Citations

Background: Ulnar collateral ligament (UCL) reconstruction is frequently performed in throwing athletes, but outcomes of UCL reconstruction requiring excision of bone, either within the substance of or replacing the UCL, have not been studied. Hypothesis: Clinical outcome for throwing athletes after UCL reconstruction with gracilis tendon will be less favorable for patients requiring concurrent excision of bone from within the substance of the UCL than for patients with no bone excision within, or replacing, the ligamentous anatomy. Study Design: Cohort Study; Level of evidence, 3. Methods: One hundred twenty pitchers of competitive levels between high school and major league who underwent UCL reconstruction using contralateral gracilis autografts completed a phone survey, and their medical charts were reviewed. Follow-up was a minimum of 2 years. Among the 120 patients, 42 (35%) had bone within, or replacing, the substance of the native UCL (bony group), and 78 (65%) had no bony abnormalities (nonbony group). The latter group of 78 underwent UCL reconstruction using gracilis tendon graft due to the absence of a palmaris longus tendon. Clinical outcomes were compared between the 2 study groups using t tests and χ 2 analyses. Results: There were no statistical differences regarding time to return to throwing, time to return to competition, postoperative complications, or need for additional surgeries. The percentage of patients who returned to the same or higher level was higher in the nonbony group (91%) than in the bony group (81%), but this trend was not statistically significant ( P = .083), likely due to a relatively small sample size. Changes in self-reported pitch control were different ( P = .029) between the 2 groups, with a greater percentage of pitchers experiencing decreased control in the bony group. Conclusion: The presence of bone concomitant with UCL damage can lead to pitch control problems after UCL reconstruction and may also decrease the chance of return to play.

Abstract Purpose: miRNA plays an important role in human disease and cancer. We seek to investigate the expression status, clinical relevance, and functional role of miRNA in non–small cell lung cancer. Experimental Design: We conducted miRNA expression profiling in matched lung adenocarcinoma and uninvolved lung using 56 pairs of fresh-frozen (FF) and 47 pairs of formalin-fixed, paraffin-embedded (FFPE) samples from never smokers. The most differentially expressed miRNA genes were evaluated by Cox analysis and log-rank test. Among the best candidate, miR-708 was further examined for differential expression in two independent cohorts. Functional significance of miR-708 expression in lung cancer was examined by identifying its candidate mRNA target and through manipulating its expression levels in cultured cells. Results: Among the 20 miRNAs most differentially expressed between tested tumor and normal samples, high expression level of miR-708 in the tumors was most strongly associated with an increased risk of death after adjustments for all clinically significant factors including age, sex, and tumor stage (FF cohort: HR, 1.90; 95% CI, 1.08–3.35; P = 0.025 and FFPE cohort: HR, 1.93; 95% CI, 1.02–3.63; P = 0.042). The transcript for TMEM88 gene has a miR-708 binding site in its 3′ UTR and was significantly reduced in tumors high of miR-708. Forced miR-708 expression reduced TMEM88 transcript levels and increased the rate of cell proliferation, invasion, and migration in culture. Conclusions: miRNA-708 acts as an oncogene contributing to tumor growth and disease progression by directly downregulating TMEM88, a negative regulator of the Wnt signaling pathway in lung cancer. Clin Cancer Res; 18(13); 3658–67. ©2012 AACR.

Abstract The Ras GTPase-activating-like protein IQGAP1 is a multimodular scaffold that controls signaling and cytoskeletal regulation in fibroblasts and epithelial cells. However, the functional role of IQGAP1 in T cell development, activation, and cytoskeletal regulation has not been investigated. In this study, we show that IQGAP1 is dispensable for thymocyte development as well as microtubule organizing center polarization and cytolytic function in CD8+ T cells. However, IQGAP1-deficient CD8+ T cells as well as Jurkat T cells suppressed for IQGAP1 were hyperresponsive, displaying increased IL-2 and IFN-γ production, heightened LCK activation, and augmented global phosphorylation kinetics after TCR ligation. In addition, IQGAP1-deficient T cells exhibited increased TCR-mediated F-actin assembly and amplified F-actin velocities during spreading. Moreover, we found that discrete regions of IQGAP1 regulated cellular activation and F-actin accumulation. Taken together, our data suggest that IQGAP1 acts as a dual negative regulator in T cells, limiting both TCR-mediated activation kinetics and F-actin dynamics via distinct mechanisms.

What's known on the subject? and What does the study add? Postoperative complications for open radical nephrectomy ( ORN ), laparoscopic radical nephrectomy ( LRN ), and open partial nephrectomy ( OPN ) and its relationship with hospitalisation costs and mortality remain poorly described. The present population‐based study suggests modest differences in postoperative complications estimated at 27%, 23%, and 24% among patients with kidney cancer undergoing ORN , LRN , and OPN , respectively. Moreover, postoperative complications were associated with higher mortality, length of stay and total costs of hospitalisation. Objectives The association of complications after renal surgery for renal cell carcinoma ( RCC ) with in‐hospital mortality and costs remains to be defined. To describe the incidence of complications after open radical nephrectomy ( ORN ), laparoscopic RN ( LRN ), and open partial nephrectomy ( OPN ); and to evaluate its relationship with in‐hospital mortality and total costs. Patients and Methods We identified 49 983 individuals who underwent ORN (35 712), LRN (5327), or OPN (8944) for RCC at 2037 hospitals from the Nationwide Inpatient Sample 2001–2008. The outcomes assessed were in‐hospital mortality and total hospitalisation costs. Multivariable logistic regression and generalised estimating equations were used to test the associations between complications and in‐hospital mortality and total costs. Results With 26.0% of patients experiencing postoperative complications, there were modest differences in the proportion of patients with complications after ORN , LRN , and OPN at 27.0%, 22.6%, and 24.0%, respectively ( P < 0.001). After adjusting for patient and hospital variables, postoperative complications resulted in higher odds of in‐hospital death for ORN (odds ratio [ OR ] 7.20; P < 0.001), LRN ( OR 12.04; P < 0.001), and OPN ( OR 7.82; P < 0.001). Adjusted total costs also rose significantly with the presence of any postoperative complications compared with those without any complications for ORN ($21 242 vs $13 183; P < 0.001), LRN ($19 548 vs $12 555; P < 0.001), and OPN ($18 883 vs $12 098; P < 0.001). Conclusions With about a quarter of patients experiencing postoperative complications, adverse events for ORN , LRN , and OPN carry a significant risk of in‐hospital death and higher total costs. Efforts to reduce postoperative complications may correlate with substantial reductions in hospital mortality and total costs.

Abstract B39 Background The breast glandular epithelium is composed of lobules that undergo age-related involution that increases as women age and has been associated with lowered breast cancer risk. Mammographic density (MD) is an established risk factor for breast cancer that has been shown to decrease with age. This study examined the association of age-related lobular involution with mammographic breast density. Materials and Methods The study sample was selected from approximately 20,000 healthy women who were enrolled in a screening cohort at the Mayo Clinic (Mayo Mammography Health Study) from 2003 to 2006 and had a benign breast biopsy (BBD) within 2 years of the enrollment mammogram. A quantitative measure of mammographic density, percent density (PD) was estimated on the enrollment mammogram, in addition to its components dense and nondense area (NDA). All biopsies were reviewed by a breast pathologist for the type of benign breast disease (BBD) as well as lobular involution status. Involution was defined as the proportion of terminal ductal lobular units (TDLUs) in the background tissue on biopsy that showed at least 50% decrease in size and number of acini from normal lobules and was subjectively assessed as: No- 0% involution, Partial- 1 to 74%, or Complete- &gt;75% involution. Mean density was estimated for the 3 categories of involution using generalized linear models and square root transformation. Confounders were assessed including age, parity, body mass index (BMI), type of BBD, menopausal status, age at first birth and family history Results A total of 317 women from the MMHS had BBD within 2 years of enrollment. Mean age at BBD diagnosis in this sample was 55 years. Age- and BMI- adjusted analyses suggested an inverse association of involution and percent density with adjusted mean PD values of 23.3 (95%CI [17.2, 30.3]) for no involution, 21.9 (95%CI [20.0, 23.9]) for partial involution, and 17.8 (95% CI [14.7, 21.3]) for complete involution (p for trend 0.05). This trend was driven primarily by the positive association of involution with nondense area with adjusted mean NDA values of 103.1cm2 (95% CI [86.1, 121.7]) for no involution, 104.9 cm2 (95% CI [99.4, 110.7]) for partial involution, and 126.2 cm2 (95% CI [115.0, 137.9]) for complete involution (p for trend 0.004). Discussion Our findings suggest that MD is inversely associated with involution of breast tissues, providing a plausible mechanism through which MD influences breast cancer risk. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B39.

Context— Posttransplant quality of life can be significantly affected by personality characteristics identified before transplant. Objective— Although overall quality of life in heart transplant patients improves after transplant, many studies reveal poorer mental health outcomes after transplant. We aimed to determine whether transplant recipients with an optimistic explanatory style had improved quality of life, fewer depressive symptoms, and increased survival. Design— We reviewed 68 patients who had completed a Minnesota Multiphasic Personality Inventory a mean of 2 years before transplant and examined associations between scores on the Optimism-Pessimism scale, survival rates, and results from the Health Status Questionnaire nearly 4 years after transplant. Results— Optimism was significantly associated with higher quality of life even after age (at the time of transplant), sex, depression score before transplant, time from the personality inventory to transplant, and time from transplant to the Health Status Questionnaire were controlled for. Furthermore, a pessimistic explanatory style was significantly associated with self-reported depressive symptoms, even after depression before transplant was adjusted for. Neither optimism nor pessimism was associated with length of survival. Conclusions— Pretransplant patients with a pessimistic explanatory style reported depressive symptoms nearly 5 years later. Furthermore, over the same time span, patients with an optimistic explanatory style described a significantly higher quality of life than the pessimists described.

What's known on the subject? and What does the study add? There is great variability in the utilization of partial nephrectomy, but the causes of these variations are not well understood. The present study underscores the already observed phenomenon of surgical volume influencing surgical planning and outcomes, but it gets at why this might be so. We observe that high‐volume renal surgeons have different thresholds of ‘technical feasibility’. Objective To investigate why there continues to be wide variability in the application of partial nephrectomy ( PN ) for treating small renal masses despite guidelines in the US and E urope stating that a PN is a standard of care for a patient with a T 1 renal mass. Patients and Methods In June 2009, 764 surgeon‐members of the A merican U rologic A ssociation ( AUA ) participated in a survey evaluating the management of renal masses. Renal mass complexity was graded by nephrometry score ( NS ). Multivariable logistic regression models with generalized estimating equations were constructed to evaluate how tumour, surgeon and practice‐setting characteristics influence the use of PN . Results The survey response rate was 19%. Each urological surgeon responded to eight scenarios, providing 6112 evaluable cases. Tumour NS ranged from 4 to 10, and each unit increase in NS was associated with 59% increased likelihood of a surgeon offering RN on multivariable analysis (odds ratio [ OR ] = 1.59; 95% CI : 1.52–1.64). When holding patient and tumour characteristics constant, the following surgeon and practice‐setting characteristics significantly increased the odds of offering a PN: increasing renal case volume ( OR = 1.57; 95% CI : 1.27–1.95), academic practice ( OR = 1.80; 95% CI : 1.42–2.29), increasing PN % volume ( OR = 3.7; 95% CI : 2.46–5.55) and younger surgeon age (≤40 vs >50 years) ( OR = 1.64; 95% CI : 1.35–1.96). Conclusion The characteristics of a surgeon and the setting in which he or she practices influence the utilization of PN , the adherence to professional guidelines, and the threshold of tumour complexity at which a surgeon stops offering PN .