Young Taik Oh

A Smart Polysaccharide/Drug Conjugate for Photodynamic Therapy

Recent improvements in drug-carrier design for photodynamic therapy (PDT) have brought about significant advances for treating skin, breast, and lung tumors. The local high-dose strategy of PDT suggests beneficial therapeutic efficacy with high selectivity when using photosensitizing drugs for the target site, as well as reduced side effects for normal tissues. A variety of drug-carrying vehicles, such as nanoparticles, drug conjugates, and polymeric micelles have frequently exhibited characteristics that may make possible the successful delivery of photosensitizing drugs, thus improving cell entry and residence in tumor sites. However, these approaches have, thus far, achieved rather limited success, owing primarily to the practical obstacles inherent to natural in vivo conditions. In this study, we describe a novel molecular “Trojan horse” system that quickly switches into an aggressive molecule for tumor destruction within the environment of the tumor. Advances in functionality have enabled our system to exhibit an intelligent switch from a threedimensional supramolecular assembly (i.e., self-quenched state of photosensitizing drugs) into extended random molecules (i.e., dequenched state for singlet-oxygen production), which corresponds to a change in surface charge (Figure 1). This system may be more significant than any known photosensitizing drug conjugate thus far developed.

Solid Pseudopapillary Tumor of the Pancreas: Typical and Atypical Manifestations

OBJECTIVE The purpose of this pictorial essay is to illustrate the various appearances of solid pseudopapillary tumor of the pancreas. CONCLUSION Solid pseudopapillary tumor of the pancreas is a rare neoplasm usually found in young women. Typical solid pseudopapillary tumor is characterized by a well-encapsulated mass with varying amounts of intratumoral hemorrhage. However, the tumor can have an atypical appearance, such as metastasis, ductal obstruction, parenchymal and extracapsular invasion, simulation of islet cell tumor, intratumoral calcification, and occurrence in a male patient. The typical and atypical manifestations of solid pseudopapillary tumor can be visualized with cross-sectional imaging.

Diagnosis and staging of primary ovarian cancer: Correlation between PET/CT, Doppler US, and CT or MRI

PURPOSE To compare the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT), pelvic Doppler ultrasonography (US), abdomino-pelvic computed tomography (CT), and pelvic magnetic resonance imaging (MRI) for detection of ovarian cancer and to assess the role of PET/CT in evaluating the dissemination of ovarian cancer. PATIENTS AND METHODS One hundred thirty-three women suspected to have ovarian cancer were enrolled in a prospective study before surgery between March 2005 and August 2007. The accuracy of each modality in detection of malignancy was estimated by computing the relevant areas under a receiver operating characteristics curve. Histopathologic results served as the reference standard. RESULTS Histopathology showed benign tumors in 25 patients, borderline tumors in 13 patients, and malignant tumors in 95 patients. In distinguishing malignant/borderline from benign ovarian tumors, the accuracy of PET/CT (0.921) was higher than that of pelvis US (0.830) and abdomino-pelvic CT or pelvis MRI (0.749; P=0.013). Radiologic staging by PET/CT was concordant with surgical staging in 78% of patient and PET/CT revealed 15 (15.8%) unpredicted extra-abdominal lymph node metastasis in 95 patients with ovarian cancer. In addition, PET/CT detected new, unexpected co-existing malignant tumors in five (3.8%) cases including two thyroid tumors, two breast tumors, and one pancreatic neuroendocrine cancer. CONCLUSION PET/CT is superior to pelvis US, abdomino-pelvic CT, and pelvic MRI for diagnosis of malignant ovarian tumors and is useful in revealing metastatic ovarian cancer and co-existing malignant tumors. Therefore, we suggest that PET/CT could be used during pre-operative evaluation of patients suspected to have ovarian cancer.

Predictors of Kidney Volume Change and Delayed Kidney Function Recovery After Donor Nephrectomy

PURPOSE To our knowledge the effects of preoperative kidney volume in living donors on the post-donation change in size and function of the remaining kidney have not been investigated. We studied the association between preoperative kidney volume, and volume change and delayed kidney function recovery in donors. MATERIALS AND METHODS From 2007 to 2008 we investigated 222 living donors. Kidney volume before and 6 months after surgery was estimated using the voxel count method. We analyzed correlations of kidney volume with patient characteristics, kidney function and actual kidney weight. To identify predictors of the volume increase of the remaining kidney and predictors of delayed kidney function recovery we performed regression analysis. RESULTS Mean +/- SD total kidney volume was 311.9 +/- 50.6 cc and it correlated with weight, body surface area and kidney function (p <0.001). The mean volume increase in the remaining kidney was 27.6% +/- 9.7% (range 4.5% to 66.1%). Younger age (p <0.001) and lower preoperative volume of the remaining kidney (p = 0.019) were significant predictors of a greater increase in kidney volume on multiple linear regression analysis. Older age (OR 1.07, p <0.001), higher body mass index (OR 1.20, p = 0.008), lower preoperative kidney volume of the remaining kidney (OR 0.98, p = 0.003) and a lower preoperative diethylenetetramine pentaacetic acid glomerular filtration rate in the remaining kidney (OR 0.95, p = 0.017) were significant predictors of delayed kidney function recovery on multiple regression analysis. CONCLUSIONS Kidney volume measured by the voxel count method was accurate and correlated with kidney function. Preoperative kidney volume is an independent predictor of the volume increase and delayed kidney function recovery in donors that could be used clinically.

A smart flower-like polymeric micelle for pH-triggered anticancer drug release

Novel pH-responsive flower-like micelles were developed to provide the mechanism for pH-triggered drug release from drug carriers. The micelles (particle size: approximately 165 nm; critical micelle concentration (CMC): approximately 4 microg/ml), constructed from poly(N(epsilon)-(3-diethylamino)propyl isothiocyanato-L-lysine)-b-poly(ethylene glycol)-b-poly(L-lactide) [poly(DEAP-Lys)-b-PEG-b-PLLA], were designed to have a self-assembled flower-like arrangement consisting of two hydrophobic blocks [deprotonated poly(DEAP-Lys) block and PLLA block] and a petal-like hydrophilic PEG block at physiological pH. As the pH decreases to slightly acidic pH (<pH 7.0), as in tumor extracellular pH (pH(e)), the flower-like micelles undergo a change in the hydrophobicity of the micellar core. The protonation of poly(DEAP-Lys) changed the physical property of the polymer from hydrophobic to hydrophilic, resulting in disintegration of the micellar core. The co-presence of a pH-insensitive PLLA block in the micellar core affected the protonation of poly(DEAP-Lys), allowing the micelle to be stable at pH 7.0-7.4. In this study using doxorubicin (DOX) as the model drug, DOX release from the micelles accelerated in response to tumor pH(e).

Binary mixing of micelles using Pluronics for a nano-sized drug delivery system

Pluronics with different structural compositions and properties are used for several applications, including drug delivery systems. We developed a binary mixing system with two Pluronics, L121/P123, as a nano-sized drug delivery carrier. The lamellar-forming Pluronic L121 (0.1 wt%) was incorporated with Pluronic P123 to produce nano-sized dispersions (in case of 0.1 and 0.5 wt% P123) with high stability due to Pluronic P123 and high solubilization capacity due to Pluronic L121. The binary systems were spherical and less than 200-nm diameter, with high thermodynamic stability (at least 2 weeks) in aqueous solution. The CMC of the binary system was located in the middle of the CMC of each polymer. In particular, the solubilization capacity of the binary system (0.1/0.1 wt%) was higher than mono-systems of P123. The main advantage of binary systems is overcoming limitations of mono systems to allow tailored mixing of block copolymers with different physicochemical characteristics. These nano-sized systems may have potential as anticancer drug delivery systems with simple preparation method, high stability, and high loading capacity.

Prostate Cancer: PI-RADS Version 2 Helps Preoperatively Predict Clinically Significant Cancers

Purpose To retrospectively analyze whether Prostate Imaging Reporting and Data System (PI-RADS) version 2 is helpful for the detection of clinically significant prostate cancer. Materials and Methods Institutional review board approved this retrospective study. A total of 425 patients with prostate cancer who had undergone magnetic resonance (MR) imaging and radical prostatectomy were included. Preoperative parameters such as prostate-specific antigen, biopsy Gleason score, greatest percentage of the core, percentage of the positive core number, and score at PI-RADS version 2 with MR imaging were investigated. Two independent readers performed PI-RADS scoring. Clinically significant prostate cancer was defined as follows: (a) Gleason score of 7 or greater, (b) tumor volume of 0.5 cm(3) or greater, or a (c) positive extracapsular extension or seminal vesicle invasion. The reference standard was based on review of surgical specimen. Logistic regression was conducted to determine which parameters are associated with the presence of clinically significant cancer. Interreader agreement (ie, score ≥4 or not) was investigated by using κ statistics. Results At univariate analysis, all of the preoperative parameters were significant for clinically significant prostate cancer (P < .05). However, multivariate analysis revealed that PI-RADS score was the only significant parameter for both readers (reader 1: odds ratio = 28.170, P = .002; reader 2: odds ratio = 5.474, P = .007). The interreader agreement was excellent for PI-RADS score of 4 or greater (weighted κ = 0.801; 95% confidence interval: 0.737, 0.865). Conclusion The use of PI-RADS version 2 may help preoperatively diagnose clinically significant prostate cancer. (©) RSNA, 2016.

Benign Lesions After Partial Nephrectomy for Presumed Renal Cell Carcinoma in Masses 4 cm or Less: Prevalence and Predictors in Korean Patients

OBJECTIVES To investigate the prevalence and predictors associated with benign lesions in Korean patients after partial nephrectomy for presumed renal cell carcinoma (RCC) for lesions measuring ≤ 4 cm. METHODS We retrospectively investigated the medical records of 376 patients who underwent partial nephrectomy for presumed RCC with renal masses of size ≤ 4 cm between June 1997 and December 2008. Demographic and clinicopathologic parameters were compared between benign lesions and RCC. Logistic regression was done to identify parameters associated with benign lesions. RESULTS In the 376 patients, 81 tumors (21.5%) were benign, including 35 angiomyolipomas (9.3%), 26 complicated cysts (6.9%), 11 oncocytomas (2.9%), and 9 others (2.4%). Univariate analysis showed that time of surgery, female sex, younger age, and normal body mass index (body mass index (BMI) < 23 kg/m(2)) were associated with benign pathologic findings. On multiple logistic regression analysis, female sex (OR, 4.91; 95% CI, 2.76-08.75; P < .001), age (OR, 0.97; 95% CI, 0.95-0.99; P = .009), and time of surgery (OR, 0.33; 95% CI, 0.11-0.95; P = .040) were independent predictors of benign histologic features. Tumor size, incidental diagnosis, and BMI were not significant predictors (P > .05). CONCLUSIONS Our study with a large cohort of Asian patients showed that the prevalence of benign lesions was similar to previously reported Western studies. However, the most common benign lesion was angiomyolipoma, compared with oncocytoma in Western countries. The results of this study may help clinicians counsel female and younger patients recently diagnosed with small renal masses and decide the most appropriate treatment, including renal biopsies and close observation.

Optimal Scan Window for Detection of Hypervascular Hepatocellular Carcinomas During MDCT Examination

OBJECTIVE The purpose of this study was to define the optimal scan window for acquiring arterial phase images in the detection of hypervascular hepatocellular carcinomas (HCCs). MATERIALS AND METHODS Biphasic arterial phase CT examinations were performed using a 16-MDCT scanner on 198 patients (159 men and 39 women; mean age, 59 years; age range, 25-82 years) with nodular HCC. All examinations were performed after administering 120-150 mL of a nonionic contrast media (370 mg I/mL) at a rate of 3-4 mL/s. The scan delay--the interval between when the bolus-tracking program detected the threshold enhancement of 100 H in the abdominal aorta and the start of the first arterial scan-was progressively lengthened by 2-second intervals, from 10 seconds in group 1 to 20 seconds in group 6. The second arterial phase scan was started 6 seconds after the end of the early scan. A tube collimation of 1.5 mm, a table feed of 18 mm per rotation, an image thickness of 3 mm, and 3-mm increments were used. The duration of each phase scan was 4.5-8.8 seconds. Tumor-to-liver attenuation difference (TLAD) at the first (TLAD1) and second (TLAD2) arterial phase images were compared lesion by lesion. Four observers assigned subjective ratings of visual conspicuity and individual preferences for each phase in each group. RESULTS The mean threshold time (100 H) was 18.4 +/- 3.1 seconds, and 97% of patients were within the range of 13-24 seconds. The mean TLAD1 of groups 3 to 6 and the mean TLAD2 of groups 1 to 5 were all comparable; they were also all significantly (p < 0.005) higher than the mean TLAD1 of groups 1 and 2 and the mean TLAD2 of group 6. In groups 1 and 2, the mean TLAD2 was significantly higher than the mean TLAD1 (p < 0.001); in groups 5 and 6, the mean TLAD1 was significantly higher than the mean TLAD2 (p < 0.001). In groups 3 and 4, the mean TLAD1 and TLAD2 were similar. The visual conspicuity and individual preferences were higher for the first-phase image in groups 3 to 6 and the second-phase image in groups 1 and 2. CONCLUSION The optimal scan window for arterial phase images in the detection of HCC seems to be approximately 14-30 seconds from the 100-H threshold.

Detection and characterization of focal hepatic lesions: Mangafodipir vs. Superparamagnetic iron oxide-enhanced magnetic resonance imaging

To compare the mangafodipir‐enhanced magnetic resonance (MR) and superparamagnetic iron oxide (SPIO)‐enhanced images for their ability to detect and characterize focal hepatic lesions.