Checkpoint immunotherapy of cutaneous squamous cell carcinoma in patients suffering from chronic lymphocytic leukaemia: divergent outcomes in two men treated with PD-1 inhibitors.

Cutaneous squamous cell carcinoma (cSCC) numbers among the most common types of skin cancer and is known as one of the cancer entities with the highest mutational burden among all solid tumours. Due to the positive correlation between mutational burden and response rate to inhibitors of the programmed cell death 1 (PD-1), those inhibitors are considered promising candidates for the systemic therapy of cSCC. Recently, the PD-1 inhibitors pembrolizumab, nivolumab and cemiplimab demonstrated efficacy in the systemic treatment of locally advanced or metastatic cSCC leading to the approval of cemiplimab by the FDA (U.S. Food and Drug Administration) in 2018 and the EMA (European Medicines Agency) in 2019. Patients with haematological malignancies tend to develop skin cancers of high aggressiveness, enhanced cumulative recurrence rate and higher rates of metastases with subsequent death. Chronic lymphocytic leukaemia (CLL) is the most frequent type of leukaemia in the United States and Europe with the majority of patients older than 50 years of age. This neoplasm predominantly originates from B -cells leading to an impaired immune system of the patient. Although CLL is a B-cell malignancy, studies have also described the involvement of T cells in the pathogenesis and progression of the disease with contradictory findings on the effects of PD-1 inhibitors in CLL. Due to their underlying hematologic malignancy, these patients have commonly no access to PD-1 inhibitor trials for treatment of advanced cSCC. We report on two patients with locally advanced or metastatic cSCC. Both patients had been suffering from a CLL for many years without indication for treatment. Despite a potential immunosuppressive state of the patients due to their CLL, both were treated with the PD-1 inhibitor pembrolizumab resulting in different therapy outcomes.

[Modern ulcer surgery : Invasive treatment options using the example of therapy-resistant venous leg ulcers]. / Moderne Ulkuschirurgie : Invasive Behandlungsoptionen am Beispiel des therapieresistenten Ulcus cruris venosum.

The socioeconomic significance of chronic venous leg ulcers is considerable due to the high number of patients, the costs of diagnosis and therapy, the deterioration in quality of life, and the loss of working capacity during the disease. This is further increased by a progressive course and an increased tendency to recurrence. Taking these facts into account, surgical treatment options are of particular importance, especially in otherwise therapy-refractory courses. For this purpose, an extensive spectrum of surgical and new, partly not yet finally evaluated, invasive techniques are now available. Venous surgery and endovenous closure techniques are suitable for eliminating primary or secondary varicosis as a causal therapy for venous leg ulcers. Shave therapy is the method of choice in the presence of dermatolipo(fascio)sclerosis. Current long-term results show good results with cure rates of 70-80%. In individual cases, surgical techniques involving fascia cruris (faciotomy, fasciotomy) can also be used. Recurrence ulcers can often be successfully treated by repeated shave therapy, optionally with simultaneous vacuum-assisted dressing techniques or by a fasciotomy. In addition, local invasive techniques such as autologous fat tissue transplantation or autologous platelet-rich plasma can be used to promote wound healing. Thus, both surgically invasive local therapy and advanced surgery of the causes of chronic venous leg ulcers play a key role in the overall therapy concept.

[Quality of self-applied compression bandages in patients with chronic venous ulcers : Results of a prospective clinical study]. / Qualität von selbst angelegten Kompressionsverbänden bei Patienten mit chronischem Ulcus cruris venosum : Resultate einer prospektiven klinischen Studie.

BACKGROUND: For effective compression therapy in patients with venous leg ulcers, sufficient pressure is essential. In everyday life, it is often the patients themselves who apply the compression bandages. Many of these patients have restriction in their movement and had been rarely trained adequately. Hence, there was the question of how efficient are the autonomously applied compression bandages of those patients. PATIENTS AND METHODS: In all, 100 consecutive patients with venous leg ulcer were asked to apply compression bandages on their own leg. We documented both the achieved compression and formal criteria of correct performance. RESULTS: A total of 59 women and 41 men with an average age of 70.3 years were included in the study. Overall 43 patients were not able to apply a compression bandage because of physical limitations. The measured pressure values in the remaining 57 patients ranged between 6 and 93 mm Hg (mean 28.3 mm Hg). Eleven patients reached the prescribed effective compression pressure. Of these, formal errors were found in 6 patients, so that only 5 patients had correctly applied the compression bandages. CONCLUSION: Our data show that most patients with venous leg ulcers are not able to apply effective compression therapy with short-stretch bandages to themselves. Multilayer systems, adaptive compression bandages, and ulcer stocking systems today are possibly easier and more effective therapy options. Alternatively short-stretch bandages could be applied by trained persons but only under the control with pressure measuring probes.

Photoacoustic imaging of real-time oxygen changes in chronic leg ulcers after topical application of a haemoglobin spray: a pilot study.

OBJECTIVE: To use a non-invasive measurement of oxygen saturation in chronic leg ulcers after the application of a topical haemoglobin spray to investigate if photoacoustic tomography is able to measure the oxygen saturation and if the stimulated oxygen increase can be demonstrated. METHOD: We measured the oxygen saturation of the ulcer tissue in five patients with chronic leg ulcers before application and 5 and 20 minutes after application of the haemoglobin spray, using photoacoustic tomography as a new method to assess oxygenation in real-time. RESULTS: The average oxygen saturation showed a significant increase from 56.4% before to 69% (p=0.042) after 5 minutes and 78.8% (p=0.043) 20 minutes after the topical haemoglobin application. CONCLUSION: The oxygenation status of chronic, hard-to-heal wounds is gaining increasing interest in modern wound therapy. Topical haemoglobin spray is a new and effective method to increase the oxygenation in the ulcer tissue, but until now the link between clinical results and the mode of action was unclear. We were able to show for the first time that the use of a topical haemoglobin spray leads to an increase in oxygen saturation in vivo using photoacoustic tomography. DECLARATION OF INTEREST: Joachim Dissemond received financial support from the company SastoMed for several scientific projects as well as for lectures and as an advisor. The haemoglobin spray was provided by SastoMed GmbH (Georgsmarienhütte, Germany).

Reliability and cost-effectiveness of complete lymph node dissection under tumescent local anaesthesia vs. general anaesthesia: a retrospective analysis in patients with malignant melanoma AJCC stage III.

BACKGROUND: Complete lymph node dissection (CLND) in melanoma patients with a positive sentinel lymph node (SLN) is currently being debated, as it is a cost-intensive surgical intervention with potentially high morbidity. OBJECTIVE: This clinical study seeks to clarify the effectiveness, reliability and cost-effectiveness of CLND performed under tumescent local anaesthesia (TLA) compared with procedures under general anaesthesia (GA). METHODS: We retrospectively analysed the data from 60 patients with primary malignant melanoma American Joint Committee on Cancer stage III who underwent CLND. RESULTS: Altogether 26 (43.3%) patients underwent CLND under TLA and 34 (56.7%) patients underwent CLND under GA. Fifteen of 43 (34.9%) patients had a complication, such as development of seromas and/or wound infections. The rate of complications was 25.0% (3/12) in the axilla subgroup and 28.6% (4/14) in the groin subgroup of the TLA group. In the GA group, the complication rate was 31.3% (5/16) in the axilla subgroup and 44.4% (8/18) in the groin subgroup. The costs for CLND were significantly less for the CLND in a procedure room performed under TLA (mean €67.26) compared with CLND in an operating room under GA (mean €676.20, P < 0.0001). CONCLUSIONS: In conclusion, this study confirms that TLA is an excellent, safe, effective and cost-efficient alternative to GA for CLND in melanoma patients.

Radio-guided surgery: advantages of a new portable γ-camera (Sentinella) for intraoperative real time imaging and detection of sentinel lymph nodes in cutaneous malignancies.

BACKGROUND: The histological status of the sentinel lymph node (SLN) is one of the most relevant prognostic factors for the overall survival of patients with cutaneous malignancies, independent of tumour depth of the primary tumour. OBJECTIVES: Our study seeks to evaluate the reliability and medical benefit of SLN excision (SLNE) performed with a portable γ-camera for intraoperative real time imaging of SLN. METHODS: Therefore our study compares the visualization of SLN performed with preoperative lymphoscintigraphy and preoperative SPECT/CT with the intraoperative real time imaging of SLN performed with a new portable γ-camera (Sentinella) in 60 patients who were treated with a SLNE for early stage melanoma (n = 38), high risk cutaneous squamous cell carcinoma (n = 16), Merkel cell carcinoma (n = 4), sebaceous gland carcinoma (n = 1), and sweat glands carcinoma or porocarcinoma (n = 1). RESULTS: Sixty patients were enrolled in this study. The portable γ-camera visualized all 126 preoperatively identified SLN. 23 additional SLN (15.4%) in 15 patients were only identified using the portable γ-camera. Two of these additional SLN showed metastatic involvement. CONCLUSION: The portable γ-camera is an innovative imaging technique, reliable and providing additional information in the detection of SLN. Therefore SLNE with intraoperative γ-camera use is an attractive option to improve the detection of SLN in cutaneous malignancies and could help to reduce false negative SLN results.

Advantages of preoperative ultrasound in conjunction with lymphoscintigraphy in detecting malignant melanoma metastases in sentinel lymph nodes: a retrospective analysis in 221 patients with malignant melanoma AJCC Stages I and II.

BACKGROUND: Sentinel lymph node excision (SLNE) for the detection of regional nodal metastases and staging of malignant melanoma has resulted in some controversies in international discussions as it is a surgical intervention with potential morbidity. OBJECTIVE: The present retrospective study seeks to clarify the reliability of preoperative ultrasonography (US) in direct comparison to the result of SLNE and seeks to identify potential advantages of preoperative ultrasound if performed in conjunction with lymphoscintigraphy in detecting malignant melanoma metastases in sentinel lymph node (SLN). PATIENTS: We retrospectively analysed data from 221 patients with primary malignant melanoma with a Breslow index of ≥ 1.0 mm. RESULTS: Of the 221 patients, 77.4% (n = 171) had a negative SLN. In 50 patients (22.6%), the histopathological investigation of 71 excised lymph nodes resulted in a positive SLN. The US examination demonstrated a sensitivity of 13.6%, a specificity of 96.9%, a positive predictive value of 97.2% and a negative predictive value of 12.6%. SLNE alone shows a sensitivity of 94%, a specificity of 98.6%, a positive predictive value of 100% and a negative predictive value of 98.3%. Preoperative US in conjunction with dynamic lymphoscintigraphy, followed by SLNE, demonstrated a detecting ratio of 100% (n = 28) for micrometastases and 98.6% (n = 42/43) for macrometastases. CONCLUSION: In conclusion, this study confirms that preoperative US alone cannot replace the vital information obtained during dynamic lymphoscintigraphy. But preoperative US is an important component of the staging procedure in melanoma patients and has clear advantages when performed in conjunction with dynamic lymphoscintigraphy. Therefore, we recommend preoperative US before every SLNE.

Relationship between the seasonal onset of chronic venous leg ulcers and climatic factors.

BACKGROUND: There have been reports indicating seasonal differences in the onset of chronic leg ulcers. The reasons for such seasonal fluctuations are not well understood. Therefore we decided to examine the seasonal incidence of chronic leg ulcers in our patient population, caused by chronic venous insufficiency (CVI) or mixed arterial and venous disorders, for any correlation with climatic factors. METHODS: We retrospectively analysed the data of 183 patients with chronic leg ulcers, evaluated the monthly and seasonal onset of the leg ulcers and investigated correlations between the incidence and climatic factors. RESULTS: The onset of chronic leg ulcers showed significant seasonal fluctuations with a decrease in summer and an increase in autumn-winter. The ulcer onset in the cold months, autumn and winter, was significantly higher (P = 0.026) compared with spring and summer. Furthermore, in the bivariate correlation analysis of the variables temperature and ulcer onset, there was a statistically significant negative correlation between temperature and new ulcer onset. The colder the temperature was, the higher was the new ulcer onset with a correlation coefficient of -0.613 (P = 0.034). CONCLUSION: The onset of chronic leg ulcers caused by CVI and mixed arterial and venous disorders in our patient population showed significant seasonal variations and demonstrated an inverse relationship to temperature. In summary, climatic factors appear to play an important role in the onset of chronic leg ulcers. Climatic factors may therefore need consideration in future clinical investigations and in the development of prophylactic therapeutic strategies.

Advantages of preoperative hybrid SPECT/CT in detection of sentinel lymph nodes in cutaneous head and neck malignancies.

BACKGROUND: There is some controversy around the value of sentinel lymph node excision (SLNE). Especially SLNE of cutaneous head and neck malignancies has been debated intensively, in part because of the complexity of the lymphatic drainage in this region associated with potential high morbidity. In order to improve preoperative three-dimensional mapping of sentinel lymph nodes (SLN), in the head and neck region, by means of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) is gaining significance. Our study seeks to identify the potential medical and economic advantages of preoperative SPECT/CT in direct comparison to standard SLNE without SPECT/CT in patients with cutaneous head and neck malignancies. METHODS: We retrospectively analysed the data of 48 clinically lymph node-negative patients with early stage melanoma, high risk cutaneous squamous cell carcinoma and porocarcinoma, who underwent SLNE with or without preoperative SPECT/CT within 4 years. RESULTS: The SLNE in the head and neck region with SPECT/CT-technique demonstrated better postoperative aesthetic results had lower morbidity and significantly reduced operating time. Moreover, SLNE with SPECT/CT-technique in the head and neck region was feasible using local anaesthesia (LA) and significantly reduced resulting costs (€32.65/SLNE with LA vs. €334.57/SLNE with general anaesthesia, P < 0.0001). CONCLUSION: SPECT/CT is an innovative imaging technique, reliably and readily providing additional anatomical/functional information to detect and to excise SLN in the head and neck region. Therefore, SLNE with SPECT/CT-technique is an attractive option to improve the detection of SLN in cutaneous head and neck malignancies.

Investigation of adhesion of modern wound dressings: a comparative analysis of 56 different wound dressings.

INTRODUCTION: In the process of chronic wound care, adhesive wound dressings may cause pain and injury in the wound environment during dressing changes. At present, no standardized test procedures are available for the investigation of adhesion of wound dressings. Therefore, our study aimed to test the adhesion of different wound dressings on steel as well as on healthy skin. METHODS: Within an open, comparative study, the adhesive areas of 56 wound dressings were investigated. The adhesives were categorized into acrylate (n = 23), silicone (n = 9), hydrocolloid (n = 17) and polyurethane groups (n = 7). Using an especially modified testing machine, the adhesion of the wound dressings was measured on steel as well as on the skin of healthy study participants, in compliance with the European EN 1939:2003 standard. RESULTS: The energy required to remove the wound dressings from human skin, was measured in Newton (N) and the following median values were obtained: hydrocolloid (2.25 N) > acrylate (1.14 N) > polyurethane (0.9 N) > silicone (0.7 N). The subjective pain intensity during the removal of the wound dressings was recorded using the visual analogue scale (VAS) with values ranging from 0 to 10. For hydrocolloid, it was 6.8, for acrylate 4.9, for polyurethane 3.1 and for silicone 2.5 points VAS. In comparison with human skin, the adhesion of wound dressings was significantly higher on steel (P < 0.0001), but was different for the different groups of wound dressings. Moreover, there was a statistically significant correlation between the adhesion and pain intensity (correlation coefficient 0.806; P = 0.01). CONCLUSION: The knowledge about the widely differing adhesion properties of different wound dressings on the skin of patients should nowadays be considered during the individual selection of the applied products. Based on these data, different types of wound dressings could be developed, guaranteeing a good adhesion and a low traumatic risk when removed.

Reliability and cost-effectiveness of sentinel lymph node excision under local anaesthesia versus general anaesthesia for malignant melanoma: a retrospective analysis in 300 patients with malignant melanoma AJCC Stages I and II.

BACKGROUND: Sentinel lymph node excision (SLNE) for the detection of regional nodal metastases and staging of malignant melanoma has resulted in some controversies in international discussions, as it is a cost-intensive surgical intervention with potentially significant morbidity. OBJECTIVE: The present retrospective study seeks to clarify the effectiveness and reliability of SLNE performed under tumescent local anaesthesia (TLA) and whether SLNE performed under TLA can reduce costs and morbidity. Therefore, our study is a comparison of SLNE performed under TLA and general anaesthesia (GA). PATIENTS: We retrospectively analysed data from 300 patients with primary malignant melanoma with a Breslow index of ≥1.0 mm. RESULTS: Altogether, 211 (70.3%) patients underwent SLNE under TLA and 89 (29.7%) patients underwent SLNE under GA. A total of 637 sentinel lymph nodes (SLN) were removed. In the TLA group 1.98 SLN/patient and in the GA group 2.46 SLN/patient were removed (median value). Seventy patients (23.3%) had a positive SLN. No major complications occurred. The costs for SLNE were significantly less for the SLNE in a procedures room performed under TLA (mean € 30.64) compared with SLNE in an operating room under GA (mean € 326.14, P<0.0001). CONCLUSION: In conclusion, SLNE performed under TLA is safe, reliable, and cost-efficient and could become the new gold standard in sentinel lymph node diagnostic procedures.

[The impact of silicone spray on scar formation. A single-center placebo-controlled double-blind trial]. / Einfluss eines Silikonsprays auf die Narbenbildung. Doppelblinde, placebokontrollierte, unizentrische Studie.

For more than two decades silicone has successfully been employed in the treatment and prevention of hypertrophic scars and keloids as a painless noninvasive modality with few side effects. In the present trial, after 3 months of treatment the Patient Scar Assessment Scale demonstrated that patient satisfaction with the silicone application was significantly higher compared to placebo. When treatment was stopped after 3 months, the topical silicone spray did not exhibit any lasting long-term impact on the objective results of scar formation. Due to the significant differences in patient satisfaction once treatment has ended and since the administration is safe and simple, any final decision on treatment indication should be tailored to the patient and include the psychological well-being of the patient as well as the temporary improvement in scar formation during treatment.