Surgical treatment of malignant melanoma

Incidenca in umrljivost zaradi malignega melanoma (MM) rasteta v svetu in pri nas. Kljub temu je prognoza bolezni danes boljša zaradi zgodnejšega odkrivanjaMM. MM je v zgodnjem kliničnem obdobju ozdravljiv s preprostim kirurškim izrezom sumljivo spremenjenega tkiva z varnostnim robom. Primerjava debeline tumorja in uspešnosti lokalnega nadzora bolezni ob izrezih različno širokega varnostnega pasu je zožila varnostni pas iz prejšnjih 5 in več cm ("široka ali razširjena ekscizija") na 1 do 2 cm. Zato lahko danes pri večini bolnikov z malignim melanomom zapremo nastalo tkivno vrzel po odstranitvi tumorja zgolj z neposrednim šivom rane, le redko pa s prostimi kožnimi presadki in lokalnimi, oddaljenimi ali prostimi režnji. Izbirna (elektivna) odstranitev področnih bezgavk ni smiselna. Za terapevtsko odstranitev področnih bezgavk se odločimo pri pozitivni varovalni bezgavki oz. pri na otippovečanih regionalnih bezgavkah brez znakov sistemskega razsoja. Osamljene(solitarne) oddaljene zasevke odstranimo izjemoma in le v tistih primerih, ko postanejo simptomatski. (npr.zvišan intrakranialni tlak, mehanskaovira v prehodnosti cevastih organov, motnje dihanja, pojav zlatenice).Although the incidence and the mortality rates of malignant melanoma (MM) havebeen increasing worldwide and in Slovenija for the last several decades, the survival rates are improving. The apparent contradiction may be expained by the increase in early diagnnosis of MM. If detected early in its clinical course MM can be cured by a simple surgical excision in majority of patients. The decision about the margins of the surgical excision of the primary melanoma site has been made more rational through correlations of rates of local control with different margins of resection in relation to the domianantprognostic factor for localized melanoma, the thickness of the lesion. When possible, primary closure of the post-excisional defect should beperformed. If primary closure is impossible, the wound may be closed by split or full thickness skin grafting, local, regional or free flaps. Electivedissection has not been shown in prospective randomized trials to alter survival significantly. Surgical treatment of distant metastases is indicated only as palliation of a solitary symptomatic lesion (brain metastases, lung or gastrointestinal metastases)

Surgical treatment of malignant epithelial skin tumors

Kožni tumorji spadajo med najpogostejše novotvorbe pri človeku. Delimo jih v tri skupine: benigni, predmaligni in maligni kožni tumorji. Zlasti na obrazu starejših ljudi se pojavijo značilne kožne spremembe, ki so posledica kronološke starosti bolnika in škodljivih zunanjih dejavnikov, zlasti solarno-klimatskih učinkov. Med malignimi tumorji sta najpomembnejša bazalno in spinalno celični karcinom, ki nezdravljena povzročata hudo lokalno uničenjetkiva. Hitra in pravilna diagnoza ter čimprejšnja kirurška odstranitevs histološko preiskavo omogoča učnkovito zdravljenje z dobrim estetskim rezultatom. Rano po eksciziji tumorja neposredno zašijemo s posameznimi ali tekočim intradermalnim šivom. Majhne kožne vrzeli pokrijemo s prostimi presadki kože različne debeline ali lokalnimi transpozicijskimi in rotacijskimi naključnimi kožnimi režnji. Pri velikih tkivnih vrzelih pa je potrebna rekonstrukcija z vezanimi režnji ali prostim prenosom tkiv.Skin tumors are considered one of the most common neoplasms in humans. They can be benign, premalignant or malignant. Most often they occur on photodamaged skin in ederly population. The most important malignant tumors are the basal and the squamous cell carcinoma. if untreated, they cause large local tissue destruction. Early and accurate diagnosis and early surgical removal of tumor togeher with histological verification of th etumor and surgical margins ensure efficient treatment and good aesthetic results. Skin tumors should always be excised to healthy margins (tumor-free tissue). When there is no tenson int ewoound primary wound closure shoould be performed by interrupted sutures or continuous intradermal suture. When the skin defect after tumor excision is small split or full thickness skin grafts or local rotation and transposition flaps are used for coverage. Large defect are covered by distant or free flaps. The flap transfer usually leaves a secondarydefect which is closed either by direct suture or covered by a skin graft

Analysis of the N-terminal region of human MLKL, as well as two distinct MLKL isoforms, reveals new insights into necroptotic cell death

© 2016 Authors. The pseudokinase mixed lineage kinase domain-like (MLKL) is an essential effector of necroptotic cell death. Two distinct human MLKL isoforms have previously been reported, but their capacities to trigger cell death have not been compared directly. Herein, we examine these two MLKL isoforms, and further probe the features of the human MLKL N-terminal domain that are required for cell death. Expression in HEK293T cells of the N-terminal 201 amino acids (aa) of human MLKL is sufficient to cause cell death, whereas expression of the first 154 aa is not. Given that aa 1125 are able to initiate necroptosis, our findings indicate that the helix that follows this region restrains necroptotic activity, which is again restored in longer constructs. Furthermore, MLKL isoform 2 (MLKL2), which lacks much of the regulatory pseudokinase domain, is a much more potent inducer of cell death than MLKL isoform 1 (MLKL1) in ectopic expression studies in HEK293T cells. Modelling predicts that a C-terminal helix constrains the activity of MLKL1, but not MLKL2. Although both isoforms are expressed by human monocyte-derived macrophages at the mRNA level, MLKL2 is expressed at much lower levels. We propose that it may have a regulatory role in controlling macrophage survival, either in the steady state or in response to specific stimuli

A review on the eco-epidemiology and clinical management of human granulocytic anaplasmosis and its agent in Europe

Anaplasma phagocytophilum is the agent of tick-borne fever, equine, canine and human granulocytic anaplasmosis. The common route of A. phagocytophilum transmission is through a tick bite, the main vector in Europe being Ixodes ricinus. Despite the apparently ubiquitous presence of the pathogen A. phagocytophilum in ticks and various wild and domestic animals from Europe, up to date published clinical cases of human granulocytic anaplasmosis (HGA) remain rare compared to the worldwide status. It is unclear if this reflects the epidemiological dynamics of the human infection in Europe or if the disease is underdiagnosed or underreported. Epidemiologic studies in Europe have suggested an increased occupational risk of infection for forestry workers, hunters, veterinarians, and farmers with a tick-bite history and living in endemic areas. Although the overall genetic diversity of A. phagocytophilum in Europe is higher than in the USA, the strains responsible for the human infections are related on both continents. However, the study of the genetic variability and assessment of the difference of pathogenicity and infectivity between strains to various hosts has been insufficiently explored to date. Most of the European HGA cases presented as a mild infection, common clinical signs being pyrexia, headache, myalgia and arthralgia. The diagnosis of HGA in the USA was recommended to be based on clinical signs and the patient’s history and later confirmed using specialized laboratory tests. However, in Europe since the majority of cases are presenting as mild infection, laboratory tests may be performed before the treatment in order to avoid antibiotic overuse. The drug of choice for HGA is doxycycline and because of potential for serious complication the treatment should be instituted on clinical suspicion alone

Introduction of chronical wounds healing with Lucilia sericata larvae in Slovenia

Izhodišča Ker so kronične rane danes pogosto okužene z bakterijskimi sevi, odpornimi na antibiotike, je njihovo zdravljenje težavno. Namen raziskovalnega projekta je bil uvesti v Slovenijo novo metodo zdravljenja kroničnih ran z uporabo ličink muh Lucilia sericata. Metode Za zdravljenje kroničnih ran smo uporabili sterilne larve L. sericata, pridobljene v kontinuirani kulturi na Oddelku za biologijo Biotehniske fakultete UL. Na ta način smo zdravili 32 ran pri 30 bolnikih. Ličinke smo na rani pustili delovati dva do tri dnič nato smo jih odstranili in po potrebi ponovno namestili. Pred namestitvijo in po njej smo jemali mikrobiološke brise tkiva vrani in iz njih osamili ter identificirali bakterijske vrste. Med biokirurskim zdravljenjem smo spremljali potek zdravljenja, bolnikovo počutje, morebitne bolečine, pokretnost, samostojnost in psiholoski odziv ob terapiji. Rezultati Z biokirurskim zdravljenjem smo uspeli zaceliti in očistiti 24 ran od 32 (75%). V primeru kombinirane arterijsko-venske razjede smo uspeli popolnoma zaceliti eno rano in očistiti 8 ran, v primeru venske razjede na nogi in sestih diabetičnih razjed so se vse rane očistile. V primerih preležanin in pooperativnih kroničnih ran smo z biokirurgijo vse ranev celoti očistili. 16 bolnikov je med nosenjem ličink občutilo neprijeten občutek, pri dveh so se pojavile bolečine, ki so se po dodatku analgetikov pomirile. Med zdravljenjem si je pri hoji z berglami pomagalo 17 (57%) bolnikov. Ugotovili smo, da je 17 bolnikov (57%) čutilo strah in depresijo ter nelagoden občutek. Zaključki Metoda zdravljenja z ličinkami muhe L. sericata je bila uspešno uvedena v Slovenijo. Zaradi enostavnosti in uspešnosti bi jo bilo potrebno kot način zdravljenja uvesti tudi v vsakdanjo slovensko klinično prakso. Z biokirurgijo se kronične rane hitreje celijo, preprečimo nadaljnja vnetja in propadanje tkiva ter bolniku omogočimo normalno vključevanje v vsakdanje življenje.Background Due to infection of chronic wounds with antibiotic resistant bacterial strains, their healing can be very difficult. The main purpose of the presented research study was the introduction of a new method for chronic wounds healing, using Lucilia sericata fly larvae into Slovenia. Methods For chronic wound healing sterile larvae of L. sericata fly were prepared from a continuous fly culture, maintained at the Department of Biology, Biotechnical Faculty, University of Ljubljana. In this way 32 wounds of 30 patients were treated. Larvae were applied on the wounds for two to three days. Than they were washed off and replaced, if necessary. Microbiological smears were collected before and after the application of the larvae on the wounds. Microorganisms were then isolated and identified. During larval therapy healing improvement, patientćs general state, potential presence of pain, mobility, patientćs independence and psychological reaction to the therapy were monitored. Results Using biosurgical therapy 24 (75%) out of 32 wounds were cleaned and healed. In the case of combined arterio-venous leg ulcers onewound was completely healed and eight of them were cleaned of necrosis and infection. In the case of a venous leg ulcer, six diabetic ulcers, eight casesof chronic postoperative wounds and pressure ulcers, wounds were completely cleaned after the treatment. 16 patients reported unpleasant feeling during larval treatment and two patients felt pain which diminished after the treatment with analgesics. 17 (57%) patients had to use crutches during biosurgical treatment and the same number of patients felt uncomfortable, frightened and depressed during the application of larvae