Development of a novel microneedle platform for biomarker assessment of atopic dermatitis patients.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease whose pathogenesis, cause, and treatment have been extensively studied. The association of AD with Th2 cytokines is well known; therefore, the analysis of this association is crucial for the diagnosis and treatment of AD. This study aimed to present a new method for measuring protein biomarkers in patients with AD, before and after treatment, using minimally invasive microneedles. MATERIALS AND METHODS: First, hyaluronic acid-loaded microneedle patches (HA-MNs) for skin sample collection were fabricated. Next, after Institutional Review Board approval, 20 patients with AD were recruited and skin samples were taken before and after treatment using four different sampling techniques: (1) tape stripping, (2) hydrocolloid patches, (3) hollow microneedles, and (4) HA-MNs. Lastly, proteins were isolated from the collected samples, and AD-related biomarkers were analyzed by enzyme-linked immunosorbent assay. RESULTS: Proteins were successfully extracted from the skin samples collected by tape stripping, hydrocolloid patches, and HA-MNs, except hollow microneedles. Interleukin (IL)-4, IL-13, and interferon-γ were detected in the HA-MNs only. By comparing the biomarker level correlation before and after treatment and the improvement score of the patients, we observed a significant negative correlation between IL-4 and IL-13 with an improvement in AD symptoms. CONCLUSION: Overall, our results verified that HA-MNs can be used to effectively analyze protein levels of biomarkers from skin metabolites of patients with AD and can be applied to monitor the treatment progress of patients with AD in a minimally invasive manner.

Enhancing autophagy leads to increased cell death in radiation-treated cervical cancer cells.

This study was carried out to determine the effect of autophagy modulation in radiation treatment of cervical cancer cells. HeLa and CaSki cells were irradiated with γ-rays (2 Gy/min) after treatment with an autophagy inducer (rapamycin) and inhibitor (3-MA). Expression of LC3 and cell death in two cell preparations were examined. In addition, expression of Caspase-3 and PARP were examined after radiation alone and with autophagy inhibitor treatment. A notable increment of LC3 expression was detected after radiation in both cell lines. Cell viability was observed to decrease in 3-MA-treated cells compared to radiation alone, and even further in rapamycin-treated cells. Apoptosis was confirmed to occur later than autophagy in radiation treatment, and inhibition of autophagy derived a decrease in apoptosis. In conclusion, radiation-induced autophagy may be regulated by modulators, and autophagy augmentation yields an increase in cervical cancer cell death under radiation.Impact statementWhat is already known on this subject? Autophagy is known to contribute both to tumour cell survival and death against radiation therapy. The effect of induction or inhibition of radiation-induced autophagy on cervical cancer cell death is not clear.What the results of this study add? Cell viability was observed to decrease in 3-MA-treated cells compared to radiation alone, and even further in rapamycin-treated cells. Apoptosis occurred later than autophagy in radiation treatment, and inhibition of autophagy derived a decrease in apoptosis.What the implications are of these findings for clinical practice and/or further research? Our results suggest that radiation-induced autophagy may be regulated by modulators, and autophagy augmentation yields an increase in cervical cancer cell death under radiation.

How does long thoracolumbar realignment surgery of adult spinal kyphotic deformity affect lower extremity compensation? Using full body radiograph.

PURPOSE: By using full body radiograph, the aim of the current study was to elucidate the expected degree of lower extremity compensatory change after long thoracolumbar realignment surgery with adult spinal deformity patient who had normal or only mild osteoarthritis on lower extremities. METHODS: Two novel parameters were used for assessment of regional compensation of the lower extremity. The Pearson correlation test was used to assess the correlation of postoperative changes of lower extremity compensation with the other spinopelvic parameters. RESULTS: Overall, 113 spinal deformity patients (mean age was 54.5 years) were recruited and the average number of fused vertebrae was 13.3 ± 3.5. Except pelvic tilt (PT), postoperative sacrum-femur angle (SF) changes showed only moderate correlation with all angular spinopelvic parameters (r = 0.323-0.374; p < .001 to p = .001). Also C7 sagittal vertical axis showed no significant correlation with SF (p = .584-.621). However, postoperative changes of sagittal femur-tibia angle (SFT) reported strong correlation with all parameters evaluated (r = 0.455-0.586; p < .001 to p = .046). CONCLUSION: For adult spinal deformity patients who had normal or only mild osteoarthritis on the lower extremities underwent long thoracolumbar realignment surgery, the surgeon could expect improvement of compensatory change of the knee with correction of spinopelvic parameters. However, the degree of hip compensation improvement was relatively difficult to predict than that of the knee, except PT.

Effectiveness of adjuvant treatment for morcellated, International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma: A Korean multicenter study.

AIM: To evaluate the effectiveness of adjuvant treatment for morcellated, uterus-confined leiomyosarcoma in a multicenter setting. METHODS: We identified patients with International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma primarily treated with surgery between 2003 and 2016. Among them, patients who underwent one of the following morcellation methods were included: (i) power morcellation; (ii) intracorporeal morcellation using scalpels or electrocautery; and (iii) vaginal morcellation. Patients' survival outcomes were compared according to the implementation of adjuvant treatment. RESULTS: From 13 institutions, 55 patients were included; 31 for adjuvant treatment group and 24 for surgery only group. The clinicopathological characteristics including the mass size, morcellation methods, extent of surgery, and mitotic count were similar between the groups. In the adjuvant treatment group, 67.7%, 19.4% and 12.9% of patients received chemotherapy, chemoradiation and radiation, respectively. After a median follow-up of 50.5 months, the adjuvant treatment and surgery only groups showed similar overall survival (5-year rate, 92.0% vs 90.4%; P = 0.959). No significant difference in progression-free survival was observed between the two groups (3-year rate, 46.1% vs 78.2%; P = 0.069). On multivariate analyses, adjuvant treatment did not affect progression-free survival (adjusted HR, 2.138; 95% CI, 0.550-8.305; P = 0.273). The adjuvant treatment group showed a trend towards more common distant metastasis, compared to the surgery only group (25.8% vs 4.2%; P = 0.062). The incidences of pelvic, retroperitoneal, and abdominal recurrences were not different between the groups. CONCLUSION: Despite its frequent use in clinical practice, adjuvant treatment did not improve the survival outcomes of patients with morcellated, International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma.

Effects of Tegoprazan, a Novel Potassium-Competitive Acid Blocker, on Rat Models of Gastric Acid-Related Disease.

Tegoprazan, a novel potassium-competitive acid blocker (P-CAB), is a next-generation therapeutics developed for the treatment of acid-related gastrointestinal diseases such as gastroesophageal reflux disease (GERD) and peptic ulcers. In the present study, the in vitro and in vivo pharmacological properties of tegoprazan were compared with those of esomeprazole, a representative proton pump inhibitor. In vitro enzyme assays were performed using ion-leaky vesicles containing gastric H+/K+-ATPases isolated from pigs. The in vivo efficacies of tegoprazan were evaluated in rat models of GERD and peptic ulcer. Tegoprazan inhibited the activity of porcine H+/K+-ATPase with an IC50 value of 0.53 µM in a reversible manner, whereas esomeprazole showed weak and irreversible inhibition with an IC50 value of 42.52 µM. In a GERD model, tegoprazan showed dose-dependent efficacy in inhibiting esophageal injury and gastric acid secretion with an ED50 of 2.0 mg/kg, which was 15-fold more potent than that of esomeprazole. In peptic ulcer models, tegoprazan exhibited superior antiulcer activity compared with esomeprazole. The ED50 of tegoprazan in the naproxen-, ethanol-, and water-immersion restraint stress-induced peptic ulcer models were 0.1, 1.4, and 0.1 mg/kg, respectively. In the acetic acid-induced peptic ulcer model, the curative ratio of tegoprazan at 10 mg/kg was higher than that of esomeprazole at 30 mg/kg (44.2% vs. 32.7%, respectively), after 5 days of repeated oral administration. Thus, tegoprazan is a novel P-CAB that shows potent and reversible inhibition of gastric H+/K+-ATPase and may provide stronger efficacy compared with previous proton pump inhibitors.

Outcomes of non-high grade serous carcinoma after neoadjuvant chemotherapy for advanced-stage ovarian cancer: a Korean gynecologic oncology group study (OV 1708).

BACKGROUND: Outcomes of patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied, but there is limited information on the outcomes of patients with non-HGSC. This study aimed to evaluate the outcomes of NAC in non-HGSC patients with advanced-stage ovarian cancer. METHODS: We conducted a retrospective cohort study of patients who underwent NAC for advanced stage non-HGSC between 2002 and 2017 in 17 institutions. Demographics, surgical outcomes, and survival rates were evaluated according to histological subtypes. RESULTS: A total of 154 patients were included in this study, comprising 20 cases (13.0%) of mucinous adenocarcinoma, 31 cases (20.1%) of endometrioid adenocarcinoma, 28 (18.2%) cases of clear cell carcinoma, 29 (18.8%) cases of low-grade serous carcinoma and 12 cases (7.8%) of carcinosarcoma. Complete remission/partial remission after the third cycle of NAC was achieved in 100 (64.9%) patients and optimal debulking surgery (residual disease ≤1 cm) at interval debulking surgery was achieved in 103 (66.9%) patients. The most common reason for performing NAC was high tumor burden (n = 106, 68.8%). The median progression-free survival (PFS) was 14.3 months and median overall survival (OS) was 52.9 months. In multivariate analyses, mucinous and clear cell carcinoma were negative prognostic factors for both PFS (p = 0.007 and p = 0.017, respectively) and OS (p = 0.002 and p = 0.013, respectively). CONCLUSIONS: In this study, poor survival outcomes were observed in patients with mucinous and clear cell carcinoma undergoing NAC. Different treatment strategies are urgently required to improve survival outcomes for this disease subset.

Comparative efficacy and safety of intravenous ferric carboxymaltose and iron sucrose for the treatment of preoperative anemia in patients with menorrhagia: An open-label, multicenter, randomized study.

AIM: To compare ferric carboxymaltose (FCM) with iron sucrose (IS) for the effective and timely treatment of preoperative iron deficiency anemia (IDA) in women with menorrhagia. METHODS: This open-label, multicenter, two-arm study randomized patients to receive either a single dose of FCM or multiple doses of IS. The primary endpoint was the proportion of patients who achieved hemoglobin (Hb) levels ≥10 g/dL within 2 weeks after the first administration. Secondary endpoints included mean Hb levels, time to reach Hb ≥10 g/dL and quality of life (QoL). RESULTS: In total, 101 patients (FCM n = 52; IS n = 49) were randomized to the study treatments. FCM was as effective as IS in achieving Hb ≥10 g/dL within 2 weeks after the first administration (78.8% vs 72.3%). The time to reach Hb ≥10 g/dL was significantly shorter in the FCM group than in the IS group (7.7 days vs 10.5 days). Mean Hb levels were higher in the FCM-treated patients than in the IS-treated patients with borderline significance. QoL scores did not differ between the two groups. CONCLUSION: Ferric carboxymaltose is as effective as IS in correcting preoperative IDA among patients with menorrhagia. The added benefits of FCM over IS included significant rapid correction of IDA, replenishment of iron stores and reduced hospital visits.

Ultrathin Metal Crystals: Growth on Supported Graphene Surfaces and Applications.

Controlled nucleation and growth of metal clusters in metal deposition processes is a long-standing issue for thin-film-based electronic devices. When metal atoms are deposited on solid surfaces, unintended defects sites always lead to a heterogeneous nucleation, resulting in a spatially nonuniform nucleation with irregular growth rates for individual nuclei, resulting in a rough film that requires a thicker film to be deposited to reach the percolation threshold. In the present study, it is shown that substrate-supported graphene promotes the lateral 2D growth of metal atoms on the graphene. Transmission electron microscopy reveals that 2D metallic single crystals are grown epitaxially on supported graphene surfaces while a pristine graphene layer hardly yields any metal nucleation. A surface energy barrier calculation based on density functional theory predicts a suppression of diffusion of metal atoms on electronically perturbed graphene (supported graphene). 2D single Au crystals grown on supported graphene surfaces exhibit unusual near-infrared plasmonic resonance, and the unique 2D growth of metal crystals and self-healing nature of graphene lead to the formation of ultrathin, semitransparent, and biodegradable metallic thin films that could be utilized in various biomedical applications.

Single-Site Robot-Assisted Laparoscopic Staging Surgery for Presumed Clinically Early-Stage Ovarian Cancer.

STUDY OBJECTIVE: To present the demonstration of robotic-assisted laparoendoscopic single-site (R-LESS) staging surgery in presumed clinically early-stage ovarian cancer. DESIGN: A step-by-step presentation of the procedure using video (Canadian Task Force classification III). SETTING: A university hospital. PATIENT: A 29-year-old woman was referred from a local clinic for an 8 × 6 cm left ovarian tumor suggesting malignancy. Her serum cancer antigen 125 level was 1636 U/mL. There was no evidence of a metastatic tumor or lymph node enlargement on magnetic resonance imaging or positron emission tomographic/computed tomographic imaging. INTERVENTION: Under general anesthesia, a 2-cm vertical intraumbilical incision was made, and a Lap Single trocar (Sejong Medical, Ltd, Gyeonggi-do, South Korea) was applied. The entire abdominal cavity was clear without any seeding tumor or adhesion. We performed laparoendoscopic single-site left salpingo-oophorectomy. On frozen section, high-grade epithelial malignancy was diagnosed. We started R-LESS staging surgery with the Da Vinci Xi system (Intuitive Surgical, Inc, Sunnyvale, CA). Fenestrated bipolar forceps and a permanent cautery hook were introduced. Both pelvic and inferior mesenteric para-aortic lymphadenectomy was performed. The patient was tilted in a reverse Trendelenburg position while performing infracolic omentectomy. MAIN RESULTS: The total operation took 280 minutes, and the console time was 135 minutes. The estimated blood loss was 100 mL. The patient was discharged on the next day after surgery. Histopathologic evaluation revealed a poorly differentiated endometrioid carcinoma. A total of 15 pelvic lymph nodes and 7 para-aortic lymph nodes were retrived. Among them, 2 para-aortic lymph nodes showed malignancy. CONCLUSION: We could successfully perform R-LESS staging surgery for presumed clinically early-stage ovarian cancer without any complications.

Zinc induces apoptosis on cervical carcinoma cells by p53-dependent and -independent pathway.

OBJECTIVE: There is evidence that the mineral zinc is involved in the apoptotic cell death of various carcinoma cells. In this study, we aim to determine whether zinc in the form of CIZAR induces apoptosis in cervical carcinoma cells by increasing intracellular zinc concentration. STUDY DESIGN: CaSki and HeLa cervical carcinoma cells and HPV-16 DNA-transformed keratinocyte (CRL2404) were treated with different concentrations of CIZAR. The cell viability test was carried out, the intracellular level of zinc was determined, and apoptosis was confirmed by flow cytometry after propidium iodide (PI) staining and fluorescence microscopy under DAPI staining. The expression of cell-cycle regulators was analyzed by Western blot, including the knock down of p53 and expression of HPV E6 and E7 genes by RT-PCR. RESULTS: Intracellular zinc accumulation induced the down-regulation of E6/E7 proteins through targeting of the specific transcriptional factors in the upstream regulatory region. p53 was induced after CIZAR treatment and p53-dependent apoptosis did not occur after knock down by p53 siRNA. In cervical carcinoma cells, regardless of HPV-infection, CIZAR induces apoptosis by the activation of the p53-independent pathways through the up-regulation of p21waf1, the down-regulation of c-Myc, and by decreasing the Bcl-2/Bax ratio. CONCLUSIONS: CIZAR induces apoptosis not only through the restoration of p53/Rb-dependent pathways in HPV-positive cells, but also through the activation of p53/Rb-independent pathways and the mitochondrial death-signal pathway in cervical carcinoma cells regardless of HPV-infection.

Inhibition of ERK activity enhances the cytotoxic effect of peroxisome proliferator-activated receptor γ (PPARγ) agonists in HeLa cells.

In this study, we examined whether the peroxisome proliferator-activated receptor γ (PPARγ) agonists, ciglitazone (CGZ) and troglitazone (TGZ), induce cell death in human cervical cancer HeLa cells. The cells were treated with a range of CGZ or TGZ doses for 24 or 48 h. Low concentrations of CGZ (≤10 µM) or TGZ (≤20 µM) had no effect on cell viability whereas higher doses induced cell death in a time- and dose-dependent manner as evidenced by the detection of activated caspase-3 and PARP cleavage. Treatment with the PPARγ antagonist GW9662 followed by PPARγ agonists did not increase CGZ- or TGZ-induced cell death, indicating that PPARγ agonists induced HeLa cell death independently of PPARγ. Moreover, ERK1/2 activation was observed at a CGZ concentration of 25 µM and a TGZ concentration of 35 µM, both of which induced cell death. To elucidate the role of ERK1/2 activated by the two PPARγ agonists, the effect of U0126, an inhibitor of ERK1/2, on PPARγ-agonist-induced cell death was examined. Treatment with 10 or 20 µM U0126 followed by CGZ or TGZ induced the down-regulation of ERK1/2 activity and a decrease in Bcl-2 expression accompanied by the collapse of mitochondrial membrane potential, which in turn significantly enhanced CGZ- or TGZ-induced apoptotic cell death. Our results suggest that PPARγ agonists are capable of inducing apoptotic cell death in HeLa cells independently of PPARγ and that inhibition of ERK1/2 activity offers a strategy to enhance the cytotoxicity of PPARγ agonists in the treatment of cervical cancer.

Identification of large genomic rearrangement of BRCA1/2 in high risk patients in Korea.

BACKGROUND: While the majority of germline inactivating mutations in BRCA1/2 are small-scale mutations, large genomic rearrangements (LGRs) are also detected in a variable proportion of patients. However, routine genetic methods are incapable of detecting LGRs, and comprehensive genetic testing algorithm is necessary. METHODS: We performed multiplex ligation-dependent probe amplification assay for small-scale mutation negative patients at high-risk for LGR, based on previously published LGR risk criteria. The inclusion criteria for the high-risk subgroup were personal history of 1) early-onset breast cancer (diagnosed at ≤36 years); 2) two breast primaries; 3) breast cancer diagnosed at any age, with ≥1 close blood relatives (includes first-, second-, or third-degree) with breast and/or epithelial ovarian cancer; 4) both breast and epithelial ovarian cancer diagnosed at any age; and 5) epithelial ovarian cancer with ≥1 close blood relatives with breast and/or epithelial ovarian cancer. RESULTS: Two LGRs were identified. One was a heterozygous deletion of exon 19 and the other was a heterozygous duplication of exon 4-6. The prevalence of LGRs was 7% among Sanger-negative, high-risk patients, and accounted for 13% of all BRCA1 mutations and 2% of all patients. Moreover, LGRs reported in Korean patients, including our 2 newly identified cases, were found exclusively in families with at least one high-risk feature. CONCLUSIONS: Our result suggests that selective LGR screening for Sanger-negative, high-risk patients is necessary for Korean patients.

Comparison study of consecutive 100 cases of single port vs. multiport laparoscopic myomectomy; technical point of view.

We report our experience with single-port and multiple-port laparoscopic myomectomy with operative outcomes and surgical skills. Hundred consecutive patients underwent single-port laparoscopic myomectomy (SP-LM) and 69 multi-port laparoscopic myomectomy (MP-LM). The operative outcomes were compared between the two methods. All procedures were successfully completed without conversion to abdominal myomectomy. The mean maximum diameter of the largest myoma was 7.4 (5-13) vs. 6.8 (5-12) cm and the mean number of myomas was 1.7 vs. 1.6 in SP-LM and MP-LM group, respectively. Mean operative time was 134.2 vs. 122.9 min in SP-LM and MP-LM group (p = .109). We showed that SPL myomectomy is a safe and feasible technique compared to MPL myomectomy with respect to postoperative pain, mean operating time, mean estimated blood loss and length of stay. To improve suturing technique of SP-LM, the working instruments were placed external to the telescope with 'micro-triangulation'.

Excision of painful dorsal wrist ganglion by open or arthroscopic approach : a compariso n study.

Dorsal wrist ganglion can be removed through open or arthroscopic excision. The better method for relieving pain remains unknown. In this study, we addressed the following questions: (1) does open excision provide better pain relief than arthroscopic? (2) is there any difference in patient satisfaction, functional outcome, and re-operation rate? Forty-five patients with painful dorsal wrist ganglions underwent open or arthroscopic excision. Posterior interosseous neurectomy was performed during open excision. Clinical outcomes were assessed with a focus on pain relief. Patient satisfaction, recurrence, and reoperation due to residual pain were also assessed. The average pain scores improved significantly after both, open and arthroscopic excision. However, five patients who underwent arthroscopic excision reported the same or worse pain, whereas all patients who underwent open excision reported postoperative alleviation of pain. The recurrence rate was comparable. Patient satisfaction was better in those who underwent open excision. Reoperation was performed in four patients who had residual pain after arthroscopic excision. Both, open and arthroscopic methods can alleviate pain in patients with painful dorsal wrist ganglion. However, 20% of the patients who underwent arthroscopic excision reported residual or persistent pain.

Role of the focal adhesion protein TRIM15 in colon cancer development.

The tripartite motif containing (TRIM) proteins are a large family of proteins that have been implicated in many biological processes including cell differentiation, apoptosis, transcriptional regulation, and signaling pathways. Here, we show that TRIM15 co-localized to focal adhesions through homo-dimerization and significantly suppressed cell migration. Domain mapping analysis indicated that B-box2 and PRY domains were essential for TRIM15 localization to focal adhesions and inhibition of cell migration. Our protein-protein interaction screen of TRIM15 with the integrin adhesome identified several TRIM15 interacting proteins including coronin 1B, cortactin, filamin binding LIM protein1, and vasodilator-stimulated phosphoprotein, which are involved in actin cytoskeleton dynamics. TRIM15 expression was tissue-restricted and downregulated in colon cancer. Level of TRIM15 expression was associated with colon cancer cell migration, as well as both in vitro and in vivo tumor growth. These data provide novel insights into the role of TRIM15 as an additional component of the integrin adhesome, regulating cell migration, and suggest that TRIM15 may function as a tumor suppressor of colon cancer.

Incidence and Risk Factors of Lower Extremity Lymphedema After Gynecologic Surgery in Ovarian Cancer.

OBJECTIVE: There is no standard method to establish an early diagnosis of lower extremity lymphedema (LEL). Lower extremity lymphedema can be diagnosed by physical examination and laboratory tests when patients complain of typical clinical symptoms. The objective of this study was to investigate the incidence and risk factors of LEL in patients with ovarian cancer. METHODS: The medical records were reviewed retrospectively in patients with ovarian cancer treated at Seoul St. Mary's Hospital from January 2000 to July 2014. RESULTS: A total of 413 patients with epithelial ovarian cancer were analyzed. Forty-six patients (11.1%) developed LEL, and 67.4% of these patients had LEL within 1 year after surgery. The mean number of resected lymph nodes (LNs) was larger in patients with LEL (43.1 ± 16.7; range, 12-80) than in those without (32.3 ± 19.8; range, 0-99) (P < 0.0001). The number of resected LNs was significantly associated with the occurrence of LEL (odds ratio, 1.025; 95% confidence interval, 1.005-1.045; P < 0.05). CONCLUSION: A significant proportion of patients with ovarian cancer could develop LEL after surgery. This study suggests that the occurrence of LEL is associated with the number of resected LNs.

Methylation of Cervical Neoplastic Cells Infected With Human Papillomavirus 16.

OBJECTIVE: This study was conducted to evaluate the role of methylation of adenylate cyclase activating peptide 1 (ADCYAP1), paired box gene 1 (PAX1), cell adhesion molecule 1 (CADM1), and T-lymphocyte maturation-associated protein (MAL) during carcinogenesis. METHODS: We evaluated the methylation of 4 genes by using the cervical carcinoma cell lines (CaSki, SiHa, HeLa, and C33A) and cervical neoplastic cells from 56 subjects with human papillomavirus 16 (HPV16)-infected low-grade squamous intraepithelial lesions (LSILs), 50 subjects with HPV16-infected high-grade squamous intraepithelial lesions (HSILs), and 24 subjects with HPV16-infected invasive cervical cancer who attended Seoul St. Mary's Hospital. Methylation of the 4 genes was evaluated using quantitative bisulfate pyrosequencing. RESULTS: The ADCYAP1 promoter was hypermethylated in the 4 cell lines (CaSki, 97.40 ± 1.39; SiHa, 82.04 ± 17.02; HeLa, 96.14 ± 2.08; and C33A, 78 ± 10.18). PAX1 and CADM1 were hypermethylated in the HPV16/18-infected cell lines CaSki (PAX1, 91.18 ± 9.91; CADM1, 93.5 ± 7.33), SiHa (PAX1, 96.14 ± 2.08; CADM1, 93.15 ± 8.81), and HeLa (PAX1, 82.04 ± 17.02; CADM1, 92.43 ± 9.95). MAL was hypermethylated in the CaSki cell line (96.04 ± 4.74). Among human cervical neoplastic cells, the methylation indices of ADCYAP1 were 7.8 (95% confidence interval [95% CI], 7.0-8.6) in subjects with LSILs and 39.8 (95% CI, 29.0-54.7) in those with cervical cancer (P < 0.001); for PAX1, 7.2 (95% CI, 6.1-8.5) and 37.8 (95% CI, 27.1-52.7), respectively; for CADM1, 3.5 (95% CI, 3.0-4.0) and 17.7 (95% CI, 10.8-29.1), respectively; for MAL, 2.7 (95% CI, 2.5-3.0) and 13.0 (95% CI, 7.6-22.0), respectively (P < 0.001 for each). Immunohistochemical staining results were positive in the cytoplasm of subjects with low methylation of the 4 gene promoters; however, they were negative in the cytoplasm of those with hypermethylation of the 4 gene promoters. CONCLUSIONS: The results of this study suggest that the methylation of ADCYAP1, PAX1, CADM1, and MAL may be highly associated with the development of cervical cancer, and that gene expression can be suppressed by gene promoter hypermethylation.

Autoamputation of an ovarian mature cystic teratoma: a case report and a review of the literature.

BACKGROUND: Torsion is known to be the most frequent complication of ovarian teratomas. Torsion of the adnexa usually manifests with severe abdominal pain and is treated as an acute surgical emergency. However, it may be asymptomatic. Autoamputation of an ovary, along with other adnexal structures, due to previous torsion is extremely rare. CASE PRESENTATION: A parasitic ovarian teratoma that underwent torsion, autoamputation, and reimplantation was found incidentally during laparoendoscopic single-site surgery (LESS). The amputated tumor was located in the omentum of the right upper abdomen of a patient with concomitant torsion of a left ovarian teratoma. The right ovary and tube were absent even though she had no surgical history. This finding could be interpreted as an autoamputation of the adnexa due to torsion of a previous ovarian cyst arising from the right ovary. We removed all masses by LESS. CONCLUSIONS: Although both ultrasonography and computed tomography were performed preoperatively in our patient, the correct diagnosis of autoamputation and exact localization of the teratoma were extremely difficult. Physicians should consider the possibility of an autoamputated ovarian cyst even if preoperative radiography shows no calcification.

Multispectral autofluorescence imaging for detection of cervical lesions: A preclinical study.

AIM: The aim of this study was to develop a novel optical imaging system for detecting protoporphyrin IX (PpIX) autofluorescence, to prove that PpIX autofluorescence is as useful as 5-aminolevulinic acid (5-ALA)-induced fluorescence for detecting and localizing cervical cancer, and to monitor the change in PpIX autofluorescence or induced PpIX fluorescence before, during, and after photodynamic therapy (PDT). METHODS: TC-1 cells - highly tumorigenic cells immortalized using human papillomavirus type 16 proteins E6 and E7 - were subcutaneously grafted into the thighs of nude mice. The suspected tumor tissues were visualized using autofluorescence imaging and induced fluorescence imaging under 5-ALA administration. When the 5-ALA-induced PpIX was sufficiently accumulated in tumor tissues, PDT was performed using a 635-nm laser. We observed the change in fluorescence intensity during PDT. For 3 weeks after PDT, we monitored tumor remission by using white-light imaging and fluorescence imaging. RESULTS: The transplanted cells were visualized by PpIX autofluorescence, which was induced by heme synthesis. After 5-ALA administration, PpIX could be targeted by using PDT, which decreased PpIX autofluorescence. Photobleaching is useful for monitoring PDT dosimetry and for determining the photodynamic response to therapy. CONCLUSION: PpIX autofluorescence clearly differentiated the tumor from adjacent normal tissues. The results of PpIX autofluorescence imaging and 5-ALA-induced fluorescence imaging were identical. PpIX autofluorescence imaging is a simple and cost-effective cervical cancer screening method that could be performed during or after PDT to ensure effective treatment or remission as a change in fluorescence intensity can be observed in real time without a blinding effect.