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ABSTRACT Background Many female residents choose to start families during training, and they want to breastfeed their infants. Continuing lactation while balancing service and education demands can be challenging. Objective We hypothesized that the presence of a dedicated and fully equipped lactation room with a hospital-grade pump (HGP) would increase ease and efficiency of lactation during residency. Methods A quiet HGP was purchased for resident use, and it was stored in a designated room with a computer, telephone, and dictation system. Lactating residents provided information about pumping time and production using their own portable double electric pump (PP) versus the HGP based on the first pump of the morning (for consistency), averaged over the first month back from maternity leave. Results Among 6 residents, lactation time with PP averaged 24 minutes (range, 15–40 minutes) versus 15.5 minutes with HGP (range, 10–32 minutes). Use of the HGP reduced total pumping time by 8.5 minutes (95% confidence interval 3.8–12.2, P = .045). Production volume increased from 6 ounces (range, 3.5–8.5 ounces) with PP to 8.8 ounces (range, 8–11 ounces) with HGP, for a mean increase of 2.8 ounces (95% confidence interval 1.2–4.3, P = .06) despite decreased lactation time. Conclusions In our pilot, an HGP significantly decreased lactation time, while increasing expressed milk volume. Residents completed clinical and educational tasks while pumping. Providing an HGP and equipped lactation space helped residents continue breastfeeding and decreased the burden of lactation on patient care and educational tasks.

24 Background: The use of radical prostatectomy (RP) as initial treatment of high-risk/locally-advanced prostate cancer is increasing but patients (pts) with adverse pathologic features such as positive surgical margins or T3 disease have up to 70% recurrence risk. These high-risk pts may be managed with adjuvant radiotherapy (ART) or early salvage radiotherapy (ESRT). The optimal timing of post-operative radiotherapy is unclear. Methods: Individual data from 1566 consecutive pts with pT2N0M0/R1 or pT3N0M0/R0-1 disease who underwent post-prostatectomy ART or ESRT (1987-2013) at 10 academic centers were pooled. Post-irradiation freedom from biochemical failure (FFBF), freedom from distant metastases (FFDM), prostate-cancer specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier and multivariate competing-risks regression (MVA) analyses. Propensity score (PS) matching was used to account for covariates potentially associated with treatment allocation. All outcomes were measured from the date of surgery to address lead time bias. Results: After PS-matching, median follow-up after surgery was 66 vs. 73 months for the ART and ESRT groups, respectively, and baseline characteristics were well-matched. ART was associated with higher FFBF (12-yr: 69% vs. 43%; log-rank P < 0.0001), FFDM (12-yr: 95% vs. 85%; log-rank P = 0.03), PCSS (12-yr: 99% vs. 94%; log-rank P = 0.048), and OS (12-yr: 91% vs. 79%; log-rank P = 0.01). ART, lower Gleason score, lower T-stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on MVA for BF. Sensitivity analysis demonstrated that the decreased risk of BF associated with ART remained significant unless more than 56% of ART pts were cured by surgery alone. This threshold is greater than the estimated 12-yr FFBF of 46% after RP alone as determined by a contemporary nomogram. Conclusions: To the best of our knowledge, this represents the largest multi-institutional study to date comparing ART to ESRT. ART was associated with reduced biochemical recurrence, distant metastases, and death compared to ESRT for high-risk pts, pending prospective validation.

MMP ‐14 and MMP ‐9 are two well‐established cancer targets for which no specific clinically relevant inhibitor is available. Using a powerful combination of computational design and yeast surface display technology, we engineered such an inhibitor starting from a nonspecific MMP inhibitor, N‐ TIMP 2. The engineered purified N‐ TIMP 2 variants showed enhanced specificity toward MMP ‐14 and MMP ‐9 relative to a panel of off‐target MMP s. MMP ‐specific N‐ TIMP 2 sequence signatures were obtained that could be understood from the structural perspective of MMP /N‐ TIMP 2 interactions. Our MMP ‐9 inhibitor exhibited 1000‐fold preference for MMP ‐9 vs. MMP ‐14, which is likely to translate into significant differences under physiological conditions. Our results provide new insights regarding evolution of promiscuous proteins and optimization strategies for design of inhibitors with single‐target specificities.

Abstract Stereotactic Radiosurgery ( SRS ) is considered standard of care for patients with 1–3 brain metastases ( BM ). Recent observational studies have shown equivalent OS in patients with 5+ BM compared to those with 2–4, suggesting SRS alone may be appropriate in these patients. We aim to review outcomes of patients treated with SRS with 2–4 versus 5+ BM . This analysis included consecutive patients from 1994 to 2015 treated with SRS . Of 1017 patients, we excluded patients with a single BM and patients without adequate survival data, resulting in 391 patients. All risk factors were entered into univariate analysis using Cox proportional hazards model, and significant factors were entered into multivariate analysis ( MVA ). We additionally analyzed outcomes after excluding patients with prior surgery or whole‐brain radiotherapy ( WBRT ). Median follow‐up was 7.1 months. Median KPS was 90, mean age was 59, and most common histologies were melanoma and lung. Median tumor volume was 3.41 cc. Patients with 2–4 BM had a median OS of 8.1 months compared to 6.2 months for those with 5+ BM ( P = 0.0136). On MVA , tumor volume, KPS , and histology remained significant for OS , whereas lesion number did not. Similar results were found when excluding patients with prior surgery or WBRT . Rather than lesion number, the strongest prognostic factors for patients undergoing SRS were tumor volume >10 cc, KPS , and histology. BM number may therefore not be the most important criterion for candidacy for SRS . Patients with 5 or more BM should be considered for SRS .

Clusterin, a widely expressed, tissue-specific glycoprotein, is a diagnostic marker of several tumor types, including anaplastic large cell lymphoma, follicular dendritic cell sarcoma, and tenosynovial giant cell tumor. A recent study has suggested it is highly expressed by well-differentiated neuroendocrine tumors (NET) arising at most anatomic sites, with the exception of jejunoileal tumors, and that it is similarly not expressed by poorly differentiated neuroendocrine carcinomas (NEC). We sought to validate this result in a large cohort of NETs and NECs. Clusterin immunohistochemistry was performed on tissue microarrays of 255 NETs [45 lung, 4 stomach, 8 duodenum, 75 pancreas (62 primary, 13 metastatic), 107 jejunoileum (69 primary, 38 metastatic), 16 appendix] and 88 NECs (43 visceral, 45 Merkel cell). Extent (%) and intensity (0, 1+, 2+, 3+) of staining were assessed and an H-score (extent x intensity) calculated. An average H-score >5 was considered positive. Clusterin expression was noted in 82.4% of 148 nonjejunoileal NETs (average H-score 183) and only 8.4% of 107 jejunoileal NETs (average H-score, 31), as well as 19.3% of NECs (average H-score, 36). Clusterin is frequently, strongly expressed by NETs of diverse anatomic sites, with the exception of jejunoileal tumors, in which it is only rarely, weakly expressed. It is occasionally, weakly expressed by NECs. Most metastatic NETs of occult origin arise in the pancreas or the jejunoileum. For cases in which an initial site of origin immunopanel (eg, islet 1, PAX6, CDX2) is ambiguous, addition of clusterin may be diagnostically useful, with absence of expression suggesting a jejunoileal origin.