Myofibroblastic tumor of the esophagus - a case report of long-term follow-up and literature review.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm with intermediate malignant potential. Although most often seen in the lungs, it can occur at multiple anatomical locations, including the gastrointestinal tract. An esophageal lesion is extremely rare, however. IMTs present most commonly in children and young adults. The main therapeutic approach is surgical resection. CASE REPORT: We report on the follow-up of a case in a 13-year-old boy with IMT in the esophagus. He underwent surgical resection in 2013 and is free of disease to date. CONCLUSION: Surgical resection is the most preferred therapy. If the resection is complete, the risk of recurrence is low. Nevertheless, every patient should be carefully followed up after the resection.

Fatal progression of multifocal infection of Aspergillus sp. and multi-resistant Pseudomonas aeruginosa in a patient with toxic epidermal necrolysis and renal cancer.

Toxic epidermal necrolysis is an autoimmune disease expressed predominantly on the skin and mucous membranes. It is a serious bullous disease manifesting itself by induction of apoptosis in the dermo-epidermal junction. In most cases,it is attributable to the use of some drug. The basic approach to stopping progression of the disease is immunosuppression. Unfortunately, patients with such extensive loss of epidermis and defective mucosa are confronted by a variety of opportunistic, potentially pathogenic microorganisms. Unsurprisingly, infectious complications are today a predominant cause of death in patients thusly affected. Despite thorough review of the literature, we found no comprehensive case report concerning the development of multifocal Aspergillus infection in patients with this disease.

Vascular anatomy of the stomach related to resection procedures strategy.

This study is focused on the vascular anatomy of the stomach in relation to the gastric pull-up construction. The vascular anatomy was studied on forty-one human specimens. We find out the differences in blood supplement between anterior and posterior wall. It was maked an review of the main trunk arteries of the stomach. To display the vessels of the stomach we used diaphanoscopy, digital shooting in special mode and micro preparation of the vessels. We find out that left gastric artery gives more branches to the posterior wall and right gastroepiploic artery (RGEA) gives more branches to the anterior wall. But brunches of RGEA are longer on the posterior wall than on the anterior. Also we are offering the new classification of the RGEA related to gastric pull-up construction. This classification based not only on the anatomical shapes of RGEA but on the properties of the flow dynamics through the artery.

Patient with inoperable pheochromocytoma.

Malignant pheochromocytoma is a tumour with a very low incidence that occurs sporadically or in the presence of multiple endocrine neoplasia. We present the case of a woman with a sporadic occurrence of pheochromocytoma diagnosed in the phase of multiple dissemination in the abdominal cavity and overexpressing adrenaline, noradrenaline, and dopamine. Local transarterial chemoembolization and systemic treatment with lanreotide resulted in a very good response, a decrease in the production of catecholamines for 12 months and a partial decrease for another 8 months, with stabilization of disease determined by imaging. Systemic treatment with tegafur resulted in disease stabilization lasting 50 months, after which the drug was discontinued because of adverse effects. Maintenance therapy with lanreotide continues, and no disease progression has been observed for 4 months. The treatment algorithm for such patients is multidisciplinary and must always take into account the current scope of the disease, intercurrence, and the general condition of the patient.

Clinical impact of PAI 1 4G/5G gene polymorphism in colorectal carcinoma patients.

Plasminogen activator ihnibitor (PAI 1) belongs to the plasminogen activator system, which is part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumors. Its plasma level is normally low but 4G/4G homozygotes have higher concentrations of PAI 1. This genotype may be associated with worse prognosis and proximal location of colorectal cancer than 5G/5G homozygotes. In our prospective evaluation we examined plasma level PAI 1 (using photometric microplate method ELISA) pre-surgery and, subsequently, 6-8 weeks later, from 80 patients. For the PAI 1 rs1799889 -675 4G/5G polymorphism test the PCR amplification was used.Analysis of collected data was confirmed that significantly higher plasma levels of PAI 1 were found in patients before starting therapy, which decreased (p=0.004) after initiation of treatment. Patients with higher plasma level PAI 1 before (p=0.013) and after therapy (p=0.004) had significantly shorter survival. We found no relationship between polymorphisms of PAI 1 (-675 4G/5G) in relation to stage, survival or tumor location. PAI 1 is useful as a negative marker of prognosis and could be advantageous when planning adjuvant treatment of patients with colorectal carcinoma. Although opinions on the importance of polymorphisms of PAI 1 in relation to the prognosis are not uniform, it does seem that their role in the prognosis of patients with colorectal cancer is not essential.

[Significance of urokinase and its inhibitors in the invasiveness and metastasing of malignant tumors]. / Význam urokinázy a jejích inhibitoru pro invazi a metastazování zhoubných nádoru

Fibrinolysis is process, which leads to the degradation of fibrin to fibrin monomers. Fibrinolysis helps to regulate hemostasis and prevents the creation of inappropriately large thrombus, which could reduce blood flow to the bloodstream. The main enzyme involved in fibrinolysis is plasmin. Tissue plasminogen activator (tPA) and urokinase (uPA) are agents converting plasminogen into active plasmin, together with urokinase receptor (uPAR) and urokinase inhibitors (PAI 1, PAI 2, PAI 3 and protease nexin) form plasminogen activator system (PAS) which is among others also part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumours. In contrast to tPA that is fundamental in fibrinolysis, uPA plays an essential role in tissue degradation as part of physiological and pathological processes. uPAR is a GPI (glycosylphosphatidylinositol)-anchored protein. The binding of uPA to uPAR results in activation of protein tyrosine kinase, protein kinase C and MAP kinase. At the same time, direct signalling pathway via Jak/STAT cascade utilising signalling transduction of Scr-like protein tyrosine kinase have also been described. uPAR expression is regulated by many growth factors, e.g. EGF, FGF-2 and HGF. It seems that individual PAS factors are involved in the process of rendering malignant tumors invasive. To what degree this influence is essential to specific malignancies, should be answered by further research. In the article the authors present a summary of findings about the interaction of fibrinolysis and tumor process, especially on the effects of urokinase and other activators and their inhibitors in metastasis of malignant tumors. The text contains information on the factors theirs introduction into practice is still the subject of numerous discussions, but in the future, individual PAS factors could play an important role in planning treatment strategies and also could become targets of targeted therapy.

Clinical significance of the plasminogen activator system in relation to grade of tumor and treatment response in colorectal carcinoma patients.

Urokinase (uPA) plays an essential role in the activation of plasminogen to plasmin, and together with its receptor (uPAR), tissue activator (tPA) and urokinase inhibitors (PAI 1, PAI 2, PAI 3 and protease nexin) forms the plasminogen activator system (PAS), a component of metastatic cascade importantly contributing to the invasive growth and angiogenesis of malignant tumours. In our project we examined the expression of uPA, uPAR, PAI 1 and PAI 2 in tumor tissue and we also studied the plasma levels of PAI 1 before and after the initiation of therapy in patients with colorectal carcinoma in relationship to grade of tumor and the treatment response. In our prospective evaluation we included 80 patients treated for adenocarcinoma of the colon and rectum. Analysis of collected data revealed statistically significant evidence of a relationship between the level of PAI 1 in plasma before treatment and grade of the tumor, which increases with tumor grade (p=0.025). We demonstrated that there exists a statistically significant relationship between the expression of PAI 2 (p<0.001) and uPAR (p=0.031) and grade of tumor. We also confirmed a statistically significant relationship between soluble levels of PAI 1 before treatment and therapeutic response (p=0.021). In our group of patients the expression of uPA, uPAR, PAI 1 and 2 in tumor tissue in relation to response to treatment was also assessed. Our results suggest that the greater expression of these parameters in tumor tissue is linked to a worse response to therapy. In conclusion, PAS factors help as a prognostic indicators and could also act as a predictive factor in colorectal carcinoma.

[Plasminogen activator system and its clinical significance in patients with a malignant disease]. / Plazminogen aktivátor systém a jeho klinický význam u pacientu s nádorovým onemocnením.

Urokinase (uPA) plays an essential role in the activation of plasminogen to plasmin, a serine protease participating in the activation of matrixmetaloproteinases, latent elastases, growth factors and cytokines involved in the degradation of extracellular matrix elements. Together with its receptor (uPAR), tissue activator (tPA) and urokinase inhibitors (PAI-1, PAI-2, PAI-3 and protease nexin), it forms the plasminogen activator system (PAS), a component of metastatic cascade importantly contributing to the invasive growth and angiogenesis of malignant tumours. Plasminogen activator inhibitor 1 inhibits uPA-dependent invasiveness of some cancer cell lines. The vitronectin-PAI-1 complex inhibits migration of smooth muscle cells by binding alpha(v)beta3 integrin to vitronectin. PAI-1 or its deficiency interferes with signalling pathways such as PI3K/Akt and JAK/STAT and it is included in the processes of maintaining the integrity of the endothelial cells and thereby regulation of cell death. PAI-1 affects apoptosis by reducing cell adhesion and functioning of intracellular signalling pathways. The individual components of PAS undoubtedly play an important role in angiogenesis and metastasising of malignant tumours. In the near future, results of published studies with various types of cancer could be reflected in diagnostic and therapeutic algorithms and, at the same time, could serve as the goal for targeted therapies.

Juxtaglomerular cell tumor--a rare cause of secondary hypertension.

Secondary hypertension (SH) is much more common in children than in adults. We report a 17-year-old girl with severe hypertension, hypokalemia and metabolic alkalosis. Because of these findings, primary or secondary hyperaldosteronism was suspected. Her initial treatment with spironolactone and ACE inhibitor was unsuccessful. With consideration of high plasma renin activity, the renal computed tomography angiography was performed and showed tumor mass in the left kidney. An uncomplicated partial left nephrectomy was performed. Histopathological examination and electron microscopy showed typical features of juxtaglomerular cell tumor (JCT). Imunohistochemistry of tumor was positive for CD34 and CD117 and this finding is effective in the diagnosis of JCT if immunostain for renin is unavailable. After the resection of JCT, the patient's blood pressure and hypokalemia returned to normal range. JCT is a rare renal neoplasm and an unusual cause of SH in children or adolescents (Fig. 2, Ref. 12).

[Our experience in using fluorescence in situ hybridization FISH-Uro Vysion in diagnostics of urothelial carcinoma]. / Nase zkusenosti s metodou fluorescencní in situ hybridizace pri detekci uroteliálního karcinomu.

UNLABELLED: Urothelial carcinoma is a disease at high risk of recurrence after the initial therapy (70-80%) and with the tendency to progression accomplishing the recurrence (30%). Long lasting monitoring of patients with urothelial carcinoma is necessary. Cystoscopy and cytology are currently the primary modalities used to detect and monitor urothelial carcinoma. However, cytology has relatively poor sensitivity especially in well differentiated tumors. Cystoscopy is an invasive and relatively expensive method. Therefore, methods improving detection of urothelial carcinoma from urine specimens are employed. Uro Vysion (Vysis) fluorescence in situ hybridization (FISH) for improved detection of urothelial carcinoma was evaluated. MATERIALS AND METHODS: Bladder tumor progression is accompanied by increased chromosomal instability and aneuploidy of chromosomes 3, 7, 17 and loss of locus 9p21. A total of 124 patients were analyzed at Dpts. of Urology and Pathology, Faculty Hospital in Brno. Cytologically analyzed urine specimens were tested by FISH and simultaneously cystoscopy was employed including biopsy for histological examination. RESULTS: FISH analysis was positive in 35 cases, including 5 cases with negative biopsy and cytology. Negative FISH result was detected in 24 cases where the malignant status was determined. The sensitivity of FISH in our series was 58.9% and the specificity 88.1%. CONCLUSIONS: FISH is a relatively simple, speedy and non invasive diagnostic method. It detects the symptoms of malignity on the molecular level, which leads to earlier diagnosis and therapy and, hence, to potential extended survival. FISH makes it possible to take decision in cases of atypical or unclear cytological finding. The FISH method using the Uro Vysion kit appears as a prospective non invasive method capable of early UK detection, with a higher sensitivity than the standard cytology of urine.

[Expression of CD34 and CD117 in juxtaglomerular cell tumor of kidney]. / Exprese CD34 a CD117 v nádoru z juxtaglomerulárních bunek ledviny.

Juxtaglomerular cell tumor (JGCT) is an uncommon tumor of the kidney, typically found in young adults. Patients with this tumor suffer from hypertension, hyperaldosteronism and hypokalaemia. Expression of renin and intracytoplasmatic rhomboid crystals or granules in electron microscopic picture are diagnostic features of this tumor. CD34 and CD117 immunoreactivity have recently been reported as helpful markers of JGCT.

[Malignant fibrous histiocytoma of the breast: report of two cases]. / Maligní fibrózní histiocytom prsu--popis 2 prípadu.

Two cases of malignant fibrous histiocytoma (MFH) of the breast are presented. The first case was a 63-year-old patient with MFH of myxoid type, the second case was a 79-year-old patient with MFH of pleiomorphic type. MFH is one of the most common tumors of the soft tissues, but its primary occurrence in the breast is rare. Immunohistochemical detection of antigens in the cytoplasm of histiocytes by antibdy LN 5 (Anti-Macrophage, BioGenex) can be helpful in rendering of the right diagnosis.

[An unusual cause of the chronic ileus state--the absence of the intestinal wall muscularis layer]. / Neobvyklá prícina chronického ileózního stavu--absence muscularis strevní steny.

In this study the authors describe a rare histological finding in the resected small intestine, which was a cause of continuous ileal difficulties in a young female patient, and which increased in their intensity and finally resulted in an acute state which had to be solved by an urgent surgical procedure. The situation was defined as "absence of the muscularis layer" of the intestinal wall by a pathologist. The pathologist also stated that he had never come across such a case, neither in our literature, nor in the foreign one and that the condition was diagnosed with difficulties when using a standard visualization examination methods.

Proliferative activity in pancreatic intraepithelial neoplasias of chronic pancreatitis resection specimens: detection of a high-risk lesion.

Patients with chronic pancreatitis have a markedly increased risk of pancreatic cancer compared with general population. Mechanism of the increased risk is not completely known. The current progression model for pancreatic ductal adenocarcinoma proposes the progression from normal ductal epithelium through a series of lesions called pancreatic intraepithelial neoplasias (PanINs) to invasive cancer. These lesions are frequently seen in chronic pancreatitis tissue. Proliferative activity in PanINs of chronic pancreatitis tissue has not been separately studied using the current nomenclature. Our study included 36 chronic pancreatitis resection specimens. A total number of 106 PanINs found within 32 resection specimens was histologically graded and then immunolabeled using a monoclonal antibody against Ki-67 that is expressed in dividing cells. The Ki-67 labeling indices in the increasing grades of PanINs were counted with following results: PanIN-1A, 0.77%; PanIN-1B, 3.26%; PanIN-2, 14.68%; and PanIN-3, 25.4%. The difference in Ki-67 labeling indices among these types of lesions was statistically significant (p<0.001, t-test). These results correlate with known genetic alterations found in chronic pancreatitis, especially with p16 inactivation that was recently described in PanINs arising in patients with chronic pancreatitis. Moreover, our findings support the currently accepted pancreatic progression model and Ki-67 immunohistochemistry might represent an efficient tool for an identification of a high-risk lesion.

[Segmental absence of intestinal musculature]. / Segmentální chybení strevní svaloviny.

Herein we describe a case of 33-year old woman repeatedly affected by incomplete ileus. Primary segmental absence of lamina muscularis propria has been found in this patient. Histological examination revealed areas of small intestine with total absence of muscularis propria followed by areas of the intestinal wall characterised by normal histological structure. No necrosis, inflammation, and fibrosis supporting the secondary origin of this lesion was found.

[Apoptosis--selected methods of detection of apoptosis and associated regulatory factors on tissue sections of tumors]. / Apoptóza--vybrané metody detekce apoptózy a asociovaných regulacních faktoru na tkánových rezech z nádorového materiálu.

Methods for identification of apoptotic (AP) cells in tissue sections include light and electron microscopy and immunohistochemical (IHC) detection of apoptotic antigens. Bcl-2 at many tumors inversely correlates with AP and is an indirect marker of AP index. Transglutaminase is often expressed in nonapoptotic cells, and thus represents a non specific marker of AP. Likewise, expression of FAS does not necessarily represent a transformation into AP. IHC detection of caspases does not distinguish between active and nonactive forms of the proteases. Immunolabeling of biotin-conjugated Annexin V is used for the identification of phosphatidylserine residues exposed on the surface of AP cells. Annexin V immuno-gold labeling by means of electron microscopy will allow a more refined description of the morphological events occurring during apoptosis. TUNEL, ISEL and ISNTA methods detect DNA breaks. The rate of AP detected by TUNEL is about 20% higher then by apoptotic figure counting. DNA strand breaks can also occur during DNA repair, electrocoagulation, autolysis, fixation and paraffin embedding. With Apostain, DNA is selectively denaturated by heating with formamide and stained by monoclonal antibody specific to single-strand DNA. It specifically stains condensed chromatin of apoptotic cells. M30 IHC uses a monoclonal antibody binding to the product resulting from cleavage of cytokeratin 18 by activated caspases. M30 is negative in necrotic cells and in progressively degraded cells (AP bodies). In contrast to some pilot studies, we have not reached sufficient sensitivity and specificity of IHC detection with M30 (Roche) in breast carcinomas.

Downregulation of plasma membrane expression/cytoplasmic accumulation of beta-catenin predicts shortened survival in non-small cell lung cancer. A clinicopathologic study of 100 cases.

The E-cadherin-catenin complex proteins function in cell-cell adhesion and have been reported to be dysregulated in various human malignancies. Beta catenin is a cytoplasmic protein that associates with tyrosine kinase receptors and modulates cytoskeletal dynamics. It also plays a role in the Wnt signaling pathway. During neoplastic transformation, the phosphorylation of beta-catenin causes a loss of intercellular adhesions resulting in increased tumor cell motility and invasiveness. Tissue sections from 100 cases of non-small cell lung cancer (NSCLC) were immunostained with a monoclonal beta-catenin antibody. There were 47 squamous cell carcinomas (SCC) and 53 adenocarcinomas (AC) in the study group. Plasma membrane/cytoplasmic beta-catenin immunoreactivity was scored for intensity and distribution and correlated with tumor stage, grade and survival. Plasma membrane/cytoplasmic immunoreactivity for beta-catenin protein was observed in 71 (71%) of 100 NSCLC. 44 (94%) of 47 SCC and 27 (51%) of 53 AC expressed beta catenin. On univariate analysis, loss of beta catenin expression correlated with high tumor stage (p = 0.025), large tumor size (p = 0.02) and decreased patient survival (p = 0.04). The loss of beta catenin expression associated with high grade NSCLC reached near significance (p = 0.07). On multivariate analysis, the loss of beta catenin expression independently predicted shortened overall patient survival in NSCLC (p = 0.05). Beta catenin expression loss is associated with advanced tumor stage and is an independent predictor of shortened patient survival in NSCLC.

[Acute hemorrhage of the upper digestive tract--personal experience]. / Akutní krvácení z horní cásti trávicí trubice--nase zkusenosti.

The authors submit a retrospective investigation of 50 patients hospitalized at the intensive care unit of the Medical gastroenterological department, Faculty Hospital Brno treated in 1999 with the diagnosis of acute haemorrhage into the upper digestive tract. In the investigated group the most frequent cause of haemorrhage was portal hypertension (21 patients, 32.8%) and a peptic gastroduodenal lesion (15 patients, 23.4%). During the investigation period 12 patients died (18.8%), 6 developed haemorrhage as a complication of a serious condition (decompensated cirrhosis of the liver). In haemorrhage from oesophageal and gastric varicosities pharmacotherapy is equally important as endoscopic intervention.

[Congenital myopathy with type 2 fiber hypoplasia]. / Kongenitální myopatie s hypoplazií vláken 2. typu.

An atypical case of congenital myopathy characterised by a low frequency of hypoplastic type 2A fibres, type 2B fibre deficiency and type 1 fibre predominance is reported. Our patients are siblings, a 10 year old girl and a 7 year old boy. Both children suffered from ophthalmoplegia and muscle weakness, and the boy also showed signs of psychomotoric retardation. A muscle biopsy from musculus trapezius has shown type 1 fibre predominance and hypoplastic type 2 fibres.