Faculty Bibliography

BACKGROUND:Biologic prophylaxis is used to prevent postoperative recurrence (POR) of Crohn's disease (CD) in high-risk patients who have undergone ileocolonic resection (ICR). There are limited data to guide clinicians' choice of prophylactic biologic class to prevent POR in patients previously exposed to biologics. We aimed to determine if reutilizing a prophylactic biologic class is associated with lower risk of POR in patients preoperatively exposed to biologics. METHODS:Adult CD patients who underwent ICR between 2009 and 2020 and were ever preoperatively exposed to biologics were included. Composite POR, including endoscopic (Rutgeerts ≥ i2b) and/or radiographic recurrence, was compared between patients who: received no prophylaxis, reutilized prophylaxis, or received a new class of prophylaxis (≤3 months from ICR) using Kaplan-Meier analysis. A multivariate Cox proportional hazards regression model was utilized to compare the 3 groups along with clinically established risk factors. RESULTS:A total of 635 biologic-exposed patients (≥2 biologics: 46%) who postoperatively received no prophylactic biologic (63.8%), who reutilized prophylactic biologic (30.7%), or who received a new class of prophylactic biologic (5.5%) were included. On multivariable analysis, no biologic prophylaxis was associated with a higher risk of recurrence (adjusted hazard ratio, 1.33; 95% confidence interval, 1.01-1.74; P = .04), and new biologic prophylaxis (adjusted hazard ratio, 1.50; 95% confidence interval, 0.89-2.53; P = .13) was associated with a similar risk of recurrence when compared with reutilization. Recurrence-free survival was similar among the 3 groups (P = .08); however, in patients undergoing their first ICR (P = .026) and in patients previously exposed only to anti-tumor necrosis factor agents (P = .051), the reutilization group demonstrated longer recurrence-free survival. CONCLUSIONS:Reutilization of biologic classes can be a valid strategy to prevent postoperative CD recurrence.

INTRODUCTION/BACKGROUND:Following ileocolic resection (ICR), the clinical importance and prognostic implications of histologic activity on biopsies in Crohn's disease (CD) patients with endoscopic remission are not well defined. The aim of this study was to determine if histologic activity in patients with endoscopic remission is associated with future risk of endoscopic and/or radiologic postoperative recurrence (POR). METHODS:In this multicenter retrospective cohort study, adult patients with CD who underwent ICR between 2009 and 2020 with endoscopic biopsies of ileal mucosa from Rutgeerts i0 on index colonoscopy were included. The composite rate of endoscopic (Rutgeerts score ≥i2b) and radiologic (active inflammation on imaging) recurrence was compared in patients with and without histologic activity using a Kaplan-Meier survival analysis. A multivariable Cox proportional hazard regression model including clinically relevant risk factors of POR, postoperative biologic prophylaxis, and histology activity was designed. RESULTS:A total of 113 patients with i0 disease on index colonoscopy after ICR were included. Of these, 42% had histologic activity. Time to POR was significantly earlier in the histologically active versus normal group ( P = 0.04). After adjusting for clinical risk factors of POR, histologic activity (HR 2.37, 95% CI 1.17-4.79; P = 0.02) and active smoking (HR 2.54, 95% CI 1.02-6.33; P = 0.05) were independently associated with subsequent composite POR risk. DISCUSSION/CONCLUSIONS:In patients with postoperative CD, histologic activity despite complete endoscopic remission is associated with composite, endoscopic, and radiographic recurrence. Further understanding of the role of histologic activity in patients with Rutgeerts i0 disease may provide a novel target to reduce disease recurrence in this population.

An important biological feature of prostate cancer (PCa) is its marked preference for bone marrow as a metastatic site. To identify factors that may support the growth of PCa in bone marrow, expression of receptor and nonreceptor tyrosine kinases by androgen-independent PCa bone marrow metastases was assessed. Bone marrow biopsies largely replaced by PCa were analyzed using reverse transcriptase-polymerase chain reaction amplification with degenerate primers that amplified the conserved kinase domain. Sequence analyses of the cloned products demonstrated expression of multiple kinases. Expression of the receptor and nonreceptor tyrosine kinases, alpha platelet-derived growth factor receptor and Jak 1, respectively, was confirmed by immunohistochemistry. In contrast, the type 1 insulin-like growth factor receptor, thought to play a role in PCa development, was lost in metastatic PCa. These results implicate several specific growth factors and signaling pathways in metastatic androgen-independent PCa and indicate that loss of the type 1 insulin-like growth factor receptor contributes to PCa progression.