Jaroslava Dušková

Narrow Band Imaging Cystoscopy Improves the Detection of Non-muscle-invasive Bladder Cancer

OBJECTIVES To determine whether narrow band imaging (NBI) improves detection of non-muscle-invasive bladder cancer over white-light imaging (WLI) cystoscopy. METHODS We conducted a prospective, within-patient comparison on 103 consecutive procedures on 95 patients scheduled for (re-) transurethral resection of a bladder tumor (84) or bladder biopsies (19) in the Academic Medical Center, Amsterdam (September 2007-July 2009) and in the General Faculty Hospital, Prague (January 2009-July 2009). WLI and NBI cystoscopy were subsequently performed by different surgeons who independently indicated all tumors and suspect areas on a bladder diagram. The lesions identified were resected/biopsied and sent for histopathological examination. Number of patients with additional tumors detected by WLI and NBI were calculated; mean number of urothelial carcinomas (UCs) per patient, detection rates, and false-positive rates of both techniques were compared. RESULTS A total of 78 patients had a confirmed UC; there were 226 tumors in total. In 28 (35.9%) of these patients, a total of 39 additional tumors (17.3%) (26pTa, 6pT1, 1pT2, 6pTis) were detected by NBI, whereas 4 additional tumors (1.8%) (1pTa, 1pT1, 2pTis) within 3 patients (2.9%) were detected by WLI. The mean (SD, range) number of UCs per patient identified by NBI was 2.1 (2.6, 0-15), vs 1.7 (2.3, 0-15) by WLI (P <.001). The detection rate of NBI was 94.7% vs 79.2% for WLI (P <.001). The false-positive rate of NBI and WLI was 31.6% and 24.5%, respectively (P <.001). CONCLUSIONS NBI cystoscopy improves the detection of primary and recurrent nonmuscle invasive bladder cancer over WLI. However, further validation of the technique with comparative studies is required.

Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinomas

The frequency and prognostic relevance of RET proto-oncogene somatic mutations in sporadic medullary thyroid carcinoma (MTC) remain controversial. In order to study somatic mutations in the RET proto-oncogene in sporadic MTCs found in the Czech population and to correlate these mutations with clinical and pathological characteristics, we investigated 48 truly sporadic MTCs by sequencing classical risk exons 10, 11, 13, 14, 15 and 16. From the 48 tumors studied, 23 (48%) had somatic mutation in the RET proto-oncogene in exons 10, 11, 15 or 16. The classical somatic mutation Met918Thr in exon 16 was only found in 13 tumors (27%). In five cases, multiple somatic mutations and deletions were detected. A statistically significant correlation between the presence of somatic mutation with more advanced pathological TNM stages was observed. Other clinical and pathological characteristics did not show any statistical significant association with the presence or absence of somatic mutation.

Diagnostic terminology for reporting thyroid fine needle aspiration cytology: European Federation of Cytology Societies thyroid working party symposium, Lisbon 2009

G. Kocjan, B. Cochand‐Priollet, P. P. de Agustin, C. Bourgain, A. Chandra, Y. Daneshbod, A. Deery, J. Duskova, C. Ersoz, G. Fadda, A. Fassina, P. Firat, B. Jimenez‐Ayala, P. Karakitsos, O. Koperek, N. Matesa, D. Poller, L. Thienpont, A. Ryska, U. Schenck, T. Sauer, F. Schmitt, E. Tani, T. Toivonen, M. Tötsch, G. Troncone, L. Vass and P. Vielh
Diagnostic terminology for reporting thyroid fine needle aspiration cytology: European Federation of Cytology Societies thyroid working party symposium, Lisbon 2009

Exon 5 of the RET proto-oncogene: a newly detected risk exon for familial medullary thyroid carcinoma, a novel germ-line mutation Gly321Arg.

Familial medullary thyroid carcinoma (FMTC) is an autosomal dominant inherited disease, characterized by germ-line mutations in the RET proto-oncogene, mainly in exons 10 and 11, but also in exons 13, 14 and 15. Recently, mutations in exons 8 and 16 associated with FMTC were also described. In the herein presented study, single strand conformation polymorphism (SSCP) method for rapid screening of mutations in the RET proto-oncogene and fluorescent sequencing method were used. In one Czech family with FMTC, we have identified a novel missense point mutation of the RET proto-oncogene in exon 5, that results in substitution of arginine by glycine at codon 321 in the cadherin-like domain of ret protein. It seems that this mutation causes FMTC as no other mutation was found in the classical risk exons (10, 11, 13, 14, 15 and 16) of the RET proto-oncogene. The mutation cosegregates with medullary thyroid carcinoma (MTC) or C cell hyperplasia (CCH) in two patients; two other family members are mutation carriers without clinical signs of MTC so far. To improve the diagnosis of FMTC, analysis of exon 5 of the RET proto-oncogene should be considered in families with no identified classical RET mutations.

BRAFV600E mutation in the pathogenesis of a large series of papillary thyroid carcinoma in Czech Republic.

Background: Activating point mutation of the BRAF gene, the most common genetic alteration reported in papillary thyroid carcinomas (PTC), has been associated with poor prognostic characteristics. Aim: Our objective was to determine the frequency of BRAFV600E mutation in PTC tumor tissues from the period 1960–2007 and to correlate it with clinicopathological parameters. Subjects and methods: DNAs were extracted from 242 PTCs, 23 sporadic medullary carcinomas, one anaplastic carcinoma and 6 poorly differentiated carcinomas. The presence of BRAFV600E mutation was determined using single strand conformation polymorphism method and verified by direct sequencing. Results: BRAFV600E mutation was detected in 81 of 242 PTCs (33.5%), in one of 6 poorly differentiated carcinomas (16.7%) and in anaplastic carcinoma. BRAFV600E mutation was much less frequent in the follicular variant compared to classical variant and mixed follicular-classical variant of PTCs (p=0.001). BRAFV600E mutation was significantly associated with presence of nodal metastasis (p=0.029), more advanced TNM stage (p=0.014) and recurrence of disease (p=0.008). The mutation correlated with a higher age at diagnosis (p=0.049) and with a greater tumor size (p=0.041). Multivariate analysis confirmed these findings. The prevalence of BRAFV600E mutation before 1986 was significantly lower than after it (p=0.008). Conclusions: Our data suggest that BRAFV600E mutation is associated with high-risk clinicopathological characteristics of PTC and worse prognosis of patients. The frequency of the mutation significantly varied during the observed period but rather because of the different age distribution of patients in particular periods than as a consequence of Chernobyl accident.

Leptin concentrations in the abdominal subcutaneous adipose tissue of patients with anorexia nervosa assessed by in vivo microdialysis

OBJECTIVE The adipocyte-derived hormone leptin is involved in energy metabolism and body weight regulation. Plasma leptin concentrations are significantly reduced in patients with anorexia nervosa (AN) and with severe malnutrition. Whether reduced plasma leptin is reflected by its decreased production by the adipose tissue is unknown. METHODS In the present study we measured leptin concentrations locally in the abdominal subcutaneous adipose tissue of 9 female AN patients and 11 healthy controls by in vivo microdialysis. RESULTS Adipose tissue free leptin levels were not different in patients with AN compared to controls (2.59+/-1.99 vs 2.36+/-0.25 ng/ml, P>0.05). Plasma leptin soluble receptor (sOb-R) levels were significantly higher in patients with AN than in healthy subjects (58.05+/-38.69 vs 12.79+/-5.08 U/ml, P<0.01). The area of adipocyte in AN was considerably smaller than in the controls (183+/-104.01 microm2 compared to 2145.8+/-1003.41). CONCLUSIONS We conclude that decreased plasma leptin levels in patients with AN are not directly related to dialysate leptin levels in the abdominal subcutaneous adipose tissue.

Does the Expression of Fascin-1 and Tumor Subclassification Help to Assess the Risk of Recurrence and Progression in T1 Urothelial Urinary Bladder Carcinoma?

Introduction: To evaluate the prognostic value of T1 subclassification and fascin-1 expression in T1 human urothelial cell carcinoma of the bladder. Materials and Methods: In a prospective study with 105 consecutive patients, T1 tumors were subclassified into 2 groups according to the depth of tumor invasion. The tunica muscularis mucosae was used as a landmark. The expression of fascin-1 was examined by using an anti-fascin-1 mouse monoclonal antibody and was evaluated semiquantitatively for both intensity and distribution. The patients were followed up for 27.3 ± 13.7 months. Results: The T1 tumor subclassification was feasible in 99 patients (94%). T1a tumor was detected in 77 patients (73%), T1b tumor in 22 patients (21%). An invasive tumor was found in 5 patients (4.8%) during the restaging transurethral resection of the bladder. The risk of understaging in patients with T1b tumor was 18%. There was not a significant difference in time to the recurrence in the T1a and the T1b group. The progression-free survival rates were significantly different between both groups (p = 0.0034). No correlation was found between fascin-1 positivity and the depth of tumor invasion. Fascin-1 positivity did not correlate with recurrence or the progression-free intervals. In the multivariate analysis, only the extent of lamina propria invasion was an independent predictor of the tumor progression. The fascin positivity was not an independent prognostic factor relating to the risk of recurrence or progression. Conclusion: The finding of T1b tumor was connected with a significantly higher risk of progression and understaging. The fascin-1 expression did not correlate with the depth of tumor invasion or with the tumor recurrence or progression.

Survey of medical training in cytopathology carried out by the journal Cytopathology

Anshu, A. Herbert, B. Cochand‐Priollet, P. Cross, M. Desai, R. Dina, J. Duskova, A. Evered, A. Farnsworth, W. Gray, S. S. Gupta, K. Kapila, I. Kardum‐Skelin, V. Kloboves‐Prevodnik, T. K. Kobayashi, H. Koutselini, W. Olszewski, B. Onal, M. B. Pitman, Ž. Marinšek, T. Sauer, U. Schenck, F. Schmitt, I. Shabalova, J. H. F. Smith, E. Tani, L. Vass, P. Vielh and H. Wiener
Survey of medical training in cytopathology carried out by the journal Cytopathology

The expression of PAX5, p53 immunohistochemistry and p53 mutation analysis in superficial bladder carcinoma tissue. Correlation with pathological findings and clinical outcome.

Objectives: The expression pattern of PAX5 in thetissue of superficial bladder transitional cell carcinoma (TCC), itsprognostic value and its correlation with p53immunohistochemistry and p53 mutation analysis were evaluated.Methods: Study comprised 61 patients with histologicallyconfirmed superficial bladder TCC. Expression level of PAX5mRNA was investigated using reverse transcriptase-polymerase chainreaction (RT-PCR) and determined semiquantitatively. The presence ofp53 mutations was determined by SSCP and confirmed by directsequencing. The p53 immunohistochemistry was performed with DO1antibody and semiquantitatively evaluated using HSCORE (HS) method. Asthe control group for the evaluation of the PAX5 expressionserved 8 men with benign prostatic hyperplasia. Results:PAX5 expression was found in 50 patients with bladder TCC butin no patient from the control group. Its quantity however correlatedneither with the stage nor with the grade of the tumor. P53mutation was confirmed only in 1 patient with pTaG2 tumor in exon 5(deletion of proline 128). On the contrary, positive immunohistochemicalstaining of p53 was detected in most patients. Using the cutoffvalue of HS 200, 56.9% of patients showed p53overexpression. Quantity of p53 immunochistochemical positivitydid not correlate with the quantity of PAX5 expression. Usingthe cutoff values of HS 200 for p53 and of 0.2 forPAX5, 7 of 8 patients with future progression had p53and 4 had PAX5 overexpression respectively.Conclusion: The expression of gene PAX5 is a frequentevent in superficial TCC of the bladder.

Coincidence of thyroid tumor and thyroglossal duct remnants. Review of the literature and presentation of three cases

Aims and Background The coincidence of benign or malignant thyroid tumors with thyroglossal duct remnant (TDR) cysts is rare. Although the precise etiology is still unclear, thyroid origin and spread from a primary site have been suggested and this obviously has important implications for the therapeutic approach. Three cases of thyroglossal duct carcinoma are presented and its management is discussed on the basis of the current rationale for treatment of thyroid cancer. The indication for surgery depends on positive findings in the thyroid gland (nodules, FNAB). The aim of this study was to review our experience in the management of papillary thyroid diseases associated with TDR. Materials and Methods The records of three patients with thyroid tumors associated with TDR treated at the Department of ENT and Head and Neck Surgery of the First Medical Faculty UK of Prague between January 1991 and January 2001 were analyzed. We searched for risk factors of thyroid carcinoma: history of ionizing radiation, history of thyroid diseases, age, tumor size, tumor spread and histopathological factors. Results We used a triple approach consisting of clinical and ultrasound examination and fine-needle aspiration biopsy for preoperative assessment. Our diagnostic and therapeutic procedures included TDR excision (Sistrunk or Schlange procedure) and total thyroidectomy. Although the therapeutic approach could be a matter of discussion, most patients agreed with our suggestion of relatively radical but non-mutilating treatment. Postoperative radiation or radioiodine ablation is considered in cases of TDR carcinoma or thyroid carcinoma associated with TDR. Oncological follow-up included clinical and ultrasound examination three times during the first year, twice in the second year, and once yearly thereafter. Tumor marker evaluation and/or scintigraphy were performed 6, 12 and/or 24 months following surgery.