AIMS\nMETHODS\nRESULTS\nCONCLUSION\n To assess safety and tolerability and explore pharmacodynamics and efficacy of omiganan in external anogenital warts (AGW) and vulvar high-grade squamous... Show moreAIMS\nMETHODS\nRESULTS\nCONCLUSION\n To assess safety and tolerability and explore pharmacodynamics and efficacy of omiganan in external anogenital warts (AGW) and vulvar high-grade squamous intraepithelial lesions (HSIL).\nTwo randomized controlled trials in patients with external AGW and vulvar HSIL were conducted. Patients received topical omiganan 2.5% or placebo gel once daily for 12 weeks with a follow-up of 12 weeks. Safety and tolerability were monitored and pharmacodynamics and clinical efficacy of omiganan were assessed by analysing lesion count, size and viral load. Self-reported pain, itch and quality of life were assessed by an electronic diary and questionnaire.\nTwenty-four AGW and 12 vulvar HSIL patients were enrolled. All patients had a high treatment adherence (99%). No serious adverse events occurred and all adverse events (n = 27) were mild, transient and self-limiting. The treatment groups were not different in terms of safety and tolerability, lesion count and size, and patient-reported outcomes pain, itch and quality of life. Human papillomavirus load significantly reduced after 12 weeks of treatment with omiganan compared to placebo (-96.6%; 95% confidence interval -99.9 to -7.4%; P = .045) in AGW patients only.\nTopical omiganan appears to be safe in patients with AGW and vulvar HSIL and reduced human papillomavirus load after 12 weeks of treatment in AGW patients. Show less
Rijsbergen, M.; Rijneveld, R.; Todd, M.; Feiss, G.L.; Kouwenhoven, S.T.P.; Quint, K.D.; ... ; Poelgeest, M.I.E. van 2020
Aims To assess safety and tolerability and explore pharmacodynamics and efficacy of omiganan in external anogenital warts (AGW) and vulvar high-grade squamous intraepithelial lesions (HSIL).... Show moreAims To assess safety and tolerability and explore pharmacodynamics and efficacy of omiganan in external anogenital warts (AGW) and vulvar high-grade squamous intraepithelial lesions (HSIL). Methods Two randomized controlled trials in patients with external AGW and vulvar HSIL were conducted. Patients received topical omiganan 2.5% or placebo gel once daily for 12 weeks with a follow-up of 12 weeks. Safety and tolerability were monitored and pharmacodynamics and clinical efficacy of omiganan were assessed by analysing lesion count, size and viral load. Self-reported pain, itch and quality of life were assessed by an electronic diary and questionnaire. Results Twenty-four AGW and 12 vulvar HSIL patients were enrolled. All patients had a high treatment adherence (99%). No serious adverse events occurred and all adverse events (n =27) were mild, transient and self-limiting. The treatment groups were not different in terms of safety and tolerability, lesion count and size, and patient-reported outcomes pain, itch and quality of life. Human papillomavirus load significantly reduced after 12 weeks of treatment with omiganan compared to placebo (-96.6%; 95% confidence interval -99.9 to -7.4%;P =.045) in AGW patients only. Conclusion Topical omiganan appears to be safe in patients with AGW and vulvar HSIL and reduced human papillomavirus load after 12 weeks of treatment in AGW patients. Show less
AbstractBACKGROUND: The clinical appearance of cutaneous warts is highly variable and not standardized.OBJECTIVES: To develop and validate a reproducible clinical tool for the standardized... Show moreAbstractBACKGROUND: The clinical appearance of cutaneous warts is highly variable and not standardized.OBJECTIVES: To develop and validate a reproducible clinical tool for the standardized assessment of cutaneous warts to distinguish these lesions accurately.METHODS: Nine morphological characteristics were defined and validated regarding intra- and interobserver agreement. Based on literature and semistructured interviews, a systematic dichotomous assessment tool, the Cutaneous WARTS (CWARTS) diagnostic tool was developed. The validation consisted of two independent parts performed with photographs from the recent WARTS-2 trial. In part A, the CWARTS diagnostic tool was tested by 28 experienced physicians who assessed photographs of 10 different warts to investigate interobserver concordance. In part B, morphological characteristics were validated by masked and independent scoring of 299 photographs by six different observers. Part B also entailed reassessment of the photographs after at least 1 week. The primary outcome measurement was the intraclass correlation coefficient (ICC).RESULTS: Presence of black dots (capillary thrombosis) had the greatest ICC (0·85) for interobserver agreement in part A, followed by arrangement (0·65), presence of border erythema (0·64) and sharpness of the border (0·60). In part B, results were similar for interobserver agreement with presence of black dots having the highest ICC (0·68), followed by border erythema (0·64), arrangement (0·58) and colour (0·55). For intraobserver agreement, presence of black dots had the highest agreement (0·70), followed by presence of border erythema (0·694) and colour (0·59).CONCLUSIONS: Wart phenotype can be reliably assessed using the CWARTS diagnostic tool. Show less
AbstractBACKGROUND: Cutaneous warts have a cure rate after therapy of no more than approximately 50%. Recently, we developed and validated a standard assessment tool for warts (Cutaneous WARTS... Show moreAbstractBACKGROUND: Cutaneous warts have a cure rate after therapy of no more than approximately 50%. Recently, we developed and validated a standard assessment tool for warts (Cutaneous WARTS diagnostic tool, CWARTS) based on phenotypical characteristics.OBJECTIVES: To assess whether patient and morphological wart characteristics predict the human papillomavirus (HPV) type in a specific wart and whether these characteristics as well as the HPV type predict a favourable treatment response.METHODS: Photographs were used to score nine morphological wart characteristics using the newly developed CWARTS tool. Genotyping of 23 wart-associated HPV types was performed using the hyperkeratotic skin lesion-polymerase chain reaction/multiplex genotyping assay. The results were correlated with a favourable response to treatment with monochloroacetic acid, cryotherapy or a combination of cryotherapy and salicylic acid. Odds ratios were calculated using logistic regression in a generalized estimating equations model.RESULTS: Black dots (capillary thrombosis) strongly predicted the presence of any HPV type in a wart. From all characteristics tested, the HPV type most strongly predicted the treatment response when the warts were treated with monochloroacetic acid or a combination of cryotherapy and salicylic acid with a significantly decreased treatment response if the warts contained HPVs of the alpha genus (HPV2, HPV27 or HPV57). When cryotherapy alone was used for common warts, HPV type did not play a role, but cryotherapy was less effective in the presence of callus and when the wart was located deeper in the skin.CONCLUSIONS: Morphological characteristics of the warts and the HPV genotype influence treatment outcome and thus potentially influence future treatment decisions for common and plantar warts Show less
Kouwenhoven, S.T.P.; Kester, M.S. van; Genders, R.E. 2017
Aims: The purpose of this study was to determine if Computed Tomography Arterial Portography (CTAP) has additional value to Contrast Enhanced helical CT (CE-CT) in selecting patients for hepatic... Show moreAims: The purpose of this study was to determine if Computed Tomography Arterial Portography (CTAP) has additional value to Contrast Enhanced helical CT (CE-CT) in selecting patients for hepatic surgery or Isolated Hepatic Perfusion/systemic chemotherapy. Materials and methods: Forty-one patients were included. All CT's were performed in the normal pre-operative work-LIP of patients with liver metastases in our regular clinical setting and reviewed blinded by a radiologist. For CE-CT and CTAP the number, size (largest diameter) and location of all suspected malignant liver lesions were recorded. The favourable treatment option was determined based on the results of CE-CT and CTAP independently. The therapeutic decision based on CE-CT and CTAP was compared with the definite treatment. For all patients with recorded findings during surgery, consisting of intra-operative ultrasound, liver palpation and histology a standard of reference for lesion detection was available. For these patients detection rates and the fraction of false positive lesions were calculated. Results: Twenty-seven patients were treated with hepatic resection and/or RFA. Fourteen patients were treated with chemotherapy, 4 with Isolated Hepatic Perfusion (IHP) and 10 with systemic therapy. Based on the findings on CE-CT 31 patients were classified as surgical candidates and 10 as non-surgical patients. Based on the findings on CTAP, surgery should be the treatment of choice in 29 patients and 12 patients were classified non-surgical. CE-CT and CTAP disagreed in two cases (4.9%). Seventy-four metastases were identified at surgery and pathologically proved. CE-CT and CTAP showed 53 (.72) and 66 (.89) metastases, respectively. Conclusion: Despite a significantly higher detection rate for hepatic metastases, CTAP has no added value in the therapeutic stratification in candidates for resection of hepatic metastases of colorectal cancer. (C) 2009 Elsevier Ltd. All rights reserved. Show less
Kouwenhoven, S.T.P.; Liefers, G.J.; Erkel, A.R. van 2010
AIMS: The purpose of this study was to determine if Computed Tomography Arterial Portography (CTAP) has additional value to Contrast Enhanced helical CT (CE-CT) in selecting patients for hepatic... Show moreAIMS: The purpose of this study was to determine if Computed Tomography Arterial Portography (CTAP) has additional value to Contrast Enhanced helical CT (CE-CT) in selecting patients for hepatic surgery or Isolated Hepatic Perfusion/systemic chemotherapy. MATERIALS AND METHODS: Forty-one patients were included. All CT's were performed in the normal pre-operative work-up of patients with liver metastases in our regular clinical setting and reviewed blinded by a radiologist. For CE-CT and CTAP the number, size (largest diameter) and location of all suspected malignant liver lesions were recorded. The favourable treatment option was determined based on the results of CE-CT and CTAP independently. The therapeutic decision based on CE-CT and CTAP was compared with the definite treatment. For all patients with recorded findings during surgery, consisting of intra-operative ultrasound, liver palpation and histology a standard of reference for lesion detection was available. For these patients detection rates and the fraction of false positive lesions were calculated. RESULTS: Twenty-seven patients were treated with hepatic resection and/or RFA. Fourteen patients were treated with chemotherapy, 4 with Isolated Hepatic Perfusion (IHP) and 10 with systemic therapy. Based on the findings on CE-CT 31 patients were classified as surgical candidates and 10 as non-surgical patients. Based on the findings on CTAP, surgery should be the treatment of choice in 29 patients and 12 patients were classified non-surgical. CE-CT and CTAP disagreed in two cases (4.9%). Seventy-four metastases were identified at surgery and pathologically proved. CE-CT and CTAP showed 53 (.72) and 66 (.89) metastases, respectively. CONCLUSION: Despite a significantly higher detection rate for hepatic metastases, CTAP has no added value in the therapeutic stratification in candidates for resection of hepatic metastases of colorectal cancer. Show less
