Short-Term Results of Operative Treatment of Primary Ileocecal Crohn's Disease: Retrospective, Comparative Analysis between Early (Luminal) and Complicated Disease.

Early surgical treatment for patients with ileocecal Crohn's disease (CD) could be an alternative to biological therapy. The aim of this study is to compare operative outcomes following ileocecal resection for patients with luminal and complicated CD. Patients operated for primary ileocecal CD during 8 years in one tertiary-referral hospital were allocated into 2 groups: those operated for early (luminal) disease (ECD), and for complications of CD (CCD). A retrospective comparative analysis was performed. A total of 273 patients were included in the analysis, 85 (31%) of which were in the ECD group. No difference was found regarding time from diagnosis to surgery. Surgical procedures were longer in the CCD group, with lower rates of laparoscopic approach (93 vs. 99%, p = 0.035) and higher conversion rates (20 vs. 2%, p < 0.001). ECD had non-significant differences in terms of major postoperative complications (9.4 vs. 14.9%, p = 0.215), shorter hospital stays, and lower rates of anastomotic leakage (3.5 vs. 6.8%, p = 0.285). Conversely, the CCD group had higher reoperation and re-hospitalization rates. Adequate timing for the indication of surgery in primary ileocecal CD, including an early discussion considering both medical and surgical treatment as options, could positively influence operative outcomes.

Review of Blood-Based Colorectal Cancer Screening: How Far Are Circulating Cell-Free DNA Methylation Markers From Clinical Implementation?

Colorectal cancer (CRC) is a leading cause of cancer related deaths worldwide, and late stages (III-IV) in particular have low 5-year survival rates. Stage shifting by CRC screening programs has proven effective by decreasing morbidity and mortality and in many countries national CRC screening programs have been implemented. Currently, European, Asian, and American authorities recommend screening for CRC using fecal occult blood testing, sigmoidoscopy, or colonoscopy. Because these approaches all have weaknesses (eg, poor compliance, high costs, test invasiveness), much effort has been put into the development of alternative screening approaches, many of which are blood-based. Blood-based strategies especially present the advantages of minimally invasiveness compared to endoscopies and an expectantly higher compliance rate compared to stool-based tests. The last decades have seen many discovery studies identifying promising blood-based biomarkers of CRC; however, common to all of these markers is that their clinical usefulness remains evasive. At present only one blood-based CRC screening marker has been approved in the United States. The aim of this review is to discuss the development of blood-based cell-free DNA methylation marker candidates for CRC screening. On the basis of a methodical literature search, the past, present, and future of cell-free DNA screening markers for CRC are revised and discussed. Resource limitations and technical challenges related to sensitivity and specificity measurements keep many markers at bay. Possible solutions to these problems are offered to enable markers to benefit future screening participants.

Comparative analysis of 12 different kits for bisulfite conversion of circulating cell-free DNA.

Blood circulating cell-free DNA (cfDNA) is becoming popular in the search of promising predictive and prognostic biomarkers. Among these biomarkers, cfDNA methylation markers have especially gained considerable attention. A significant challenge in the utilization of cfDNA methylation markers is the limited amount of cfDNA available for analyses; reportedly, bisulfite conversion (BSC) reduce cfDNA amounts even further. Nevertheless, few efforts have focused on ensuring high cfDNA conversion efficiency and recovery after BSC. To compare cfDNA recovery of different BSC methods, we compared 12 different commercially available BSC kits. We tested whether DNA recovery was affected by the molecular weight and/or quantity of input DNA. We also tested BSC efficiency for each kit. We found that recovery varied for DNA fragments of different lengths: certain kits recovered short fragments better than others, and only 3 kits recovered DNA fragments of <100 bp well. In contrast, DNA input amount did not seem to affect DNA recovery: for quantities spanning between 820 and ∼25,000 genome equivalents per BSC, a linear relation was found between input and recovery amount. Overall, mean recovery ranged between 9 and 32%, with BSC efficiency of 97-99.9%. When plasma cfDNA was used as input for BSC, recovery varied from 22% for the poorest and 66% for the best performing kits, while conversion efficiency ranged from 96 to 100% among different kits. In conclusion, clear performance differences exist between commercially available BSC kits, both in terms of DNA recovery and conversion efficiency. The choice of BSC kit can substantially impact the amount of converted cfDNA available for downstream analysis, which is critical in a cfDNA methylation marker setting.