Health-Related Quality of Life, Satisfaction with Care, and Cosmetic Results in Relation to Treatment among Patients with Keratinocyte Cancer in the Head and Neck Area: Results from the PROFILES Registry.

BACKGROUND: Little is known about the impact of keratinocyte cancer (KC) and its treatment on health-related quality of life (HRQoL). OBJECTIVES: The objectives of the present study were (1) to evaluate HRQoL among patients with KC in a population-based setting and compare this with an age- end sex-matched normative population and (2) to compare HRQoL, satisfaction with care, and cosmetic results among patients who underwent conventional excision, Mohs' micrographic surgery, or radiotherapy. METHOD: A random sample of 347 patients diagnosed with cutaneous basal cell or squamous cell carcinoma in the head and neck area between January 1, 2010, and December 31, 2014, were selected from the Netherlands Cancer Registry (NCR) and were invited to complete a questionnaire on HRQoL, satisfaction with care, and cosmetic results. Data were collected within Patient-Reported Outcomes Following Initial Treatment and Long-term Evaluation of Survivorship (PROFILES). Outcomes were compared to an age- and sex-matched normative population. RESULTS: Two hundred fifteen patients with KC returned a completed questionnaire (62% response). Patients with KC reported better global quality of life (79.6 vs. 73.3, p < 0.01) and less pain (p < 0.01) compared to the normative population. No statistically significant differences in HRQoL, satisfaction with care, and cosmetic results were found between patients with KC who underwent conventional excision, Mohs' micrographic surgery, or radiotherapy. CONCLUSIONS: The impact of KC and its treatment seems relatively low and more positive than negative as patients reported better HRQoL compared to an age- and sex-matched normative population, probably due to adaptation. No statistically significant differences between treatment types were found concerning HRQoL, patient satisfaction, and cosmetic results. This information could be used by healthcare professionals involved in KC care to improve patients' knowledge about different aspects of the disease as patient's preference is an important factor for treatment choice.

The effect of Mindfulness-Based Stress Reduction on wound healing: a preliminary study.

Psychological factors have been shown to influence the process of wound healing. This study examined the effect of Mindfulness-Based Stress Reduction (MBSR) on the speed of wound healing. The local production of pro-inflammatory cytokines and growth factors was studied as potential underlying mechanism. Forty-nine adults were randomly allocated to a waiting-list control group (n = 26) or an 8-week MBSR group (n = 23). Pre- and post-intervention/waiting period assessment for both groups consisted of questionnaires. Standardized skin wounds were induced on the forearm using a suction blister method. Primary outcomes were skin permeability and reduction in wound size monitored once a day at day 3, 4, 5, 6, 7, and 10 after injury. Secondary outcomes were cytokines and growth factors and were measured in wound exudates obtained at 3, 6, and 22 h after wounding. Although there was no overall condition effect on skin permeability or wound size, post hoc analyses indicated that larger increases in mindfulness were related to greater reductions in skin permeability 3 and 4 days after wound induction. In addition, MBSR was associated with lower levels of interleukin (IL)-8 and placental growth factor in the wound fluid 22 h after wound induction. These outcomes suggest that increasing mindfulness by MBSR might have beneficial effects on early stages of wound healing. Trial Registration NTR3652, http://www.trialregister.nl.

Cancer survivors' preference for follow-up care providers: a cross-sectional study from the population-based PROFILES-registry.

BACKGROUND: The best practice for the organization of follow-up care in oncology is under debate, due to growing numbers of cancer survivors. Understanding survivors' preferences for follow-up care is elementary for designing patient-centred care. Based on data from prostate cancer and melanoma survivors, this study aims to identify: 1) preferences for follow-up care providers, for instance the medical specialist, the oncology nurse or the general practitioner; 2) characteristics associated with these preferences and 3) the preferred care provider to discuss cancer-related problems. MATERIAL AND METHODS: Survivors diagnosed with prostate cancer (N = 535) and melanoma (N = 232) between 2007 and 2013 as registered in The Netherlands Cancer Registry returned a questionnaire (response rate was 71% and 69%, respectively). A latent class cluster model analysis was used to define preferences and a multinomial logistic regression analysis was used to identify survivor-related characteristics associated with these preferences. RESULTS: Of all survivors, 29% reported no preference, 40% reported a preference for the medical specialist, 20% reported a preference for both the medical specialist and the general practitioner and 11% reported a preference for both the medical specialist and the oncology nurse. Survivors who were older, lower/intermediate educated and women were more likely to have a preference for the medical specialist. Lower educated survivors were less likely to have a preference for both the medical specialist and the general practitioner. Overall, survivors prefer to discuss diet, physical fitness and fatigue with the general practitioner, and hereditary and recurrence with the medical specialist. Only a small minority favored to discuss cancer-related problems with the oncology nurse. CONCLUSION: Survivors reported different preferences for follow-up care providers based on age, education level, gender and satisfaction with the general practitioner, showing a need for tailored follow-up care in oncology. The results indicate an urgency to educate patients about transitions in follow-up care.

[Childhood melanoma in the Netherlands]. / Melanomen bij kinderen in Nederland.

Childhood melanoma is a rare disorder which is often associated with a diagnostic delay. Worldwide, the incidence of cutaneous melanoma is rising in both adults and children. We describe three cases of childhood melanoma in the Netherlands which illustrate different aetiological aspects of the disease. The epidemiology of childhood melanoma in the Netherlands is discussed. In reviewing the literature, we wish to draw attention to important clinical aspects which may contribute to the early recognition of melanoma in children.

Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in Caucasians. Trichoepithelioma (TE) is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF) tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1) and mechanistic/mammalian target of rapamycin (mTOR) are key players in these pathways. OBJECTIVES: To determine whether HIF1/mTOR signalling is involved in BCC and TE. METHODS: We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45) and TE (n = 35) samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, <30%, 30-80% and >80%). RESULTS: Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3), 73% and 75% (CAIX), 79% and 86% (GLUT1), 50% and 19% (HIF1α), 89% and 88% (pAKT), 55% and 61% (pS6), 15% and 25% (pMTOR), 44% and 63% (PHD2) and 44% and 49% (VEGF-A). CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included. CONCLUSIONS: HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE.

Fractionated 5-aminolevulinic acid photodynamic therapy after partial debulking versus surgical excision for nodular basal cell carcinoma: a randomized controlled trial with at least 5-year follow-up.

BACKGROUND: Although effective in superficial basal cell carcinoma (BCC), the treatment effect of photodynamic therapy (PDT) in nodular BCC (nBCC) is still questionable. The relation between tumor thickness and PDT failure is unclear. OBJECTIVE: We sought to compare long-term effectiveness of fractionated 20% 5-aminolevulinic acid (ALA)-PDT with prior partial debulking versus surgical excision in nBCC. The effect of tumor thickness on ALA-PDT failure was analyzed. METHODS: 173 primary, histologically proven nBCCs in 151 patients were randomized to fractionated ALA-PDT (n = 85) or surgical excision (n = 88). Two PDT illuminations were performed with a 1-hour interval. Follow-up was at least 5 years posttreatment. Clinical recurrences were confirmed histologically. RESULTS: A total of 171 nBCCs were treated and had a median follow-up of 67 months (range 0-106). At 60 months, 23 tumors had recurred in the ALA-PDT group and 2 tumors in the surgical excision group. Cumulative recurrence probabilities 5 years posttreatment were 30.7% (95% confidence interval [CI] 21.5%-42.6%) for ALA-PDT and 2.3% (95% CI 0.6%-8.8%) for surgical excision (P < .0001). Two tumors in the ALA-PDT group recurred at 72 and 91 months posttreatment. Cumulative probability of recurrence-free survival post-PDT was 65.0% (95% CI 51%-76%) for nBCC measuring greater than 0.7 mm in thickness and 94.4% (95% CI 67%-99%, P = .018) for tumors less than or equal to 0.7 mm. LIMITATIONS: Tumor thickness on punch biopsy specimen might differ from the total lesion thickness. CONCLUSIONS: In nBCC, 5-year cumulative probability of recurrence after surgical excision is lower than after fractionated ALA-PDT with prior debulking. Although surgical excision remains the gold standard of treatment, PDT might be an alternative for inoperable patients with thin (≤0.7 mm) nBCC.

[The acrolentiginous melanoma: how to recognise and when to refer?]. / Het acrolentigineus melanoom: hoe te herkennen en wanneer te verwijzen?

In Caucasians, the acrolentiginous melanoma is a rare type of melanoma and may appear on hands, feet and subungually. It has the worst prognosis of all melanomas, due to the high rate of misdiagnosis. In 30% of the patients, it presents amelanotic and may resemble for example a common wart, paronychia, ulceration or mycosis. We present 4 patients, aged 48 years and older, in whom an acrolentiginous melanoma was contemplated. One of the lesions was highly suspected of a subungual acrolentiginous melanoma, because of the presence of Hutchinson's sign. Another lesion presented amelanotic and mimicked a foot ulcer. Acrolentiginous melanoma should be considered in case of uncertain diagnosis, delay in healing, enlargement of the lesion and when a pigmented lesion is larger than 7 mm. In these situations, early histopathological examination should be performed.

Differentiation between basal cell carcinoma and trichoepithelioma by immunohistochemical staining of the androgen receptor: an overview.

Clinical and histopathological differentiation between basal cell carcinoma (BCC) and trichoepithelioma (TE) is a frequent problem. Attempts have been made to identify immunohistochemical markers helpful in differentiating them. A correct diagnosis is important because the tumours are treated differently. Recent studies showed the absence of androgen receptor (AR) expression in benign hair follicle tumours like TE. This study examines whether AR immunostaining is a useful diagnostic test to differentiate between BCC and TE. We randomly selected 75 cases with histological diagnoses of either BCC (subtypes: superficial, nodular or infiltrative) or TE (subtypes: classic or desmoplastic) from the database of the pathology department of Maastricht University Medical Centre. The available haematoxylin & eosin (H&E) slides were reviewed by three independent investigators using predetermined characteristics. Fifty-six slides (38 BCC and 18 TE) with unequivocal histological characteristics of either tumour were used for immunohistochemistry with AR antibodies. Any nuclear expression within the tumour was considered positive. AR expression was present in 5/8 classic TE, 0/10 desmoplastic TE, 22/23 superficial or nodular BCC and in 10/15 infiltrative BCC. Immunohistochemical stain for AR is useful to differentiate between TE and BCC; particularly in desmoplastic TE versus infiltrative BCC (specificity and positive predictive value of 100%).

Correlation between histologic findings on punch biopsy specimens and subsequent excision specimens in recurrent basal cell carcinoma.

BACKGROUND: The type of treatment for a basal cell carcinoma (BCC) depends on the histologic subtype. Histologic examination is usually performed on incisional biopsy specimens. In primary BCC, the histologic subtype is correctly identified with a punch biopsy in 80.7% of cases. In recurrent BCC, correct identification is more difficult because of discontinuous growth caused by scar formation. Because an aggressive histologic subtype has a significantly higher risk for recurrence in these tumors, the histologic subtype is at least as important in recurrent BCC as it is in primary BCC. OBJECTIVE: To investigate the correlation between histologic findings on punch biopsy specimens and subsequent excision specimens in recurrent BCC. Furthermore, we sought to clarify how often an aggressive histologic subtype was missed, based on the punch biopsy specimen. METHODS: We compared the histologic subtype in a punch biopsy specimen with the subsequent excision specimen in recurrent BCC. All BCCs were coded and judged randomly by the same dermatopathologist. RESULTS: In 24 of 73 investigated BCCs (32.9%), the histologic subtype of the initial biopsy did not match with the histologic subtype of the subsequent excision. Of the 37 excised BCCs with an aggressive histologic subtype, 7 (19%) were missed by the initial punch biopsy. LIMITATIONS: Intraobserver variation may have affected the results of this study. CONCLUSIONS: Discriminating tumors with any aggressive growth is relevant for treatment. However, in recurrent BCC, the histology of the biopsy specimen does not always correlate with the histology of the definitive excision. This may have important therapeutic implications.

Histology-based treatment of basal cell carcinoma.

Basal cell carcinoma is the most common type of skin cancer and its incidence is still rising. In recent years, new treatment modalities have been developed and existing modalities refined. The aim of this article is to give a histology-based overview of the available evidence-based research. The literature was searched for randomized controlled trials from which the efficacy of investigated treatments was obtained. Where possible, treatment modalities were evaluated specifically. Selection criteria were histological subtype, primary or recurrent basal cell carcinoma and tumour localization. Although surgery remains the preferred treatment for most basal cell carcinomas, patient and tumour characteristics should be taken into account when choosing the most suitable treatment.

Surgical excision versus curettage plus cryosurgery in the treatment of basal cell carcinoma.

BACKGROUND: Both cryosurgery, with and without prior curettage, and surgical excision (SE) are common therapeutic strategies for basal cell carcinoma (BCC). OBJECTIVE: The objective was to compare the efficacy between curettage plus cryosurgery (C&C) and SE in nonaggressive BCC of the head and neck. MATERIALS AND METHODS: A randomized controlled trial was carried out, in which tumors were assigned to either C&C (n=51) or SE (n=49). C&C was performed with a double freeze-thaw cycle after prior curettage of the tumor. SE was performed with a margin of 3 mm and with delayed histologic examination. RESULTS: Recurrences occurred 9 times after C&C (17.6%) and 4 times after SE (8.2%). The overall 5-year recurrence probability was 19.6% for C&C and 8.4% for SE (p=.10). A hazard ratio of 2.57 (95% CI, 0.79-8.34) indicated a putative, but not statistically significant, advantage of SE. CONCLUSION: These data reflect the outcome of the first randomized controlled trial with long-term follow-up in the treatment of BCC, comparing C&C with SE. Although not statistically significantly different, the observed differences could still be of clinical relevance. Owing to the trend toward lower recurrence rates, better cosmetic results, and reduced wound healing time, we believe that SE should be preferred to C&C in the treatment of primary, nonaggressive BCC of the head and neck.

Similar effectiveness of methyl aminolevulinate and 5-aminolevulinate in topical photodynamic therapy for nodular basal cell carcinoma.

BACKGROUND: Photodynamic therapy (PDT) for basal cell carcinoma (BCC) is a treatment modality that is increasingly used in dermato-oncology. Currently, 2 topical photosensitizers, 5-aminolevulinate (ALA) and methyl aminolevulinate (MAL) are widely used, but their efficacy in BCC has not yet been compared in a clinical setting. OBJECTIVE: To evaluate the effect, degree of pain, and costs of ALA-PDT versus MAL-PDT in nodular BCC (nBCC). METHODS: Patients suffering from BCC were randomly assigned to either ALA-PDT (n=22) or MAL-PDT (n=21) in a pilot study. In each group, half of the tumors were debulked prior to PDT. Eight weeks after treatment, the therapeutic outcome was checked histologically. Pain scores were assessed using a visual analogue scale. RESULTS: Residual tumor tissue was detected in 6 BCCs of each study group. No significant difference between ALA-PDT and MAL-PDT was found with regard to therapeutic efficacy and pain scores. Of note, however, the costs of MAL-PDT were 6-fold higher than those of ALA-PDT. CONCLUSIONS: In this study we did not observe any differences in short-term efficacy between ALA-PDT and MAL-PDT. Therefore, both ALA and MAL can be equally recommended as topical photosensitizers in PDT.

Different pain sensations in photodynamic therapy of nodular basal cell carcinoma Results from a prospective trial and a review of the literature.

BACKGROUND: Pain is a major side effect of topical photodynamic therapy (PDT), a relatively new and non-invasive treatment for particular types of basal cell carcinoma (BCC). In this study, we sought to characterise in more detail the quality and intensity of pain associated with PDT. Furthermore, we studied if gender, tumour size and localization as well as different light sources with comparable wavelengths had an influence on the pain. METHODS: A total of 64 nodular BCCs in 55 patients, of which 48 BCCs underwent preceding debulking, were treated with 5-aminolevulinic acid (ALA-PDT). Two metal halogen light sources were randomly used. Pain assessment was performed using a visual analogue scale (VAS). RESULTS: All patients experienced pain during illumination and 41.8% after illumination. The mean pain intensity was 3.88 with most patients experiencing burning (82.5%) or stinging (36.8%) sensations. Illumination with the Medeikonos(®) light source was experienced less painful than the Waldmann(®) lamp (4.64 versus 3.40; p=0.027). Gender as well as tumour localization and size did not alter the pain scores. Likewise, no differences were observed between patients who underwent debulking and those who did not. CONCLUSIONS: Treatment of single BCCs with ALA-PDT rarely results in unbearable pain. However, the degree of pain can vary depending on the light source used. Further studies are needed to unravel the pathomechanisms underlying the development of pain in PDT in order to develop adequate solutions for this undesirable side effect.

Basal cell carcinoma: treatment options and prognosis, a scientific approach to a common malignancy.

The incidence of basal cell carcinoma is rapidly increasing and a number of treatment modalities are available. Treatment of basal cell carcinoma includes both surgical and nonsurgical approaches, some of which are traditional, and others experimental. The treatment modality utilized is dependent on both the tumor type and the patient. In order to choose between therapies, evidence-based research is necessary. In an extensive review of the literature concerning treatment options for patients with basal cell carcinoma, we found that there are a limited number of comparative, prospective, randomized, long-term follow-up studies. Based on the results of the available studies, surgical excision, Mohs surgery and cryosurgery are the three standard therapies of choice. Other treatment modalities should be considered secondary choices. There are also promising new treatment options, such as photodynamic therapy, which need further investigation. Special attention is needed when treating the more aggressive subtypes of the disease, such as the micronodular, infiltrative, adenoid and morpheic forms of basal cell carcinoma, as well as bigger basal cell carcinomas and basal cell carcinoma recurrences.

PpIX fluorescence kinetics and increased skin damage after intracutaneous injection of 5-aminolevulinic acid and repeated illumination.

Photodynamic therapy with topically applied 5-aminolevulinic acid is used successfully for superficial skin lesions. The results for thicker, nodular lesions are less favorable. The method of aminolevulinic acid administration, the concentrations of aminolevulinic acid, and the irradiation schemes used so far have not been investigated thoroughly. As aminolevulinic acid photodynamic therapy has high potential for the increasing problem of skin cancer, we investigated both visually and histopathologically the photodynamic-therapy-induced skin damage after intracutaneous administration of aminolevulinic acid in normal porcine skin. We also investigated the kinetics of the aminolevulinic-acid-induced photosensitizer protoporphyrin IX fluorescence after irradiation in relation to fluence and irradiance. Finally we investigated the effect on photodynamic-therapy-induced damage of a fractionated irradiation. This study demonstrates that intracutaneous administration of aminolevulinic acid leads to higher fluorescence levels and thus to formation of higher protoporphyrin IX concentrations than topical application of aminolevulinic acid cream. The peak level of protoporphyrin IX after intracutaneous administration of aminolevulinic acid is reached earlier than after topical administration. The comeback of fluorescence, indicating re-synthesis of protoporphyrin IX after irradiation, is inhibited with increasing fluence. Photodynamic-therapy-induced damage increases with increasing fluence, but is independent of the irradiance. Finally, the photodynamic-therapy-induced skin damage seems to be greater after fractionated irradiations with two equal light fractions of 15 J per cm2 separated by a dark interval of 2 h.