No abstract

The mainstay of treatment for ovarian cancer is platinum-based cytotoxic chemotherapy. However, therapeutic resistance and recurrence is a common eventuality for nearly all ovarian cancer patients, resulting in poor median survival. Recurrence is postulated to be driven by a population of self-renewing, therapeutically resistant cancer stem cells (CSCs). A current limitation in CSC studies is the inability to interrogate their dynamic changes in real time. Here we utilized a GFP reporter driven by the NANOG-promoter to enrich and track ovarian CSCs. Using this approach, we identified a population of cells with CSC properties including enhanced expression of stem cell transcription factors, self-renewal, and tumor initiation. We also observed elevations in CSC properties in cisplatin-resistant ovarian cancer cells as compared to cisplatin-naïve ovarian cancer cells. CD49f, a marker for CSCs in other solid tumors, enriched CSCs in cisplatin-resistant and -naïve cells. NANOG-GFP enriched CSCs (GFP+ cells) were more resistant to cisplatin as compared to GFP-negative cells. Moreover, upon cisplatin treatment, the GFP signal intensity and NANOG expression increased in GFP-negative cells, indicating that cisplatin was able to induce the CSC state. Taken together, we describe a reporter-based strategy that allows for determination of the CSC state in real time and can be used to detect the induction of the CSC state upon cisplatin treatment. As cisplatin may provide an inductive stress for the stem cell state, future efforts should focus on combining cytotoxic chemotherapy with a CSC targeted therapy for greater clinical utility.

OBJECTIVES: The Pancreatitis Activity Scoring System (PASS) has been derived by an international group of experts via a modified Delphi process. Our aim was to perform an external validation study to assess for concordance of the PASS score with high face validity clinical outcomes and determine specific meaningful thresholds to assist in application of this scoring system in a large prospectively ascertained cohort. METHODS: We analyzed data from a prospective cohort study of consecutive patients admitted to the Los Angeles County Hospital between March 2015 and March 2017. Patients were identified using an emergency department paging system and electronic alert system. Comprehensive characterization included substance use history, pancreatitis etiology, biochemical profile, and detailed clinical course. We calculated the PASS score at admission, discharge, and at 12 h increments during the hospitalization. We performed several analyses to assess the relationship between the PASS score and outcomes at various points during hospitalization as well as following discharge. Using multivariable logistic regression analysis, we assessed the relationship between admission PASS score and risk of severe pancreatitis. PASS score performance was compared to established systems used to predict severe pancreatitis. Additional inpatient outcomes assessed included local complications, length of stay, development of systemic inflammatory response syndrome (SIRS), and intensive care unit (ICU) admission. We also assessed whether the PASS score at discharge was associated with early readmission (re-hospitalization for pancreatitis symptoms and complications within 30 days of discharge). RESULTS: A total of 439 patients were enrolled, their mean age was 42 (±15) years, and 53% were male. Admission PASS score >140 was associated with moderately severe and severe pancreatitis (OR 3.5 [95% CI 2.0, 6.3]), ICU admission (OR 4.9 [2.5, 9.4]), local complications (3.0 [1.6, 5.7]), and development of SIRS (OR 2.9 [1.8, 4.5]) as well as prolongation of hospitalization by a mean of 1.5 (1.3–1.7) days. For the prediction of moderately severe/severe pancreatitis, the PASS score (AUC = 0.71) was comparable to the more established Ranson’s (AUC = 0.63), Glasgow (AUC = 0.72), Panc3 (AUC = 0.57), and HAPS (AUC = 0.54) scoring systems. Discharge PASS score >60 was associated with early readmission (OR 5.0 [2.4, 10.7]). CONCLUSIONS: The PASS score is associated with important clinical outcomes in acute pancreatitis. The ability of the score to forecast important clinical events at different points in the disease course suggests that it is a valid measure of activity in patients with acute pancreatitis.

Several treatment options are available for the management of hydatid disease of the liver and the treatment modality chosen should be tailored to the individual patient. While percutaneous drainage (with PAIR/PAIR-D) is reserved for more favourable cases of type I and II cysts, the others are best managed surgically. Complete excision (cystopericstectomy or resection) of the hydatid cyst is the preferred approach and 61 of the 94 patients who were managed surgically were suitable for it. Although excisional surgery minimizes the risk of long-term recurrence and cavity-related complications, it may be hazardous in cysts located close to major biliovascular channels. In these cases (considering that it is benign disease), a drainage operation is preferable. Both conservative and radical surgery can be safely performed laparoscopically.