Integrated genomic analyses of cutaneous T-cell lymphomas reveal the molecular bases for disease heterogeneity.

Cutaneous T-cell lymphomas (CTCLs) are a clinically heterogeneous collection of lymphomas of the skin-homing T cell. To identify molecular drivers of disease phenotypes, we assembled representative samples of CTCLs from patients with diverse disease subtypes and stages. Via DNA/RNA-sequencing, immunophenotyping, and ex vivo functional assays, we identified the landscape of putative driver genes, elucidated genetic relationships between CTCLs across disease stages, and inferred molecular subtypes in patients with stage-matched leukemic disease. Collectively, our analysis identified 86 putative driver genes, including 19 genes not previously implicated in this disease. Two mutations have never been described in any cancer. Functionally, multiple mutations augment T-cell receptor-dependent proliferation, highlighting the importance of this pathway in lymphomagenesis. To identify putative genetic causes of disease heterogeneity, we examined the distribution of driver genes across clinical cohorts. There are broad similarities across disease stages. Many driver genes are shared by mycosis fungoides (MF) and Sezary syndrome (SS). However, there are significantly more structural variants in leukemic disease, leading to highly recurrent deletions of putative tumor suppressors that are uncommon in early-stage skin-centered MF. For example, TP53 is deleted in 7% and 87% of MF and SS, respectively. In both human and mouse samples, PD1 mutations drive aggressive behavior. PD1 wild-type lymphomas show features of T-cell exhaustion. PD1 deletions are sufficient to reverse the exhaustion phenotype, promote a FOXM1-driven transcriptional signature, and predict significantly worse survival. Collectively, our findings clarify CTCL genetics and provide novel insights into pathways that drive diverse disease phenotypes.

Multispecialty retrospective review of the clinical utility of pelvic magnetic resonance imaging in the setting of pelvic pain.

BACKGROUND: Pelvic pain is a common complaint, and management of it is often difficult. We sought to evaluate the utility of magnetic resonance imaging (MRI) in the diagnosis of male pelvic pain. Though MRIs are commonly ordered to evaluate pelvic pain, there are very few studies obtaining the efficacy of pelvic MRI in determining a definitive diagnosis. The primary aim of our study was to evaluate the clinical utility of pelvic MRI for a diagnosis code that included pain. METHODS: After receiving institutional review board approval, a retrospective study was performed of all pelvic MRIs completed at our institution from January 2, 2010 to December 31, 2014. These were further delineated into ordering providers by specialty and urology-specific International Classification of Diseases, Ninth Revision (ICD-9) code diagnoses (male pelvic pain, prostatitis, groin pain, scrotal pain, testicular pain, and penile pain). Clinical utility was defined as positive if MRI findings resulted in a change in management. Subanalysis was performed on patients with an ICD-9 co-diagnosis of previous oncologic concern. RESULTS: A total of 2,643 pelvic MRIs were ordered at our institution over a 5-year period. Of these, 597 pelvic MRIs (23%) were ordered for a diagnosis code that included pain (hip pain, rectal pain, joint pain, penile pain, scrotal pain, male pelvic pain and orchitis). Total utility for MRIs to find anatomic abnormalities potentially responsible for the present pain was 34% (205/597). When ordered by urologic providers, utility was 23%. Oncologists represented the highest positivity rate at 57%. CONCLUSIONS: Chronic pelvic pain is a multispecialty complaint that is difficult to treat. We were surprised to find the large number of both specialists and generalists invested in the management of pelvic pain. The increasing availability of MRI technology makes it a likely candidate to test for a clinically significant anatomic reason for pain. Though MRI is a test with minimal adverse effect and no increased risk of radiation exposure, the cost on the healthcare system should be offset by a clear clinical utility. We found total utility to be 34% across all ordering providers and an increase in positivity with concern of oncologic disease. Therefore, we would recommend pelvic MRIs in the evaluation of patients with refractory pelvic pain.

Assessment of Perioperative Variables That Predict the Need for Surgical Drains Following Robotic Partial Nephrectomy Utilizing Quantitative Drain Creatinine Analysis.

OBJECTIVE: To utilize body fluid creatinine analysis to determine which patients will require a surgical drain following robotic-assisted partial nephrectomy (RAPN). MATERIALS AND METHODS: One hundred fifty consecutive RAPN performed by a single surgeon were reviewed. Postoperative day (POD) 1 drain creatinine was compared to serum creatinine to calculate the drain to serum creatinine ratio (D/S ratio). Elevated D/S ratio was defined as any value >1.2. RESULTS: From February 2008 to April 2015, 140 patients underwent RAPN and had a drain placed (124 had D/S ratio available on POD 1). In the 103 patients with a D/S ratio of <1.2 and the 21 with D/S ratio of >1.2, the mean tumor size was 3.0 and 3.9 cm (P = .001) and mean RENAL score was 7.6 and 8.1 (P = .270), respectively. Collecting system entry occurred in 68.2% of patients with a D/S ratio of <1.2 and 71.4% of patients with a D/S ratio of >1.2. Mean drain time was 2.4 and 4.2 days (P = .001), hospital stay was 2.7 and 3.3 days (P = .036) for the D/S ratio <1.2 and D/S ratio >1.2 groups, respectively. Those with renal mass size of 4-7 cm had increased likelihood of D/S ratio >1.2 (OR 2.78; P = .041). CONCLUSIONS: Most RAPN do not require a surgical drain. A POD 1 elevated D/S ratio is more likely to occur with larger masses (those approaching or greater than 4 cm) and can be associated with prolonged drain time and hospital stay.

Has Sliding-Clip Renorrhaphy Eliminated the Need for Collecting System Repair During Robot-Assisted Partial Nephrectomy?

OBJECTIVE: We evaluated whether single-layer renorrhaphy (SLR) without collecting system (CS) closure is sufficient following robot-assisted partial nephrectomy (RAPN). PATIENTS AND METHODS: One hundred fifty consecutive patients underwent RAPN by a single surgeon and were prospectively labeled with regard to CS entry during surgery. Patients with CS entry were subdivided into two groups: those with classical renorrhaphy (CR) (i.e., two-layer repair) and those with SLR (i.e., without CS repair). Perioperative variables and outcomes were compared between CR and SLR groups. RESULTS: Ninety patients had CS entry during RAPN. Of these 90 patients, 64 had CR, and 26 had SLR, with mean ages of 62 and 59 years (p = 0.22), tumor sizes of 3.4 and 3.3 cm (p = 0.61), Mayo Adhesive Probability scores of 1.8 and 1.8 (p = 0.95), and radius, exophytic/endophytic, nearness to CS, and laterality scores of 8.5 and 8.0 (p = 0.16), respectively. Mean warm ischemia times (WITs) were 19.6 and 17.3 minutes (p = 0.04), hospital stays of 3.0 and 2.8 days (p = 0.62), and drain times of 2.9 and 2.7 days (p = 0.65), for the CR and SLR groups, respectively. Using the Clavien-Dindo classification, there were a total of six grade III or higher complications, with no difference between the CR and SLR subgroups (p = 1.0). Renal function using creatinine or glomerular filtration rate as surrogates showed no difference between groups preoperatively or up until 2 years postoperatively. CONCLUSIONS: Omitting CS repair during RAPN with SLR decreases WIT without altering complications, hospital stay, or drain time. Long-term renal function was not associated with CS repair.