Prabin Thapa

3 Tesla magnetic resonance imaging with and without corticotropin releasing hormone stimulation for the detection of microadenomas in Cushing's syndrome

Objective  We sought to determine if higher resolution 3 Tesla (T) magnetic resonance imaging (MRI) with or without ovine corticotropin releasing hormone (o‐CRH) stimulation would increase the sensitivity for detection of pituitary microadenomas in ACTH‐dependent Cushing’s syndrome (CS).

Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades

CONTEXT Thiazide diuretics, the antihypertensive agent prescribed most frequently worldwide, are commonly associated with hypercalcemia. However, the epidemiology and clinical features are poorly understood. OBJECTIVE To update the incidence of thiazide-associated hypercalcemia and clarify its clinical features. PATIENTS AND METHODS In a population-based descriptive study, Olmsted County, Minnesota, residents with thiazide-associated hypercalcemia were identified through the Rochester Epidemiology Project and the Mayo Clinic Laboratory Information System from 2002-2010 and were added to the historical cohort beginning in 1992. MAIN OUTCOME Incidence rates were adjusted to the 2010 United States white population. RESULTS Overall, 221 Olmsted County residents were identified with thiazide-associated hypercalcemia an average of 5.2 years after initiation of treatment. Subjects were older (mean age, 67 years) and primarily women (86.4%). The incidence of thiazide-associated hypercalcemia increased after 1997 and peaked in 2006 with an annual incidence of 20 per 100,000, compared to an overall rate of 12 per 100,000 in 1992-2010. Severe hypercalcemia was not observed in the cohort despite continuation of thiazide treatment in 62.4%. Of patients discontinuing thiazides, 71% continued to have hypercalcemia. Primary hyperparathyroidism was diagnosed in 53 patients (24%), including five patients who underwent parathyroidectomy without thiazide discontinuation. CONCLUSIONS Many patients with thiazide-associated hypercalcemia have underlying primary hyperparathyroidism. Additionally, a sharp rise in thiazide-associated hypercalcemia incidence began in 1998, paralleling the increase observed in primary hyperparathyroidism in this community. Case ascertainment bias from targeted osteoporosis screening is the most likely explanation.

High grade neuroendocrine carcinoma of the urinary bladder treated by radical cystectomy: a series of small cell, mixed neuroendocrine and large cell neuroendocrine carcinoma

Summary High grade neuroendocrine carcinomas (HGNEC) treated by cystectomy often carry an original diagnosis of typical urothelial carcinoma (UC). The correct diagnosis of HGNEC is critical in influencing the decision for early chemotherapy, potentially followed by cystectomy. The objective of this study was to characterise the features of HGNEC treated by radical cystectomy. The study consisted of 79 patients with HGNEC including small cell (68 patients), large cell neuroendocrine (LCNEC) (5 patients) and mixed neuroendocrine (mixed-NEC) carcinoma (6 patients) matched with 122 patients with UC, treated at our institution between 1987 and 2014. Morphometric analysis for cell and nuclear size as well as immunophenotyping for neuroendocrine markers and cell-cycle regulators were applied to tissue microarrays. Small cell, LCNEC and mixed-NEC are a morphological spectrum of high grade neuroendocrine carcinoma with overlapping histological features, identical immunophenotype, Ki-67 proliferative rate and patient outcomes. Finally, the nuclear size criteria is misleading as HGNEC, particularly cases of LCNEC and mixed-NEC, may have enlarged nuclei compared to small cell carcinomas and are more prone to be misdiagnosed as UC, thereby preventing appropriate management.

PD67-10 INCIDENCE AND RISK FACTORS FOR PERITONEAL CARCINOMATOSIS FOLLOWING OPEN RADICAL CYSTECTOMY

lymph node dissection, and number of lymph nodes removed. Perioperative outcomes measured included length of stay (LOS), 30-day and 90-day postoperative mortality rates, as well as 30-day readmission following surgery. To minimize selection bias, observed differences in baseline characteristics between patients who received RARC vs. ORC were controlled for using a weighted propensity score analysis. Using weighted data, all endpoints were assessed using propensity-adjusted logistic regression analyses. RESULTS: Of 9,561 patients who underwent RC, 2,048 (21.4%) and 7,513 (78.6%) underwent RARC and ORC, respectively. The use of RARC has increased over time, from 16.7% in 2010 to 25.3% in 2013. With regard to oncologic outcomes, RARC was associated with similar positive surgical margins (9.4% vs. 10.7% OR:0.86, 95%CI 0.72-1.04, p1⁄40.12), higher rates of lymphadenectomy (96.4% vs. 92.0%, OR: 2.31, 95%CI 1.68-3.19, p<0.001), higher median lymph node count (17 vs. 12, p<0.001) and higher rates of lymph node count above the median (56.8% vs. 40.4%, OR: 1.95, 95%CI 1.56-2.43, p<0.001). With regard to postoperative outcomes, receipt of RARC was associated with a shorter median LOS (7 vs. 8, p<0.001), lower rates of pLOS (45.1% vs. 54.8%, OR: 0.68, 95%CI 0.58-0.79, p<0.001), lower 30-day (1.5% vs. 2.8%, OR: 0.49, 95%CI 0.29-0.82, p1⁄40.007) and 90day postoperative mortality (5.0% vs. 6.8%, OR: 0.72, 95%CI 0.54-0.95, p1⁄40.023). CONCLUSIONS: Our large contemporary study shows the increased adoption of RARC between 2010 and 2013, with currently more than 1 out of 4 patients undergoing RARC. RARC was associated with higher LN counts, shorter LOS and lower postoperative mortality.

MP34-03 ONCOLOGIC OUTCOMES FOR PATIENTS WITH RESIDUAL CANCER AT CYSTECTOMY FOLLOWING PREOPERATIVE CHEMOTHERAPY: A PATHOLOGIC STAGE-MATCHED COMPARATIVE ANALYSIS

INTRODUCTION AND OBJECTIVES: While neoadjuvant chemotherapy prior to radical cystectomy (RC) has been demonstrated to improve survival compared to RC alone for urothelial carcinoma of the bladder (UCB), the bulk of this survival benefit has been attributed to patients who achieve ypT0 status at RC. The implications of having residual UCB (rUCB) at RC after preoperative chemotherapy (POC) are less clear. As such, we evaluated survival for patients with and without rUCB at RC after POC compared with pathologic stage-matched RC patients who did not receive POC. METHODS: Patients undergoing RC for UCB between 19802010 at Mayo Clinic were identified. All RC pathology was re-reviewed by a single genitourinary pathologist. Patients who received POC for T2-T4 and/or N1-3 M0 UCB were matched 1:2 to patients not exposed to prior chemotherapy based on pT and pN-stage, soft tissue surgical margin status, and year of RC. Kaplan Meier and Cox regression analyses were used to evaluate the associations between POC and cancer-specific (CSS) and overall survival (OS), stratified by presence or absence of rUCB at RC. RESULTS: We matched 111 patients who underwent POC + RC to 222 RC-alone patients. Median age was 68 yrs (IQR 60,74); 59 (18%) were female. Median follow-up was 7.2 yrs (IQR 6,16), during which time a total of 248 patients died, with 148 dying from UCB. In patients without rUCB at RC, there was no difference in 5-yr CSS (86% vs. 90%, p1⁄40.85) or OS (82% vs. 84%, p1⁄40.46) between patients who did versus did not receive POC. Moreover, on multivariable analysis, chemotherapy exposure was not significantly associated with CSS (HR1⁄41.0; 95%CI 0.3-3.1; p1⁄40.9) or OS (HR1⁄40.9; 95%CI 0.4-1.9; p1⁄40.8) in this subgroup. Conversely, among patients with rUCB at RC, receipt of POC was associated with significantly worse 5-yr CSS (32% vs. 56%, p<0.001) and OS (25% vs. 48%, p<0.001). Moreover, on multivariable analysis, chemotherapy exposure remained independently associated with adverse CSS (HR1⁄42.2; 95%CI 1.6-3.1; p<0.001) and OS (HR1⁄42.0; 95%CI 1.5-2.7; p<0.001) among the patients with rUCB. CONCLUSIONS: While patients who achieve a complete response to POC have excellent survival outcomes, patients with residual UCB at RC after POC have a worse prognosis compared to stage-matched RC patients not exposed to chemotherapy. Such patients should be considered for enrollment in novel adjuvant therapy trials, while continued investigation of which patients are most likely to achieve ypT0 status remains warranted.