The aim of this study was to evaluate the findings of CT scans in patients with pathologically confirmed primary colorectal squamous-cell carcinoma (SCC). The clinical presentation and CT findings in eight patients with pathologically confirmed primary colorectal squamous-cell carcinoma were retrospectively reviewed by two gastrointestinal radiologists. Hematochezia was the most common symptom (n = 5). The tumors were located in the rectum (n = 7) and sigmoid colon (n = 1). The tumors showed circumferential wall thickening (n = 4), bulky mass (n = 3), or eccentric wall thickening (n = 1). The mean maximal wall thickness of the involved segment was 29.1 mm ± 13.4 mm. The degree of tumoral enhancement observed via CT was well enhanced (n = 4) or moderately enhanced (n = 4). Necrosis within the tumor was found in five patients. The mean total number of metastatic lymph nodes was 3.1 ± 3.3, and the mean short diameter of the largest metastatic lymph node was 16.6 ± 5.7 mm. Necrosis within the metastatic node was observed in six patients. Invasions to adjacent organs were identified in five patients (62.5%). Distant metastasis was detected in only one patient. In summary, primary SCCs that arise from the colorectum commonly present as marked invasive wall thickening or a bulky mass with heterogeneous well-defined enhancement, internal necrosis, and large metastatic lymphadenopathies.

Thermal Injury to the Subhepatic Appendix Following Percutaneous Ultrasound-Guided Radiofrequency Ablation for Hepatocellular Carcinoma: A Case Report.

We present the first documented case of a fistula between the treated zone and the appendix after RFA in a patient with HCC. Contrast-enhanced CT and MRI revealed a subcapsular hepatic nodule with image findings of HCC located adjacent to the ascending colon and cecum. An ultrasound-guided core needle biopsy was subsequently performed to distinguish between hepatic metastasis and HCC. Post-RFA imaging identified a low-attenuating ablated area adjacent to an air-filled appendix. The patient later experienced complications, including increased liver enzymes and an abscess at the ablation site. Imaging revealed a fistulous tract between the RFA zone and the appendix. Over the following months, the patient underwent conservative treatment involving intravenous antibiotics and repeated percutaneous drainage, exhibiting eventual symptom relief and an absence of the fistulous tract upon subsequent imaging. This case highlights the rare complications that can arise during RFA due to peculiar anatomical variations, such as a subhepatic appendix, resulting from midgut malrotation and previous surgery. It is imperative for operators to be cognizant of potential anatomical variations when considering RFA treatment, ensuring comprehensive pre-procedural imaging and post-procedure monitoring. This case also emphasizes the potential viability of nonoperative management in complex scenarios in which surgical interventions pose significant risks.

Tumor-targeted liposomes with platycodin D2 promote apoptosis in colorectal cancer.

Conventional chemotherapy for colorectal cancer (CRC), though efficacious, is discouraging due to its limited targeting capability, lack of selectivity, and chemotherapy-associated side effects. With the advent of nanomedicines, a liposomal delivery system making use of a combination of anticancer phytochemicals is fast gaining popularity as one of the most promising nanoplatforms for CRC treatment. Rising evidence supports phytochemicals such as platycosides for their anticancer potency. To this end, a combination therapy including tumor-targeted liposomes along with phytochemicals might have a greater therapeutic potential against cancer. In this study, we developed acidity-triggered rational membrane (ATRAM) along with conjugated platycodin D2 (PCD2) and liposomes (PCD2-Lipo-ATRAM) as a tumor-targeting therapy. The PCD2-Lipo-ATRAM treatment demonstrated a successful tumor-targeting ability in the CRC xenografts, in which PCD2 not only exerted a potent antitumor effect by inducing apoptotic cell death and but also functioned as a liposome membrane stabilizer. Moreover, PCD2-Lipo-ATRAM suppressed antiapoptotic BCL-2 family proteins, resulting in enhanced cytotoxicity toward CRC cells by inducing intrinsic caspase-9/-3 mediated apoptosis. Thus, our data has shown that tumor-targeting PCD2-based liposomal systems represent a promising strategy for CRC therapy, since they directly target the tumors, unlike other therapies that can miss the target.

Fibroblast-targeting polymeric nanovehicles to enhance topical wound healing through promotion of PAR-2 receptor-mediated endocytosis.

The level of collagen production critically determines skin wound contraction. If an intelligent skin drug delivery technology that enables collagen production in a specific wound skin area is developed, a breakthrough in wound healing treatment would be expected. However, such an intelligent drug delivery technology has not yet been developed as much as in the field of anticancer therapy. In this study, we propose a smart drug delivery system using polymeric nanovehicles (PNVs), in which the periphery is conjugated with a fibroblast-targeting collagen-derived peptide, KTTKS (Lys-Thr-Thr-Lys-Ser). We showed that surface engineering of PNVs with simultaneous PEGylation and peptide patching improved the dispersibility of PNVs, while promoting selective cellular uptake to fibroblasts via PAR-2 receptor-mediated endocytosis. In vitro collagen production and in vivo wound healing assays revealed that curcumin-loaded fibroblast-targeting PNVs significantly enhanced collagen production and wound healing activities, thus promising effective skin tissue regeneration.

Retardation of Capillary Force between Janus Particles at the Oil-Water Interface.

Interactions among colloidal particles govern the hierarchical microstructure and its physical properties. Here, optical laser tweezers and Monte Carlo simulations are used to evaluate the effects of azimuthal rotation of Janus particles at the oil-water interface on interparticle interactions. We find that the capillary-induced attractive force between two Janus particles at the interface can be relaxed by azimuthal rotation around the critical separation region, at which the capillary force is ∼0.053 pN. Force relaxation leads to a decrease in capillary force around the critical separation region, resulting in a slight increase in the scaling exponent, compared to the theoretical prediction.

Facile and scalable fabrication of exosome-mimicking nanovesicles through PEGylated lipid detergent-aided cell extrusion.

We report a scalable fabrication method to generate exosome-mimicking nanovesicles (ENVs) by using a biocompatible, cell-binding lipid detergent during cell extrusion. A PEGylated mannosylerythritol lipid (MELPEG) detergent was rationally engineered to strongly associate with phospholipid membranes to increase cell membrane deformability and the corresponding friction force during extrusion and to enhance the dispersibility of ENVs. Compared to cell extrusion without detergent, cell extrusion in the presence of MELPEG increased the ENV production yield by approximately 20 times and cellular protein content per MELPEG-functionalized ENV by approximately 2-fold relative to that of unmodified ENVs. We verified that MELPEG strongly binds to ENV membranes and increases membrane deformability via expansion/swelling while preserving the integrity of the phospholipid bilayer structure. The results highlight that the MELPEG-aided cell extrusion process broadly applies to various cell lines; hence, it could be helpful in the production of ENVs for tissue regeneration, drug delivery, and cancer nanomedicine.

Polyphenol-modified nanovesicles for synergistically enhanced in vitro tumor cell targeting and apoptosis.

Tannic acid (TA) not only prevents drug carriers from sticking to the glycocalyx layer of vascular endothelial cells but also has anti-cancer properties, thereby improving drug delivery efficiency in cancer treatment. This study proposes a TANNylated nanovesicle-based cancer treatment approach by utilizing the aforementioned advantages of TA. We fabricated cancer cell-targeting BC71 peptide-conjugated TANNylated nanovesicles (TANVBC71) by covalently bonding the TA derivative and BC71 (cyclo[ßA-kRK(3-maleimidopropionyl)-D-(D-2-naphthyl)]) with thiol-modified phospholipids through the thiol-maleimide reaction. We demonstrated that TANVBC71 was absorbed faster in high amounts by cancer cells than nanovesicles owing to its high affinity for the epidermal growth factor receptor and extracellular matrix components that are driven by van der Waals attraction as well as hydrogen bonding and hydrophobic interactions in a complex manner. These complex attractions of TANVBC71 for cancer cells led to the effective induction of cancer cell apoptosis. The findings obtained in this study highlight that the TANVBC71 system has the potential for intelligent high-efficacy cancer cell drug delivery.

Effects of Irradiation on Brain Tumors Using MR-Based Electrical Conductivity Imaging.

Ionizing radiation delivers sufficient energy inside the human body to create ions, which kills cancerous tissues either by damaging the DNA directly or by creating charged particles that can damage the DNA. Recent magnetic resonance (MR)-based conductivity imaging shows higher sensitivity than other MR techniques for evaluating the responses of normal tissues immediately after irradiation. However, it is still necessary to verify the responses of cancer tissues to irradiation by conductivity imaging for it to become a reliable tool in evaluating therapeutic effects in clinical practice. In this study, we applied MR-based conductivity imaging to mouse brain tumors to evaluate the responses in irradiated and non-irradiated tissues during the peri-irradiation period. Absolute conductivities of brain tissues were measured to quantify the irradiation effects, and the percentage changes were determined to estimate the degree of response. The conductivity of brain tissues with irradiation was higher than that without irradiation for all tissue types. The percentage changes of tumor tissues with irradiation were clearly different than those without irradiation. The measured conductivity and percentage changes between tumor rims and cores to irradiation were clearly distinguished. The contrast of the conductivity images following irradiation may reflect the response to the changes in cellularity and the amounts of electrolytes in tumor tissues.

Image-Based Evaluation of Irradiation Effects in Brain Tissues by Measuring Absolute Electrical Conductivity Using MRI.

Radiation-induced injury is damage to normal tissues caused by unintentional exposure to ionizing radiation. Image-based evaluation of tissue damage by irradiation has an advantage for the early assessment of therapeutic effects by providing sensitive information on minute tissue responses in situ. Recent magnetic resonance (MR)-based electrical conductivity imaging has shown potential as an effective early imaging biomarker for treatment response and radiation-induced injury. However, to be a tool for evaluating therapeutic effects, validation of its reliability and sensitivity according to various irradiation conditions is required. We performed MR-based electrical conductivity imaging on designed phantoms to confirm the effect of ionizing radiation at different doses and on in vivo mouse brains to distinguish tissue response depending on different doses and the elapsed time after irradiation. To quantify the irradiation effects, we measured the absolute conductivity of brain tissues and calculated relative conductivity changes based on the value of pre-irradiation. The conductivity of the phantoms with the distilled water and saline solution increased linearly with the irradiation doses. The conductivity of in vivo mouse brains showed different time-course variations and residual contrast depending on the irradiation doses. Future studies will focus on validation at long-term time points, including early and late delayed response and evaluation of irradiation effects in various tissue types.

Skin protein-derived peptide-conjugated vesicular nanocargos for selected skin cell targeting and consequent activation.

Several studies have reported that a drug nanocarrier conjugated with ligands having cell binding ability improves drug delivery performance, but multiple cell-targeting and the resultant activation in designated cells has not been investigated yet. This study reports a skin cell multi-targeting vesicular nanocargo system. We selectively conjugated several skin protein-derived cell-targeting peptides (CTPs), including KTTKS, NAP-amide, and Lam332, to amphiphilic polymer-reinforced lipid nanovesicles (PLNVs) to specifically target fibroblasts, melanocytes, and keratinocytes, respectively, through effective association with the corresponding cell membrane receptors. We then showed that CTP-conjugated PLNVs specifically bind to the designated skin cells, even in a mixture of different types of skin cells, eventually leading to skin cell multi-targeting and consequent activation. These results highlight that this CTP-conjugated PLNV system has significant potential for developing an intelligent cellular drug delivery technology for dermatological applications.

Assessment of Liver Fibrosis Stage Using Integrative Analysis of Hepatic Heterogeneity and Nodularity in Routine MRI with FIB-4 Index as Reference Standard.

Image-based quantitative methods for liver heterogeneity (LHet) and nodularity (LNod) provide helpful information for evaluating liver fibrosis; however, their combinations are not fully understood in liver diseases. We developed an integrated software for assessing LHet and LNod and compared LHet and LNod according to fibrosis stages in chronic liver disease (CLD). Overall, 111 CLD patients and 16 subjects with suspected liver disease who underwent liver biopsy were enrolled. The procedures for quantifying LHet and LNod were bias correction, contour detection, liver segmentation, and LHet and LNod measurements. LHet and LNod scores among fibrosis stages (F0-F3) were compared using ANOVA with Tukey's test. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristics (AUROC) curve. The mean LHet scores of F0, F1, F2, and F3 were 3.49 ± 0.34, 5.52 ± 0.88, 6.80 ± 0.97, and 7.56 ± 1.79, respectively (p < 0.001). The mean LNod scores of F0, F1, F2, and F3 were 0.84 ± 0.06, 0.91 ± 0.04, 1.09 ± 0.08, and 1.15 ± 0.14, respectively (p < 0.001). The combined LHet × LNod scores of F0, F1, F2, and F3 were 2.96 ± 0.46, 5.01 ± 0.91, 7.30 ± 0.89, and 8.48 ± 1.34, respectively (p < 0.001). The AUROCs of LHet, LNod, and LHet × LNod for differentiating F1 vs. F2 and F2 vs. F3 were 0.845, 0.958, and 0.954; and 0.619, 0.689, and 0.761, respectively. The combination of LHet and LNod scores derived from routine MR images allows better differential diagnosis of fibrosis subgroups in CLD.

Is delayed gastric emptying associated with pylorus ring preservation in patients undergoing pancreaticoduodenectomy?

BACKGROUND/OBJECTIVE: A high incidence of delayed gastric emptying (DGE) is observed in patients undergoing pylorus-preserving pancreaticoduodenectomy (PpPD). However, DGE incidence after pancreaticoduodenectomy varied because of heterogeneity in surgical techniques, number of surgeons, and DGE definition. This study aimed to evaluate the difference in the incidence of DGE following PpPD and pylorus-resecting pancreaticoduodenectomy (PrPD) and to analyze the risk factor of DGE by a single surgeon to determine whether pylorus preservation was the main factor of DGE. METHODS: This retrospective study included 115 patients who underwent PpPD (with pylorus ring preservation) and PrPD (without pylorus ring preservation) with laparotomy by a single surgeon at a tertiary center. RESULTS: The overall incidence of DGE was 23.1%. For comparison, 20 patients (39.2%) in the PpPD group and 5 patients (8.8%) in the PrPD group had DGE, showing a significant difference (p < 0.001). On univariate analysis, hypertension, PpPD, operation time, intraoperative bleeding, packed red blood cell transfusion ≥500 mL, and clinically relevant postoperative pancreatic fistula were associated with DGE. Multivariate analysis identified pylorus preservation and clinically relevant postoperative pancreatic fistula as risk factors for DGE. CONCLUSION: Compared with PpPD, PrPD significantly reduced the incidence of DGE.

Cell-penetrating peptide-conjugated lipid/polymer hybrid nanovesicles for endoplasmic reticulum-targeting intracellular delivery.

The endoplasmic reticulum (ER) apparatus is a part of the secretory pathway that transports proteins to the plasma membrane through vesicle trafficking, enabling post-translational modification of the newly synthesized proteins. Several diseases such as inflammation, neurodegenerative disorder, and bipolar disorder are closely associated with dysfunction of the ER stress response. Herein, we present an ER-targeting, intracellular delivery approach that utilized cell-penetrating peptide (CPP)-conjugated lipid/polymer hybrid nanovehicles (LPNVs). For this, we patched Penetratin, a type of CPP, onto the LPNVs with vesicular membranes formulated with poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO-b-PCL-b-PEO) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). We found that the Penetratin-conjugated LPNV (LPNVPnt) was readily taken up by cells and showed specific ER-targeting ability, which was comparable to that of LPNVs conjugated with other types of CPPs. Moreover, we observed that remarkable lysosomal escape of the LPNVs occurred due to effective pH buffering with the aid of PEO-b-PCL-b-PEO. These results highlighted that our LPNVPnt system could pave the way for the development of an elaborate drug delivery technology for ER-targeting at the intracellular level.

Pleural Effusion after Hepatic Radiofrequency Ablation with Artificial Ascites: Clinical Spectrum and Significance.

PURPOSE: To retrospectively investigate incidence, clinical outcome, and risk factors of iatrogenic pleural effusion in patients with hepatic tumors undergoing radiofrequency (RF) ablation using artificial ascites (AA). MATERIALS AND METHODS: Patients (N = 163) who underwent RF ablation using AA were classified into pleural effusion and non-pleural effusion groups according to the presence of pleural effusion on immediate follow-up CT and chest radiograph after RF ablation. The pleural effusion group included asymptomatic and symptomatic subgroups. The incidence and subsequent clinical outcomes of patients developing pleural effusion after RF ablation were evaluated. RESULTS: Overall, 96 patients (58.9%) developed pleural effusion, which resolved in 4.4 d ± 3.1. Hospital length of stay in the pleural effusion group was longer than the non-pleural effusion group (6.5 d ± 2.6 vs 5.7 d ± 2.8, P < .01). The pleural effusion group had longer AA infusion time (P = .01), larger infused AA volume (P < .01), and longer ablation time (P < .01) than the non-pleural effusion group. Eighteen patients (18.8%) developed symptomatic pleural effusion and had a larger infused AA volume than asymptomatic patients with pleural effusion (P < .01). Pleural effusion duration and hospital length stay were also longer in the symptomatic pleural effusion subgroup than in the asymptomatic subgroup (P < .01). Infused AA volume was the only independent prognostic factor of pleural effusion duration in multivariate analysis (P = .038). CONCLUSIONS: Pleural effusion frequently occurs after RF ablation using AA. Although generally considered negligible, pleural effusion could be a clinical problem and prolong hospitalization. Therefore, operators should be careful not to infuse too much AA when performing RF ablation.

Comparison of Different Rectal Cleansing Methods for Reducing Post-Procedural Infectious Complications After Transrectal Ultrasound-Guided Prostate Biopsy.

PURPOSE: To compare the efficacy of three different rectal cleansing methods for reducing post-procedural infectious complications after transrectal ultrasound (TRUS)-guided prostate biopsy. MATERIALS AND METHODS: A total of 451 consecutive patients who underwent TRUS-guided prostate biopsy were prospectively included in this study. All patients received targeted antimicrobial prophylaxis and underwent bowel preparation through laxative administration. The patients were divided into three groups on the basis of the method of rectal cleansing immediately before the procedure. Group I patients (n=165) underwent cleansing of the perianal skin using povidone-iodine cotton balls; group II patients (n=116) received an injection of povidone-iodine solution (0.1 g/mL) into the anal and lower rectal canals; and group III patients (n=170) received direct manual cleansing of the mucosal surface of the anus and lower rectum using povidone-iodine cotton balls. The three groups were compared regarding the incidence of post-procedural infectious complications, re-hospitalization rates, and mean length of hospital stay using one-way ANOVA, the Chi-square test, and multiple logistic regression analysis. RESULTS: Post-procedural infectious complications occurred in 21.8%, 11.2%, and 6.5% of groups I, II, and III, respectively (P < .001). The incidence of overall infectious complications was significantly lower in group II (95% CI: 0.232-0.958, OR = 0.472, P = .038) and group III (95% CI: 0.129-0.555, OR = 0.267, P < .001) than in group I. Re-hospitalization rates were 9.7%, 2.6%, and 0.6% in groups I, II, and III, respectively (P < .001). The incidence of re-hospitalization was significantly lower in group II (95% CI: 0.070-0.869, OR = 0.247, P = .029) and group III (95% CI: 0.007-0.421, OR = 0.055, P = .005) than in group I. The mean length of hospital stay was significantly longer in group I than in group III (P = .009). CONCLUSION: Combined with targeted antimicrobial prophylaxis, direct manual cleansing of the mucosal surface of the anus and lower rectum using povidone-iodine cotton balls was most effective in preventing post-procedural infectious complications among the three different rectal cleansing methods.

Intrahepatic adrenocortical adenoma arising from adrenohepatic fusion mimicking hepatic malignancy: Two case reports.

RATIONALE: Intrahepatic adrenocortical adenoma (IAA) arising from adrenohepatic fusion (AHF) is rare and its imaging findings are not well established. Moreover, it is easily misdiagnosed as malignant hepatic tumor in patients at risk of malignancy. Its key finding is the connection between the tumor and adrenal gland. When IAA from AHF is suspected, biopsy should be considered to avoid unnecessary surgery. Herein, we report 2 cases of IAA from AHF. PATIENT CONCERNS: A 59-year-old woman was admitted due to a 1.5-cm hypoechoic nodule in the right hepatic lobe detected on ultrasound for hepatocellular carcinoma (HCC) surveillance due to chronic hepatitis B. Contrast-enhanced computed tomography (CT) and gadoxetic acid-enhanced magnetic resonance imaging (MRI) were performed to evaluate the hepatic mass. Another 75-year-old woman was admitted due to rectal adenocarcinoma detected on colonoscopy. Contrast-enhanced CT depicted a 2.5-cm mass in the right hepatic lobe. DIAGNOSIS: In case 1, CT and MRI showed a 1.5-cm subcapsular mass in the right hepatic lobe with typical findings of HCC in a patient with chronic hepatitis B. The mass was confirmed as IAA from AHF after the laparoscopic surgery. In case 2, CT showed advanced rectal malignancy and a 2.5-cm poorly enhancing mass in the right hepatic lobe. The tentative diagnosis was hepatic metastasis. However, based on the connection between the tumor and adrenal gland during preoperative review, the presumed diagnosis was changed to IAA from AHF, which was confirmed on biopsy. INTERVENTIONS: The hepatic mass connected with the right adrenal gland was laparoscopically resected in case 1. Laparoscopic lower anterior resection for rectal malignancy and percutaneous biopsy for the hepatic mass were performed in case 2. OUTCOMES: The first patient had an uneventful recovery, without recurrence on the 3-year follow-up CT. The second patient had an uneventful postoperative course and has been alive for 12 months postoperatively without pathologically proven IAA changes on follow-up CT. LESSONS: When hepatic mass is found adjacent to the right adrenal gland on imaging, the connection between the tumor and adrenal gland should be investigated. When IAA arising from AHF is suspected, biopsy should be considered to avoid unnecessary surgery.

Change in Perfusion Angiography During Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Predicts Short-Term Outcomes.

OBJECTIVE. The purpose of this study is to quantitatively assess perfusion reductions occurring in hepatocellular carcinoma (HCC) during transcatheter arterial chemoembolization (TACE) using 2D perfusion angiography and to evaluate the relationships between various 2D perfusion angiography parameter changes and short-term tumor response. SUBJECTS AND METHODS. This prospective study included 172 patients (144 men and 28 women; mean [± SD] age, 65.4 ± 10.2 years) who underwent TACE for HCC between November 2015 and November 2017. Two-dimensional perfusion angiography was performed before and after TACE. Pre- and postprocedural CT images were also reviewed. Index lesions were defined as all discrete lesions 1.5 cm or larger. The tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors. Periprocedural 2D perfusion angiography parameters, including the arrival time, time to peak, wash-in rate, width, AUC, and mean transit time, were compared using the Wilcoxon signed rank test. Correlations between 2D perfusion angiography parameter changes and objective tumor response were evaluated using multivariate logistic regression analysis. RESULTS. A total of 187 lesions meeting the inclusion criteria were identified in 172 patients. All analyzed 2D perfusion angiography parameters were significantly different after versus before TACE (p < 0.001). A significant relationship between periprocedural change in AUC and short-term tumor response was found (odds ratio, 1.535; 95% CI, 1.314-1.793; p < 0.001). CONCLUSION. Two-dimensional perfusion angiography could objectively quantify perfusion reductions and predict short-term tumor response to TACE in patients with HCC.

Fabrication of cell membrane-adhesive soft polymeric nanovehicles for noninvasive visualization of epidermal-dermal junction-targeted drug delivery.

We propose a polymeric nanovehicles (PNVs)-based enhanced transdermal delivery platform. A technical advance can be found in that delivery efficiency is significantly enhanced by effective adhesion of PNVs to the cell membrane, which is characterized noninvasively by using a confocal laser scanning microscopy (CLSM)-based skin visualization technique. To this end, the PNVs with a soft core phase were fabricated through co-assembly of two amphiphilic triblock copolymers, poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO-b-PCL-b-PEO) and poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-b-PPO-b-PEO). The softness of PNVs was tuned successfully, while maintaining the particle size at ∼110 nm, by incorporation of PEO-b-PPO-b-PEO into the PNVs to a volume fraction of 0.3. Through an ex vivo skin penetration test, we showed that transactivating transcriptional activator (TAT)-decorated soft PNVs could not only exert strong adhesion to skin but also increase cellular uptake, leading to a transdermal delivery efficiency that is twice that of a hard PNV control. Moreover, CLSM-based noninvasive visualization of a fluorescent drug probe in the skin showed that the adhesiveness and softness of the PNVs contributed directly to the enhancement of transdermal delivery.