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PubMed1992

Diagnostic value of sialic acid in malignant pleural effusions.

In this study, we measured pleural fluid and serum sialic acid levels in 70 consecutive patients hospitalized with pleural effusions and serum sialic acid concentrations in 20 healthy individuals chosen as control group. The cause of 26 pleural effusions was malignancy, and diseases other than malignant neoplasms were determined as the cause of 44 cases. Mean serum sialic acid levels in the patients with malignancies were higher than the levels in patients with nonmalignant diseases and the control group. Mean sialic acid level in the patients with nonmalignant diseases was increased compared with control group, but this increase was not as high as that in the patients with malignancies. In the patients with malignant neoplasms, mean pleural fluid sialic acid content was also higher than that found in other diseases. Sialic acid concentration of pleural fluid was correlated with serum concentration. However, pleural fluid to serum sialic acid ratio in malignant diseases was greater than that in the others. The specificity and sensitivity of pleural fluid sialic acid level in excess of 0.075 mg/ml in distinguishing malignant effusions were 68 percent and 77 percent, respectively. These values for pleural fluid/serum sialic acid ratio with the cut-off level of 0.7 were 55 percent and 65 percent. Our findings indicate that determination of sialic acid level in malignant pleural effusions has a diagnostic value.

Biomarkers, Tumor↗

PubMed2002

Clinical role of F-18 fluorodeoxyglucose positron emission tomography imaging in patients with lung cancer and suspected malignant pleural effusion.

STUDY OBJECTIVES: The goals of this study were to determine the sensitivity, specificity, and predictive accuracy of F-18 fluorodeoxyglucose positron emission tomography (PET-FDG) imaging in detecting metastatic disease involvement of pleura and/or presence of malignant pleural effusion in patients with proven lung cancer. We wanted to compare efficacy of PET-FDG imaging to CT scanning in differentiating benign pleural effusion from malignant effusion and/or pleural involvement in patients with lung cancer. METHODS: We studied 35 patients with biopsy-proven lung cancer and abnormal findings on CT scanning for presence of pleural effusion (n = 34) and/or pleural thickening or nodular involvement (n = 4). The results of positron emission tomography and CT scanning were compared to pleural cytology (n = 31), histologic findings of pleural biopsy (n = 3), and/or clinical follow-up (n = 3) for at least 1 year for presence or absence of malignant pleural effusion. RESULTS: PET-FDG imaging correctly detected the presence of malignant pleural effusion and malignant pleural involvement in 16 of 18 patients and excluded malignant effusion or pleural metastatic involvement in 16 of 17 patients (sensitivity, specificity, and accuracy of 88.8%, 94.1%, and 91.4% respectively). CONCLUSION: PET-FDG imaging is a highly accurate and reliable noninvasive test to differentiate malignant from benign pleural effusion and/or pleural involvement in patients with lung cancer and findings of suspected malignant pleural effusion on CT scanning.

Diagnosis, Differential↗

PubMed2004

Use of a panel of tumor markers (carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 15-3, and cytokeratin 19 fragments) in pleural fluid for the differential diagnosis of benign and malignant effusions.

STUDY OBJECTIVE: The diagnostic value of tumor markers in pleural fluid is subject to debate. The aim of this study was to evaluate the diagnostic performance of several tumor markers in common use for detecting malignant pleural disease. DESIGN: Blinded comparison of four tumor markers in pleural fluid with a confirmatory diagnosis of malignancy by pleural cytology or thoracoscopic biopsy. SETTING: Two teaching hospitals in Spain. PATIENTS AND METHODS: A total of 416 patients (166 with definite malignant effusions, 77 with probable malignant effusions, and 173 with benign effusions) were enrolled. Among them, there were 42 patients recruited from one of the participant centers with thoracoscopic facilities, who had false-negative fluid cytology findings and malignancy confirmed by medical thoracoscopy. Tumor markers in pleural fluid were determined either by electrochemiluminescence immunoassay (carcinoembryonic antigen [CEA], carbohydrate antigen 15-3 [CA 15-3], cytokeratin 19 fragments [CYFRA 21-1]) or microparticle enzyme immunoassay (cancer antigen 125 [CA 125]) technologies. Cutoff points that yielded 100% specificity (ie, all patients with benign effusions had levels below this cutoff) were selected for each marker. RESULTS: Malignant pleural effusions (PEs) had higher levels of pleural fluid markers than did effusions due to benign conditions. At 100% specificity, a pleural CEA > 50 ng/mL, CA 125 > 2,800 U/mL, CA 15-3 > 75 U/mL, and CYFRA 21-1 > 175 ng/mL had 29%, 17%, 30%, and 22% overall sensitivities, respectively. The combination of the four tumor markers reached 54% sensitivity, whereas the combined use of the cytology and the tumor marker panel increased the diagnostic yield of the former by 18% (95% confidence interval, 13 to 23%). More than one third of cytology-negative malignant PEs could be identified by at least one marker of the panel. CONCLUSIONS: No single pleural fluid marker seems to be accurate enough as to be introduced in the routine workup of PE diagnosis. However, a tumor marker panel may represent a helpful adjunct to cytology in order to rule in malignancy as a probable diagnosis, thus guiding the selection of patients who might benefit from further invasive procedures.

Aged↗

PubMed2005

Predictors of pleural malignancy in patients with pleural effusion undergoing thoracoscopy.

STUDY OBJECTIVES: Thoracoscopic pleural biopsy is highly accurate in the diagnosis of pleural malignancy. However, no scientific evidence is currently available to guide the physician's decision as to when and in which patients with pleural effusion thoracoscopy is indicated. The application of predictive criteria of malignancy might improve the indication of thoracoscopy in patients with undiagnosed pleural effusion. METHODS: Prospective study of 93 patients referred for thoracoscopy at a tertiary hospital. Clinical variables were obtained prior to thoracoscopy by clinical history and review of previous data, patient interview, and physical examination. Radiologic variables were obtained by evaluation of chest radiograph and chest CT images by two independent readers. After thoracoscopy, all patients without a diagnosis were sent for long-term follow-up. RESULTS: Thoracoscopy demonstrated 94% sensitivity and 100% specificity in the diagnosis of pleural malignancy. Variables, which in a multivariate model are associated with pleural malignancy, include a symptomatic period > 1 month, absence of fever, blood-tinged pleural fluid, and chest CT scan findings suggestive of malignancy. Receiver operating characteristic analysis showed that the use of these four criteria offered adequate classification in 95% of patients. Twenty-eight patients had all four criteria, and all had malignancy; 21 patients had at most one criterion, and none had malignancy. CONCLUSION: Clinical and radiologic criteria of patients with pleural effusion permit different risk levels for pleural malignancy to be distinguished. Consequently, application of the four proposed criteria permits better indication of thoracoscopy in patients with undiagnosed pleural effusion.

Biopsy, Needle↗

PubMed2006

Influence of lymphocytes in malignant pleural effusion on the therapeutic efficacy of intrapleural OK-432 in lung cancer patients.

OBJECTIVES: Malignant pleural effusion, a common complication seen in advanced lung cancer patients, is often treated with intrapleural administration of chemical agents. In Japan, OK-432, a biological response modifiers, which activates the cytotoxic activity of lymphocytes and boosts antitumor immunity, is among the most frequently used chemical agents. The purpose of this study was to determine, in a case-control study, whether or not the rate of lymphocytes in malignant pleural effusion (lymphocyte rate) influences the therapeutic efficacy of intrapleural OK-432. PATIENTS AND METHODS: We enrolled 20 lung cancer patients with malignant pleural effusion treated with intrapleural OK-432 who were admitted to our hospital between January 2000 and December 2004. Therapeutic efficacy was assessed from the response rate, duration of chest drainage after treatment with intrapleural OK-432, time to progression of malignant pleural effusion, and survival time. RESULTS: Response rate in patients who had a high lymphocyte rate (the High lymphocyte rate group) was significantly higher than in patients who had a low lymphocyte rate (the Low lymphocyte rate group). Lymphocyte rate did not correlate with duration of chest drainage after treatment with intrapleural OK-432, time to progression of malignant pleural effusion, or survival time. CONCLUSIONS: The lymphocyte rate in malignant pleural effusion influences the response rate to treatment by intrapleural OK-432. In the High lymphocyte rate group, intrapleural OK-432 for malignant pleural effusion was effective. We conclude that intrapleural OK-432 is useful for malignant pleural effusion patients with a high lymphocyte rate before treatment.

Aged↗

PubMed2000

[The significance of detecting tumor necrosis factor-alpha and its receptors in serum and pleural effusion in differentiating tuberculosis and malignant pleural effusions].

OBJECTIVE: To investigate the significance of TNF-alpha and its soluble receptors (sTNFR-I and sTNFR-II) in differentiating benign and malignant pleural disease. METHODS: TNF-alpha and its soluble receptors (sTNFR-I and sTNFR-II) were detected using ELISA method in the serum and pleural effusion of 25 cases of tuberculosis pleural effusion and 28 cases of malignant pleural effusion, and in the serum of 32 cases of normal control. RESULTS: TNF-alpha level in the serum of tuberculosis patients with pleural effusion is (16.4 +/- 6.2) ng/L, lower than that in the serum of malignant pleural effusion patients (20.5 +/- 10.9) ng/L (P < 0.01), but higher than that in the serum of normal control (11.0 +/- 2.9) ng/L (P < 0.01). TNF-alpha level in the pleural effusion of tuberculosis patients is (29.4 +/- 10.3) ng/L, significantly higher than that of malignant pleural effusion (11.7 +/- 2.0) ng/L (P < 0.01). The sTNFR-I and sTNFR-II level in the serum of malignant pleural effusion is (1,132 +/- 303) ng/L and (1,548 +/- 489) ng/L respectively, significantly higher than that in tuberculosis pleural effusion which is (979 +/- 146) ng/L and (977 +/- 93) ng/L (P < 0.01) respectively. The sTNFR-I and sTNFR-II level in malignant pleural effusion is (1,404 +/- 306) ng/L and (2,195 +/- 418) ng/L respectively, markedly higher than those in tuberculosis pleural effusion which is (1,185 +/- 215) ng/L and (1,195 +/- 300) ng/L (P < 0.01). CONCLUSION: There are highly elevated TNF-alpha in tuberculosis pleural effusion; The sTNFR-I and sTNFR-II level in the serum and pleural effusion of malignant pleural effusion patients are significantly higher than those in tuberculosis pleural effusion patients, suggesting they may play some role in differentiating benign and malignant pleural diseases.

Adult↗

PubMed1953

Early diagnosis of malignant melanoma of the skin.

About five per cent of all malignant lesions of the skin are malignant melanomas. The poor prognosis associated with this malignant lesion emphasizes the importance of early diagnosis. A large proportion of malignant melanomas arise in preexisting lesions such as junction nevi, precancerous melanoses and, much more rarely, blue nevi. Early malignant changes in these precursor lesions include increasing pigmentation, enlargement, thickening, crusting, bleeding, ulceration, tumor formation, and development of satellite lesions. Many pigmented, and some non-pigmented, lesions of the skin must be differentiated from malignant melanoma. Since even with radical surgical treatment the prognosis of malignant melanoma is poor, junction nevi which are subject to continual trauma or have signs of probable malignant degeneration should be prophylactically excised.

Early Diagnosis↗

PubMed2003

[Diagnostic efficiency of serum lipid-bound sialic acid level in malignant pleural effusions].

In this study, pleural fluid and serum lipid-bound sialic acid (LBSA) levels of 68 cases with pleural effusion hospitalised at the department of Chest Diseases in the Medical School of Selçuk University, and serum LBSA levels of 30 healthy individuals as control group were studied. Pleural effusions of 32 cases were due to malignancy of which considerably lung cancer. In the other 36 cases the causes were nonmalignant in origin. Levels of mean serum LBSA in malignant and benign groups were significantly higher than control group (p< 0.001). However, difference of the mean serum LBSA levels of malignant and benign groups was not statistically significant. We found the mean pleural fluid LBSA level of 23.34 mg/dL in malignant group and it was significantly higher than benign group (17.97 mg/dL) (p< 0.05). It was observed that there was no significant statistical difference between the pleural fluid to serum LBSA ratios of malignant and benign groups. In differential diagnosis of malignant pleural effusions, sensitivity and specificity of pleural fluid LBSA were 91%, and 51%, respectively. In conclusion, for the differentiation of malignant pleural effusions LBSA is not believed to be a reliable tumor marker since it may also increase in various chronic and inflammatory diseases. Despite of that, in cases with a suspicion of malignancy, the increased level of pleural fluid LBSA may be useful as a supportive parameter.

Biomarkers, Tumor↗

PubMed2005

Clinical significance of the expression of tumor-associated antigen, RCAS1, and its soluble protein in pleural fluid in malignant mesothelioma.

RCAS1 is a type II membrane protein which is also secreted as a soluble protein. RCAS1 may play a role in evading immune surveillance by tumor cells and be responsible for the aggressive behavior of tumors. We examined the usefulness of RCAS1 in the follow-up of malignant mesothelioma. In addition, we examined the usefulness of its soluble protein (sRCAS1) in pleural effusion for the diagnosis of malignant mesothelioma. We studied 38 patients with pleural malignant mesothelioma and examined the correlation between RCAS1 expression, clinicopathologic variables and overall survival. We also determined the pleural fluid sRCAS1 concentration with an enzyme-linked immunosorbent assay (ELISA). We found that 34 out of 38 (89.5%) malignant mesothelioma cells stained for RCAS1. The positive rate was 90.9% in biphasic type, 78.6% in epithelioid type, and 100% in sarcomatoid type. No statistically significant correlation was observed between RCAS1 expression and gender, age, histology or clinical stage. Interestingly, survival of the malignant mesothelioma patients with RCAS1 expression was significantly increased compared with those without (median survival time: 13.0 vs. 4.3 months, p=0.011). Multivariate analysis of prognostic factors, using the Cox proportional hazards model, revealed that RCAS1 expression had a significantly positive effect on survival. sRCAS1 concentrations in pleural fluid in malignant mesothelioma were lower than those in lung cancer (2.18+/-2.20 vs. 46.3+/-129 U/ml; p=0.019). RCAS1 expression is informative for the follow-up of malignant mesothelioma patients. In addition, sRCAS1 in pleural fluid may be useful for the diagnosis of malignant mesothelioma.

Adult↗

PubMed1989

[Pathophysiology and prognosis in malignant hypertension: comparison by underlying diseases].

Pathophysiological characteristics and long-term prognosis were studied retrospectively in 69 malignant hypertensives associated with grade III or IV retinopathy and the diastolic blood pressure greater than 120 mmHg. Thirty three (48%) cases had essential hypertension (EHT) as the underlying disease, 26 (38%) as chronic glomerulonephritis (CGN), and the remaining 10 (14%) as others including chronic pyelonephritis, renovascular hypertension, hydronephrosis, multiple calyceal diverticula, and unknown original disease. The role of the renin-angiotensin system in malignant hypertension was investigated by measuring plasma renin activity (PRA) and determining the blood pressure response to angiotensin (ANG)II antagonist, (Sar1, Ile8) ANG II. Basal PRA was significantly higher in the EHT group than the CGN group, and the ANG II antagonist-induced reduction of blood pressure was only evident in the former group. The regression analysis revealed that PRA was linearly correlated with both mean blood pressure (MBP) and serum creatinine prior to antihypertensive treatment in the EHT group but not in CGN patients, although there was inverse correlation between PRA and serum sodium in both groups. Therefore, the renin-angiotensin system seems to play a significant role in elevating blood pressure and deteriorating renal function in malignant hypertension developed from EHT, while it is less important in that from CGN. The 5-year survival rate was 90% in total 69 patients with malignant hypertension, while the 5-year renal survival rate defined as the probability of surviving without maintenance hemodialysis was 37%, indicating that the treatment with hemodialysis as well as antihypertensive drug therapy contributed to an improvement of prognosis of malignant hypertension. The EHT group showed a poor prognosis for life compared with the CGN group, while in the latter group most patients rapidly developed endstage renal failure. Although the pretreatment serum creatinine levels were matched, the renal function more rapidly deteriorated after development of malignant hypertension in the CGN group than did in the EHT group, indicating renal survival rate to be shorter in the former group. Hence, underlying diseases may affect the long-term prognosis of malignant hypertension. The results obtained from this study suggest that the pathophysiological characteristics of malignant hypertension are different and its long-term prognosis is varied by underlying diseases such as EHT and CGN.

Adult↗

PubMed1985

Malignant hypertension in general practice.

A diagnosis of malignant hypertension was recorded for 165 patients in the national morbidity study between 1970 and 1973. Three patients with benign hypertension were selected as age- and sex-matched controls for each case. The general practitioners in the study were asked to complete a further questionnaire about the patients and 66% of the practices agreed to take part. Information about the retinal findings for the patients was requested and less than half of those in the national morbidity study proved to have a strict diagnosis of accelerated or malignant hypertension although they were originally recorded as patients with malignant hypertension. Of those patients originally classified as having benign hypertension 5% had the retinal appearance of accelerated or malignant hypertension.Patients had been diagnosed as having hypertension for a mean of more than five years prior to entry into the national morbidity study and the survival of patients with both benign and accelerated or malignant hypertension was good. Thirtyfour per cent of those with confirmed benign hypertension and 62% of those with definite accelerated or malignant hypertension died in the follow-up period which was on average 10 years from entry into the national morbidity study.The survival of patients registered with doctors who did not collaborate and of patients whose clinical details were missing was similar to the survival of patients for whom full details were provided.Blood pressure control was only fair with a mean of 172/101 mmHg for the group with benign hypertension and 177/107 mmHg for the group with accelerated or malignant hypertension. Blood pressure control was the poorest for those who died from a stroke. A high proportion (78%) of deaths in association with accelerated or malignant hypertension were from cardiovascular or renal causes.

Aged↗

PubMed1990

Dermatomyositis. Disease associations and an evaluation of screening investigations for malignancy.

Fifty-three adult patients (19 men, 34 women) with dermatomyositis were studied. Two had dermatomyositis associated with benign disorders. Twenty-three (43%) had a malignancy; the risk of malignancy increased with age, but there was no sex difference. Seven malignancies were recurrences and 9 were diagnosed during investigation of dermatomyositis; these 16 were suspected clinically or from abnormal results of simple investigations. Extensive screening tests did not increase the number of malignancies diagnosed. In 7 patients, a diagnosis of malignancy was made more than 9 months after onset of dermatomyositis, although a relationship between malignancy and dermatomyositis was uncertain in two cases; the diagnosis of gynecological malignancy was missed in 2 patients despite appropriate investigations, 1 patient had poorly controlled dermatomyositis, and in 2 patients late diagnosis of malignancy was due to failure to reinvestigate relapse of previously stable dermatomyositis.

Adult↗

PubMed1998

Autopsy diagnoses of malignant neoplasms: how often are clinical diagnoses incorrect?

CONTEXT: Autopsy often reveals new diagnoses of malignant neoplasms, but as technological advances to improve diagnosis during life have improved, autopsy rates have declined dramatically. OBJECTIVE: To determine if there is still a high discordance rate between clinical and autopsy diagnoses of malignant neoplasms despite increasing technological advances in diagnostic methods. DESIGN AND SETTING: A 10-year retrospective study (1986-1995) of all autopsies performed at the Medical Center of Louisiana at New Orleans. PARTICIPANTS: All patients autopsied, excluding preterm fetuses, at the Medical Center of Louisiana at New Orleans, by both Tulane and Louisiana State University Schools of Medicine in which consent was obtained or authorization given from the Orleans Parish Coroner's Office. MAIN OUTCOME MEASURES: Discordance between clinical and autopsy diagnoses of malignant neoplasms. RESULTS: A total of 1625 cases were reviewed of which 520 preterm fetuses were excluded. Of the remaining 1105 cases, 654 were male and 451 were female. The mean age was 48.3 years (range, 1-98 years). A total of 433 neoplasms were diagnosed, 250 of which were malignant. One hundred eleven malignant neoplasms in 100 patients had been either undiagnosed or misdiagnosed, and in 57 patients, the immediate cause of death could be attributed to the malignant neoplasm. The discordance between clinical and autopsy diagnoses of malignant neoplasms in this study is 44%, which is similar to previously reported studies. CONCLUSION: The discordance rate between clinical and autopsy diagnoses of malignant neoplasms is large and confirms the importance of the postmortem examination.

Adolescent↗

PubMed2003

Risk factors for pediatric human immunodeficiency virus-related malignancy.

CONTEXT: Although cancers occur with increased frequency in children with human immunodeficiency virus (HIV) infection, the specific clinical, immunological, and viral risk factors for malignancy have not been identified. OBJECTIVE: To identify risk factors for malignancy among HIV-infected children. DESIGN, SETTING, AND PATIENTS: A multicenter case-control study of children with HIV at 26 institutions participating in the Pediatric Oncology Group. Forty-three case patients with a new malignancy and 74 control patients without a malignancy were matched based on the duration of their infection. Patients were enrolled between January 1992 and July 1998. MAIN OUTCOME MEASURES: Clinical and laboratory factors assessed as putative risk factors included demographic characteristics, HIV characteristics, prior antiretroviral treatment, and CD4 cell count. Coviral infections with Epstein-Barr virus (EBV), cytomegalovirus, and human herpesvirus 6 were assessed by semiquantitative polymerase chain reaction assays and serological testing. RESULTS: Case malignancy diagnoses included 28 non-Hodgkin lymphoma, 4 B-cell acute lymphoblastic leukemia, 1 Hodgkin disease, 8 leiomyosarcoma, 1 hepatoblastoma, and 1 schwannoma. Epstein-Barr virus viral load of more than 50 viral genome copies per 105 peripheral blood mononuclear cells was strongly associated with cancer risk but only for children with CD4 cell counts of at least 200/ microL (odds ratio [OR], 11.33; 95% confidence interval [CI], 2.09-65.66, P<.001). High EBV viral load was not associated with cancer for children with CD4 cell counts of less than 200/ microL (OR, 1.12; 95% CI, 0.13-9.62; P =.99). Zidovudine antiretroviral therapy did not confer a significant protective effect for either the high (OR, 0.81; 95% CI, 0.22-3.09; P =.77) or the low CD4 cell count groups (OR, 0.27; 95% CI, 0.04-1.46; P =.16). The route of HIV infection was not associated with increased cancer risk. CONCLUSIONS: Route of infection, demographic characteristics, and zidovudine use were not associated with the development of malignancy in HIV-infected children. High viral burden with EBV was associated with the development of malignancy in HIV-infected children although the effect was modified by CD4 cell count. The pathogenesis of HIV-related pediatric malignancies remains unclear and other contributing risk factors can be elucidated only through further study.

Antiviral Agents↗

PubMed2006

Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials.

CONTEXT: Tumor necrosis factor (TNF) plays an important role in host defense and tumor growth control. Therefore, anti-TNF antibody therapies may increase the risk of serious infections and malignancies. OBJECTIVE: To assess the extent to which anti-TNF antibody therapies may increase the risk of serious infections and malignancies in patients with rheumatoid arthritis by performing a meta-analysis to derive estimates of sparse harmful events occurring in randomized trials of anti-TNF therapy. DATA SOURCES: A systematic literature search of EMBASE, MEDLINE, Cochrane Library, and electronic abstract databases of the annual scientific meetings of both the European League Against Rheumatism and the American College of Rheumatology was conducted through December 2005. This search was complemented with interviews of the manufacturers of the 2 licensed anti-TNF antibodies. STUDY SELECTION: We included randomized, placebo-controlled trials of the 2 licensed anti-TNF antibodies (infliximab and adalimumab) used for 12 weeks or more in patients with rheumatoid arthritis. Nine trials met our inclusion criteria, including 3493 patients who received anti-TNF antibody treatment and 1512 patients who received placebo. DATA EXTRACTION: Data on study characteristics to assess study quality and intention-to-treat data for serious infections and malignancies were abstracted. Published information from the trials was supplemented by direct contact between principal investigators and industry sponsors. DATA SYNTHESIS: We calculated a pooled odds ratio (Mantel-Haenszel methods with a continuity correction designed for sparse data) for malignancies and serious infections (infection that requires antimicrobial therapy and/or hospitalization) in anti-TNF-treated patients vs placebo patients. We estimated effects for high and low doses separately. The pooled odds ratio for malignancy was 3.3 (95% confidence interval [CI], 1.2-9.1) and for serious infection was 2.0 (95% CI, 1.3-3.1). Malignancies were significantly more common in patients treated with higher doses compared with patients who received lower doses of anti-TNF antibodies. For patients treated with anti-TNF antibodies in the included trials, the number needed to harm was 154 (95% CI, 91-500) for 1 additional malignancy within a treatment period of 6 to 12 months. For serious infections, the number needed to harm was 59 (95% CI, 39-125) within a treatment period of 3 to 12 months. CONCLUSIONS: There is evidence of an increased risk of serious infections and a dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy. The formal meta-analysis with pooled sparse adverse events data from randomized controlled trials serves as a tool to assess harmful drug effects.

Adalimumab↗

PubMed2000

p53 immunoexpression in non-malignant oral mucosa adjacent to oral squamous cell carcinoma: potential consequences for clinical management.

p53 is a tumour suppressor gene encoding a protein whose function is impaired in a very large proportion of human cancers. The objectives of this study were to determine the natural history of p53 alterations during stages of oral carcinogenesis, by comparing p53 immunoexpression in oral squamous cell carcinomas (OSCCs), their non-malignant adjacent mucosa, and respective metastases; and to define the potential practical consequences for clinical management of p53 staining in the non-malignant adjacent mucosa. Forty-two samples of non-malignant mucosa adjacent to OSCCs, the respective carcinomas, and six lymph node metastases derived from six of the OSCCs were investigated for p53 protein expression by immunohistochemistry. Seven out of 42 (17%) non-malignant mucosal samples immediately adjacent to OSCC showed suprabasal p53 staining and this was significantly associated with moderate/severe dysplasia (p=0.02). In six of these cases (86%), the respective carcinoma showed p53 immunoexpression in more than 50% of the neoplastic cells and in the remaining case, p53 immunoexpression was found in more than 25% of the neoplastic cells. In all p53-negative carcinomas that showed p53 immunoexpression in the non-malignant adjacent mucosa, p53 staining was never detected above the basal cell layer. Lymph node metastases showed the same patterns of p53 immunoexpression as the carcinomas from which they were derived. When suprabasal p53 staining is present in non-malignant mucosa immediately adjacent to OSCCs, this suggests stable p53 alterations which are maintained upon progression to overt malignancy. The immunostaining in non-malignant mucosa of the resection margins of OSCCs might be a valuable predictor for local recurrences and may therefore have implications for the management of patients who have received surgical treatment for OSCC.

Adult↗

PubMed1996

Coexistence of renal cell carcinoma and malignant lymphoma. A causal relationship or coincidental occurrence?

BACKGROUND: Secondary malignant neoplasms are increasingly being observed in cancer populations and a considerable amount of data have accumulated in the literature. Among the secondary malignant neoplasms that occur with a higher incidence in cancer patients are lymphomas and renal cell carcinoma (RCC), as well as melanoma, lung/bronchus carcinoma. METHODS: The authors analyzed the patient population at the Memorial Sloan-Kettering Cancer Center in New York City between 1985 and 1995 for coexisting carcinomas, and identified 15 patients who had both RCC and malignant lymphoma among a total of 1262 patients with RCC and 1660 patients with malignant lymphoma. The occurrence and time of diagnosis of both malignant neoplasms and their clinical features, types, and stages, as well as short term follow-up, results, are presented. RESULTS: The data show a greater than coincidental coexistence of RCC and malignant lymphoma (P < 0.01). In addition, there was a significant increase in the number of patients with both melanoma and RCC (P < 0.01), as well as melanoma and malignant lymphoma (P < 0.01). No significant increase was found in cases of coexisting RCC or malignant lymphoma with either lung/bronchus carcinoma or colorectal carcinoma (P > 0.05). CONCLUSIONS: Causes of this increased coexistence may include a genetic predisposition to cancer, similar immune mechanisms associated with these neoplasms, closer scrutiny of this group of patients, or a combination of these factors. Studies are underway to elucidate a common genetic component in these patients.

Adult↗

PubMed1999

Value of Ki67 immunostain in identification of malignancy in serous effusions.

The distinction between malignant and benign serous effusions continues to be a challenging and a frequent problem to cytopathologists. Recently, immunostains employing various antibodies have improved the diagnostic accuracy of malignant effusions. We investigated the usefulness of Ki67 (MIB1) antigen immunostaining in the evaluation and diagnosis of malignant serous effusions. Cell block sections from a total of 54 cases of serous effusions cytologically diagnosed as malignant (28), suspicious (6), and benign (20) were immunostained with MIB1 monoclonal antibody to the Ki67 nuclear proliferation antigen according to the avidin-biotin immunoperoxidase method. The patients were 30 women and 24 men with an average age of 58 yr. Ki67 (MIB1) immunostain labeling index (LI) values were higher than 20% in 23 of 28 (82%) cytologically malignant, in 3 of 6 (50%) suspicious, and in 1 of 20 (5%) benign/reactive. Further investigation revealed histologic, radiologic, and/or clinical evidence of malignancy in the 3 suspicious (but not in the benign/reactive) cases with Ki67 LI values higher than 20%. Correlation between Ki67 LI (> 20%) and cytologic effusion type (benign, suspicious, or malignant) was statistically significant (P < 0.0001). Ki67 immunostaining has value as an adjunct testing to cytomorphology and other immunostains in distinguishing benign from malignant effusions. The addition of Ki67 immunostaining to conventional cytology appears more sensitive than cytomorphology alone and may assist in arriving at accurate diagnoses in suspicious cases with inconclusive cytomorphologic features.

Adenocarcinoma↗