Effect of music on colonoscopy performance: A propensity score-matched analysis.

BACKGROUND: Music has been used to reduce stress and improve task performance during medical therapy. AIM: To assess the effects of music on colonoscopy performance outcomes. METHODS: We retrospectively reviewed patients who underwent colonoscopy performed by four endoscopists with popular music. Colonoscopy performance outcomes, such as insertion time, adenoma detection rate (ADR), and polyp detection rate (PDR), were compared between the music and non-music groups. To reduce selection bias, propensity score matching was used. RESULTS: After one-to-one propensity score matching, 169 colonoscopies were selected from each group. No significant differences in insertion time (4.97 vs 5.17 min, P = 0.795) and ADR (39.1% vs 46.2%, P = 0.226) were found between the two groups. Subgroup analysis showed that the insertion time (3.6 vs 3.8 min, P = 0.852) and ADR (51.1% vs 44.7%, P = 0.488) did not significantly differ between the two groups in experts. However, in trainees, PDR (46.9% vs 66.7%, P = 0.016) and ADR (25.9% vs 47.6%, P = 0.006) were significantly lower in the music than in the non-music group. CONCLUSION: The current study found that listening to music during colonoscopy did not affect procedure performance. Moreover, it suggested that music may distract trainees from appropriately detecting adenomas and polyps.

The Specific Gravity-Free Method for the Isolation of Circulating Tumor KRAS Mutant DNA and Exosome in Colorectal Cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) and exosome have been widely researched in the field of medical technology and diagnosis platforms. The purpose of our study was to improve the capturing properties of ctDNA and exosome, which involved combining two beads using approaches that may provide a new method for cancer diagnoses. METHODS: We present a dual isolation system including a polydopamine (PDA)-silica-coated alginate bead for circulating tumor DNA (ctDNA) capture and an anti-CD63 immobilized bead for exosome capture. We examined the ctDNA mutation in pre-operative plasma samples obtained from 91 colorectal cancer (CRC) patients using a droplet digital PCR (ddPCR). RESULTS: The area under the curve (AUROC) of ctKRAS G12D mutation in the buffy coat was 0.718 (95% CI: 0.598-0.838; p = 0.001). Patients with CRC that had unmethylation of MLH1 and MSH2 showed significantly higher buffy coat ctKRAS G12D mutations, ascites ctKRAS G12D mutations, miR-31-5, and mixed scores than the patients with a methylation of MLH1 and MSH2. CONCLUSION: Our proposed alginate bead using the specific gravity-free method suggests that the screening of mutated ctKRAS DNA and miR-31-5 by liquid biopsy aids in identifying the patients, predicting a primary tumor, and monitoring in the early detection of a tumor.

Use of 3D Human Liver Organoids to Predict Drug-Induced Phospholipidosis.

Drug-induced phospholipidosis (PL) is a storage disorder caused by the formation of phospholipid-drug complexes in lysosomes. Because of the diversity of PL between species, human cell-based assays have been used to predict drug-induced PL in humans. We established three-dimensional (3D) human liver organoids as described previously and investigated their liver characteristics through multiple analyses. Drug-induced PL was initiated in these organoids and in monolayer HepG2 cultures, and cellular changes were systemically examined. Organoids that underwent differentiation showed characteristics of hepatocytes rather than HepG2 cells. The organoids also survived under PL-inducing drug conditions for 48 h and maintained a more stable albumin secretion level than the HepG2 cells. More cytoplasmic vacuoles were observed in organoids and HepG2 cells treated with more potent PL-induced drugs, but to a greater extent in organoids than in HepG2 cells. Lysosome-associated membrane protein 2, a marker of lysosome membranes, showed a stronger immunohistochemical signal in the organoids. PL-distinctive lamellar bodies were observed only in amiodarone-treated organoids by transmission electron microscopy. Human liver organoids are thus more sensitive to drug-induced PL and less affected by cytotoxicity than HepG2 cells. Since PL is a chronic condition, these results indicate that organoids better reflect metabolite-mediated hepatotoxicity in vivo and could be a valuable system for evaluating the phospholipidogenic effects of different compounds during drug development.

Epithelioid sarcoma associated with neurofibromatosis type I.

In general, patients with neurofibromatosis type I have a higher risk than those with other types of neurofibromatosis of developing soft-tissue sarcomas related to the nervous system. We here present a 42-year-old man with neurofibromatosis type I who developed a protruding mass over only 2 weeks. The histopathological diagnosis was epithelioid sarcoma. Epithelioid sarcomas are rare and, to the best of our knowledge, no epithelioid sarcomas have been reported in patients with neurofibromatosis type I. Radical excision of the primary lesion was performed and postoperative radiotherapy and chemotherapy administered, as is recommended for epithelioid sarcoma. Our case emphasizes that patients with neurofibromatosis type I may develop malignant tumors.

ABL001, a Bispecific Antibody Targeting VEGF and DLL4, with Chemotherapy, Synergistically Inhibits Tumor Progression in Xenograft Models.

Delta-like-ligand 4 (DLL4) is a promising target to augment the effects of VEGF inhibitors. A simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways leads to more potent anti-cancer effects by synergistic anti-angiogenic mechanisms in xenograft models. A bispecific antibody targeting VEGF and DLL4 (ABL001/NOV1501/TR009) demonstrates more potent in vitro and in vivo biological activity compared to VEGF or DLL4 targeting monoclonal antibodies alone and is currently being evaluated in a phase 1 clinical study of heavy chemotherapy or targeted therapy pre-treated cancer patients (ClinicalTrials.gov Identifier: NCT03292783). However, the effects of a combination of ABL001 and chemotherapy on tumor vessels and tumors are not known. Hence, the effects of ABL001, with or without paclitaxel and irinotecan were evaluated in human gastric or colon cancer xenograft models. The combination treatment synergistically inhibited tumor progression compared to each monotherapy. More tumor vessel regression and apoptotic tumor cell induction were observed in tumors treated with the combination therapy, which might be due to tumor vessel normalization. Overall, these findings suggest that the combination therapy of ABL001 with paclitaxel or irinotecan would be a better clinical strategy for the treatment of cancer patients.

Subretinal transplantation of human embryonic stem cell-derived retinal pigment epithelium (MA09-hRPE): A safety and tolerability evaluation in minipigs.

This study aimed to determine the safety and tolerability of the subretinal injection of hESC-derived RPE cells at higher doses than the established clinical dose (5 × 104 cells/150 µL) by using minipigs. The hESC-derived RPE cells (60 or 120 × 104 cells/150 µL) were injected in subretinal region, and minipigs were sacrificed at Weeks 4, 8, and 12 post-surgery. Time-course examination was performed by using fundus photography, optical coherence tomography (OCT), histopathology, and fluorescence in situ hybridization (FISH). After surgery, retinal bleb and pigmentation were seen and retinal bleb became smaller gradually. In histopathology, cell clusters consisting of a uniform population of the round to oval cells were seen at the subretinal injection site. In immunohistochemistry, most of the cells were positive for anti-CD3 and CD45 antibodies but negative for anti-human nuclei antibody; transplanted cells were not detectable by DNA probe in FISH assay. Cell clusters were thought to be a host immune response to trauma or transplanted cells. There were no other changes related to subretinal RPE cell injection. These results suggested that subretinal injection of hESC-derived RPE cells (60 and 120 × 104 cells/150 µL) in minipigs is well-tolerated and safe.

Malignant melanoma on a thermal burn scar.

Chronic burn scars often cause various skin malignancies at rates of up to 2%. These lesions are usually squamous cell carcinomas, but rarely, malignant melanoma is reported. We report a 67-year-old male with a malignant melanoma on a burn scar with regional metastasis. This patient presented an ulcerative lesion only in 2 weeks. After histopathological diagnosis, we performed only palliative surgery on patient's demand, and followed up the subsequent deterioration course. Our case reemphasizes the need for rapid diagnosis and treatment when suspect lesions are present on chronic burn scar. Also, physician should be in mind and inform the patient about malignant melanoma and its aggressive course.

Nasal Elongation with Septal Half Extension Graft: Modification of Conventional Septal Extension Graft Using Minimal Septal Cartilage.

BACKGROUND: In Asian rhinoplasty, a septal extension graft can be used for both tip projection and derotation of the alar cartilage. However, patients often do not have enough harvestable septal cartilage to create the septal extension graft. We therefore devised a method with which to fix the derotated alar cartilage with a small amount of septal cartilage. METHODS: From January 2012 to December 2016, 23 patients underwent short nose correction with a septal half extension graft made of septal cartilage and were postoperatively monitored for at least 6 months. The alar cartilage was completely separated from the adjacent structures, especially the scroll area and hinge complex, for caudal derotation. The septal half extension graft was then harvested from the septal cartilage and secured to the caudal septum and the lateral crura of the alar cartilage. Photographs of the patients were compared immediately before surgery and 1 year after surgery. RESULTS: Of the 23 patients, 21 (91%) had satisfactory results without short nose recurrence. Two (9%) patients developed recurrence: undercorrection and poor tip projection in one patient each. Aesthetic assessment of short nose correction was performed by comparing the columellar labial angle before and after surgery. Our method reduced the columellar labial angle by 6.2% (paired t test, p < 0.05, t = 31.698). CONCLUSION: In patients who cannot undergo conventional septal extension graft due to insufficient amounts of septal cartilage, the septal half extension graft could be a promising alternative technique for short nose correction with minimal septal cartilage harvesting. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Development of a Mouse Model of Prostate Cancer Using the Sleeping Beauty Transposon and Electroporation.

The Sleeping Beauty (SB) transposon system is non-viral and uses insertional mutagenesis, resulting in the permanent expression of transferred genes. Although the SB transposon is a useful method for establishing a mouse tumor model, there has been difficulty in using this method to generate tumors in the prostate. In the present study, electroporation was used to enhance the transfection efficiency of the SB transposon. To generate tumors, three constructs (a c-Myc expression cassette, a HRAS (HRas proto-oncogene, GTPase) expression cassette and a shRNA against p53) contained within the SB transposon plasmids were directly injected into the prostate. Electroporation was conducted on the injection site after the injection of the DNA plasmid. Following the tumorigenesis, the tumors were monitored by animal PET imaging and identified by gross observation. After this, the tumors were characterized by using histological and immunohistochemical techniques. The expression of the targeted genes was analyzed by Real-Time qRT-PCR. All mice subjected to the injection were found to have prostate tumors, which was supported by PSA immunohistochemistry. To our knowledge, this is the first demonstration of tumor induction in the mouse prostate using the electroporation-enhanced SB transposon system in combination with c-Myc, HRAS and p53. This model serves as a valuable resource for the future development of SB-induced mouse models of cancer.

EZH2 Expression in Naturally Occurring Canine Tumors.

Enhancer of zeste homolog 2 (EZH2) shows upregulated expression in tumors and is an important driver of tumor development and progression. However, the mechanism underlying the mediation of tumor aggressiveness by EZH2 remains unclear. We here investigated the levels of EZH2 in various normal and tumorous dog tissues and compared these patterns with those of the corresponding human tissues. Immunohistochemical analysis showed positive staining for EZH2 in 76 of 82 cases of canine tumors, whereas low or negligible staining occurred in normal tissues and other canine tumors, including hepatocellular adenoma and lipoma. In particular, canine lymphoma, melanoma, basal cell tumors, squamous cell carcinoma, and prostate cancer all show EZH2 overexpression, as do their human counterparts. Given the similarities of spontaneous canine tumors to human cancers, we believe that these canine tumors can be used as animal models in future research and clinical trials in the development of EZH2 inhibitors.

Efficacy of HL036 versus Cyclosporine A in the Treatment of Naturally Occurring Canine Keratoconjunctivitis Sicca.

PURPOSES: To (i) evaluate the efficacy and safety of HL036, a tumor-necrosis factor (TNF)-α-blocking protein, in the treatment of naturally occurring canine keratoconjunctivitis sicca (KCS) and (ii) compare these features with those of 1% cyclosporine A (CsA). MATERIALS AND METHODS: Dogs (n = 29) diagnosed with KCS were randomly assigned to receive one drop topical aqueous HL036 (0.2, 1, or 5 mg/mL) or 1% CsA in the affected eye(s) at 12-h intervals for 42 days. Schirmer's tear test (STT), fluorescein corneal staining (FCS), and clinical-sign scores were evaluated prior to application (day-0) and on days 14, 28, and 42 post-treatment. Of the 29 dogs enrolled, 19 (65.5%) received HL036 (HL036 group) and 10 (34.5%) received 1% CsA (CsA group). A linear mixed-effects model analysis was performed to determine score differences between groups and over time. RESULTS: After treatment, clinical-sign scores and STT values had significantly improved compared with baseline levels in dogs of both treatment groups. Decreases in total clinical-sign scores for the HL036-group were greater than those of 1% CsA group. No severe adverse reactions were noted in either group. CONCLUSIONS: Our findings suggest that topical aqueous HL036 is well-tolerated and more effective than 1% CsA for treating naturally occurring canine KCS.

New anthropometric data for preoperative planning in orbital wall fracture treatment: the use of eyelid drooping.

BACKGROUND: The presence of enophthalmos is an important determinant in the decision of orbital wall fracture surgery. We proposed eyelid drooping as a new anthropometric diagnostic measure and analyzed whether eyelid drooping is associated with enophthalmos. METHODS: This retrospective study was performed from January 2014 to December 2016. A total of 75 patients with blowout fractures were studied. One experimenter measured the degree of enophthalmos using a Hertel exophthalmometer at 1 week after trauma and at 3 months after surgery. The height change of the upper eyelid was measured using the marginal reflex distance (MRD) on both sides, and the degree of eyelid drooping was calculated by comparing the two lengths. We analyzed statistically the correlation between enophthalmos and eyelid drooping. RESULTS: We found a highly significant correlation between the degree of enophthalmos and the reduction rate of MRD (RRM, as an indicator of eyelid drooping) at 1 week after trauma (r = 0.845). Approximately 2.0 mm of enophthalmos was associated with a 30.8% reduction in MRD on the affected side as compared with the normal side. At 3 months after surgery, patients showed improved eyelid appearance, with a moderate association between enophthalmos and RRM. CONCLUSION: We demonstrated that the degree of enophthalmos, measured using an exophthalmometer, is associated with a change in the height of the upper eyelid. Thus, upper eyelid drooping can be used as another indicator for orbital wall fracture surgery. Compared with conventional methods, measurements of eyelid drooping are easy to perform, offering a great advantage and understanding to the patient.

Renal oncocytoma in a cat with chronic renal failure.

CASE SUMMARY: A 9-year-old male neutered domestic shorthair cat presented with anorexia. Ultrasonography showed an irregularly shaped hypoechoic mass in the cranial pole of the right kidney. Ultrasound-guided fine-needle aspiration of the renal mass was performed. Cytology revealed moderate cellularity smears composed of epithelial cell clusters, which consisted of an exclusive population of oncocytic cells seen in sheets and papillary clusters along with abundant single cells. A moderate-to-abundant amount of densely stained granular cytoplasm with round nuclei and indistinct nucleoli was seen. The cytological diagnosis was renal oncocytic neoplasm. CT and surgical resection revealed a firm tan mass in the right kidney. A final diagnosis of renal oncocytoma was made on the basis of histology, immunohistochemical staining profile (positive for cytokeratin, and negative for chromogranin A, neuron-specific enolase and vimentin) of neoplastic cells, together with the electronic microscopy results. RELEVANCE AND NOVEL INFORMATION: We believe that this is the first report of the cytological features of feline renal oncocytoma.

Significance of EZH2 expression in canine mammary tumors.

BACKGROUND: Current studies report that aberrations in epigenetic regulators or chromatin modifications are related to tumor development and maintenance. EZH2 (Enhancer of zeste homolog 2) is one of the catalytic subunits of Polycomb repressive complex 2, a crucial epigenetic regulator. EZH2 has a master regulatory function in such processes as cell proliferation, stem cell differentiation, and early embryogenesis. In humans, EZH2 is linked to oncogenic function in several carcinomas, including breast cancer, and dysregulation of EZH2 has been particularly associated with loss of differentiation and the development of poorly differentiated breast cancer. In our present study, we were interested in determining whether EZH2 is increased in canine mammary tumors, which show similarities to human breast cancer. RESULTS: Investigation of the expression of EZH2 in canine mammary tumors revealed that EZH2 protein was overexpressed in canine mammary carcinomas, as in human breast cancer. In addition, the immunohistochemical expression level of EZH2 was associated with the degree of malignancy in canine mammary carcinoma. This is the first report to describe EZH2 expression in canine mammary tumors. CONCLUSIONS: Because the expression of EZH2 was similar in canine mammary carcinoma and human breast cancer, spontaneous canine mammary tumors may be a suitable model for studying EZH2 and treatment development.

A Straightforward Method of Predicting Enophthalmos in Blowout Fractures Using Enophthalmos Estimate Line.

PURPOSE: Measuring the change in orbital volume may help to predict enophthalmos, but it is time consuming and difficult to apply. We devised a new and straightforward method with which to estimate the degree of enophthalmos. MATERIALS AND METHODS: This retrospective cohort study was performed from January 2013 to December 2015. Patients who underwent initial computed tomography (CT) examination and surgical reconstruction in our hospital were selected. An imaginary line connecting the edges of the bony defects (defect line) was drawn on 2-dimensional CT images. The distance from the defect line to the farthest fracture segment or soft tissue was defined as the length of the enophthalmos estimate line. The length of this line was a predictor variable, and the degree of enophthalmos at 1 week after the injury was an outcome variable. Age, gender, and type of injury are other variables that may affect the results. We statistically analyzed each variable using SPSS software (IBM, Armonk, NY). RESULTS: Of the patients, 22 had isolated inferior wall fractures, 14 had isolated medial wall fractures, and 17 had inferomedial wall fractures. There was high correlation between the length of the enophthalmos estimate line and the degree of enophthalmos in patients with isolated inferior fractures, medial wall fractures, and inferomedial wall fractures with internal orbital buttress fractures (Pearson correlation coefficient [r] = 0.783, r = 0.806, and r = 0.820, respectively). Approximately 2.0 mm of enophthalmos was associated with 9.3- and 10.0-mm enophthalmos estimate lines in patients with isolated inferior wall fractures and medial wall fractures, respectively. CONCLUSIONS: The most important advantages of our method are its simplicity, convenience, and swiftness. Using only 2-dimensional CT images, we identified the correlation between the degree of orbital wall fracture and enophthalmos and calculated the predicted value of enophthalmos. This technique is expected to provide useful information to clinicians and patients to determine if an operation is needed.