Search

Background Dasatinib is a potent BCR-ABL1 and Src family tyrosine kinase inhibitor. It is approved at a dose of 100 mg orally daily for the treatment of chronic myeloid leukemia in chronic phase (CML-CP). This dose schedule is associated with myelosuppression and pleural effusions. Anecdotal data suggest that lower doses may be as effective and less toxic. The aim of this study was to assess the efficacy and safety of a lower dose of dasatinib (50 mg daily) in patients with newly diagnosed CML-CP. Methods Seventy-five patients with newly diagnosed CML-CP received dasatinib 50 mg daily. The eligibility and response criteria were standards used in previous protocols. Results At a median follow-up of 9 months, 60 patients were evaluable for a response at 3 months. The rates of patients achieving BCR-ABL1 transcript levels ≤ 10% and ≤ 1% at 3 months by the International Standard were 93% and 72%, respectively. The rates of complete cytogenetic response by conventional cytogenetics or fluorescence in situ hybridization at 6 and 12 months were 86% and 88%, respectively. At 12 months, 79%, 71%, and 46% of the patients had achieved a major molecular response, a molecular response with a 4.0-log reduction, and a molecular response with a 4.5-log reduction, respectively. Nine patients had a dose interruption for ≤14 days. Only 1 patient developed a pleural effusion requiring a dose reduction to 20 mg. All patients remained alive and with no transformation so far. Conclusion Dasatinib 50 mg daily is active and well tolerated in patients with newly diagnosed CML-CP. It should be further explored as a new potential standard-of-care option for chronic myeloid leukemia. Cancer 2018;124:2740-2747. © 2018 American Cancer Society.

BACKGROUND: Inhibiting src kinases (non-receptor tyrosine kinase signaling intermediates) reduces melanoma cell proliferation and invasion. Dasatinib inhibits c-kit, PDGFβR, and EPHA2 and src kinases c-src, c-Yes, Lck, and Fyn. A phase 2 trial of dasatinib in melanoma was conducted to assess response rate (RR), progression-free survival (PFS), and toxicity. METHODS: Adults with stage 3/4 chemotherapy-naive unresectable melanoma were eligible. Dasatinib was initially administered at 100 mg twice daily continuously to 17 patients. Due to toxicity, the starting dosage was decreased to 70 mg twice daily. Tumor assessments occurred every 8 weeks. RESULTS: Thirty-nine patients were enrolled, 36 of whom were evaluable for activity and toxicity. Five, 4, and 3 patients had acral-lentiginous, ocular, or mucosal primaries, respectively. Two patients had confirmed partial responses lasting 64 and 24 weeks (RR 5%). Three patients had minor responses lasting 136, 64, and 28 weeks, and 1 patient who was responding discontinued due to noncompliance. The median PFS was 8 weeks; the 6-month PFS rate was 13%. One patient with an exon-13 c-kit mutation had a partial response, whereas disease in another patient with an exon-11 c-kit mutation progressed. Common toxicities were fatigue, dyspnea, and pleural effusion. CONCLUSIONS: Daily dasatinib has minimal activity in unselected melanoma patients, excluding those with c-kit mutations. The study did not meet the prespecified endpoints of 30% response rate or 6-month PFS. Dasatinib was poorly tolerated overall, often requiring dose reduction or interruption. Because activity was observed in a small subset without c-kit mutations, identifying predictive biomarkers is important for future development of dasatinib in melanoma alone or in combination trials. Cancer 2011. © 2010 American Cancer Society.

BACKGROUND: The current study was conducted to assess the efficacy and toxicity of sorafenib as front-line therapy in patients with stage IIIB (pleural effusion) or IV nonsmall cell lung cancer (NSCLC). METHODS: Patients received sorafenib 400 mg twice daily by mouth continuously, and were evaluated every 2 weeks during the first 8 weeks. Patients who manifested clinical progression during this period proceeded to receive standard of care. The primary endpoint was confirmed objective tumor response. A 2-stage Fleming design was used such that if at most 1 confirmed partial response (PR) or complete response was observed in the first 20 patients (stage 1), the treatment would be considered ineffective, and further enrollment would be discontinued. RESULTS: Only 1 PR was observed in the first 20 patients. By the time of study closure, 5 additional patients who were already being screened for study inclusion were enrolled. Of the 25 patients (15 women, 10 men; 4 stage IIIB, 21 stage IV; median age, 67 years [range, 45-85 years]), there were 3 (12%) PRs and 6 (24%) cases with stable disease observed. The median time-to-progression and progression-free survival was 2.8 months. Seven (28%) patients remained progression-free at 24 weeks. No grade 3 or higher hematologic adverse events were observed. Thirteen (52%) patients had a grade 3 nonhematologic adverse event, with fatigue (20%), diarrhea (8%), and dyspnea (8%) being the most common. CONCLUSIONS: Sorafenib is not effective as front-line therapy in the general unselected NSCLC population. The window of opportunity design is feasible for estimating the activity of novel compounds. Cancer 2010. © 2010 American Cancer Society.

Dasatinib is a highly potent Bcr-Abl inhibitor that is approved for the treatment of imatinib-resistant or -intolerant chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia. Across a series of phase 2 and 3 trials, dasatinib was associated with durable treatment responses in all phases of the disease and was well tolerated. For this article, the authors reviewed available information on specific side effects associated with the use of dasatinib. On the basis of more than 2 years' experience of dasatinib treatment during clinical trials, they provide practical recommendations for side-effect management.

BACKGROUND Malignant pleural effusion of advanced lung adenocarcinoma may be a valid source for detection of biomarkers, such as N-glycosylated proteins (N-GP), because tumor cells grow during weeks in this liquid. The authors aimed for creation of N-GP effusion profiles from routine cytology specimens to detect relevant biomarkers. METHODS Hundred microliters of malignant pleural effusions of 5 patients with lung adenocarcinoma and 5 nonmalignant controls were used for triplicate N-GP capture by solid-phase extraction. After trypsin digest and PNGase F release, a liquid chromatography separation connected online to a tandem mass spectrometer was performed by liquid chromatography/tandem mass spectrometry (LC/MS/MS). RESULTS In the total of 10 samples, 170 and 278 nonredundant proteins were detected with probabilities of ≥.9 and ≥.5, respectively. The specificity for the N-glycomotif was 88% at P ≥ .9. Penetration into the moderate to low protein concentration range (μg-ng/mL) occurred, and several proteins associated with tumor progression or metastasis were identified, including CA-125, CD44, CD166, lysosome-associated membrane glycoprotein 2 (LAMP-2), multimerin 2, and periostin. MS identifications were correlated with the corresponding immunoreactivity in either effusion fluid or tumor tissue. CONCLUSIONS In conclusion, reduction of sample complexity by N-GP capturing allows detection of proteins in the μg to ng/mL range. Pleural effusion is a useful source for biomarker research in lung cancer. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.

BACKGROUND The diagnosis of malignant mesothelioma (MM) in serous effusions is difficult but may be achieved by the application of adjuvant methods. METHODS The authors cytologically diagnosed 33 effusions as suspicious or positive for MM cells by using DNA-image cytometry (DNA-ICM), immunocytochemistry and AgNOR analysis. The authors further detected 9p21 deletions by chromosomal fluorescence in situ hybridization (FISH). In addition, 31 cases of metastatic carcinomas and 39 of tumor cell-negative effusions were investigated. All diagnoses were confirmed by histologic and/or clinical follow-up. RESULTS DNA aneuploidy was found in 71% of MMs, 100% of metastatic carcinomas, and in none of the negative effusions. Calretinin was positive in 100% of MMs, in none of the metastatic carcinomas, and in 94.9% of negative effusions. BerEP4 showed positivity in 15.6% of MMs, 87.1% of metastatic carcinomas, and in none of the negative effusions. With AgNOR analysis, 89.3% of MMs and 96.7% of metastatic carcinomas showed ≥2.5 AgNOR dots as satellites and ≥4.5 as total AgNOR counts. 9p21 deletions were demonstrated in 90.9% of MM cases, 45.2% of metastatic carcinomas, and in none of the negative effusions. By cytology alone, 81.8% of MMs were identified unequivocally. Addition of DNA-ICM improved the prevalence of tumor cell detection to 87.9% and of AgNOR analysis to 97%. The introduction of 9p21 deletions by FISH improved this prevalence to 100%. CONCLUSIONS Because of these results, the authors propose the sequential application of immunocytochemistry, DNA-ICM, and AgNOR analysis to establish a cytological diagnosis of malignant mesothelioma in serous effusions. In persistent doubtful diagnoses, the authors recommend fluorescence in situ hybridization to analyze the 9p21 deletion. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.

BACKGROUND. Immunohistochemistry is helpful in distinguishing metastatic carcinoma from atypical mesothelial cells; however, it is not useful in differentiating atypical mesothelial cells from malignant mesothelial cells. K homolog domain containing protein overexpressed in cancer (KOC), a member of the insulin-like growth factor mRNA-binding protein (IMP) family, also known as L523S and IMP3, is expressed during embryogenesis and in various malignancies. Using a mouse monoclonal antibody (L523S) against KOC, KOC expression was investigated in malignant tumors and reactive mesothelial cells in serous effusions. METHODS. Seventy-six cases with paraffin-embedded pleural, pericardial, and peritoneal serous effusion cell blocks including 60 malignant serous effusions (11 malignant pleural mesotheliomas and 49 metastatic carcinomas) and benign pleural effusions (14 cases with reactive mesothelial cells and 2 cases with atypical cells with uncertain significance) were selected for immunohistochemical analysis with L523S, calretinin, and CK5/6. RESULTS. Immunohistochemical studies showed that positive staining for KOC of variable degrees of intensity was observed in 47 of 60 cases in malignant serous effusions including 10 of 11 mesotheliomas and 36 of 49 metastatic carcinomas. The associated reactive mesothelial cells were negative for KOC but positive for calretinin and CK5/6. All 11 malignant mesotheliomas exhibited positivity for calretinin, and 9 of 11 cases had CK5/6 staining. In addition, 16 cases that were originally diagnosed either as pleural effusions with reactive mesothelial cells (14) or atypical cells with uncertain significance (2) were also tested for KOC expression. Interestingly, 3 of 16 cases exhibited various degrees of positivity for KOC, 2 of which were diagnosed as lung adenocarcinoma with a recurrence after tumor resection and 1 as malignant pleural mesothelioma. CONCLUSIONS. Anti-L523S antibody is a useful marker for the detection of malignant cells in serous effusions and it can have significant utility in differentiating reactive mesothelial cells from malignant mesothelioma and metastatic carcinoma in combination with calretinin and CK5/6 staining. Cancer (Cancer Cytopathol) 2008. © 2007 American Cancer Society.

BACKGROUND Radiofrequency ablation (RFA) has become an accepted alternative for treating intrathoracic malignancies; however, the incidence and characteristics of peri- and postprocedural complications are not well described. The purpose of the study was to assess the safety and technical feasibility of percutaneous RFA in unresectable intrathoracic malignancies. METHODS Percutaneous RFA was performed in patients with intrathoracic malignancies between June 2001 and December 2004. In total, 366 tumors were treated in 137 patients in 211 sessions. All patients were nonsurgical candidates or had refused surgery. Three hundred and thirty-six lesions were subjected to RFA for the treatment of metastases and 30 lesions for primary lung carcinoma. RESULTS Although no procedural mortality occurred, 2 patients died during the course of the study because of intractable pneumothorax and massive hemoptysis (0.9%). The overall major complication rate was 17.1% (pneumothoraces requiring tube drainage in 25, pleuritis in 6, pleural effusion requiring tube drainage in 4, lung abscess in 1, and intrapulmonary hemorrhage with hemothorax in 1). Minor complications included pneumothoraces not requiring tube drainage in 108 sessions, pleural effusion without drainage in 34, hemosputum in 9, nausea and/or vomiting in 3, subcutaneous emphysema in 3, cough in 2, skin burn in 2, atelectasis in 1, and subileus in 1. High fever and/or chest pain were seen in 33.8% and 39.3% of patients, respectively. CONCLUSIONS With over 200 procedures, RFA appears to be a safe and minimally invasive option with negligible mortality and little morbidity in selected patients with unresectable intrathoracic malignancies. Cancer 2007. © 2007 American Cancer Society.

BACKGROUND Advanced breast carcinoma almost always leads to a malignant pleural effusion, conditioning the performance status of patients and consequently quality of life. The treatment of malignant pleural effusion should be a priority in the management of such patients. The results of videothoracoscopic approach (VATS) chemical pleurodesis was analyzed in patients with recurrent pleural effusion from breast carcinoma. METHODS From October 1998 to June 2004, 71 consecutive patients with breast carcinoma-related pleural effusion were treated by the same thoracic-surgeon team with intracavitary nebulization of 8 g of asbestos-free sterilized talc via VATS. Multiple pleural biopsies were performed to determine biologic characteristics of recurrent disease. RESULTS Talc pleurodesis was performed in all cases, with no intraoperative or postoperative complications. Median length of hospital stay was 5 days (range, 5–8). The overall success rate of the surgical procedure was 89% (confidence interval [CI], 79–95%) with a mean follow-up of 22 months (range, 2–81 mos). The overall survival time was 17 months (range, 2–80). Biopsies showed a switch on receptor status and c-erB-2 status from negative (primary tumor) to positive (pleural metastasis) in 11 (15%) patients. In another 7 (9.8%) patients, we obtained completely new information that was hitherto unknown. CONCLUSION Talc pleurodesis via VATS is an effective and safe procedure that yields a high rate of success at the first attempt and achieves long-term control of malignant pleural effusion due to breast carcinoma. Concomitant biopsies performed during the VATS procedure were a determining factor in the subsequent decision-making process. Cancer 2006. © 2005 American Cancer Society.

BACKGROUND The authors conducted a pilot clinical trial to explore the vaccination of patients with late-stage lung carcinoma with dendritic cells (DCs) pulsed with necrotic tumor cells derived from malignant pleural effusion specimens, and to evaluate the antitumor immune response induced by this therapy. METHODS Autologous DCs were generated by culturing adherent mononuclear cells with interleukin-4 and granulocyte-macrophage–colony-stimulating factor for 7 days. Day-7 DCs were cocultured overnight with autologous necrotic tumor cells derived from pleural effusion specimens to allow internalization of tumor antigens. DCs were then treated with tumor necrosis factor-alpha for 16 hours. The antigen-loaded DCs were injected into each patient's inguinal lymph nodes under sonographic guidance. Eight patients with late-stage nonsmall cell lung carcinoma were treated in this manner. Patients were vaccinated once weekly for 4 weeks and then boosted twice biweekly. RESULTS The authors found that there was no Grade II/III toxicity and autoimmune response in all patients after intranodal injection of the DC vaccine. Minor to moderate increases in T-cell responses against tumor antigens were observed after DC vaccination in six of eight patients. Five patients had progressive disease. One patient had minor tumor response and two patients had stable disease. The two patients who had longer disease control also had better T-cell responses. CONCLUSIONS The results indicated that it was feasible to immunize patients with lung carcinoma intranodally with DCs pulsed with necrotic tumor cells enriched from pleural effusion specimens, and this approach may generate T-cell responses and provide clinical benefit in some patients. Cancer 2005. © 2005 American Cancer Society.

BACKGROUND The most common causes of malignant pleural effusions in women are metastatic lung carcinomas and breast carcinomas. It is often very difficult to distinguish between breast carcinomas and other metastatic carcinomas when they share a similar morphology and a similar cytokeratin profile (CK7-positive/CK20-negative [CK7+/CK20−]). To better differentiate between metastatic mammary carcinomas and other metastatic carcinomas in pleural effusion cytology, the authors studied the potential use of a novel antibody, CRxA-01, which was identified by a cDNA subtraction library, together with a well characterized antibody against mammaglobin. METHODS A computer search for patients with malignant pleural effusion specimens between January 1992 and November 2002 generated 228 patients, 71 of whom had cell block material and a known clinical history. Primary malignancies among these patients included 20 breast carcinomas, 32 lung carcinomas, 4 endometrial carcinomas, 9 ovarian carcinomas, 4 gastrointestinal carcinomas, and 2 genitourinary carcinomas. All specimens were immunostained with anti-CK7, CK20, CRxA-01, and mammaglobin antibodies. Only CK7-positive/CK20-negative (CK7+/CK20−) specimens were included in the current study, and only definitive membranous staining for CRxA-01 and cytoplasmic staining for mammaglobin were considered to be positive. RESULTS For patients with metastatic breast carcinomas, mammaglobin was positive in 11 of 20 (55%) tissue specimens and CRxA-01 was positive in 12 of 20 (60%) tissue specimens. When CRxA-01 and mammaglobin were used together, 16 of 20 (80%) tissue specimens were positive for mammaglobin or/and CRxA-01 antibodies. This staining pattern was not seen for tissue specimens from patients with other metastatic carcinomas. Two of 4 (50%) uterine carcinoma specimens and 6 of 9 (67%) ovarian carcinoma specimens were positive for CRxA-01 only. CONCLUSIONS CRxA-01 and mammaglobin were expressed in most metastatic breast carcinoma specimens. Other CK7+/CK20− carcinoma specimens did not express mammaglobin and showed weak or negative staining for CRxA-01. When used together, CRxA-01 and mammaglobin greatly improved the sensitivity and specificity for the detection of metastatic breast carcinoma in pleural effusion specimens. Cancer (Cancer Cytopathol) 2004. © 2004 American Cancer Society.

BACKGROUND The mortality rate associated with fever accompanied by pulmonary infiltrates after chemotherapy for hematologic malignancies remains higher than the corresponding rate associated with febrile neutropenia without pulmonary infiltrates. Nonetheless, few studies have focused on the factors that predict outcome for patients with lung infiltrates. The purpose of the current study was to construct a risk model for clinical use by assessing the factors that affect outcome for patients with fever and pulmonary infiltrates. METHODS A historical cohort of 110 patients with hematologic malignancies who developed fever and pulmonary infiltrates was examined. Using parameters for which data were available at the onset of lung infiltrates, univariate and multivariate analyses were performed to assess factors affecting outcome. After a value of one point was assigned to each significant variable, a prediction score was calculated for each patient; scores were used to generate a system for identifying patients with a low risk of death due to fever accompanied by pulmonary infiltrates. RESULTS The crude mortality rate associated with pulmonary infiltrates was 23%; factors associated with cure included a favorable change in white blood cell counts (odds ratio [OR], 5.6; 95% confidence interval [CI], 1.7–18.9; P = 0.001), C-reactive protein levels < 10 mg/dL (OR, 4.6; 95% CI, 1.6–13.8; P = 0.001), and serum albumin levels ≥ 3 g/dL (OR, 3.2; 95% CI, 1.4–7.3; P = 0.004). Low-risk patients (risk score, 2–3) and high-risk patients (risk score, 0–1) had survival rates of 95% and 46%, respectively (P < 0.0001). The risk model had a specificity of 88% and a positive predictive value of 95%. CONCLUSIONS The risk model tested in the current study accurately predicted the survival of patients with hematologic malignancies who developed fever with pulmonary infiltrates. Once prospectively validated, the model could be used to select patients for trials involving novel diagnostic and therapeutic strategies. Cancer 2004. © 2004 American Cancer Society.

BACKGROUND The distinction between benign reactive mesothelial cells and malignant mesothelial cells in serous effusions is difficult and has an unusually high false negative rate. Unfortunately, there are no generally accepted markers to distinguish between benign reactive and malignant mesothelial cells. Homozygous deletion of CDKN2A is frequent in mesothelioma (present in > 70% of tumors). Therefore, detection of CDKN2A deletion by fluorescence in situ hybridization (FISH) was evaluated as an ancillary test in the cytologic diagnosis of malignant mesothelioma. METHODS Dual-color FISH for CDKN2A and chromosome 9 centromere was performed on cytolyt-fixed Thinprep slides from 6 cytologically suspicious and 7 cytologically positive effusions (all with histologically confirmed mesothelioma) and in 19 cytologically benign effusions (14 pleural effusions, 3 pericardial effusions, and 2 abdominal fluid specimens). Specimens containing ≥ 15 nuclei that lacked signals for CDKN2A but showed at least 1 signal for chromosome 9 centromere were considered positive. In samples with negative cytology, the nuclei of at least 100 mesothelial cells were evaluated; whereas, in specimens with positive or suspicious cytology, counting nuclei was done only if < 15% of nuclei showed homozygous loss of CDKN2A. RESULTS Homozygous deletion was detected in mesothelial cells in six of seven specimens with positive cytology and in six of six specimens with suspicious cytology. Cytologically, there were numerous tumor cells in a single positive specimen without homozygous deletion. All 19 cytologically negative specimens were negative for CDKN2A deletion. CONCLUSIONS The detection of homozygous CDKN2A deletion by FISH would have been helpful in confirming a diagnosis of mesothelioma over reactive mesothelial cells in 12 of 13 samples with positive or suspicious cytology. Further studies on larger series of patients with suspicious cytology are needed to evaluate the validity and efficiency of this approach for improving the diagnostic accuracy of effusion cytology. Cancer (Cancer Cytopathol) 2003;99:51–56. © 2003 American Cancer Society.

BACKGROUND Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing transcription factor selectively expressed in thyroid, lung and diencephalon. It has been shown to label pulmonary adenocarcinoma, thyroid tumors, and small cell carcinoma (pulmonary and extrapulmonary) with relatively high sensitivity and specificity. The usefulness of this immunostain in cytology specimens has not been thoroughly discussed in the literature. METHODS The authors evaluated 36 effusion cytology cases (17 pleural effusion, 18 ascitic fluid, and 1 pericardial effusion) diagnosed as metastatic adenocarcinoma and with cell blocks prepared from the file of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a three-year period from 1998 to early 2001. The clinical, radiologic, cytologic, and histologic (if any) findings were reviewed. A provisional diagnosis of the primary site was deduced for each of the 36 cases by clinical, radiologic, and/or histologic correlation. Immunohistochemical study was performed on the cell block sections of the effusion cytology specimens using mouse monoclonal antibody against TTF-1, after microwave heat-antigen retrieval. The results were correlated with the primary origin of the metastatic adenocarcinoma. RESULTS Among the 17 cases of metastatic pulmonary adenocarcinoma, 15 cases showed nuclear staining for TTF-1 in most of the tumor cells (sensitivity, 88.2%). None of the 19 cases of metastatic extrapulmonary adenocarcinoma expressed TTF-1 (specificity, 100%). CONCLUSIONS The current study validates TTF-1 as a highly sensitive and specific immunomarker for distinguishing between metastatic pulmonary and extrapulmonary adenocarcinoma in effusion cytology specimens, which are known to be associated with intrinsic artifact due to less than ideal cellular preservation. Cancer (Cancer Cytopathol) 2002;96:43–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10310

BACKGROUND Ascites fluid or a pleural effusion are common events in metastatic carcinoma, but they also can be associated with several other medical conditions. The standard for determination of malignancy in these situations is cytologic evaluation of these fluids. Although this method is frequently successful, there are times when it fails, even when the patient has a malignancy, either because of insufficient cells in the fluid or for other reasons. This study addresses this problem taking advantage of the recent advances in technology for detection of rare epithelial cells in liquid specimens. METHODS The authors examined fluid specimens from 59 patients to determine the frequency of recovery of epithelial cells compared with that achieved by conventional cytopathology. The Dynal CELLection Epithelial Enrich (Dynal AS, Oslo, Norway) method was used. This method is based on immunomagnetic selection of cells binding to EpCAM antibodies. Carcinoma cells were confirmed by morphology and, when there was sufficient material, by E-cadherin staining. RESULTS Grouping the cases by cytologic diagnosis, the authors found malignant cells using the cell enrichment assay in 11 of 12 malignant cases, 2 of 5 atypical cases, and 3 of 42 negative cases. Further investigations were conducted on the five cases that were cytologically negative or atypical but yielded epithelial cells after immunomagnetic enrichment. Four cases ultimately were proven malignant by other methods and one had incomplete follow-up. CONCLUSIONS The new methods available for epithelial cell enrichment in liquids may be used successfully on cytologic fluid specimens and may lead to increased sensitivity for detection of malignancy, and consequently more accurate staging. Cancer 2002;94:205–11. © 2002 American Cancer Society.

BACKGROUND A small number of microwave electrode insertions and microwave irradiations were used to obtain complete tumor necrosis in hepatocellular carcinomas (HCC) measuring > 2.0 cm but ≤ 3.0 cm in greatest dimension. The efficacy of combining transcatheter arterial chemoembolization (TACE) with subsequent percutaneous microwave coagulation therapy (PMCT) was assessed in this study. METHODS Eighteen patients with cirrhosis and HCCs measuring > 2.0 cm but ≤ 3.0 cm in greatest dimension underwent TACE followed within 1–2 days by ultrasonographically guided PMCT. RESULTS On dynamic computed tomography, 17 of the 18 patients showed complete necrosis of their tumor lesions and the treated tumor margins (≥ 5 mm). Necroses of tumors and noncancerous margins surrounding the tumors were obtained using 4 microwave irradiations (1 session) in 14 patients, 5 microwave irradiations (2 sessions) in 2 patients, and 6 microwave irradiations (2 sessions) in 1 patient. The follow-up period was short (12–31 mos), and all patients remained alive. No local recurrences in the treated areas were detected. No fatal complications were observed. Pleural effusion was observed in 1 patient only. CONCLUSIONS This combined therapy of PMCT applied within 1–2 days of TACE effectively treated HCCs measuring > 2.0 cm but ≤ 3.0 cm in greatest dimension. A small number of microwave electrode insertions and microwave irradiations were used. Cancer 2000;89:1245–51. © 2000 American Cancer Society.

BACKGROUND The differential diagnosis between reactive mesothelial cells (RMs), malignant mesotheliomas (MMs), and adenocarcinomas (ACs) is often difficult in cytologic specimens, and the utility of various immunohistochemical markers have been explored. Because recent immunohistologic studies have suggested that E-cadherin (E-cad) and calretinin (Cal) may be useful markers for epithelial and mesothelial differentiations, respectively, the authors investigated their utility in cytologic diagnosis. METHODS In this retrospective study, immunostaining was performed on smears retrieved from Papanicolaou-stained slides of effusions using the labeled streptavidin-biotin method. Sixteen cases of RM, 9 cases of MM, and 52 cases of AC from various sites, including 13 pulmonary primaries, were examined with primary antibodies against E-cad and Cal. RESULTS The positive rates for E-cad and Cal, respectively, were as follows: RM, 0/16 (0%) and 16/16 (100%); MM, 9/9 (100%) and 8/8 (100%); and AC, 45/52 (86.5%) and 0/51 (0%). The E-cad expression by neoplastic cells was strongest in the intercellular junctions, and poorly differentiated neoplastic cells in the single cell form showed the weakest expression. CONCLUSIONS In contrast to the results of previous immunohistochemical studies, the current study indicates that MMs constantly express E-cad, whereas RMs lack its expression in cytologic specimens, which would be useful in the differential diagnosis between the two. On the other hand, E-cad expression is not reliable for distinguishing AC from MM. The Cal expression can be a very useful marker for the distinction between AC and the mesothelial lineage. The combined immunostaining for E-cad and Cal has utility in differential diagnosis among RM, MM, and AC. Cancer (Cancer Cytopathol) 2000;90:55–60. © 2000 American Cancer Society.

BACKGROUND Evaluation of effusion specimens for the presence of adenocarcinoma often is complicated by the presence of reactive mesothelial cells that can mimic adenocarcinoma. Ancillary studies, in particular immunohistochemistry, can be helpful in making this distinction. MOC-31 is an antibody that recently was reported to be useful in distinguishing adenocarcinoma from mesothelioma in tissue specimens. In this study we examined the utility of this antibody in pleural effusions. METHODS Eighty-nine archival, formalin fixed, paraffin embedded cell blocks representing 59 adenocarcinomas, 12 other neoplasms (including 6 mesotheliomas), and 18 reactive effusions were retrieved. After protease digestion, recut slides were immunostained with the MOC-31 antibody utilizing a modified avidin-biotin complex technique. Only membrane-based reactivity was considered as positive. RESULTS In two adenocarcinomas there was insufficient material remaining in the cell block. Among the 57 remaining cases, reactivity was observed in 54 cases. Reactivity also was observed in one of six mesotheliomas and one small cell carcinoma. The remaining cases, including all 18 reactive effusions, were nonreactive. In distinguishing adenocarcinoma from reactive mesothelial cells, the presence of MOC-31 reactivity was found to be 95% sensitive and 100% specific with a positive predictive value of 100% and a negative predictive value of 95%. CONCLUSIONS MOC-31 is useful in differentiating between adenocarcinoma and reactive mesothelial cells in pleural effusion specimens. Cancer (Cancer Cytopathol) 1999;87:390–4. © 1999 American Cancer Society.

Background Findings of isolated (disseminated or circulating) tumor cells (ITC) by immunocytochemistry and molecular pathology methods have led to varied interpretations and different applications of the TNM system. Methods An analysis of the relevant literature was undertaken. In addition, optional proposals for the classification of ITC, micrometastasis, and cytologic results in pleural and peritoneal washings are presented. Results Immunocytochemistry has a lower false-positive rate than nonmorphologic methods such as flow cytometry or the polymerase chain reaction; therefore the method(s) used always should be recorded. At the current time, the independent prognostic significance of ITC in regional lymph nodes and in the general circulation (blood, bone marrow, and other distant sites) is difficult to assess. To enable comparisons of treatment results and to avoid variation in staging, a finding of ITC should not be considered in the TNM and residual tumor (R) classifications, at least not at the current time. However, for future evaluation of their prognostic significance, the respective findings should be documented according to uniform criteria. Conclusions ITC should be distinguished from micrometastasis. To investigate the independent prognostic significance of ITC and of positive lavage cytology, uniform data collection according to the proposed coding schema is recommended.

BACKGROUND The purpose of this study was to compare the effectiveness and safety of a chronic indwelling pleural catheter with doxycycline pleurodesis via tube thoracostomy in the treatment of patients with recurrent symptomatic malignant pleural effusions (MPE). METHODS In this multi-institutional study conducted between March 1994 and February 1997, 144 patients (61 men and 83 women) were randomized in a 2:1 distribution to either an indwelling pleural catheter or doxycycline pleurodesis. Patients receiving the indwelling catheter drained their effusions via vacuum bottles every other day or as needed for relief of dyspnea. RESULTS The median hospitalization time was 1.0 day for the catheter group and 6.5 days for the doxycycline group. The degree of symptomatic improvement in dyspnea and the quality of life was comparable in each group. Six of 28 patients who received doxycycline (21%) had a late recurrence of pleural effusion, whereas 12 of 91 patients who had an indwelling catheter (13%) had a late recurrence of their effusions or a blockage of their catheter after the initially successful treatment (P = 0.446). Of the 91 patients sent home with the pleural catheter, 42 (46%) achieved spontaneous pleurodesis at a median of 26.5 days. CONCLUSIONS A chronic indwelling pleural catheter is an effective treatment for the management of patients with symptomatic, recurrent, malignant pleural effusions. When compared with doxycycline pleurodesis via tube thoracostomy, the pleural catheter requires a shorter hospitalization and can be placed and managed on an outpatient basis. Cancer 1999;86:1992–9. © 1999 American Cancer Society.

BACKGROUND Pleural effusion is reported in up to 20% of patients with non-Hodgkin's lymphoma (NHL), most often at presentation. However, the prognostic implications of such findings are not clear. The majority of the information in the literature is based on minor observational studies or case reports. Therefore, a case-controlled study was performed to verify the clinical significance of pleural effusion in NHL. METHODS Seventeen patients with pleural effusion at the time of presentation of NHL were identified. They were categorized by grade of NHL (based on the Working Formulation). Twenty-nine control patients with similar histopathologic characteristics who had Stage III/IV NHL without pleural effusion were matched to these cases by age, time of diagnosis, and treatment. RESULTS Ten patients with intermediate grade NHL were matched with 23 controls. No statistically significant difference in complete remission or survival rates between these groups was found (P = 0.69 and P = 0.7, respectively). The remission and survival rates also were similar in the subgroup of patients and controls who were treated with aggressive chemotherapy. Similarly, no difference was found in these parameters between four cases and six matched controls with low grade lymphoma. No matched controls were found for the patients with high grade lymphoma, but these patients had an unfavorable outcome. Fourteen of the 17 studied patients had an exudative type of pleural effusion. Thoracentesis yielded a positive cytologic finding in every case. CONCLUSIONS The presence of pleural effusion at the time of presentation of NHL does not adversely affect complete remission or survival rates. Cancer 1998;83:1607-1611. © 1998 American Cancer Society.

BACKGROUND In a previous FONICAP trial, the combination of doxorubicin (D) and cisplatin (P) yielded an objective response rate of 25% and a subjective response rate of 50% in patients with mesothelioma. In human mesothelioma cell lines, mitomycin (M) showed a synergic activity with P and in a recent randomized study, the combination of M and P showed slightly superior activity when compared with the PD regimen. METHODS The authors tested the activity and toxicity of a combination chemotherapy regimen including P, 60 mg/m2, D, 60 mg/m2, and M, 10 mg/m2, all by intravenous infusion on Day 1 every 28 days in a Phase II study. RESULTS Twenty-four chemotherapy-naive mesothelioma patients were enrolled in the study. Patient characteristics were the following: the median age was 58 years; the median performance status was 1; there were 6 Stage I patients, 15 Stage II patients, 2 Stage III patients, and 1 Stage IV patient; and 10 patients had previous asbestos exposure. All patients had pretreatment symptoms: 13 had chest pain, 9 had pleural effusion, and 7 had dyspnea. A total of 78 cycles of chemotherapy were administered. The only significant side effect was myelosuppression, with only 9.5% of patients having Grade 4 toxicity. Among 23 patients evaluable for response, 5 achieved a partial response (20.8%; 95% confidence interval, 7.1-42.1%), 9 had stable disease, and 9 had progressive disease (including 1 early death). One patient was not evaluable because of treatment refusal. A clinical improvement was observed in 7 of 24 patients (29%). CONCLUSIONS The combination of PDM in patients with pleural mesothelioma is feasible and moderately active. However, the observed level of activity is similar to that obtained with other two-drug regimens. Cancer 1997; 79:1897-902. © 1997 American Cancer Society.

Background. Lymphoepithelioma-like carcinoma (LELC), best known to occur in the nasopharynx, can arise in a variety of sites, such as the salivary gland, thymus, lung, stomach, and skin. Primary LELC of the lung is very rare, with only limited information in the literature. Methods. The clinicopathologic features of 11 patients with pulmonary LELC collected from two regional hospitals in Hong Kong are described. Results. The patients, all Chinese, were aged 38 to 73 years (median, 54 years), with equal sex incidence. Two of the 8 patients were smokers. Four presented with coin lesions incidentally discovered on chest X-ray, five with cough and blood-stained sputum, and two with pleural effusion. The tumor formed a discrete (9 patients) or an ill-defined (1 patient) nodule in the lung, or, rarely, showed extensive bilateral pulmonary involvement (1 patient). The major bronchi were not involved except in 1 patient. Three patients had lymph node metastasis at presentation; two of them had bone metastasis, one at presentation and one after 9 months. The tumors had pushing margins, and grew in the form of anastomosing islands and sheets, comprising syncytial-appearing large cells with vesicular nuclei and prominent nucleoli. They were infiltrated by an appreciable number of small lymphocytes and plasma cells. Intratumoral amyloid globules were found in one tumor. In five patients, the tumor showed intraepithelial growth within the small bronchi; this could represent either the in-situ phase of the tumor or pagetoid spread into the bronchial epithelium. The neoplastic cells of all patients harbored Epstein–Barr virus (EBV) as demonstrated by in situ hybridization for EBV-encoded small nuclear RNAs. All eight Asian patients with pulmonary LELC previously reported in the literature similarly have been EBV-positive, whereas the four reported Caucasian patients all have been EBV-negative. Conclusion. Lymphoepithelioma-like carcinoma of lung occurring in Asians is an EBV-associated neoplasm; it also appears to occur at a higher frequency in Asians than Caucasians. It usually presents as a solitary sub-pleural nodule, and there is no strong association with cigarette smoking. Most patients have early stage disease at presentation. From the limited available data, the behavior of LELC of lung is highly variable, ranging from apparent curability by excision (particularly for localized disease) to highly aggressive, extensive disease at presentation. Cancer 1995; 76:413–22.

Background. The management of malignant pleural effusions secondary to breast cancer is a difficult problem. In the 1980s tetracycline was probably the most commonly used sclerosing agent, but parenteral tetracycline is no longer available. Therefore, it is important to evaluate alternative sclerosing agents. This prospective study was designed to determine the efficacy of insufflated talc in producing pleurodesis in patients with pleural effusions secondary to breast cancer. Methods. Fifty-two patients admitted between May 1985 and November 1992 to the Department of Thoracic Surgery underwent thoracoscopy and had 2 gm sterile asbestos free talc insufflated throughout the pleural space at the time of the procedure. One or two chest tubes were inserted and left in place until fluid drainage was less than 100 ml per day. Results. Of the 52 patients, 5 were not evaluable. Two patients died within 30 days of the procedure. In three additional patients the lung did not expand after thoracoscopy. The intrapleural insufflation of talc was effective in preventing recurrence of pleural effusion. At 30 days there was no recurrence of the pleural fluid in 45 of the 47 (95.7%) patients. One of these patients had a recurrence of the effusion 2 months after the procedure but the remaining 44 (93.6%) had no recurrence for the duration of the study. Aerosolized talc was associated with a moderate morbidity. Six (11.5%) patients had re-expansion edema, but all recovered. Empyema developed in one patient after the procedure. No episodes of respiratory distress syndrome were observed after talc pleurodesis. Conclusion. The insufflation of 2 gm talc into the pleural space is an effective method to control pleural effusions secondary to breast cancer. Cancer 1995;75:2688–92.

Background. The authors report a feasibility study of intrapleural cisplatin in a patient with inoperable malignant pleural mesothelioma. Methods. Total and filterable platinum in pleural effusion and in plasma were monitored for two intrapleural courses of 120 mg/m2 cisplatin, and a weekly schedule was adopted. Platinum concentrations in pleural effusion, plasma, and urine were determined by flameless atomic absorption spectroscopy. Results. A lower peak of filterable platinum in plasma, a decrease in systemic filterable platinum exposure (AUC [area under the concentration-time curve]), and a greater pleural exposure to filterable platinum were observed after Course 2 compared with Course 1. After the second cycle of intrapleural treatment, the systemic AUC for filterable platinum was reduced by 40%. Conclusions. The authors' findings may have some implications for the clinical use of intrapleural chemotherapy with high doses of cisplatin. Both infusions of cisplatin were generally well tolerated by the patient and were associated with the local pharmacologic advantage of sustained exposure to cisplatin of the pleural cavity. No sign of myelosuppression, neuropathy, or ototoxicity was observed, and acute toxicity consisted of mild nausea, vomiting, and prolonged anorexia. A transient presence of granular casts was the only observed nephrotoxic effect of cisplatin. Excellent local control of the disease with absence of recurrence of the effusion was observed.

BACKGROUND: Ovarian cancer cells in malignant effusions lack attachment to solid-phase matrix substrata and receive survival stimuli through cell–cell and cell–soluble matrix molecule interactions. We hypothesized that adhesion-related survival and proliferation pathway signals can inform clinical outcomes and guide targeted therapeutics. METHODS: Lysed cell pellets from a blinded set of benign (n = 20) and malignant (n = 51) peritoneal and pleural ovarian cancer patient effusions were applied to reverse-phase protein arrays and examined using validated antibodies to adhesion-associated protein endpoints. Results were subjected to hierarchical clustering for signature development. Association between specimen type, protein expression, and clinicopathologic associations were analyzed using the Mann-Whitney U test. Survival outcomes were estimated using the Kaplan-Meier method with log-rank comparison. RESULTS: A cell adhesion protein signature obtained from unsupervised clustering distinguished malignant from benign effusions (P = 6.18E-06). Protein subset analyses from malignant cases defined 3 cell adhesion protein clusters driven by E-cadherin, epithelial cell adhesion molecule, and N-cadherin, respectively. The components of the E- and N-cadherin clusters correlated with clinical outcome by Kaplan-Meier statistics. Univariate analysis indicated that FAK and phosphorylated AKT were associated with higher overall and progression-free survival (PFS) (P = .03), and Akt, phosphorylated paxillin, and E- and N-cadherin were associated with improved PFS (P ≤ .05). If 4 or 5 of the index adhesion proteins were high, PFS was improved by multivariate analysis (P ≤ .01). CONCLUSIONS: This hypothesis-testing examination of tumor cell adhesion molecules and pathways yielded potential predictive biomarkers with which to triage patients to selected molecular therapeutics and may serve as a platform for biomarker-based stratification for clinical application. Cancer 2011;. Published 2011 by the American Cancer Society.

Background. Acquired immunodeficiency syndrome (AIDS)-associated Kaposi sarcoma (KS) cells have not been reported in pleural effusions. This study identifies the effusional form of AIDS-KS cells with the CD34 antibody, a newly recognized marker for vascular neoplasia. Methods. In the pleural effusion of a patient with AIDS and biopsy proven pulmonary KS, the authors found bizarre amoeboid cells. Parallel sections from the cell blocks of the pleural effusions from the index patient and six other patients with AIDS were immunostained for cytokeratin, CD68, leukocyte common antigen (LCA), Factor VIII:R, and CD34. Results. The atypical cells were not observed in the pleural effusions of the other six patients with AIDS

Background To compare the diagnostic value of thoracoscopic biopsy, fluid cytology, and Abrams needle biopsy, the authors analyzed prospectively the records of 188 patients with malignant pleural mesothelioma examined between 1973 and 1990. Symptoms were pleural effusion in 173 patients, empyema in 1, spontaneous pneumothorax in 1, and radiologic tumor without effusion in 13. Methods Thoracoscopy was performed using a rigid thoracoscope under local anesthesia with neuroleptanalgesia. A total of 10-20 biopsies were taken from the parietal, diaphragmatic, and visceral pleura. Each diagnosis was confirmed by the French panel of mesothelioma pathologists. To prevent parietal seeding, radiation therapy at a dose of 21 Gy was administered during a period of 3 days to all points of entry. Results Tolerance to thoracoscopy was good. The only complications were subcutaneous emphysema (1 patient), local pleural infection (4 patients), hemorrhage of less than 100 ml (3 patients), and temperature of 38-38.5 degrees C (26 patients). In 137 patients, the cavity was free, and complete endoscopic inspection was achieved. In 51 patients, inspection was limited by adhesions that were severed to obtain biopsy. Nonspecific inflammation was observed in 12 patients (6.5%), nodules in 92 (49%), thickening in 21 (11%), and mixed lesions in 63 (33.5%). Diagnosis was achieved by thoracoscopy in 98% of patients, by fluid cytology in 26%, and by needle biopsy in 21%. Conclusion In most patients, thoracoscopy allows complete visualization of the pleural cavity and provides high-quality biopsy samples. The diagnostic accuracy of thoracoscopy is similar to open thoracotomy, but the procedure is far less invasive, usually requiring that the patient remain in the hospital only 1 day.

Background and Methods. Between 1978 and 1990, 51 cases of pericardial effusion secondary to lung cancer were treated at the National Cancer Center Hospital by creating a pericardial window, using the subxiphoid approach, that was connected to a water-sealed drainage system. Results. Most patients had advanced disease, such as distant metastasis (76%), pleural effusion (88%), and clinical Stage N2 or N3 disease (98%). Forty-five patients had cardiac tamponade, and six had no symptoms attributable to pericardial effusion. Cardiac tamponade was the initial manifestation of lung cancer in only 3 patients; it was a late manifestation in 48. Of those specimens that were examined cytologically, 92% had positive findings. The interval from creation of the pericardial window until removal of the drainage tube ranged from 4–135 days (median, 11 days). The interval was significantly longer in patients who previously had received thoracic radiation therapy (P < 0.05). The overall median survival was 80 days, and the 1-year survival rate was 10.5%. Postmortem examination showed that constrictive heart failure caused by pericardial lesions was the major contributory cause of death in 32% of patients. Using multivariate analysis, factors indicating a poor prognosis were: (1) the interval from the diagnosis of lung cancer to pericardial effusion development (P = 0.005) and (2) the absence of prior surgery (P = 0.007). Conclusions. The creation of a pericardial window effectively treated pericardial effusion in 85% of cases. However, the role of intrapericardial instillation of anti-cancer or sclerosing agents was unclear in this retrospective analysis. Cancer 1993; 71:93-8.

BACKGROUND: Little information exists regarding the prevalence and natural history of pericardial disease in patients with leukemia. Recently, it has been reported that the use of histone deacetylase inhibitors is associated with an increased incidence of pericardial effusions (PEs). To study the characteristics and treatment relationships of PEs in patients with leukemia, the authors retrospectively analyzed a cohort of patients with leukemia evaluated at a single center. METHODS: The authors reviewed 2592 patients with acute myeloid leukemia (AML, n = 1282, 49%), acute lymphocytic leukemia (ALL, n = 336, 13%), or myelodysplastic syndrome (MDS, n = 974, 38%), who were evaluated from August 2003 to July 2008. Electronic medical records were reviewed to select patients who had undergone at least 1 echocardiographic evaluation. Data regarding diagnosis, timing, effusion size, survival, and prior therapy were collected for the patients who had echocardiographic evidence of PEs. RESULTS: PEs were detected in 325 (20%) of the patients who had echocardiograms: 21% in AML, 23% in ALL, and 18% in MDS patients. Only a small portion of PEs were detected before the initiation of therapy: 26% in AML, 25% ALL, and 15% in MDS patients. Most PEs were of minimal size (70%) overall. No significant differences in effusion characteristics, including severity, were observed among different types of therapies. The presence of PEs had no impact on the survival of the patients evaluated. CONCLUSIONS: PEs are relatively common in patients with leukemia and do not appear to be related to specific types of therapy or to survival. Cancer 2010. © 2010 American Cancer Society.

A prospective randomized study to compare the effectiveness of pleurodesis by two new sclerosing agents: OK-432 and mitomycin C were conducted in 53 patients with malignant pleural effusion caused by lung cancer. None of the patients received concomitant systemic chemotherapy or radiation therapy during the study. After complete drainage of pleural fluid, the patients were allocated randomly to receive 10 Klinische Einheit units of OK-432 or 8 mg of mitomycin C by intrapleural injection at weekly intervals. The treatment was terminated if the pleural effusion disappeared or the patients had received four consecutive procedures. There were 26 patients who received pleurodesis with OK-432 and 27, with mitomycin C. Patient characteristics in the two treatment groups (age, sex, histologic type, performance status, and prior treatment before pleurodesis) were compatible. These results showed that pleurodesis with OK-432 achieved a higher complete response rate (73%) than that of mitomycin C (41%). The rates of objective treatment response (complete response plus partial response) were comparable in both groups (88% for OK-432 and 67% for mitomycin C). The average number of intrapleural injections needed to achieve complete response was fewer in the OK-432 group (1.9 +/- 0.9) than in mitomycin C group (2.8 +/- 0.9). There was no significant difference in the median survival of the patients who received pleurodesis with OK-432 (5.8 months) or mitomycin C (5.1 months). However, the effusion-free period in the OK-432 group was significantly longer than that in the mitomycin C group (7.0 months versus 1.5 months). Patients who underwent OK-432 pleurodesis had a higher complication rate (80%) than did those in the mitomycin C group (30%). Transient febrile reaction was the most common reaction encountered. The immunologic study in OK-432 group showed an increase in peripheral leukocyte count and decrease in the OKT4/OKT8 ratio. The mitomycin C group had a mild reduction in peripheral blood leukocyte count and no significant change in the OKT4/OKT8 ratio. It was concluded that pleurodesis with OK-432 is an effective alternative treatment for malignant effusion in patients with lung cancer.

BACKGROUND: Phase 1 studies demonstrated evidence of recombinant human IL-18 (rhIL-18)-mediated immunomodulatory and clinical activity, and defined a biologically active dose range. METHODS: A phase 2 study of rhIL-18 was conducted in untreated AJCC stage IV melanoma. Patients were randomized to 1 of 3 dose groups (0.01, 0.1, and 1.0 mg/kg/d) of rhIL-18 administered as 5 daily intravenous infusions repeated every 28 days. A 2-stage design with a stopping rule was used. RESULTS: A total of 64 patients (median age, 57.5 years) with metastatic melanoma (M1a/b (30), M1c (34)) were accrued to stage I, and randomized to 3 groups (21 [0.01 mg/kg/d], 21 [0.1 mg/kg/d], 22 [1.0 mg/kg/d]). Five patients experienced 10 grade 3 drug-related adverse events (AEs): polyarthritis (1 subject: 0.01 mg/kg); deep vein thrombosis, pulmonary embolism (1:0.01 mg/kg); cognitive disorder (1:0.1 mg/kg); fatigue, dyspnea, pleural effusion, lymphopenia (1:1.0 mg/kg); fatigue, lymphopenia (1:1.0 mg/kg). One patient experienced a grade 4 AE of increased lipase (0.1 mg/kg) that led to permanent discontinuation from the study. Among 63 subjects evaluable for response, 1 (M1c; 0.01 mg/kg) achieved a partial response after 4 cycles. Four subjects (3 at 0.01 mg/kg and 1 at 1.0 mg/kg) had stable disease maintained for 6 months or longer. Due to the low apparent level of clinical efficacy using RECIST criteria, the study was terminated at the end of stage 1. The median progression free survival for the 3 groups was 7.5 (0.01), 7.4 (0.1), and 7.3 (1.0) weeks. CONCLUSIONS: rIL-18 as tested in this trial was well tolerated, but had limited activity as a single agent in patients with metastatic melanoma. Cancer 2009. © 2009 American Cancer Society.

Ten patients with recurrent pleural effusions due to advanced cancer were treated by intracavitary methylprednisolone acetate (Depo-Medrol [DM], Upjohn, Kalamazoo, MI). They received one to six courses of DM (median, three courses per patient) with doses ranging from 80 to 160 mg per course. Effusion cells were cryopreserved before and during DM installation for subsequent determination of ploidy by flow cytometry. Pleural effusion in all three patients with advanced breast cancer resolved and did not reaccumulate throughout follow-up for 11+, 10+, and 8+ months. Pleural effusion in a patient with metastatic gastric cancer and in two of four patients with adenocarcinoma of unknown origin partially resolved. Altogether six of ten patients (60%) subjectively and objectively benefited from this therapy. All patients tolerated the treatment well with no local or systemic side effects. Flow cytometry showed a reduction in ploidy of effusion cells in all three patients with breast cancer, from a peak mean channel of 6C to nearly 2C after therapy. Transient reduction of ploidy was seen also in the effusion of a patient with unknown primary tumor associated with clinical improvement. The clinical and laboratory data reported offers initial evidence that DM when instilled into the pleural cavity after incomplete thoracentesis may act as effective palliative therapy either alone or in combination with other anticancer agents.

Cryosurgery, the in situ freezing of cancer, has been proposed in the past as a possible treatment for unresectable hepatic tumors. Its advantage lies in the fact that it is a very focal treatment sacrificing less normal tissue than surgical resection, allowing treatment of multiple lobes. Because cryosurgery does not affect large vessels, tumors in difficult locations, such as adjacent to the inferior vena cava (IVC), can be treated. With the use of intraoperative ultrasound to place the cryoprobes and monitor the freezing process, 18 patients with unresectable metastatic colon carcinoma confined to the liver were treated. Of the 18 patients treated, 4 (22%) are in complete remission as determined by computed tomography (CT) scans and carcinoembryonic antigen (CEA) levels, with a mean follow-up of 28.8 months. Four patients (22%) were not adequately treated at the time of cryosurgery. The number of lesions frozen in each patient ranged from 1 to 12, with a mean of 6 lesions. Fourteen patients had bilobar disease; three patients had previous right lobectomies with recurrences in their remaining left lobes prior to cryosurgery, and one patient had unilobar disease. Mean survival of the 14 cases with recurrence was 21.4 months, with 2 of the 14 still alive. Ultrasound-guided hepatic cryosurgery appears to be an effective treatment for metastatic colon carcinoma to the liver that is unresectable (including patients with bilobar and multiple lesions). These preliminary results indicate that the procedure warrants further study.

BACKGROUND. The aim was to determine the long-term outcome for patients with FIGO stage IV epithelial ovarian carcinoma (EOC) treated with intraperitoneal (IP) chemotherapy after second-look assessment. METHODS. By using data from a retrospective cohort of 433 patients who received IP therapy after second-look assessment after primary surgery and initial systemic therapy for EOC between 1984 and 1998 at our institution, all FIGO stage IIIC and IV patients were identified. Standard statistical methods were used. RESULTS. Overall, 297 patients met study criteria (246 stage IIIC; 51 stage IV). The median survival for patients with stage IV disease was 34 months compared with 42 months for patients with stage IIIC disease (P = .02). The only significant predictor of overall survival in patients with stage IV disease was the presence of gross residual disease at initiation of IP therapy (P = .027). When comparing stage IV patients with and without pleural effusions to all stage IIIC patients, there was a significant trend toward improved survival in the patients with pleural effusions only compared with other stage IV patients (P = .01). CONCLUSIONS. Prolonged overall survival was observed in patients with no gross residual disease at the time of IP chemotherapy initiation. When compared with similarly treated stage IIIC patients, stage IV patients with malignant pleural effusions appear to have a better outcome than those with other sites of metastasis. Future prospective trials should evaluate the use of IP therapy for patients with stage IV EOC by virtue of malignant pleural effusions only who responded to initial systemic therapy. Cancer 2008. ©2008 American Cancer Society.

BACKGROUND. The objective of this study was to investigate the diagnostic value of methylation profiles for discrimination between malignant and benign pleural effusions. A secondary objective was to examine the concordance of methylation in samples of serum and pleural fluid. METHODS. The authors used methylation-specific polymerase chain reaction (MSP) analysis to examine the promoter methylation status of 4 genes in patients with pleural effusion: death-associated protein kinase (DAPK), Ras association domain family 1A (RASSF1A), retinoic acid receptor β (RARβ), and p16/INK4a. Pleural effusions were collected from 87 patients who had their diagnoses confirmed on cytologic and/or histologic examinations and clinical evolution. Pleural effusions were classified as malignant (n = 53 patients) or benign (n = 34 patients). RESULTS. Methylation was detected in serum from 45.3% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions, and it was detected in pleural fluid samples from 58.5% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions (P = .001). The sensitivity of MSP was greater than that of cytologic examination alone (39.1%; P = .001). When MSP was used together with cytologic examination, sensitivity increased to 69.8% (P = .001). CONCLUSIONS. Cell-free methylated DNA in pleural fluid can be detected in patients with neoplastic malignancy in a single extraction by thoracocentesis. Adequate management of the extracted pleural fluid can provide a rapid and reliable diagnosis in patients with pleural effusions who have suspected malignancy. MSP, used together with cytologic examination, may obviate the need for other invasive diagnostic tests. Cancer 2006. © 2006 American Cancer Society.

BACKGROUND The objective of this study was to determine the impact of malignant pleural effusions on survival in patients with optimally debulked, advanced epithelial ovarian carcinoma. METHODS The authors conducted a retrospective review of all patients with advanced epithelial ovarian carcinoma who underwent optimal primary cytoreduction at their institution between January 1987 and August 2000. Survival rates were compared between patients with optimally debulked Stage IIIC epithelial ovarian carcinoma and patients with optimally debulked Stage IV epithelial ovarian carcinoma (according to the International Federation of Gynecology and Obstetrics [FIGO] staging system) based on cytology-proven malignant pleural effusions. RESULTS Ninety-nine patients were identified, and 97 of those patients were evaluable. The group with Stage IIIC disease included 76 patients, and the group with Stage IV disease included 21 patients. The median age at diagnosis was 55 years (range, 26–88 years). The majority of patients received platinum-based chemotherapy after undergoing optimal primary cytoreduction. Age, tumor grade and histology, and the percentage of patients with ascites were similar in the two groups. The median survival rate was 58 months for patients who had Stage IIIC disease and 30 months for patients who had Stage IV disease (P = 0.016). CONCLUSIONS Although both groups underwent optimal cytoreduction in the abdomen/pelvis and were treated in a similar fashion, the median survival rate of patients with malignant pleural effusions was significantly shorter than the survival of patients without effusions. Many factors that led to or were manifested by pleural effusions, such as undetected bulky residual intrathoracic disease, may have been the cause for this survival difference. In the patients with effusions, one or more of these contributing factors may have led to the observed decreased survival rate, warranting further investigation. Cancer 2005. © 2005 American Cancer Society.

BACKGROUND Gastrin-releasing peptide (GRP) is an autocrine growth factor in patients with small cell lung carcinoma (SCLC). The authors developed a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of SCLC cells in the peripheral blood and the pleural effusion using preproGRP mRNA as a target. METHODS The current study was conducted to determine the utility of preproGRP-specific nested RT-PCR on the peripheral blood, bone marrow, and pleural effusion samples from 32 patients with SCLC, 39 patients with non-small cell lung carcinoma (NSCLC), 28 patients with nonmalignant pulmonary disease, and 20 healthy volunteers. The internal primers were designed to amplify a 244-base pair PCR product, a sequence encompassing exon 1 and exon 2 by the nested RT-PCR assay. RESULTS Amplification of the preproGRP message was detected in SCLC cell lines (LU165, SBC1, SBC2, and SBC3) but not in other NSCLC cell lines (A549, ABC1, EBC1, and Oka-1). The SCLC cells (LU165) were detected in dilutions of tumor cells of up to 10−7 in hematopoietic cells from healthy donors. The preproGRP mRNA was detected in 16 of 32 (50%) blood samples, 2 of 11 (18%) marrow samples, and in all 6 (100%) pleural effusion samples. Blood samples gave positive results in 11 of 19 (58%) patients with extensive disease compared with 5 of 13 (38%) patients with limited disease. In contrast, only 1 blood sample (2.6%) from a patient with lung adenocarcinoma gave a positive result among patients with NSCLC. No other samples of blood, bone marrow, and pleural effusion from patients with NSCLC and none of the blood samples from patients with nonmalignant diseases and healthy volunteers were positive. CONCLUSIONS The current RT-PCR approach may be a sensitive and specific assay to detect SCLC cells in circulating blood as well as in pleural effusions from SCLC patients. Cancer 2003;97:2504–11. © 2003 American Cancer Society. DOI 10.1002/cncr.11378

The distinction between pleural mesothelioma (MS), reactive mesothelium (RM), and adenocarcinoma (AC) in serous effusions continues as a diagnostic problem in pathology. Immunohistochemistry can help, especially in surgical samples, but the optimum panel of antibodies has yet to be reported. The application of these antibodies to serous effusions has displayed variable results. The aim of this study was to evaluate the usefulness of eight monoclonal antibodies in the differential diagnosis of MS, RM, and AC in serous effusions.A total of 44 cytologic specimens of serous effusions (26 pleural, 15 peritoneal, and 3 pericardial) from 30 ACs, 3 MSs, and 11 RMs, previously stained with Papanicolaou stain, were selected retrospectively from our files and stained with HBME-1, thrombomodulin, calretinin, MOC-31, Ber-EP4, E-cadherin, CEA, and CD-15. The immunoreactions were evaluated independently by two pathologists. A stepwise logistic regression analysis was applied to the data to select an appropriate panel of antibodies.Statistical significance was found with HBME-1, thrombomodulin, MOC-31, Ber-EP4, and CD-15, when comparing both AC versus MS, and AC versus any type of mesothelial proliferation (MS or RM). Using HBME-1, 80% of ACs were negative whereas all three MSs reacted strongly with P = 0.003. A P = 0.02 was reached with thrombomodulin with 76.5% of ACs showing no immunoreactivity. Ber-EP4 and MOC-31 displayed good results with a P0.001 and 0.01, respectively. CD-15 reached a P = 0.034. No differences were found using the other antibodies. Ten ACs, all 3 MSs, and 10 RMs were double immunostained with HBME-1 and/or MOC-31 and Ber-EP4 successfully.Immunohistochemical studies performed on Papanicolaou stained cytologic smears proved to be useful in the differentiation between metastatic AC and mesothelial proliferation. HBME-1, thrombomodulin, MOC-31, Ber-EP4, and CD-15 were the most useful. In selected cases, it appeared that double immunostaining aided the differential diagnosis. Cancer (Cancer Cytopathol)

Because of morphologic similarities, the differential diagnosis of granulocytic sarcoma (GS) in fine-needle aspiration (FNA) specimens includes non-Hodgkin or Hodgkin lymphoma, extramedullary hematopoiesis, poorly differentiated carcinoma, and infection.Twenty-six FNAs and 1 pleural effusion fluid specimen of GS obtained from 23 patients were reviewed for cytomorphologic features and clinical characteristics. The cases were categorized as blastic, immature, or mature GS based on the population of the cells present on the smears.The patients included 18 men and 5 women (mean age, 54 years). Aspiration sites included subcutaneous or soft tissue (15 cases), lymph nodes (5 cases), bones (3 cases), testis (1 case), ileum (1 case), and liver (1 case). One sample of pleural effusion fluid also was included. Review of the patients' clinical history revealed that GS was secondary to chronic myelogenous leukemia (CML) in 17 patients, was secondary to chronic myelomonocytic leukemia (CMML) in 2 patients, and was secondary to acute myelogenous leukemia in 2 patients. GS preceded the manifestation of CML in one patient and of CMML in another patient. Based on the proportions of cells, morphologic classification was attempted and revealed blastic GS in 8 aspirates and 1 pleural effusion fluid specimen, immature GS in 13 aspirates, and mature GS in 5 aspirates. Twelve of 22 specimens from extranodal sites (55%) demonstrated lymphoglandular bodies in the background. Five aspirates showed rare eosinophilic myelocytes. Auer rods were not identified in any of the aspirates. Immunophenotypic and histochemical studies confirmed myeloid and/or myelomonocytic differentiation.GS especially can be confused with non-Hodgkin lymphoma because of morphologic similarities of the blasts to large cell lymphoma, the presence of lymphoglandular bodies, and the rarity of Auer rods and eosinophilic myelocytes. In conjunction with careful cytomorphologic evaluation, knowledge of the patient's clinical history and use of appropriate immunophenotypic studies should lead to a correct diagnosis.

The differentiation between malignant mesothelioma and adenocarcinoma based on morphology alone can be a diagnostic challenge. The majority of the available antibodies recognize molecules expressed by adenocarcinoma whereas to the authors' knowledge specific markers for mesothelial cells are lacking. Calretinin, a calcium-binding protein, has been reported to be a selective marker for mesothelioma and largely is absent from adenocarcinoma on histologic material. The results with cytologic preparations have been inconsistent.To evaluate the specificity of calretinin in differentiating mesothelioma from adenocarcinoma in cytologic preparations, 21 paraffin embedded cells blocks of serous effusions from 15 patients with metastatic adenocarcinoma and 16 cell blocks from 9 patients with malignant mesothelioma were stained with a monoclonal antibody against calretinin. The immunoreactivity was evaluated blindly by two observers. Positive staining was defined as nuclear and cytoplasmic staining with or without intense membranous decoration. The former resulted in a characteristic "fried egg" appearance.Calretinin staining was positive in all but 2 cases of mesothelioma (14 of 16 cases; 87.5%). The latter contained predominantly spindle-shaped neoplastic mesothelial cells in the cell block preparations. All adenocarcinoma specimens were classified as negative for calretinin staining; 9 (42.9%) lacked any immunoreactivity and 12 (57.1%) showed weak, sparse, coarse, granular cytoplasmic staining without nuclear or membranous staining. Benign reactive mesothelial cells, when observed in association with adenocarcinoma, also showed the characteristic "fried egg" appearance. The difference in the staining pattern of calretinin between cells of mesothelial origin and adenocarcinoma cells was statistically significant.Calretinin is a useful marker in differentiating mesothelioma of the epithelial type from adenocarcinoma in serous effusions. The "fried-egg" appearance or cytoplasmic and nuclear staining pattern is characteristic of cells of mesothelial origin.

BACKGROUND To the authors' knowledge the role of tumor marker determination in the differential diagnosis of pleural effusions has not been established definitively. The current article reports the results of a study of CYFRA 21-1, carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), squamous cell antigen (SCC), and neuron specific enolase (NSE) in the serum and pleural fluid of patients with pleural effusions of diverse etiologies. METHODS One hundred forty-six patients with pleural effusions (43 malignant, 47 tuberculous, 32 miscellaneous benign, and 24 paramalignant) were studied prospectively. Levels of CYFRA 21-1, CA 125, CEA, NSE, and SCC were measured by radioimmunoassay in the pleural fluid in all patients and in the serum in 118 patients. RESULTS There were no significant differences between the serum and pleural fluid levels of tumor markers with the exception of CA 125, which was higher in the pleural fluid. With maximum specificity, the highest sensitivity in the diagnosis of pleural malignancy was obtained with a combination of CYFRA 21-1 (with a cutoff value of 150 U/L), CEA (with a cutoff value of 40 ng/mL), and CA 125 (with a cutoff value of 1000 ng/mL) in pleural fluid. NSE and SCC added no diagnostic value. The simultaneous use of tumor markers and cytology in pleural fluid increased the sensitivity from 55.8% to 81%. CONCLUSIONS These findings suggest that a combination of CYFRA 21-1, CEA, and CA 125 in the pleural fluid can be a useful addition to pleural cytology in the diagnosis of malignant pleural effusion. Cancer 1999;86:1488–95. © 1999 American Cancer Society.

Telomerase is a ribonucleoprotein that maintains telomeric base pair repeats at the ends of mammalian chromosomes during DNA replication. Telomerase is expressed in various human tumors, some normal tissues, and immortalized cell lines. The assay of telomerase activity has potential as an adjunct for cancer detection in cytologic fluids.Twenty-four unfixed cytologic fluids, including 13 ascitic fluids, 7 pleural fluids, 3 pelvic washings, and 1 bronchial washing, were prepared for polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (Oncor, Inc., Gaithersburg, MD). Telomerase activity was determined by PCR. The presence of a ladder of products with 6 base pair increments, separated by polyacrylamide gel electrophoresis and detected by phosphoimaging, was considered a positive result. Results were compared with cytologic evaluation of alcohol fixed, Papanicolaou stained smears.Of the 14 cytologically malignant specimens, 11 (79%) contained detectable telomerase activity. Two cytologically malignant samples could not be evaluated for telomerase activity due to the presence of inhibitory substances of PCR reaction. Of the 10 cytologically negative specimens, 1 (10%) was positive for telomerase activity; this specimen was from a patient with history of both endometrial and lung carcinomas.Telomerase activity can be detected in malignant cytologic specimens and thus has potential as a diagnostic adjunct in cytopathology.

The distinction between malignant mesothelioma (MM) and adenocarcinoma (ACA) in cytologic specimens frequently is difficult, often requiring immunocytochemistry to support the diagnosis. Recent reports have proposed the utilization of antibodies to mesothelial cell clone HBME-1 and thrombomodulin (TM), because they are immunoreactive in MM and less commonly reactive in ACA. Immunoreactivity for the monoclonal antibody CA 19-9 has been observed in many ACAs and reportedly is absent in MM.In this study, immunostaining was performed on formalin fixed, paraffin embedded cell blocks from effusions or fine-needle aspirations using the avidin-biotin-peroxidase method. Thirty-eight MMs and 49 ACAs were tested using antibodies to CA 19-9, HBME-1, and TM.Anti-CA 19-9 stained only 1 of the 37 cases of MM tested (3%), but stained 24 of the 49 cases of ACA (49%). Anti-HBME-1 stained 34 of 38 cases of MM (89%), and 28 of 43 cases of ACA tested (65%). Anti-TM stained 24 of 36 cases of MM (67%), and 21 of 40 cases of ACA tested (53%).CA 19-9 has utility as part of an immunocytochemical panel for distinguishing ACA from MM, because a positive staining reaction would make the diagnosis of MM unlikely. Although HBME-1 and TM can identify MM positively, each frequently is detected in ACA, thus limiting the utility of these antibodies in cytologic specimens.

Sarcomas account for6% of malignant effusions and their diagnosis usually is made in the setting of a known primary tumor. However, these tumors often exhibit a variety of features that can differ from those of the original neoplasm and may preclude the correct diagnosis. This article evaluates the cytomorphology of sarcomas in fluids and determines characteristic features for identification and classification.The study included 24 Papanicolaou-stained fluid samples (15 pleural, 8 peritoneal, and 1 pericardial) from patients with a diagnosis of sarcoma. The following features were evaluated: cellular arrangement, cellularity, nuclear/cytoplasmic ratio, background, quality and quantity of cytoplasm, cell borders, and nuclear details.All cytology specimens were diagnosed accurately as malignant. The histopathologic diagnoses were eight malignant fibrous histiocytomas, five leiomyosarcomas, three rhabdomyosarcomas, three liposarcomas, two high grade sarcomas, one osteogenic sarcoma, one synovial sarcoma, and one chondrosarcoma. Cytomorphologic features shared by sarcomas in metastatic sites included single cell arrangement (23 of 24; 95.8%), indistinct cell borders (18 of 24; 75.0%), nuclear pleomorphism (18 of 24; 75.0%) multinucleation (13 of 24; 54.2%), and proteinaceous background with lysed blood (17 of 24; 70.8%).Sarcomas in effusions share morphologic features that allow their correct diagnosis. Further subclassification can be attempted in the proper clinical setting and by comparison with the primary lesion.

Effusions in patients with esophageal carcinoma have only been reported rarely, and the cytologic findings in these specimens have not been well described.The authors reviewed 70 effusion specimens from 45 patients with known esophageal carcinoma, 37 of whom underwent resection.Seventeen specimens were from 10 patients with squamous cell carcinoma; only 1 specimen contained malignant cells. Fifty-three specimens were from 35 patients with adenocarcinoma. Twenty-one specimens from 10 patients with adenocarcinoma contained malignant cells; these included 17 pleural, 2 pericardial, and 2 peritoneal fluids. Lymph node involvement at the time of resection was a significant risk factor for the development of a malignant effusion. The cytologic features were similar to those of other adenocarcinomas, but50% of the specimens were hypocellular and neoplastic cells were rare. Three of 48 negative specimens contained markedly atypical mesothelial cells that were misinterpreted as possibly malignant; in each case the findings resolved over time. These cells were smaller and the chromatin more smudgy than in the neoplastic cells. Patients with positive effusions were significantly more likely to die of disease than those with a negative effusion, and the average time to death was shorter (5.3 months vs. 17 months).Malignant effusions are more common in patients with esophageal adenocarcinoma than those with squamous cell carcinoma. Markedly atypical mesothelial cells are a diagnostic pitfall in patients who undergo resection.

Paclitaxel is an antimitotic agent isolated from the Pacific yew tree. It has demonstrated antitumor activity in several cancers and is the first of a new class of antineoplastic agents containing a taxane ring system. Its levels in serum and urine have been measured previously by high performance liquid chromatography (HPLC). In this study, the authors developed two competitive radioimmunoassay methods to determine whether they could reliably be used to measure levels of paclitaxel in sera and in cerebrospinal, ascitic, and pleural fluids.A monoclonal antibody prepared against paclitaxel was employed in an immunoradiometric assay (IRMA), in which 125I-labeled antibody was used, and in a more conventional tritiated radioimmunoassay (RIA),in which 3H-paclitaxel was used.Both radioimmunoassays detected levels of paclitaxel in sera that were comparable to those observed with HPLC. However, the IRMA was the most sensitive. Only the IRMA was able to detect low levels of paclitaxel in cerebrospinal fluid after paclitaxel infusion and in sera 3 weeks after infusion. Both the IRMA and RIA methods were able to detect paclitaxel in ascitic and pleural fluids.Monitoring paclitaxel levels reliably in sera and other bodily fluids is possible with these radioimmunoassays and may be of value in predicting and preventing toxicity and optimizing paclitaxel treatments.

BACKGROUND The differential diagnosis of pleural effusion is a frequent clinical problem. Several tumor markers have been evaluated in pleural fluid, but the value of CA 72-4 assay and of combinations of tumor marker assays has not been firmly established. To find a minimally invasive tool for differentiating between pleural effusions of malignant or benign origin, the authors assessed the diagnostic value of CA 72-4, carcinoembryonic antigen (CEA), CA 15-3, and CA 19-9 assays in pleural fluid individually and in combination. METHODS The authors prospectively studied 207 patients with pleural effusion (65 malignant, 48 tuberculous, 24 parapneumonic, 26 transudates, 14 miscellaneous, and 30 of unknown nonneoplastic origin). The levels of CA 72-4, CEA, CA 15-3, and CA 19-9 were measured in pleural fluid by radioimmunoassay. RESULTS CA 72-4 assay in pleural fluid had an acceptable sensitivity and very good specificity for diagnosing malignant pleural effusion. The combination of CA 72-4 plus CEA plus CA 15-3 yielded the best accuracy, 0.90 (95% confidence interval [CI] 0.85-0.94), with a sensitivity of 0.78 (95% CI, 0.67-0.88), specificity of 0.95 (95% CI, 0.90-0.98), positive predictive value of 0.88 (95% CI, 0.77-0.95), and negative predictive value of 0.91 (range, 0.85-0.94). A good clinical strategy may be to begin with a CEA assay (specificity of 1) and then, if it is negative, to add CA 15-3 or even CA 72-4 assays to improve sensitivity. The diagnosis of mesothelioma is more likely with a high CA 15-3 level and normal CEA and CA 19-9 levels. CONCLUSIONS Assays of CEA, CA 72-4, and CA 15-3 in pleural fluid, or the combination of CEA with CA 15-3 and CA 72-4, was useful in differentiating between pleural effusion of malignant and benign origin. Cancer 1996;78:736-40.