Nicole W J Kelleners-Smeets

Maastricht University, Maastricht, Provincie Limburg, Netherlands

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Publications (26)104 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Diagnosis and subsequent treatment of cutaneous squamous cell carcinoma are frequently based on punch biopsies. Regarding the current TNM classification and stage grouping for cutaneous squamous cell carcinoma, it is important to identify the high-risk features (infiltration depth > 4 mm, perineural and/or lymphovascular invasion and poor differentiation). This study investigates the agreement of histological high-risk features and TNM grouping stage on 3 mm punch biopsies and subsequent surgical excision in 105 patients diagnosed with cutaneous squamous cell carcinoma. On punch biopsy, infiltration depth > 4 mm is not identified in 83.3% (30/36), perineural invasion in 90.9% (10/11) and poor differentiation in 85.7% (6/7) of cases. The TNM stage was underestimated on punch biopsy in 15.4% (16/104). This study shows that on a 3 mm punch biopsy, high-risk features in cSCC can remain undetected and that the actual TNM stage is not identified in 1 out of 6 tumours.
    Acta Dermato-Venereologica 02/2014;
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    ABSTRACT: Bowen's disease is an in situ squamous cell carcinoma of the skin with various treatment modalities available. A major advantage of surgical excision is the opportunity to histologically examine the resection margins. There is no consensus about the most appropriate margin. This retrospective study evaluates the clearance rates achieved by excision with a 5 mm margin and estimates how that might change after fictitiously reducing the resection margin by 1 or 2 mm. Patients with histologically confirmed Bowen's disease were selected at the Maastricht University Medical Centre from 2002 until 2007. Surgical margins and complete excision rates were evaluated and histological slides were re-examined. To our knowledge this is the first study investigating the safety margin for Bowen's disease. As Bowen's disease is not an invasive disease, minimisation of healthy tissue excision is desirable. Our data show that a hypothetical reduction of the safety margin from 5 mm to 4 or 3 mm decreases the complete excision rate from 94.4% to 87% and 74.1%, respectively.
    Acta Dermato-Venereologica 12/2013;
  • Journal of the American Academy of Dermatology 11/2013; 69(5):e262-e264. · 4.91 Impact Factor
  • Nicole W J Kelleners-Smeets, Klara Mosterd
    Journal of the American Academy of Dermatology 08/2013; 69(2):317-8. · 4.91 Impact Factor
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    ABSTRACT: 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.
    Journal of the American Academy of Dermatology 04/2013; · 4.91 Impact Factor
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    ABSTRACT: Cutaneous squamous cell carcinomas (cSCC) can recur locally and can metastasize. The objective of this study was to identify clinical and histopathological prognostic factors for local recurrence and metastasis in cSCCs at any body site. Clinical and histopathological data were collected from 224 patients with cSCC. During the median follow-up period of 43 months (range 0-73 months) the cumulative probabilities of recurrence-free survival at 1, 2 and 4 years post-treatment were 98.0%, 96.9% and 94.7%, respectively, and for metastasis-free survival 98.1%, 97.0% and 95.9%, respectively. In univariate survival analyses, predictors for local recurrence were every millimetre increase in tumour diameter and in tumour thickness. Predictors for metastasis this was location on the ear, invasion of deeper structures, no surgical treatment, poor differentiation, every millimetre increase in tumour diameter and in tumour thickness. In multivariate survival analysis, every millimetre increase in both tumour diameter and tumour thickness were independent predictors for local recurrence as well as for metastasis and, therefore, it is important to report these in patients' files. Defining prognostic valuables is important for diagnostic work-up, treatment and follow-up for an individual patient.
    Acta Dermato-Venereologica 11/2012;
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    ABSTRACT: Background  Diagnosis of clinically suspected basal cell carcinoma (BCC) by histological confirmation with punch biopsy has been recommended before treatment. Even shave biopsy has been proposed as useful to predict the correct subtype in primary BCC in 76-81%, whereas the agreement between histological BCC subtype on punch biopsy and subsequent excision specimens in recurrent BCC is 67.1%. However, no large studies on the agreement between histological BCC subtype seen on punch biopsy and the following surgical excision are performed in primary BCC. Objective  The aims of this study were (i) to establish the agreement between histological BCC subtype on punch biopsy and the subsequent surgical excision of primary BCC and; (ii) to investigate the proportion of primary BCCs in which punch biopsy enables identification of the most aggressive growth pattern. Methods  Retrospective analyses of 243 primary BCCs with both punch biopsy and subsequent surgical excision. Analyses were based on the most aggressive histological subtype of the tumour. Results  The agreement between BCC subtype on punch biopsy and the subsequent surgical excision of primary BCCs was 60.9%. A punch biopsy can predict the most aggressive growth pattern of primary BCCs in 84.4%. Seventy-four percentage of all primary BCCs consisted of more than one histological subtype. Conclusion  Dermatologists and other physicians have to be aware of the limited diagnostic value of a punch biopsy to determine the histological BCC subtype of the whole lesion. Misdiagnosis of the subtype will lead to undertreatment in one of six primary BCCs.
    Journal of the European Academy of Dermatology and Venereology 06/2012; · 2.69 Impact Factor
  • M H Roozeboom, A H H M Arits, P J Nelemans, N W J Kelleners-Smeets
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    ABSTRACT: Background  Several noninvasive treatment modalities are available for superficial basal cell carcinoma (sBCC). Objectives  This systematic review aims to determine residue, recurrence and tumour-free survival probabilities of patients with primary sBCC treated with the currently most frequently used therapies. Methods  The PubMed (January 1946 to October 2010), EMBASE (January 1989 to October 2010) and Cochrane (January 1993 to October 2010) databases, and reference lists were searched without date restriction. Inclusion criteria were studies that included primary, histologically proven sBCCs, that reported on residue and/or recurrence probabilities after treatment, and had a minimum follow-up period of 12 weeks. Both randomized and nonrandomized studies were included. The primary and secondary outcomes were the probability of complete response and tumour-free survival, respectively. Two independent reviewers selected 36 studies (14 randomized and 22 nonrandomized), and extracted residue, cumulative recurrence and tumour-free survival probabilities. Results  Pooled estimates of percentages of sBCC with complete response at 12 weeks post-treatment, derived from 28 studies, were 86·2% [95% confidence interval (CI) 82-90%] for imiquimod treatment, and 79·0% (95% CI 71-87%) for photodynamic therapy (PDT). With respect to tumour-free survival at 1 year, the pooled estimates derived from 23 studies were 87·3% for imiquimod (95% CI 84-91%) and 84·0% for PDT (95% CI 78-90%). Only a small number of studies reported on the results of sBCC treatment with 5-fluorouracil (one), surgical excision (one) and cryotherapy (two). Conclusions  Pooled estimates from randomized and nonrandomized studies showed similar tumour-free survival at 1 year for imiquimod and PDT. The PDT tumour-free survival was higher in studies with repeated treatments. However, these results were largely derived from nonrandomized studies, and randomized studies with head-to-head comparison of imiquimod and PDT are lacking. There is a need for head-to-head comparison studies between PDT, imiquimod and other treatments with long-term follow-up to enable better recommendations for optimal sBCC treatment.
    British Journal of Dermatology 05/2012; 167(4):733-56. · 3.76 Impact Factor
  • Clinical and Experimental Dermatology 04/2012; 37(3):322-4. · 1.33 Impact Factor
  • K Mosterd, A H M M Arits, P J Nelemans, N W J Kelleners-Smeets
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    ABSTRACT: Background  Cosmetic results following non-invasive treatments are difficult to compare. Although qualified objective scar assessment scales are available, they are not used in dermatological studies. Usually a 4-point scale is used in dermatological scars. The reproducibility of this method has never been evaluated. Moreover, significant specific scar characteristics are lacking. The patient and observer scar assessment scale (POSAS) is a scale qualified for the assessments of surgical scars. It has proven to be as reliable as the widely used Vancouver Scar Scale, but has the advantage that it includes the patient's opinion and specifies different scar characteristics. Objective  Both methods were used to evaluate cosmetic results following non-invasive treatments of superficial basal cell carcinoma (BCC). Methods  A total of 54 lesions following non-invasive treatment for BCC in 54 patients were evaluated with the traditional 4-point scale and the POSAS. Results  The 4-point scale showed the best reproducibility and had an intra-class correlation coefficient (ICC) of 0.66 (95% CI: 0.52-0.77) for a single observer and 0.85 (95% CI: 0.77-0.91) for multiple observers. The ICC of the POSAS was 0.41 (95% CI: 0.21-0.58) for a single observer and 0.67 (95% CI: 0.45-0.81) for three observers. The scar characteristics, vascularity and pigmentation were most decisive for the overall opinion. Conclusion  The use of the 4-point scale is a valid method to compare scars of non-invasive dermatological treatments. Supplementary registering vascularity and pigmentation can be useful in future studies.
    Journal of the European Academy of Dermatology and Venereology 11/2011; · 2.69 Impact Factor
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    ABSTRACT: 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%).
    European journal of dermatology: EJD 08/2011; 21(6):870-3. · 1.76 Impact Factor
  • A H M M Arits, M H J Schlangen, P J Nelemans, N W J Kelleners-Smeets
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    ABSTRACT: As a result of the high prevalence, basal cell carcinoma (BCC) causes a significant and expensive health care problem. In this study, we evaluate the proportional increase in BCC by histological subtype over the last two decades. We retrospectively reviewed all primary histological confirmed BCCs diagnosed in the Maastricht University Medical Centre in The Netherlands in the years 1991, 1999 and 2007. An annual increase of the number of BCCs of 7% for both genders was shown. The age-standardized incidence rates for BCC increased between 1991 and 2007 from 54.2 to 162.1 per 100, 000 men and from 61.7 to 189.8 per 100, 000 women. The proportion of superficial BCC increased significantly from 17.6% to 30.7%. The incidence of BCC is continuing to increase this century. The observed shift to the superficial histological subtype, which can be treated non-surgically, might reduce the workload in the busy dermatologists practice.
    Journal of the European Academy of Dermatology and Venereology 05/2011; 25(5):565-9. · 2.69 Impact Factor
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    ABSTRACT: 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. 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. 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. 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. Intraobserver variation may have affected the results of this study. 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.
    Journal of the American Academy of Dermatology 02/2011; 64(2):323-7. · 4.91 Impact Factor
  • Source
    Acta Dermato-Venereologica 09/2010; 90(5):529-30.
  • A H M M Arits, M M van de Weert, P J Nelemans, N W J Kelleners-Smeets
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    ABSTRACT: The major drawback of the widely used photodynamic therapy (PDT) is treatment-related pain. Gain insight into the intensity of and predictive factors for painful burning sensation associated with PDT. A prospective cohort study was performed at the department of Dermatology in the Maastricht University Medical Centre in Maastricht, a reference centre for dermatological oncology in The Netherlands. A total of 141 lesions in 108 patients were included, treated from November 2008 until June 2009 with PDT for superficial basal cell carcinoma, Bowen's disease (BD) or actinic keratosis (AK). Painful burning sensation was scored based on an 11-point pain intensity numeric rating scale (PI-NRS) (0=no pain; 10=worst possible pain). The percentage of patients with a PI-NRS score over six was 32.6% and 37.9% during the primary and follow-up PDT session respectively. A total of 76.6% (95/124) of the patients was consistent in pain intensity score reporting. Factors associated with higher PI-NRS scores were treatment of AK or BD, tumour localization in the head/neck region, patient's age over 70, Fitzpatrick skintype I/II, photosensitizer 5-aminolevulinic acid and use of oral analgesics. After mutual adjustment of these factors, Fitzpatrick skintype remained the only independent predictor of PI-NRS scores during PDT. It remains difficult to decide which patients should be considered for pain relieving measures. The solution remains to support all patients treated with PDT with pain relieving techniques or to let the support of pain relieving measures depend on the reported pain score for the primary session.
    Journal of the European Academy of Dermatology and Venereology 04/2010; 24(12):1452-7. · 2.69 Impact Factor
  • Dermatologic Surgery 12/2009; 35(12):2051-3. · 1.87 Impact Factor
  • Nederlands tijdschrift voor geneeskunde 06/2009; 153(19):899-905.
  • K Mosterd, N Kelleners-Smeets
    The Lancet Oncology 02/2009; 10(1):10. · 25.12 Impact Factor
  • Source
    Klara Mosterd, Aimee H M M Arits, Monique R T Thissen, Nicole W J Kelleners-Smeets
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    ABSTRACT: 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.
    Acta Dermato-Venereologica 02/2009; 89(5):454-8.
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    ABSTRACT: Difficulty in differentiation between a solitary basal cell carcinoma, which is known as a malign skin lesion and a benign trichoepithelioma, is a frequent problem in all day dermatologic practice. Clinically as well as histopathologically there are a lot of resemblances between these skin tumors. By means of two real life cases, we give here an overview of the possible problems and appliances in distinguishing these two entities; at the end we do some recommendation about the policy.
    International journal of dermatology 12/2008; 47 Suppl 1:13-7. · 1.18 Impact Factor