Risk of Ankylosing Spondylitis in Patients With Endometriosis: A Population-Based Retrospective Cohort Study.

Objectives: Previous research has shown a possible relationship between endometriosis and autoimmune diseases. However, the relationship between endometriosis and ankylosing spondylitis (AS) is lacking. Therefore, we intended to find possible associations between endometriosis and AS using ICD-9 coding data in a population-based retrospective cohort study in Taiwan. Method: Data for this retrospective cohort study were collected from the Taiwan National Health Insurance Research Database (NHIRD) between 2000-2012. We collected 13,145 patients with endometriosis and a 78,870 non-endometriosis comparison cohort. Diagnoses of endometriosis and AS were defined by the International Classification of Diseases-9 (ICD-9-CM) code for at least 3 outpatients or 1 hospitalization. Propensity score matching by comorbidities, corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) usage were done for baseline comparability. Cox proportional hazard models were used to evaluate crude and adjusted hazard ratios. Results: The cumulative incidence of AS was higher in patients with endometriosis compared to the non-endometriosis comparison cohort (log-rank test, p = 0.015). The adjusted hazard ratio (aHR) of incidental AS in patients with endometriosis was 1.61 (95% CI = 1.11 to 2.35) in comparison to the non-endometriosis comparison cohort. An increased risk of AS was also observed in subjects with major depressive disorder (aHR = 5.05, 95% CI = 1.85 to 13.78). Stratified analyses of age subgroups showed consistent results. NSAID users had a lower risk of AS than NSAID non-users (aHR 4.57 vs 1.35, p for interaction = 0.031). Conclusions: In this retrospective population-based cohort study, we found a higher risk of AS in patients with endometriosis. We suggest that clinicians should pay attention to the occurrence of AS in patients with endometriosis.

Reciprocal Regulation Between Indoleamine 2,3-Dioxigenase 1 and Notch1 Involved in Radiation Response of Cervical Cancer Stem Cells.

Cervical cancer is the fourth most common cancer in women around the world. Cancer stem cells (CSCs) are responsible for cancer initiation, as well as resistance to radiation therapy, and are considered as the effective target of cancer therapy. Indoleamine 2,3-dioxygenase 1 (IDO1) mediates tryptophan metabolism and T cell suppression, but the immune-independent function of IDO1 in cancer behavior is not fully understood. Using tumorsphere cultivation for enriched CSCs, we firstly found that IDO1 was increased in HeLa and SiHa cervical cancer cells and in these two cell lines after radiation treatment. The radiosensitivity of HeLa and SiHa tumorsphere cells was increased after the inhibition of IDO1 through RNA interference or by the treatment of INCB-024360, an IDO1 inhibitor. With the treatment of kynurenine, the first breakdown product of the IDO1-mediated tryptophan metabolism, the radiosensitivity of HeLa and SiHa cells decreased. The inhibition of Notch1 by shRNA downregulated IDO1 expression in cervical CSCs and the binding of the intracellular domain of Notch (NICD) on the IDO1 promoter was reduced by Ro-4929097, a γ-secretase inhibitor. Moreover, the knockdown of IDO1 also decreased NICD expression in cervical CSCs, which was correlated with the reduced binding of aryl hydrocarbon receptor nuclear translocator to Notch1 promoter. In vivo treatment of INCB-0234360 sensitized SiHa xenograft tumors to radiation treatment in nude mice through increased DNA damage. Furthermore, kynurenine increased the tumorsphere formation capability and the expression of cancer stemness genes including Oct4 and Sox2. Our data provide a reciprocal regulation mechanism between IDO1 and Notch1 expression in cervical cancer cells and suggest that the IDO1 inhibitors may potentially be used as radiosensitizers.

Synthesis of Polymeric Janus Superstructures via a Facile Synthesis Method.

Polymeric Janus particles can be exploited for a myriad of applications. Through the understanding of interfacial tensions, theragnostic agents such as drugs or nanomaterials can be successfully encapsulated into Janus particles without losing their anisotropic structure. In this work, it is reported that how Janus superstructures, as a further extension of the Janus morphology, can be obtained by blending other synthesis parameters into the solvent emulsion process, while adhering to the requirements of the Harkin's spreading coefficient (HSC) theory. Designing such unique structures for drug delivery can provide a broader range of possibilities and applications beyond conventional Janus particles.

Local experience with radiosurgery for vestibular schwannomas and recommendations for management.

INTRODUCTION: There are many treatment options for vestibular schwannomas (VSs), including radiosurgery. Previous studies have shown good outcomes for smaller tumours. We report the results of a seven-year cohort of patients with VS who were treated at our centre using a linear accelerator-based stereotactic radiosurgery system. METHODS: We retrospectively reviewed the case notes and magnetic resonance (MR) images of patients with VS treated with radiosurgery. Treatment was administered as either a single 13 Gy session or 25 Gy in five sessions. At our centre, only larger or higher Koos grade VSs, were routinely treated with hypofractionated radiosurgery. Tumour response and hearing were assessed using RECIST criteria and Gardner-Robertson scale, respectively. Other toxicities were assessed using physical examination and history-taking. Freedom from radiological progression was estimated with the Kaplan-Meier method. RESULTS: 46 patients received single-fraction radiosurgery and 31 received hypofractionated radiosurgery. Median follow-up duration was 40.6 months. 29 patients had prior surgery to remove the tumour (median size 1.68 cm3). One patient who had symptomatic increase in tumour size (> 20% in largest diameter) was treated conservatively and subsequently showed stable disease on MR imaging. Progression-free survival was 98.7%. Another patient had symptomatic oedema requiring ventriculoperitoneal shunt insertion. 11 patients had serviceable hearing before radiotherapy and 72.7% of them retained useful hearing (20.1 dB mean decline in pure tone average). Facial and trigeminal nerve functions and sense of equilibrium were preserved in > 90% of patients. CONCLUSION: Radiosurgery is effective and safe for small VSs or as an adjunct therapy after microsurgery.

Intravenous leiomyomatosis of the uterus: A clinicopathological analysis of nine cases and literature review.

OBJECTIVE: Intravenous/intravascular leiomyomatosis is characterized by intravenous proliferation of a histologically benign smooth muscle cell tumor mass that is non-tissue-invasive. Although benign, intravenous leiomyomatosis may cause remarkable systematic complications, presents significant diagnostic difficulties, and also is characterized by a relatively increased possibility of recurrence. We determine patients' characteristics, and recurrence and treatment of intravenous leiomyomatosis. MATERIALS AND METHODS: Prognostic factors are analyzed with univariate analysis. Differences in categorical data are evaluated by the X2 test. A P value below 0.05 is regarded as indicating a significant difference. RESULTS: The data results accord with the widely held view that complete excision of intravenous leiomyomata achieves favorable prognoses regarding remission. The efficacy of using Gonadotropin releasing hormone agonists to prevent growth or recurrence of tumors in unresected or incompletely resected intravenous leiomyomatosis foci. CONCLUSION: If complete surgical resection is not possible, partial resection followed by hormone therapy using gonadotropin-releasing hormone agonists is recommended, which in this study achieved the same favorable prognosis with regard to remission.

The expression of ribonucleotide reductase M2 in the carcinogenesis of uterine cervix and its relationship with clinicopathological characteristics and prognosis of cancer patients.

BACKGROUND: To investigate the implication of ribonucleotide reductase M2 (RRM2) in the carcinogenesis of uterine cervix and its relationship with clinicopathological characteristics and prognosis of cancer patients. METHODOLOGY AND PRINCIPAL FINDINGS: The impact of RRM2 on cell viability was investigated in SiHa cervical cancer cells after RRM2 knockdown and the addition of cisplatin, which induces inter- and intra-strand DNA crosslinks. RRM2 immunoreactivity was evaluated by semi-quantitative H score among 29 normal, 30 low-grade dysplasia, 30 high-grade dysplasia and 103 invasive cancer tissue specimens of the uterine cervix, using tissue microarrays. RRM2 was then correlated with the clinicopathological variables of cervical cancer and patient survival. A greater toxic effect on cell viability using cisplatin was reflected by the greater reduction in RRM2 protein expression in SiHa cells. The RRM2 expression in cancer tissues was higher than that in high-grade dysplasia, low-grade dysplasia or normal cervical tissues. RRM2 upregulation was correlated with deep stromal invasion, large tumors and parametrial invasion and predicted poor survival. CONCLUSIONS: RRM2 is a new molecular marker for the diagnosis and clinical outcomes of cervical cancer. It is involved in cervical carcinogenesis and predicts poor survival, and may be a potential therapeutic target including in cisplatin treatment.