Multispectral optoacoustic tomography to differentiate between lymph node metastases and coronavirus-19 vaccine-associated lymphadenopathy.

INTRODUCTION: Worldwide mass vaccination for COVID-19 started in late 2020. COVID-19 vaccines cause benign hypermetabolic lymphadenopathies. Clinical stratification between vaccine-associated benign lymphadenopathies and malignant lymphadenopathies through ultrasound, MRI or FDG PET-CT is not feasible. This leads to unnecessary lymph node biopsies, excisions and even radical lymph node dissections. Therefore, to avoid unnecessary surgeries, we assessed whether noninvasive multispectral optoacoustic tomography (MSOT) enables a better differentiation between benign and malignant lymphadenopathies. PATIENTS AND METHODS: All patients were vaccinated for COVID-19. We used MSOT to image deoxy- and oxyhaemoglobin levels in lymph nodes of tumour patients to assess metastatic status. MSOT imaging results were compared with standard ultrasound and pathological lymph node analysis. We also evaluated the influences of gender, age and time between vaccination and MSOT measurement of lymph nodes on the measured deoxy- and oxyhaemoglobin levels in patients with reactive lymph node changes. RESULTS: Multispectral optoacoustic tomography was able to identify cancer-free lymph nodes in vivo without a single false negative (33 total lymph nodes), with 100% sensitivity and 50% specificity. A statistically significant higher deoxyhaemoglobin content was detected in patients with tumour manifestations in the lymph node (p = 0.02). There was no statistically significant difference concerning oxyhaemoglobin (p = 0.65). Age, sex and time between vaccination and MSOT measurement had statistically non-significant impact on deoxy- and oxyhaemoglobin levels in patients with reactive lymph nodes. CONCLUSION: Here, we show that MSOT measurement is an advantageous clinical approach to differentiate between vaccine-associated benign lymphadenopathy and malignant lymph node metastases based on the deoxygenation level in lymph nodes.

Patient-Derived Human Basal and Cutaneous Squamous Cell Carcinoma Tissues Display Apoptosis and Immunomodulation following Gas Plasma Exposure with a Certified Argon Jet.

Reactive oxygen species (ROS) have been subject of increasing interest in the pathophysiology and therapy of cancers in recent years. In skin cancer, ROS are involved in UV-induced tumorigenesis and its targeted treatment via, e.g., photodynamic therapy. Another recent technology for topical ROS generation is cold physical plasma, a partially ionized gas expelling dozens of reactive species onto its treatment target. Gas plasma technology is accredited for its wound-healing abilities in Europe, and current clinical evidence suggests that it may have beneficial effects against actinic keratosis. Since the concept of hormesis dictates that low ROS levels perform signaling functions, while high ROS levels cause damage, we investigated herein the antitumor activity of gas plasma in non-melanoma skin cancer. In vitro, gas plasma exposure diminished the metabolic activity, preferentially in squamous cell carcinoma cell (SCC) lines compared to non-malignant HaCaT cells. In patient-derived basal cell carcinoma (BCC) and SCC samples treated with gas plasma ex vivo, increased apoptosis was found in both cancer types. Moreover, the immunomodulatory actions of gas plasma treatment were found affecting, e.g., the expression of CD86 and the number of regulatory T-cells. The supernatants of these ex vivo cultured tumors were quantitatively screened for cytokines, chemokines, and growth factors, identifying CCL5 and GM-CSF, molecules associated with skin cancer metastasis, to be markedly decreased. These findings suggest gas plasma treatment to be an interesting future technology for non-melanoma skin cancer topical therapy.

[Long-term healing of a therapy-refractory venous leg ulcer after crural fasciectomy and split skin graft transplantation]. / Langfristige Abheilung eines therapierefraktären Ulcus cruris venosum nach kruraler Fasziektomie und Spalthauttransplantation.

A 59-year-old obese woman had been suffering from a painful, chronic leg ulcer since 1986. We diagnosed a venous leg ulcer due to functional chronic venous insufficiency in the context of obesity per magna (dependency syndrome) and arthrogenic congestion syndrome due to immobility. Although a high ligation and stripping of the great saphenous vein and several so-called shave therapies with split skin transplantation after appropriate wound bed preparation had been previously performed, the wound persisted. In 2012, the patient wanted to amputate her leg because the course of wound healing was so refractory to therapy and she suffered from severe pain. As an alternative to amputation, we performed a crural fascietomy and, after a wound bed preparation with two cycles of negative pressure wound therapy, we covered the defect with a split skin graft using the mesh graft technique. The surgery could be performed without complications and the skin healed completely. At the current presentation 7 years after the intervention, complete healing of the previously therapy-refractory venous leg ulcer was shown despite the persistent obesity per magna and immobility. This case report shows that a crural fasciectomy should be considered, especially in the case of otherwise therapy-refractory courses of venous leg ulcers.

Salivary cortisol levels and anxiety in melanoma patients undergoing sentinel lymph node excision under local anesthesia versus general anesthesia: a prospective study.

BACKGROUND: Sentinel lymph node excision (SLNE) can be performed in tumescent local anesthesia (TLA) or general anesthesia (GA). Perioperative cortisol level changes and anxiety are common in surgical interventions and might be influenced by the type of anesthesia. In this study, we intended to determine whether the type of anesthesia impacts the patients' perioperative levels of salivary cortisol (primary outcome) and the feeling of anxiety evaluated by psychological questionnaires (secondary outcome). METHODS: All melanoma patients of age undergoing SLNE at the University Hospital Essen, Germany, could be included in the study. Exclusion criteria were patients' intake of glucocorticoids or psychotropic medication during the former 6 months, pregnancy, age under 18 years, and BMI ≥ 30 as salivary cortisol levels were reported to be significantly impacted by obesity and might confound results. RESULTS: In total, 111 melanoma patients undergoing SLNE were included in our prospective study between May 2011 and April 2017 and could choose between TLA or GA. Salivary cortisol levels were measured three times intraoperatively, twice on the third and second preoperative day and twice on the second postoperative day. To assess anxiety, patients completed questionnaires (Hospital Anxiety and Depression Scale (HADS), State-Trait Anxiety Inventory (STAI)) perioperatively. Patients of both groups exhibited comparable baseline levels of cortisol and perioperative anxiety levels. Independent of the type of anesthesia, all patients showed significantly increasing salivary cortisol level from baseline to 30 min before surgery (T3) (TLA: t = 5.07, p < 0.001; GA: t = 3.09, p = 0.006). Post hoc independent t tests showed that the TLA group exhibited significantly higher cortisol concentrations at the beginning of surgery (T4; t = 3.29, p = 0.002) as well as 20 min after incision (T5; t = 277, p = 0.008) compared to the GA group. CONCLUSIONS: The type of anesthesia chosen for SLNE surgery significantly affects intraoperative cortisol levels in melanoma patients. Further studies are mandatory to evaluate the relevance of endogenous perioperative cortisol levels on the postoperative clinical course. TRIAL REGISTRATION: German Clinical Trials Register DRKS00003076, registered 1 May 2011.

Can integrated 18F-FDG PET/MR replace sentinel lymph node resection in malignant melanoma?

PURPOSE: To compare the sensitivity and specificity of 18F-fluordesoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), 18F-FDG PET/magnetic resonance (18F-FDG PET/MR) and 18F-FDG PET/MR including diffusion weighted imaging (DWI) in the detection of sentinel lymph node metastases in patients suffering from malignant melanoma. MATERIAL & METHODS: Fifty-two patients with malignant melanoma (female: n = 30, male: n = 22, mean age 50.5 ± 16.0 years, mean tumor thickness 2.28 ± 1.97 mm) who underwent 18F-FDG PET/CT and subsequent PET/MR & DWI for distant metastasis staging were included in this retrospective study. After hybrid imaging, lymphoscintigraphy including single photon emission computed tomography/CT (SPECT/CT) was performed to identify the sentinel lymph node prior to sentinel lymph node biopsy (SLNB). In a total of 87 sentinel lymph nodes in 64 lymph node basins visible on SPECT/CT, 17 lymph node metastases were detected by histopathology. In separate sessions PET/CT, PET/MR, and PET/MR & DWI were assessed for sentinel lymph node metastases by two independent readers. Discrepant results were resolved in a consensus reading. Sensitivities, specificities, positive predictive values and negative predictive values were calculated with histopathology following SPECT/CT guided SLNB as a reference standard. RESULTS: Compared with histopathology, lymph nodes were true positive in three cases, true negative in 65 cases, false positive in three cases and false negative in 14 cases in PET/CT. PET/MR was true positive in four cases, true negative in 63 cases, false positive in two cases and false negative in 13 cases. Hence, we observed a sensitivity, specificity, positive predictive value and negative predictive value of 17.7, 95.6, 50.0 and 82.3% for PET/CT and 23.5, 96.9, 66.7 and 82.3% for PET/MR. In DWI, 56 sentinel lymph node basins could be analyzed. Here, the additional analysis of DWI led to two additional false positive findings, while the number of true positive findings could not be increased. CONCLUSION: In conclusion, integrated 18F-FDG PET/MR does not reliably differentiate N-positive from N-negative melanoma patients. Additional DWI does not increase the sensitivity of 18F-FDG PET/MR. Hence, sentinel lymph node biopsy cannot be replaced by 18F-FDG-PE/MR or 18F-FDG-PET/CT.

A purpose-designed monofilament-fibre pad for debridement of hard-to-reach wounds: experience in clinical practice.

OBJECTIVE: Effective and comfortable debridement is an important part of managing complex wounds. This user test evaluated a monofilament-fibre pad (with handle) (Debrisoft Lolly, Lohmann & Rauscher GmbH & Co. KG) in the debridement of various hard-to-reach wounds. METHOD: The multicentre, international user test was performed by experienced physicians and nurses in Germany and the UK, who used the monofilament-fibre pad in their clinical practice. After debridement, using the monofilament-fibre pad, the clinicians completed an evaluation questionnaire. The assessment comprised of performance, usability, tolerability, safety and suitability of the device for debridement, comparing it with standard methods used in the clinicians' centres. RESULTS: A total of 23 clinicians in 20 centres each treated between six and 10 patients with the monofilament-fibre pad (a total of 155 wounds of different aetiologies). Most participating patients had deep wounds (n=63 (41%)) or cavity (n=31 (20%)) wounds. When compared with the standard debridement method used at the centres, the tested device was scored as 'easier' or 'equally easy' to use in all cases. When comparing the standard debridement procedure with the monofilament-fibre pad, debridement duration was reported as equal to or shorter than the standard method in 90% of cases when using the monofilament-fibre pad. Debridement efficacy was scored by the clinician as 'better' or 'equal' for the monofilament-fibre pad in 67% of cases. Overall, patients reported that the study device was comfortable. CONCLUSION: The monofilament-fibre pad effectively, easily and safely removed slough and debris from wounds of various aetiologies and was effective in wounds of different shapes, such as in cavity wounds and those in hard-to-reach locations.

Photoaging Mobile Apps in School-Based Melanoma Prevention: Pilot Study.

BACKGROUND: Around 90% of melanomas are caused by exposure to ultraviolet (UV) radiation and are therefore eminently preventable. Tanning behavior is mostly initiated in early adolescence, often with the belief that it increases attractiveness; the problems related to malignant melanoma and other skin cancers are too far in the future to fathom. Given the substantial amount of time children and adolescents spend in schools, as well as with their mobile phones, addressing melanoma prevention via both of these ways is crucial. However, no school-based intervention using mobile apps has been evaluated to date. We recently released a photoaging mobile app, in which a selfie is altered to predict future appearance dependent on UV protection behavior and skin type. OBJECTIVE: In this pilot study, we aimed to use mobile phone technology to improve school-based melanoma prevention and measure its preliminary success in different subgroups of students with regard to their UV protection behavior, Fitzpatrick skin type and age. METHODS: We implemented a free photoaging mobile phone app (Sunface) in 2 German secondary schools via a method called mirroring. We "mirrored" the students' altered 3-dimensional (3D) selfies reacting to touch on mobile phones or tablets via a projector in front of their whole grade. Using an anonymous questionnaire capturing sociodemographic data as well as risk factors for melanoma we then measured their perceptions of the intervention on a 5-point Likert scale among 205 students of both sexes aged 13-19 years (median 15 years). RESULTS: We measured more than 60% agreement in both items that measured motivation to reduce UV exposure and only 12.5% disagreement: 126 (63.0%) agreed or strongly agreed that their 3D selfie motivated them to avoid using a tanning bed, and 124 (61.7%) to increase use of sun protection. However, only 25 (12.5%) disagreed with both items. The perceived effect on motivation was increased in participants with Fitzpatrick skin types 1-2 in both tanning bed avoidance (n=74, 71.8% agreement in skin types 1-2 vs n=50, 53.8% agreement in skin types 3-6) and increased use of sun protection (n=70, 68.0% agreement in skin types 1-2 vs n=52, 55.3% agreement in skin types 3-6), and also positively correlated with higher age. CONCLUSIONS: We present a novel way of integrating photoaging in school-based melanoma prevention that affects the students' peer group, considers the predictors of UV exposure in accordance with the theory of planned behavior, and is particularly effective in changing behavioral predictors in fair-skinned adolescents (Fitzpatrick skin types 1-2). Further research is required to evaluate the intervention's prospective effects on adolescents of various cultural backgrounds.

A Medical Student-Delivered Smoking Prevention Program, Education Against Tobacco, for Secondary Schools in Germany: Randomized Controlled Trial.

BACKGROUND: More than 8.5 million Germans suffer from chronic diseases attributable to smoking. Education Against Tobacco (EAT) is a multinational network of medical students who volunteer for school-based prevention in the classroom setting, amongst other activities. EAT has been implemented in 28 medical schools in Germany and is present in 13 additional countries around the globe. A recent quasi-experimental study showed significant short-term smoking cessation effects on 11-to-15-year-old adolescents. OBJECTIVE: The aim of this study was to provide the first randomized long-term evaluation of the optimized 2014 EAT curriculum involving a photoaging software for its effectiveness in reducing the smoking prevalence among 11-to-15-year-old pupils in German secondary schools. METHODS: A randomized controlled trial was undertaken with 1504 adolescents from 9 German secondary schools, aged 11-15 years in grades 6-8, of which 718 (47.74%) were identifiable for the prospective sample at the 12-month follow-up. The experimental study design included measurements at baseline (t1), 6 months (t2), and 12 months postintervention (t3), via questionnaire. The study groups consisted of 40 randomized classes that received the standardized EAT intervention (two medical student-led interactive modules taking 120 minutes total) and 34 control classes within the same schools (no intervention). The primary endpoint was the difference in smoking prevalence from t1 to t3 in the control group versus the difference from t1 to t3 in the intervention group. The differences in smoking behavior (smoking onset, quitting) between the two groups, as well as gender-specific effects, were studied as secondary outcomes. RESULTS: None of the effects were significant due to a high loss-to-follow-up effect (52.26%, 786/1504). From baseline to the two follow-up time points, the prevalence of smoking increased from 3.1% to 5.2% to 7.2% in the control group and from 3.0% to 5.4% to 5.8% in the intervention group (number needed to treat [NNT]=68). Notable differences were observed between the groups for the female gender (4.2% to 9.5% for control vs 4.0% to 5.2% for intervention; NNT=24 for females vs NNT=207 for males), low educational background (7.3% to 12% for control vs 6.1% to 8.7% for intervention; NNT=30), and migrational background (students who claimed that at least one parent was not born in Germany) at the 12-month follow-up. The intervention appears to prevent smoking onset (NNT=63) but does not appear to initiate quitting. CONCLUSIONS: The intervention appears to prevent smoking, especially in females and students with a low educational background.

May-Thurner syndrome: an often overlooked cause for refractory venous leg ulcers.

We report a 53-year-old female patient presenting with a refractory venous leg ulcer and unremarkable findings in the doppler Ultrasound venous mapping of the leg veins. Further comprehensive diagnostics demonstrated an underlying May-Thurner syndrome. After resolution of the primary mechanical obstruction, rapid wound healing in the following 3 weeks was documented. Iliac vein compression syndrome, commonly known as May-Thurner syndrome, is a distinguishable anatomical variant that results from an external compression over the left iliac vein exerted by the overriding adjacent right common iliac artery. It is mostly seen among young, healthy female patients and can easily be under-diagnosed. Lower extremities duplex ultrasonography remains the gold standard in diagnosing venous insufficiency, but it should not solely depend on it. Instead, clinicians should consider other possibilities, assessing the patency within the truncal veins, which in turn might contribute to the venous insufficiency along the lower limbs. An active early diagnostic approach can prevent significant overall morbidity and help patients to ease back into their daily-life activities. Therefore, it is recommended that all patients with suspected venous insufficiency and normal lower limbs duplex findings should undergo further evaluation of the truncal venous system pattern. May-Thurner syndrome, along with other causes of iliac veins compression, should be considered in the differential diagnosis in unclear persistent cases of unilateral venous symptoms.

Evaluation of a radioactive and fluorescent hybrid tracer for sentinel lymph node biopsy in head and neck malignancies: prospective randomized clinical trial to compare ICG-(99m)Tc-nanocolloid hybrid tracer versus (99m)Tc-nanocolloid.

PURPOSE: There is some controversy about the value of sentinel lymph node excision (SLNE) in patients with head and neck malignancies. The gold standard for detection and targeted extirpation of the SLN is lymphoscintigraphy with (99m)Tc-nanocolloid. The purpose of this prospective randomized study was to analyse the feasibility and clinical benefit of a hybrid tracer comprising the near-infrared (NIR) fluorescent indocyanine green (ICG) and (99m)Tc-nanocolloid (ICG-(99m)Tc-nanocolloid) in direct comparison with standard (99m)Tc-nanocolloid for guiding SLNE in patients with head and neck cutaneous malignancies. METHODS: We analysed the data from 40 clinically lymph node-negative patients with melanoma, high-risk cutaneous squamous cell carcinoma, Merkel cell carcinoma or sweat gland carcinoma who underwent SLNE with ICG-(99m)Tc-nanocolloid (cohort A) or with the standard (99m)Tc-nanocolloid (cohort B). RESULTS: Overall SLNs were identified preoperatively in all 20 patients (100%) in cohort A and in 18 of 20 patients (90%) in cohort B. The SLN basin was detected preoperatively in 18 patients (90%) in cohort A and also in 18 patients (90%) in cohort B. SLNs were identified intraoperatively in all 20 patients (100%) in cohort A and in 19 patients (95%) in cohort B (p = 0.487). Metastatic SLNs were detected in 9 patients (22.5%), 3 (15.0%) in cohort A and 6 (30.0%) in cohort B (p = 0.228). CONCLUSION: The hybrid tracer ICG-(99m)Tc-nanocolloid is an innovative imaging tracer, reliably and readily providing additional information for the detection and excision of SLN in the head and neck region. Therefore, SLNE with combined radioactive and NIR fluorescence guidance is an attractive option for improving the SLN detection rate in patients with cutaneous head and neck malignancies.

Cost-effectiveness of preoperative SPECT/CT combined with lymphoscintigraphy vs. lymphoscintigraphy for sentinel lymph node excision in patients with cutaneous malignant melanoma.

PURPOSE: Malignant melanoma has become a major growing interdisciplinary problem in public health worldwide. Sentinel lymph node excision (SLNE) in conjunction with preoperative SPECT/CT is considered the most sensitive and specific staging test for the detection of micrometastatic melanoma in regional lymph nodes. Among patients with clinically lymph node-negative melanoma, the use of SPECT/CT-aided SLNE compared with SLNE alone has been found to be associated with a higher frequency of metastatic involvement and a higher rate of disease-free survival. The aim of this study was to analyse the cost-effectiveness of SLNE with preoperative SPECT/CT for detecting sentinel lymph nodes versus that of standard SLNE with preoperative lymphoscintigraphy from a single-institution database. METHODS: Cost-effectiveness analysis of two surgical approaches for SLNE for malignant melanoma at the University Hospital Essen, Skin Cancer Center in Essen, Germany. Between March 2003 and April 2011 464 patients eligible for SLNE were identified . Of these patients, 403 with clinically negative lymph nodes who underwent SLNE with or without preoperative SPECT/CT qualified for subsequent analysis. RESULTS: Between March 2003 and October 2008, 254 patients were operated upon with the standard technique. From November 2008, 149 patients underwent the SPECT/CT technique. Cost analysis showed a mean cost saving of 710.50 when SPECT/CT was added to preoperative imaging. This was achieved by a reduction in operative time (median, Q1;Q3, 40 min, 40;50 min, vs. 45 min, 35;60 min; p = 0.002), hospital stay duration (5 days, 3;8 days, vs. 8 days, 4.5;14.5 days; p < 0.001) and more frequent use of local anaesthesia (90.6 % vs. 70.5 %; p < 0.001). The median cost of SLNE using SPECT/CT was 1,619.7 (Q1;Q3 1,317.0;2,603.4) and of SLNE without SPECT/CT was 2,330.2 ( 1,468.3;4,058.1; p < 0.001), a cost saving of 30.5 %. CONCLUSION: In patients with cutaneous melanoma, the use of preoperative SPECT/CT-aided SLNE compared with standard SLNE was associated not only with higher detection of metastatic involvement but also with a significant cost reduction.

Correlation of tumor PD-L1 expression in different tissue types and outcome of PD-1-based immunotherapy in metastatic melanoma - analysis of the DeCOG prospective multicenter cohort study ADOREG/TRIM.

BACKGROUND: PD-1-based immune checkpoint inhibition (ICI) is the major backbone of current melanoma therapy. Tumor PD-L1 expression represents one of few biomarkers predicting ICI therapy outcome. The objective of the present study was to systematically investigate whether the type of tumor tissue examined for PD-L1 expression has an impact on the correlation with ICI therapy outcome. METHODS: Pre-treatment tumor tissue was collected within the prospective DeCOG cohort study ADOREG/TRIM (CA209-578; NCT05750511) between February 2014 and May 2020 from 448 consecutive patients who received PD-1-based ICI for non-resectable metastatic melanoma. The primary study endpoint was best overall response (BOR), secondary endpoints were progression-free (PFS) and overall survival (OS). All endpoints were correlated with tumor PD-L1 expression (quantified with clone 28-8; cutoff ≥5%) and stratified by tissue type. FINDINGS: Tumor PD-L1 was determined in 95 primary tumors (PT; 36.8% positivity), 153 skin/subcutaneous (34.0% positivity), 115 lymph node (LN; 50.4% positivity), and 85 organ (40.8% positivity) metastases. Tumor PD-L1 correlated with BOR if determined in LN (OR = 0.319; 95% CI = 0.138-0.762; P = 0.010), but not in skin/subcutaneous metastases (OR = 0.656; 95% CI = 0.311-1.341; P = 0.26). PD-L1 positivity determined on LN metastases was associated with favorable survival (PFS, HR = 0.490; 95% CI = 0.310-0.775; P = 0.002; OS, HR = 0.519; 95% CI = 0.307-0.880; P = 0.014). PD-L1 positivity determined in PT (PFS, HR = 0.757; 95% CI = 0.467-1.226; P = 0.27; OS; HR = 0.528; 95% CI = 0.305-0.913; P = 0.032) was correlated with survival to a lesser extent. No relevant survival differences were detected by PD-L1 determined in skin/subcutaneous metastases (PFS, HR = 0.825; 95% CI = 0.555-1.226; P = 0.35; OS, HR = 1.083; 95% CI = 0.698-1.681; P = 0.72). INTERPRETATION: For PD-1-based immunotherapy in melanoma, tumor PD-L1 determined in LN metastases was stronger correlated with therapy outcome than that assessed in PT or organ metastases. PD-L1 determined in skin/subcutaneous metastases showed no outcome correlation and therefore should be used with caution for clinical decision making. FUNDING: Bristol-Myers Squibb (ADOREG/TRIM, NCT05750511); German Research Foundation (DFG; Clinician Scientist Program UMEA); Else Kröner-Fresenius-Stiftung (EKFS; Medical Scientist Academy UMESciA).

Association between sentinel lymph node excision with or without preoperative SPECT/CT and metastatic node detection and disease-free survival in melanoma.

CONTEXT: Malignant melanoma has become an increasing interdisciplinary public health challenge worldwide. Sentinel lymph node excision (SLNE) is considered the most sensitive and specific staging test for the detection of micrometastatic melanoma in regional lymph nodes. OBJECTIVE: To compare metastatic node detection and disease-free survival using single-photon emission computed tomography/computed tomography (SPECT/CT)-aided SLNE vs standard SLNE in patients with melanoma. DESIGN, SETTING, AND PATIENTS: A prospective, computerized melanoma patient database at the University Hospital Essen, Skin Cancer Center, Essen, Germany, was used to identify a cohort of 464 patients eligible for SLNE between March 2003 and April 2011. A total of 403 patients with clinically negative lymph nodes, who underwent SLNE with or without preoperative SPECT/CT, qualified for subsequent analysis. MAIN OUTCOME MEASURES: Metastatic node detection and disease-free survival. RESULTS: Between March 2003 and October 2008, 254 patients underwent the standard SLNE technique. After November 2008, 149 patients underwent the SPECT/CT technique. Patients who did not receive SNLE in both intervals (46/300 [15.34%] for standard cohort vs 15/164 [9.15%] for SPECT/CT cohort; P = .06) did not differ in either age (difference, 69.20 years; 95% CI, 62.84-72.07 years; P = .38), tumor depth (difference, 2.90 mm; 95% CI, 2.87-4.54 mm; P = .54), or ulceration of the primary tumor (difference, -8.00%; 95% CI, -35.74% to 19.81%; P = .59). However, using SPECT/CT allowed SLNE in the head and neck area more frequently (2.0% for standard vs 23.5% for SPECT/CT; difference, 21.1%; 95% CI, 14.1%-28.2%; P < .001). In the SPECT/CT cohort, more sentinel lymph nodes per patient were detected than in the standard cohort (2.40 vs 1.87; 95% CI, 1.93-2.18; P < .001). The number of positive sentinel lymph nodes per patient was significantly higher in the SPECT/CT cohort than in the standard cohort (0.34 vs 0.21; 95% CI, 0.21-0.31; P = .04). The local relapse rate in the SPECT/CT cohort was lower than in the standard cohort (6.8% vs 23.8%, P = .03), which prolonged 4-year disease-free survival (93.9% vs 79.2%; P = .02). CONCLUSION: Among patients with clinically lymph node-negative melanoma, the use of SPECT/CT-aided SLNE compared with SLNE alone was associated with a higher frequency of metastatic involvement and a higher rate of disease-free survival.

Indocyanine green fluorescence-guided sentinel lymph node biopsy in dermato-oncology.

BACKGROUND: Sentinel lymph node biopsy (SLNB) for cutaneous malignancies usually carried out with radioactive nanocolloids (Tc-99m). The SLNE is controversially discussed internationally. This is especially given to the high false-negative rate up to 44 %. An alternative could be the fluorescent dye indocyanine green (ICG). MATERIAL AND METHODS: We investigated the advantage of intraoperative fluorescence detection of lymphatic vessels and SLN with a Near-Infrared (NIR) camera in comparison to conventional methods using preoperative lymphoscintigraphy and SPECT/CT in 22 patients with malignant melanoma. RESULTS: A total of 61 SLNs were removed in 22 operative procedures. In 7 SLN (10.3 %; 7/68) the histopathological assessment could demonstrate a metasta-tic involvement. 11 additional SLN (19.1 %) in 8 patients were only identified using the fluorescent labeling. Two of these additional SLN (9.1 %; 2/22) showed metastatic involvement. CONCLUSION: The ICG fluorescence-guided SLNB is an innovative imaging technique for dermato-oncology, reliable and providing additional information in the detection of SLN. Therefore SLNB with fluorescence-dye is an attractive option with intraoperative real-time lymphoscintigraphy to improve the detection of SLN in cutaneous malignancies and potential reduction of the false negative rate in SLN.

Virtual and Augmented Reality in Cardiac Surgery.

Virtual and augmented reality can be defined as a three-dimensional real-world simulation allowing the user to directly interact with it. Throughout the years, virtual reality has gained great popularity in medicine and is currently being adopted for a wide range of purposes. Due to its dynamic anatomical nature, permanent drive towards decreasing invasiveness, and strive for innovation, cardiac surgery depicts itself as a unique environment for virtual reality. Despite substantial research limitations in cardiac surgery, the current literature has shown great applicability of this technology, and promising opportunities.

Multispectral optoacoustic tomography might be a helpful tool for noninvasive early diagnosis of psoriatic arthritis.

Currently used imaging methods for diagnosis of psoriatic arthritis (PsA) frequently come along with exposure to radiation and can often only show long-term effects of the disease. The aim of the study was to check the feasibility of a new optoacoustic imaging method to identify PsA. 22 psoriasis patients and 19 healthy volunteers underwent examination using multispectral optoacoustic tomography (MSOT). The presence of arthritis was assessed via quantification of optoacoustic signal intensity of the endogenous chromophores oxy- and deoxyhemoglobin. We conducted high-resolution real-time ultrasound images of the finger joints. The semi quantitative analysis of the optoacoustic signals for both hemoglobin species showed a significant higher blood content and oxygenation in PsA patients compared to healthy controls. Our results indicate that MSOT might allow detection of inflammation in an early stage. If the data is further confirmed, this technique might be a suitable tool to avoid delay of diagnosis of PsA.

Coronavirus disease 2019 vaccine mimics lymph node metastases in patients undergoing skin cancer follow-up: A monocentre study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has changed the lives of people around the world. Fortunately, sufficient vaccines are now available. Local reactions with ipsilateral lymphadenopathy are among the most common side effects. We investigated the impact of lymphadenopathy after COVID-19 vaccination on the value of ultrasound in tumour patients. PATIENTS AND METHODS: Patients with melanoma or Merkel cell carcinoma were included who underwent lymph node excision and received COVID-19 vaccination within 6 weeks before surgery. The consistency of the preoperative ultrasound findings with the histopathologic findings was investigated. RESULTS: Eight patients were included (two Merkel cell carcinoma and six melanoma patients) who underwent lymph node excision between 16th April 2021 and 19th May 2021 and had previously received COVID-19 vaccination. In three of the eight patients (one Merkel cell carcinoma and two melanoma patients), lymph node metastases were erroneously diagnosed preoperatively during tumour follow-up with physical examination, ultrasound, and or fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT). In these three patients, the suspected lymph node metastases were located in the left axilla after COVID-19 vaccination in the left upper arm, which resulted in selective lymph node removal in two patients and complete lymphadenectomy in one patient. CONCLUSION: COVID-19 vaccine-associated lymphadenopathy is expected to be observed much more frequently in the near future because of increasing vaccination rates. This cause of lymphadenopathy, which may in ultrasound as well as in FDG PET/CT resemble lymph node metastases, must be considered, especially in oncologic patients undergoing tumour follow-up. In addition, COVID-19 vaccination should be given as far away as possible from an underlying primary on the contralateral side to avoid oncologic misdiagnosis followed by malpractice.

High-resolution three-dimensional imaging for precise staging in melanoma.

INTRODUCTION: Many cancer guidelines include sentinel lymph node (SLN) staging to identify microscopic metastatic disease. Current SLN analysis of melanoma patients is effective but has the substantial drawback that only a small representative portion of the node is sampled, whereas most of the tissue is discarded. This might explain the high clinical false-negative rate of current SLN diagnosis in melanoma. Furthermore, the quantitative assessment of metastatic load and microanatomical localisation might yield prognosis with higher precision. Thus, methods to analyse entire SLNs with cellular resolution apart from tedious sequential physical sectioning are required. PATIENTS AND METHODS: Eleven melanoma patients eligible to undergo SLN biopsy were included in this prospective study. SLNs were fixed, optically cleared, whole-mount stained and imaged using light sheet fluorescence microscopy (LSFM). Subsequently, compatible and unbiased gold standard histopathological assessment allowed regular patient staging. This enabled intrasample comparison of LSFM and histological findings. In addition, the development of an algorithm, RAYhance, enabled easy-to-handle display of LSFM data in a browsable histologic slide-like fashion. RESULTS: We comprehensively quantify total tumour volume while simultaneously visualising cellular and anatomical hallmarks of the associated SLN architecture. In a first-in-human study of 21 SLN of melanoma patients, LSFM not only confirmed all metastases identified by routine histopathological assessment but also additionally revealed metastases not detected by routine histology alone. This already led to additional therapeutic options for one patient. CONCLUSION: Our three-dimensional digital pathology approach can increase sensitivity and accuracy of SLN metastasis detection and potentially alleviate the need for conventional histopathological assessment in the future. GERMAN CLINICAL TRIALS REGISTER: (DRKS00015737).