Patient-reported outcome measurements in facial skin surgery and a comparison between Mohs micrographic surgery and conventional excisions.

BACKGROUND: Knowledge of the psychosocial impact of facial skin surgery on patients can help improve counselling strategies. OBJECTIVES: The objective was to measure the psychological impact of facial skin cancer surgery on patients over a 1-year period. Secondary objective was to measure the difference between Mohs micrographic surgery (MMS) and conventional excision (CE) on these parameters. METHODS: This observational survey study was conducted between March 2019 and July 2020. Patients who had facial skin surgery using MMS or CE were selected. Five surveys were conducted on four timepoints (preoperative, 1 week, 3 months and 1 year post-operative) measuring the quality of life, perceived stigmatization, body image, satisfaction with facial appearance and psychosocial distress. RESULTS: A total of 228 patients (MMS 154 patients, CE 74 patients) were included for the analysis. Scores for quality of life did not significantly change, in the year after surgery (PCS-12 mean 50.5, SD 9.3 and MCS-12 50.6, SD 9.4); however, stigmatization (F (3, 235,39) 7,26, p < 0.01, d = -0.07), body image concerns (F (3, 198,28) = 3.75, p < 0.01, d = -0.14), satisfaction with facial appearance (F (3, 205,18) = 10.74, p < 0.01, d = 0.43) and psychosocial distress (F (3, 208,69) = 9.26, p < 0.01, d = -0.15) did change over time. The use of MMS or CE did not significantly affect outcome scores after 1 year. CONCLUSION: Patients receiving facial skin cancer surgery exhibited low scores for perceived stigmatization and body image concerns. Their quality of life was not statistically influenced by facial surgery, and their satisfaction with their facial appearance and psychosocial distress even improved after 1 year. The results suggest that the surgical treatment type (MMS or CE) does not influence the outcome. The overall results can help in counselling strategies to improve expectations for patients receiving facial surgery.

Update of advanced cutaneous squamous cell carcinoma.

The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing. A growing part of this patient group is formed by immunocompromised patients, for example organ-transplant recipients (OTR). Although over 90% of the cSCC show a relatively harmless clinical behaviour, there is also a chance of developing advanced cSCC and metastases. Locally advanced cSCC are defined as cSCC that have locally advanced progression and are no longer amenable to surgery or radiation therapy. Better understanding of the clinical behaviour of cSCC is essential to discriminate between low- and high-risk cSCC. Staging systems are important and have recently been improved. Genetic characterisation of SCC will likely become an important tool to help distinguish low and high-risk cSCC with an increased potential to metastasise in the near future. Available treatments for high-risk and advanced cSCC include surgery, radiotherapy, chemotherapy and targeted therapy with epidermal growth factor receptors inhibitors. Anti-PD-1 antibodies show promising results with response rates of up to 50% in both locally advanced and metastatic cSCC but, in its present form, is not suitable for OTR.

Risk factors for incomplete excision of cutaneous squamous cell carcinoma: a large cohort study.

BACKGROUND: The standard treatment for cutaneous squamous cell carcinoma (cSCC) is surgical excision. Failure to radically remove a cSCC is a risk for recurrence, progression and metastasis. OBJECTIVES: This study investigates several risk factors for incomplete excision of cSCC. METHODS: All consecutive patients in a single institution treated with wide local excision for primary cSCC over a 10-year period were included in this study. Risk factors such as: gender, age, immunosuppression, tumour size, location, differentiation grade, tumour depth, perineural and lymphovascular invasion (PNI and LVI) were extracted from the database. Univariable and (if applicable) multivariable logistic regression analysis were used to identify risk factors (P < 0.05). Generalized estimating equations (GEEs) were used for multiple tumours within the same patients. RESULTS: A total of 566 patients with 1159 cSCC were identified. Univariable and multivariable logistic regression analysis showed that depth beyond the dermis (OR: 5.7 95% CI: 3.1-10.5) was the only risk factor for incomplete excision of cSCC. Immunosuppression was only a risk factor in the deep plane (OR: 2.5, 95% CI: 1.3-4.6). CONCLUSION: Tumour depth beyond the dermis is the most important risk factor for incomplete excision of cSCC. Immunosuppression is a risk factor in the deep plane but its relevance is uncertain. Immunosuppression is not consistently included in the current cSCC staging systems, but care should be taken when treating these patients.

Metastasis of cutaneous squamous cell carcinoma in organ transplant recipients and the immunocompetent population: is there a difference? a systematic review and meta-analysis.

BACKGROUND: Organ transplant recipients (OTR) have a higher risk of developing cutaneous squamous cell carcinoma (cSCC) compared to the immunocompetent population. Immunosuppression is often stated as a risk factor for metastasis. However, evidence for this is scarce. OBJECTIVES: To investigate the cSCC metastasis risk in OTR and the immunocompetent population by systematically reviewing the literature. METHODS: A systematic review of the literature was performed up to January 2018 using: Medline; Embase; Web of Science and ISI Science Citation Index. Studies assessing cSCC metastasis risk in ORT or immunocompetent cohorts were considered. A pooled risk estimate for metastasis was calculated for the immunocompetent population and OTR separately. RESULTS: The pooled metastasis risk estimate for OTR was, respectively, 7.3% (95% CI 6.2-8.4) for cSCC on total body, and 11.0% (95% CI 7.7-14.8) for cSCC of the head neck area. For the immunocompetent population reported risk estimate analysis showed a pooled metastatic risk of 3.1% (95% CI 2.8-3.4) in total body cSCC and of 8.5% (95% CI 7.3-9.8) in cSCC of the head and neck area. Pooled risk estimate per single cSCC in OTR was 1.3% (95% CI 1.0-1.7) in total body cSCC and 4.0% (95% CI 2.7-5.5) in cSCC of the head and neck area. In the immunocompetent population, these pooled risk estimates were, respectively, 2.4% (95% CI 2.1-2.6) and 6.7% (95% CI 5.7-7.8). CONCLUSIONS: Organ transplant recipients show a higher overall risk of cSCC metastasis compared to the immunocompetent population. Metastasis risks per single cSCC were substantially lower in both groups. However, due to heterogeneity and differences between studies, comparisons are difficult. Comprehensive follow-up studies with defined cohorts are necessary to adequately asses the risk for cSCC metastasis.

Topical ionic contra-viral therapy comprised of digoxin and furosemide as a potential novel treatment approach for common warts.

BACKGROUND: DNA viruses such as HPV rely on K+ influx for replication. Both digoxin and furosemide inhibit the K+ influx by interacting with cell membrane ion co-transporters (Na+ /K+ -ATPase and Na+ -K+ -2Cl- co-transporter-1, respectively). We therefore hypothesized that these two compounds in a topical formulation may be valuable in the treatment of HPV-induced warts. This new approach is called Ionic Contra-Viral Therapy (ICVT). OBJECTIVE: To evaluate systemic exposure, safety and tolerability of ICVT with a combination of furosemide and digoxin after repeated topical application in subjects with common warts. Furthermore, we aimed to evaluate pharmacodynamics effects of ICVT. METHODS: Twelve healthy subjects with at least four common warts on their hands were included in the study and treated with a fixed dose of 980 mg topical gel containing 0.125% (w/w) digoxin and 0.125% (w/w) furosemide for 7 consecutive days on their lower back to assess safety and systemic exposure. Two warts were treated with 10 mg each and two served as negative controls to obtain preliminary evidence of treatment effect. RESULTS: ICVT was well tolerated topically, and there was no evidence of systemic exposure of digoxin or furosemide. There were no clinical relevant safety findings and no serious adverse events (SAEs). A rapid and statistically significant reduction in diameter, height and volume of the warts was already observed at day 14. CONCLUSION: ICVT was found to be safe for administration to humans and 7 days of active treatment showed a statistical significant wart reduction compared to untreated control lesions, clearly indicating pharmacological activity.

Pain identifies squamous cell carcinoma in organ transplant recipients: the SCOPE-ITSCC PAIN study.

Organ transplant recipients (OTR) are at high risk for cutaneous squamous cell carcinomas (SCC). We aimed to define clinically meaningful patient-reported warning signals predicting the presence of invasive SCC.Patient-reported signs and symptoms of 812 consecutively biopsied skin lesions from 410 OTR were determined by questionnaire and physical examination and related to the subsequent biopsy-proven diagnoses. Receiver-operating characteristic (ROC) curve analyses were used as a measure of distinction between the predictive values of patient-reported warning signals and the occurrence of SCC. Pain was an independent predictive patient-reported warning signal for a biopsy-proven invasive SCC. The odds ratio from the fully adjusted model predicting SCC was 4.4(95% confidence interval: 2.4­8.2). Higher scores on the visual analog scale (VAS) for pain were associated witha greater likelihood for the presence of SCC compared to none or mild pain. The for scores on the VAS from 1to 3, 4 to 6 and 7 to 10 were 4.9 (2.2­10.5), 2.3 (0.96­5.5)and 16.5 (3.6­75.8), respectively. Pain is the most powerful patient-reported warning signal for invasive cutaneous SCC in OTR. Empowerment of patients by education could accelerate diagnosis and treatment of cutaneous SCC.

Characterization of skin lesions induced by skin-tropic α- and ß-papillomaviruses in a patient with epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a rare, lifelong, autosomal recessive skin disease associated with an unusual susceptibility to infections with ubiquitous ß-human papillomaviruses (ß-HPVs), and in some cases also skin-tropic α genotypes. In this case report, HPV infection patterns were correlated with pathology and clinical manifestations of skin lesions from a patient with EV, without loss-of-function mutations in the EVER genes. HPV infection was investigated by both polymerase chain reaction (PCR) and laser capture microdissection (LCM) PCR, alongside immunofluorescence for the viral proteins E4 and L1. Analysis of eyebrow hair bulbs revealed multiple ß-genus HPV infections, including HPV20 and HPV24, which were consistently found in all 11 skin lesions on the patient. Six lesions were also positive for the skin tropic α-genotype, HPV27. Clear-cut differences between two wart-like lesions, one caused by a skin-tropic α-genotype and the other by ß-genotypes (as detected by LCM PCR) are shown, including the high cellular proliferation rate in ß-HPV-induced lesions. Widespread expression of the early protein E4 was also evident in skin lesions positive for HPV20 by LCM PCR in both tumours and nearby intraepidermal proliferative areas. L1 expression was restricted to areas of intraepidermal proliferation showing productive infection. The patient's inability to control HPV infections is conclusive to the uncontrolled replication of few genotypes from both α and ß genera, which cause proliferative lesions with clear-cut clinical and histological features.

Skin hardening effect in patients with polymorphic light eruption: comparison of UVB hardening in hospital with a novel home UV-hardening device.

BACKGROUND: An effective prophylactic treatment of patients with polymorphic light eruption (PLE) consists of repeated low, gradually increasing exposures to UVB radiation. This so-called UV(B) hardening induces better tolerance of the skin to sunlight. OBJECTIVE: SunshowerMedical company (Amsterdam) has developed an UV (B) source that can be used during taking shower. The low UV fluence of this apparatus makes it an interesting device for UV hardening. In a group of PLE patients, we compared the effectiveness of the irradiation with SunshowerMedical at home with that of the UVB treatment in the hospital. METHODS: The PLE patients were randomized for one of the treatments. The hospital treatment consisted of irradiations with broad-band UVB (Waldmann 85/UV21 lamps) twice a week during 6 weeks. The home UV-device was used each day with the maximal irradiation time of 6 min. The outcome assessment was based on the information obtained from patients' dermatological quality of life (DLQI) questionnaires, the ability of both phototherapies to reduce the provocation reaction and from the patients' evaluation of the long-term benefits of their phototherapies. RESULTS: Sixteen patients completed treatment with SunshowerMedical and thirteen completed treatment in hospital. Both types of phototherapy were effective. There was a highly significant improvement in DLQI with either treatment. In most cases, the hardening reduced or even completely suppressed clinical UV provocation of PLE. The patients using SunshowerMedical at home were, however, much more content with the treatment procedure than the patients visiting the dermatological units. CONCLUSIONS: Both treatments were equally effective in the induction of skin tolerance to sunlight in PLE patients. However, the home treatment was much better accepted than the treatment in the hospital.

A misleading urethral smear with polymorphonuclear leucocytes and intracellular diplococci; case report of urethritis caused by Neisseria meningitidis.

The primary pathogens found in men with urethritis are Chlamydia trachomatis and Neisseria gonorrhoeae. Rapid diagnosis of N. gonorrhoeae infection can be made based on a Gram- or methylene blue-stained urethral smear. We describe a case of a man with purulent penile discharge, in which microscopic examination led to the presumptive diagnosis of gonorrhoea. A nucleic acid amplification test was negative for N. gonorrhoeae but positive for C. trachomatis. Culture showed Gram-negative diplococci which were identified as Neisseria meningitidis. N. meningitidis can be sporadically pathogenic in the genito-urinary tract and mimicks gonococcal urethritis, and appears identical by microscopy. When a gonococcal urethritis is suspected based on clinical signs and microscopic examination, but investigatory tests cannot confirm the diagnosis, a N. meningitidis infection should be considered.