We hypothesise that regression may have an impact on the effectiveness of adjuvant IFN therapy, based on its role in the host immune response. Our purpose is to investigate regression and ulceration as prognostic factors in case of interferon-alpha (IFN)-treated melanoma patients. We followed 357 IFN-treated melanoma patients retrospectively, investigating progression-free survival (PFS) and overall survival (OS) depending on the presence of ulceration and regression. A Kaplan–Meier analysis was performed, and we used a Cox regression analysis to relate risk factors. The survival function of the Cox regression was used to measure the effect of regression and ulceration on PFS and OS depending on the Breslow thickness (T1–T4) of the primary tumour. Regression was significantly positively related to PFS ( P = 0.0018, HR = 0.352) and OS ( P = 0.0112, HR = 0.380), while ulceration showed a negative effect (PFS: P = 0.0001, HR = 2.629; OS: P = 0.0001, HR = 2.388). They influence survival independently. The most favourable outcome was measured in the regressed/non-ulcerated group, whereas the worse was in the non-regressed/ulcerated one. Of risk factors, Breslow thickness is the most significant predictor. The efficacy of regression is regardless of Breslow thickness, though the more favourable the impact of regression was in the thicker primary lesions. Our results indicate that regression is associated with a more favourable outcome for IFN-treated melanoma patients, whereas ulceration shows an inverse relation. Further studies are needed to analyse the survival benefit of regression in relation to innovative immune checkpoint inhibitors.
The proper functioning of mesenchymal stem cells (MSCs) is of paramount importance for the homeostasis of the body. Inflammation and infection can alter the function of MSCs, which can also affect the regenerative potential and immunological status of tissues. It is not known whether human herpes simplex viruses 1 and 2 (HSV1 and HSV2), well-known human pathogens that can cause lifelong infections, can induce changes in MSCs. In non-healing ulcers, HSV infection is known to affect deeper tissue layers. In addition, HSV infection can recur after initially successful cell therapies. Our aim was to study the response of adipose-derived MSCs (ADMSCs) to HSV infection in vitro. After confirming the phenotype and differentiation capacity of the isolated cells, we infected the cells in vitro with HSV1-KOS, HSV1-532 and HSV2 virus strains. Twenty-four hours after infection, we examined the gene expression of the cells via RNA-seq and RT-PCR; detected secreted cytokines via protein array; and determined autophagy via Western blot, transmission electron microscopy (TEM) and fluorescence microscopy. Infection with different HSV strains resulted in different gene-expression patterns. In addition to the activation of pathways characteristic of viral infections, distinct non-immunological pathways (autophagy, tissue regeneration and differentiation) were also activated according to analyses with QIAGEN Ingenuity Pathway Analysis, Kyoto Encyclopedia of Genes and Genome and Genome Ontology Enrichment. Viral infections increased autophagy, as confirmed via TEM image analysis, and also increased levels of the microtubule-associated protein light chain 3 (LC3B) II protein. We identified significantly altered accumulation for 16 cytokines involved in tissue regeneration and inflammation. Our studies demonstrated that HSV infection can alter the viability and immunological status of ADMSCs, which may have implications for ADMSC-based cell therapies. Alterations in autophagy can affect numerous processes in MSCs, including the inhibition of tissue regeneration as well as pathological differentiation.
Absztrakt: Bevezetés: Az őrszemnyirokcsomó-biopszia (SNB) jelentősége az előrehaladott – 4 mm-nél vastagabb – melanomák kezelésében eddig vitatott volt a szakirodalomban. Manapság azonban az adjuváns terápiák alkalmazásának előfeltétele a regionális nyirokcsomók érintettségének szövettani igazolása. Ugyanakkor az SNB szükségességének kritériumai Magyarországon sem egységesek, van, ahol jelenleg a vastag melanomák esetén nem végzik el ezt a beavatkozást. Célkitűzés: Klinikánkon az elmúlt években konzekvensen elvégeztük az őrszemnyirokcsomók vizsgálatát 4 mm-nél vastagabb melanomák esetén is, így érdemesnek tartottuk értékelni, hogy ebben a betegcsoportban milyen arányban fordul elő a tájéki nyirokcsomók klinikailag nem, szövettanilag viszont detektálható áttéte. Módszer: A klinikánkon 2007 és 2011 között melanomával diagnosztizált 1133 beteg közül kiválasztottuk azokat a pácienseket, akiknek 4 mm-nél vastagabb primer tumoruk volt, és retrospektíven értékeltük a betegek demográfiai adatait, primer daganatuk klinikai, valamint szövettani jellegzetességeit az őrszemnyirokcsomó szövettani paramétereinek függvényében. Eredmények: Az 5 éves időszakban 116 olyan, melanomában szenvedő beteget diagnosztizáltunk, akinél vastag melanoma került sebészi kimetszésre. 78 páciensnél történt SNB, mely 50 esetben szövettanilag pozitívnak bizonyult. A betegek átlagos életkora közel 58 év volt. Következtetés: Klinikánkon évente tíz olyan, vastag melanomás beteget kezelünk, akinél az őrszemnyirokcsomó szövettani pozitivitása alapján igazoltuk a betegség metastaticus stádiumát. Eredményeink és a Nemzeti Rákregiszter adatai alapján akár 100 körülire becsülhető azoknak a pácienseknek a száma Magyarországon, akiknél ezzel a patológiai stádiumot meghatározó módszerrel az adjuváns kezelés szükségessége megállapítható. A betegcsoport fiatal életkorát figyelembe véve, hatékony target/immunterápia adjuváns alkalmazásával eredményesebben csökkenthető lehet az elvesztett életévek száma, mint a belszervi metastaticus stádiumban megkezdett kezelésekkel. Orv Hetil. 2020; 161(39): 1675–1680.
Napjaink felgyorsult tempójában a plasztikai és rekonstrukciós beavatkozások, kezelések terén jelentős változások jelentek
Aim of the Study: During the reconstruction of alar defects involving the upper lip, reconstructive surgeons face the need for various thicknesses of tissues crucial to preserving the facial sulcus which is important for a cosmetically acceptable result. Our aim was to reconstruct the deep perialar and thinner lateral nasal alar defect in a single step procedure with a suitable flap which is reliable, has appropriate blood supply and provides an esthetically good result. Materials and Methods: Extended alar defect was reconstructed with a combined flap in 10 cases. During the procedure, a subcutaneous pedicle was created and the proximal part of the flap was rotated into the defect as a rotational flap. The procedure and the follow-up have been photo-documented in all cases. Furthermore, the perfusion of the flaps was monitored by means of laser Doppler flowmetry. Postoperative complications were evaluated with a semi-quantitative score and the patients completed a patient satisfaction questionnaire, too. Results: An optimal esthetic result was obtained in all cases after the operation. The lateral nasal alar part of the defect was reconstructed with the thinner proximal part of the flap while the deeper perialar region involving the upper lip was covered with the thicker distal part. The flaps have shown sufficient blood flow after the operation. There was no significant pin cushioning or "trap-door" effect in any case. Mild erythema and edema was found in few cases. The patients were satisfied with the cosmetic result of the intervention. Conclusions: The flap is suitable for the reconstruction of alar defects involving the perialar region. It has the advantage of covering the deeper perialar and the thinner alar defects, whilst eliminating the pin cushioning effect of the conventional subcutaneous island pedicle flaps.
BACKGROUND:Nasal deformity associated with cleft lip and palate is a highly challenging reconstructive problem in rhinoplasty. In the literature, several operative solutions and evaluation methods have been described, however these do not offer a standard procedure for the surgeon. Our aim was to standardize our surgical technique-as much as the uniqueness of each case allowed it-based on the most frequent deformities we had faced; and to evaluate our results via a postoperative patient satisfaction questionnaire. Between 2012 and 2014 12 consecutive patients with combined cleft lip and palate deformities underwent secondary nasal and septal correction surgery with the same method by the same surgeon. The indications of surgery were, on one hand, difficult nasal breathing and altered nasal function (tendency for chronic rhinosinusitis) and on the other hand the aesthetic look of the nose. No exclusion criteria were stated. In our follow-up study we evaluated our results by using a modified Rhinoplasty Outcome Evaluation (ROE) questionnaire: patients answered the same four questions pre- and postoperatively. Data were statistically analyzed by t-test.RESULTS:Based on the questionnaire, all patients experienced improvement of nasal breathing function, improved appearance of the nose and less stigmatization from the society. According to the t-test, all scores of the four questions improved significantly in the postoperative 4-6 months, compared with the preoperative scores.CONCLUSIONS:In our opinion with our standardized surgical steps satisfactory aesthetic and functional results can be achieved. We think the modified ROE questionnaire is an adequate and simple method for the evaluation of our surgical results.
ÖSSZEFOGLALÁSA rosszindulatú fej-nyaki daganatok radikális eltávolítása után visszamaradt, speciális anatómiai lokalizációjú defektusok pótlása (részleges vagy teljes orrhiány) vagy a szövődmények (oro-és pharyngocutan fisztula) sebészi megoldása bonyolult, kihívást jelentő feladat