A case of uterine adenomyoma of endocervical type that was suspected as minimal deviation adenocarcinoma on biopsy, MRI findings, and literature review.

Uterine adenomyomas of endocervical type are rare benign tumors of the uterine cervix commonly presented as cyst-like, dilated glandular structures within polypoid masses. A premenopausal woman in her 50s was referred to our hospital because of an increasing watery vaginal discharge. A multifocal cyst measuring 5 × 4.5 cm in size projecting into the endocervical canal was revealed on a contrast-enhanced MRI. The fluid within the tumor showed a hypointense signal on T1-weighted imaging (T1WI) and a hyperintense signal on T2-weighted imaging (T2WI). On T2WI, most of the septa within the tumor showed a slightly hyperintense to hypointense signal, whereas some areas revealed a strong hypointense signal; the contrast effect on the septum was satisfactory. On the T2WI taken 2 years previously, the tumor was a 4.5 × 3.5 cm polypoid mass protruding from the posterior endocervical wall. Contrastingly, the current T2WI showed that the stem was no longer identifiable because of tumor growth. Because previous imaging showed that the tumor was a stalked tumor protruding from the posterior endocervical wall, the imaging diagnosis was uterine adenomyoma of the endocervical type. A biopsy suggested the possibility of a minimal deviation adenocarcinoma (MDA). Hence, a total hysterectomy was performed. The final diagnosis confirmed the uterine adenomyoma of endocervical type. Uterine adenomyoma of the endocervical type might be difficult to differentiate from MDA in small biopsy specimens; therefore, evaluation of morphology by MRI is considered important in preoperative diagnosis.

In Vitro Characterization of Drug-Loaded Superabsorbent Polymer Microspheres: Absorption and Release Capacity of Contrast Material, Antibiotics and Analgesics.

PURPOSE: To examine the characteristics of drug-loaded superabsorbent polymer microspheres (SAP-MS) such as drug absorption, drug release, diameter, and visibility. MATERIALS AND METHODS: SAP-MS (HepaSphere150-200 µm; Merit Medical, South Jordan, UT, USA) were suspended in drug solutions: (a) cefazolin, (b) lidocaine, (c) iopamidol and cefazolin, (d) iopamidol and lidocaine, and (e) iopamidol, cefazolin, and lidocaine. The concentrations of drugs were measured, and the amount of each drug absorbed was calculated. Filtered drug-loaded SAP-MS were mixed with saline, and the drug release rates were calculated. The diameter changes of SAP-MS during absorption were observed. Radiography of drug-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio (CNR). RESULTS: The drug concentration did not change during absorption. The release rates increased for 10 min and then came to an equilibrium. The mean amounts of drug absorbed at 180 min and mean release rates at 24 h were (a) cefazolin: 265.4 mg, 64.2%; (b) lidocaine: 19.6 mg, 75.6%; (c) iopamidol: 830.2 mg, 22.5%; cefazolin: 137.6 mg, 21.2%; (d) iopamidol: 1620.6 mg, 78.5%; lidocaine: 13.5 mg, 81.4%; and (e) iopamidol: 643.7 mg, 52.9%; cefazolin: 194.0 mg, 51.6%; lidocaine: 5.3 mg, 58.4%. The diameter of SAP-MS increased for approximately 15 min. Finally, the diameters of SAP-MS were (a) 3.9 times, (b) 5.0 times, (c) 2.2 times, (d) 5.5 times, and (e) 3.6 times larger than the original size. Drug-loaded SAP-MS containing iopamidol were visible under X-ray imaging, with CNRs of (c) 3.0, (d) 9.0, and (e) 4.5. CONCLUSION: SAP-MS can absorb and release iopamidol, cefazolin, and lidocaine.

Targeting cis-regulatory elements of FOXO family is a novel therapeutic strategy for induction of leukemia cell differentiation.

Differentiation therapy has been proposed as a promising therapeutic strategy for acute myeloid leukemia (AML); thus, the development of more versatile methodologies that are applicable to a wide range of AML subtypes is desired. Although the FOXOs transcription factor represents a promising drug target for differentiation therapy, the efficacy of FOXO inhibitors is limited in vivo. Here, we show that pharmacological inhibition of a common cis-regulatory element of forkhead box O (FOXO) family members successfully induced cell differentiation in various AML cell lines. Through gene expression profiling and differentiation marker-based CRISPR/Cas9 screening, we identified TRIB1, a complement of the COP1 ubiquitin ligase complex, as a functional FOXO downstream gene maintaining an undifferentiated status. TRIB1 is direct target of FOXO3 and the FOXO-binding cis-regulatory element in the TRIB1 promoter, referred to as the FOXO-responsive element in the TRIB1 promoter (FRE-T), played a critical role in differentiation blockade. Thus, we designed a DNA-binding pharmacological inhibitor of the FOXO-FRE-T interface using pyrrole-imidazole polyamides (PIPs) that specifically bind to FRE-T (FRE-PIPs). The FRE-PIPs conjugated to chlorambucil (FRE-chb) inhibited transcription of TRIB1, causing differentiation in various AML cell lines. FRE-chb suppressed the formation of colonies derived from AML cell lines but not from normal counterparts. Administration of FRE-chb inhibited tumor progression in vivo without remarkable adverse effects. In conclusion, targeting cis-regulatory elements of the FOXO family is a promising therapeutic strategy that induces AML cell differentiation.

Granulomatosis with polyangiitis presenting as multiple renal masses: A case report with MRI findings.

It is extremely rare for granulomatosis with polyangiitis to form masses in the kidneys. Magnetic resonance imaging findings of renal masses caused by this disease have been infrequently reported. In this study, we report a case of renal masses caused by granulomatosis with polyangiitis with different findings. While on steroid treatment for a recently diagnosed granulomatosis with polyangiitis, a man in his 60s underwent computed tomography for a hepatic dysfunction. Computed tomography showed incidental findings of a 40 mm × 35 mm mass in the left kidney and two 8 mm × 8 mm masses in the right kidney; all masses were hypovascular. On magnetic resonance imaging, the left renal mass showed a hyperintense signal with slightly hypointense signal rim on T2-weighted imaging. The left renal mass showed a strong hypointense signal where the mass abutted the renal capsule. On diffusion-weighted imaging, the left renal mass showed an isointense signal with a hyperintense signal rim. Both right renal masses showed an isointense signal with slightly hypointense signal rim on T2-weighted imaging and hyperintense signal on diffusion-weighted imaging. Suspecting renal masses caused by the disease, the patient was then treated with steroids and methotrexate. After 6 months of treatment, both right renal masses resolved; however, the left renal mass shrank but abnormal signal remained. Based on the treatment course, it is conceivable that the renal masses were caused by granulomatosis with polyangiitis.

Usefulness of peripherally inserted central catheter port system (PICC-PORT) implantation in the sitting position: a new technique for cases unsuitable for conventional implantation.

PURPOSE: Totally implantable central venous access port implantation is typically performed in the supine position. However, some patients cannot adopt the supine position due to severe pain and/or dyspnea. The present study evaluated the technical feasibility of peripherally inserted central catheter port system (PICC-PORT) implantation in the sitting position in such cases. MATERIALS AND METHODS: In the sitting position method, PICC-PORT implantation was performed with the patients seated on a videofluoroscopy chair positioned between the limbs of an angiographic C-arm and the operative upper arm positioned on an arm stand. From January 2019 to September 2021, eight patients underwent PICC-PORT implantations using this sitting method. We also evaluated 251 consecutive patients with conventional supine position PICC-PORT implantation as controls. Differences in technical success, procedure time and complications were retrospectively assessed between the two groups. RESULTS: Procedural success rates were 100% in both groups. Median procedure times in the sitting and conventional groups were 42 and 44 min, respectively. No complications were observed in the sitting group. There were no significant differences between the two groups in procedure time (p = 0.674) and complications (p = 1.000). CONCLUSION: Implantation of PICC-PORT in the sitting position is technically feasible and useful.

A RUNX-targeted gene switch-off approach modulates the BIRC5/PIF1-p21 pathway and reduces glioblastoma growth in mice.

Glioblastoma is the most common adult brain tumour, representing a high degree of malignancy. Transcription factors such as RUNX1 are believed to be involved in the malignancy of glioblastoma. RUNX1 functions as an oncogene or tumour suppressor gene with diverse target genes. Details of the effects of RUNX1 on the acquisition of malignancy in glioblastoma remain unclear. Here, we show that RUNX1 downregulates p21 by enhancing expressions of BIRC5 and PIF1, conferring anti-apoptotic properties on glioblastoma. A gene switch-off therapy using alkylating agent-conjugated pyrrole-imidazole polyamides, designed to fit the RUNX1 DNA groove, decreased expression levels of BIRC5 and PIF1 and induced apoptosis and cell cycle arrest via p21. The RUNX1-BIRC5/PIF1-p21 pathway appears to reflect refractory characteristics of glioblastoma and thus holds promise as a therapeutic target. RUNX gene switch-off therapy may represent a novel treatment for glioblastoma.

Targeting chemoresistance in Xp11.2 translocation renal cell carcinoma using a novel polyamide-chlorambucil conjugate.

Renal cell carcinoma with Xp11.2 translocation involving the TFE3 gene (TFE3-RCC) is a recently identified subset of RCC with unique morphology and clinical presentation. The chimeric PRCC-TFE3 protein produced by Xp11.2 translocation has been shown to transcriptionally activate its downstream target genes that play important roles in carcinogenesis and tumor development of TFE3-RCC. However, the underlying molecular mechanisms remain poorly understood. Here we show that in TFE3-RCC cells, PRCC-TFE3 controls heme oxygenase 1 (HMOX1) expression to confer chemoresistance. Inhibition of HMOX1 sensitized the PRCC-TFE3 expressing cells to genotoxic reagents. We screened for a novel chlorambucil-polyamide conjugate (Chb) to target PRCC-TFE3-dependent transcription, and identified Chb16 as a PRCC-TFE3-dependent transcriptional inhibitor of HMOX1 expression. Treatment of the patient-derived cancer cells with Chb16 exhibited senescence and growth arrest, and increased sensitivity of the TFE3-RCC cells to the genotoxic reagent etoposide. Thus, our data showed that the TFE3-RCC cells acquired chemoresistance through HMOX1 expression and that inhibition of HMOX1 by Chb16 may be an effective therapeutic strategy for TFE3-RCC.

Tumor Accumulation of PIP-Based KRAS Inhibitor KR12 Evaluated by the Use of a Simple, Versatile Chicken Egg Tumor Model.

BACKGROUND: The KRAS inhibitor KR12, based on pyrrole-imidazole polyamide (PIP), has been developed and shown to exhibit efficacy in mouse experiments. Because some PIP species exhibit tumor accumulation capability, we decided to evaluate whether the PIP portion of KR12 exhibits tumor accumulation. We employed the CAM assay that provides a simple method for tumor accumulation evaluation. METHODS: KR12 PIP was synthesized and conjugated to TAMRA to produce a fluorescently labeled reagent (KR12-TAMRA). This reagent was injected into a fertilized chicken egg that has been transplanted with human cancer cells. Distribution of the red fluorescence was examined by cutting out tumor as well as various organs from the embryo. RESULTS: The red fluorescence of KR12-TAMRA was found to overlap with the green fluorescence of the tumor formed with GFP-expressing cancer cells. We also observed nuclear localization of KR12-TAMRA. Treatment of KR12 that contained the alkylating agent CBI in the tumor-bearing chicken egg resulted in tumor growth inhibition. CONCLUSIONS: KR12 contains a PIP that has two key features: tumor accumulation and nuclear localization. KR12 conjugated with CBI exhibits inhibition of tumor growth in the CAM model.

Stent graft treatment for coronary sinus hemorrhage associated with esophageal cancer.

Hemorrhage arising from the coronary sinus is very rare and can be lethal. It has historically been treated surgically. The present patient had coronary sinus rupture secondary to esophageal cancer and an abscess in the pericardium. Due to her poor general status, this patient was contraindicated for surgery and underwent endovascular therapy. The hemorrhage was treated by stent graft deployment and the patient was temporarily discharged. Two months later, CT showed that the stent graft was occluded by thrombosis. The patient died without hemorrhage 2.5 months thereafter.

Distribution of scatter radiation by C-arm cone-beam computed tomography in angiographic suite: measurement of doses and effectiveness of protection devices.

Distribution of radiation by C-arm cone-beam computed tomography (CBCT) in the angiographic suite and effectiveness of protection devices were assessed. CBCT image of a human phantom was obtained by a rotation of 220 degrees during 8 seconds of exposure. One hundred and twelve dosimeters were placed at different positions around the beam entry site, and color maps of dose distributions were drawn for horizontal and vertical planes. The measurements showed the highest radiation dose over 600 µGy by a single CBCT image acquisition at a distance of 60 cm from the beam entry site and a height of 90 cm from the floor. The color maps demonstrated the dose distribution to be more intense at the bilateral directions of the phantom. With the use of a ceiling-mounted transparent lead-acryl screen and a table-suspended lead curtain, the doses were reduced by 45-92 % at a direction of 210 degrees and a distance of 120 cm.

A synthetic transcription factor pair mimic for precise recruitment of an epigenetic modifier to the targeted DNA locus.

We developed an epigenetically active, cooperative DNA binding transcription factor platform assisted by cucurbit[7]uril (CB7) host-guest modules. This new type of molecule termed ePIP-HoGu not only mimics the operation of transcription factors as a pair but also recruits the epigenetic modifier to a particular DNA locus.

Percutaneous Retrieval of a Misinserted Pigtail Catheter Straightener during Infra-Renal Abdominal Aortic Stenting: A Case Report.

Percutaneous retrieval of an intravascular foreign body is a minimally invasive technique. Using cone-beam computed tomography and the lateral grasp technique, we successfully retrieved a pigtail catheter straightener that had been misinserted into the right common iliac artery. Some examples of catheter straightener retrieval have been reported; however, it is important to take care not to accidentally insert a catheter straightener into a vessel via an angiographic sheath.

In vitro evaluation of radiopacity of contrast-loaded superabsorbent polymer microspheres (SAP-MS) with static imaging and flow model.

PURPOSE: To evaluate the radiopacity of contrast-loaded superabsorbent polymer microspheres (SAP-MS) under X-ray imaging. MATERIALS AND METHODS: SAP-MS were suspended in contrast material (iodixanol) and the diameter change was assessed. The diameter of contrast-loaded SAP-MS in saline was measured sequentially. Radiography of the contrast-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio and visibility by multiple reader scoring. Under digital subtraction angiography, contrast-loaded SAP-MS were injected into a flow model. The flow speed was 1-10 cm/s, and images were acquired at 1-7.5 frames per second using a pulse width of 10-85 ms. Images were assessed by multiple reader scoring. RESULTS: The diameter of SAP-MS increased to 4.0-5.0 times its original size for approximately 15 min. The diameter of contrast-loaded SAP-MS in saline further increased by 10-30% within several minutes and returned to the previous size. Radiopacity and visibility of contrast-loaded SAP-MS decreased in 30 min after mixing with saline. Visibility was better with slow flow speed and narrow pulse width. CONCLUSION: For effective observation, contrast-loaded SAP-MS should be kept in non-diluted contrast material until use. The conditions of slower flow and use of a narrow pulse width are recommended.

Polidocanol Sclerotherapy Combined with Transarterial Embolization Using n-Butyl Cyanoacrylate for Extracranial Arteriovenous Malformations.

PURPOSE: To assess the safety and effectiveness of polidocanol sclerotherapy combined with transarterial embolization using a liquid adhesive agent (n-butyl cyanoacrylate, NBCA) for treatment of extracranial arteriovenous malformations (AVMs). MATERIALS AND METHODS: Twenty-three patients with symptomatic AVMs in the head and neck (6), upper (7) and lower extremity (10) with a mean age of 42 years (range 4-74) treated with polidocanol sclerotherapy were retrospectively assessed. AVMs were classified according to the angiographic morphology of the nidus. There were 2 type I, 6 type II, 6 type IIIa and 9 type IIIb. Arterial embolization using NBCA was performed to reduce arterial flow before sclerotherapy. Polidocanol mixed with contrast material or carbon dioxide was delivered by percutaneous direct puncture. RESULTS: Treatment was successfully performed in all patients. In the mean follow-up period of 38 months, symptoms resolved or improved in 20/23 patients (87.0%). AVMs were devascularized 100% in 2 patients, 76-99% in 13, 50-75% in 7 and < 50% in 1. More than 50% devascularization was seen in 22 patients (95.6%). Two (8%) patients had complete remission, 17 (74%) had partial remission and 3 (13%) had no remission. There was no aggravation. Treatment was considered effective (complete and partial remission) in 20 patients (87.0%). Minor complications including localized arterial thrombosis (2) and spontaneously healing skin ulcer (1) were seen in 2 patients (8.7%). There were no major procedure-related complications. CONCLUSION: Polidocanol sclerotherapy combined with transarterial embolization using NBCA is safe and effective for treating extracranial AVMs with an acceptable risk of minor complications.

Nanochannel-Confined TAMRA-Polypyrrole Stained DNA Stretching by Varying the Ionic Strength from Micromolar to Millimolar Concentrations.

Large DNA molecules have been utilized as a model system to investigate polymer physics. However, DNA visualization via intercalating dyes has generated equivocal results due to dye-induced structural deformation, particularly unwanted unwinding of the double helix. Thus, the contour length increases and the persistence length changes so unpredictably that there has been a controversy. In this paper, we used TAMRA-polypyrrole to stain single DNA molecules. Since this staining did not change the contour length of B-form DNA, we utilized TAMRA-polypyrrole stained DNA as a tool to measure the persistence length by changing the ionic strength. Then, we investigated DNA stretching in nanochannels by varying the ionic strength from 0.06 mM to 47 mM to evaluate several polymer physics theories proposed by Odijk, de Gennes and recent papers to deal with these regimes.

Renal dysfunction after abdominal or thoracic endovascular aortic aneurysm repair: incidence and risk factors.

PURPOSE: To determine the incidence and risk factors of renal dysfunction after abdominal endovascular aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR). MATERIALS AND METHODS: The study consisted of 227 patients treated with EVAR and 90 with TEVAR for aortic aneurysms. Parameters, including patients' background factors, preoperative renal function, contrast dose and aortic wall irregularity on CT images were assessed in relation to postoperative renal dysfunction. RESULTS: Deterioration of renal function was observed in 33 of 218 patients (15.1%) after EVAR and in 7 of 79 (8.9%) patients after TEVAR. Hemodialysis was required in one patient after EVAR. In EVAR, renal dysfunction correlated with age (p = 0.034) and occlusion of accessory renal artery (p = 0.0001). In TEVAR, renal dysfunction correlated with age (p = 0.021), contrast dose (p = 0.042) and irregularity of the descending aortic wall (p = 0.023). In a multiple regression analysis, postoperative renal dysfunction was correlated with occlusion of accessory renal artery (p = 0.0003) after EVAR, and age (p = 0.02), contrast dose (p = 0.026) and irregularity of the descending aortic wall (p = 0.042) after TEVAR. CONCLUSION: Occlusion of accessory renal artery in EVAR, and age, contrast dose and irregularity of the descending aortic wall in TEVAR were considered to be predictors of postoperative renal dysfunction.

Uterine artery embolization by use of porous gelatin particles for symptomatic uterine leiomyomas: comparison with hand-cut gelatin sponge particles.

PURPOSE: To evaluate the results of uterine artery embolization (UAE) for symptomatic uterine leiomyoma by use of porous gelatin particles (PGP) in comparison with conventional hand-cut gelatin sponge particles. MATERIALS AND METHODS: One hundred and fifteen consecutive patients who had undergone UAE were retrospectively assessed. The first 64 patients were treated with hand-cut gelatin sponge and the last 51 with PGP. Extent of infarction, volume reduction of the dominant leiomyoma on magnetic resonance (MR) imaging, and change in symptoms were assessed. RESULTS: UAE was successfully performed for all patients. No major complications were observed. MR images one month after UAE showed that the mean extent of infarction of the dominant leiomyoma was 97 % for patients treated with PGP and 96 % for those treated with hand-cut gelatin sponge. Volume reductions of the dominant leiomyoma after 3, 6, 12, and 24 months were, respectively, 45, 56, 62, and 66 % for use of PGP and 45, 57, 63, and 68 % for use of hand-cut gelatin sponge. Symptoms including heavy menstrual bleeding, heavy menstrual pain, and abdominal heaviness had improved by 95-100 % at 12 months. There was no difference between the two groups. CONCLUSION: UAE with PGP is safe, and as effective as conventional gelatin sponge particles.

Non-enzymatic DNA cleavage reaction induced by 5-ethynyluracil in methylamine aqueous solution and application to DNA concatenation.

DNA can be concatenated by hybridization of DNA fragments with protruding single-stranded termini. DNA cleavage occurring at a nucleotide containing a DNA base analogue is a useful method to obtain DNA with designed protruding termini. Here, we report a novel non-enzymatic DNA cleavage reaction for DNA concatenation. We found that DNA is cleaved at a nucleotide containing 5-ethynyluracil in a methylamine aqueous solution to generate 5'-phosphorylated DNA fragment as a cleavage product. We demonstrated that the reaction can be applied to DNA concatenation of PCR-amplified DNA fragments. This novel non-enzymatic DNA cleavage reaction is a simple practical approach for DNA concatenation.

Ethanolamine oleate sclerotherapy combined with transarterial embolization using n-butyl cyanoacrylate for extracranial arteriovenous malformations.

PURPOSE: This study was designed to assess the safety and effectiveness of ethanolamine oleate (EO) sclerotherapy combined with transarterial embolization using a liquid adhesive agent (n-butyl cyanoacrylate, NBCA) for treatment of extracranial arteriovenous malformations (AVMs). METHODS: Twenty-four patients with symptomatic AVMs in the head and neck (n = 15), extremity (n = 5), and trunk (n = 4) with a mean age of 44 years (range, 18-78) treated with EO sclerotherapy were retrospectively assessed. AVMs were classified according to the angiographic morphology of the nidus. There were 7 type II (arteriolovenous fistulae), 6 type IIIa (arteriolovenulous fistulae with nondilated fistula), and 11 type IIIb (arteriolovenulous fistulae with dilated fistula). Transarterial embolization using NBCA was performed to reduce arterial flow before sclerotherapy. EO mixed with contrast material was delivered by percutaneous direct puncture or by catheterization into the draining vein under balloon occlusion. RESULTS: Three (13%) of 24 patients were cured, 17 (71%) had partial remission, and 4 (16%) no remission. Treatment was considered effective (cure and partial remission) in 20 patients (83%). Four patients (16%) experienced transient minor complications, including self-healing skin ulcer (n = 3) and localized deep venous thrombosis (n = 1). There were no major complications. CONCLUSIONS: EO sclerotherapy combined with transarterial embolization using NBCA is safe and effective for treating extracranial AVMs with an acceptable risk of minor complications.