Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker

Most cases of pancreatic cancer are not diagnosed until they are no longer curable with surgery. Therefore, it is critical to develop a sensitive, preferably noninvasive, method for detecting the disease at an earlier stage. In order to identify biomarkers for pancreatic cancer, we devised an in vitro positive/negative selection strategy to identify RNA ligands (aptamers) that could detect structural differences between the secretomes of pancreatic cancer and non-cancerous cells. Using this molecular recognition approach, we identified an aptamer (M9-5) that differentially bound conditioned media from cancerous and non-cancerous human pancreatic cell lines. This aptamer further discriminated between the sera of pancreatic cancer patients and healthy volunteers with high sensitivity and specificity. We utilized biochemical purification methods and mass-spectrometric analysis to identify the M9-5 target as cyclophilin B (CypB). This molecular recognition–based strategy simultaneously identified CypB as a serum biomarker and generated a new reagent to recognize it in body fluids. Moreover, this approach should be generalizable to other diseases and complementary to traditional approaches that focus on differences in expression level between samples. Finally, we suggest that the aptamer we identified has the potential to serve as a tool for the early detection of pancreatic cancer

Surgical Management of Ulcerative Colitis in Children and Adolescents: A Systematic Review from the APSA Outcomes and Evidence-Based Practice Committee.

INTRODUCTION: The incidence of ulcerative colitis (UC) is increasing. Roughly 20% of all patients with UC are diagnosed in childhood, and children typically present with more severe disease. Approximately 40% will undergo total colectomy within ten years of diagnosis. The objective of this study is to assess the available evidence regarding the surgical management of pediatric UC as determined by the consensus agreement of the American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee (APSA OEBP). METHODS: Through an iterative process, the membership of the APSA OEBP developed five a priori questions focused on surgical decision-making for children with UC. Questions focused on surgical timing, reconstruction, use of minimally invasive techniques, need for diversion, and risks to fertility and sexual function. A systematic review was conducted, and articles were selected for review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of Bias was assessed using Methodological Index for Non-Randomized Studies (MINORS) criteria. The Oxford Levels of Evidence and Grades of Recommendation were utilized. RESULTS: A total of 69 studies were included for analysis. Most manuscripts contain level 3 or 4 evidence from single-center retrospective reports, leading to a grade D recommendation. MINORS assessment revealed a high risk of bias in most studies. J-pouch reconstruction may result in fewer daily stools than straight ileoanal anastomosis. There are no differences in complications based on the type of reconstruction. The timing of surgery should be individualized to patients and does not affect complications. Immunosuppressants do not appear to increase surgical site infection rates. Laparoscopic approaches result in longer operative times but shorter lengths of stay and fewer small bowel obstructions. Overall, complications are not different using an open or minimally invasive approach. CONCLUSIONS: There is currently low-level evidence related to certain aspects of surgical management for UC, including timing, reconstruction type, use of minimally invasive techniques, need for diversion, and risks to fertility and sexual function. Multicenter, prospective studies are recommended to better answer these questions and ensure the best evidence-based care for our patients. LEVEL OF EVIDENCE: Level of evidence III. STUDY TYPE: Systematic review

Development of a multidisciplinary colorectal and pelvic health program: Program implementation and clinical impact

© 2020 Elsevier Inc. Introduction: Pediatric patients with complex colorectal and genitourinary conditions often require coordinated multidisciplinary care; however, this coordinated care can be hard to structure and deliver. The purpose of this paper is to review the development and implementation of a multidisciplinary colorectal and pelvic health program, one year after the program\u27s initiation. Methods: This is an observational retrospective 1-year study (10/1/2017 to 9/30/2018). In fiscal year (FY) 2018, a multidisciplinary colorectal and pelvic health program was initiated. The program development incorporated bimonthly team meetings, educational conferences, and initiation of three clinics: a complex colorectal and genitourinary reconstruction clinic, a bowel management clinic, and a colonic motility clinic. Conditions treated included complex anorectal and cloacal malformations, Hirschsprung disease, and idiopathic constipation. The fiscal year was selected to provide comparative administrative data after program implementation. Results: During the study period, 121 patients underwent comprehensive collaborative evaluation of which 58 (47%) were new to the institution compared to 12 (19%) new patients in the previous year (p \u3c 0.001). In FY 2018, there were 130 procedures performed and 512 collaborative visits with an average of 47 visits per month. This was a 3.4-fold increase in visits compared to FY2017 (171 visits). Of the new patients, 60% (35/58), traveled a median of 181 miles, representing 33 statewide counties, and 4 states compared to a median of 93 miles in the previous fiscal year (p = 0.004). Conclusion: The development of a colorectal and pelvic health program is feasible and requires a collaborative approach, necessitating multiple service lines within an institution. Program creation and implementation can result in rapid institutional clinical growth by filling a local and regional need through coordinated multidisciplinary care. Level of evidence: I

Evaluation and Management of Primary Spontaneous Pneumothorax in Adolescents and Young Adults: A Systematic Review From the APSA Outcomes & Evidence-Based Practice Committee.

INTRODUCTION: Controversy exists in the optimal management of adolescent and young adult primary spontaneous pneumothorax. The American Pediatric Surgical Association (APSA) Outcomes and Evidence-Based Practice Committee performed a systematic review of the literature to develop evidence-based recommendations. METHODS: Ovid MEDLINE, Elsevier Embase, EBSCOhost CINAHL, Elsevier Scopus, and Wiley Cochrane Central Register of Controlled Trials databases were queried for literature related to spontaneous pneumothorax between January 1, 1990, and December 31, 2020, addressing (1) initial management, (2) advanced imaging, (3) timing of surgery, (4) operative technique, (5) management of contralateral side, and (6) management of recurrence. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: Seventy-nine manuscripts were included. Initial management of adolescent and young adult primary spontaneous pneumothorax should be guided by symptoms and can include observation, aspiration, or tube thoracostomy. There is no evidence of benefit for cross-sectional imaging. Patients with ongoing air leak may benefit from early operative intervention within 24-48 h. A video-assisted thoracoscopic surgery (VATS) approach with stapled blebectomy and pleural procedure should be considered. There is no evidence to support prophylactic management of the contralateral side. Recurrence after VATS can be treated with repeat VATS with intensification of pleural treatment. CONCLUSIONS: The management of adolescent and young adult primary spontaneous pneumothorax is varied. Best practices exist to optimize some aspects of care. Further prospective studies are needed to better determine optimal timing of operative intervention, the most effective operation, and management of recurrence after observation, tube thoracostomy, or operative intervention. LEVEL OF EVIDENCE: Level 4. TYPE OF STUDY: Systematic Review of Level 1-4 studies