The Intestinal Tumour Microenvironment.

The tumour microenvironment (TME) of intestinal tumours is highly complex and comprises a network of stromal cells, tumour cells, immune cells and fibroblasts, as well as microorganisms. The tumour location, environmental factors and the tumour cells themselves influence the cells within the TME. Immune cells can destroy tumour cells and are associated with better patient prognosis and response to therapy; however, immune cells are highly plastic and easily influenced to instead promote tumour growth. The interaction between local immune cells and the microbiome can lead to progression or regression of intestinal tumours. In this chapter, we will discuss how tumour development and progression can influence, and be influenced by, the microenvironment surrounding it, focusing on immune and fibroblastic cells, and the intestinal microbiota, particularly in the context of colorectal cancer.

Perspectives of oncology health workers in Flanders on caring for patients of non-Western descent.

This study was undertaken to gain insight in the views and experiences of oncology healthcare providers in Flanders, the Dutch-speaking part of Belgium, on caring for patients of non-Western descent. A qualitative research design with the constant comparative method was used. Data were collected through five focus group interviews, with 23 oncology health workers as participants. Barriers and difficulties were paramount in the provision of care to patients of non-Western descent. Participants want to act according to their professional standards, which call for treating all patients equally and providing appropriate care. However, a focus on medical aspects occurs, wherein 'cure' takes precedence over 'care', when participants were not willing or not fully able to overcome barriers. This results in feelings of inadequacy in those participants who equate professional standards to care of equal quality. Participants who interpreted their professional standard as equivalent care were irritated by 'these' patients who restrained them from providing appropriate care. The findings indicate that professional standards provide protection against possible discrimination that may result from personal beliefs. Extending professional standards from 'treating all patients equally' to 'care attuned to each patient' might be a way to prevent 'cure' taking precedence over 'care'.

Balancing truth-telling: relatives acting as translators for older adult cancer patients of Turkish or northwest African origin in Belgium.

The first generation of Turkish and Northwest African immigrants in Belgium are ageing and at risk for developing cancer. Relatives play an important role and provide both emotional and practical care, including mental support and acting as a contact person and/or a translator for improving access to healthcare, as most patients and their spouses have only a limited command of the language. Although access to professional interpreters has shown to be the best guarantee for qualitative healthcare, oncology health providers working with relatives as interpreters is much more common than professional interpreters. The aim of this study was to provide insight into the process wherein relatives balance truth-telling in translating for an older family member diagnosed with cancer. This was a qualitative research study, with elements of constructivist grounded theory. Twenty-eight loosely structured interviews were conducted. Most relatives consider it their responsibility to contribute to a positive attitude of the patient. Relatives decided to what extent they inform the patient, based on several motives and embedded in their assessment of the patient's emotional strength, understanding and need to be informed. What they decide influences the way they act as a translator and/or a contact person between the patient and health professional(s). Some considered it best to omit medical information while others considered it best to inform the patient fully. The results emphasise the importance for healthcare providers to take into account the complexity and unpredictable character of the process of balancing truth-telling when family members translate for their ill older relative.

Sequential use of biologics in the treatment of moderate-to-severe plaque psoriasis.

A number of biologic agents, including the tumour necrosis factor (TNF) antagonists etanercept, adalimumab and infliximab, and the interleukin (IL)-12/IL-23 antagonist ustekinumab, are available for the treatment of moderate-to-severe plaque psoriasis in the U.K. Currently, the selection of the first biologic, and the choice of sequential biologics in the event of efficacy/tolerability concerns, is made using a limited evidence base. The efficacy of biologics, the potential mechanisms of primary and secondary failure and the evidence for sequencing therapy among TNF antagonists and between TNF antagonists and IL-12/IL-23 blockade are reviewed. As psoriasis biologics registers begin to produce long-term safety and efficacy data, therapy decisions in plaque psoriasis may become more objective, and it may be possible to individualize treatment based on clinical or pharmacogenetic information.

Cutaneous mucinosis associated with dermatomyositis and nephrogenic fibrosing dermopathy: fibroblast hyaluronan synthesis and the effect of patient serum.

BACKGROUND: Dermal mucin is an amorphous gelatinous substance composed primarily of hyaluronan (HA) and sulphated glycosaminoglycans (GAGs). In primary cutaneous mucinosis, accumulation of mucin is a characteristic feature of lichen myxoedematosus, scleromyxoedema and reticular erythematous mucinosis. Secondary mucinoses are disorders where mucin deposition is an additional finding, and deposition is associated with lupus erythematosus, dermatomyositis, scleroderma and granuloma annulare. The underlying cause of the abnormal mucin deposition is unknown. An increasing number of cases of a fibromucinous scleromyxoedema-like disorder associated with renal dysfunction, recently termed nephrogenic fibrosing dermopathy (NFD), is being reported. OBJECTIVES: To examine the synthesis of sulphated GAGs and HA by fibroblasts derived from uninvolved and involved skin of a patient with dermatomyositis and two patients with NFD, and the effect of patient serum. METHODS: GAGs were quantified by a radiometric assay and HA was determined by an enzyme-linked HA-binding protein assay. RESULTS: We found that fibroblasts derived from active lesions of NFD synthesize elevated levels of GAGs, and in particular HA, compared with normal controls, while serum from the patient with dermatomyositis and the two patients with NFD stimulates GAG synthesis, including HA synthesis, by both control and patient fibroblasts. CONCLUSIONS: Fibroblasts from patients with active NFD are either activated to synthesize elevated levels of HA or contain another cell type, possibly derived from circulating fibrocytes. In both disorders, there is additionally a serum-derived factor that stimulates production of sulphated GAGs and HA by fibroblasts.

Outcomes and pathological review of a cohort of children with melanoma.

BACKGROUND: Prepubertal malignant melanoma is rare, pathological criteria are difficult and follow-up data on patients are lacking in the literature. OBJECTIVES: To review prepubertal cases of melanoma diagnosed in the West of Scotland 1979-2002. METHODS: Twenty cases were identified in whom melanoma was diagnosed before the age of 15. Pathological review was possible for 13 of 20 cases, and current follow-up information is available for all 20. Three pathologists not responsible for the original diagnosis reviewed the slides independently, in every case without knowledge of the outcome. RESULTS: Of the 13 cases reviewed, there was concordance of diagnosis between the three pathologists in 12 cases. Eight of the 13 cases reviewed were considered to be unusual naevi rather than melanoma. One child has died of melanoma and all three pathologists agreed with the original pathological diagnosis. One patient has experienced nodal metastases but is alive and disease-free 12 years later. The remaining 18 cases have had no recurrence since primary surgery 2-21 years ago. CONCLUSIONS: There may be a tendency to overdiagnose prepubertal melanoma. Good communication between clinician and pathologist and the use of an expert pathology panel is recommended before making the diagnosis.

Screening of SLC26A4 (PDS) gene in Pendred's syndrome: a large spectrum of mutations in France and phenotypic heterogeneity.

Sensorineural hearing defect and goiter are common features of Pendred's syndrome. The clinical diagnosis of Pendred's syndrome remains difficult because of the lack of sensitivity and specificity of the thyroid signs. The identification of PDS as the causative gene allowed molecular screening and enabled a re-evaluation of the syndrome to identify potential diagnostic characteristics. This report presents the clinical and genotypic findings of 30 French families, for whom a diagnosis of Pendred's syndrome had been made. Twenty-seven families had at least one mutated allele. Twenty-eight different mutations were identified, 11 of which had never been previously reported. The main clinical characteristics were: early hearing loss, fluctuation in terms of during deafness evolution, and the presence of an enlarged vestibular aqueduct.

A Crohn's disease-associated insertion polymorphism (3020insC) in the NOD2 gene is not associated with psoriasis vulgaris, palmo-plantar pustular psoriasis or guttate psoriasis.

A C-insertion polymorphism in the NOD2 gene (3020insC) on chromosome 16 is a rare mutation associated with Crohn's disease. Crohn's disease and psoriasis are more commonly observed together than expected by chance. Furthermore a susceptibility locus for psoriasis has been identified on chromosome 16q which overlaps the recently identified susceptibility locus for Crohn's disease. Thus, NOD2 may potentially be important as a candidate susceptibility gene for psoriasis. We tested this hypothesis by genotyping psoriasis patients for the C-insertion polymorphism using the Taqman ABI 7700 sequencing system. No statistically significant differences were observed between psoriasis vulgaris (n = 216), palmo-plantar pustular psoriasis (PPP) (n = 100), guttate psoriasis (n = 118) and the control group (n = 283). In both patient and control groups, no mutant homozygotes were observed and approximately 4% were heterozygotes. This particular insertion mutation in the NOD2 gene does not appear to contribute to the genetic susceptibility of psoriasis vulgaris, PPP or guttate psoriasis. However, other mutations exist in the NOD2 gene, which may potentially have a role in psoriasis susceptibility.

Randomized comparison of photodynamic therapy with topical 5-fluorouracil in Bowen's disease.

BACKGROUND: Bowen's disease (BD; intraepithelial squamous cell carcinoma) is therapeutically challenging because lesions, which may be multiple, are frequently located at sites that heal poorly. There is a small risk of progression to invasive carcinoma. Photodynamic therapy (PDT) is an effective treatment for certain non melanoma skin cancers, but comparison studies with other, better-established therapies are limited. OBJECTIVES: To compare the efficacy and tolerability of PDT and topical 5-fluorouracil (5-FU) in BD. METHODS: Forty patients from two centres were randomized to either topical PDT or 5-FU. The PDT group was treated with 20% 5-aminolaevulinic acid (ALA) applied 4 h before illumination with 100 J cm-2 narrowband red light (630 +/- 15 nm). 5-FU was applied to lesions for 4 weeks. A repeat treatment cycle was performed after 6 weeks if required. Results Twenty-nine of 33 (88%) lesions treated with PDT initially responded completely, compared with 22 of 33 (67%) after 5-FU. After 12 months, two recurrences in the PDT group and six in the 5-FU group reduced complete clinical clearance rates to 82% and 48%, respectively. PDT was significantly more effective (P = 0.006, odds ratio 4.78, 95% confidence interval 1.56-14.62). In the 5-FU group, severe eczematous reactions developed around seven lesions, ulceration in three and erosions in two. No such reactions occurred following PDT. There was no difference in overall pain experienced during each therapy. CONCLUSIONS: Topical ALA-PDT is more effective than topical 5-FU in the treatment of BD, with fewer adverse events. ALA-PDT should be considered one of the first-line therapeutic options for BD.

Topical 5-ALA photodynamic therapy for the treatment of cutaneous T-cell lymphoma.

Therapeutic options for cutaneous T cell lymphoma (CTCL) include topical steroids, topical chemotherapy and phototherapy. Patients with limited disease that is unresponsive to these therapies present a particular challenge. We report successful treatment of a patient with two plaques of CTCL using topical photodynamic therapy (PDT). 5-aminolaevulinic acid (5-ALA) was applied 6-24 h preillumination with 100 J/cm2 red light. Treatment was repeated on four occasions with clinical and histological clearance. ALA-PDT may be a useful addition to the therapeutic options for CTCL. Further studies are required to define optimal treatment protocols.

Photodynamic therapy: applications in dermatology.

Photodynamic therapy (PDT) offers the potential of an effective new treatment in several areas of medicine. Topical photodynamic therapy is practical and non-invasive and is particularly suited to dermatological indications. A variety of pre-malignant and malignant skin lesions including Bowen's disease, actinic keratoses (AKs) and basal cell carcinoma (BCC) have been treated with success. The role of PDT in inflammatory dermatoses remains to be established. The currently available literature is reviewed.

Localized papular cutaneous schistosomiasis: two cases in travellers.

Schistosomiasis is endemic in many parts of the tropics and subtropics with an estimated 200 million people, at least, infected worldwide. The symptoms and signs of vesical and gastrointestinal forms are readily recognized but ectopic forms are rare even in endemic areas and present a greater diagnostic challenge, particularly when they are encountered in nontropical climes. We now report two cases of cutaneous schistosomiasis presenting in Edinburgh with subtle, but remarkably similar, skin lesions.

Verrucas. Guidelines for management.

Most people will experience infection with human papilloma virus (HPV) at some point in their life. Diagnosis, based on clinical examination, is usually straight forward. Treatment can, however, be challenging. Indications for treatment include pain, interference with function, cosmetic embarrassment, and risk of malignancy. Clearance rates are highest in young, healthy individuals with short duration of infection. Treatment may be with destructive agents (keratolytics, cryotherapy, curettage and cautery, laser, photodynamic therapy), with antimitotic agents (podophyllin, bleomycin, retinoids), with immune stimulants (topical sensitizers, cimetidine), or with topical virucidal agents [formaldehyde (formalin), glutaral (gluteraldehyde)]. As yet, there is no single totally effective treatment for viral warts. Some patients may choose to leave their warts untreated until spontaneous resolution. In those who seek intervention, simple, well tolerated therapies should be chosen initially in preference to more complicated, potentially harmful agents. It is likely that future research will be directed to developing an antiviral agent specific for HPV which would be safe, effective and not prohibitively expensive.

Surface activity, film formation, and emulsifying properties of milk proteins.

This overview indicates that simple, reliable standardized methods for measuring emulsifying activity and for determining ES are not yet available. One of the major shortcomings of most of the current methods is the inability to detect very small fat globules (less than 0.5 micron), which may be very important in stable emulsions. Several of the methods are time consuming and destructive. To minimize the time required to evaluate emulsions, techniques that monitor instability under the influence of accelerated aging (increased temperature and gravitational field) have been used with varying degrees of success. These methods, e.g., centrifugation, are useful, but processes occurring during centrifugation or heating may not be characteristic of those occurring in a stored emulsion. Generally, there is no method that simultaneously determines changes in emulsions due to the aggregation coalescence, flocculation, creaming, of the droplets and/or oiling off. No single criterion of emulsion instability is sufficient to characterize all the changes occurring in the system. A nonintrusive technique that can monitor dynamic changes in emulsions is needed. Ideally, it should be simple, rapid, inexpensive, and applicable to both diluted and concentrated emulsions. Scientists must continue research to develop such a standard universal method for determining ES, because data from different laboratories cannot currently be validly compared. Reliable methods are also required to elucidate relationships between the physical properties of proteins as emulsifiers and their performance in food emulsions. There is a need for opportunities for systematic research to determine the interfacial behavior of food emulsifiers, particularly food proteins. Research to describe the kinetics and thermodynamics of adsorption at an interface, the extent of unfolding, the degree of packing and polypeptide interactions in an interface during film formation, and information concerning the physical and mechanical properties of interfacial films is needed to describe emulsifying behavior of different proteins. The effects of components in the continuous and discontinuous phase, parameters of manufacture, and interactions between different types of surface-active materials that occur in food need to be studied.