Łukasz Szylberg

Expression of metalloproteinases 2 and 9 and tissue inhibitors 1 and 2 as predictors of lymph node metastases in oropharyngeal squamous cell carcinoma.

The matrix metalloproteinases (MMPs) and their tissue inhibitor of metalloproteinases (TIMPs) can decompose extracellular matrix (ECM) components and brake down basement membranes and, thus, promote tumor local invasion and metastasis.

Deep anterior cerebellar stimulation reduces symptoms of secondary dystonia in patients with cerebral palsy treated due to spasticity.

INTRODUCTION Deep anterior cerebellar stimulation (DACS) is a neuromodulation therapy of spasticity. Bilateral DACS is applied in young patients with cerebral palsy (CP). In these patients symptoms of spasticity coexist with symptoms of focal or segmental dystonia, which can cause chronic pain. We performed the study to investigate the therapeutic effects of DACS in spasticity, secondary dystonia and pain. METHODS We examined 10 from 13 patients with CP treated with DACS due to spasticity in years 2006-2012. We compared Ashworth scores of spasticity, VAS scale of pain and UDRS (Unified Dystonia Rating Scale) score before DACS and after it in follow-up lasting from 2 to 11 years it in these patients basing on clinical examination and evaluating forms given by the patients or parents. RESULTS We received statistically significant reduction of spasticity in upper extremities (median: from 3 to 1,5 in Ashworth scale) in 8 patients (p = 0,01), in lower extremities in 7 patients (median: from 3 to 1,75) (p = 0,02). Symptoms of focal dystonia were reduced. Total score for the UDRS (median = 18,0 before surgery) after DACS decreased significantly (median = 10,3) (p = 0,043). Change in consecutive parts of UDRS before (median = 1,6) and after (median = 1,0) surgery in 7 patients had statistical significance (p = 0,0179). There were not significant changes in intensity of pain before and after surgery (p = 0,108). DISCUSSION Chronic bilateral DACS aimed for spasticity treatment not only decreases muscular tone in quadriplegic or paraplegic patients with CP but also is associated with reduction of symptoms of focal or segmental, secondary dystonia.

Tumor progression driven by pathways activating matrix metalloproteinases and their inhibitors.

BACKGROUND Laryngeal squamous cell carcinoma (LSCC) is still a problem worldwide. In some publications interactions between the expression of matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, and their tissue inhibitors (TIMPs) implicated during cancer progression were suggested. METHODS The immunohistochemical staining using primary antibody against MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 were performed. The research group consists of primary N(0) LSCC (20 cases), primary N(+) LSCC (17 cases), and 18 cases of normal mucosa. RESULTS Studied MMPs and TIMPs were localized in tumor cells and tumor stroma compartment. MMP-2 expression was higher in stroma compared to tumor cells. MMP-9, TIMP-1, TIMP-2, and TIMP-3 expression was higher in tumor cells than in tumor stroma (P < 0.05). In tumor stroma MMP-2, MMP-9, TIMP-1, and TIMP-3 expression, in LSCC N(0) vs. LSCC N(+) was significantly higher (P < 0.05). The ratios between MMP-2 and TIMP-3 expression were statistically significant (N(0) vs. N(+); P = 0.012). The analyses using classification trees predicted the probability of metastases according to TIMP-3/MMP-14/MMP-2 and MMP-9/TIMP-1 expression levels. CONCLUSIONS The presence of MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-3 expression in tumor cells and in tumor stroma, and additionally different expression according to lymph node involvement suggested of their impact during cancer progression. The significant correlation between TIMP-3 expression and the presence of lymph node metastases and MMP-2 expression might suggest the importance of TIMP-3 as a prognostic factor during tumor progression. The evaluation of molecular markers which participate in MMP-2 activation pathway have a major impact during metastasis.

Expression of COX-2, IL-1β, TNF-α and IL-4 in epithelium of serrated adenoma, adenoma and hyperplastic polyp

Introduction Colon polyps and inflammatory process play the key role in neoplasia of colorectal cancer. In recent years there have been many publications on the malignancy of hyperplastic polyp (HP) which according to the WHO classification is a non-neoplastic polyp. The aim of this study is to determine the expression of inflammatory proteins COX-2, IL-1β, TNF-α and IL-4 in the epithelium of colorectal polyps. Material and methods In the study, 144 colorectal polyps were analyzed. The groups of HP, classical (A) and serrated adenomas (SA) and normal mucosa (control) according to histopathological studies were selected. Immunohistochemical examinations Rusing antibodies against COX-2, IL-1β, TNF-α and IL-4 were performed. The expression of analyzed protein was evaluated using modified Remmele-Stegner scale (0-16). Results Statistical analysis revealed higher expression of TNF-α (16 ±3.87 vs. 1 ±5.06), IL-1β (12 ±4 vs 8 ±2.72), COX-2 (9 ±2.54 vs. 8 ±3.14) and IL-4 (12 ±3.45 vs. 4 ±3.35) in SA polyps compared to the control (p < 0.001). The HP had an increased level of expression of TNF-α (12 ±3.72 vs. 1 ±5.06, p < 0.005), COX-2 (8.5 ±1.97 vs. 8 ±3.14, p < 0.012) and IL-4 (12 ±3.46 vs. 4 ±3.35, p < 0.001). Significantly higher expression of IL-4 (12 ±2.32 vs. 4 ±3.35, p < 0.001) and IL-1β (16 ±4.32 vs. 8 ±2.72, p < 0.044) in A compared to the control were observed. Conclusions Expression of inflammatory factors differed between polyps. Inflammation accompanied the serrated structures which occur in polyps. The inflammatory process affects the development of colorectal polyps. The HP may predispose to malignancy.

Emerging strategies in BRCA-positive pancreatic cancer

PurposeWe propose a treatment algorithm for PDAC with particular emphasis on BRCA1 or 2 mutation-positive patients. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest diseases in the United States and Europe. BRCA1 and BRCA2 are among the most common of the known genetic mutations involved in familial PDAC. The optimal chemotherapy regimen to use for BRCA1 or 2 mutation carriers with PDAC is not yet established. As new treatment options emerge, algorithms must balance the need to give the best drugs first with ensuring that there are still beneficial options available for later.MethodsWe conducted a review of the literature for data on possible therapies in BRCA-positive and BRCA-negative pancreatic cancer.ResultsThere is accumulating evidence of increased sensitivity to platinum-based therapy and poly-ADP-ribose polymerase inhibitors (PARPi) in BRCA-associated PDAC. There are no studies relating to borderline BRCA-associated PDAC and, therefore, same treatment as for sporadic PDAC seems appropriate. Treatment of unresectable PDAC varies depending on stage of the disease. Patients with BRCA-associated locally advanced PDAC can benefit from targeted therapy with PARPi (olaparib) as a second-line therapy after antimetabolite treatment failure. Patients with unresectable metastatic BRCA-positive PDAC may benefit from platinum-based therapy.ConclusionTargeted therapies are shifting the treatment paradigms and increasing survival for patients with PDAC, a group that used to have a grim prognosis.

Expression of FoxP3 Protein Plays a Key Role in Thyroid Tumors in Children

The expression of FoxP3 in tumor cells might play an important role in cancer progression. We evaluated the immunoexpression of FoxP3 in thyroid tumors in children. Studies revealed high nuclear FoxP3 expression in follicular adenoma, papillary carcinoma, follicular carcinoma and low in goiter. Malignant tumors and adenomas, revealed a statistically significant higher expression of FoxP3 compared with the thyroid goiter. High FoxP3 expression in malignant lesions compared with low expression in goiter, may be indirect evidence of its role in carcinogenesis. Revealed high expression of FoxP3 in benign tumor, may suggest a strong activation of oncogenic processes in this lesion.

Pathologic aspects of skull base tumors

Skull base tumors form a highly heterogeneous group. As there are several structures in this anatomical site, a large number of different primary malignancies might develop, as well as a variety of secondary (metastatic) tumors. In this article, the most common malignancies are presented, along with a short histopathologic description. For some entities, an immunohistochemical profile is also given that should be helpful in proper diagnosis. As many pathologic diagnoses nowadays also include genetic studies, the most common genetic abnormalities in skull base tumors are presented.

Diagnostic Difficulties With Atrophy, Atypical Adenomatous Hyperplasia, and Atypical Small Acinar Proliferation: A Systematic Review of Current Literature.

Prostate cancer is the second leading cause of cancer death in men, behind only lung cancer. In some cases, the proper diagnosis of prostatic neoplasia can be challenging, and the differential diagnosis includes atypical nonmalignant lesions such as atrophy, atypical adenomatous hyperplasia (AAH), and atypical small acinar proliferation (ASAP). Atrophy and AAH have a benign clinical outcome, and if detected on needle biopsy or transurethral resection of the prostate, clinical follow-up seems appropriate. In contrast, ASAP cannot be determined to be benign or malignant. In clinical practice, the diagnosis of ASAP is an indication for repeat biopsy because the chance of finding prostate adenocarcinoma is even greater than that with an earlier diagnosis of high-grade prostatic intraepithelial neoplasia. Malignant lesions require more restrictive treatment; therefore, differentiation among atrophy, AAH, ASAP, and adenocarcinoma is essential. We performed a systematic review of the current data allow to the creation of a diagnostic algorithm for atrophy, AAH, ASAP, and adenocarcinoma. We propose an algorithm that covers the practical issues related to interpretation of the biopsy findings and how to proceed further.

Chondrosarcoma of the maxilla: a case report and review of current literature

Chondrosarcoma is a malignant mesenchymal tumour that is the second most common bone tumour after osteosarcoma. Its diagnosis is among the most difficult ones in tumour pathology. Here, we report a very unique case of chondrosarcoma in maxillary sinus. A 45-year-old woman presented with a tumour on the left side of the maxillary sinus. CT and MRI imaging showed an abnormal mass destructing surrounding tissues. The final diagnosis of chondrosarcoma could not be made for a long time due to lack of correlation between clinical and microscopic examinations. The patient underwent left subtotal maxillectomy via Weber-Ferguson incision, bilateral ethmoidectomy, sphenoidectomy, and right upper turbinectomy, and excision of nasal septum, left frontal sinus, and left exenteration of orbit. Histological changes in the small biopsy specimen may be not sufficient for definitive diagnosis. Our case shows that radiography combined with histopathology is necessary to make the final diagnosis. The presented case revealed that chondrosarcoma can be a heterogeneous tumour. Collecting tissue samples from different locations is essential for improving diagnosis and reducing diagnostic error. Combining clinical data even with uncertain microscopic examination may be a solution in borderline and complicated cases.

The diagnosis and management of congenital and adult-onset hyperinsulinism (nesidioblastosis) – literature review

Congenital and adult-onset hyperinsulinism (CHI) must be taken under consideration in the differential diagnosis of hypoglycaemia symptoms with endogenous hyperinsulinism, especially in cases in which there was failure to find an insulinoma. Histological examination is necessary for a definitive diagnosis. CHI is a disorder with three histopathological variants: focal CHI, diffuse CHI, and atypical CHI. These variants are clinically indistinguishable. According to published statistics, 0.5 to 5% of nesidioblastosis cases occur in adults. Clinical manifestation ranges from mildly symptomatic up to life-threatening hypoglycaemia. Early diagnosis and treatment are important in young and very young patients because early treatment accounts for favourable mental outcomes.