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Malignant pleural effusions in lymphoproliferative disorders.

In order to determine variables that correlate with malignant pleural effusion and mortality in patients with lymphoproliferative disorders and pleural effusion, a retrospective study was performed. Clinical data of hospitalized patients with a lymphoid malignancy and pleural effusion who underwent thoracentesis from January 1993 to December 2002 were collected. A logistic regression analysis was carried out to determine prognostic variables that predict malignant pleural effusion and hospital mortality. There were 86 patients who were admitted on 91 occasions. The median age was 70 years (range 4 - 92) and the male:female ratio was 44:42. Sixty-four patients (74%) had advanced disease, 43 (50%) had received prior chemotherapy and 9 (10%) were in remission. Of 91 cases of pleural effusions, 44 (48%) were bilateral, 80 (88%) were exudates and 48 (53%) were due to malignant involvement of pleura. In multivariate analysis, symptomatic pleural effusion (odds ratio 10.3, 95% confidence interval 1.7 - 98.3), pleural fluid mesothelial cell count < 5% (odds ratio 8.0, 95% confidence interval 1.4 - 58.2), pleural fluid:serum lactate dehydrogenase (LDH) > or =1 (odds ratio 6.4, 95% confidence interval 1.2 - 45.6) and pleural fluid lymphocyte percentage > or =50 (odds ratio 6.4, 95% confidence interval 1.2 - 50) were significantly correlated with malignant effusion. A secondary cancer (odds ratio 11.9, 95% confidence interval 2.3 - 88.8), pleural fluid:serum LDH > or =1 (odds ratio 10.9, 95% confidence interval 2.6 - 64.9), and pneumonia (odds ratio 6.4, 95% confidence interval 1.7 - 28.6) were significantly correlated with hospital mortality. In conclusion, malignant pleural effusion is the common etiology of pleural effusion in patients with lymphoid malignancy. Many clinical and cytochemical markers have discriminatory values in identifying malignant effusion. A high pleural fluid to serum LDH level correlates with malignant pleural involvement and hospital mortality.

Adolescent↗

Excess smoking in malignant-phase hypertension.

The smoking habits of 82 patients with malignant-phase hypertension were compared with those of subjects in three control groups matched for age and sex. Sixty-seven (82%) of the patients with malignant-phase hypertension were smokers compared with 41 (50%) and 71 (43%) of the patients in two control groups with non-malignant hypertension, and 43 people (52%) in a general population survey. The excess of smokers in the malignant-phase group was significant for men and women, together and separately, for cigarette smoking alone, and for all forms of smoking. There were no significant differences between the control groups. The chance of a hypertensive patient who smoked having the malignant phase was five times that of a hypertensive patient who did not. Twelve patients in the malignant-phase group had never smoked. All were alive three and a half years on average after presentation (range 11 months to seven years). Twenty-four (36%) of the smokers with malignant-phase hypertension died during the same period. The mortality rate was significantly higher among patients with renal failure, as was the prevalence of smoking. Eighteen patients with malignant-phase hypertension had a serum creatinine concentration higher than 250 mumol/l (2.8 mg/100 ml); 17 were smokers and one an ex-smoker. Eleven of these 18 patients died.It is concluded that hypertensive patients who smoke are much more likely to develop the malignant phase than those who do not, and that once the condition has developed it follows a particularly lethal course in smokers.

Age Factors↗

Expression of Fas and Fas ligand and apoptosis in tumor-associated lymphocytes and in tumor cells from malignant pleural effusions.

The CD95 (APO-1/Fas)-Fas ligand (FasL) system is an important mediator of antitumor T cell cytotoxicity. The aim of the current study was to assess its significance in human cancer. Malignant effusions were selected as an environment allowing direct cell-to-cell contact in a fluid phase. Malignant pleural effusions collected from 23 patients with metastatic carcinoma of the bronchus, ovary, stomach or breast were examined by means of flow cytometry. The expression ofFas and FasL, probed with the appropriate antibodies, apoptosis of tumor cells and the characteristics of tumor-associated lymphocytes (TAL) were determined by TUNEL reaction in malignant and nonmalignant (control) effusions. All malignant cells had partially or completely lost the expression of CD95 and expressed an elevated level of FasL. In contrast, TAL obtained from malignant pleural effusions demonstrated a marked decrease in the expression of surface FasL and an increase in surface-bound Fas. The percentage of apoptotic malignant cells was significantly decreased, as compared to TAL and lymphocytes from nonmalignant pleural effusions. There were also differences in the expression of Fas and FasL among mononuclear cells from malignant and nonmalignant pleural effusions. The ability of TAL from malignant pleural effusions to induce apoptosis of K562 cells was diminished, as compared to peripheral blood lymphocytes. Taken together, these data suggest that tumor cells in the microenvironment of malignant pleural effusions can evade immune attack by downregulation of the CD95 receptor and by killing lymphocytes through the expression of FasL. These results confirm earlier reports which showed that lymphocytes from a tumor microenvironment appear to have a depressed cytotoxic action.

Apoptosis↗

Intrapleural cisplatin and cytarabine in the management of malignant pleural effusions: a Lung Cancer Study Group trial.

Malignant pleural effusions are a common and significant problem in patients with advanced malignancies. Pleurodesis with tetracycline or other sclerosing agents is the usual treatment for malignant pleural effusions. In contrast to this approach, intrapleural chemotherapy has the potential advantage of treating the underlying malignancy in addition to controlling the effusion. Intracavitary cisplatin-based chemotherapy, which is cytotoxic rather than sclerosing, has proven safe and effective via the intraperitoneal route in ovarian cancer and malignant mesothelioma. There has been little previous experience, however, with intrapleural cisplatin-based chemotherapy. As part of a planned series of trials in malignant mesothelioma, the Lung Cancer Study Group first evaluated intrapleural cisplatin and cytarabine in patients with malignant pleural effusions from a variety of solid tumors. From April 1986 to November 1987, 46 patients with cytologically proven, symptomatic, and previously untreated malignant pleural effusions were entered on study. A single dose of cisplatin 100 mg/m2 plus cytarabine 1,200 mg was instilled into the pleural space via a chest tube, which was then immediately removed. Patients were evaluated for toxicity and response at 24 hours; 1, 2, and 3 weeks; and then monthly. No recurrence of the effusion was considered a complete response (CR). Partial response (PR) was defined as a 75% or greater decrease in the amount of the effusion on serial chest radiographs. One patient experienced reversible grade 4 renal toxicity, four patients had grade 3 hematologic toxicity, and five patients had grade 3 cardiopulmonary toxicity. The overall response rate (CR plus PR) at 3 weeks was 49% (18 of 37 patients). The median length of response was 9 months for a CR and 5.1 months for a PR. The outcome of this trial was sufficiently encouraging that this regimen has been incorporated into subsequent trials for malignant pleural mesothelioma.

Adenocarcinoma↗

Usefulness of argyrophilic nucleolar organizer regions score to differentiate suspicious malignancy in pulmonary cytology.

OBJECTIVE: Pulmonary cytologic specimens reported as "suspicious for malignancy" pose problems in clinical management. Silver staining for argyrophilic nucleolar organizer regions (AgNOR) has proved useful in making a cytopathologically differential diagnosis between benign and malignant cells. This study aimed to evaluate the usefulness of AgNOR score in the diagnosis of pulmonary cytologic specimens deemed inconclusive by conventional staining methods. METHODS: Pulmonary cytologic specimens initially reported as suspicious for malignancy with Papanicolaou or May-Grünwald-Giemsa (MGG) staining obtained from 35 proved cases were destained then restained using the AgNOR technique. Another 35 cases with clear cytologic diagnosis were also examined for comparison. The median number of dots, defined as the AgNOR score, was used to differentiate malignant from benign specimens. RESULTS: Malignant cases had significantly higher AgNOR scores than benign ones (p<0.001). There were no significant differences among smears previously stained with Papanicolaou or MGG method, among specimens obtained via bronchoscopic brushing, fine-needle aspiration of lung or pleural effusion, or among subgroups of malignant diseases. Based on the results of our previous study, the cutoff value of the AgNOR score to differentiate benignancy from malignancy was set at 6. At this setting, the sensitivity and specificity of AgNOR score were 88% and 80%, respectively, in aiding a differential diagnosis of pulmonary cytologic specimens initially classified as suspicious for malignancy. For those cases with a clear cytologic diagnosis, the sensitivity and specificity of AgNOR score were 92% and 100%, respectively. For all cases, the sensitivity of AgNOR score was 90% and the specificity was also 90%. CONCLUSIONS: The AgNOR score is of value in aiding a differential diagnosis between benign and malignant lesions in pulmonary specimens with equivocal cytologic features.

Artifacts↗

[Malignant hyperthermia].

Malignant hyperthermia susceptibility is a rare pharmacogenetic muscular disorder that may lead to potentially fatal complications in routine anesthesia. Malignant hyperthermia is triggered by volatile anesthetics and succinylcholine. In this article the pathophysiology of malignant hyperthermia, its signs, symptoms and treatment as well as safe anesthetic agents for individuals susceptible to malignant hyperthermia are discussed. Although progress is made in our knowledge of the genetics behind malignant hyperthermia, muscle biopsy and in-vitro contracture testing is still the only way to diagnose malignant hyperthermia susceptibility in the vast majority of cases. Danish Malignant Hyperthermia Center at the Anesthetic Department of Herlev University Hospital, DK-2730 Herlev, takes care of all testing for malignant hyperthermia in Denmark and keeps a registry of all Danes with known or suspected susceptibility to malignant hyperthermia.

Anesthetics, Inhalation↗

Manual and automated AgNOR count in differentiating reactive mesothelial from metastatic malignant cells in serous effusions.

OBJECTIVE: To distinguish reactive mesothelial cells from malignant cells in serous effusions using manual and automated methods of enumeration of argyrophilic nucleolar organizer regions (AgNORs). STUDY DESIGN: In this prospective study, 38 samples of benign (19 cases) and malignant (19 cases) serous effusions were included. AgNOR stain was used in each case along with routine Papanicolaou stain. The smears were examined under an oil immersion objective, and AgNOR dots were counted by direct observation independently by 2 observers. Automated AgNOR counting and morphometry were performed with a Quantimet 600 image cytometer (Leica, Cambridge, England). At least 100 cells were counted in each case. The number of AgNOR dots in individual cells, AgNOR area, nuclear area, AgNOR vs. nuclear area and nuclear perimeter were measured. Data on benign and malignant cells were compared. RESULTS: The AgNOR dots were discrete and smaller in benign effusion cases as compared to coarse and aggregated in malignant effusion cases. In benign reactive effusion cases the mean number of AgNOR dots per nucleus was 2.33 +/- 0.71 and 2.83 +/- 1.15 by the manual and automated method, respectively, whereas that for malignant effusion cases was 7.48 +/- 2.51 and 8.09 +/- 1.69 by the manual and automated method, respectively. Mean total AgNOR areas in benign and malignant groups were 4.77 +/- 2.66 microns 2 and 38.22 +/- 13.71 microns 2, respectively. Mean nuclear area, nuclear perimeter and ratio of AgNORs vs. nuclear area were 48.72 +/- 19.30 microns 2, 24.68 +/- 10.25 microns and .098 in benign effusion cases as compared to 174.25 +/- 82.36 microns 2, 69.03 +/- 27.23 microns and 0.22 in malignant effusion samples. All these values were significantly higher (P < .001, Student's t test) in malignant cells as compared to benign reactive cells. CONCLUSION: AgNOR dot enumeration, AgNOR area and ratio of AgNORs to nuclear area are valuable adjuncts to cytomorphology in differentiating reactive mesothelial cells from malignant cells in serous effusions. Automated AgNOR counting is rapid and less cumbersome.

Adenocarcinoma↗

Porcine malignant hyperthermia susceptibility: increased calcium-sequestering activity of skeletal muscle sarcoplasmic reticulum.

This study tested the hypothesis that calcium-sequestration by isolated sarcoplasmic reticulum was abnormal in skeletal muscle of malignant hyperthermia-susceptible swine. A heavy sarcoplasmic reticulum fraction was isolated from malignant hyperthermia and control muscle using differential and density-gradient centrifugation. Prior to onset of malignant hyperthermia, calcium-sequestering activity (Vmax at 37 degrees C, mumol calcium/mg/min) was twofold increased in malignant hyperthermia sarcoplasmic reticulum compared to control sarcoplasmic reticulum (1.96 +/- 0.50 versus 4.00 +/- 0.87, P less than 0.01), although thermodynamic and kinetic properties of this activity were otherwise indistinguishable between groups. This increased activity of the malignant hyperthermia sarcoplasmic reticulum fraction was associated with twofold increased concentration of Ca-ATPase and calsequestrin protein. When a malignant hyperthermia-reaction developed, calcium-uptake was depressed to less than 5% of control values. These data indicate that malignant hyperthermia is not initiated due to a defect in the calcium-sequestration mechanism, however, loss of calcium-uptake activity occurring after the onset of malignant hyperthermia might result in the propagation and irreversibility of the malignant hyperthermia reaction.

Animals↗

Secondary malignant neoplasms in 71 patients with Sézary syndrome.

BACKGROUND: Sézary syndrome (SS) is characterized by a malignant proliferation of CD4+ve T cells, which may result in a degree of immunoparesis. Immunosuppression is associated with an increased incidence of internal malignant neoplasms and a high rate of nonmelanoma skin cancer, particularly squamous cell carcinoma. Therefore, we reviewed the incidence of secondary malignant neoplasms in patients with SS. OBSERVATIONS: Of 71 patients with SS, 16 (23%) developed 19 secondary and tertiary malignant neoplasms. These malignant neoplasms included 8 cutaneous squamous cell carcinomas, 2 squamous cell carcinomas of the oral mucosa, and 9 other internal malignant neoplasms. The incidence of internal malignant neoplasms was twice that reported in patients of similar age treated for Hodgkin disease (P = .02). Furthermore, the incidence of cutaneous squamous cell carcinoma in the cohort was 42 times that observed in a study conducted in England of an age-matched population (1657 per 1 x 10(5) vs 39 per 1 x 10(5) person-years [95% confidence interval, 626-2856]). CONCLUSIONS: A number of therapeutic modalities for SS are known to be carcinogenic. We compared the different therapeutic modalities received by our patients and found no significant difference between the total cohort of patients with SS and the patients who developed secondary malignant neoplasms. These data indicate that the high incidence of secondary malignant neoplasms in patients with SS is due, at least in part, to the disease itself. The clonal proliferation of CD4+ve T cells and the relative lymphopenia (compared with a healthy population) of nonneoplastic T cells may result in compromised immunosurveillance, so that early neoplasia, whether arising spontaneously or as a result of therapy, are not dealt with appropriately.

Adult↗

A "malignant" variant of status epilepticus.

BACKGROUND: Status epilepticus (SE) frequently does not respond to common first-line anticonvulsants. In a substantial portion of patients, administration of anticonvulsant anesthetics is inevitable. Even this aggressive approach fails to terminate SE in an undefined number of cases. We have coined the term malignant SE for this most severe variant of SE. OBJECTIVE: To assess frequency, risk factors, and in-hospital outcome of malignant SE. DESIGN: Retrospective cohort study. SETTING: Neurologic intensive care unit of a large university hospital. Patients Sample of 35 episodes of SE not responding to first-line anticonvulsants in 34 patients. MAIN OUTCOME MEASURES: Predictive and prognostic features of episodes of malignant SE with persistent epileptic activity after high-dose anesthetics compared with features of the remainder of cases with refractory SE and persistent epileptic activity after failure of first-line anticonvulsants. RESULTS: Status epilepticus that could not be controlled by first-line anticonvulsants resulted in malignant SE in 20% of cases. Patients with malignant SE were significantly younger than patients with refractory SE (P = .03). Encephalitis was identified as an independent risk factor for malignant SE (P = .008). Outcome in malignant SE was poor, with significantly longer duration of seizure activity (P<.001), longer stay in the neurologic intensive care unit (P<.001) and in the hospital (P = .007), and more patients with functional dependency at discharge from the hospital (P = .04). CONCLUSIONS: Malignant SE is not rare after failure of first-line anticonvulsants. The patient at risk is typically young and suffers from encephalitis. Such patients should be treated aggressively early in the course of SE to prevent malignant SE.

Adolescent↗

Preoperative predictors of malignancy in pancreatic intraductal papillary mucinous neoplasms.

HYPOTHESIS: Malignant intraductal papillary mucinous neoplasms (IPMNs) can be predicted before surgery. DESIGN: Retrospective review of a prospectively collected database. SETTING: Academic, urban, tertiary care hospital. PATIENTS: Sixty-four consecutive patients with a pathological diagnosis of IPMN. INTERVENTIONS: All 64 patients underwent surgical intervention for IPMN between December 8, 1988, and October 16, 2002. MAIN OUTCOME MEASURES: Reliable predictors of malignancy. RESULTS: The 64 patients underwent 69 operations: 39 pancreaticoduodenectomies, 18 distal pancreatectomies, 7 total pancreatectomies, 4 neck and/or body pancreatectomies, and 1 cystgastrostomy with pancreatic biopsy. Twenty-three of 69 specimens were malignant-12 in situ (high-grade dysplasia) and 11 invasive. In a univariate analysis of 12 clinical signs or symptoms recorded, diabetes mellitus and jaundice showed a significant association with malignancy of IPMN. Of 24 serum chemistry studies, hematologic studies, and tumor marker analyses (in serum, bile, and pancreatic fluid), elevation of serum alkaline phosphatase and glucose levels showed correlation with malignancy. Computed tomography, ultrasound, and endoscopic retrograde cholangiopancreatography findings did not distinguish between benign and malignant tumors. Atypia on preoperative cytologic analysis was specific for malignancy (93%) but lacked the same degree of sensitivity (40% in situ, 91% invasive, and 67% overall). CONCLUSIONS: Malignancy of IPMNs is suggested by new-onset diabetes mellitus, jaundice, and elevations in serum glucose or alkaline phosphatase levels. Atypia on preoperative cytologic testing is the finding most predictive of malignancy. The absence of these features does not predict benign disease. These findings may help guide patient and physician decision making.

Adenocarcinoma, Mucinous↗

Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery.

BACKGROUND: In the treatment of prostate carcinoma, radiotherapy and surgery are common choices of comparable efficacy; thus a realistic comparison of the potential long term sequelae, such as the risk of second malignancy, may be of relevance to treatment choice. METHODS: Data regarding the rate of incidence from the Surveillance, Epidemiology, and End Results Program cancer registry (1973-1993) were used to compare directly second malignancy risks in 51,584 men with prostate carcinoma who received radiotherapy (3549 of whom developed second malignancies) with 70,539 men who underwent surgery without radiotherapy (5055 of whom developed second malignancies). Data were stratified by latency period, age at diagnosis, and site of the second malignancy. Directly comparing the risks in the radiotherapy group with those in the surgery group largely avoids problems associated with underreporting second malignancies. RESULTS: Radiotherapy for prostate carcinoma was associated with a small, statistically significant increase in the risk of solid tumors (6%; P = 0.02) relative to treatment with surgery. Among patients who survived for >/= 5 years, the increased relative risk reached 15%, and was 34% for patients surviving >/= 10 years. The most significant contributors to the increased risk in the irradiated group were carcinomas of the bladder, rectum, and lung, and sarcomas within the treatment field. No significant increase in rates of leukemia was noted. CONCLUSIONS: Radiotherapy for prostate carcinoma was associated with a statistically significant, although fairly small, enhancement in the risk of second solid tumors, particularly for long term survivors. The pattern of excess second malignancies among men treated with radiotherapy was consistent with radiobiologic principles in terms of site, dose, and latency. In absolute terms, the estimated risk of developing a radiation-associated second malignancy was 1 in 290 for all prostate carcinoma patients treated with radiotherapy, increasing to 1 in 70 for long term survivors (>/= 10 years). Improvements in radiotherapeutic techniques, along with diagnosis at younger ages and earlier stages, are resulting in longer survival times for patients with prostate carcinoma. Because of the long latency period for radiation-induced tumors, this may result in radiation-related second malignancy risk becoming a more significant issue.

Adult↗

Malignant (fibrous) histiocytoma of bone--fact or fancy?.

Malignant (fibrous) histiocytoma is currently defined as a malignant primary bone tumor that contains a mixture of fibrogenic cells and cells that are histologically similar but which appear to be histiocytic. In this type of histiocytoma the nuclei are often indented; cytoplasm is usually abundant and may be slightly foamy; nucleoli are often large; and multinucleated malignant cells are usually a prominent feature. Many dedifferentiated chondrosarcomas, osteosarcomas, and fibrosarcomas of bone contain areas that resemble what we regard as malignant (fibrous) histiocytoma. When the entirety of a malignant tumor of bone fits the outlined histologic pattern, the designation of malignant (fibrous) histiocytoma seems appropriate. From 158 fibrosarcomas of bone and 962 osteosarcomas of bone in our files, 35 tumors were segregated because they appeared to be properly designated as malignant (fibrous) histiocytoma. A wide age range was represented by affected patients, and a large variety of bones harbored these tumors. Approximately one-third of patients eligible for 5-year follow-up were long-term, symptom-free survivors. Four deaths occurred from the tumor after more than 5 years, and one patient had radiographic evidence of pulmonary metastasis 7 years after amputation. Radiation therapy has been curative in at least two cases. The correct designation for these tumors in the light of current knowledge is malignant tumor, consistent with malignant (fibrous) histiocytoma.

Adolescent↗

Patients with malignant meningitis presenting with neuropsychiatric manifestations.

BACKGROUND: Malignant meningitis is often thought of as a late event in the course of cancer. At one time, it was thought to be rare, but it has been recognized more frequently in recent times. Clinical suspicion of malignant meningitis is prompted by neurologic symptoms and signs in patients at risk for this oncologic complication. Neuropsychiatric symptoms previously were not considered as presenting symptoms of malignant meningitis. METHODS: Three patients with cancer with no neurologic symptoms were examined for malignant meningitis based on neuropsychiatric symptoms. Cerebrospinal fluid was examined for malignant cells to confirm the diagnosis of malignant meningitis. RESULTS: The clinical presentation of malignant meningitis for three patients was neuropsychiatric. None of the patients had delirium during their initial presentation. CONCLUSIONS: It is important that clinicians recognize that psychiatric symptoms without neurologic findings may indicate malignant meningitis and that malignant meningitis needs to be included in the differential diagnosis of neuropsychiatric disorders in patients with cancer.

Female↗

Predictive risk factors and prevalence of malignancy in patients with iron deficiency anemia in Taiwan.

Gastrointestinal (GI) tract malignancy is one of the important causes of chronic iron deficiency anemia (IDA). The present study was designed to find out the prevalence and the predictive risk factors of malignancy in the IDA patients. We performed a prospective study in 148 patients with chronic IDA. A series of examinations to explore the GI tract were performed either by radiology and/or endoscopy. A Tc-RBC GI bleeding study was also performed, and prevalence and risk factors of malignancy were calculated. Totally 148 patients were enrolled, with mean age 66.2 years; 88 were male. Eighteen patients (12.2%) were found to have malignant tumors. Ten (6.8%) had benign tumors, and 96 (64.9%) had other benign conditions. No lesions could be detected in 24 patients (16.2%). Clinical symptoms and presence of fecal occult blood could not predict malignancy or any GI lesions. Multivariate logistic regression analysis showed serum ferritin < or =10 microg/L, LDH >250 U/L, and aging as the risk factors of malignancy in the IDA patients (P = 0.003, 0.002, and 0.027; and OR = 7.614, 8.955, and 1.062, respectively). An IDA patient with both serum ferritin < or =10 microg/L and LDH >250 U/L ran a 74.33-times higher risk of malignancy than the patient without (95% CI: 7.115-776.479). Malignancy was an important cause of IDA. High LDH, low serum ferritin, and aging were the risk factors of malignancy in the IDA patients.

Adult↗

Enhanced expression of poly(ADP-ribose) synthetase gene in malignant lymphoma.

Over-expression of cellular protooncogenes has been proposed to function in the initiation and maintenance of malignancies. In order to distinguish malignant lymphoma from reactive proliferative diseases, we surveyed the expression levels of three protooncogenes(c-myc, c-fos and c-myb) in malignant lymphoma and reactive proliferative diseases. An increased level of c-myc or c-fos mRNA was observed in one case, respectively, out of three malignant lymphomata. The other cases exhibited no enhancement in protooncogenes. These oncogenes are critically regulated during differentiation, but the half-life of c-myc mRNA was very short, and the level of the mRNA decreased to the initial level very quickly. Thus, the high level of the expression of these oncogenes may not always be maintained in all malignant cells. We then examined the level of mRNA for poly(ADP-ribose) synthetase in those cases. An enhanced expression for the synthetase gene was observed in all five malignant lymphomata tested, but no increase in the level of the mRNA was observed in any reactive proliferative cases or normal lymph nodes. These results suggest that enhanced expression of poly(ADP-ribose) synthetase gene seems to be a common characteristic of protopathic malignant lymphoma. By using the characteristics of malignant lymphoma, the level of mRNA for the synthetase may be applicable for differential diagnosis of malignant lymphoma from several pathologically indistinguishable diseases.

Blotting, Northern↗

Thyroid neoplasms after therapeutic radiation for malignancies during childhood or adolescence.

BACKGROUND: Recent data indicate that the risk of developing a thyroid neoplasm clearly is increased after high-dose, therapeutic radiation therapy during childhood. To better understand the time course, natural history, and histopathology of thyroid lesions that develop after high-dose irradiation, the authors undertook a retrospective study of all survivors of childhood and adolescent malignancies who were treated at Memorial Sloan-Kettering Cancer Center and who developed a clinically apparent thyroid neoplasm. METHODS: The authors searched the data base of the Department of Pediatrics, the hospital-based tumor registry, and the hospital medical records database for patients with thyroid neoplasms. RESULTS: Thirty-three patients were identified who developed a thyroid neoplasm after therapeutic radiation. Primary diagnoses were Hodgkin disease (n = 18 patients), non-Hodgkin lymphoma (n = 10 patients), acute lymphoblastic leukemia (n = 2 patients), acute myeloid leukemia (n = 1 patient), Wilms tumor (n = 1 patient), and neuroblastoma (n = 1 patient). The median age at the time of diagnosis of the primary malignancy was 12.0 years (range, 3.7-18.3 years), the median radiation dose to the thyroid gland was 2400 centigrays (cGy; range, 1000-4200 cGy), and the median interval from the time of radiation therapy until the recognition of thyroid disease was 13.0 years (range, 6.2-30.1 years). Thirteen of 33 thyroid lesions (39%) were malignant (11 papillary carcinomas and 2 follicular carcinomas). Age at diagnosis, gender ratio, and time elapsed since initial treatment did not differ between patients with malignant and benign lesions, but the median radiation dose to the thyroid was lower in patients who had malignant disease compared with patients who had benign disease (2000 cGy vs. 2950 cGy; P = 0.03). Disease was confined to the neck in all patients who had malignant thyroid lesions; after a median follow-up of 6.5 years (range, 0.9-12 years), none of the patients developed progressive or recurrent disease. CONCLUSIONS: Data from this study suggest that a high proportion of clinically apparent thyroid neoplasms that develop after therapeutic radiation for a childhood malignancy are malignant. However, most of these thyroid malignancies do not appear to behave in an aggressive fashion. Because thyroid neoplasms may not become evident for decades after radiation therapy, all individuals who are at risk require life-long follow-up.

Adenoma↗

Long-term risk of malignant neoplasm associated with gestational glucose intolerance.

BACKGROUND: Previous studies have demonstrated an association between diabetes mellitus and cancer risk. However to the author's knowledge, no data regarding the risk of cancer associated with subclinical impaired glucose tolerance have been published to date. An association between various types of cancer and any continuum of risk across the spectrum of glucose tolerance may be important in determining the nature of the association between diabetes mellitus and the risk of malignancy. METHODS: The current study was conducted to examine the long-term risk of malignant neoplasms associated with maternal glucose intolerance. A 20-year follow-up study of a cohort of women who had previously taken part in a study in 1980 that investigated maternal glucose metabolism and fetal outcome was performed. Gestational glucose metabolism, smoking behavior, and weight and height measured at the time of index pregnancy, as well as weight, height, and smoking behavior assessed by questionnaire in 1999, were examined. The main endpoint of the study was hospital admission with a diagnosis of malignant neoplasm as ascertained by linkage data. RESULTS: Thirty-four of the 753 women living in Grampian (4.5%) were admitted to the hospital with a diagnosis of malignant neoplasm; of these, 18 cases were malignant neoplasms of the breast. After adjustment for known risk factors, both malignant neoplasm and malignant neoplasm of the breast were found to be significantly associated with gestational glucose intolerance. CONCLUSIONS: Subclinical glucose intolerance during pregnancy was found to be associated with a dose-related increase in the risk of malignant neoplasm, particularly malignant neoplasm of the breast.

Adult↗