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Correlation between DNA content, expression of Ki-67 antigen of tumor cells and immunophenotype of lymphocytes from malignant pleural effusions.

Malignant cells isolated from 26 malignant pleural effusions, collected from patients bearing metastatic carcinoma, were examined using flow cytometry. Expression of Ki-67 antigen, DNA ploidy, S phase fraction, DNA index of tumor cells and the percentage of aneuploid cell populations were determined. Lymphoid cells from the same malignant effusions and from 10 nonmalignant ones were examined using a panel of monoclonal antibodies (mAb) versus several CD antigens. While the percentages of T cells (CD3+, CD4+, CD8+) and B cells (CD19+) did not differ significantly in malignant versus nonmalignant effusions, those of CD56+ lymphocytes were found to be significantly depressed in malignant diploid and malignant aneuploid effusions as compared to benign ones. Expression of IL-2 receptors on lymphocytes, demonstrated by anti-CD25 mAb, was significantly higher in malignant diploid and malignant aneuploid effusions as compared with nonmalignant ones. An increase in the percentage of Ki-67-positive malignant cells was significantly correlated with the decrease of NK cells. S phase fraction, DNA index and the percentage of aneuploid populations did not correlate with the picture of lymphoid cells from pleural effusion. On the other hand, the percentage of Ki-67-positive tumor cells in pleural effusions was inversely proportional to the patients' survival time, although it was not statistically significant. Our data suggest that the poor prognosis of cancer characterized by the presence of an aneuploid cell population of malignant cells and the high percentage of proliferating cells in pleural effusions can be linked to the depression of NK cells.

Adenocarcinoma↗

Endothelin in the kidney in malignant phase hypertension.

A role for endothelin in malignant phase hypertension has been suggested on the basis of reported increases of circulating plasma immunoreactive endothelins in animal models. Recently, a hypertensive rat model that exhibits a genetically determined tendency for developing spontaneous onset malignant hypertension has been described. Expression of the three genes endothelin-1, endothelin-2, and endothelin-3 was quantified in the kidney by specific RNase protection assays in rats with established malignant hypertension, in rats with benign hypertension with and without a genetic susceptibility to malignant hypertension, and in normotensive Sprague-Dawley rats. Endothelin-1 mRNA levels were significantly elevated in the group with malignant hypertension compared with the other three groups. For determination of whether endothelin-1-mediated effects were crucial in the transition from benign to malignant phase hypertension, an oral nonspecific combined endothelin-A and endothelin-B receptor antagonist (bosentan) was given to hypertensive rats susceptible to malignant hypertension. No hypotensive effects were observed, and no significant difference in the incidence of malignant hypertension was observed between treated and control groups. In conclusion, although increased endothelin-1 mRNA expression was found in kidney tissue from rats developing malignant hypertension, blockade of endothelin-1-mediated effects did not prevent the transition from benign phase hypertension. Hence, increased renal endothelin-1 expression in this model of malignant hypertension does not appear to have a causative role and may simply reflect cellular damage and ischemia.

Animals↗

T-helper type 1/T-helper type 2 balance in malignant pleural effusions compared to tuberculous pleural effusions.

STUDY OBJECTIVES: Malignant and tuberculous pleurisies are two major causes of lymphocyte-dominant pleurisy. Several studies have already reported that tuberculous pleurisy is a T-helper type 1(Th1)-dominant disease. In this study, we sought to examine the Th1/T-helper type 2 (Th2) balance, especially focusing on the polarizing status of T-cells to Th1/Th2 in malignant pleural effusions by measuring cytokines in pleural effusions and by evaluating the polarizing status of T-cells on the point of stimulation with interleukin (IL)-12 and/or IL-18. Furthermore, we evaluated inhibitors of interferon (IFN)-gamma production in effusions to rule out the possibility of direct inhibition of T-cell polarization. PATIENTS: Effusion samples were collected from 19 patients with malignant pleurisy caused by lung cancer and from 7 patients with tuberculous pleurisy. MEASUREMENTS: Concentrations of pleural fluid IFN-gamma, IL-12, and IL-4 were measured. IFN-gamma production of T-cells enriched from malignant pleural effusions in the presence of IL-12 and/or IL-18 was also examined. We further compared the inhibitory activity of malignant pleural effusions against IFN-gamma production and analyzed the expression of T-cell immunoglobulin mucin, mucin domain (Tim-3), a Th1-specific molecule in pleural fluid T-cells. RESULTS: Although malignant pleural effusions showed low levels of Th1 and Th2 cytokines and ratios of IFN-gamma and IL-12 to IL-4 were low, isolated T-cells produced a significant level of IFN-gamma in the presence of IL-12 and IL-18. Soluble factors were not found to inhibit IFN-gamma production in malignant pleural effusions. In tuberculous pleural effusion, ratios of IFN-gamma and IL-12 to IL-4 were significantly higher, and T-cells showed the expression of Tim-3 messenger RNA. CONCLUSIONS: We confirmed that T-cells in the malignant pleural effusions are mainly naïve or not definitely polarized to Th1. Moreover, malignant tumor does not actively distort the cytokine condition through production of soluble inhibitors within effusions. The present study indicates that antitumor immunity may be enhanced by restored IFN-gamma activity through combination of IL-12 and IL-18, and that it will lead to new therapies for malignant effusion.

Aged↗

P53-immunoreactive cells in benign and malignant effusions: diagnostic value using a panel of monoclonal antibodies and comparison with CEA-staining.

The diagnosis of malignancy in peritoneal and pleural effusions can be difficult, because activated mesothelial cells may resemble malignant cells. P53 mutations are the most frequent genetic changes in human cancer and translate into an overexpression of the p53 protein detectable by immunocytochemistry. In this study, we investigated the sensitivity and specificity of 4 different monoclonal antibodies (moAB) against p53 for the diagnosis of malignancy in effusions. We also compared p53 staining with CEA immunocytochemistry which previous work had established as a specific marker of malignancy in body cavity effusions. Normal and malignant cells from 28 benign and 52 malignant effusions (pleura and ascites) were examined by indirect immuno-alkaline phosphatase method. Four different moAB against p53 (PAB 1801, PAB 240, DO-1 and DO-7) and one moAB against CEA (CEA-84) were used. Antibodies p1801, p240 and DO-1 react with 52-75% of cases of effusions with malignant cells, but also with 38-80% of benign effusions. Only the antibody DO-7 and the CEA moAB show specificity for malignant cells reacting respectively with 20 (55%) of cases. A combination of these 2 markers does not enhance the sensitivity for the detection of tumor cells. No direct correlation between CEA and p53 immunostaining could be established. The sensitivity and specificity of staining p53 in malignant cells by immunocytochemistry depend strongly on the antibody used. Some p53 moAB are positive with reactive cells in ascites and pleural effusions. Currently, p53 staining of expressing cells does not improve the identification of malignant cells in comparison with CEA immunocytochemistry, but may help to screen for patients with p53 mutations.

Antibodies, Monoclonal↗

What is the clinical significance of transudative malignant pleural effusion?

BACKGROUND: A few reports of transudative malignant effusion on a small number of patients have suggested the need to perform routine cytologic examination in all cases of transudative pleural effusion, whether encountered for malignancy or not. The purpose of this study was to investigate whether cytologic examination should be performed in all cases of transudative pleural effusion for the diagnosis of malignancy. METHODS: We performed a retrospective study of 229 consecutive patients with malignant pleural effusion, proven either cytologically or with biopsy. In patients with transudative pleural effusion, we reviewed medical records, results of transthoracic echocardiography, fiberoptic bronchoscopy, chest X-ray, chest CT scan, and ultrasonogram of the abdomen. These data were examined with particular attention to identifying whether or not the malignancy was suggested on chest X-ray, examining the involvement of the superior vena cava, great vessels, and lymph nodes, determining the presence of pericardial effusion, and observing the endobronchial obstruction. RESULTS: Transudative malignant pleural effusion was observed in seven (3.1%) of the 229 patients, and was caused either by the malignancy itself (6 patients) or by coexisting cardiac diseases (1 patient). All the patients showed evidence suggesting the presence of malignancy at the time of initial thoracentesis, which facilitated the decision of most clinicians on whether to perform cytologic examination for the diagnosis of malignancy. CONCLUSION: Therefore, in all cases of transudative pleaural effusion, no clinical implications indicating malignancy were found on cytologic examination.

Biopsy↗

The diagnostic yield of pleural fluid cytology in malignant pleural effusions.

BACKGROUND: The development of a pleural effusion in a patient with a known malignancy often raises the possibility that the effusion is due to malignant involvement of the pleura. Accurate diagnosis of the cause of the pleural effusion in such a patient is essential as the treatment and prognosis may vary. Currently, thoracentesis and cytologic analysis of pleural fluid cytology is usually the initial diagnostic step. AIM: To assess the diagnostic yield of pleural fluid cytologic examination in patients with suspected malignant pleural effusions seen at our centre. METHODS: Retrospective review of the results of pleural fluid cytologic examination performed on 103 patients who presented with suspected malignant pleural effusions. RESULTS: The underlying malignancies in these patients were as follows: bronchogenic carcinoma (51.5%), breast carcinoma (29.1%), hepatocellular carcinoma (1.9%), carcinoma of the stomach (1.9%), malignant mesothelioma, nasopharyngeal carcinoma, renal cell carcinoma, carcinoma of the oesophagus, lymphoma, carcinoma of the colon (1% each), unknown (9.7%). Initial pleural fluid cytology was positive for malignancy in 48.5% of patients. The yield of this diagnostic procedure was improved with repeated pleural fluid cytologic specimens and when combined with a percutaneous pleural biopsy. There was no statistically significant difference in the clinical features and pleural fluid characteristics of patients with malignant pleural effusions and those in whom the pleural effusions were paramalignant. CONCLUSION: Pleural fluid cytologic examination is a useful initial step in the diagnostic work-up of patients with suspected malignant pleural effusions. The diagnostic yield of such examination is improved with repeated pleural fluid cytologic specimens and when combined with a percutaneous pleural biopsy. Clinical presentation and pleural fluid characteristics were inadequate in differentiating between malignant and paramalignant effusions.

Biopsy, Needle↗

[Diagnostic value of tissue polypeptide antigen in pleural effusions with malignant pleural mesothelioma].

There are no known tumor makers of malignant pleural mesothelioma. We measured the concentration of TPA in the pleural effusions from patients with malignant pleural mesothelioma and from patients with other pleural diseases, evaluate its clinical usefulness. The concentration of TPA was more than 7,000 U/l (mean: 18,600 +/- 9,867 U/l, n = 5) in all patients with malignant pleural mesothelioma, but it was less than 4,000 U/l in those with benign asbestos pleurisy and other benign pleural effusion (benign asbestos pleurisy 1,598 +/- 570, n = 5: p < 0.01, tuberculous pleurisy 1.37 +/- 759, n = 11: p < 0.01, others 2,497 +/- 2,152 n = 3: p < 0.05). The concentration of TPA in the pleural effusions was not significantly different between malignant pleural mesothelioma and lung cancer (12,287 +/- 17,070 U/l). However, in all patients with lung cancer and high TPA concentrations, cytologically malignant cells were detected in the pleural effusions. TPA was high in all five patients with malignant pleural mesothelioma, but cytologically malignant cells were detected in only one patient. Only in malignant pleural mesothelioma (not in other benign disease or in lung cancer) was the concentration of TPA more than 4,000 U/l, and no evidence of malignancy was obtained by cytological methods. These findings suggest that assessing TPA in the pleural effusion might contribute to the diagnosis of malignant pleural mesothelioma.

Adult↗

Intrapleural chemotherapy without pleurodesis for malignant pleural effusions. LCSG Trial 861.

Malignant pleural effusions are a common and significant problem in patients with advanced malignancies. In contrast to traditional sclerosing agents, intrapleural chemotherapy has the potential advantage of treating the underlying malignancy, in addition to treating the effusion. The Lung Cancer Study Group evaluated intrapleural cisplatin and cytarabine in patients with malignant pleural effusions from a variety of solid tumors. Forty-six patients with cytologically proven symptomatic and previously untreated malignant pleural effusions were entered. Cisplatin, as a single dose of 100 mg/m2, plus cytarabine 1,200 mg, were instilled into the pleural space via a chest tube that was then immediately removed. The overall response rate, complete plus partial at 3 weeks, was 49% (18/37 patients). One patient experienced reversible grade 3 renal toxic reactions, four patients had grade 3 hematologic toxic reactions, and five patients had grade 3 cardiopulmonary toxic reactions. Median length of response was 9 months for a complete remission and 5.1 months for a partial remission. Although chemotherapy has the potential advantage of treating the underlying malignancy in addition to controlling the malignant effusion, intracavitary cisplatin and cytarabine therapy as administered in this trial appears inferior to existing sclerosing agents for the control of malignant pleural effusions. Although administration is safe, it cannot be recommended for the standard control of malignant pleural effusions, but it may have a role incorporated into combination modality therapies for diseases such as malignant pleural mesothelioma.

Antineoplastic Combined Chemotherapy Protocols↗

Incidence of malignant skin tumors in 14,140 patients after grenz-ray treatment for benign skin disorders.

During the years 1949 to 1975, 14,237 patients received therapeutic doses of grenz rays for the treatment of benign skin disorders such as chronic eczema, psoriasis, and warts. The records of 14,140 of these patients (99.3%) formed the basis for an epidemiologic study of the incidence of skin malignancies in this population. Information about the patients, diagnoses, doses, and sites of treatment was obtained from separate records. The follow-up time was 15 years on the average. We searched the Swedish Cancer Registry, Stockholm, for records reporting the incidence of malignant skin tumors in the study population (incidences of basal cell carcinoma are not registered). The expected number of malignancies was calculated on the basis of age- and sex-standardized incidence data from the Swedish Cancer Registry. In 58 patients, a malignant skin tumor was diagnosed more than five years after grenz-ray therapy had first been administered. Nineteen patients had malignant melanomas, and 39 patients had other malignant skin tumors. The expected number of melanomas was 17.8, and that of other malignant skin tumors was 26.9. None of the patients with melanomas, and only eight of the patients with other malignant skin tumors, had received grenz-ray therapy at the site of the tumor. Six of these eight patients had also been exposed to other known carcinogens. Four hundred eighty-one patients had received an accumulated high dose of grenz rays (greater than or equal to 10 000 rad [greater than or equal to 100 Gy]) on one and the same area. No malignancies were found on those areas. Although we cannot exclude grenz-ray therapy as a risk factor in the development of nonmelanoma skin malignancies, this risk, if any, is small, if recommendations for therapy are followed.

Adolescent↗

Parotid mass as first symptom of a malignant lymphoma.

BACKGROUND AND OBJECTIVES: Primary malignant lymphoma in the parotid gland is rare and seldom described in the literature. We studied the medical history and outcome of seven patients with a primary malignant parotid lymphoma. We looked for prognostic variables and for different behavior of these lymphomas in comparison to lymphomas in the usual sites. METHODS: Between 1985 and 1995, we conducted a retrospective study of the medical histories of malignant parotid tumors operated at our hospital. There were 18 malignancies, of which 7 were primary malignant lymphomas. We classified them according to Rosenberg et al. [Blood 1994;84: 1359-1392]. Outcome and survival time were compared with malignant lymphomas in usual sites. Further we looked for possible prognostic factors. RESULTS: We found an unusually high percentage of primary malignant lymphomas in the parotid gland in our series: 38% of all malignancies. Histological workup showed one Hodgkin lymphoma, two marginal zone B-cell non-Hodgkin lymphomas, two lymphoplasmocytoid non-Hodgkin lymphomas, and two follicular non-Hodgkin lymphomas. The clinical course of these lymphomas is comparable to that in lymphomas in the usual sites. CONCLUSIONS: Primary malignant lymphomas in the parotid gland have no different behavior compared to lymphomas in usual sites. There are no prognostic variables that distinguish a malignant lymphoma in the parotid gland. The only difference is a rather difficult operation to obtain a histologic specimen.

Aged↗

Undiagnosed malignancy in patients with deep vein thrombosis: incidence, risk indicators, and diagnosis.

BACKGROUND: The reported incidence of a subsequent diagnosis of malignancy in patients presenting with deep vein thrombosis (DVT) varies from 2-25%. Risk indicators and diagnostic procedures to be performed in these patients are controversial. METHODS: Four hundred consecutive patients with confirmed DVT included in a randomized clinical trial were followed prospectively for 6 months. The incidence of a subsequent diagnosis of malignancy was calculated and compared between patients with unexplained DVT and patients with secondary DVT. Potential risk indicators for subsequent malignant disease were evaluated. RESULTS: Of the 400 patients, 70 already had been diagnosed with malignancy; another four patients were lost to follow-up. Of the remaining 326 patients, 10 new malignancies were diagnosed among 137 patients with unexplained DVT (7.3%) and 3 new malignancies were diagnosed in 189 patients with secondary DVT (1.6%). The relative risk was 4.6 (95% confidence interval, 1.3-16; P=0.009). Age, gender, or location of the DVT had no significant effect on the incidence of diagnosis when adjusted for unexplained DVT. Ten of these 13 patients (77%) had abnormal clinical findings suggestive of malignancy at the time of presentation with DVT. CONCLUSIONS: Unexplained DVT is a significant risk indicator of underlying malignancy. The majority of patients with undiagnosed malignancy have some clinical abnormality suggestive of underlying malignancy at the time of presentation with unexplained DVT. A simple clinical evaluation comprised of medical history, physical examination, routine laboratory tests, and chest X-ray can detect such patients. Extensive screening of all patients presenting with unexplained DVT does not appear to be justified.

Adult↗

Malignant phyllodes tumours show stromal overexpression of c-myc and c-kit.

Phyllodes tumours are fibroepithelial neoplasms of the breast, the stroma of which can undergo malignant progression to sarcoma. The frequency of malignant lesions varies in different series from 5% to 30%. The aim of this study was to elucidate potential molecular mechanisms in the progression to malignancy in phyllodes tumours. c-myc and c-kit were studied at the protein, RNA(c-myc only) and DNA level. We chose to study c-myc as we have previously shown that Wnt signalling is important in benign, but not malignant, phyllodes tumours. If c-myc is constitutively activated in malignant tumours, this may provide an explanation for why the Wnt pathway is no longer important in these tumours. c-kit is a membrane-bound tyrosine kinase receptor and overexpression is characteristic of gastrointestinal stromal tumours. A previous report suggested that this may also be the case in malignant phyllodes tumours, and we wished to confirm this. We assessed expression of c-myc and c-kit in 30 phyllodes tumours (10 malignant) using in situ hybridization (c-myc) and immunohistochemistry (c-myc and c-kit). 9/10 malignant tumours showed c-myc expression in the stroma, compared to 7/20 benign tumours (p = 0.006, Fisher's exact test). Stromal c-kit expression was found in 5/10 malignant tumours, compared to 1/20 benign tumours (p = 0.008, Fisher's exact test). One tumour had high-level amplification of c-myc, but we found no evidence of mutations of c-kit. We hypothesize that the overexpression of c-myc may drive stromal proliferation in malignant phyllodes tumours, and that c-kit overexpression contributes to the growth of these lesions. c-kit may also be a new therapeutic target in these tumours.

Breast Neoplasms↗

Proteomic analysis of normal and malignant prostate tissue to identify novel proteins lost in cancer.

BACKGROUND: Alterations of important protein pathways, including loss of prostate secretory granules, and disruption of the prostatic secretory pathway have been identified as early events in malignancy. In this study, proteomics was used to map the differences in protein expression between normal and malignant prostate tissues and to identify and analyze differentially expressed proteins in human prostate tissue with particular regard to the proteins lost in malignancy. METHODS: Small quantities of normal and malignant prostate tissue were taken fresh from 34 radical prostatectomy cases. After histological examination, proteins were solubilized from selected tissues and separated using two-dimensional electrophoresis. Using image analysis, the proteome of normal and malignant tissues were mapped and differentially expressed proteins (present in normal and absent in malignant tissue) were identified and subsequently analyzed using peptide mass finger printing and N-terminal sequencing. Western blotting and immunohistochemistry were performed to examine expression profiles and tissue localization of candidate proteins. RESULTS: Comparison of protein maps of normal and malignant prostate were used to identify 20 proteins which were lost in malignant transformation, including prostate specific antigen (PSA), alpha-1 antichymotrypsin (ACT), haptoglobin, and lactoylglutathione lyase. Three of the 20 had not previously been reported in human prostate tissue (Ubiquitin-like NEDD8, calponin, and a follistatin-related protein). Western blotting confirmed differences in the expression profiles of NEDD8 and calponin, and immunohistochemistry demonstrated differences in the cellular localization of these two proteins in normal and malignant prostate glands. CONCLUSIONS: The expression of NEDD8, calponin, and the follistatin-related protein in normal prostate tissues is a novel finding and the role of these important functional proteins in normal prostate and their loss or reduced expression in prostate malignancy warrants further investigations.

Blotting, Western↗

Which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings and is there a way of making a correct diagnosis?

OBJECTIVES: To determine which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings, and to determine if the use of logistic regression models for calculation of individual risk of malignancy would improve the diagnostic accuracy in difficult tumors. METHODS: In a prospective, international, European multicenter study involving nine centers, 1066 women with a pelvic mass judged to be of extrauterine origin underwent transvaginal ultrasound examination by an experienced ultrasound examiner before surgery. A standardized examination technique and predefined definitions of ultrasound characteristics were used. On the basis of subjective evaluation of ultrasound findings, the examiner classified each mass as being certainly benign, probably benign, unclassifiable, probably malignant or certainly malignant. Even when the examiner found the mass unclassifiable (i.e. difficult mass) he or she was obliged to state whether the mass was more likely to be benign or malignant. Borderline tumors were classified as malignant. RESULTS: There were 90 (8%) unclassifiable masses. Multiple logistic regression analysis showed papillary projections, >10 locules in a cyst without solid components, low-level echogenicity of cyst fluid, and moderate vascularization as assessed subjectively at color Doppler examination to be ultrasound variables independently associated with unclassifiable mass. Borderline malignant tumors (n = 55) proved to be most difficult to assess with only 47% being correctly classified (i.e. classified as malignant), 29% being incorrectly classified (i.e. classified as benign) and 24% being unclassifiable vs. 90% of non-borderline tumors being correctly classified, 3% being incorrectly classified and 8% being unclassifiable (P < 0.0001). Papillary cystadeno(fibro)mas, myomas and cases of struma ovarii were also more common among the unclassifiable masses than among the classifiable ones (5.6% vs. 1.1%, P = 0.008; 4.4% vs. 0.9%, P = 0.02; 4.4% vs. 0.2%, P = 0.0006). No ultrasound variable or clinical variable (including CA 125) entered a logistic regression model to predict malignancy in difficult masses. A model could be constructed for difficult masses containing papillary projections but this model performed no better than subjective evaluation of the ultrasound image. Sensitivity and specificity of subjective evaluation with regard to malignancy in the group of unclassifiable masses were 56% (14/25) and 77% (50/65) vs. 91% (220/241) and 97% (712/735) in the classifiable masses. CONCLUSIONS: Borderline tumors cause great diagnostic difficulties, but so do papillary cystadeno(fibro)mas, struma ovarii and some myomas. Logistic regression models do not solve the diagnostic problem in difficult pelvic masses.

Adnexa Uteri↗

Altered CD45 expression in malignant B-1 cells.

CD45 is an important surface glycoprotein which has an intrinsic tyrosine phosphatase activity and has been implicated in cell proliferation, signaling, and differentiation and is associated with the B cell receptor during signaling. In this manuscript, the role of CD45 expression in the development of B-1 malignancies in NZB mice, which serve as a model for human diseases such as chronic lymphocytic leukemia, was investigated. B-1 cells spontaneously hyperproliferate and form a clonal hyperdiploid malignant population in aging NZB mice. Phenotypic analysis indicates that the NZB malignant B-1 cells are bright for IgM, but have reduced levels of CD45 relative to normal, nonmalignant B cells (both B-1 and B-2) and are characterized by dull or negative expression of the CD45 isoform B220/6B2 normally found on all B cells. Malignant B-1 cells demonstrated decreased RNA levels of CD45 relative to IgM expression, while nonmalignant B-2 cells showed similar levels of RNA expression for both CD45 and IgM. As CD45 exists in several isoforms and B cells express the highest molecular weight isoform (B220), malignant B-1 cells were further analyzed with respect to their isoform usage. Although, at the RNA level malignant B-1 cells showed the presence of the of the B220 form of CD45, western blot analysis of B220 protein suggested a posttranslational glycosylation defect in the CD45/B220 expression recognized by the mAb 6B2. F1 recipients of premalignant NZB B-1 cells which had been sorted for IgMhi, B220/6B2negative cells developed hyperdiploid malignant donor B-1 clones earlier than did recipients of NZB B-1 cells which were bright for B220/6B2. However, all the malignant B-1 clones of NZB origin which developed in recipients of both transfer populations were B220/6B2 negative. This indicated that abnormal expression of CD45 may be prerequisite for long-term growth and malignant transformation. Thus alterations in CD45 may result in abnormal functioning of the malignant B-1 cells which may further affect the proliferation of, or signaling within, these cells.

Animals↗

High incidence of malignant pheochromocytoma in a surgical unit. 26 cases out of 100 patients operated from 1971 to 1991.

In this surgical series of 100 pheochromocytomas (PH), where 91 cases were studied and followed up, the frequency of malignancy appears high (29%) on macroscopic criteria observed at the first operation (25 out 26 cases of malignant PH) or thanks to the occurrence of metastases (1 case out of 26 malignant PH). While some clinical signs are suggestive, there is no excretory profile predictive of malignancy. Isolated or predominant secretion of dopamine is not specific of malignancy event if it occurs more frequently and severely in malignant PH. Bilateral involvement, occurring in the setting of phacomatosis or of multiple endocrine neoplasia (MEN II), or in a sporadic case, is not a predictor for malignancy. Contrarily, extraadrenal involvement is a major feature indicative of malignancy. A CT scan which demonstrates possible locoregional invasion, and a MIGB scan revealing distant localizations raise the suspicion of malignancy. The preferred surgical approach is via a laparotomy, thus allowing the exploration of all possible abdominal chromaffin site and the search for intraabdominal metastases. Intraoperative MIBG scanning checks the completeness of the excision. Flow cytometric DNA ploidy studies have been performed in 25 of our patients. The follow up of benign or malignant PH, after excision "for cure" must be life-long: clinically, biologically and by MIGB scan. Persistence of the disease after surgery or recurrence with unresectable metastases can benefit from MIGB and chemotherapy.

3-Iodobenzylguanidine↗

The risk of second malignancy after adjuvant chemotherapy for stomach cancer.

BACKGROUND: Although many trials have been conducted to evaluate the feasibility and effectiveness of adjuvant chemotherapy (ACT) for patients with stomach cancer, the benefits of ACT remain unclear. Moreover, some authors have reported that ACT increased the incidence of second malignancy. The risk of second malignancy was evaluated in patients who underwent treatment for stomach cancer in the past 20 years at Osaka Medical Center for Cancer and Cardiovascular Diseases.METHODS: The study population consisted of 1925 patients who underwent gastrectomies for stomach cancer between the years 1978 and 1992 and who received follow-up examinations to check for second malignancies. They included 1114 patients who underwent surgery only (group A) and 811 who underwent surgery and received chemotherapy (group B). The observed incidence of second malignancy (O) was compared with the expected incidence (E), calculated by the person-year method, using data from the Cancer Registry in Osaka.RESULTS: The average follow-up period was 7.99 years. The total number of patients with a second malignancy was 127 (men, 97; women, 30); 72 patients had the second malignancy in digestive organs; 27 in respiratory organs; and 28 in other organs. The relative risks of a second malignancy in group A and B patients were 1.05 and 1.02 (differences between the two groups were not significant). The relative risks of a second malignancy in patients who received ACT with 5-fluorouracil, Tegafur and Uracil, and FT207 were 0.79, 1.01, and 1.06, respectively (differences between the groups were not significant).CONCLUSION: The risk of second malignancy after chemotherapy for stomach cancer was not high in comparison with the expected incidence. Adjuvant chemotherapy did not increase the risk of a second malignancy.

Journal Article↗

MRI patterns in orbital malignant lymphoma and atypical lymphocytic infiltrates.

OBJECTIVE: To evaluate the potential of MRI in differentiating between malignant lymphomas and atypical lymphocytic infiltrates in the orbit. MATERIALS AND METHODS: MRI, clinical and histopathological findings in 30 patients presenting with orbital lymphoproliferative diseases (malignant lymphoma and atypical lymphocytic infiltrates) were evaluated. RESULTS: MRI detected 28 out of 30 (93%) orbital lymphoid tumors. Seven out of eight (87.5%) atypical lymphocytic infiltrates and 21/22 (95.4%) of malignant lymphomas were detected. One conjunctival malignant lymphoma and one conjunctival atypical lymphocytic infiltrate were missed. Only malignant lymphoma lesions were hyperintense compared to the extraocular muscles on precontrast and postcontrast T1-weighted images. The lacrimal duct was involved only with malignant lymphoma. Bilateral disease was more likely to be malignant lymphoma. Intraconal lesions were more likely to be associated with lesions elsewhere. No malignant lymphoma involved the extraconal fat. Only intraconal atypical lymphocytic infiltrates had indistinct margins. CONCLUSION: In the orbit, MRI features alone may not allow clear-cut differentiation of malignant lymphomas from atypical lymphocytic infiltrates. However, certain imaging features increase the likelihood of distinguishing them. MRI may miss conjunctival disease. Both orbits should be imaged when orbital lymphoid disease is a probability. The presence of intraconal disease should prompt a search for lesions elsewhere. The use of a head coil instead of a superficial coil may be advantageous by eliminating coil shine effect and allowing evaluation of both orbits. Comparison of lesion signal to extraocular muscle signal appears to be a better alternative than cerebral gray matter or periorbital fat in differentiating malignant lymphoma from atypical lymphocytic infiltrates. Since imaging findings overlap, histopathological diagnosis is necessary in all cases.

Adult↗