THE ASSOCIATION BETWEEN LYMPH NODE METASTASIS AND MOLECULAR MARKERS IN DIFFERENTIATED THYROID CANCER.

CONTEXT: There is no consensus regarding routine usage and benefits of molecular markers for prediction of prognosis and assessment of risk groups in differentiated thyroid cancer (DTC). OBJECTIVE: We aimed to investigate NIS, Galectin-3, PTEN, P53 and Ki67 expressions in tumor tissue and metastatic lymph nodes in PTC and their association with lymph node metastasis and prognosis. MATERIAL AND METHODS: Ninety two papillary thyroid cancer patients who underwent total thyroidectomy and central lymph node dissection were included in this study. NIS, Galectin-3, PTEN, P53 and Ki67 immunohistochemical stainings were performed for all surgical tumor tissues and metastatic lymph nodes of the 38 patients. Age, gender, tumor size, multifocality, capsular invasion, extrathyroidal extension and lymphocytic thyroiditis were assessed retrospectively. RESULTS: Seventy three females (79.3%) and nineteen males (20.7%) were included in this study. Risk of lymph node metastasis was higher in tumors with capsular invasion and extrathyroidal extension (p=0.03 and p < 0.001). NIS, PTEN and Galectin-3 protein expressions in tumor tissue were not associated with gender, tumor size, multifocality, extrathyroidal extension, capsular invasion, lymph node metastasis and tumor recurrence. Mean Ki 67 proliferation index was 2.08±0.95%. Ki 67 proliferation index was associated with tumor size (p=0.012). Intensity and expression of NIS and PTEN in tumor tissue were concordant with intensity and expression in metastatic lymph nodes (p<0.001). Ki 67 proliferation index in tumor was concordant with metastatic lymph nodes (p=0.02). CONCLUSIONS: NIS, PTEN, Galectin-3, Ki67 and P53 expressions were not associated with the risk of lymph node metastasis in PTC patients. Routine analysis of these markers does not seem to be favorable. Further studies with new markers are necessary to determine prognostic predictors.

Incidental localized (solitary) mediastinal malignant mesothelioma.

Primary mediastinal mesotheliomas are rare tumours. The mesothelial lining cells of the the pericardium are suggested as the most probable cells of origin. Most of these tumours appear either as a diffuse or nodular thickening of the pericardium that encase and even invade the heart. Localized mediastinal mesotheliomas are distinctly uncommon. We report the imaging findings of a solitary malignant mediastinal mesothelioma that presented mainly as a cystic anterior mediastinal mass. On chest radiography, the tumour appeared as a right paramediastinal soft tissue mass located adjacent to the right middle and lower lobes. On CT, a large, well-circumscribed, right anterior mediastinal mass with a central zone of fluid attenuation was observed. This mass had a thin, smooth wall of uniform thickness as well as a small component that demonstrated soft tissue attenuation. There was no plane of separation between the tumour and aorta/superior vena cava. At surgery the tumour could be dissected easily free from the pericardium and great vessels and it was removed totally. Histopathological examination of the tumour revealed a malignant epitheloid mesothelioma.

Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group.

Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m(-2) intravenously (i.v.) on day 1, respectively, and it was 175 mg m(-2) on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P=0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines.

Implantation metastasis caused by fine needle aspiration biopsy following curative resection of stage IB non-small cell lung cancer.

Fine needle aspiration is a useful procedure in the diagnosis of lung cancer, however controversy still remains as to whether it should be employed particularly in patients with operable lung cancer. We report herein a case of metastatic tumor at the site of transthoracic needle biopsy following a curative resection in a patient with stage IB bronchogenic carcinoma. The patient was managed with aggressive chest wall resection and subsequent musculocutaneus flap transposition, however he died 11 months after the initial operation. The tumor implantation risk and the related complications should be considered in patients with operable bronchogenic carcinoma undergoing a tranthoracic needle aspiration biopsy.

Changing patterns of lung cancer; (3/4 in.) 1.9 cm; still a safe length for bronchial resection margin?

BACKGROUND: Surgical resection is the best treatment modality in non-small cell lung cancer (NSCLC). As a guideline, it is suggested that at least a bronchial resection margin of 1.9 cm from the macroscopic tumor might provide a tumor-free margin in lung cancer. In some recent reports, there is great emphasis on the changing histopathological patterns of lung cancer, but no concern for the proximal extension of lung cancer. The aim of this study was to determine the validity of this guideline in the current time. METHODS: Surgically resected specimens of NSCLC cases (n = 70) were examined. The bronchial tree including tumor was dissected and beginning from the edge of the visible tumor, the bronchus were cut into serials in its transverse plane, 5 mm apart from each other. Cut sections were examined for proximal extension of tumor at different levels. RESULTS: Microscopic proximal extension was observed in 24.2% (n = 17/70) of all the cases. Peribronchial extension (n = 9/17) (52.9%) was more predominant compared with bronchial extension (n = 8/17) (47.0%). Squamous cell carcinoma (n = 11/38) (28.9%) showed proximal extension more than adenocarcinoma (n = 5/23) (21.7%). Adenocarcinoma showed more peribronchial extension (n = 4/5) (80.0%) whereas squamous cell carcinoma (n = 7/11) (63.6%) showed more bronchial extension. The farthest extension was 3.0 cm for adenocarcinoma and 2.0 cm for squamous cell carcinoma. Excluding tumor positive specimens beyond 1.5 cm level to the bronchial resection margin, all tumors accounted for 96% of the whole series. CONCLUSIONS: Microscopic proximal extension of lung cancer occurs in 24.2% of NSCLC cases. Squamous cell carcinoma extends more proximally compared with adenocarcinoma in ratio whereas adenocarcinoma extends more in length. A bronchial resection of 1.5 cm in length from the macroscopic tumor will provide clear margins in 93% of NSCLC cases.

Fibrohistiocytic tumor of the trachea in a child.

A 10-year-old girl who had been treated for presumed asthma during the previous year, was admitted to our hospital with dyspnea and wheezing. An endotracheal tumor was detected and a tracheal resection was performed. The tumor was diagnosed as a fibrohistiocytic tumor. Biologic behavior of fibrohistiocytic tumors of the trachea is not clear and morphologically similar cases are interpreted as malignant or benign by different authors. However, an analysis of the present case and 11 well documented cases in the literature shows that this tumor must be evaluated as a low-grade malignancy and initial complete tumor resection is necessary.

Effects of chronic treatment with indomethacin at clinically relevant doses on intestinal tissue 6-keto prostaglandin F1 alpha and leukotriene B4 level in relation to gastroenteropathy.

This study investigated the effects of indomethacin at clinically relevant doses and its chronic usage on intestinal pathology, survival time and intestinal tissue 6-keto prostaglandin F1 alpha and leukotriene B4 level in rats during various periods with different doses. Indomethacin was administered ranging from 0.625 to 5 mg/kg. When used in doses of 0.625 and 1.25 mg/kg, indomethacin caused no apparent intestinal lesions or death during a treatment period of 30 days. On the other hand, all rats died in 7 days when 5 mg/kg of indomethacin was given. Mortality rate reached 53.3% in seven days in the group where 3.75 mg/kg indomethacin was given. The minimal dose of indomethacin, which induced intestinal ulcer and death, was 2.5 mg/kg. The main pathological findings were intestinal ulcers, but no macroscopic and microscopic changes were observed in the stomach. Intestinal tissue 6-keto prostaglandin F1 alpha and leukotriene B4 levels were quantified by enzyme immunoassay after homogenisation and extraction of tissue. In dose-dependent studies, only the dose of indomethacin, 3.75 mg/kg, significantly inhibited intestinal tissue 6-keto prostaglandin F1 alpha levels during seven days application period (197.39 +/- 24.26 vs 383.66 +/- 46.68 ng/g tissue, treatment vs control). 2.5 mg/kg of indomethacin caused no intestinal ulceration on 4th day, however, it significantly inhibited intestinal tissue 6-keto prostaglandin F1 alpha levels on 4th day in time-dependent studies (190.3 +/- 26.62 vs 383.66 +/- 46.68 ng/g tissue, treatment vs control). Neither dose-dependent nor time-dependent indomethacin administration changed intestinal tissue leukotriene B4 level. The results of this study indicated that indomethacin produced enteropathy rather than gastropathy when used chronically in clinically relevant doses in rats. Inhibition of prostaglandin synthesis, which was estimated by quantification of intestinal tissue 6-keto prostaglandin F1 alpha level, seemed not to be a prerequisite for its enteropathic effect.

Immunohistochemical determination of p53 protein in prostatic cancer and prostatic intraepithelial neoplasms.

A role of genetic alterations in the p53 tumor suppressor gene has been implicated in many types of human malignancies. In this study, we examined the prevalence of immunohistochemically detectable p53 accumulation in prostatic tissues obtained from patients with prostatic adenocarcinoma, benign prostate hyperplasia and prostatic intraepithelial neoplasms. Six of 36 (16.7%) cancer cases and 2 of 11 (18.2%) cases of high-grade prostatic intraepithelial neoplasms showed p53 expression while no nuclear staining was observed in normal and hyperplastic prostatic tissues. Correlation of p53 expression with cancer stage, Gleason score and serum prostate-specific antigen level demonstrated that there was no statistically significant relationship between p53 expression and these clinicopathological parameters. Also, no significant association between p53 expression and prognosis was observed.

Carcinosarcoma of the prostate. A case report and a possible evidence on the role of hormonal therapy.

A case of prostatic carcinosarcoma is presented with histopathologic and immunohistochemical characteristics. A 70-year-old man presented with a history of anti-androgen (cyproterone acetate) therapy for prostatic adenocarcinoma. Diffuse and strong staining for progesterone receptor was observed in the carcinosarcoma specimen although it was completely negative in the previous adenocarcinoma specimen. It may be speculated that hormonal therapy might have facilitated the selection of a progesterone-dependent subclone of tumor cells with the ability of mesenchymal differentiation and that genetic instability due to p53 inactivation might have played a role in this process.

High dose rate transurethral brachytherapy as a boost dose for localized adenocarcinoma of the prostate.

From September 1989 to February 1993, 11 patients with localized adenocarcinoma of the prostate were treated with pelvic external-beam radiation therapy followed by high dose rate (HDR) transurethral brachytherapy as a boost dose. External-beam radiation therapy was administered through opposed pelvic fields using a 60Co teletherapy unit to a tumor dose of 46-50 Gy in 23-25 fractions and followed by three fractions of transurethral brachytherapy, delivered using a 60Co HDR remote afterloading equipment. The treatment time was calculated using the prostatic capsule as the reference point. The dose calculated to be delivered to the capsule was 5 Gy/fraction, making a total of 15 Gy. The follow-up period ranged from 11 to 65 months, with a median follow-up time of 30 months. Local control was achieved in all patients. The prostate-specific antigen levels were normalized within 3 months of radiotherapy in 9 patients and within 3-6 months in the remaining 2. Transurethral brachytherapy appears to be a simple and feasible form of brachytherapy. Preliminary local control and radiotherapy-related morbidity rates are comparable to those of other forms of brachytherapy. Further follow-up is required for assessment of long-term local control and delayed radiotherapy-related morbidity.

The significance of pre-epiglottic space invasion in supraglottic laryngeal carcinomas.

It is widely accepted that tumoral invasion of the pre-epiglottic space (PES) has a significant prognostic importance in supraglottic laryngeal carcinomas. The lymphatics of the supraglottic larynx drain to cervical lymph nodes via the PES. Since the supraglottic larynx is an embryological unit that contains the PES, malignant lesions of this region must be resected with en bloc surgery, including the PES. Tumors with PES invasion are already considered to be T3 in TNM staging. The purpose of this study was to review the clinical experience we have had with these tumors at Ankara University. The study comprised 150 patients with squamous cell carcinomas of the supraglottic larynx treated with either partial or total laryngectomies. Findings suggested that PES invasion occurred at early stages of supraglottic tumor progression. Suprahyoid epiglottic lesions behaved less aggressively than tumors originating from other supraglottic subsites and did not invade the PES until advanced stages. PES invasion was not considered to be a significant prognostic factor because the majority of the supraglottic lesions studied demonstrated PES invasion regardless of cervical lymph node metastases. Analysis of oncological and functional results revealed that en bloc resection of the supraglottis with the PES was facilitated by preservation of the hyoid bone.

Radiation therapy for stage I primary orbital non-Hodgkin's lymphomas.

AIMS AND BACKGROUND: The orbit is an uncommon primary site for non-Hodgkin's lymphomas (NHL), and it accounts for less than 1% of all sites of primary presentations. We report the experience of the Department of Radiation Oncology at Ankara University Faculty of Medicine with radiation therapy in treatment of patients with stage I primary orbital NHL. METHODS: From February 1978 through August 1993, 14 patients with stage I primary orbital NHL were treated with radiation therapy. According to the Working Formulation classification, 8 patients had low-grade and 6 had intermediate-grade lymphomas. The most commonly used radiation therapy technique was a single anterior field with a Cobalt-60 unit, delivering 40 Gy in 2 Gy daily fractions. Two patients with intermediate-grade lymphomas received the CHOP regimen following radiation therapy. RESULTS: Follow-up ranged from 0.8 to 18.3 years (median, 10.3 years). Local control was achieved in all patients. Two patients with low-grade lymphomas relapsed locally and were successfully salvaged with radiation therapy. Three patients with intermediate-grade lymphomas failed systemically. Salvage therapy consisted of combination chemotherapy for 2 of them but was unsuccessful. Overall survival probabilities at 2, 5 and 10 years were 78.6%, 61.1% and 52.4%, respectively, for the entire group of 14 patients. Overall, cause-specific and disease-free survival probabilities were higher for patients with low-grade lymphomas than for those with intermediate-grade lymphomas (P = 0.03, P = 0.03 and P = 0.06, respectively). Cataracts were observed in 9 and lacrimal disorders in 4 patients. CONCLUSIONS: The study suggests that among stage I primary orbital NHL, low-grade lymphomas could be treated with radiation therapy alone, whereas combination chemotherapy could accompany radiation therapy for intermediate-grade lymphomas.

Overexpression of p53 in laryngeal carcinoma: clinicopathological implications.

The aims of this study were to determine the incidence of p53 overexpression in squamous cell carcinoma of the larynx and to establish whether or not this bore any relationship to survival, location, stage, histological differentiation, nuclear atypia, mitotic activity, stromal desmoplasia, tumor-associated tissue eosinophilia, or stromal lymphoplasmocytic infiltration. Paraffin blocks from 51 cases of laryngeal squamous cell carcinoma with a minimum follow-up period of 36 months were recut and stained immunohistologically with anti-p53 antibody using the streptavidin-biotin technique. Results were compared with clinicopathological features with Kruskal-Wallis and Mann-Whitney tests. Sixty-three percent of tumors showed positive staining for p53, and in addition, 15% of the sections with adjacent normal or dysplastic mucosa showed positive staining. No relationship between p53 staining and prognosis or any other one of the aforementioned clinicopathological parameters was observed. Although p53 overexpression is a common feature in laryngeal carcinomas, it does not seem to have an impact on prognosis and it does not bear any relationship to the aforementioned clinicopathological parameters.

Human chorionic gonadotropin in serum and neoplastic tissue from patients with bladder carcinoma.

Serum levels and tissue expression of beta subunit of human chorionic gonadotropin were determined in 25 patients with bladder carcinoma. Elevated gonadotropin levels in serum were observed in 5 (20%) patients and immunoreactive cells were found in 5 (20%) tumours. The correlation was poor between serum level and immunohistochemical gonadotropin status. Only one patient showed both elevated serum level and immunohistochemical gonadotropin expression. Our observations suggest that elevated serum levels of gonadotropin may be an indicator of poor prognosis. However, immunohistochemical expression of gonadotropin did not seem to have a similar impact on prognosis in this series.