Topography of Prostate Cancer Recurrence After Radiation Therapy: A Detailed Mapping Study of Salvage Radical Prostatectomy Specimens

In men who do not respond to initial radiation therapy, accurate knowledge of the site of cancer recurrence or persistence is necessary to understand treatment failure. We evaluated the pathologic characteristics of recurrent/persistent prostate cancer with tumor maps from the whole-mount slides of salvage radical prostatectomies performed between 2000 and 2014. Of 216 consecutive patients, detailed tumor maps were available for 77. Sixty-nine patients (90%) were found to have tumor in the apex, of which 46% occurred in the most apical 3 mm. Fifty-three patients (69%) had tumors at a distance of ≤5 mm from the urethra. Five patients had tumor directly involving the urethra, all of whom had urethral invasion at the apex. Seminal vesicle involvement was seen in 32 patients (42%), two of whom had tumor only in the seminal vesicles. Sixty-two patients (81%) had tumors in the distal apex, periurethral area, or seminal vesicles, that is, areas that are not routinely biopsied. Targeting these areas could improve the accuracy of biopsy when cancer recurrence is suspected.

Impact of Trauma System Structure on Injury Outcomes: A Systematic Review and Meta-Analysis

Background

The effectiveness of trauma systems in decreasing injury mortality and morbidity has been well demonstrated. However, little is known about which components contribute to their effectiveness. We aimed to systematically review the evidence of the impact of trauma system components on clinically important injury outcomes.

Methods

We searched MEDLINE, EMBASE, Cochrane CENTRAL, and BIOSIS/Web of Knowledge, gray literature and trauma association Web sites to identify studies evaluating the association between at least one trauma system component and injury outcome. We calculated pooled effect estimates using inverse-variance random-effects models. We evaluated quality of evidence using GRADE criteria.

Results

We screened 15,974 records, retaining 41 studies for qualitative synthesis and 19 for meta-analysis. Two recommended trauma system components were associated with reduced odds of mortality: inclusive design (odds ratio [OR] = 0.72 [0.65–0.80]) and helicopter transport (OR = 0.70 [0.55–0.88]). Pre-Hospital Advanced Trauma Life Support was associated with a significant reduction in hospital days (mean difference [MD] = 5.7 [4.4–7.0]) but a nonsignificant reduction in mortality (OR = 0.78 [0.44–1.39]). Population density of surgeons was associated with a nonsignificant decrease in mortality (MD = 0.58 [?0.22 to 1.39]). Trauma system maturity was associated with a significant reduction in mortality (OR = 0.76 [0.68–0.85]). Quality of evidence was low or very low for mortality and healthcare utilization.

Conclusions

This review offers low-quality evidence for the effectiveness of an inclusive design and trauma system maturity and very-low-quality evidence for helicopter transport in reducing injury mortality. Further research should evaluate other recommended components of trauma systems and non-fatal outcomes and explore the impact of system component interactions.

     

A feasibility double-blind randomized placebo-controlled trial of extracorporeal shockwave therapy as a novel treatment for intermittent claudication

Background

Intermittent claudication is the most common symptom of peripheral arterial disease. Previous research has suggested that extracorporeal shockwave therapy (ESWT) may induce angiogenesis in treated tissue. The objective of this feasibility pilot trial was to assess the safety, tolerability, and efficacy of ESWT as a novel treatment.

Response to sirolimus in capillary lymphatic venous malformations and associated syndromes: Impact on symptomatology,quality of life,and radiographic response

Background

Capillary lymphatic venous malformations (CLVM) and associated syndromes, including Klippel–Trenaunay syndrome (KTS) and congenital lipomatous overgrowth, vascular malformation, epidermal nevi, skeletal, and spinal syndrome (CLOVES), are underrecognized disorders associated with high morbidity from chronic pain, recurrent infections, bleeding, and clotting complications. The rarity of these disorders and heterogeneity of clinical presentations make large-scale randomized clinical drug trials challenging. Identification of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [gene]) mutations in CLVM has made targeted medications, such as sirolimus, attractive treatment options. The aim of this study was to investigate the safety and efficacy of sirolimus therapy in CLVM.

Procedure

A combined prospective and retrospective cohort of pediatric and young adult patients with CLVM treated with sirolimus was evaluated for disease response, including symptom improvement, quality of life (QOL), and radiologic response. Sirolimus dosing regimens and toxicities were also assessed.

Results

Twenty-nine patients with CLVM, including KTS and CLOVES, were included. Ninety-three percent of patients reported improved QOL, and 86% had improvement in at least one symptom. Most significantly, improvement was noted in 100% of patients with bleeding and 89% with thrombotic complications with corresponding decreases in mean D-dimer (p = .008) and increases in mean fibrinogen (p = .016). No patients had progressive disease on sirolimus. Most common side effects included neutropenia, lymphopenia, infection, and aphthous ulcers/stomatitis. No toxicities were life-threatening, and none required long-term discontinuation of sirolimus.

Conclusion

Sirolimus appears to be effective at reducing complications and improving QOL in patients with CLVM and associated syndromes. In this patient cohort, sirolimus was well tolerated and resulted in few treatment-related toxicities.     

Decreasing Use of Axillary Dissection in Node-Positive Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Background

Neoadjuvant chemotherapy (NAC) may downstage axillary disease in node-positive breast cancer. Several clinical trials have shown that sentinel lymph node (SLN) surgery after NAC is feasible for these patients. We sought to evaluate the use of SLN surgery and ALND in cN1 patients undergoing NAC.

Methods

We identified all patients with biopsy-proven cN1 breast cancer treated with NAC at our institution between January 2009 and December 2017. Approximated biologic subtype was determined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. Cochran–Armitage trend and Chi square tests were used for statistical analysis.

Results

Of 430 cN1 patients treated with NAC, 93 (22%) underwent SLN surgery only, 100 (23%) underwent SLN and ALND, and 237 (55%) underwent ALND only. The use of SLN surgery (±?ALND) increased from 28% in 2009 to 86% in 2017 (p?<?0.001), while the performance of ALND decreased from 100% in 2009 to 38% in 2017 (p?<?0.001). Among SLN+ patients who underwent ALND, disease was limited to the SLNs in 25/73 (34%) patients. The nodal pathologic complete response rate was 46% and varied by tumor subtype (p?<?0.001). Among patients undergoing SLN surgery, ALND was avoided in 48% of patients overall and varied by biologic subtype: 55% ER?/HER2+, 61% ER+/HER2+, 62% ER?/HER2?, and 31% ER+/HER2? (p?=?0.001). With short-term follow-up, no nodal recurrences have occurred in patients without ALND.

Conclusions

We observed a significant shift in axillary surgery for cN1 breast cancer patients treated with NAC, with increasing use of SLN surgery to assess nodal treatment response, and decreasing use of ALND.

     

Screening for ADHD in adults with cystic fibrosis: Prevalence,health-related quality of life,and adherence

Background

International guidelines recommend depression and anxiety screening in individuals with cystic fibrosis (CF), but Attention-Deficit Hyperactivity Disorder (ADHD) remains understudied.

Impact of pubertal timing and depression on error-related brain activity in anxious youth

Anxiety disorders are associated with enhanced error-related negativity (ERN) across development but it remains unclear whether alterations in brain electrophysiology are linked to the timing of puberty. Pubertal timing and alterations of prefrontal and limbic development are implicated in risk for depression, but the interplay of these factors on the ERN–anxiety association has not been assessed. We examined the unique and interactive effects of pubertal timing and depression on the ERN in a sample of youth 10–19 years old with anxiety disorders (n = 30) or no history of psychopathology (n = 30). Earlier pubertal maturation was associated with an enhanced ERN. Among early, but not late maturing youth, higher depressive symptoms were associated with a reduced ERN. The magnitude of neural reactivity to errors is sensitive to anxiety, depression, and development. Early physical maturation and anxiety may heighten neural sensitivity to errors yet predict opposing effects in the context of depression.