The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identifi ed Janus kinase 3 (JAK3) somatic-activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Further validation of the prevalence of JAK3 mutations was determined by Sanger sequencing and high-resolution melt (HRM) analysis in an additional 61 cases. In total, 23 of 65 (35.4%) cases harbored JAK3 mutations. Functional characterization of the JAK3 mutations support its involvement in cytokine-independent JAK/ STAT constitutive activation leading to increased cell growth. Moreover, treatment of both JAK3-mutant and wild-type NKTCL cell lines with a novel pan-JAK inhibitor, CP-690550, resulted in dose-dependent reduction of phosphorylated STAT5, reduced cell viability, and increased apoptosis. Hence, targeting the deregulated JAK/STAT pathway could be a promising therapy for patients with NKTCLs. SIGNIFICANCE:Gene mutations causing NKTCL have not been fully identifi ed. Through exome sequencing, we identifi ed activating mutations of JAK3 that may play a signifi cant role in the pathogenesis of NKTCLs. Our fi ndings have important implications for the management of patients with NKTCLs.Cancer Discov; 2(7); 591-7.

No abstract

Extra-nodal NK/T-cell lymphoma was associated with a poorer prognosis compared with PTCL and is likely to comprise two distinct variants with different clinical behavior and prognosis.

No abstract

ObjectiveSynchronous occurrence of endometrial and ovarian tumors is uncommon, and they affect less than 10% of women with endometrial or ovarian cancers. The aim of this study is to describe the epidemiological and clinical factors; and survival outcomes of women with these cancers.MethodsThis is a retrospective cohort study in a large tertiary institution in Singapore. The sample consists of women with endometrial and epithelial ovarian cancers followed up over a period of 10 years from 2000 to 2009. The epidemiological and clinical factors include age at diagnosis, histology types, grade and stage of disease.ResultsA total of 75 patients with synchronous ovarian and endometrial cancers were identified. However, only 46 patients met the inclusion criteria. The median follow-up was 74 months. The incidence rate for synchronous cancer is 8.7% of all epithelial ovarian cancers and 4.9% of all endometrial cancers diagnosed over this time frame. Mean age at diagnosis was 47.3 years old. The most common presenting symptom was abnormal uterine bleeding (36.9%) and 73.9% had endometrioid histology for both endometrial and ovarian cancers. The majority of the women (78%) presented were at early stages of 1 and 2. There were 6 (13.6%) cases of recurrence and the 5 year cumulative survival rate was at 84%.ConclusionIn our cohort, we found that majority of women afflicted with synchronous cancer of the endometrium and ovary were younger at age of diagnosis, had early stage of cancer and good survival.

Objectives: This study aimed to determine which factors contribute to frequent visits at the emergency department (ED) and what proportion were inappropriate in comparison with nonfrequent visits.Methods: This study was a retrospective, case-control study comparing a random sample of frequent attenders and nonfrequent attenders, with details of their ED visits recorded over a 12-month duration. Frequent attenders were defined as patients with four or more visits during the study period.Results: In comparison with nonfrequent attenders (median age = 45.0 years, interquartile range [IQR] = 28.0 to 61.0 years), frequent attenders were older (median = 57.5 years, IQR = 34.0 to 74.8 years; p = 0.0003). They were also found to have more comorbidities, where 53.3% of frequent attenders had three or more chronic illnesses compared to 14% of nonfrequent attenders (p < 0.0001), and were often triaged to higher priority (more severe) classes (frequent 52.2% vs. nonfrequent 37.6%, p = 0.0004). Social issues such as bad debts (12.7%), heavy drinking (3.3%), and substance abuse (2.7%) were very low in frequent attenders compared to Western studies. Frequent attenders had a similar rate of appropriate visits to the ED as nonfrequent attenders (55.2% vs. 48.1%, p = 0.0892), but were more often triaged to P1 priority triage class (6.7% vs. 3.2%, p = 0.0014) and were more often admitted for further management compared to nonfrequent attenders (47.5% vs. 29.6%, p < 0.001). The majority of frequent attender visits were appropriate (55.2%), and of these, 81.1% resulted in admission. For the same number of patients, total visits made by frequent attenders ($174,247.60) cost four times as much as for nonfrequent attenders ($40,912.40). This represents a significant economic burden on the health care system.Conclusions: ED frequent attenders in Singapore were associated with higher age and presence of multiple comorbidities rather than with social causes of ED use. Even in integrated health systems, repeat ED visits are frequent and expensive, despite minimal social causes of acute care. EDs in aging populations must anticipate the influx of vulnerable, elderly patients and have in place interventional programs to care for them.ACADEMIC EMERGENCY MEDICINE 2015;22:1025-1033 by the Society for Academic Emergency Medicine C are at the emergency department (ED) is usually focused on acutely ill patients facing life-threatening conditions. Worldwide, EDs have faced problems of overcrowding, long patient wait times, and admission bed blocks related to increasing numbers of patients.1-7 ED visits in Singapore's seven public hospiFrom the Duke-NUS Graduate

No abstract

Patients with N(0) disease and RLN appear to share a similar prognosis to patients with N(1) disease.