Iron Chelation in Transfusion-Dependent Patients With Low- to Intermediate-1-Risk Myelodysplastic Syndromes: A Randomized Trial.

Background: Iron chelation therapy (ICT) in patients with lower-risk myelodysplastic syndromes (MDS) has not been evaluated in randomized studies. Objective: To evaluate event-free survival (EFS) and safety of ICT in iron-overloaded patients with low- or intermediate-1-risk MDS. Design: Multicenter, randomized, double-blind, placebo-controlled trial (TELESTO). (ClinicalTrials.gov: NCT00940602). Setting: 60 centers in 16 countries. Participants: 225 patients with serum ferritin levels greater than 2247 pmol/L; prior receipt of 15 to 75 packed red blood cell units; and no severe cardiac, liver, or renal abnormalities. Intervention: Deferasirox dispersible tablets (10 to 40 mg/kg per day) (n = 149) or matching placebo (n = 76). Measurements: The primary end point was EFS, defined as time from date of randomization to first documented nonfatal event (related to cardiac or liver dysfunction and transformation to acute myeloid leukemia) or death, whichever occurred first. Results: Median time on treatment was 1.6 years (interquartile range [IQR], 0.5 to 3.1 years) in the deferasirox group and 1.0 year (IQR, 0.6 to 2.0 years) in the placebo group. Median EFS was prolonged by approximately 1 year with deferasirox versus placebo (3.9 years [95% CI, 3.2 to 4.3 years] vs. 3.0 years [CI, 2.2 to 3.7 years], respectively; hazard ratio, 0.64 [CI, 0.42 to 0.96]). Adverse events occurred in 97.3% of deferasirox recipients and 90.8% of placebo recipients. Exposure-adjusted incidence rates of adverse events (≥15 events per 100 patient treatment-years) in deferasirox versus placebo recipients, respectively, were 24.7 versus 23.9 for diarrhea, 21.8 versus 18.7 for pyrexia, 16.7 versus 22.7 for upper respiratory tract infection, and 15.9 versus 0.9 for increased serum creatinine concentration. Limitations: The protocol was amended from a phase 3 to a phase 2 study, with a reduced target sample size from 630 to 210 participants. There was differential follow-up between treatment groups. Conclusion: The findings support ICT in iron-overloaded patients with low- to intermediate-1-risk MDS, with longer EFS compared with placebo and a clinically manageable safety profile. Therefore, ICT may be considered in these patients. Primary Funding Source: Novartis Pharma AG.

Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial.

JUMP is a phase 3b expanded-access trial for patients without access to ruxolitinib outside of a clinical study; it is the largest clinical trial to date in patients with myelofibrosis who have been treated with ruxolitinib. Here, we present safety and efficacy findings from an analysis of 1144 patients with intermediate- or high-risk myelofibrosis, as well as a separate analysis of 163 patients with intermediate-1-risk myelofibrosis - a population of patients not included in the phase 3 COMFORT studies. Consistent with ruxolitinib's mechanism of action, the most common hematologic adverse events were anemia and thrombocytopenia, but these led to treatment discontinuation in only a few cases. The most common non-hematologic adverse events were primarily grade 1/2 and included diarrhea, pyrexia, fatigue, and asthenia. The rates of infections were low and primarily grade 1/2, and no new or unexpected infections were observed. The majority of patients achieved a ≥50% reduction from baseline in palpable spleen length. Improvements in symptoms were rapid, with approximately half of all patients experiencing clinically significant improvements, as assessed by various quality-of-life questionnaires. The safety and efficacy profile in intermediate-1-risk patients was consistent with that in the overall JUMP population and with that previously reported in intermediate-2- and high-risk patients. Overall, ruxolitinib provided clinically meaningful reductions in spleen length and symptoms in patients with myelofibrosis, including those with intermediate-1-risk disease, with a safety and efficacy profile consistent with that observed in the phase 3 COMFORT studies. This trial was registered as NCT01493414 at ClinicalTrials.gov.

Is routine cholecystectomy indicated for asymptomatic cholelithiasis in patients undergoing gastric bypass?

BACKGROUND: The purpose of this study was to evaluate the natural history of patients undergoing Roux-en-Y gastric bypass (RYGBP) with known asymptomatic cholelithiasis in whom prophylactic cholecystectomy was not performed at the time of surgery. METHODS: The records of 144 consecutive patients from a single year experience in RYGBP surgery at the University of California, Davis Medical Center were reviewed. Patients undergoing RYGBP were routinely screened for cholelithiasis by ultrasound. Patients who did not have cholecystectomy were managed with ursodiol for 6 months postoperatively. RESULTS: 13 males (9.0%) and 131 females (91%) underwent RYGBP. The mean age was 43 years (SD 8.55), and mean BMI was 46 kg/m2 (SD 6.5). The comorbidities of our patient population included diabetes (14%), hypertension (48%), gastroesophageal reflux disease (50%), dyslipidemia (35%), obstructive sleep apnea (31%), and musculoskeletal complaints (69%). 22 patients were diagnosed with cholelithiasis by ultrasonography preoperatively. 9 of these patients (41%) were symptomatic and underwent concurrent cholecystectomy and RYGBP. The remaining 13 patients (59%) had asymptomatic cholelithiasis preoperatively but did not undergo cholecystectomy at the time of surgery. Only one of these asymptomatic patients eventually developed symptoms necessitating cholecystectomy at up to 1 year follow-up. CONCLUSIONS: Our data suggest that it may not be absolutely indicated to perform prophylactic cholecystectomy at the time of RYGBP surgery for asymptomatic cholelithiasis. We believe that this phenomenon needs to be further studied in a randomized trial.

Robotic cholecystectomy: learning curve, advantages, and limitations.

BACKGROUND: Robotic cholecystectomy is safe, feasible procedure. Initial studies showed significant set up time and operating time but no clear clinical advantage of the robotic involvement. We have investigated the learning curve, advantages and limitation of the procedure. MATERIAL AND METHODS: We reviewed all (n = 51) robotic cholecystectomies performed between July 2004 and December 2005. The surgery was performed using the da Vinci system. We recorded operative time, setup time of robotics instrumentation, conversion to laparoscopic or open cholecystectomy and complication of the procedure. RESULTS: Forty-eight of the 51 procedures (94%) were completed robotically. We did not experience any significant complications directly related to robotics surgery. The mean +/- SD operating time was 77 +/- 22.3 min. The mean setup time for robotics (from incision until robot was in place, including draping the robot) was 24 +/- 8.8 min. However, the setup time significantly improved as we gained more experience: from 30.6 +/- 10.7 min (first 16 cases) to 18.3 +/- 4.0 min (cases 33-48). The mean robotic time was 34 +/- 16.1 min. We observed no significant improvement in robotic procedure time. CONCLUSIONS: Robotic cholecystectomy offers significant advantages such as three-dimensional view, easier instrument manipulations and possibility of remote site surgery. We observed some shortcomings of robotic surgery such as need for larger and additional ports, and need for undocking the machine in case of cholangiography or change of patient position. Our data shows that the learning curve is between 16 to 32 procedures to significantly decrease the setup time and total operating time.