Purpose: Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligonucleotide microarrays to interrogate mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel molecular pathways dysregulated in the development and progression of pancreatic cancer. Experimental Design: RNA was hybridized to Affymetrix Genechip HG-U133 oligonucleotide microarrays. A relational database integrating data from publicly available resources was created to identify candidate genes potentially relevant to pancreatic cancer. The protein expression of one candidate, homeobox B2 (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry. Results: We identified aberrant expression of several components of the retinoic acid (RA) signaling pathway (RARa, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, and HOXB2), many of which are known to be aberrantly expressed in pancreatic cancer and PanIN. HOXB2, a downstream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pancreas. Immunohistochemistry revealed ectopic expression of HOXB2 in15% of early PanIN lesions and 48 of 128 (38%) pancreatic cancer specimens. Expression of HOXB2 was associated with nonresectable tumors and was an independent predictor of poor survival in resected tumors. Conclusions: We identified aberrant expression of RA signaling components in pancreatic cancer, including HOXB2, which was expressed in a proportion of PanIN lesions. Ectopic expression of HOXB2 was associated with a poor prognosis for all patients with pancreatic cancer and was an independent predictor of survival in patients who underwent resection.Pancreatic cancer is the fifth leading cause of cancer death in Western societies with a 5-year survival rate of <10% (1). Pancreatic cancer presents at an advanced stage; thus, only 10% to 20% of patients are suitable for surgical treatment at the time of presentation (1). Clinical management of these patients is complicated by inconsistencies in the influence of conventional clinicopathologic variables on outcome suggesting that some of these variables lack accuracy. In addition, preoperative assessment of some variables such as lymph node metastases is difficult. Whereas in other cancers assessment of aberrations in gene expression that cosegregate with therapeutic response and outcome are being adopted routinely to increase predictive power (e.g., ER and HER-2/neu in breast cancer), there remain no molecular markers of clinical utility in pancreatic cancer. This highlights the need for the identification of novel regulatory pathways important in pancreatic cancer that may also have diagnostic, therapeutic and prognostic utility.There is now compelling histopathologic and molecular evidence to support the evolution of pancreatic cancer through a series of noninvasive duct...

Background Cardiopulmonary transplantation is becoming a more common treatment option for advanced heart and/or lung disease. Specialist rehabilitation programs may assist recovery and enhance functional independence following transplantation. Objective To quantify the outcomes of multidisciplinary inpatient rehabilitation following cardiopulmonary transplantation and describe cohort characteristics. Design Retrospective cohort study. Setting Subacute inpatient rehabilitation facility, located on‐site at Australia's largest cardiopulmonary transplant center. Participants Heart and/or lung transplant recipients (n = 116), admitted for multidisciplinary inpatient rehabilitation, between 2009 and 2016. Interventions All participants received multidisciplinary rehabilitation as part of their standard care. Main Outcome Measurements Participants' functional independence was scored using the Functional Independence Measure (FIM) upon rehabilitation admission and discharge. Physical measures of mobility and balance were assessed at the same time points, including the 6‐minute walk test, 10 m walk, Timed Up and Go, and Berg Balance Scale. Process measures of interest included rehabilitation length of stay, interruptions to rehabilitation, and discharge destination. Results Average length‐of‐stay in rehabilitation was 26.9 ± 21.2 days (mean ± SD). FIM scores improved from 79.8 ± 20.3 on admission to 101.8 ± 29.1 at discharge (P < .001) for the pooled cohort. Physical measures of mobility and balance also improved: 6‐minute walk test distances improved from 103.6 ± 80.1 to 183.2 ± 104.8 m (P < .001); Timed Up and Go results decreased from 26.4 ± 18.3 seconds to 16.5 ± 14.1 seconds (P < .001); and Berg Balance Scale scores increased from 26.8 ± 17.1 to 45.0 ± 9.4 (P < .001). Approximately one‐third (33.6%) of admissions were interrupted by an acute medical complication; however, this did not preclude completion of rehabilitation or achievement of functional gains. Ninety‐four percent of the cohort was discharged to a private residence following rehabilitation. No significant differences were observed between heart versus lung transplant recipients. Conclusions For debilitated patients following heart and/or lung transplantation, physical function, mobility, and independence significantly improved following multidisciplinary inpatient rehabilitation. Level of Evidence III

The association of high cyclin E expression with poor outcome in some cancers, in particular breast cancer, suggests that it may play an important role in tumor biology. Because the influence of cyclin E expression on outcome is yet to be examined in pancreatic cancer, we assessed the relationship between the expression of cyclin E, p27 Kip1 , and survival in a large cohort of pancreatic cancer patients with long-term follow-up. Expression of cyclin E and p27Kip1 was assessed by immunohistochemistry using tissue microarrays of tumor samples from 118 patients with pancreatic ductal adenocarcinoma (75 resections and 43 biopsies). High cyclin E expression (>10% positive nuclei) was identified in 39 of 118 (33%) patients. This was associated with poor prognosis on univariate analysis in the whole cohort (P = 0.005), as well as in the subgroup of 75 patients who underwent operative resection (P = 0.04). On multivariate analysis, high cyclin E expression was an independent predictor of poor survival in both the entire cohort (P = 0.005) and the resected subgroup (P = 0.03), and was superior to all tested clinicopathologic factors (tumor size, lymph node metastases, differentiation, margin involvement, and perineural invasion) as a marker of survival. Low p27Kip1 expression (<5% positive nuclei) was present in 41 of 111 (37%) patients, but was not associated with survival, and coexpression of p27Kip1 did not influence the association of high cyclin E expression with poor survival. High cyclin E expression is a strong independent predictor of poor outcome in patients with pancreatic cancer. Thus, if these data are confirmed in independent cohorts, measurement of cyclin E may add significant prognostic information to the currently used clinicopathologic variables and hence have potential clinical utility in the management of this disease. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1941-7)