Adam Maciejewski

Epidermal differentiation complex (locus 1q21) gene expression in head and neck cancer and normal mucosa.

Epidermal differentiation complex (EDC) comprises a number of genes associated with human skin diseases including psoriasis, atopic dermatitis and hyperkeratosis. These genes have also been linked to numerous cancers, among them skin, gastric, colorectal, lung, ovarian and renal carcinomas. The involvement of EDC components encoding S100 proteins, small proline-rich proteins (SPRRs) and other genes in the tumorigenesis of head and neck squamous cell cancer (HNSCC) has been previously suggested. The aim of the study was to systematically analyze the expression of EDC components on the transcript level in HNSCC. Tissue specimens from 93 patients with HNC of oral cavity and 87 samples from adjacent or distant grossly normal oral mucosawere analyzed. 48 samples (24 tumor and 24 corresponding surrounding tissue) were hybridized to Affymetrix GeneChip Human 1.0 ST Arrays. For validation by quantitative real-time PCR (QPCR) the total RNA from all180 samples collected in the study was analyzed with Real-Time PCR system and fluorescent amplicon specific-probes. Additional set of samples from 14 patients with laryngeal carcinoma previously obtained by HG-U133 Plus 2.0 microarray was also included in the analyses. The expression of analyzed EDC genes was heterogeneous. Two transcripts (S100A1 and S100A4) were significantly down-regulated in oral cancer when compared to normal mucosa (0.69 and 0.36-fold change, respectively), showing an opposite pattern of expression to the remaining S100 genes. Significant up-regulation in tumors was found for S100A11, S100A7, LCE3D, S100A3 and S100A2 genes. The increased expression of S100A7 was subsequently validated by QPCR, confirming significant differences. The remaining EDC genes, including all encoding SPRR molecules, did not show any differences between oral cancer and normal mucosa. The observed differences were also assessed in the independent set of laryngeal cancer samples, confirming the role of S100A3 and LCE3D transcripts in HNC. In HNC of oral cavity only one family of EDC genes (S100 proteins) showed significant cancer-related differences. A number of other transcripts which showed altered expression in HNC require further validation.

Tracheal Reconstruction With the Use of Radial Forearm Free Flap Combined With Biodegradative Mesh Suspension

The main aim of tracheal restoration is to provide a noncollapsible construction with a functional epithelial lining and well-vascularized coverage. The authors present the case of a successful tracheal reconstruction in a patient with recurrent thyroid gland cancer infiltrating the trachea. The free radial forearm flap was formed as a tube and suspended to the mesh rings placed outside. Currently the patient has no problems with breathing.

The Risk of Relapse in Papillary Thyroid Cancer (PTC) in the Context of BRAFV600E Mutation Status and Other Prognostic Factors.

Introduction The risk of over-treatment in low-advanced PTC stages has prompted clinicians to search for new reliable prognostic factors. The presence of BRAF mutation, the most frequent molecular event in PTC, seems to be a good candidate. However, there is still lack of randomised trials and its significance has been proved by retrospective analyses, involving a large group of patients. The question arises whether this factor is useful in smaller populations, characterised for specialised centres. Thus, the aim of the study was to evaluate the use of BRAF mutation as a potential predictive marker in PTC patients. Material 233 PTC subjects treated between 2004-2006, were retrospectively analysed. Stage pT1 was diagnosed in 64.8% patients and lymph node metastases in 30.9%. Median follow-up was 7.5 years. BRAFV600E mutation was assessed postoperatively in all cases. Results BRAF V600E mutation was found in 54.5%. It was more frequent in patients > 45 years (p=0.0001), and associated with larger tumour size (p=0.004). Patients with tumours <= 10 mm were over-represented among BRAF negative population (p=0.03). No association between BRAF mutation and other clinicopathological factors was observed. BRAF status was associated neither with relapse nor with disease-free survival (DFS) (p=0.76). Nodal status, extrathyroidal invasion and tumour size significantly influenced DFS. Conclusion The risk of PTC recurrence is mainly related to the presence of lymph node metastases and extrathyroidal invasion, whereas no impact of BRAF V600E mutation has been demonstrated.

Intraoperative Radiotherapy (IORT) with Low-Energy Photons as a Boost in Patients with Early-StageOral Cancer with the Indications for Postoperative Radiotherapy

Purpose:To evaluate the feasibility and preliminary results of intraoperative radiotherapy (IORT) with low-energy photons as a boost in patients with early-stage oral cancer with the indications for postoperative radiotherapy.Patients and Methods:Between 2003 and 2006, 16 patients with early-stage cancer of mobile tongue (n = 10 [63%]) or floor of the mouth (n = 6 [37%]) treated at Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland, were evaluated for IORT boost with the INTRABEAM®System (Carl Zeiss Surgical GmbH; IORT-PRS) because of the high risk of local recurrence due to positive margins on frozen pathologic section. After tumor resection, the applicator was positioned in the tumor bed. The applicator’s diameter (range: 1.5–5 cm) was selected to encompass high-risk area of tumor recurrence. The dose (5 Gy, 7 Gy, or 7.5 Gy) was applied according to tumor volume and bone proximity. External-beam radiotherapy (EBRT) was provided to the tumor bed in all patients (50 Gy) and to the nodal area, when needed. Toxicity and local tumor control were assessed.Results:Median follow-up was 36 months. IORT did not increase acute mucosal reaction. Local tumor control was found in all cases. Early mucosal reaction did not exceed 3 according to the RTOG scale and healed in median time of 35 days after completion of EBRT. No late adverse effects were observed.Conclusion:This preliminary report has demonstrated the feasibility of IORT-PRS for patients with early oral cancer with the indications for postoperative radiotherapy. This method may be considered an alternative boost technique, although additional studies are needed to establish long-term results in a larger group of patients.ZusammenfassungZiel:Auswertung der Anwendbarkeit und ersten Ergebnisse der intraoperativen Radiotherapie (IORT) mit niedrigenergetischen Photonen als Boost bei Patienten mit Mundhöhlenkarzinom in einem frühen klinischen Stadium, bei denen Indikationen zur postoperativen Radiotherapie bestehen.Patienten und Methodik:In den Jahren 2003–2006 wurden im Onkologischen Zentrum am Maria-Skłodowska-Curie-Institut in Gliwice, Polen, 16 Patienten mit Mundhöhlenkarzinom in einem frühen klinischen Stadium behandelt. Bei zehn Patienten befand sich das Karzinom im beweglichen Zungenteil, und bei sechs Patienten lag ein Mundbodenkarzinom vor. Aufgrund des hohen Risikos für ein Lokalrezidiv kam die IORT mit dem INTRABEAM®System (Carl Zeiss Surgical GmbH; IORT-PRS) zur Anwendung. Risiko- faktoren für ein Lokalrezidiv wurden anhand der pathologischen Beurteilung im Gefrierschnitt ermittelt. Als Risikofaktoren wurden schmale oder positive Absetzungsränder, Infiltration der Lymphgefäße und/oder der Blutgefäße durch das Karzinom, perineurale Karzinominfiltration, ungünstiger Infiltrationstyp, Tiefe der Infiltration und geringgradige histopathologische Differenzierung des Karzinoms eingestuft. Nach chirurgischer Entfernung des Karzinoms wurde der Applikator auf das Tumorbett aufgesetzt. Der Durchmesser des Applikators (Bereich 1,5–5 cm) wurde so gewählt, dass der Applikator das gesamte Gebiet mit Risiko eines Rezidivs bedeckte. Die Strahlendosis (5 Gy, 7 Gy, 7,5 Gy) richtete sich nach dem Tumorvolumen und dem Zustand der Absetzungsränder. Bei allen Patienten kam eine externe Strahlentherapie (EBRT) auf das Tumorbett (50 Gy) und, wenn indiziert, auf die lokalen Lymphknoten zum Einsatz. Ausgewertet wurden die Therapieverträglichkeit und das Ausmaß der lokalen Ausheilung.Ergebnisse:Die mediane Beobachtungszeit lag bei 36 Monaten. Die IORT führte zu keiner Zunahme akuter Reaktionen der Mundschleimhaut auf die Strahlentherapie. Bei allen Patienten wurde eine gute Wundheilung beobachtet. Die Frühreaktionen der Mundschleimhaut auf die Strahlentherapie wurden nicht höher als Grad 3 nach dem RTOG/EORTC-Score eingestuft. Die mediane Zeit bis zur kompletten Ausheilung von Frühreaktionen lag bei 35 Tagen. Spätreaktionen nach Strahlentherapie wurden nicht beobachtet.Schlussfolgerung:Die Ergebnisse der Studie bestätigen die Anwendbarkeit von IORT-PRS bei Patienten mit einem frühen Mundhöhlenkarzinom, bei denen Indikationen zur postoperativen Strahlentherapie bestehen. Diese Methode kann als alternative Technik für eine Boostapplikation in Erwägung gezogen werden. Weitere Studien sind jedoch erforderlich, damit die Langzeitergebnisse in einer größeren Patientenpopulation ausgewertet werden könnten.

Intraoperative radiotherapy (IORT) with low-energy photons as a boost in patients with early-stage oral cancer with the indications for postoperative radiotherapy : treatment feasibility and preliminary results.

Purpose:To evaluate the feasibility and preliminary results of intraoperative radiotherapy (IORT) with low-energy photons as a boost in patients with early-stage oral cancer with the indications for postoperative radiotherapy.Patients and Methods:Between 2003 and 2006, 16 patients with early-stage cancer of mobile tongue (n = 10 [63%]) or floor of the mouth (n = 6 [37%]) treated at Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland, were evaluated for IORT boost with the INTRABEAM®System (Carl Zeiss Surgical GmbH; IORT-PRS) because of the high risk of local recurrence due to positive margins on frozen pathologic section. After tumor resection, the applicator was positioned in the tumor bed. The applicator’s diameter (range: 1.5–5 cm) was selected to encompass high-risk area of tumor recurrence. The dose (5 Gy, 7 Gy, or 7.5 Gy) was applied according to tumor volume and bone proximity. External-beam radiotherapy (EBRT) was provided to the tumor bed in all patients (50 Gy) and to the nodal area, when needed. Toxicity and local tumor control were assessed.Results:Median follow-up was 36 months. IORT did not increase acute mucosal reaction. Local tumor control was found in all cases. Early mucosal reaction did not exceed 3 according to the RTOG scale and healed in median time of 35 days after completion of EBRT. No late adverse effects were observed.Conclusion:This preliminary report has demonstrated the feasibility of IORT-PRS for patients with early oral cancer with the indications for postoperative radiotherapy. This method may be considered an alternative boost technique, although additional studies are needed to establish long-term results in a larger group of patients.ZusammenfassungZiel:Auswertung der Anwendbarkeit und ersten Ergebnisse der intraoperativen Radiotherapie (IORT) mit niedrigenergetischen Photonen als Boost bei Patienten mit Mundhöhlenkarzinom in einem frühen klinischen Stadium, bei denen Indikationen zur postoperativen Radiotherapie bestehen.Patienten und Methodik:In den Jahren 2003–2006 wurden im Onkologischen Zentrum am Maria-Skłodowska-Curie-Institut in Gliwice, Polen, 16 Patienten mit Mundhöhlenkarzinom in einem frühen klinischen Stadium behandelt. Bei zehn Patienten befand sich das Karzinom im beweglichen Zungenteil, und bei sechs Patienten lag ein Mundbodenkarzinom vor. Aufgrund des hohen Risikos für ein Lokalrezidiv kam die IORT mit dem INTRABEAM®System (Carl Zeiss Surgical GmbH; IORT-PRS) zur Anwendung. Risiko- faktoren für ein Lokalrezidiv wurden anhand der pathologischen Beurteilung im Gefrierschnitt ermittelt. Als Risikofaktoren wurden schmale oder positive Absetzungsränder, Infiltration der Lymphgefäße und/oder der Blutgefäße durch das Karzinom, perineurale Karzinominfiltration, ungünstiger Infiltrationstyp, Tiefe der Infiltration und geringgradige histopathologische Differenzierung des Karzinoms eingestuft. Nach chirurgischer Entfernung des Karzinoms wurde der Applikator auf das Tumorbett aufgesetzt. Der Durchmesser des Applikators (Bereich 1,5–5 cm) wurde so gewählt, dass der Applikator das gesamte Gebiet mit Risiko eines Rezidivs bedeckte. Die Strahlendosis (5 Gy, 7 Gy, 7,5 Gy) richtete sich nach dem Tumorvolumen und dem Zustand der Absetzungsränder. Bei allen Patienten kam eine externe Strahlentherapie (EBRT) auf das Tumorbett (50 Gy) und, wenn indiziert, auf die lokalen Lymphknoten zum Einsatz. Ausgewertet wurden die Therapieverträglichkeit und das Ausmaß der lokalen Ausheilung.Ergebnisse:Die mediane Beobachtungszeit lag bei 36 Monaten. Die IORT führte zu keiner Zunahme akuter Reaktionen der Mundschleimhaut auf die Strahlentherapie. Bei allen Patienten wurde eine gute Wundheilung beobachtet. Die Frühreaktionen der Mundschleimhaut auf die Strahlentherapie wurden nicht höher als Grad 3 nach dem RTOG/EORTC-Score eingestuft. Die mediane Zeit bis zur kompletten Ausheilung von Frühreaktionen lag bei 35 Tagen. Spätreaktionen nach Strahlentherapie wurden nicht beobachtet.Schlussfolgerung:Die Ergebnisse der Studie bestätigen die Anwendbarkeit von IORT-PRS bei Patienten mit einem frühen Mundhöhlenkarzinom, bei denen Indikationen zur postoperativen Strahlentherapie bestehen. Diese Methode kann als alternative Technik für eine Boostapplikation in Erwägung gezogen werden. Weitere Studien sind jedoch erforderlich, damit die Langzeitergebnisse in einer größeren Patientenpopulation ausgewertet werden könnten.

Evaluation of Outcomes and Treatment Safety of Patients with Metastatic Colorectal Cancer to the Liver with Estimation of Prognostic Factors

UNLABELLED Liver resection is essential part of colorectal cancer liver metastases (CLM) treatment. Mean 5-year overall survival after resection achieves 30-45%. There are many factors influencing long-term outcomes, and among them the inflammatory response to tumor plays an important role. THE AIM OF THE STUDY was evaluation of outcomes and treatment safety of patients with metastatic colorectal cancer to the liver with estimation of prognostic factors. MATERIAL AND METHODS 130 consecutive patients (70 men and 60 women) operated in MSC Institute and Cancer Center in Gliwice from 2001 to 2009 due to colorectal liver metastases were analysed. Age of the patients ranged from 33 to 82 years (median 60 years). 96 (74%) patients underwent potentially radical resection, and in remaining 34 (26%) was performed radiofrequency ablation (RFA) alone or combined with the resection. In the resection group 37 right hepatectomies, 11 left hepatectomies, 28 segmentectomies and 20 metastasectomies were performed. Disease-free survival (DFS) and overall survival (OS) were statistically analysed using the Kaplan-Meier method. Factors determining DFS and OS were analysed using Cox regression model. RESULTS In the resection group the 3- and 5-years OS was 64,5% and 46,6% respectively, and the 3- and 5-years DFS was 32% and 30,5% respectively. In the RFA group the 3- and 5-years OS was 33% and 9,5%. Statistically significant prognostic factors in the resection group in uni- and multivariate analysis were: grade and nodal involvement of the primary tumor, diameter of metastatic focus, positive and narrow (<1 mm) resection margins, preoperative fibrinogen level, preoperative neutrophil to lymphocyte ratio and leukocyte amount of the peripheral blood. The perioperative mortality rate was 3%. CONCLUSIONS Liver resection due to colorectal liver metastases is a safe and effective method resulting in high survival rates. We confirmed some generally accepted prognostic factors influencing longterm outcomes and shown the impact of inflammatory response. We also confirmed the hypothesis that preoperative plasma fibrinogen level influences outcomes after liver resection due to CLM.

Triple skin island fibula free flap: a good choice for combined mandible and tongue defect reconstruction.

Resections of malignant tumors involving the mandible and anterior tongue result in complex defects that are still real challenges for reconstructive surgeons. Whereas there are preferred methods for mandible reconstruction involving isolated or limited loss of soft tissues, there are no standards for extended bone-soft tissue intraoral defects. This article documents the modification of the fibula free flap where triple skin islands are used for reconstruction of anterior tongue and floor of the mouth. The technique also includes filing the submandibular space with an isolated part of the flexor hallucis longus muscle, based on individual perforator. The details of flap designing, harvesting, and insetting are also presented. Eight such reconstructions have been performed on patients who underwent complex resection of the anterior mandible together with the mobile part of the tongue. Flap survival rate was 100%. In all eight cases, understandable speech and return to unrestricted diet mastication and swallowing were achieved. Analysis of aesthetic effects showed generally very good results. The presented modification of fibula free flap can be an alternative to double flaps in complex reconstruction of the mandible and mobile tongue.

Maxillary Reconstruction Using a Multi-Element Free Fibula Flap Based on a Three-Dimensional Polyacrylic Resin Model

Preoperative preparation of working models of the skull and free bone flaps using the digital print technology and photocured polyacrylic resins may be of a great benefit to the patient, for whom a virtual resection and reconstruction procedure may be planned in detail and performed. The purpose of mid-facial reconstruction using 3D models is to plan a functional mid-facial reconstruction procedure in order to restore supportive function of intraorbital structures and to make placement of dental implants and further prosthetic rehabilitation possible.Maxillary and mid-facial reconstruction using a free fibula flap based on a three-dimensional working model was performed in a patient diagnosed with a squamous cell carcinoma of the left maxillary sinus penetrating to the orbit, the ethmoid complex, and the pterygopalatine fossa. The use of three-dimensional polyacrylic models allowed for detailed preoperative planning and a virtual resection and reconstruction procedure with a highly satisfying functional and cosmetic effect.A procedure based on methods discussed here may be significantly shorter and more precise.

Face Transplant in an Advanced Neurofibromatosis Type 1 Patient

BACKGROUND The human face is a one-of-a-kind structure with unique morphology, complexity, and function, in which different subunits are not even similar to other parts of the body. Therefore, extended complex deficits of the face are usually difficult to reconstruct, and autologous tissue restoration is generally not able to give a satisfactory aesthetic and functional outcome. The main goal of face allotransplantation is to restore symmetry, contour, and appearance as well as function of the face, especially control of orbicularis oculi and oris muscle physiology. We present the case of a total face transplant in an advanced neurofibromatosis type 1 patient - the second face transplant in Poland. CASE REPORT The recipient was a 28-year-old female with neurofibromatosis type I limited to the head region. During 24 years she underwent more than 35 surgical procedures, but for the last 3 years a significant decrease of her functionality and appearance was observed, including serious problems with speech, eating, and vision. In December 2013 she was qualified for a face transplant procedure. When the donor was found, she was matched on several clinical and biochemical characteristics including negative T and B cell cross-matching. Similarly, the transplantation procedure was done using two connected operating rooms; in the first, the donors face was harvested, and in the second, the recipients face was prepared - the tumor mass was resected and vascular and nervous structures were prepared. Due to the extension and complexity of the potential defect, more than 75% of head soft tissues were harvested including both auriculae, left and right eyelids, and scalp down to the occipital lower line. CONCLUSIONS Our case showed that neurofibromatosis is a real indication for a face transplantation procedure. Also, the results of rehabilitation, quality of life, motor and sensory recovery, and physiological status were comparable, showing that face transplantation based on careful selection of recipients and procedure planning is a real alternative, allowing achievement of excellent results that are far away from the outcomes of conventional reconstructions.

Dermoscopy in near-full facial transplantation.

From an O th Th In Publ Fund Conf CLINICAL PRESENTATION We report the case of a 32-year-old male recipient of a life-saving near-full facial transplant performed in May 2013 (Fig 1, A). Induction immunosuppression consisted of anti-thymocyte globulin, tacrolimus, mofetil mycophenolate, and high-dose methylprednisolone. On day 36 posttransplant, confluent erythema with edema of transplanted skin developed (Fig 1, B) and was diagnosed as acute graft rejection, which was successfully treated with methylprednisolone 2 mg/kg body weight tapered after 3 days. No further episodes of graft rejection have been observed (Fig 1, C ).