Serum metallothionein - a potential oncomarker?

INTRODUCTION: Metallothionein's (MT) overexpression has been demonstrated immunohistochemically in neoplastic cells of many tumour types. Its elevation above the physiological level has been confirmed in circulation of their hosts. The results of studies dealing with the topic have been summarized to verify if this marker can be applied in the current oncologic practise. METHODS: The Pubmed and Google Scholar medical databases were reviewed for full-text articles focused on MT blood (plasma / serum) levels in patients with malignant tumours. RESULTS: In our review, after a precise selection, we included 8 prospective randomized trials encompassing 561 blood samples taken from patients with a large histopathological spectrum of malignancies. In general, significant differences in blood MT levels between oncological patients and healthy subjects were confirmed. No particular value of the MT level has been demonstrated to be unequivocally predictive of oncologic diseaseCONCLUSION: The results of our review suggest that although the elevation of MT in blood serum in patients with solid malignancy can be regarded as a promising tumour marker, the recommendations of its applicability in clinical practice require to be derived from further research on extended cohorts of patients (Tab. 1, Fig. 1, Ref. 49).

Cyst of the right lymphatic duct.

INTRODUCTION: Cysts originating from cervical lymphatic ducts are very rare affections. However, they play an important role in the differential diagnosis of supraclavicular masses. The aetiology remains unclear. Practically all cases arise from the thoracic duct; those affecting the right lymphatic duct are encountered very exceptionally. CASE REPORT: In the presented case report of a right lymphatic duct cyst, we analyzed the possible reasons for the diametrically differing incidence of cysts arising from the thoracic duct and those related to the right lymphatic duct. DISCUSSION: The cysts manifest themselves clinically as an otherwise asymptomatic supraclavicular swelling. The diagnosis is based on imaging. High T-lymphocytes and triglyceride levels in an aspirate are pathognomonic. There is no uniform opinion on the therapy. The majority of authors recommend surgical removal. Lymphatic vessels entering the cyst must be intraoperatively ligated to prevent lymph leakage.

Differing Lymphatic Vessels Density in Salivary Adenoid Cystic Carcinoma and Pleomorphic Adenoma.

Benign and malignant tumours are known to express various factors inducing lymphangiogenesis. Despite their different biological behaviour, salivary pleomorphic adenomas (PA) and adenoid cystic carcinomas (SACC) show similar lymphatic network. Authors compare density of lymphatic network in these tumours. The retrospective study included 20 SACC and 20 PA from salivary tumours. Lymphatic vessel density (LVD) was identified using D2-40 antibody and counted. In SACC, intratumoral, respectively peritumoral, lymphatic vessels were identified in 100 %, respectively 93.8 %, of cases. The intratumoral and peritumoral LVD did not significantly differ from each other. However, they both were higher than normal parenchyma density. In PA, intratumoral LVD, with a single exception, revealed values of 0 and 1. The intratumoral was found to be lower than peritumoral density. The LVD in healthy gland, similar to peritumoral one, was significantly higher than intratumoral values. Direct comparison showed intratumoral and peritumoral LVD in PA to be lower than in SACC. This study comparing LVD in PA and SACC revealed higher values in SACC, outnumbering those in healthy salivary parenchyma and PA. It suggests the capability of this biologically aggressive neoplasm to induce lymphangiogenesis.

Recidivous cholesteatoma: DWI MR after canal wall up and canal wall down mastoidectomy.

OBJECTIVES: To investigate the correlation between preoperative non-echo planar diffusion-weighted (non-EPI DWI) MR imaging with surgical findings of recidivous middle ear cholesteatoma after canal wall up (CWU) and canal wall down (CWD) mastoidectomy. BACKGROUND: The detection of recidive cholesteatoma after CWU and after CWD procedures, when the trepanation cavity is spontaneously closed by soft tissue, is possible by second-look and revision surgery. However, many cases prove to be negative of the disease. To avoid unnecessary operational risks we adopted a novel imaging method to evaluate its potential in the detection of recidivous cholesteatoma. MATERIAL AND METHODS: The prospective study included 27 cases. Fifteen cases were revised after CWD and 12 cases were second-look surgeries after CWU procedures. All patients underwent the MR protocol: T2-weighted, T1-weighted and non-EPI DWI. The finding on MR correlated with peroperative presence of cholesteatoma. RESULTS: Non-EPI DWI sequence showed an increased signal intensity in 16/27 (59 %) cases. This correlated with surgical findings in all 7 patients after CWU and in 8 patients after CWD. The overall sensitivity, specificity, positive and negative predictive values of non-EPI DWI were 83.3 %, 88.8 %, 93.8 % and 72.7 %, respectively. DWI presented a sensitivity of 100 % and specificity of 85.7 % in the subgroup of patients after CWD mastoidectomy. CONCLUSION: Residual and/or recurrent cholesteatoma can be accurately detected by DWI MR. It can be used as a screening method to select patients, who are indicated to second-look or revision surgery after CWU and CWD mastoidectomy (Tab. 1, Fig. 3, Ref. 49).

Neither expression of VEGF-C/D nor lymph vessel density supports lymphatic invasion as the mechanism responsible for local spread of recurrent salivary pleomorphic adenoma.

Recent research suggests that multinodular recurrent pleomorphic adenoma (PA) might result from cell migration through lymphatics. Lymphangiogenesis in malignancies is mediated by vascular endothelial growth factors C and D (VEGF-C/D). We studied the expression of VEGF-C/D in PA by immunohistochemistry as well as lymphatic vessel density (LVD). In 6 non-recurrent, 4 primary-to-recur, and 10 recurrent PAs, VEGF-C/D expression was assessed by immunohistochemistry. Staining was scored in terms of staining intensity (0 = absent to 3 = strong), and the percentage of positive tumor cells (scored as 0 (0-19 %), 1 (20-39 %), 2 (40-50 %), and 3 (60-100 %)) and a sum score were calculated. Intra- and peritumoral LVD was assessed by counting of LV after immunostaining, using the D2-40 antibody. All but one sample were VEGF-C negative. The differences in VEGF-D expression between non-recurrent, primary-to-recur, and recurrent PAs were not significant (p>0.05). VEGF-D expression did not correlate with peritumoral LVD (p>0.05). Our study revealed a significant difference between intra- and peritumoral LVD values when comparing individual and all sample groups (p=0.01). The lack of VEGF-C expression and of significant differences in VEGF-D expression and peritumoral LVD between patients with non-recurrent, primary-to-recur, and recurrent PAs does not support the lymphangiogenic local spread hypothesis

Efficacy and safety of erdosteine in the treatment of chronic rhinosinusitis with nasal polyposis - a pilot study.

BACKGROUND: Erdosteine was originally developed as a mucolytic agent. It is a multimechanism substance with anti-bacterial, anti-oxidant, and most importantly anti-inflammatory effects. Given similar mechanisms of action (suppression of cytokines, including tumor necrosis factor α), it could become a reasonable alternative to currently used treatments with macrolides or steroids. OBJECTIVE: To assess efficacy and safety of erdosteine in the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODOLOGY: A prospective non-interventional post-authorisation study comparing patients treated with erdosteine only or the combination of erdosteine and nasal corticosteroid spray for CRSwNP. The end-points were pre- and post-treatment changes in endoscopic score and subjective evaluation of CRSwNP related symptoms using a 22-item Sinonasal Outcome Test questionnaire. Patients underwent nasal endoscopy and filled the questionnaire before and after the treatment. RESULTS: No patient experienced any adverse effect during the study. A comparison of pre- and post-treatment endoscopic findings and questionnaire values revealed significant reduction in both patient groups, with a significantly better response in the erdosteine only group. CONCLUSION: Based on this pilot study, erdosteine seems effective in the treatment of CRSwNP and might become a reasonable alternative to currently used medication. The therapeutical role of erdosteine needs to be further assessed.

[Sentinel lymph node biopsy in oral and oropharyngeal carcinomas]. / Biopsie sentinelové uzliny u pacientu s karcinomem ústní dutiny a orofaryngu.

BACKGROUND: The aim of our study was to assess feasibility and accuracy of sentinel lymph node biopsy in patients with head and neck squamous cell carcinoma with clinically N0 neck. METHODS AND RESULTS: The sentinel lymph node was localised preoperatively by lymphoscintigraphy and intraoperatively by hand-held gamma probe after peritumoral injection of a Tc99m-labeled colloidal human serum albumin. The histology of the sentinel lymph node was compared with the histology of the nodes of the elective neck dissection performed in all patients. 27 patients with oral and oropharyngeal carcinomas accessible to injection in local anaesthesia were enrolled into a prospective trial between July 1993 and December 2005. The sentinel lymph node was localised by preoperative lymphoscintigraphy in 26 of 27 patients. Sentinel lymph node was identified perioperatively by hand-held gamma probe in all 28 necks of 27 patients. Occult metastases were found in 4 sentinel lymph nodes in 4 cases. In one case (3.6 %) the result of sentinel lymph node biopsy was false negative. The sentinel lymph node biopsy correctly predicted the positivity and negativity of the neck in 27 of 28 cases (96.4 %). CONCLUSIONS: Sentinel lymph node biopsy in patients with oral and oropharyngeal carcinomas is feasible and seems to accurately predict the status of the regional lymph nodes.

Non-invasive (intracapsular) carcinoma ex pleomorphic adenoma: recognition of focal carcinoma by HER-2/neu and MIB1 immunohistochemistry.

AIMS: Non-invasive carcinoma ex pleomorphic adenoma is defined as a carcinoma arising within the boundaries of a pleomorphic adenoma (PA), but which fails to display invasion beyond the capsule of host PA. Alternative names are intracapsular, in situ, or focal carcinoma. The true nature of non-invasive carcinoma ex-PA is still controversial; for example, it is not clear whether it represents early but genuine carcinomatous changes with the genetic make-up of malignant cells, or simply cytological, possibly metaplastic or 'bizarre' changes in PA. Strong overexpression and amplification of HER-2/neu protein has recently been demonstrated in invasive carcinoma ex-PA. In addition, data from breast cancer studies suggest that amplification of HER-2/neu and overexpression of its gene product is mainly involved in the initiation of breast oncogenesis. We sought to establish whether this method could help to demonstrate that what is described as non-invasive carcinoma ex-PA is really a genuine malignancy, albeit in an early phase. METHODS AND RESULTS: Eleven cases of non-invasive carcinoma (in situ) ex-PA were studied for HER-2/neu status using immunohistochemistry and fluorescent in-situ hybridization (FISH). Cells of focal non-invasive carcinoma ex-PA were strongly positive for HER-2/neu protein, while the cells of the maternal PA were always negative. Two cases of low-grade non-invasive myoepithelial carcinoma ex-PA were negative. In four cases out of a total of six tumours studied by FISH, we detected amplification of HER-2/neu gene signals in tumour cells of focal, non-invasive, carcinoma. CONCLUSIONS: The current data suggest that non-invasive carcinoma ex PA is a genuine carcinoma within a PA. However, the presence of cyto-nuclear atypia is not sufficient to make a definite diagnosis of malignant change, which requires a combination of morphology and immunohistochemistry.

Expression of HER-2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in-situ hybridization and immunohistochemistry.

AIMS: Salivary duct carcinoma is a highly malignant salivary gland tumour with aggressive clinical behaviour, characterized by histological resemblance to invasive ductal carcinoma of the breast. Amplification of HER-2/neu oncogene and over-expression of its gene product have both prognostic and therapeutic implications in breast cancer. Recent report on salivary duct carcinomas for HER-2/neu using immunohistochemistry (IHC) has shown over-expression in most cases. However, correlation between IHC and molecular genetic analysis of HER-2/neu in salivary duct carcinoma has not yet been performed. METHODS AND RESULTS: We have now evaluated 11 cases of salivary duct carcinomas for HER-2/neu status using IHC and fluorescent in-situ hybridization (FISH). To our knowledge, this is the first molecular genetic analysis of HER-2/neu in salivary duct carcinoma. CONCLUSIONS: In immunohistochemistry, over-expression of HER-2/neu protein was identified as distinct membrane staining in most carcinoma cells in all our salivary duct carcinoma cases, while only four cases revealed an amplification of HER-2/neu gene by means of FISH analysis. Both amplified and non-amplified salivary duct carcinomas with strong immunohistochemical staining for HER-2/neu protein were associated with poor clinical outcome for the patients. Apparently, HER-2/neu protein over-expression could also be controlled by mechanisms other than gene amplification. In the group of salivary gland tumours other than salivary duct carcinoma, strong over-expression was detected only in three cases of carcinoma ex pleomorphic adenoma. Thus, over-expression of HER-2/neu protein is also a useful marker of malignant transformation in pleomorphic adenomas.

Sclerosing polycystic adenosis of parotid gland with dysplasia and ductal carcinoma in situ. Report of three cases with immunohistochemical and ultrastructural examination.

We describe three cases of sclerosing polycystic adenosis (SPA) of the parotid gland, a salivary condition analogous to fibrocystic disease of the breast. For the first time, immunoreactivity for oestrogen and progesterone receptors was demonstrated, suggesting a possible participation of hormone stimulation in its pathogenesis. In addition, all our cases showed foci of dysplasia of the ductal epithelium, which in one case was severe enough to amount to carcinoma in situ. This feature that has not previously been reported in SPA.

[Amplification and overexpression of HER-2/neu in parotid gland salivary duct carcinoma. Immunohistochemical study and fluorescence in situ hybridization]. / Amplifikace a overexprese HER-2/neu v salivárním duktálním karcinomu príusní zlázy. Imunohistochemická studie a fluorescencní in situ hybridizace.

Salivary duct carcinoma (SDC) is highly malignant salivary gland tumour with aggressive clinical behaviour, characterised by its histological resemblance to invasive ductal carcinoma of the breast. Amplification of gene HER-2/neu and overexpression of its gene product have been shown to have both prognostic and treatment implications in breast cancer. The reports concerning the expression of c-erbB2/HER-2/neu in salivary gland tumours are few and controversial. Thus, eleven cases of SDC were evaluated for HER-2/neu status using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). To the best of our knowledge, this is the first molecular genetic analysis of SDCs using FISH. HER-2/neu overexpression, identified as strong membrane staining, was observed in all but one case of SDC in majority of neoplastic cells while only four tumours, of nine cases analysed, revealed HER-2/neu gene amplification by means of FISH analysis. SDCs were associated with poor clinical outcome, 6 patients (55%) died of disseminated carcinoma within 4 to 44 months after therapy. There was no difference in outcome of patients with IHC positive-nonamplified and IHC positive-amplified tumours.

Spindle cell myoepithelial tumours of the parotid gland with extensive lipomatous metaplasia. A report of four cases with immunohistochemical and ultrastructural findings.

We report four cases of parotid gland tumours composed predominantly of spindle-shaped myoepithelial cells and mature adipocytes. The central portion of one tumour showed extensive adipose differentiation, whereas in the peripheral parts there were small foci of ductal epithelium arranged in cords and tubules within an abundant myxoid stroma. The other cases were adipose spindle cell myoepitheliomas without an obvious glandular component. Under high-power examination, a transition between modified spindle-shaped myoepithelial cells and adipocytes was observed, and this was confirmed with immunohistochemistry. Ultrastructurally, the modified myoepithelial cells showed intracytoplasmic tonofilaments, bundles of actin microfilaments and lipid droplets. A possible pathogenesis is proposed of true metaplastic transformation of myoepithelial cells to adipocytes. This lesion is important to identify correctly, as inadequate surgery can lead to recurrence.

Malignancy-simulating change in parotid gland oncocytoma following fine needle aspiration. Report of 3 cases.

We report here there cases of benign parotid gland oncocytoma with pseudomalignant change that mimic acinic cell carcinoma. All patients underwent fine-needle aspiration biopsy of the tumor 62, 725 and 33 days before surgical excision. In histologic sections, there were clusters of pigmented cells with PAS-positive foamy to finely granular cytoplasm similar to those seen in salivary gland acinic cell carcinomas. This report provides another, previously undescribed, example of a diagnostic pitfall that may be observed in histologic tissue specimens removed after FNA of oncocytic tumors.

An ultrastructural study of the biostimulative effect of He-Ne laser radiation on the early postnatal differentiation of the rat submandibular gland.

Submandibular gland of the rat during the first week of postnatal development was used for the study of the ultrastructural changes after the He-Ne laser radiation. In the experimental group we observed an increase of the dark cells with greater quantity of the granular endoplasmic reticulum and an increased number of specific secretory granules. These changes show positive biostimulative effect of He-Ne laser radiation on the morphologic differentiation of the submandibular gland of the rat in the early postnatal period.

Well-differentiated acinic cell carcinoma of salivary glands associated with lymphoid stroma.

In a multicenter study, 69 acinic cell carcinomas of the salivary glands were identified, of which 12 constituted what the authors believe to be a distinct subgroup. Their most noticeable feature was a dense lymphoid stroma with well-developed germinal centers, surrounding a sometimes scanty epithelial component, which in each case had a microcystic growth pattern. All these tumors were enveloped by a thin fibrous pseudocapsule, thus mimicking an intraparotid lymph node containing a metastasis. All 12 cases showed low MIB1 proliferative activity, with a mean index of 1.7% (range, 0.5 to 3.7). All patients remained well without recurrence or metastasis in followup periods of 19 months to 14 years. A second subgroup of nine acinic cell carcinomas also possessed a heavy lymphoid stroma with germinal centers, but its distribution was more patchy than in the first subgroup, and in addition, the fibrous pseudo-capsule was incomplete or absent. In each case the epithelial growth pattern was other than microcystic. These tumors had significantly higher MIB1 indices (mean, 17%; range, 3.4 to 45). In contrast to the first subgroup, only three of nine patients remained well with no further disease. The other six patients developed recurrences or metastases, and two died of disseminated cancer. In view of the clinical and pathological data, it is speculated that the tumor foci lacking lymphoid stroma in each of the second subgroup possibly represented a clone of high-grade malignancy arising within a low-grade acinic cell carcinoma with lymphoid stroma.

Expression of estrogen receptors and estrogen-induced proteins in tumors of "hormone non-dependent tissues".

Estrogen receptors (ER), progesterone receptors (PR) and some other estrogen-induced proteins (EIP) were found in the cells of salivary gland carcinomas, thyroid carcinomas, in gliomas and in various farther neoplasms as well as in some normal tissues. The positivity was demonstrated in both females and males. The results indicate that steroid hormones and their receptors could play, both in normal and tumorous tissues, more important biological role than expected so far.

[Otorhinolaryngologic aspects of chronic inflammations of the masticatory muscles]. / ORL aspekty chronických zánetu ve zvýkacích svalech.

Chronic and usually odontogenic inflammations of the masticatory muscles may be, due to anatomical conditions and inconspicuous inflammatory symptomatology, difficult to differentiate from tumours in this region. The differential diagnosis of both affections is based on the clinical course, sialography and CT examination which along with modern ATB treatment significantly modify hitherto used surgical therapy.

[The importance of CT examination in the diagnosis and therapy of rhino-otogenic intracranial complications]. / Význam CT vysetrení pro diagnostiku a lécbu rinootogennich intrakraniálních komplikací.

Computed tomography in the diagnosis of rhino-otogenic intracranial inflammatory complications made it possible to reduce significantly the morbidity and mortality. It provides more reliable information, than hitherto used pretentious and invasive methods, on the development of inflammatory foci, the dynamics of their development, localization and extent. In correlation with the clinical course and laboratory findings it makes it possible to select an optimal time for operation and to select an optimal surgical approach, or in exceptional instances a conservative procedure. However, false negative findings may also be encountered. In those instances, with regard to the course and symptomatology of these complications, CT must be repeated or another diagnostic method must be selected.

[Preauricular fistulae]. / Príspevek k problematice preaurikulárních pístelí.

Preauricular fistulae and their relapses are not exceptional in ENT practice. Simple topographic and anatomical relations in this area tempt us to underrate the surgical risk which is mainly the danger of incomplete removal and subsequent relapses. The elimination of nonidentifiable remnants of branchiomas in the granulation and scar tissue calls for resection extending to sound neighbouring structures which require more pretentious knowledge of clinical and anatomical conditions in this region. The authors operated successfully during the past 10 years 10 preauricular fistulae (primary operations) and two relapses. They outline the principles of surgery which were formulated with regard to their own experience, data in the literature and based on the most recent embryological findings; they emphasize preventive aspects of surgical treatment of preauricular fistulae.