Prognostic value of FDG-PET in Hodgkin lymphoma for posttreatment evaluation. Long term follow-up results.

Determining the viability of residual tumor masses is a great challenge after primary treatment of Hodgkin lymphoma. FDG-PET may play a crucial role in this procedure. In this study, files of 128 Hodgkin lymphoma patients were reviewed, who were treated in three Hungarian hematology centers between January 1995 and February 2005. CT scan showed residual tumor mass by all of them. Their median follow-up was 75.5 months from PET examination. The number of true-positive, true-negative, false-positive, false-negative subjects were 29, 83, 10, 6, respectively. Sensitivity of post-treatment FDG-PET was 83 %, specificity 93 %, positive predictive value 74 %, negative predictive value 93 %, and accuracy 88 %. The difference between the event free survival of PET positive and negative cases is highly significant (p=0.0000), according to the Mantel-Cox test. Our results in the largest cohort of patients, in accordance with literature, clearly indicates that patients with negative FDG-PET results are unlikely to progress or relapse during the longest follow-up.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)-clinicopathological features based on the data of two Hungarian lymphoma centres.

UNLABELLED: Clinicopathological features of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) differ from those of the classical Hodgkin lymphoma (cHL). Our aim was to examine clinical presentation, therapeutic and survival results of NLPHL patients in Hungary based on the data of two centres, and incidentally we analyzed the clinicopathological characteristics and differential diagnostic difficulties of this rare entity. We analyzed the clinical features, treatment and survival data of 536 Hodgkin lymphoma patients who had been diagnosed and primarily treated in our institutes between 1995 and 2004. Mean follow-up time was 82.7 (3-144) months of the total 536 HL patients. Sixteen (3%) of the patients were diagnosed with NLPHL, 93% of them presented with early-stage disease. None of the patients showed extranodal or splenic involvement or bulky disease. One patient received chemotherapy alone, six received only involved field radiotherapy while six underwent combined modality treatment. We applied watch and wait strategy in three cases. Overall response rate was 100% (93.75% complete). Two NLPHL cases transformed to non-Hodgkin's lymphoma. In contrast to the classical HL, the 10-year prognosticated overall survival rate was 100 vs. 82%, the event free survival was: 75% vs. 70%. In NLPHL group there were no late or multiple relapses and none of them died. CONCLUSIONS: NLPHL is a rare disease, thus these are limited experiences with its diagnosis and treatment. Since the disease has an excellent outcome, it is very important to prefer less toxic or local therapies to reach long term survival similar to that of the normal population.

Second malignancies after treatment for Hodgkin's disease.

The occurrence of treatment-related second malignancy following Hodgkin's disease (HD) has now been recognized as a major problem. The purpose of this study was to review our experience with second malignancies in patients treated for Hodgkin's disease, comparing the results with the international literature data. Six hundred and sixty five patients with HD were treated in our department, between 1978 and 1996. Second neoplasm developed in 32 cases (4.8%). Seven secondary hematological malignancies were observed: four acute nonlymphocytic leukemias, two non-Hodgkin's lymphomas and one chronic myeloid leukemia. Among patients with second hematological malignancies, the mean age at diagnosis of HD was 44 years and the mean interval until the development of second malignancy was 6.1 years. Five patients received chemo- and radiotherapy and in two cases chemotherapy was used. Three of the seven patients are alive. Twenty-five patients have had solid tumors, affecting lung (5), breast (3), colon (3), stomach (2), urinary bladder (2), head-and-neck (1), thyroid gland (1), esophagus (1), liver (1), pancreas (1), furthermore, three sarcomas and two malignant melanomas were observed. Their mean age at the diagnosis of HD was 46 years and the mean period of latency was 8.3 years. Chemotherapy was applied to nine patients, 16 patients received both chemo- and radiotherapy. Eleven patients had solid tumors in the region irradiated earlier. Ten out of the 25 patients are alive, three patients' present state is unknown. Since alkylating agents increase the risk of leukemia and irradiation contributes mainly to other malignancies, future treatment protocols should attempt to reduce the most serious consequence of therapy without compromising the survival. It is necessary to investigate the impact of additional risk factors. Careful, lifelong observation is indicated for patients with HD, with special attention given to new clinical signs and symptoms.

Sorption behavior of prochloraz in different soils.

The sorption behavior of the imidazole fungicide prochloraz [PCZ; N-propyl-N-[2-(2,4,6-trichlorophenoxy)ethyl]imidazole-1-carboxamide] was studied in batch experiments with different soils. The soil organic matter content was found to control the amount sorbed by different soils. K(d) values ranged from 56 +/- 0 to 552 +/- 10 (mean = 221 +/- 5) and K(OC) values from 7273 +/- 0 to 16250 +/- 1300 (mean = 11829 +/- 303). As calculated from a linear regression of K(d) versus %OC, K(OC) was 12900 +/- 1300. Additionally, the pH value of the soil had considerable influence on the sorption of the weakly basic PCZ (pK(a) = 3.8), giving rise to stronger sorption at lower pH. K(d) values determined on pH-modified soils confirmed the pH dependency. Sorption isotherms on two soils were recorded, initial concentrations ranging from 0.09 to 5.71 mg L(-)(1). The Freundlich isotherm was fitted to the values measured. The Freundlich exponents calculated were significantly smaller than unity, indicating nonlinear sorption. Sorption experiments with two metabolites of PCZ (PCZ-formylurea and PCZ-urea) revealed K(d) values one-fourth to one-third those for PCZ on two soils.

Bioavailability of a nonylphenol isomer in dependence on the association to dissolved humic substances.

Humic substances are important environmental components since they represent a very large part of organic compounds on earth. According to many reports, dissolved humic substances are a determinant parameter for the bioavailability of xenobiotic compounds. For the present bioavailability studies, two kinds of dissolved humic substances, a commercially available humic acid and fulvic acids isolated from peat were used. As the relevant xenobiotic, a defined branched nonylphenol isomer, 4(3',5'-dimethyl-3'-heptyl)-phenol (p353NP) was synthesised according to Friedel-Crafts alkylation. Equilibrium dialysis studies were implemented in order to investigate the association between 14C-labelled p353NP and dissolved humic substances. The biodegradability in the presence of dissolved humic substances was examined in experiments with the nonylphenol degrading bacterium strain Sphingomonas TTNP3 and with p353NP as sole carbon source. The results showed that p353NP-humic acid associates were formed in high amounts, whereas no adducts with fulvic acids occurred. In the degradation studies with Sphingomonas TTNP3, no effects of dissolved humic substances on the bioavailability of p353NP could be observed. It was assumed that the association between nonylphenol and humic acids occurs rapidly and is reversible. Thus, the formation of "labile" complexes did not influence biodegradation rates, which were quite low.

[Principles of drug therapy of malignant tumors: the role of malignant progression in the choice of effective drugs]. / A rosszindulatú daganatok gyógyszeres terápiájának irányelvei: A malignus progresszió szerepe a hatóanyagok kiválasztásában.

The progress that has been achieved in the development of antitumour drugs and the management of the untoward side effects both contributed to the increasing importance of drug-therapy beside surgery and radiotherapy in cancer treatment. The treatment of the micrometastasis which appears very frequently already at the time of the diagnosis and also the control of the metastatic progression represent the main importance of drug therapy in cancer patients. In spite of the numerous clinical trials indicating the usefulness of drug therapy both as adjuvant in the management of the primary tumours and in the treatment of metastatic tumours there are certain reservation against chemotherapy in medical circle. It is noteworthy that at the present time the strategy of cancer-therapy is subject of considerate changes. Beside to achieve cure by eradication of the tumour cells it has been recommended in various oncological center that stabilization of the malignant disease and to offer a good quality of life for the patients should also be the aim of the therapy. The purpose of this communication is to present those factors which are necessary to consider in the planning of anticancer drug therapy. Certainly to achieve cure or to improve the quality of life of cancer patients it is important to select the most appropriate drug (cytostatics, hormones, biological response modifiers or agents improving the quality of life) and treatment schedule. Since antitumour drug therapy must be classified as active, palliative/active, palliative and supportive/terminal treatments the present survey gives emphases on the underlying role of malignant progression before deciding the type of treatment.

[Treatment of methimazole-induced agranulocytosis with granulocyte-macrophage colony stimulating factor]. / Metothyrin indukált agranulocytosis kezelése granulocyta-macrophag colonia stimuláló faktorral.

The authors treated a patient with methimazol (Metothyrin)-induced agranulocytosis with human recombinant granulocyte-macrophage colony stimulating factor (GM-CSF). On day seven, after combined antibiotics, corticosteroid and at a dose of 270 ug daily subcutaneous GM-CSF therapy the septic state of the patients rapidly cured and the leucocytes reached the peripheric blood. No side effects were found. The publication of this case history might help to determine the place of human GM-CSF-s therapy in the treatment of agranulocytosis of different origin.

[Possibilities of abdominal ultrasonic diagnosis in the clinical follow up of malignant lymphomas]. / A hasi ultrahang-diagnosztika lehetöségei a malignus lymphomák klinikai követésében.

Authors performed follow-up abdominal ultrasound examinations in malignant lymphomas, with abdominal lymphoid masses, during chemotherapeutic treatment. It was measured the volume-change of the examined abdominal lymphoid masses. Authors elaborated a new method, basing upon pseudocolour-coding of the ultrasonic picture. With the use of this method it became possible to evaluate quantitatively the change of internal echo-structure of abdominal lymphoid masses during the treatment. The change in the time of the measured structural parameteres was represented graphically. In the opinion of authors, the change of structural parameteres shows a characteristic connection with the course of the disease. The clinically evident relaps can be proceded more weeks by an unfavourable trend in the change of ultrasonic structure parameters. According to the results of the authors, the abdominal ultrasound diagnostic, complemented with the method of pseudocolour-coding can successfully help the clinical follow-up of malignant lymphomas.

[Significance of ultrasonic studies of the splenic hilus in malignant lymphoma]. / A léphilus ultrahang vizsgálatának jelentösége malignus lymphomában.

In the course of abdominal ultrasonography of patients suffering from malignant lymphoma the authors observed frequently morphological alteration of the splenic vein in the hilus of spleen. Three conditions were determined which when occurring simultaneously created cases of dilated vein in the hilus of spleen. The incidence rate of dilated vein of the hilus of spleen has been determined in patient group with lymphoma and "healthy" control group. It was studied whether in cases with morphological alteration of the vein in the hilus of spleen the occurrence of abdominal nodal manifestations or the alteration of the sonographic structure of the spleen were detectable at a higher rate in the group of patients suffering from lymphoma. On the basis of the results the authors are of the opinion that when the sonographic signs of the dilated splenic vein of the hilus of spleen are present the negative result of sonography must be considered more carefully than usual and other more sensitive diagnostic methods must be applied for the detection of the abdominal manifestations of lymphoma.

[Determination of dihydropyrimidine dehydrogenase in the prediction of toxic side effects of 5-fluorouracil]. / A dihidropirimidin-dehidrogenáz meghatározás jelentösége az 5-fluorouracil toxikus mellékhatásainak elörejelzésében.

In the chemotherapy of colorectal cancers the most frequently given drug is 5-fluorouracil, which in certain cases reduces or delays the appearance of the local recurrence or metastasis. It is well known that the patient's response to 5-fluorouracil is very different concerning both, effects and side effects. More than 80% of the infused drug is catabolised in the first 20 minutes after the treatment. The first and rate limiting enzyme of the catabolism is dihydropyrimidine dehydrogenase, which has the highest activity in the liver and lymphocytes. The activity of this enzyme shows correlation with the blood level of 5-fluorouracil. The deficiency of this enzyme caused severe, in some cases lethal toxicity, its congenital deficiency is responsible for familial pyrimidinaemia. Authors intended to collect data about the dihydropyrimidine dehydrogenase activity of colorectal cancer patients, in order to screen enzyme deficiency or very low enzyme activity, which might be in connection with the appearance of severe side effects, moreover to determine the optimal dose of 5-fluorouracil before the treatment. Dihydropyrimidine dehydrogenase activity was determined in the lymphocytes of 48 colorectal cancer patients, treated by 5-fluorouracil, at the beginning of each cytostatic cycle. The enzyme activity of the patients was between 1.2 and 24.4 pmol/min/10(6) lymphocyte. The value of the enzyme activity fluctuated in a range, characteristic for the individual patients and this value was not modified by the 5-fluorouracil treatment. Dividing the patients in two groups, low (lower than 5 pmol/min 10(6) lymphocyte) and high (higher than 15 pmol/min 10(6) lymphocyte) dihydropirimidine dehydrogenase activity, we found that decrease in the white blood cell number and appearance of the side effects occurred with much higher frequency in the low activity group which resulted in the reduction of the dose or in more serious cases interruption of the treatment. Authors conclude that the determination of the dihydropyrimidine dehydrogenase activity in the lymphocytes is a valuable method in the prediction of the toxic side effects of 5-fluorouracil, in the screening of the congenital enzyme deficiency and in the individualization of the 5-fluorouracil dosage.

[Merkel cell tumor]. / Merkel-sejtes daganat.

Merkel cell cancer is a rare carcinoma arising from the neuroendocrin cells of the skin. The diagnosis is based on the clinical behaviour, histopathologic and ultrastructural findings and immunohistochemical results. An unusual case of Merkel cell carcinoma is presented. Mass from the umbiculus and a right inguinal lymph node was excised in a 63-year-old female. The histologic features of a typical, primitive small cell tumor combined with the immunohistochemical evaluations established the diagnosis. Rare polynuclear giant cells were focally present in our case. Patient was treated with combination of chemotherapy (Cisplatin, Etoposid) and radiotherapy. Control examinations showed complete respond. One year later metastasis developed. Resection of all known metastasis were performed. Two months after the laparotomy she died of metastatic disease. The autopsy did not reveal any other primary tumor. The capricious nature of the clinical course and the differences between this tumor and other carcinomas is emphasized.

[Positron emission tomography ia an effective tool in modern oncology]. / A pozitronemissziós tomográfia a korszerü onkológiai ellátás hatékony eszköze.

A total of 399 positron emission tomography (PET) examinations were carried out with a GE 4096 Plus PET scanner during the past 5 years on patients referred to the National Institute of Oncology in Budapest. The majority (n = 316) of these investigations were performed with the use of [18F]-fluorodezoxyglucose (FDG) to map the glucose metabolism; [11C]-methionine PET was indicated in 79 cases to detect protein transport and metabolism. The perfusion tracer [15O]-butanol was applied in only 4 cases to answer certain oncology-related, differential diagnostic questions. The oncological examinations were related to primary diagnostics, staging/restaging and therapy monitoring. In the staging/restaging and therapy monitoring of known tumours, conclusive results were achieved in 81-82% of the cases by using either FDG or [11C]-methionine as tracer. The concordant numerical data indicated that the PET investigation provides a definite answer to the question of the presence or absence of viable tumour tissue, with similar effectivity in any of the above indications, no matter whether FDG or [11C]-methionine is used. The search for occult primary tumours was the most frequent indication within the primary diagnostics: 10 (37%) primaries were localized by using FDG PET in the 27 investigated cases. This is a remarkably high value, especially in view of the failure of all the conventional diagnostic procedures carried out prior to the PET investigations. Application of PET may be indicated in all cases when the ultimate question is a non-invasive estimation of viable tumorous tissue.

[Clinical features and guidelines of treatment of mucosa-associated lymphoid tissue lymphoma of stomach] / A primer gyomor MALT limfóma klinikuma és korszerû kezelésének irányelvei.

The mucosa-associated lymphoid tissue (MALT) lymphoma is a very indolent disease. Its most common site is the stomach. The lymphoma begins as a reactive lymphocyte accumulation mostly due to an infection of Helicobacter pylori (HP). Through repeated mutations this tissue is transformed into the characteristic MALT lymphoma. At the time of the diagnosis the lymphoma is usually localised, but in one third of the patients the disease has already been disseminated. There are not any commonly accepted guidelines of therapy concerning this primary gastric MALT lymphoma, but certain general tendencies have already been defined. In the early disease the aim of the treatment is curative with the preservation of the stomach as much as possible. In a considerable number of cases, when the surface of the stomach is affected by HP, one can achieve histological and molecular biologic remission after eliminating the bacteria. However, there is no such therapeutic consequence to be expected in case of a deeply invasive tumour. The optimal treatment of patients of this group as well as those whose disease is resistant to HP eradication treatment together with those who are HP negative is radiotherapy or surgery with chemotherapy. In this latter case quality of life becomes worse. In an advanced case cure is impossible and chemotherapy is the most effective to ease the patient's state.

Treatment of drug-induced bone marrow suppression with recombinant human granulocyte/monocyte colony stimulating factor.

The haemopoietic growth factors are relatively new additions to the treatment of drug-induced bone marrow suppression. Treatment with growth factors may induce primitive cells to enter into cell cycle. In clinical practice they have beneficial effects on the neutropenia following cytotoxic chemotherapy, bone marrow transplantation, and it may be effective in severe chronic neutropenia by cause drugs. One of the classes of drugs which cause serious agranulocytosis are the antithyroid drugs. A thyrotoxic patient with methimazole-induced agranulocytosis was treated with recombinant human granulocyte-monocyte colony-stimulating factor (rHu GM-CSF). Seven days following treatment with daily subcutaneous injection of 270 micrograms rHu GM-CSF combined with antibiotics and glucocorticosteroids, granulocytes reappeared in the peripheral blood and the sepsis resolved. No side effects of the treatment were observed. The combination of rHu GM-CSF and glucocorticosteroids was successful in restoring normal granulocyte count.

Putative role of dihydropyrimidine dehydrogenase in the toxic side effect of 5-fluorouracil in colorectal cancer patients.

Dihydropyrimidine dehydrogenase (DPD) is the first and rate limiting enzyme in the catabolism of 5-fluorouracil (5-FU). It has been reported from various laboratories that the plasma concentration of 5-FU was influenced by DPD activities in various normal human organs (e.g. liver or lymphocytes). Since the congenital deficiency in DPD caused severe, in some cases lethal, FU-related toxicity, it was decided to collect data about the DPD activity in colorectal cancer patients in order to investigate the possible correlation between the enzyme activity and appearance of the side effects of 5-FU. Assuming that DPD activity in lymphocytes represents the 5-FU catabolic capacity of the organism, DPD activity was determined in the lymphocytes of 48 patients with colorectal cancer after surgery during the therapeutic course with 5-FU and folinic acid. On the basis of the enzyme activity, patients were divided into three categories: low (DPD <5.03 pmol/min/10(6) lymphocytes); medium (DPD = 5.04-13.25 pmol/min/10(6) lymphocytes), and high (DPD > 13.26 pmol/min/10(6) lymphocytes) activity groups. By evaluating the toxic side effects during the 5-FU + folinic acid treatment, the following results were obtained. In the low DPD activity group, 9 of 11 patients had 5-FU-related side effects (mucositis, diarrhea, myelotoxicity, angina pectoris, hypertension). In 3 patients, no change of the therapy was needed, in 3 patients symptoms could be reversed by dose reduction of 5-FU while in 3 patients interruption of 5-FU therapy was needed. In the medium DPD activity group, mild toxicity (diarrhea, transitory hypertension) occurred in 5 of 29 and in the high activity group (diarrhea) in 1 of 8 patients, respectively. In these last two groups, no dose reduction of 5-FU was necessary. The present study furnished further evidence for the possible correlation between the 5-FU side effects and DPD function. Consequently, it is recommended to measure DPD activity prior to 5-FU based chemotherapy, which might be helpful in avoiding drug-related toxicity by adjusting the dose of 5-FU individually.

Role of endothelin-1 in the development of a special type of cardiomyopathy.

The role of endothelin-1 (ET-1) in certain pathological states is still unclear. We have investigated the effect of anthracyclines (maximum dose, 450 mg/m(2) of body surface) on left ventricular systolic and diastolic function and how it influences the level of plasma ET-1 in 21 patients (12 female and nine male) with Hodgkin and non-Hodgkin lymphoma. We also studied the association between plasma ET-1 concentration and echocardiographic parameters. Serum ET-1 was measured by ELISA. Left ventricular function was analysed by echocardiography: ejection fraction (EF), velocity-time integral, E- and A-waves, E:A ratio, deceleration time (DT) and Doppler index were all measured. Statistical analysis was made by the Wilcoxon rank test. EF and serum ET-1 level decreased significantly (EF, 56.29+/-5.0% to 48.57+/-5.9%, P<0.0001; ET-1, 6.45+/-4.0 pg/ml to 2.9+/-1.0 pg/ml, P<0.0001). DT increased significantly (179.8+/-47.8 ms to 215.5+/-66.7 ms, P<0.01) after anthracycline therapy. There was no difference in other echocardiographic parameters before and after therapy. The decrease in serum ET-1 concentration might be a result of anthracycline's direct cytotoxic effect and the decreasing level of ET-1 can play a role in the reduction of EF. However, more studies are needed to evaluate the presence and severity of endothelial damage.