[Parametric monitoring of the quality of total mesorectal excision and surgical treatment of rectal carcinoma results of a multicenter study]. / Parametrické sledování kvality totální mezorektální excize a chirurgické lécby karcinomu rekta výsledky multicentrické studie.

INTRODUCTION: Tumour size and the quality of its complete surgical removal are the main prognostic factors in rectal cancer treatment. The number of postoperative local recurrences depends on whether the mesorectum has been completely removed - total mesorectal excision (TME) - and whether tumour-free resection margins have been achieved. The surgery itself and its quality depend on the accuracy of preoperative diagnosis and detection of risk areas in the rectum and mesorectum, on the surgeons skills, and finally on pathological assessment evaluating whether complete tumour excision has been accomplished including circumferential margins of the tumour, and whether mesorectal excision is complete. The aim of our study was to implement and standardize a new method of evaluation of the quality of the surgical procedure - TME - in rectal cancer treatment using an assessment of its circumferential margins (CRO) and completeness of the excision. METHODS: The study consisted of two parts. The first, multi-centre retrospective phase with 288 patients analysed individual partial parameters of the diagnosis, operations and histological examinations of the rectal cancer. Critical points were identified and a unified follow-up protocol was prepared. In the second, prospective part of this study 600 patients were monitored parametrically focusing on the quality of the TME and its effect on the oncological treatment results. RESULTS: The proportion of patients with restaging following neoadjuvant therapy increased from 60.0% to 81.7% based on preoperative diagnosis. The number of specimens missing an assessment of the mesorectal excision quality decreased from 52.9% in the retrospective part of to the study to 22.8% in the prospective part. The proportion of actually complete TMEs rose from 22.6% to 26.0%, and that of nearly complete TMEs from 10.1% to 24.0%. CONCLUSION: The introduction of parametric monitoring into routine clinical practice improved the quality of pre-treatment and preoperative diagnosis, examination of the tissue specimen, and consequently improved quality of the surgical procedure was achieved. KEY WORDS: rectal cancer TME - parametric monitoring - quality control.

Sequestration of MBNL1 in tissues of patients with myotonic dystrophy type 2.

The pathogenesis of myotonic dystrophy type 2 includes the sequestration of MBNL proteins by expanded CCUG transcripts, which leads to an abnormal splicing of their target pre-mRNAs. We have found CCUG(exp) RNA transcripts of the ZNF9 gene associated with the formation of ribonuclear foci in human skeletal muscle and some non-muscle tissues present in muscle biopsies and skin excisions from myotonic dystrophy type 2 patients. Using RNA-FISH and immunofluorescence-FISH methods in combination with a high-resolution confocal microscopy, we demonstrate a different frequency of nuclei containing the CCUG(exp) foci, a different expression pattern of MBNL1 protein and a different sequestration of MBNL1 by CCUG(exp) repeats in skeletal muscle, vascular smooth muscle and endothelia, Schwann cells, adipocytes, and ectodermal derivatives. The level of CCUG(exp) transcription in epidermal and hair sheath cells is lower compared with that in other tissues examined. We suppose that non-muscle tissues of myotonic dystrophy type 2 patients might be affected by a similar molecular mechanism as the skeletal muscle, as suggested by our observation of an aberrant insulin receptor splicing in myotonic dystrophy type 2 adipocytes.

[Successful treatment of angiomatosis with thalidomide and interferon alpha. A description of five cases and overview of treatment of angiomatosis and proliferating hemangiomas]. / Uspesná lécba angiomatózy thalidomidem a interferonem alpha. Popis peti pripadu a prehled lécby angiomatózy a proliferujícich hemangiomu.

Our paper describes 5 patients with a vascular malformation - angiomatosis. In the first patient, a young man, angiomatosis affected the stomach, intestine, the area of mesenterium and retroperitoneum as well as mediastinum. Angiomatous mass had invaded pelvic bones and vertebrae. Treatment was initiated with interferon alpha in a maximum tolerated dose of 3 million units 3 times a week. Because of low efficacy of interferon alpha, thalidomide was added at a dose of 100 mg per day. Bone pain disappeared following a few applications of zoledronate administered in regular monthly intervals. After 3 years of concomitant administration of interferon alpha and thalidomide, we changed the regimen due to adverse effects and are administering thalidomide and interferon alternatively in 4-monthly intervals. Treatment has resulted in 50% reduction, according to imaging, of angiomatous mass, reduced intensity of disseminated intravascular coagulation and disappearance of clinical signs. The second was a case of multiple angiomatosis affecting the intestine only (multiple intestinal angiodysplasias) where we used thalidomide monotherapy. This treatment reduced blood losses and haemoglobin concentrations rose to normal levels. This male patient had consumed 120 transfusion units per year before the initiation of thalidomide. The third case was a slowly progressing vascular malformation of the face. This vascular malformation troubled its sufferer by spontaneous shortening that could not be resolved surgically because of its fragility. Two years of combined treatment with interferon a 6 million unites 3 times a week and thalidomide 100 mg daily led to a reduction and flattening of the malformation, paling of its colour and ceasing of spontaneous bleeding. This development enabled minor surgery--partial excision of this large vascular malformation. Histology examination confirmed that there was no evidence of new capillary formation. Histological examination thus confirmed efficacy of the treatment. The fourth case involved a patient with large vascular malformations affecting supraclavicular region of the neck and nape in whom radiotherapy was applied (54 Gy) leading to a reduction of the malformation mass by a at least 50%. The fifth is a case of an extensive periorbital lymphangioma that diminished following treatment with interferon alpha. These cases illustrate the benefits of combined treatment including thalidomide and interferon alpha in patients with multiple angiomatosis or large proliferating hemangioma (vascular malformation). If combined treatment with thalidomide and interferon a is not possible, it is beneficial to use thalidomide monotherapy. Radiotherapy is another alternative, although it is necessary to apply doses exceeding 50 Gy which may not be always possible.

[Diffuse plane normolipemic xanthomatosis and necrobiotic xanthogranuloma associated with monoclonal gammopathy--determining the disease stage with PET-CT and treatment experience. Two case studies and literature review]. / Difuzní plosná normolipemická xantomatóza a nekrobiotický xantogranulom, asociované s monoklonální gamapatií--prínos PET-CT pro stanovení rozsahu nemoci a zkusenosti s lécbou. Popis dvou prípadu a prehled literatury.

UNLABELLED: Monoclonal gammopathy may manifest itself through a range of skin disorders, including plane normolipemic xanthoma and necrobiotic xanthogranuloma. The present paper describes two patients with these cutaneous symptoms. The first has extensive areas of skin affected by flat xanthomas, monoclonal gammopathy with > 10% infiltration of bone marrow with clonal plasmocytes and, according to PET-CT, unclear lymphadenopathy in the retroperitoneal area. The size of this lymphadenopathy (histologically no malignant infiltration and no confirmed infectious aetiology) has not changed significantly over a 4-year follow-up. Repeated PET-CT scans showed decrease in SUV value in this infiltration from 7.5 to 3.8. Four cycles of treatment with a combination of bortezomib, cyclophosphamide and dexamethasone brought neither reduction in monoclonal immunoglobulin nor change to skin morphology. We believe that the abdominal lymphadenopathy is associated with xanthomatosis but have been unable to confirm this unequivocally. The second patient is being followed up for more than 10 years, originally for MGUS, later for asymptomatic multiple myeloma. Last year, painful subcutaneous and cutaneous infiltrates, isolated on an upper limb and more frequent on lower limb, started to occur. These infiltrates are palpable. PET-CT imaging provided an excellent depiction of these infiltrates, showing no pathology on the head, chest and abdomen and no osteolytic foci on the skeleton. CT imaging showed clearly numerous infiltrates in the skin and subcutaneous tissue of lower limbs, particularly both shanks, reaching up to 2 cm in depth. The largest infiltrate, measuring 3.5 by 2 by 10 cm, was identified in the distal dorsal part of the right shank. PET imaging of lower limbs showed distinctly pathological accumulation in all infiltrates described above; the accumulation of glucose in the lower part of the right shank reached 10.0 SUV. CT images of lower limbs showed increased density saturated hypodermis even in the areas where there is no increased accumulation of 18 fluoroglucose. Following 40 Gy irradiation, the size of infiltrate in the radiated area decreased and their soreness ceased. CONCLUSION: PET-CT imaging offered information on extra-cutaneous signs of plane normolipemic xanthomas and provided excellent depiction of the areas of the skin and hypodermis affected by necrobiotic xanthogranuloma. Chemotherapy with cyclophosphamide, bortezomib and dexamethasone brought no reduction in monoclonal immunoglobulin concentration, and no reduction in plane normolipemic xanthomas. Radiotherapy targeted at large foci of xanthogranulomas led to partial regression and ceased infiltrate soreness.

[IgA pemphigus accompanying multiple myeloma has disappeared following the treatment with bortezomib (Velcade), cyclophosphamide and dexamethasone. Case study and literature review]. / IgA pemfigus provázející mnohocetný myelom vymizel pri lécbe bortezomibem (Velcade), cyklofosfamidem a dexametazonem. Popis prípadu a prehled literatury.

IgA pemphigus, resembling subcorneal pustulous dermatosis, represents a rare complication of IgA type monoclonal gammopathy. The patient dates the onset of initial symptoms of vesicular-bullous disease to 1990. She was first examined at our clinic in 2001 with the following conclusion "type IgA monoclonal gammopathy of unknown significance". The first immunosuppressive treatment of vesicular-bullous disorder was administered in 2003 (dexamethasone 20 mg on days 1-4 and 15-18 in monthly cycles + daily cyclophosphamide 50 mg). Cyclophosphamide was administered for 6 months in total and dexamethasone for further 3 months. During the treatment, intensity of the skin disorder ameliorated and monoclonal IgA levels decreased to non-detectable levels. Nevertheless, skin symptoms recurred immediately after dexamethasone treatment in its original intensity was terminated, even though the concentration of monoclonal immunoglobulin IgA remained below the sensitivity of quantitative detection for further 6 months (positive immunofixation only). Six rituximab 600 mg infusions were administered in a weekly interval after stopping cyclophosphamide and dexamethasone to prevent early recurrence of skin symptoms but this treatment was without any lasting effect. Transformation into multiple myeloma was identified in 2007. First line treatment (cyclophosphamide, adriamycin and dexamethasone - CAD) remained without any haematological or dermatological treatment response. Second line treatment (thalidomide, cyclophosphamide and dexamethasone - CTD) brought about significant deterioration of skin symptoms up to the clinical picture of erythrodermia. Third line treatment (bortezomib 1.3 mg/sqm i.v. on days 1,4, 8 and 15, cyclophosphamide 50 mg daily and dexamethasone 20 mg on days 1-4 and 15-18 in 28-day cycles - VCD) resulted in rapid decline in monoclonal immunoglobulin IgA concentrations immediately following the first cycle and to negative immunofixation after 5 cycles. In total, six VCD cycles were administered. The patient has had no skin symptoms from the third cycle of this treatment and complete skin and haematological remission has been maintained for 12 months after completion of bortezomib-containing treatment. Combined treatment containing bortezomib has proven useful in the treatment of IgA pemphigus accompanying monoclonal gammopathy of uncertain significance transformed into multiple myeloma.

[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.

Marking excision margins of surgical specimens by silver impregnation.

Marking excision margins of surgical specimens by silver impregnation has several advantages over commonly used Indian ink: during the slicing the tissue preserves its natural color, the staining is permanent, and the pigment does not smudge over cutting surfaces. The pigment is clearly visible in tissue sections. The tissue specimen is shortly dipped into a 10% water solution of argent nitrate (AgNO3 with HNO3). After slicing, the tissue specimens are developed in common black & white developer for several seconds and paraffin processed as usual. The method is suitable for formaldehyde fixed as well as fresh tissue specimens.

[Atypital localisation of pyoderma gangraenosum in patient with ulcerative colitis]. / Atypická lokalizace pyoderma gangraenosum u nemocného s ulcerózní kolitidou.

The authors present a case of 61-year-old man with ulcerative colitis and with extraintestinal manifestation of the disease in the form of pyoderma gangraenosum. Multiple skin defects, which developed in atypical localisation (extensive affection of facial and hairy parts of the head) in patient with chronically active form of ulcerative colitis were complicated with bacterial contamination of methicilin-resistant strains of Staphylococcus aureus. After application of the parenteral feeding, corticotherapy and targeted antibiotic therapy the subjective and objective status of the patient markedly improved, stool frequency was reduced, admixture of blood in the stool disappeared, temperatures fell back and there was a decrease in activity of non-specific bowel inflammation in laboratory findings. However endoscopic examination of the intestine confirmed the finding of chronically active ulcerative colitis with ulcerations and bridging polyps. Patient was indicated to total colectomy, but he refused it.

[Acquiring images with very high resolution using a composing method]. / Porizování obrazu o velmi vysokém rozlisení metodou skládání.

Composing microscopic images of very high resolution from several parts posed some problems. One of them was the necessity to adjust the focusing level when moving from one part to another. Re-focusing lead to problems with joining the image parts, which did not correspond exactly, and the area of image fusion was noticeable. A computer program was developed to overcome these problems. Our program worked with all the image parts together to find their optimal order for image fusion. Individual image parts were joined using a steep gradient running along a randomly generated curve. This method gave good results even in images with background or holes in the tissue. The method of composing large images from individual parts was used for digitizing the skin lymphoma collection of the Institute of Dermatology, University Hospital, Zürich. This collection of digital images is a part of the 6th version of Hypertext atlas of Dermatopathology at www.muni.cz/atlases.

Demonstration of MyoD1 expression in oncocytic cardiomyopathy: report of two cases and review of the literature.

Oncocytic cardiomyopathy is a rare arrhythmogenic disorder usually associated with female sex, difficult-to-control arrhythmias, or sudden death of infants and children. Morphologically, it is characterized by the presence of oncocytic cells, which are diffusely distributed or form the nodular structures within the myocardium, occasionally involving the valves, with a large number of mitochondria in cytoplasms. We present two cases of oncocytic cardiomyopathy. The first case had a fatal clinical outcome, and the other case was surgically treated. The nuclear expression of skeletal muscle transcription factor MyoD1 was demonstrated in the first case, supporting the theory that oncocytic cardiomyopathy is a conduction system developmental disorder. To confirm this hypothesis, it is necessary to further investigate myogenic transcription factor program in human cardiac conduction system cells.

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.

Therapy-related change of corpus callosum in a young patient with epilepsy.

Focal nonhemorrhagic lesion in the splenium of the corpus callosum in a patient with epilepsy treated with antiepileptic drugs was observed with MRI imaging. We have found only one such case during the past 2 years (series of MRI examinations of approximately 500 patients with various forms of epilepsy).

[A multimedia atlas of skin pathology]. / Multimediální atlas kozní patologie.

We prepared a digital atlas of non-tumourous skin pathology. Currently, the available digital atlases can go beyond the scope of written publications, especially with regards to ease of access, speed of preparation, updating information, fair price and unlimited capacity. This atlas can be used as a diagnostic aid, as well as for postgraduate and pregraduate teaching.

Gastric carcinoma in a 9-year-old boy.

Gastric carcinoma is an extremely rare cancer in children. A case is presented of a 9-year-old boy admitted to The University Hospital Brno with a 4-month history of abdominal pain, anorexia, weight loss, nausea, and vomiting. Several of his family members died from or have been treated for cancer. Barium meal examination performed 2 months prior to admission was nondiagnostic. When gastroendoscopy, laparoscopy, and abdominal computer tomography scan were performed, the diagnosis of adenocarcinoma of the stomach was established. The patient died 10 days after admission because of rapid cancer spread. Miliary metastases of the peritoneum, mesenterium, omentum, liver, bowels, lungs, heart, bone marrow, and skin were found. No penetration through the hematoencephalic barrier was noticed.

[Tests for teaching pathologic anatomy]. / Testy pro výuku patologické anatomie.

A teaching database for pathology was prepared comprising around 1250 questions. Five answers belonged to each question, only one of them being correct. Preparation of questions was partly based on testing sets from Medical School of the University of Loma Linda, Ca., partly on those used in 2nd Department of Pathology, Masaryk University Medical School, Brono. In addition, set of computer programmes for automatic generation, printing and evaluation of tests was prepared. They were verified with Brno students.

[Pathogenesis of micropolygyria]. / Formální patogeneze mikropolygyrie.

Neonatal micropolygyria (MG) was studied concerning a possible proportion of neuroblastic migration in its formal pathogenesis. Section of three selected groups of neonatal brains yielded complete series of frontal histotopograms. Findings were compared with experimental MG induced in the period of neuroblastic migration. Group A: Registration of residual neuroblastic migration in cerebral cortex. There was found that the residual migration could participate on production of MG as late as in the 27th week of gravidity (weight of 1000g). Group B: Evaluation of neuroblastic migration in partial necrosis. Migrating neuroblasts were found in neonatal cerebral cortex with hypoxic encephalopathy. A correlation existed with experimental data proving that MG neonatal cerebral cortex could be produced by neuroblastic migration through fields of partial necrosis. Group C: Detailed investigation concerned 4 neonates with MG due to hypoxic necroses- 2 cases with probable lesion of big vessels perfusion after thromboembolia and 2 cases with cortical vessels perfusion lesion in toxoplasmosis and rubella meningoencephalitis. Findings were compared with experimental MG and correlated with the data from group A and B. Results showed that the production of MG formations in neonatal brain (atypical irregular MG cortex, 4-layer-MG cortex, intracortical nodules, MG intracortical microsulci, neuronal protrusion into molecular layer and pia mater, intracortical and subcortical neuronal heterotopias) can be participated by neuroblastic migration in the transformation of injured immature cerebral cortex. Probable timing of various MG formations and of a relation of MG to ulegyria were presented.