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Malignant Effusions (malignant + effusion)
Selected AbstractsIntracavitary administration of OK-432 with subcutaneous priming for malignant ascites in a case of advanced renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2002YUKIO KAGEYAMA Abstract The intracavitary injection of OK-432 (a streptococcal preparation) with subcutaneous priming has been shown to be an effective immunotherapy for patients with malignant effusion. We applied this treatment in a case of advanced renal cell carcinoma with massive ascites. The patient received 0.2 Klinishe Einheit (KE) OK-432 in the subcutaneous injection twice (day 1 and day 7) followed by 10KE OK-432 intra-abdominal administration (day 9). The treatment was performed safely without major side-effects except for transient pyrexia. A significant reduction of ascites was noted 1 month after the treatment without subsequent re-accumulation. Intracavitary injection of OK-432 with subcutaneous priming seems to be a simple, safe and effective treatment for ascites in advanced renal cell carcinoma. [source] Thoracoscopic talc pleurodesis for malignant pleural effusionANZ JOURNAL OF SURGERY, Issue 1-2 2003David Love Background: Malignant pleural effusion (MPE) is a common and distressing condition at the end of life for many patients with disseminated cancer. The challenge for the surgeon lies in managing this problem in order to deliver the most effective palliation with the least impact on the limited time available to these patients. Methods: Herein is reported a retrospective review of outcomes for a consecutive series of 66 MPE (61 patients) treated over a 5-year period from 1995 to 2000. A standard operative technique involving a single-lung anaesthetic and two-port thoracoscopy was employed. Outcomes were determined by contacting the referring practitioner or the patients themselves. Principal outcome measures included time to recurrence of the effusion and survival. Results: Complete follow up was achieved for 60 MPE (55 patients; five of whom were treated for metachronous, bilateral disease). The three most common primary sites were breast, lung and mesothelial tissue. The planned procedure was not completed in two cases due to encasement of the underlying lung by tumour. Primary failure (immediate recurrence of the effusion) occurred in six cases. Delayed recurrence of the effusion occurred in a further 23 MPE resulting in complete control in 31 cases (52%) until death. Overall median survival was 220 days and the 30-day mortality was 0. Conclusions: Complete and permanent control of a malignant effusion is difficult to achieve. Management based on thoracoscopy and talc insufflation produces satisfactory results with an acceptable morbidity and no early mortality. The ability to inspect the pleural space, break down adhesions and completely drain pockets of fluid to achieve complete lung expansion probably contributes to this. [source] Phase II study of pemetrexed in combination with carboplatin in the first-line treatment of advanced nonsmall cell lung cancerCANCER, Issue 11 2005Ralph G. Zinner M.D. Abstract BACKGROUND The primary objectives of this study were to determine the efficacy and tolerability of a pemetrexed-carboplatin combination as first-line therapy in patients with advanced nonsmall cell lung cancer. METHODS Eligibility criteria included Zubrod performance status of 0 or 1, Stage IIIB (malignant effusion) or IV disease, and no prior chemotherapy. Treatment was pemetrexed 500 mg/m2 given intravenously and carboplatin area under the serum concentration,time curve = 6 given intravenously on Day 1 every 3 weeks for six cycles; patients could receive additional cycles at the discretion of the treating physician and patient. All patients received folic acid, vitamin B12, and dexamethasone prophylaxis. RESULTS Fifty patients (31 men and 19 women) were treated. The median age was 62 years. Ninety-six percent of patients had Stage IV disease, and 88% had a performance status of 1. The median number of cycles was 6; 15 patients received 8 or more cycles. There was Grade 3/4 neutropenia in 11 (22%) and 2 (4%) patients, respectively; Grade 3/4 thrombocytopenia in 1 (2%) and 0 patients, respectively. Three patients (6%) experienced Grade 3 nonhematologic side effects (diarrhea, neutropenic pneumonia, and fatigue). No patients had sensory neuropathy or alopecia >Grade 1. The partial response rate was 24%, median time to progression 5.4 months, 1-year survival 56.0%, and median survival 13.5 months. CONCLUSIONS This is an active, very well-tolerated regimen. Trials focused on how to integrate this doublet with novel agents are warranted. Cancer 2005. © 2005 American Cancer Society. [source] Cytology of metastatic cervical squamous cell carcinoma in pleural fluid: Report of a case confirmed by human papillomavirus typingDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2009Roberto G. Gamez M.D. Abstract Cervical squamous cell carcinomas are rarely the cause of malignant effusions. Their identification can be relatively easy when keratinizing atypical squamous cells are present, but may be very difficult when only nonkeratinizing malignant cells are present. We present the case of a 47-year-old woman who presented with a large left pleural effusion after having recently completed chemoradiation therapy for stage IIB cervical squamous cell carcinoma. Cytologic examination of the fluid showed a uniform population of single atypical cells with finely vacuolated cytoplasm, ectoendoplasmic demarcation, cell-in-cell arrangements, and short rows of cells with intervening "windows," all features reminiscent of mesothelial cells. No keratinization or three-dimensional cell clusters were identified. A panel of immunohistochemical stains was performed on the cell block material, and the atypical cells were positive for cytokeratin 5/6, p63, and p16 but not for cytokeratin 7, calretinin, WT1, or Ber-EP4 or TTF1. These findings were consistent with metastatic squamous cell carcinoma. HPV DNA determination and typing by PCR confirmed the presence of HPV16 in an aliquot of pleural fluid. This is to our knowledge the first reported case of pleural fluid involved by metastatic squamous cell carcinoma where HPV DNA testing was used to confirm the origin of the metastasis. Despite its rarity, metastatic nonkeratinizing squamous cell carcinoma should be considered when a single cell population of large atypical cells is found in effusions. Immunoperoxidase stains and HPV testing can be performed to establish the diagnosis and confirm the origin from a cervical primary. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] MUC4 is upregulated in ovarian carcinoma effusions and differentiates carcinoma cells from mesothelial cellsDIAGNOSTIC CYTOPATHOLOGY, Issue 12 2007Ben Davidson M.D., Ph.D. Abstract Using gene expression arrays, we recently showed that MUC4 expression is significantly higher in ovarian/primary peritoneal serous carcinoma (OC/PPC) compared to diffuse peritoneal malignant mesothelioma (DMPM). In the present study, we analyzed the anatomic site-related expression of MUC4 in OC/PPC and studied its prognostic role. We additionally studied the ability of MUC4 to differentiate between OC/PPC and reactive mesothelial cells (RMC). OC/PPC effusions (n = 142) and benign reactive effusions (n = 10) were immunostained for MUC4 expression. Immunoreactivity was scored in carcinoma cells and RMC and was compared with tumor cell expression in 60 previously studied primary carcinomas and solid metastases and analyzed for association with clinicopathologic parameters, including survival. MUC4 was detected in carcinoma cells in 141/142 (99%) effusions, with comparable expression in peritoneal and pleural effusions. RMC were present in 72 malignant effusions and were MUC4-negative in all specimens, as well as in the 10 reactive effusions. MUC4 expression in carcinoma cells in effusions was significantly higher than in primary carcinomas and solid metastases (P < 0.001). Higher MUC4 expression was seen in tumors from older (>60 year) patients (P = 0.049). No association was found between MUC4 expression and other clinicopathologic parameters, including survival. MUC4 is universally expressed in OC/PPC effusions and is upregulated at this anatomic site compared to primary carcinomas and solid metastases. The data in the present study, together with our earlier report, show that MUC4 is an excellent marker for differentiating OC/PPC from both benign and malignant mesothelial cells. Diagn. Cytopathol. 2007;35:756,760. © 2007 Wiley-Liss, Inc. [source] Comparison of antibodies to HBME-1 and calretinin for the detection of mesothelial cells in effusion cytology ,DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2001Patricia A. Fetsch M.T. (A.S.C.P.) Abstract The distinction of mesothelial cells in cytologic samples is often a diagnostic challenge. This is particularly true in potentially malignant effusions in which reactive mesothelial cells may simulate adenocarcinoma (ACA) cells, and in the differentiation of ACA vs. mesothelioma. We sought to determine the superior antibody for the positive identification of mesothelial cells in these circumstances. Cell block sections of 25 reactive and 8 malignant mesothelioma effusions were immunostained with an avidin-biotin procedure, using antibodies to HBME-1 and calretinin. No pretreatment of samples was necessary for the HBME-1-stained slides; microwave antigen retrieval was performed on all slides stained for calretinin. A negative control was performed on each sample. The staining intensity of tumor cells was scored on a scale of 0,3+, with the proportion of immunoreactive cells categorized as <25%, 25,50%, 50,75%, and >75%. The predominant staining pattern for HBME-1 was surface, with rare samples also exhibiting cytoplasmic staining as well. The calretinin-staining pattern was cytoplasmic, with peripheral condensation/prominence and accompanying nuclear staining. All samples were immunoreactive with both antibodies. Fifty-five percent (18/33) of samples showed significantly stronger immunoreactivity with calretinin than with HBME-1; 45% (15/33) of samples showed equivalent staining with the two markers. None of the samples in this study showed stronger immunoreactivity with HBME-1 than with calretinin. Sixty-one percent (20/33) of samples stained with HBME-1 at a moderate (2+) intensity. Fifty-five percent (18/33) of samples stained with calretinin at a strong (3+) intensity. While only 12% of samples showed >75% immunoreactivity for HBME-1, 58% of samples showed >75% of cells immunoreactive for calretinin. Calretinin is the preferred marker in identifying mesothelial cells in cytologic samples, showing the highest sensitivity for mesothelial cells, as evidenced by a more intense staining reaction in a higher percentage of cells than with HBME-1. Diagn. Cytopathol. 2001;25:158,161. Published 2001 Wiley-Liss, Inc. [source] Cell microarray platform for anticancer drug development,DRUG DEVELOPMENT RESEARCH, Issue 5 2007Min-Jung Lee Abstract Pharmacodynamic assessment of whether a drug has interacted with and modified its target is an essential component of molecularly targeted clinical trials. Although many trials are written with the intent to assess tumor biopsies, if available, thus far the great majority of early drug trials have used peripheral blood mononuclear cells (PBMC) as a tumor surrogate. Typically, PBMC are studied by low-throughput techniques such as Western blot. We present the use of a cell-based tissue microarray for assessment of anticancer drug activity in vivo. We demonstrate the utility of this technique for analysis of protein hyperacetylation in response to treatment with the histone deacetylase inhibitor, SNDX-275 in PBMC treated in vitro and in PBMC and bone marrow aspirates from patients in Phase I clinical trials with SNDX-275. We demonstrate that the cell microarray can be used to measure drug response in a high-throughput manner, allowing analysis of an entire trial on one or two glass slides. The cell microarray technique brings the advantages of the tissue microarray platform to the pharmacodynamic assessment of single cells, such as those isolated from bone marrow aspirates, fine needle aspirates, or malignant effusions, and to analysis of PBMC, the most commonly studied surrogate in oncology trials. Drug Dev Res 68:226,234, 2007. Published 2007 Wiley-Liss, Inc. [source] Role of pleural viscosity in the differential diagnosis of exudative pleural effusionRESPIROLOGY, Issue 2 2007Ozkan YETKIN Objective and background: Determining the aetiology of an effusion involves assessing if it is an exudate or a transudate. However, a reliable test for determining the aetiology of a pleural effusion is lacking. Pleural viscosity has a high sensitivity and specificity and a high positive and negative predictive value for discriminating exudative and transudative pleural effusions. The aim of this study was to use pleural fluid viscosity to discriminate between various aetiologies of exudative effusions, namely malignant, parapneumonic and tuberculous. Methods: Seventy consecutive patients (24 women, 46 men, mean age = 67 years) with exudative pleural effusion due to pneumoniae in 24 patients, tuberculous pleurisy in 21 and lung cancer in 25 were studied prospectively. Measurements of pleural fluid and plasma viscosity were performed using Brookfield DV-II viscometer. Results: Pleural viscosity and pleural LDH were highest in the tuberculous pleurisy patients and lowest in the lung cancer patients. Pleural viscosity ,1.57 was found to be indicative of tuberculous pleurisy with a sensitivity of 100% and specificity of 95%. Pleural viscosity <1.39 was found to be indicative of lung cancer with a sensitivity of 100% and specificity of 94%. Pleural viscosity was significantly correlated with pleural albumin (r = 0.34, P = 0.004), protein (r = 0.40, P = 0.001), LDH (r = 0.70, P < 0.001) and plasma viscosity (r = 0.44, P < 0.001), having the most significant value with pleural LDH. Conclusion: The pleural fluid viscosity of patients with parapneumonic, tuberculous and malignant effusions are significantly different from each other. Among these groups, tuberculous effusions had the highest viscosity, and malignant effusions from lung cancer the lowest. [source] Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma,,CANCER, Issue 8 2005Sivan Elloul M.Sc. Abstract BACKGROUND It was demonstrated previously that the Snail family of transcription factors and Smad-interacting protein 1 (Sip1) regulate E-cadherin and matrix metalloproteinase 2 (MMP-2) expression, cellular morphology, and invasion in carcinoma. For the current study, the authors analyzed the relation between the expression of Snail, Slug, and Sip1; the expression of MMP-2 and E-cadherin; and clinical parameters in patients with metastatic ovarian and breast carcinoma. METHODS One hundred one fresh-frozen, malignant effusions from patients who were diagnosed with gynecologic carcinomas (78 ovarian carcinomas and 23 breast carcinomas) were studied for mRNA expression of Snail, Slug, Sip1, MMP-2, and E-cadherin using reverse transcriptase-polymerase chain reaction analysis. Snail mRNA and E-cadherin protein expression levels also were studied in ovarian carcinoma effusions using in situ hybridization and immunocytochemistry. The results were analyzed for possible correlation with clinicopathologic parameters in both tumor types. RESULTS E-cadherin mRNA expression was lower in breast carcinoma (P = 0.001), whereas Snail expression was higher (P = 0.003). The Snail/E-cadherin ratio (P < 0.001) and the Sip1/E-cadherin ratio (P = 0.002) were higher in breast carcinomas. Sip1 mRNA expression (P < 0.001) and Slug mRNA expression (P < 0.001) were correlated with the expression of MMP-2 in ovarian carcinomas. The Sip1/E-cadherin ratio was higher in primary ovarian carcinomas at the time of diagnosis compared with postchemotherapy ovarian carcinoma effusions (P = 0.003), higher in Stage IV tumors compared with Stage III tumors (P = 0.049), and higher in pleural effusions compared with peritoneal effusions (P = 0.044). In a univariate survival analysis of patients with ovarian carcinoma, a high Sip1/E-cadherin ratio predicted poor overall survival (P = 0.018). High E-cadherin mRNA expression predicted better disease-free survival (P = 0.023), with a similar trend for a low Slug/E-cadherin ratio (P = 0.07). High Snail mRNA expression predicted shorter effusion-free survival (P = 0.008), disease-free survival (P = 0.03), and overall survival (P = 0.008) in patients with breast carcinoma. CONCLUSIONS Transcription factors that regulate E-cadherin were expressed differentially in metastatic ovarian and breast carcinoma. Snail may predict a poor outcome in patients who have breast carcinoma metastatic to effusions. E-cadherin expression generally was conserved in effusions from patients with ovarian carcinoma, but the subset of patients with postulated Sip1-induced repression of this adhesion molecule had a significantly worse outcome. This finding was in agreement with the stronger suppression of E-cadherin by Snail and Sip1 in breast carcinoma effusions, a clinical condition associated with extremely poor survival. Cancer 2005. © 2005 American Cancer Society. [source] Human epithelial ovarian carcinoma cell-derived cytokines cooperatively induce activated CD4+CD25,CD45RA+ naïve T cells to express forkhead box protein 3 and exhibit suppressive ability in vitroCANCER SCIENCE, Issue 11 2009Xiaofeng Zhao Regulatory T cells play an important role in tumor escape from host antitumor immunity. Increased frequencies of CD4+CD25+ regulatory T cells have been documented in the tumor sites, malignant effusions, and peripheral blood of patients with ovarian carcinoma. However, the mechanism involved remains unclear. In the present study, we collected high-purity human CD4+CD25,CD45RA+ naïve T cells by microbead cell separation. These cells did not express FOXP3 by single-cell analysis, and few cells expressed FOXP3 when they were activated with anti-CD3/CD28 dual signal. However, more cells expressed FOXP3 when the supernatant of human epithelial ovarian carcinoma cell culture was added, yet not the supernatant of normal human ovarian surface epithelia cell culture. Neutralization assays revealed that neutralizing antibody against transforming growth factor , (TGF-,), interleukin-10, and interleukin-4 did not abrogate elevated FOXP3 expression induced by carcinoma cell culture supernatant, whereas neutralizing leukemia inhibitory factor (LIF) partially abrogated FOXP3 expression, but LIF alone could not increase FOXP3 expression in activated naïve T cells. Further, an in vitro coculture suppression assay showed that these cells could suppress the proliferation of autologous CD4+CD25,CD45RA, T cells. In summary, our findings show that ovarian carcinoma cells are able to induce expression of FOXP3 and exhibit suppressive ability in activated naïve T cells by producing soluble substances, and multiple cytokines involve in the induction of FOXP3 expression. (Cancer Sci 2009) [source] | ||||||||||