Mohs versus surgical excision in nonmelanoma skin cancers: does location matter?

INTRODUCTION: Every year, nearly 1.2 million people are affected by nonmelanoma skin cancers (NMSCs) in the United States. Most published data focus on comparing the efficacy of Mohs micrographic surgery (MMS) versus traditional surgical excision (TSE) for NMSCs in H-zone lesions of the face. There is paucity of data regarding the 2 treatments in other areas such as the non-H-zone areas of the face, the trunk, and extremities. Our study focused on the efficacy of the 2 treatments in areas of the body where the skin was not of premium. METHOD: A retrospective chart review was performed of patients with NMSCs treated with TSE at the West Los Angeles Veterans Affairs Hospital between 2000 and 2008. Patients with at least a 3-year follow-up were selected for the study. Institutional review board approval was obtained before commencement of the study. Age, sex, and race-matched patients were selected in the MMS group. Data collected included demographic data, tumor characteristics, surgical treatment, reconstructions, recurrence rates, complications, and follow-up course. Data were analyzed using SigmaStat 3.5. RESULTS: A total of 588 patients were treated for NMSCs at our institute between 2000 and 2008, of which 289 patients had non-H-zone, extremity, and trunk lesions. The follow-up period for these patients was at least 3 years. Average age of this group was 67.1 (11.4) with 89.9% being males. Age, sex, and race-matched group of 200 patients treated with MMS for NMSCs were randomly chosen from the same time range. Average size of lesions was 17.4 (16.9) mm in the TSE group and 1.1 (0.4) mm in the MMS group (P < 0.05). Primary reconstruction was performed in non-premium areas (ie, non-H-zone areas of the face, the trunk, and extremities) in 98.7% patients in the TSE group and 61.5% patients in the MMS group (P < 0.05). Secondary reconstructive rate was 1.3% in TSE compared to 37.5% in MMS. Overall recurrence rate was 4.8% (compared to 3% with MMS). Of the 29 patients who had recurrences within the TSE group, 27 were H-zone lesions and 2 were non-H-zone lesions. DISCUSSION: One of the primary goals of NMSC management is to treat the lesion with adequate oncologic margins, while preserving maximal function and cosmesis. Our data look at the non-premium areas to quantify the clinical efficacy of TSE versus MMS. The size of lesions treated by TSE was significantly larger than those treated by MMS in all areas of the body. The primary closure rates were significantly higher and secondary procedure rates significantly lower in the TSE group compared to the MMS group, in non-premium areas. Our data suggest that patients with NMSCs may be more effectively treated with TSE than MMS in non-premium areas of the body. Additional studies are ongoing, including economic modeling and cost analysis.

Acute and Long-Term Cardiovascular Effects of Stimulant, Guanfacine, and Combination Therapy for Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES: This study examines cardiovascular (CV) effects of guanfacine immediate-release (GUAN-IR), dexmethylphenidate extended-release (DMPH), and their combination (COMB) during acute and long-term treatment of youth with attention-deficit/hyperactivity disorder. METHODS: Two hundred seven participants aged 7-14 years enrolled in an 8-week double-blind randomized trial of GUAN-IR (1-3 milligrams (mg)/day), DMPH (5-20 mg/day), or COMB with fixed-flexible dosing and titrated to optimal behavioral response. Heart rate, systolic blood pressure (BP), diastolic BP, and electrocardiograms were assessed at baseline, end of blinded optimization, and over a 1-year open-label maintenance phase. RESULTS: During acute titration, GUAN-IR decreased heart rate, systolic BP, and diastolic BP; DMPH increased heart rate, systolic BP, diastolic BP, and corrected QT (QTc) interval; COMB increased diastolic BP, but had no effects on heart rate, systolic BP, or QTc. During maintenance, GUAN-IR-associated decreases in heart rate and DMPH-associated increases in systolic BP returned to baseline values. Other variables across the three groups remained unchanged from the end of blinded titration. There were no discontinuations due to CV adverse events. CONCLUSION: GUAN-IR, DMPH, and COMB were well tolerated and safe. Expected changes in CV parameters during acute titration were seen in GUAN-IR and DMPH groups, with COMB values falling intermediately between the two other treatment groups. No serious CV events occurred in any participant. GUAN-IR- and DMPH-associated CV changes generally returned to baseline with sustained therapy. These data suggest that COMB treatment might attenuate long-term CV effects of GUAN-IR and stimulant monotherapy, possibly reducing risk of the small but statistically significant changes associated with either single treatment. Clinicaltrials.gov Identifier: NCT00429273.

Sexual satisfaction and quality of life in major depressive disorder before and after treatment with citalopram in the STAR*D study.

OBJECTIVE: Major depressive disorder (MDD) patients often experience impaired sexual satisfaction (ISS) and poor quality of life (QOL). Selective serotonin reuptake inhibitors (SSRIs), the first-line treatment for MDD, can cause sexual dysfunction, potentially worsening ISS and QOL. This study examined the impact of MDD and the SSRI citalopram on sexual satisfaction and QOL in level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial (July 2001-September 2006). METHOD: A retrospective analysis was conducted of the change in sexual satisfaction, as measured by item 9 of the Quality of Life Enjoyment and Satisfaction Questionnaire, the primary outcome measure, in 2,280 patients with DSM-IV-TR-defined MDD who were treated with citalopram for 12 weeks. The Quick Inventory of Depressive Symptomatology-Self Report was used to evaluate the impact of depression ratings on impaired sexual satisfaction and on QOL. RESULTS: Impaired sexual satisfaction was present in 64.3% of MDD patients at pretreatment, but that percentage declined to 47.1% at posttreatment with citalopram (P < .0001). Those who achieved remission had less ISS and better QOL. The prevalence of ISS in remitters was 21.2% versus 61.3% in nonremitters (P < 10(-8)). The mean ± standard deviation score for remitters increased from 2.32 ± 1.16 to 3.44 ± 1.23 (P < 10(-8); Cohen d = 0.81 [large effect size]), whereas in nonremitters it increased only from 1.99 ± 1.08 to 2.19 ± 1.19 (P < 10(-8); Cohen d = 0.16). The difference between remitters and nonremitters was highly significant (P < 10(-8)). Regression analyses at pretreatment and posttreatment demonstrated significant associations between depressive symptoms and ISS (P < .0001) and between ISS and lower QOL (P < .0001) as well as an association between citalopram and increased probability of ISS and a poorer QOL in patients who continue to have moderate-to-severe depression. CONCLUSIONS: A majority of MDD patients have impaired sexual satisfaction, a symptom associated with poor QOL. Despite the sexual side effects of the SSR citalopram, treating depression to full remission was associated with improvements in sexual satisfaction and QOL. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00021528.

Health-related quality of life in childhood cancer.

OBJECTIVE: Health-related quality of life (HRQoL) has become an increasingly important measure of research and treatment outcomes across all medical specialties. However, to date, there has not been an in-depth review of research relevant specifically to HRQoL in the populations of children and adolescents with cancer. In this review, the authors examine the effects of cancer on HRQoL from diagnosis to remission/survivorship and the end of life. DESIGN: A literature search was conducted using Medline and PsycINFO for articles published from 2002 to 2011. Studies included patients from diagnosis to remission and also the terminally ill. Twenty-nine studies specifically addressing HRQoL were selected after reaching consensus and study quality check. RESULTS: Children who are newly diagnosed with cancer and are undergoing treatment or are terminally ill have impaired HRQoL. Survivors of childhood cancer have high HRQoL (with the exception of those who experienced medical comorbidity or PTSD). The authors found that demographic differences, cancer types, and treatment regimens, all significantly influence the negative impact of cancer on patients' HRQoL. CONCLUSIONS: There are specific and identifiable impacts of childhood cancer on patients' HRQoL that are significant and complex across the span of the illness. There is a need for continued research in many areas related to this population, especially related to those with terminal illness in order to improve patient care.

Extracellular-signal-related kinase 1/2 is responsible for inhibition of osteogenesis in three-dimensional cultured MC3T3-E1 cells.

We have previously demonstrated that osteogenic differentiation is inhibited and angiogenic expression is enhanced in murine preosteoblasts (MC3T3-E1) cultured on three-dimensional (3D) poly-L-lactide-co-glycolide (PLGA) scaffolds when compared to two-dimensional (2D) PLGA films. In the present work we investigated the role of the extracellular signal-related kinase 1/2 (ERK1/2) pathway in modulating osteogenic and angiogenic differentiation in 2D and 3D systems made of two distinct biomaterials-type I collagen and PLGA. The addition of a third dimension, regardless of biomaterials, substantially increased ERK1/2 activation as demonstrated by an increase in phosphorylated ERK1/2. Western blot analysis showed significant increases in phosphorylation of ERK1/2 in cells grown in 3D versus 2D cultures at day 4 (5- and 7.7-fold increases 3D vs. 2D in collagens and PLGA, respectively) and day 7 (4.7- and 4.6-fold increases 3D vs. 2D in collagen and PLGA, respectively). Using an ERK-specific inhibitor, PD 98059, we established a correlation between ERK activation and inhibited osteogenic differentiation. Inhibition of ERK activation in 3D cultures significantly enhanced osteogenic differentiation. It in fact restored osteogenic differentiation to a level equal to that of 2D cultured cells. Inhibition of ERK1/2, however, showed little effect on angiogenic gene expression, indicating that two distinct mechanisms are involved in osteogenic and angiogenic differentiation. Taken together, these results allow us to report a mechanistic model in MC3T3-E1 cells in which distinct activation of ERK1/2 in 3D culture has an inhibitory effect on osteogenic differentiation.