Ingo Stoffels

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.

Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imaging

Optoacoustic imaging strategies can be used to identify metastasis in excised lymph nodes and to determine SLN status in patients noninvasively. Imaging melanoma metastasis Avoiding invasive biopsy altogether, an imaging technique that relies on endogenous biomolecules to generate acoustic signals could be used to detect metastases in the body. Stoffels et al. devised a multispectral optoacoustic tomography (MSOT) approach that could image the pigment melanin in lymph nodes. Melanin would only be present in the lymph nodes if the primary cancer—melanoma—had spread to distant locations. The authors used handheld MSOT detectors and a near-infrared fluorophore (which pools in lymph nodes) to image metastases in patients, and complemented these optoacoustic images with ultrasound to gain a complete picture of each lymph node’s status. Such a noninvasive approach could reduce the number of patients subjected to sentinel lymph node surgical excision by “ruling out” metastasis. Sentinel lymph node (SLN) excision is included in various cancer guidelines to identify microscopic metastatic disease. Although effective, SLN excision is an invasive procedure requiring radioactive tracing. Novel imaging approaches assessing SLN metastatic status could improve or replace conventional lymph node excision protocols. In our first-in-human study, we used noninvasive multispectral optoacoustic tomography (MSOT) to image SLNs ex vivo and in vivo in patients with melanoma, to determine metastatic status. MSOT significantly improved the tumor metastasis detection rate in excised SLN (506 SLNs from 214 melanoma patients) compared with the conventional EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group protocol (22.9% versus 14.2%). MSOT combined with the near-infrared fluorophore indocyanine green reliably visualized SLNs in vivo in 20 patients, up to 5-cm penetration and with 100% concordance with 99mTc-marked SLN lymphoscintigraphy. MSOT identified cancer-free SLNs in vivo and ex vivo without a single false negative (189 total lymph nodes), with 100% sensitivity and 48 to 62% specificity. Our findings indicate that a noninvasive, nonradioactive MSOT-based approach can identify and determine SLN status and confidently rule out the presence of metastasis. The study further demonstrates that optoacoustic imaging strategies can improve the identification of SLN metastasis as an alternative to current invasive SLN excision protocols.

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.

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.

Intraoperative Fluorescence Imaging for Sentinel Lymph Node Detection Prospective Clinical Trial to Compare the Usefulness of Indocyanine Green vs Technetium Tc 99m for Identification of Sentinel Lymph Nodes

IMPORTANCE The metastatic status of regional lymph nodes is the most relevant prognostic factor in breast cancer, melanoma, and other solid organ tumors with a lymphatic spread. The current gold standard for detection and targeted excision of the sentinel lymph node is preoperative lymphoscintigraphy with technetium Tc 99m. Because of the worldwide shortage of technetium Tc 99m, physicians are looking for nonradioactive dyes for sentinel lymph node labeling. Based on several retrospective studies, the fluorescent dye indocyanine green is considered a possible alternative to technetium Tc 99m. OBJECTIVE To analyze the feasibility and clinical benefit of intraoperative near infrared fluorescence sentinel lymph node excision (SLNE) compared with standard technetium Tc 99m-guided SLNE using malignant melanoma in which SLNE is firmly established. DESIGN, SETTING, AND PARTICIPANTS Analysis of a prospective clinical trial at the Skin Cancer Center, University Hospital Essen. Eighty patients with malignant melanoma on the trunk or extremities (upper and lower) who were scheduled to undergo SLNE were included in this study from January 1, 2013, to June 27, 2014. MAIN OUTCOMES AND MEASURES Concordance of preoperative and intraoperative sentinel lymph node detection rates. RESULTS During the study period, 80 patients were operated on with an additional intraoperative application of a near infrared fluorescent dye. In these 80 surgical procedures, 147 SLNs were excised. Detection of a technetium Tc 99m-marked SLN before surgery was possible in all cases. Intraoperative visualization of the SLN by indocyanine green before skin incision was successful in only 17 of 80 patients (21%). The number of SLNs identified using the near infrared fluorescence technique in the operative site after skin incision and initial tissue preparation was 141 of 147 (96%). CONCLUSIONS AND RELEVANCE Among patients in whom the lymph node basin cannot be predicted correctly (eg, in cutaneous melanoma on the trunk), the use of indocyanine green for SLN detection is severely limited compared with SLNE using standard technique guided by technetium Tc 99m. Therefore, SLNE with the use of radiocolloid, followed if possible by single-photon emission computed tomography, remains the gold standard. TRIAL REGISTRATION German Clinical Trials Register identifier DRKS00004619.

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.

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).

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.

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.

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).