Analysis of the surgical management of skin cancer in the nonagenarian population: Twenty-five year data analysis from a single centre.

BACKGROUND: There were 142,101 new cases of non-melanomatous skin cancers reported by the UK National Cancer Statistics in 2015. The UK statistics published that the incidence is highest in the 90+ population and that this represented an overall 61% increase in skin cancer incidence in the UK in the last decade. This article aims to first provide an understanding of the change in service requirement over the last 25 years for skin cancer management in nonagenarians, and second, understand the subtypes of skin cancer and possible differences in the management for this cohort. METHODS: All skin cancer biopsies received by a UK university teaching hospital dermato-histopathology department were analysed over a five-year period spanning 2013-2017. This was compared with snap shot data at five-year intervals dating back to 1993. The patient demographics including age, sex and anatomical region were seen along with the types of skin cancers and histological subtypes. RESULTS: A total of 1050 skin cancers were managed with surgical input between January 2013 and December 2017 in 733 patients. The number of biopsies/year has increased 7-fold from 1993 (33) to 2017 (231). The annual cost of the surgical element to this service has dramatically increased, and in 2017, it was £220k compared to £33k in 1993. CONCLUSION: Partly because of the ageing UK population, there has been a dramatic increase in the demand on the surgical service regarding managing skin cancers in those over the age of 90. There is a higher rate of incomplete excision in this population than that reported in the national British Association of Dermatologists (BAD) guidelines. Despite higher incomplete excision rates, there is a low re-operation rate in this population probably due to patient comorbidities affecting reconstructive options, patient preference and clinical decisions on surgical morbidity versus benefit.

A single centre experience of squamous cell carcinoma of the upper limb requiring digital or hand amputation and review of literature.

Squamous cell carcinoma (SCC) is one of the most common primary malignancies affecting the upper limb. A range of treatment options exist for its management; amputation being indicated under certain instances. This is the first comprehensive case series and review of the literature reporting outcomes following amputation of the affected region for treatment of upper extremity SCC. We present a series of six patients with squamous cell carcinoma of the upper limb that required amputation alongside that of data from literature review. Patient demographics, risk factors, tumour characteristics and rates of recurrence, metastasis and mortality were recorded. A total of 45 patients with 49 histologically confirmed squamous cell carcinomas were identified from case series and literature review. Patients presenting with upper limb SCC were predominantly male and in their sixth decade of life. Mean follow up time was 30.5 months and the overall recurrence and metastatic rates were 8.2% and 14.3%, respectively. Mortality was 14.3% however only 6.1% was related to SCC metastasis. Rates of recurrence and metastasis are higher for SCCs affecting the hand as compared to other body sites. Furthermore, different regions of the hand appear to behave differently. SCC affecting the nail unit has a high recurrence and a low metastatic rate, whereas, SCC involving the palm and webspaces are aggressive and this is true despite amputation of the affected site.

Promoting routine stair use: evaluating the impact of a stair prompt across buildings.

BACKGROUND: Although studies have demonstrated that stair prompts are associated with increased physical activity, many were conducted in low-rise buildings over a period of weeks and did not differentiate between stair climbing and descent. PURPOSE: This study evaluated the impact of a prompt across different building types, and on stair climbing versus descent over several months. METHODS: In 2008-2009, stair and elevator trips were observed and analyzed at three buildings in New York City before and after the posting of a prompt stating "Burn Calories, Not Electricity" (total observations=18,462). Sites included a three-story health clinic (observations=4987); an eight-story academic building (observations=5151); and a ten-story affordable housing site (observations=8324). Stair and elevator trips up and down were recorded separately at the health clinic to isolate the impact on climbing and descent. Follow-up was conducted at the health clinic and affordable housing site to assess long-term impact. RESULTS: Increased stair use was seen at all sites immediately after posting of the prompt (range=9.2%-34.7% relative increase, p<0.001). Relative increases in stair climbing (20.2% increase, p<0.001) and descent (4.4% increase, p<0.05) were seen at the health clinic. At both sites with long-term follow-up, relative increases were maintained at 9 months after posting compared to baseline: 42.7% (p<0.001) increase in stair use at the affordable housing site and 20.3% (p<0.001) increase in stair climbing at the health clinic. CONCLUSIONS: Findings suggest that the prompt was effective in increasing physical activity in diverse settings, and increases were maintained at 9 months.

Biphasic synovial sarcoma of the extremity: quadruple approach of isolated limb perfusion, surgical ablation, adipofascial perforator flap and radiation to avoid amputation.

Synovial sarcoma is a rare type of soft tissue sarcoma that occurs mostly in young adults, and it is always regarded as a high-grade tumor. Here, we report the case of a 31-year-old German Caucasian male with synovial sarcoma of the wrist who was offered amputation at his local hospital. After referral to our Reference Centre for Soft Tissue Sarcoma, the quadruple approach of isolated limb perfusion, surgical ablation, adipofascial perforator flap and radiation avoided amputation and enabled preservation of good hand function with no evidence of recurrence or metastasis after 1 year.

CD40 expression levels modulate regulatory T cells in Leishmania donovani infection.

Dendritic cell (DC)-expressed CD40 is shown to play crucial roles in eliciting effector T cell responses, primarily the proinflammatory CD4(+) Th subsets and cytotoxic CD8(+) T cells that eliminate various infections and tumors, respectively. In contrast, DCs are also implied in the generation of regulatory T cells (Tregs) that counteract the functions of the proinflammatory Th subsets and exacerbate infections. However, the role of DC-expressed CD40 in the generation of Tregs is unknown. In this study, we generated bone marrow-derived DCs from mice (on a BALB/c background) expressing different levels of CD40 and tested their relative efficiency in generating Tregs. We observed that low levels of CD40 expression were required for efficient Treg generation. DCs expressing low levels of CD40 induced Tregs, whereas DCs expressing high levels of CD40 induced effector T cells, possibly CD8(+)CD40(+) T cells with a contraregulatory activity; the adoptive transfer of the former DC exacerbated whereas the latter significantly reduced Leishmania donovani infection in BALB/c mice. Similarly, priming of mice with leishmanial Ag-pulsed DCs expressing high levels of CD40 induced host protection against L. donovani challenge infection. In contrast, priming with the low CD40-expressing DC resulted in aggravated infection as compared with the control mice. The results establish that CD40 can play differential roles in Treg differentiation and determine the course of infection. We demonstrate that the knowledge can be efficiently used in adoptive cell transfer therapy against an infectious disease.

Overreporting of deaths from coronary heart disease in New York City hospitals, 2003.

INTRODUCTION: New York City has one of the highest reported death rates from coronary heart disease in the United States. We sought to measure the accuracy of this rate by examining death certificates. METHODS: We conducted a cross-sectional validation study by using a random sample of death certificates that recorded in-hospital deaths in New York City from January through June 2003, stratified by neighborhoods with low, medium, and high coronary heart disease death rates. We abstracted data from hospital records, and an independent, blinded medical team reviewed these data to validate cause of death. We computed a comparability ratio (coronary heart disease deaths recorded on death certificates divided by validated coronary heart disease deaths) to quantify agreement between death certificate determination and clinical judgment. RESULTS: Of 491 sampled death certificates for in-hospital deaths, medical charts were abstracted and reviewed by the expert panel for 444 (90%). The comparability ratio for coronary heart disease deaths among decedents aged 35 to 74 years was 1.51, indicating that death certificates overestimated coronary heart disease deaths in this age group by 51%. The comparability ratio increased with age to 1.94 for decedents aged 75 to 84 years and to 2.37 for decedents aged 85 years or older. CONCLUSION: Coronary heart disease appears to be substantially overreported as a cause of death in New York City among in-hospital deaths.

Miltefosine promotes IFN-gamma-dominated anti-leishmanial immune response.

Leishmania donovani, a protozoan parasite, resides and replicates as amastigotes within macrophages. The parasite inflicts the disease visceral leishmaniasis by suppressing host cell function. Neither a therapeutic vaccine nor an effective anti-leishmanial drug to reverse the immunosuppression is available. Although miltefosine (hexadecylphosphocholine or HPC) is a promising orally bioavailable anti-leishmanial drug, its efficacy is seriously compromised by contra-indications in pregnant women. Further rational redesigning of the drug requires studies on its mechanism of action, which is unknown at present. Because miltefosine is proposed to have immunomodulatory functions, we examined whether miltefosine exerts its anti-leishmanial functions by activating macrophages. We observed that miltefosine's anti-leishmanial function was significantly compromised in IFN-gamma-deficient macrophages suggesting the importance of endogenous IFN-gamma in miltefosine-induced anti-leishmanial functions of macrophages. Miltefosine induced IFN-gamma, neutralization of which reduced the anti-leishmanial functions of macrophages. IFN-gamma responsiveness is reduced in L. donovani-infected macrophages but is significantly restored by miltefosine, as it enhances IFN-gamma receptors and IFN-gamma induced STAT-1 phosphorylation but reduced activation of SHP-1, the phosphatase implicated in the down-regulation of STAT-1 phosphorylation. Miltefosine induced protein kinase C-dependent and PI3K-dependent p38MAP kinase phosphorylation and anti-leishmanial function. Miltefosine promotes p38MAP kinase-dependent anti-leishmanial functions and IL-12-dependent Th1 response. Leishmania donovani-infected macrophages induced Th2 response but miltefosine treatment reversed the response to Th1-type. Thus, our data define for the first time the mechanistic basis of host cell-dependent anti-leishmanial function of miltefosine.