Sentinel lymph node biopsy in high-risk cutaneous squamous cell carcinoma of the head and neck

Conclusions: SLNB appears to carry no prognostic value for identifying recurrent disease amongst high-risk cSCC in the head and neck area. (c) 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Pub-lished by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Peer reviewe

Moniammatillinen suunnittelu edistää melanoomapotilaan hoitoa

Moniammatilliset ihokasvainkokoukset tuovat hoidon suunnitteluun monen erikoisalan asiantuntemuksen samanaikaisesti. Valtaosa tapauksista käsitellään lähetteiden ja potilasasiakirjojen perusteella, ja siksi hyvä lähete on erityisen tärkeä

Levinneen ihomelanooman kirurgia, elektrokemoterapia, sädehoito ja isoloitu raajaperfuusio

Teema: Ihomelanooma. English summar

Pelvic sentinel lymph nodes have minimal impact on survival in melanoma patients

Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.BACKGROUND: Lower limb or trunk melanoma often presents with femoral and pelvic sentinel lymph nodes (SLNs). The benefits of harvesting pelvic lymph nodes remain controversial. In this retrospective study, the frequency and predictors of pelvic SLNs (PSLNs), and the impact of PSLNs on survival and staging was investigated. METHODS: Altogether 285 patients with cutaneous melanoma located in the lower limb or trunk underwent sentinel lymph node biopsy of the inguinal/iliac lymph node basin at Helsinki University Hospital from 2009-2013. Patient characteristics, detailed pathology reports and follow-up data were retrieved from hospital files. Subgroups of patients categorized by presence of PSLNs were compared for outcome parameters including progression-free survival, melanoma-specific survival and groin recurrence. RESULTS: Superficial femoral/inguinal SLNs were present in all patients and 199 (69.8 per cent) also had PSLNs removed. Median number of SLNs per patient was five and median number of PSLNs was two. Sixty-three patients (22.1 per cent) had metastases in their SLNs and seven (2.5 per cent) had metastases in PSLNs. A single patient had metastases solely in PSLNs, while superficial SLNs remained negative. Harvesting PSLNs or the number of PSLNs retrieved had no impact on progression-free survival or overall survival. The removal of PSLNs did not affect the risk of postoperative seroma or lymphoedema. The only predictor of positive PSLNs was radioactivity count equal to or more than that of the hottest superficial SLNs. CONCLUSION: Pelvic SLNs have minimal clinical impact on the outcome of melanoma patients especially in cases with negative superficial femoral/inguinal SLNs. Removal of PSLNs should be considered when they are the most radioactive nodes or equal to the hottest superficial femoral/inguinal SLNs in lymphoscintigraphy or during surgery.Preliminary results were presented in part at the International Sentinel Node Society Biennial Meeting, Tokyo, Japan, 11-13 October 2018.Peer reviewe

BRAF immunohistochemistry predicts sentinel lymph node involvement in intermediate thickness melanomas

Background Sentinel node biopsy (SNB) is an important step in melanoma staging and prognostication. It is commonly performed for patients with intermediate thickness melanomas, based on clinicopathological features. However, only 20-25% of patients eventually demonstrate nodal involvement. The aim of this study was to evaluate whether tissue biomarkers with links to melanoma biology, together with clinicopathological parameters, could aid in the prediction of sentinel node involvement and improve selection of patients for SNB. In addition, we examined the role of these clinical or biological markers in disease outcome. Methods We collected a case-control cohort of 140 intermediate thickness (Breslow 0,9-4,0mm) melanoma patients with or without SNB involvement matched for age, gender, Breslow thickness and location. From this cohort, we tested the predictive value of common clinicopathological parameters (ulceration, mitotic count and tumor regression) and FMNL-2, ezrin and BRAF V600E immunoreactivity, for sentinel node involvement and survival. We further analyzed the correlations in the superficial spreading melanoma subtype. Results Based on our case control analysis, of the markers, BRAF V600E status (p = 0.010) and mitotic count (p = 0.036) correlated with SNB involvement. SNB status was a strong independent prognosticator for recurrence free survival (RFS p Conclusions These results demonstrate that BRAF immunohistochemistry could serve as a useful addition to a marker panel for selecting intermediate thickness melanoma patients for SNB.Peer reviewe

High-throughput ex vivo drug testing identifies potential drugs and drug combinations for NRAS-positive malignant melanoma

Therapy options for patients with metastatic melanoma (MM) have considerably improved over the past decade. However, many patients still need effective therapy after unsuccessful immunotherapy, especially patients with BRAF-negative tumors who lack the option of targeted treatment second line. Therefore, the elucidation of efficient and personalized therapy options for these patients is required. In this study, three patient-derived cancer cells (PDCs) were established from NRAS Q61-positive MM patients. The response of PDCs and five established melanoma cell lines (two NRAS-positive, one wild type, and two BRAF V600-positive) was evaluated toward a panel of 527 oncology drugs using high-throughput drug sensitivity and resistance testing. The PDCs and cell lines displayed strong responses to MAPK inhibitors, as expected. Additionally, the PDCs and cell lines were responsive to PI3K/mTOR, mTOR, and PLK1 inhibitors among other effective drugs currently undergoing clinical trials. Combinations with a MEK inhibitor were tested with other targeted agents to identify effective synergies. MEK inhibitor showed synergy with multikinase inhibitor ponatinib, ABL inhibitor nilotinib, PI3K/ mTOR inhibitor pictilisib, and pan-RAF inhibitor LY3009120. The application of the patients' cancer cells for functional drug testing ex vivo is one step further in the process of identifying potential agents and agent combinations to personalize treatment for patients with MM. Our preliminary study results suggest that this approach has the potential for larger-scale drug testing and personalized treatment applications in our expansion trial. Our results show that drug sensitivity and resistance testing may be implementable in the treatment planning of patients with MM.Peer reviewe

BRAF immunohistochemistry predicts sentinel lymph node involvement in intermediate thickness melanomas

Background Sentinel node biopsy (SNB) is an important step in melanoma staging and prognostication. It is commonly performed for patients with intermediate thickness melanomas, based on clinicopathological features. However, only 20-25% of patients eventually demonstrate nodal involvement. The aim of this study was to evaluate whether tissue biomarkers with links to melanoma biology, together with clinicopathological parameters, could aid in the prediction of sentinel node involvement and improve selection of patients for SNB. In addition, we examined the role of these clinical or biological markers in disease outcome.Methods We collected a case-control cohort of 140 intermediate thickness (Breslow 0,9-4,0mm) melanoma patients with or without SNB involvement matched for age, gender, Breslow thickness and location. From this cohort, we tested the predictive value of common clinicopathological parameters (ulceration, mitotic count and tumor regression) and FMNL-2, ezrin and BRAF V600E immunoreactivity, for sentinel node involvement and survival. We further analyzed the correlations in the superficial spreading melanoma subtype.Results Based on our case control analysis, of the markers, BRAF V600E status (p = 0.010) and mitotic count (p = 0.036) correlated with SNB involvement. SNB status was a strong independent prognosticator for recurrence free survival (RFS pConclusions These results demonstrate that BRAF immunohistochemistry could serve as a useful addition to a marker panel for selecting intermediate thickness melanoma patients for SNB.</p

Vesistö- ja valuma-aluekunnostukset Natura 2000 -alueilla: suunnittelun toimintamalli

Vesienhoidon ja luonnonsuojelun tavoitteet ovat useimmiten yhdenmukaisia. Ne tähtäävät paitsi vesiekosysteemien hyvään tilaan, myös lajien ja luontotyyppien suotuisaan suojelutasoon. Vesien ja luontotyyppien tilan parantamisen ohella vesistökunnostustoimenpiteitä voidaan suunnitella myös virkistyskäyttöedellytysten kohentamiseksi ja maisemansuojelun edistämiseksi. Vesistöjen ekologisen tilan parantaminen edellyttää useimmiten riittävää ulkoisen kuormituksen vähentämistä. Näin ollen vesiensuojelutoimet valuma-alueella ovat keskeisiä hoitotoimia vesistökunnostuksissa ja valuma-aluetasoisen kunnostussuunnittelun tarve on nostettu esille useissa ohjelmissa ja strategioissa. Toistaiseksi Natura 2000 -alueiden huomioiminen on kuitenkin jäänyt valuma-aluetason kunnostussuunnittelun ohjeistuksessa vähälle huomiolle. Vesienhoidon ja virkistyskäytön toimenpiteet voivat toisinaan aiheuttaa luontodirektiivin lajien lisääntymis- ja levähdyspaikkojen paikallista heikentymistä ja maisemansuojelulliset hoitotoimenpiteet voivat puolestaan olla ristiriidassa vesiensuojelutavoitteiden kanssa. Myös luonto- ja lintudirektiivin tavoitteet saattavat ajoittain olla ristiriidassa toistensa kanssa. Natura 2000 -alueilla tehtävien vesistökunnostusten ja vesiensuojelutoimenpiteiden tulisi parantaa paitsi vesistön tilaa, myös alueen suojeluperusteena olevan luontotyypin tilaa, sekä edistää luontotyypille ominaisten lajien elinmahdollisuuksia. Luontodirektiivin lajien suotuisan suojelutason sekä lajien lisääntymis- ja levähdyspaikkojen säilyminen on turvattava. Freshabit LIFE IP -hankkeessa (2016–2022) toteutettiin vesistö- ja valuma-aluekunnostuksia yhteensä 33 Natura 2000 -alueella, jotka sijoittuivat 11 vesistöalueelle eri puolille Suomea. Hankkeen tavoitteena oli parantaa Suomen sisävesien luonnon monimuotoisuutta ja kohdevesistöjen ekologista tilaa kehittämällä valuma-aluetason suunnittelun toimintatapoja ja testaamalla niitä hankkeen kohdevesistöissä. Hankkeen kokemusten perusteella koottiin tämä toimintamalli, jossa kuvataan vesistö- ja valuma-aluekunnostusten suunnittelun periaatteet Natura 2000 -alueilla, jotta mahdolliset ristiriidat pystytään huomioimaan ja ratkaisemaan. Natura 2000 -alueilla valuma-aluetason kunnostussuunnittelun keskiössä ovat paitsi erityistä huomiota vaativien lajien ja luontotyyppien tunnistaminen ja huomioiminen toimenpiteiden ajoituksessa ja sijoittamisessa, myös sidosryhmien osallistaminen jo suunnittelun alkuvaiheessa. Sidosryhmistä oleellisimpia ovat maa- ja vesialueiden omistajat. Vesistökunnostusmenetelmät valitaan kohdekohtaisesti, seurantatietojen perusteella tunnistettujen ongelmien ja niiden pohjalta muodostettujen tavoitteiden mukaisesti. Kunnostusten seurantaan tulee varata riittävästi resursseja, jotta vaikuttavuutta pystytään arvioimaan. Seurantaa tulisi tehdä niin vedenlaadun ja biologisten tekijöiden kuin direktiivilajien osalta myös kunnostusten jälkeen. Ulkoisen kuormituksen vähentäminen on avainasemassa, jotta kunnostuksilla voidaan saavuttaa vaikuttavuutta pitkällä tähtäimellä. Restoration and water protection of aquatic ecosystems at Natura 2000 sites: framework for planning The goals of water resource management and nature conservation are most often consistent. Both can aim at a good status of aquatic ecosystems, and at a favorable conservation status of species and habitats. In addition to improving the condition of aquatic ecosystems, restoration measures can also be targeted to improve the prerequisites for recreational use and to promote landscape protection. Improving the ecological status of water bodies typically requires a sufficient reduction of the external loading. Consequently, water protection measures in the catchment area are key management measures on a watershed level. The need for planning restoration measures at the catchment scale has been brought up in several national programs and strategies. However, the consideration of Natura 2000 sites has so far received less attention in such guidelines. Some restoration measures targeted to improve the status of water bodies and their recreational value can sometimes cause a local deterioration of breeding and resting habitats for species that are included in the European Union’s Birds and Habitats Directives. Also, some landscape protection measures can, in turn, conflict with the goals of water protection. Additionally, the objectives of the Birds and Habitats Directives may sometimes conflict with each other. The restoration of water bodies and water protection measures carried out at sites under Natura 2000 network should not only improve the status of aquatic ecosystems and certain habitat types to which protection of the areas are based on, but they should also promote the survival of species that are typical for the given habitat types. A favorable conservation status for species and habitats must be secured. In the Freshabit LIFE IP -project (2016–2022), restoration and water protection measures were carried out at a total of 33 Natura 2000 sites located in 11 separate watersheds around the country. The aim of the project was to improve the biodiversity of Finnish inland waters and the ecological status of the target lakes and streams by developing and implementing planning procedures at a catchment scale. Based on the project’s experiences, this framework for planning was put together to describe the principles of planning restoration and water protection measures at Natura 2000 sites, so that possible conflicts can be considered and resolved. At Natura 2000 sites, the focus of planning restorations at the catchment level is not only about identification and consideration of species and habitats that require special attention in the timing and placement of different measures. It is also about the involvement of stakeholders, most importantly the owners of land and water areas, already in the initial stages of planning. The restoration methods are selected site-specifically, according to the problems identified and targets set on the basis of validated monitoring data. Sufficient resources should always be set aside for monitoring the impacts of restorations, that should be carried out before, during and after the easures allowing for evaluating their effectiveness. Monitoring should include both water quality, morphology and the species included in the Directives. Reducing the external loading is always a key to achieve effectiveness in the long term