Risk Factors for Rescue Therapy in Crohn's Patients Maintained on Infliximab After Withdrawal of the Immunomodulator: A Long-Term Follow-Up.

BACKGROUND: Usefulness of thiopurine and scheduled infliximab combination therapy in non-immunomodulator (IM)-naïve Crohn's disease (CD) patients and the optimal length of dual therapy are still debated. AIMS: To determine proportion of patients developing disease flare requiring rescue therapy and risk factors associated with disease flare after de-escalation of IM from combination therapy. METHODS: Adult CD patients in clinical remission on combination therapy were identified from a large single-center database between 2002 and 2009. Patients who had their IM stopped in the absence of adverse events were included. Association between clinical and demographic variables and time until rescue therapy was analyzed using Cox-proportional hazard models. RESULTS: Forty-three CD patients on combination therapy in clinical remission at time of IM de-escalation were identified and followed up for a median duration of 61.6 months (range 5.4-129.5). Median duration of remission on combination therapy prior to IM de-escalation was 12.0 months (range 4-74). Thirty-one patients (72.1%) required rescue therapy during follow-up. On multivariable analysis, age at diagnosis < 16 years versus > 40 years (HR 4.55, 95% CI 1.18-17.62, p = 0.028), using methotrexate instead of azathioprine in combination with infliximab (HR 3.37, 95% CI 1.14, 9.96, p = 0.028), and duration of combination therapy < 6 months (HR 5.68, 95% CI 1.58, 20.36, p = 0.007) increased risk for rescue therapy. CONCLUSIONS: A large proportion of CD patients on combination therapy experienced a flare following IM withdrawal. Young age at diagnosis, short duration of combination therapy, and methotrexate use were independent predictors of the need for rescue therapy.

Effectiveness and safety of serial endoscopic ultrasound-guided celiac plexus block for chronic pancreatitis.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound - guided celiac plexus block (EUS-CPB) is an established treatment for pain in patients with chronic pancreatitis (CP), but the effectiveness and safety of repeated procedures are unknown. Our objective is to report our experience of repeated EUS-CPB procedures within a single patient. PATIENTS AND METHODS: A prospectively maintained EUS database was retrospectively analyzed to identify patients who had undergone more than one EUS-CPB procedure over a 17-year period. The main outcome measures included number of EUS-CPB procedures for each patient, self-reported pain relief, duration of pain relief, and procedure-related adverse events. RESULTS: A total of 248 patients underwent more than one EUS-CPB procedure and were included in our study. Patients with known or suspected CP (N = 248) underwent a mean (SD) of 3.1 (1.6) EUS-CPB procedures. In 76 % of the patients with CP, the median (range) duration of the response to the first EUS-CPB procedure was 10 (1 - 54) weeks. Lack of pain relief after the initial EUS-CPB was associated with failure of the next EUS-CPB (OR 0.17, 95 %CI 0.06 - 0.54). Older age at first EUS-CPB and pain relief after the first EUS-CPB were significantly associated with pain relief after subsequent blocks (P = 0.026 and P = 0.002, respectively). Adverse events included peri-procedural hypoxia (n = 2) and hypotension (n = 1) and post-procedural orthostasis (n = 2) and diarrhea (n = 4). No major adverse events occurred. CONCLUSIONS: Repeated EUS-CPB procedures in a single patient appear to be safe. Response to the first EUS-CPB is associated with response to subsequent blocks.

Dose-volume relationships associated with temporal lobe radiation necrosis after skull base proton beam therapy.

PURPOSE: We evaluated patient and treatment parameters correlated with development of temporal lobe radiation necrosis. METHODS AND MATERIALS: This was a retrospective analysis of a cohort of 66 patients treated for skull base chordoma, chondrosarcoma, adenoid cystic carcinoma, or sinonasal malignancies between 2005 and 2012, who had at least 6 months of clinical and radiographic follow-up. The median radiation dose was 75.6 Gy (relative biological effectiveness [RBE]). Analyzed factors included gender, age, hypertension, diabetes, smoking status, use of chemotherapy, and the absolute dose:volume data for both the right and left temporal lobes, considered separately. A generalized estimating equation (GEE) regression analysis evaluated potential predictors of radiation necrosis, and the median effective concentration (EC50) model estimated dose-volume parameters associated with radiation necrosis. RESULTS: Median follow-up time was 31 months (range 6-96 months) and was 34 months in patients who were alive. The Kaplan-Meier estimate of overall survival at 3 years was 84.9%. The 3-year estimate of any grade temporal lobe radiation necrosis was 12.4%, and for grade 2 or higher radiation necrosis was 5.7%. On multivariate GEE, only dose-volume relationships were associated with the risk of radiation necrosis. In the EC50 model, all dose levels from 10 to 70 Gy (RBE) were highly correlated with radiation necrosis, with a 15% 3-year risk of any-grade temporal lobe radiation necrosis when the absolute volume of a temporal lobe receiving 60 Gy (RBE) (aV60) exceeded 5.5 cm(3), or aV70 > 1.7 cm(3). CONCLUSIONS: Dose-volume parameters are highly correlated with the risk of developing temporal lobe radiation necrosis. In this study the risk of radiation necrosis increased sharply when the temporal lobe aV60 exceeded 5.5 cm(3) or aV70 > 1.7 cm(3). Treatment planning goals should include constraints on the volume of temporal lobes receiving higher dose. The EC50 model provides suggested dose-volume temporal lobe constraints for conventionally fractionated high-dose skull base radiation therapy.