Merkel Cell Carcinoma: 30-Year Experience from a Single Institution

Background

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy. Few single-institution series have been reported.

Methods

Review of MCC patients treated at our institution between 1980 and 2010. Patient, tumor, and treatment variables were analyzed to determine MCC-specific outcomes.

Results

We identified 161 patients with MCC. There was a 2.5-fold increase in cases over the last decade. Median length of follow-up was 36 months. Stage at diagnosis was I in 35 %, II in 21 %, IIIa in 12 %, IIIb in 23 %, and IV in 9 %. The 5-year MCC-specific survival rates were 87, 63, 42, and 0 % for stages I, II, III, and IV, respectively. Death from the disease occurred in 10 % of patients with T1 and in 50 % with larger lesions. One-third of patients presented with nodal disease. Sentinel lymph node biopsy (SLNB) identified micrometastases in 9 out of 27 (33 %) early-stage patients. Recurrence developed in 56 % of SLNB-positive and 39 % of SLNB-negative patients. Half of patients recurred after a median time of 9 months. Proportions of first recurrence location were distant (52 %), nodal (27 %), and local (21 %). Adjuvant treatments did not improve recurrence or survival rates. One-third of patients died of the disease.

Conclusions

SLNB identifies micrometastasis in one-third of early-stage patients. Negative SLNB may predict for improved but not necessarily favorable outcome. Initial tumor size and clinical nodal disease predict for poor outcome. High recurrence rates warrant the development of more effective adjuvant therapies, and better markers of recurrence and treatment response for MCC are needed.     

Skin substitutes with noncultured autologous skin cell suspension heal porcine full-thickness wounds in a one-stage procedure

Clinical application of skin substitute is typically a two-stage procedure with application of skin substitute matrix to the wound followed by engraftment of a split-thickness skin graft (STSG). This two-stage procedure requires multiple interventions, increasing the time until the wound is epithelialised. In this study, the feasibility of a one-stage procedure by combining bioengineered collagen-chondroitin-6-sulfate (DS1) or decellularised fetal bovine skin substitute (DS2) with autologous skin cell suspension (ASCS) in a porcine full-thickness wound healing model was evaluated. Twelve full-thickness excisional wounds on the backs of pigs received one of six different treatments: empty; ASCS; DS1 with or without ASCS; DS2 with or without ASCS. The ASCS was prepared using a point-of-care device and was seeded onto the bottom side of DS1, DS2, and empty wounds at 80 000 cells/cm². Wound measurements and photographs were taken on days 0, 9, 14, 21, 28, 35, and 42 post-wounding. Histological analysis was performed on samples obtained on days 9, 14, 28, and 42. Wounds in the empty group or with ASCS alone showed increased wound contraction, fibrosis, and myofibroblast density compared with other treatment groups. The addition of ASCS to DS1 or DS2 resulted in a marked increase in re-epithelialisation of wounds at 14 days, from 15 ± 11% to 71 ± 20% (DS1 vs DS1 + ASCS) or 28 ± 14% to 77 ± 26 (DS2 vs DS2 + ASCS) despite different mechanisms of tissue regeneration employed by the DS used. These results suggest that this approach may be a viable one-stage treatment in clinical practice.     

Development of a robotic walker for individuals with cerebral palsy

Abstract

Objective: This study describes the first use of a robotic walker in youth and young adults with cerebral palsy (CP) Gross Motor Function Classification (GMFCS) IV.

Methods: Semi-structured interviews were conducted before and after each robotic walker trial. Interviews were recorded, then transcribed and subjected to thematic analysis.

Results: Five participants (4 male, 13–22?years of age) with quadriplegia secondary to CP were recruited. Four individuals with mixed tone quadriplegia GMFCS IV were able to independently walk with the device. One individual with significant dyskinesia was unable to utilize the device. The assessment team included two physiotherapists, an occupational therapist, a physiatrist and three engineers. Major themes related to physical and social impacts were identified. Some physical advantages include the ability to walk hands-free and promotion of physical fitness. Examples of physical barriers include limited harness design and large device size. Social advantages include increased independence and peer engagement. Finally, a social disadvantage identified was limited use on uneven terrains.

Discussion: Suggestions for modifications for identified challenges and disadvantages include decreasing the size of the robotic walker, more harness designs, decreasing the force required to take an initial step, adding a joy stick for user control and creating a more versatile base that can be used on different terrains such as ice or baseball fields.

Conclusion: Robotics holds great hope for individuals with CP where mobility options are limited. Physical and social advantages are evident. Recommendations for future improvement and studies of use in exercise and participation are provided.

• IMPLICATIONS FOR REHABILITATION

• As youth and young adults with cerebral palsy age, options for mobilization can become limited with challenges in placing them in a walking device due to size and numerous other physical limitations.

• A robotic walker with a built-in mechanical lift is available for individuals with cerebral palsy.

• This study was able to gather important information and recommendations to tailor a new robotic walker prototype specifically for individuals with cerebral palsy.

     

Up-regulation of nucleotide excision repair in mouse lung and liver following chronic exposure to aflatoxin B1 and its dependence on p53 genotype

Aflatoxin B₁ (AFB₁) is biotransformed in vivo into an epoxide metabolite that forms DNA adducts that may induce cancer if not repaired. p53 is a tumor suppressor gene implicated in the regulation of global nucleotide excision repair (NER). Male heterozygous p53 knockout (B6.129-Trp53^tm1BrdN5, Taconic) and wild-type mice were exposed to 0, 0.2 or 1.0 ppm AFB₁ for 26 weeks. NER activity was assessed with an in vitro assay, using AFB₁-epoxide adducted plasmid DNA as a substrate. For wild-type mice, repair of AFB₁–N7-Gua adducts was 124% and 96% greater in lung extracts from mice exposed to 0.2 ppm and 1.0 ppm AFB₁ respectively, and 224% greater in liver extracts from mice exposed to 0.2 ppm AFB₁ (p < 0.05). In heterozygous p53 knockout mice, repair of AFB₁–N7-Gua was only 45% greater in lung extracts from mice exposed to 0.2 ppm AFB₁ (p < 0.05), and no effect was observed in lung extracts from mice treated with 1.0 ppm AFB₁ or in liver extracts from mice treated with either AFB₁ concentration. p53 genotype did not affect basal levels of repair. AFB₁ exposure did not alter repair of AFB₁-derived formamidopyrimidine adducts in lung or liver extracts of either mouse genotype nor did it affect XPA or XPB protein levels. In summary, chronic exposure to AFB₁ increased NER activity in wild-type mice, and this response was diminished in heterozygous p53 knockout mice, indicating that loss of one allele of p53 limits the ability of NER to be up-regulated in response to DNA damage.     

Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells

Although recent data suggests that osteoblasts play a key role within the hematopoietic stem cell (HSC) niche, the mechanisms underpinning this remain to be fully defined. The studies described herein examine the role in hematopoiesis of Osteopontin (Opn), a multidomain, phosphorylated glycoprotein, synthesized by osteoblasts, with well-described roles in cell adhesion, inflammatory responses, angiogenesis, and tumor metastasis. We demonstrate a previously unrecognized critical role for Opn in regulation of the physical location and proliferation of HSCs. Within marrow, Opn expression is restricted to the endosteal bone surface and contributes to HSC transmarrow migration toward the endosteal region, as demonstrated by the markedly aberrant distribution of HSCs in Opn-/- mice after transplantation. Primitive hematopoietic cells demonstrate specific adhesion to Opn in vitro via beta1 integrin. Furthermore, exogenous Opn potently suppresses the proliferation of primitive HPCs in vitro, the physiologic relevance of which is demonstrated by the markedly enhanced cycling of HSC in Opn-/- mice. These data therefore provide strong evidence that Opn is an important component of the HSC niche which participates in HSC location and as a physiologic-negative regulator of HSC proliferation.     

Egg consumption and risk of GI neoplasms: dose–response meta-analysis and systematic review

Purpose

Previous epidemiological studies on egg consumption and the risk of gastrointestinal (GI) neoplasms suggest a positive association; however, data are limited and the evidence remains controversial. This study aims to investigate and quantify the potential dose–response relationship with an evaluation of cancer site-specific differences.

Methods

Relevant studies were identified after the literature search via electronic databases until January 2014. Subgroup analysis for serving portions was performed using two standardized classification methods: (1) less than 3, or 3 or more eggs per week; (2) less than 3, 3–5, or more than 5 eggs per week. Method two excludes studies that only reported consumption frequency. Pooled adjusted odds ratios (ORs) comparing highest and lowest categories of dietary pattern scores were calculated using a random-effects model.

Results

Thirty-seven case–control and seven cohort studies were included for meta-analysis, which contained a total of 424,867 participants and 18,852 GI neoplasm cases. The combined odds ratio (OR) was calculated to 1.15 (95 % CI 1.09–1.22; p value heterogeneity <0.001), showing only a slight increase in risk. The correlation was stronger for colon cancers 1.29 (95 % CI 1.14–1.46; p value heterogeneity <0.22). Dose–response analysis revealed similar results with stratification methods, and the ORs for an intake of <3 and ≥3 eggs per week were 1.14 (95 % CI 1.07–1.22; p value heterogeneity = 0.38) and 1.25 (95 % CI 1.14–1.38; p value heterogeneity = 0.25), respectively. With method 2, the ORs for an intake of <3, 3–5, and >5 eggs per week were 1.13 (95 % CI 1.06–1.21; p value heterogeneity = 0.25), 1.14 (95 % CI 1.01–1.29; p value heterogeneity = 0.06), and 1.19 (95 % CI 1.01–1.39; p value heterogeneity <0.001), respectively.

Conclusion

This study provides evidence that egg consumption is associated with a positive dose–response association with the development of GI neoplasms.     

Is race or ethnicity associated with under-utilization of statins among women in the United States: The study of women's health across the nation

BackgroundRates of statin use among minority women are unclear.HypothesisWe hypothesized that statin use would vary by race/ethnicity with lower rates among minority women compared with Whites.MethodsData from the study of women''s health across the nation, a multiethnic cohort of women collected between 2009 to 2011 were used to examine reported statin use by race/ethnicity and risk profile. Multivariable logistic modeling was performed to estimate the odds ratio (OR) of statin treatment.ResultsOf the 2399 women included, 234 had a diagnosis of atherosclerotic disease (ASCVD), 254 were diabetic (without ASCVD), 163 had an LDL ≥190 mg/dL, and 151 had a 10 year ASCVD pooled risk score ≥7.5%. Statins were used by 49.6% of women with CVD; 59.8% of women with diabetes without known ASCVD; 42.3% of women with an LDL ≥190 mg/dL; and 19.9% of women with an ASCVD risk ≥7.5%. Rates of statin use were 43.8% for women with ≥ two prior ASCVD events and 69.4% for women with ≥ one prior ASCVD event plus multiple high‐risk conditions. Among women eligible for statins, Black women had a significantly reduced adjusted odds of being on a statin (OR 0.53, 95% confidence interval [CI] 0.36‐0.78) compared with White women.ConclusionsIn this cohort of multiethnic women, rates of statin use among women who would benefit were low, with Black women having lower odds of statin use than White women.     

The Effects of Express Lane Eligibility on Medicaid and CHIP Enrollment among Children

Objective

To estimate the impact of Express Lane Eligible (ELE) implementation on Medicaid/CHIP enrollment in eight states.

Data Sources/Study Setting

2007 to 2011 data from the Statistical Enrollment Data System (SEDS) on Medicaid/CHIP enrollment.

Study Design

We estimate difference-in-difference equations, with quarter and state fixed effects. The key independent variable is an indicator for whether the state had ELE in place in the given quarter, allowing the experience of statistically matched non-ELE states to serve as a formal counterfactual against which to assess the changes in the eight ELE states. The model also controls for time-varying economic and policy factors within each state.

Data Collection/Extraction Methods

We obtained SEDS enrollment data from CMS.

Principal Findings

Across model specifications, the ELE effects on Medicaid enrollment among children were consistently positive, ranging between 4.0 and 7.3 percent, with most estimates statistically significant at the 5 percent level. We also find that ELE increased combined Medicaid/CHIP enrollment.

Conclusions

Our results imply that ELE has been an effective way for states to increase enrollment and retention among children eligible for Medicaid/CHIP. These results also imply that ELE-like policies could improve take-up of subsidized coverage under the ACA.