Citations

Abstract In shotgun proteomics, database search algorithms rely on fragmentation models to predict fragment ions that should be observed for a given peptide sequence. The most widely used strategy (Naive model) is oversimplified, cleaving all peptide bonds with equal probability to produce fragments of all charges below that of the precursor ion. More accurate models, based on fragmentation simulation, are too computationally intensive for on-the-fly use in database search algorithms. We have created an ordinal-regression-based model called Basophile that takes fragment size and basic residue distribution into account when determining the charge retention during CID/higher-energy collision induced dissociation (HCD) of charged peptides. This model improves the accuracy of predictions by reducing the number of unnecessary fragments that are routinely predicted for highly-charged precursors. Basophile increased the identification rates by 26% (on average) over the Naive model, when analyzing triply-charged precursors from ion trap data. Basophile achieves simplicity and speed by solving the prediction problem with an ordinal regression equation, which can be incorporated into any database search software for shotgun proteomic identification.

In the English literature, only 9 cases of adenocarcinoma of the gallbladder with cutaneous metastasis have been reported so far. One case of multiple cutaneous metastases along with deposits in the breast tissue has been reported. We present a case of incidental metastatic gallbladder carcinoma with no intra-abdominal disease presenting as a series of four isolated cutaneous right chest wall, axillary nodal, breast, and pulmonary metastases following resection and adjuvant chemoradiation for her primary tumor. In spite of the metastatic disease coupled with the aggressive nature of the cancer, this patient reported that her energy level had returned to baseline with a good appetite and a stable weight indicating a good performance status and now is alive at 25 months since diagnosis. Her serially-presented, oligometastatic diseases were well-controlled by concurrent chemoradiotherapy and stereotactic radiation therapy. We report this case study because of its rarity and for the purpose of complementing current literature with an additional example of cutaneous metastasis from adenocarcinoma of the gallbladder.

Abstract Purpose: Mammographic breast density (MBD) is decreased by tamoxifen, but the effect of aromatase inhibitors is less clear. Experimental Design: We enrolled early-stage postmenopausal patients with breast cancer initiating adjuvant aromatase inhibitor therapy and ascertained mammograms before and at an average 10 months of aromatase inhibitor therapy. We matched cases to healthy postmenopausal women (controls) from a large mammography screening cohort on age, baseline body mass index, baseline MBD, and interval between mammograms. We estimated change in MBD using a computer-assisted thresholding program (Cumulus) and compared differences between cases and matched controls. Results: In predominantly White women (96%), we found 14% of the 387 eligible cases had a MBD reduction of at least 5% after an average of 10 months of aromatase inhibitor therapy. MBD reductions were associated with higher baseline MBD, aromatase inhibitor use for more than 12 months, and prior postmenopausal hormone use. Comparing each case with her matched control, there was no evidence of an association of change in MBD with aromatase inhibitor therapy [median case–control difference among 369 pairs was −0.1% (10th and 90th percentile: −5.9%, 5.2%) P = 0.51]. Case–control differences were similar by type of aromatase inhibitor (P's 0.41 and 0.56); prior use of postmenopausal hormones (P = 0.85); baseline MBD (P = 0.55); and length of aromatase inhibitor therapy (P = 0.08). Conclusions: In postmenopausal women treated with aromatase inhibitors, 14% of cases had a MBD reduction of more than 5%, but these decreases did not differ from matched controls. These data suggest that MBD is not a clinically useful biomarker for predicting the value of aromatase inhibitor therapy in White postmenopausal women. Clin Cancer Res; 19(8); 2144–53. ©2013 AACR.

What's known on the subject? and What does the study add? Variations in the type of urinary diversion exist for patients undergoing radical cystectomy. Although its use has been increasing from 2001 to 2008, patients who are older, female, and primary insured by Medicaid are less likely to receive continent diversions. Furthermore, patients treated surgically at high‐volume and teaching hospitals are more likely to receive continent diversions. Objective To describe the contemporary trends in urinary diversion among patients undergoing radical cystectomy ( RC ) for bladder cancer; and elucidate whether socioeconomic disparities persist in the type of diversion performed in the USA from a population‐based cohort. Patients and Methods Using the Nationwide Inpatient Sample, we identified patients who underwent RC for bladder cancer between 2001 and 2008. Multivariable regression models were used to identify patient and hospital covariates associated with continent urinary diversion and enumerate predicted probabilities for statistically significant variables over time. Results Overall, 55 635 (92%) patients undergoing RC for bladder cancer received incontinent urinary diversion, while 4552 (8%) patients received continent diversion from 2001 to 2008. Receipt of continent urinary diversion increased from 6.6% in 2001–2002 to 9.4% in 2007–2008 ( P < 0.001 for trend). Patients who were older (odds ratio [ OR ] 0.93; P < 0.001), female ( OR 0.52; P < 0.001) and insured by Medicaid ( OR 0.54; P = 0.002) were less likely to receive continent urinary diversion. However, patients treated at teaching ( OR 2.14; P < 0.001) and high‐volume hospitals ( OR 2.39; P = 0.04) had higher odds of continent urinary diversion. Predicted probabilities of continent diversion remained lower for female patients, Medicaid insurance status, and non‐teaching and medium/low‐volume hospitals over time. Conclusions In this nationally representative sample of hospitals from 2001 to 2008, the use of continent diversion in RC gradually increased. Although variations in urinary diversion exist by hospital teaching status, case volume, patient gender and primary health insurance, increased attention in expanding the use of continent diversions may help reduce these disparities for patients undergoing RC for bladder cancer.