Chromosome 1q21 abnormalities in multiple myeloma

Gain of chromosome 1q (+1q) is one of the most common recurrent cytogenetic abnormalities in multiple myeloma (MM), occurring in approximately 40% of newly diagnosed cases. Although it is often considered a poor prognostic marker in MM, +1q has not been uniformly adopted as a high-risk cytogenetic abnormality in guidelines. Controversy exists regarding the importance of copy number, as well as whether +1q is itself a driver of poor outcomes or merely a common passenger genetic abnormality in biologically unstable disease. Although the identification of a clear pathogenic mechanism from +1q remains elusive, many genes at the 1q21 locus have been proposed to cause early progression and resistance to anti-myeloma therapy. The plethora of potential drivers suggests that +1q is not only a causative factor or poor outcomes in MM but may be targetable and/or predictive of response to novel therapies. This review will summarize our current understanding of the pathogenesis of +1q in plasma cell neoplasms, the impact of 1q copy number, identify potential genetic drivers of poor outcomes within this subset, and attempt to clarify its clinical significance and implications for the management of patients with multiple myeloma.Subject terms: Cancer genomics, Myeloma, Myeloma     

How to Optimally Apply Impedance in the Evaluation of Esophageal Dysmotility

The utilization of impedance technology has enhanced our understanding and assessment of esophageal dysmotility. Esophageal high-resolution manometry (HRM) catheters incorporated with multiple impedance electrodes help assess esophageal bolus transit, and the combination is termed high-resolution impedance manometry (HRIM). Novel metrics have been developed with HRIM—including esophageal impedance integral ratio, bolus flow time, nadir impedance pressure, and impedance bolus height—that augments the assessment of esophageal bolus transit. Automated impedance-manometry (AIM) analysis has enhanced understanding of the relationship between bolus transit and pressure phenomena. Impedance-based metrics have improved understanding of the dynamics of esophageal bolus transit into four distinct phases, may correlate with symptomatic burden, and can assess the adequacy of therapy for achalasia. An extension of the use of impedance involves impedance planimetry and the functional lumen imaging probe (FLIP), which assesses esophageal biophysical properties and distensibility, and could detect patterns of esophageal contractility not seen on HRM. Impedance technology, therefore, has a significant impact on esophageal function testing in the present day.     

Prompt Repair of Post Cholecystectomy Bile Duct Transection Recognized Intraoperatively and Referred Early: Experience from a Tertiary Care Teaching Unit

Postcholecystectomy bile duct injuries are a cause of significant morbidity and occasional mortality. Intraoperative recognition and repair of complete biliary transection with hepaticojejunostomy is the recommended treatment; however, it is possible only in few patients as either the injury is not recognized intraoperatively or the center is not geared up to perform an urgent hepaticojejunostomy in these patients with a nondilated duct. Retrospective analysis of data from a tertiary care referral center over a period of 10 years from January 2000 to December 2009 to report the feasibility and outcomes of prompt repair was done (defined as repair within 72 h of index operation) of postcholecystectomy bile duct injury. Ten patients of postcholecystectomy bile duct injury detected intraoperatively and referred early underwent prompt repair. All patients had a complete transection of the bile duct (type of injuries as per Strasberg classification: Type E V: 1, Type E III: 5, Type E II: 3 and Type E I: 1). The mean duration between injury and bile duct repair in the form of Roux-en-Y hepaticojejunostomy (RYHJ) was 22.7 (range 5–42) hours. The mean diameter of the anastomosis was 1.63 (range1–2.1) cm, and the anastomosis was stented in 7 patients. The mean duration of surgery was 4.6 +1.7 h. One patient developed bile leak on the first postoperative day, which settled by day 5. The mean duration of hospital stay was 5.1 (range 4–8) days. With a mean follow-up of 42 (range 24–110) months, all patients had excellent (70 %) or good outcome (30 %). Prompt RYHJ (within first 72 h) for postcholecystectomy biliary transection is an effective treatment and potentially limits the morbidity to the patient.