Cetuximab, gemcitabine and capecitabine in patients with inoperable biliary tract cancer: a phase 2 study.

PURPOSE: Biliary tract cancer is rare and has dismal prognosis. Chemotherapy has its role in inoperable disease but the role of targeted agents like cetuximab remains to be defined. On the basis of high epidermal growth factor receptor expression of biliary tract cancers this study aims to investigate the efficacy of cetuximab, gemcitabine and capecitabine in an exploratory phase 2 trial. PATIENTS AND METHODS: Inoperable biliary tract cancer patients were treated with the combination of gemcitabine (1000 mg/m(2) on day 1 and 8), capecitabine (1300 mg/m(2)/d on day 1-14) and weekly cetuximab (400mg/m(2) loading and 250 mg/m(2) maintenance dose) in 21-d cycles until progression or the appearance of intolerable side-effects. RESULTS: Out of 34 patients (mean age 59.7 years) accrued in this study 16 had intrahepatic, eight extrahepatic cholangiocarcinoma and 10 gall bladder cancer. The best overall response rate was 17.6% (two complete responses and four partial responses) and the clinical benefit rate was 76.5%. After a median of 15.4 months follow-up the median progression free survival was 34.3 weeks and the median overall survival was 62.8 weeks. The performance status and chemotherapy efficacy were independent and significant markers of survival. Only moderate side-effects were registered in this study. KRAS mutation was evaluable in 24 tumours, all of these were of wild type. CONCLUSION: The efficacy of cetuximab, gemcitabine and capecitabine combination is encouraging and a well tolerated treatment of inoperable biliary tract cancers.

Molecular classification of colorectal cancer: a dream that can become a reality.

Despite thousands of studies about colorectal cancer (CRC) as much as extensively usage of prognostic antibodies÷genes and clinical trials that include the newest targeted drugs, this tumor still remains in the top of both incidence and cancer-related mortality. In this review, we intended to correlate our experience in field of colorectal cancer with the literature data and to present our vision about the prognostic and predictive role of some of the most used molecular and immunohistochemical examinations in the field. The prognostic and predictive values of parameters such as microsatellite instability, angiogenesis, Maspin gene/protein, K-ras and BRAF mutations are discussed in relationship to the classical antibodies such as Keratin 7/20, p53 or HER2. At the end, we correlated these informations and tried to realize a molecular classification of colorectal cancer, similar to breast carcinomas, in order to establish targeted groups of patients for targeted therapy.

Practical value of the new system for Maspin assessment, in colorectal cancer.

Maspin is a serine protease which belongs to the serpin family and seems to play an important role in inhibiting angiogenesis and tumor proliferation. The significance of its expression in colorectal cancer (CRC) has not been elucidated so far. In our study, we tried to identify, based on Maspin expression, four groups of CRC, with possible prognostic impact. In 121 CRC, we analyzed the Maspin expression in correlation with the clinico-pathological features, microsatellite status and other markers such as p53, bax, bcl-2, VEGF (Vascular Endothelial Growth Factor) and CD31. Based on the percentage and intensity of Maspin expression in the tumor cells, the cases were grouped in four classes: negative, with cytoplasmic predominance, nuclear predominated, and cases with mixed (cytoplasmic-nuclear) expression. 9% of the cases were negative, 44% presented cytoplasmic predominance, the nuclear predominance was revealed in 24% of the cases, and the other 23% of CRC having a mixed Maspin positivity. The cytoplasmic predominance was correlated with a better prognosis, p53 negativity, bax positivity, and lack of tumor budding. Forty percent of microsatellite instable (MSI) cases presented mixed expression, this pattern being also related to a lower angiogenesis. Nuclear predominance was associated with p53 positivity, the lowest survival rate and intense VEGF expression. In conclusion, CRC with cytoplasmic predominance and mixed Maspin expression seems to present better prognosis whereas nuclear predominance is connected with high aggressivity.

Molecular pathways and pathomorphology of colorectal cancers.

Colorectal carcinomas (CRCs) evolve through multiple pathways. These pathways may be defined based on two molecular features: (1) chromosomal instability and (2) chromosomal stability. Tumors showing chromosomal stability evolve through the so-called microsatellite instability pathway. These types of tumors show different clinico-pathological features and need different therapy so very important to separate them. As Hematoxylin-Eosin (HE) based histology is influenced by the different genetic alterations of a tumor, it is reasonable that different gene expression profiles result in different HE morphology. Our aim was to find specific histomorphological features specific for colorectal tumors showing different molecular features. We analyzed the clinicopathological parameters of 324 colorectal carcinomas, 26 hereditary non-polyposis colorectal cancers, 32 sporadic high-level microsatellite-instable (MSI-H) cancers and 266 microsatellite-stable or low-level microsatellite-instable (MSI-L) cancers among them. Our results showed that we could recognize different genetic types of tumors on the base of clinicopathological features like patient's age, tumor localization and histological characteristics of CRCs. Main histological parameters help in differentiation are inflammatory background, nuclear features and pattern of infiltration. Clinical parameters like clinical stage and localization and careful histological analysis helps to select molecular method to define molecular features and to select the most appropriate therapy of a given tumor.

Practical value of the complex analysis of sentinel lymph nodes in colorectal carcinomas.

BACKGROUND: Despite modern factors, which seem to predict outcome, lymph node (LN) status remain the main prognostic factor, which also shows the need for complex oncotherapy in colorectal carcinomas (CRC). Sentinel lymph nodes (SLNs) mapping is a very controversial method, which can increase the number of identified LN. MATERIALS AND METHODS: In 28 patients who underwent surgical intervention between December 2009 and December 2010, we performed in vivo SLNs mapping followed by ex vivo examination at 1, 10, and 48 hours. All blue nodes were separately included. In cases without LN metastases (pN0) five multilevel sections and immunohistochemical stain with cytokeratin 20 were performed in SLNs. RESULTS: Two cases were excluded because they were in pT4 stage. In one case the diameter of lymph nodes was about 10 mm and we obtained a false negative result (negative SLNs with positivity in the non-SLNs). From the other 25 cases, 13 do not presented LN metastases or micrometastases, nine had metastases only in the SLNs and the other three in both SLNs and non-SLNs. Mean identified number of LNs was 15. The blue dye intensity increased after formalin fixation and some nodes with metastases were blue stained only after 10 hours. CONCLUSIONS: SLNs mapping is a simple and inexpensive technique, which can improve the management of CRC. All in vivo and ex vivo blue LNs should be considered SLNs. Ultrastaging of SLNs is an expensive method, with uncertain results. High diameter of LNs seems to be an exclusion criterion for SLNs mapping.

The differences between the endothelial area marked with CD31 and CD105 in colorectal carcinomas by computer-assisted morphometrical analysis.

UNLABELLED: The aim of our study was to compare the CD31 and CD105 endothelial area (EA) by computer-assisted morphometrical analysis in colorectal carcinomas (CRC). Two hundred and eleven surgical specimens with CRC were immunohistochemical analyzed with markers for angiogenesis CD31 and CD105 (Endoglin). We determined the area of endothelial cells occupied in the microscope field (EA). RESULTS: The median area was 6.93 +/- 4.25% for CD31, respectively 5.65 +/- 2.23% for CD105. In the majority of cases, the CD31 EA was higher than CD105 EA. In the cases with the predominance of mature vessels, and also in the cases after radiotherapy, the CD105 EA was higher than CD31 (5.69 +/- 2.49%, respectively 10.23 +/- 5.93%). In our study, we tried to describe the clinico-morphological features of these cases. CONCLUSIONS: The CD105 seems to be the best marker for study of neoangiogenesis in CRC. Sometime, CD105 marks the activated endothelium of preexistent mature vessels. The radiotherapy destroys the neoformed but also the preexistent vessels. For the antiangiogenic treatment, it is important to determine the intensity of angiogenesis but also the type of neoformed vessels.

The angiogenesis in colorectal carcinomas with and without lymph node metastases.

UNLABELLED: Many clinical trials revealed that the anti-angiogenic treatment could improve prognosis in patients with metastatic colorectal carcinomas (CRC), when added to standard chemotherapy. In this paper, we tried to find out if the microvascular density (MVD) determined with CD31, CD105 was correlated with lymph node status, and if the intensity of angiogenesis was different in right versus left colon segments. We studied 187 CRC, with and without lymph node metastases, 128 from left and 59 from right colon. RESULTS: In the right colon, the MVD was higher in the cases where the lymph nodes did not present metastases (pN0) but also when four or more lymph nodes were involved (pN2). In the rectum and sigma, the angiogenesis presented the highest intensity in pN0 and pN1 stage (1-3 lymph nodes with metastases), decreasing in pN2 stage. In the descendent colon segment, the MVD did not present differences between the cases with and without lymph node metastases. CONCLUSIONS: Our study reveals that the most indicated cases for antiangiogenic treatment seem to be the pN0 and pN1 cases in the rectum and sigma, respectively pN0 and pN2 cases in the right colon. We tend to believe that the angiogenesis intensity in CRC is higher in early-stages of the tumoral proliferation but it is not an increasing process, having rather an oscillating character. Therefore, the angiogenesis remains an independent prognostic and predictive factor and the antiangiogenic treatment is necessary to be individualized for each patient.

Secretory breast cancer in a 7.5-year old boy.

Breast cancer is extremely rare in children, and consequently no consensus has been reached on the optimal treatment modalities. The medical history and treatment plan for a 7.5-year old male breast cancer patient is described. Radical mastectomy with sentinel node biopsy was performed in October 2002. As no malignant cells were detected in the sentinel node, and no BRCA1-2 mutations were detected, no further radio- or chemotherapy was performed. A "wait-and-see" policy was decided on. Further treatment will be given if this becomes necessary with the development of metastases.

[Human papillomavirus and cervical cancer: genetic background of the neoplastic process]. / Humán papillomavírus és méhnyakrák: a tumoros folyamat kialakulásának genetikai háttere.

In a 2-year period, 136 HPV positive cytological samples of the cervix uteri were analyzed at the Department of Molecular Pathology, National Institute of Oncology, Hungary. Comparison with the international data obtained from the literature revealed that the Hungarian epidemiological data bore closest resemblance to the European ones except some differences. The HPV18 is rather seldom encountered in this country. Similarly low occurrence was noted only in Japan. However, the 14.1% occurrence rate of HPV58 in Hungary is by far higher than that in any other country in this analysis except Japan where this virus is of similarly high frequency. In Hungary, the incidence of HPV59 is relatively high just like in Central and South America. HPV33 and HPV66 infections occur in a significantly higher number with Hungary than in any of the countries studied. In our study The European type variant of HPV16 (E-V-350G) occurred in 2/10 CIN II-III cases. The authors also compared the various clinico-pathological grouping of HPV types published, and identified several inconsistencies. Viruses considered to have high risk occurred in intact epithelium, CIN I-II-III and carcinoma alike. The general tendency was, however, that certain viruses correlated with specific clinico-pathological entities. At present there is no reason to include the PCR-based HPV typing in the mass screening of cervical cancers. HPV typing and physical state of the virus can reasonable be determined if the cervical cytology is suspect for HPV infection or even control examination after "loop" conisation. Negative cytology completed with negative HPV-DNA test means the lack of cancer risk even in the case of a previously removed CIN or carcinoma. However, a positive HPV test detected after conisation associated with negative cytology finding indicates a risk of 70% of the development of CIN within 2 years.

Angiography effectively supports the diagnosis of hepatic metastases in medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) belongs in the group of neuroendocrine tumors with early lymphatic and hepatic dissemination. A high rate of undetectable metastases is hypothesized to be responsible for the frequent mismatch between the apparent relatively small tumor burden and the elevated plasma tumor marker level. METHODS: Thirty-six MTC patients with residual/recurrent biochemical signs (elevated basal calcitonin level) and/or characteristic general symptoms (diarrhea and/or flushing) were systematically examined by conventional radiology, whole-body 18F-deoxyglucose positron emission tomography (PET), dynamic liver computed tomography and magnetic resonance imaging, and hepatic angiography. RESULTS: Conventional diagnostic imaging revealed lymph node (LN) involvement in the cervical, mediastinal, supraclavicular, and axillary regions (16 cases), and multiple pulmonary (3 cases), bony (1 solitary and 1 multiple case), and breast (1 case) metastases. (18)F-deoxyglucose PET identified all these extralymphatic metastatic lesions (except 2 cases with multiple pulmonary metastases), and also supradiaphragmatic LN involvement in 34 (94%) patients. In 32 (89%) cases, multiple small (generally < or = 1 cm) hypervascular, hepatic metastases undetectable by other imaging methods were localized angiographically. Of the 23 original pathologic specimens investigated, 18 (78%) exhibited LN involvement. The smallest primary tumor in patients with hepatic metastases was 1 cm. CONCLUSIONS: Hepatic angiography is recommended for primary staging in MTC patients with a primary tumor measuring 1 cm or larger, and/or pathologically proven LN involvement, and also during restaging for suspected recurrences to avoid unnecessary extensive surgical LN dissection in the neck and mediastinum.

Hepatocyte proliferation and cell cycle phase fractions in chronic viral hepatitis C by image analysis method.

OBJECTIVE: Chronic hepatitis is characterized by necrosis of liver cells, accompanied by an inflammatory reaction and compensatory cell proliferation. The interaction of the core and non-structural proteins of hepatitis C virus (HCV) with several cellular factors suggests that cell proliferation may be influenced by HCV. The aim of this study was to investigate hepatocyte proliferation and DNA ploidy patterns in patients with chronic viral hepatitis C (CH-C) compared with chronic non-viral hepatitis (CH-N), using a TV image analysis method. METHODS: The DNA index (DI) and cell phase fractions (G1, S, G2) were measured by means of digital picture analysis method on nuclear suspensions of Feulgen stained hepatocytes. Cells were taken from the liver biopsy specimens of 71 patients with CH-C and 24 patients with CH-N. Twenty-six normal liver samples were used as controls. RESULTS: Significantly higher G1 (94 +/- 4) and lower S (3.56 +/- 3.16) phase fractions were measured in CH-C compared with CH-N (G1, 90 +/- 6; S, 6.4 +/- 5.99). The DI of moderate (1.12 +/- 0.05) and severe (1.12 +/- 0.05) CH-C showed near-aneuploid DNA content, while diploidy (DI < 1.10) was detected in cases of CH-N. CONCLUSION: The higher G1 and lower S cell cycle phase fractions in CH-C reflect decreased hepatocyte proliferation compared with CH-N. The near-aneuploid DNA content of the HCV-infected liver samples may be a sign of increased genetic instability, which may contribute to the carcinogenic potential of HCV.

[Prognostic value of cell heterogeneity in cervical cancer determined by digital image analyzer of DNA content]. / A cervixdaganatok citometriai heterogenitásának vizsgálata sejtenkénti DNS-analízissel, a daganatheterogenitás prognosztikai értékének meghatározása céljából.

Frequency and prognostic value of cell heterogeneity in FIGO 1a-2a cervical cancer was examined, in 66 of patients underwent Wertheim type hysterectomy between 1989 and 1995 in National Institute of Cancer, Budapest, Hungary. A newly developed DNA image analyses (DNACE) was used in paraffin embedded tissues after enzymatic hydrolyses for evaluation of the DNA content in cervical cancer. In 30.3% of examined tissues (20/66) two subgroups was found. There was significant differences in the DNA indexes (DI) between the subgroups (p = 0.0001). In the remaining 69.7% of the cases only one subgroup was present. The frequency of two subgroups was higher between aneuploid (78.4%), or hyperploid (81.5%) type cervical cancer, however there was no significant difference between the two groups. On the other hand there was significant difference in the presence of two subgroups between the well and less differentiated cervical cancer. The frequency was higher between the less differentiated groups (p = 0.02). Looking at the prognostic value of subgroups, there was no significant correlation between the heterogeneity of cervical cancer and FIGO stage, or lymph node metastasis (p = 0.6855), or vascular/lymphatic space infiltration (p = 0.2558), or invasiveness of cancer (0.0823). There was neither significant value found between the outcome of disease and the number of subgroups present (p = 0.8738). It is though that the present of cellular heterogeneity in cervical cancer is connected with the differentiation of the cancer cells, and can be a good prognostic value in the anticipation of the aggressiveness of cervical cancer. Looking at the present result, there was no significant connection between the heterogeneity of cervical cancer and the outcome of the disease, so further examination should be done.

[Hepatocyte proliferation and DNA content in chronic hepatitis C]. / Hepatocyta-proliferáció és DNS-tartalom krónikus C-hepatitisben.

Apart from inflammatory reaction, the death of hepatocytes is also a characteristic of chronic hepatitis. Necroinflammation is followed by compensatory proliferation, which plays a rather important role in maintaining the liver function. Authors studied the DNA content of hepatocytes in patients with chronic hepatitis C, and determined the ratio of hepatocytes in phases G1, S and G2 to determine the hepatocyte proliferation and regeneration capacity of the liver. Liver biopsy samples were taken from 23 patients with chronic hepatitis C and from 16 with chronic hepatitis with non viral origin, from which nuclear suspension counts were done based on the histological slides. A total of 16 normal liver tissue samples served as control. The DNA index, G1, S, G2 and polyploid fraction were determined using the DNACE (Digital Image Analyzer for Nuclear Deoxyribonucleic Acid Content Estimation, KFKI/NIO, Hungary) digital imaging process. The DNA index was found to be significantly higher in the chronic hepatitis C than in the non-C group, with the verification of aneuploidy (DI > 1.10). The chronic non-C hepatitis cases showed lower G1 (88 +/- 6) and higher S (7.8 +/- 6.6) fractions. In comparison to the normal liver tissues, the chronic hepatitis C cases also revealed a significantly (p < 0.05) lower G1 (91 +/- 5) and a higher S (5.4 +/- 3.6) fraction, though staying behind the values found for the non-viral group. The deviation can be explained by the presentation of the HCV proliferation inhibitory effect. The polyploid cell fraction revealed a significantly higher value in the chronic non-viral cases as compared to the C virus group, reflecting on the decreased regeneration capacity of the liver. When comparing the HCV groups, significant differences were found between the mild and moderate cases in respect to the G1 and G2 fractions. At the same time, the moderate and severe cases showed statistical deviation regarding the DNA index. Chronic hepatitis C virus infection reduces the proliferation of hepatocytes and the regeneration capacity of the liver. The aneuploid DNA index reflects on genetic instability, which could be the basis of the malignant transformation of the cells.

Effect of hepatitis C virus on hepatocyte proliferation and DNA ploidy in patients with chronic hepatitis C.

Hepatitis C virus infection may act as a cofactor by inducing chronic hepatitis and cirrhosis, playing a promoting role in the multistep process of hepatocarcinogenesis by maintaining liver inflammation, hepatocyte necrosis and regeneration. The aim of this study was to measure the DNA ploidy and cell proliferation of hepatocytes in patients with chronic hepatitis C. Hepatocyte nucleus suspension was analyzed from 45 patients with chronic hepatitis C and from 27 patients with chronic hepatitis non-C. The histopathological pattern of chronic hepatitis samples/grade, stage/was investigated. A significantly lower cyclin A protein expression and cytometrically measured S-phase fraction was observed in chronic hepatitis C as compared to chronic hepatitis non-C, representing suppressed cell proliferation of virus infected cells. In the chronic hepatitis C groups, the S-phase fraction depression was moderate, the grade of inflammation and cyclin A protein expression were also decreased, mainly in the severe grade group. In chronic hepatitis non-C, the number of cyclin A staining-positive cells increased parallel with severity of the inflammation. In addition, the HCV infection caused a near diploid minimally aneuploid cellular DNA content in the cases of moderate and severe histological groups. In contrast, the cellular DNA content was consequently diploid-independent of histological grades in chronic hepatitis non-C. Our results suggest that in chronic viral hepatitis C, the hepatocyte proliferation is suppressed parallel with the degree of inflammation, while the DNA content becomes aneuploid. The aneuploidy is a sign of genetic instability, predisposing the affected cells to unbalanced chromosomal abnormality which finally leads to malignant transformation.

[Current diagnostic method, prognosis estimation and therapy of papillary thyroid cancer: recommendations of the medical universities and the National Oncologic Institute of Budapest]. / A papillaris pajzsmirigy-carcinoma korszerü kivizsgálása, prognózisbecslése és kezelése: az orvostudományi egyetemek és az Országos Onkológiai Intézet ajánlása.

Physical examination, cervical ultrasonography (US) and aspiration cytology are the mainstays of the preoperative diagnostics of papillary thyroid carcinoma. For the staging of suspected malignant cases, cervical and mediastinal CT (MRI for inconclusive results) is indicated before any surgery. The end-result of primary treatment is assessed by total-body iodine scintigraphy and the serum human thyroglobulin (hTG) level. For long-term follow-up, physical examination and the serum hTG level are the most reliable tools (6-monthly), supplemented by cervical US and chest X-ray (yearly), and total-body iodine scintigraphy (2-yearly). If these furnish positive results, further examinations may be indicated. In suspected relapses of hTG non-producing and iodine non-accumulating papillary carcinomas, 201thallium chloride or 99mTc-sesta-MIBI (methoxy-isobutyl-isonitrile) scintigraphy, and positron emission tomography with 18fluoro-deoxyglucose or 11C-methionine may be of help. For estimation of the prognosis (cause-specific survival) of the patients, the MACIS score system of the Mayo Clinic is widely accepted, the patients being divided into low-risk and intermediate/high-risk categories. The recommended standard surgical intervention is near-total thyroidectomy (2-4 g residual glandular tissue left at the upper pole of the less-involved lobe), with a central cervical lymph node dissection for diagnostic purposes. In cases of lymph node dissemination, dissection (radical, modified radical, selective or microdissection) of any of the involved compartments (central, right or left cervical, or upper mediastinal) is indicated for therapeutic reasons, the method of which is depending on the extent of the metastatic involvement. Following adequate surgical intervention, no adjuvant radioiodine therapy is indicated for low-risk cases with a tumour of less than 1 cm diameter. For other low-risk or intermediate/high-risk patients, radioiodine ablation (R0N0M0) or a therapeutic radioiodine dosage (R2N1M1) is indicated. In cases at high-risk of local/regional relapse and in radioiodine non-accumulating tumorous cases, external radiotherapy may be applied. Thyroid hormone medication in a TSH suppressive dose is indicated during the first 5 postsurgical years: the goal is to achieve a TSH level below 0.1 (determined by a 3rd generation assay). If no relapse occurs or the case is a low-risk one, following the 5 years, it is enough to maintain the TSH level in a subnormal range (0.1-0.3).

Prognostic significance of P53 histochemistry and DNA histogram parameters in head and neck malignancies.

BACKGROUND: The aim of the study was to determine the role of quantitative pathological parameters in prognosis of head and neck malignancies. MATERIALS AND METHODS: 51 head and neck squamous cell carcinoma patients were examined for mutant p53 gene expression (45 out of 51 patients) by immunohistochemistry and for cellular DNA-content (44 out of 51 patients) using digital picture analyzer. Statistical analysis was performed using BMDP package. RESULTS: No correlation with prognosis was found for age, sex, localization, T-classification and therapy. There was significant relationship between N-status and overall survival (p = 0.0008). No correlation was found with overall and disease-free survival for either histologic type or grading. P53: No significant correlation was detected with overall survival. A relationship was found between mutant p53 and metastasis-free time (p = 0.06). Ploidy: There were no significant differences between aneuploid and euploid tumors for either disease-free or overall survival. Synthetic (S)-phase fraction: A correlation was found for both survival rates (p = 0.029) and metastasis-free time (p = 0.05). Polyploid fraction (PF): correlation was shown for both overall survival (p = 0.0128) and metastasis-free time (p = 0.0038). CONCLUSION: There is correlation between p53 overexpression and metastatic potential and there is a significant relationship between SPF and PF value and prognosis (metastasis-free and overall survival) of head and neck cancer.

Desmoplastic small round cell tumour of the pleura: a case report with further cytogenetic and ultrastructural evidence of 'mesothelioblastemic' origin.

A typical case of desmoplastic small round cell tumour of the pleura in a 25-year-old man is described. In addition to the typical histological and immunohistological findings, the EWS-WT1 fusion product was also observed. Ultrastructurally, some tumour cells displayed intracytoplasmic neolumina, with short microvilli characteristic of submesothelial cells. These findings support the theory of a splanchnopleuric intraembryonic mesodermal, 'mesothelioblastemic' origin, both morphologically and cytogenetically.

Trisomy 12 in juvenile granulosa cell tumor of the ovary during pregnancy. A report of two cases.

BACKGROUND: Granulosa cell tumors constitute only 5% of ovarian neoplasms, and their coexistence with pregnancy is extremely rare. Juvenile granulosa cell tumor has a good prognosis if it is confined to the ovary, but this type behaves more aggressively than the adult type at advanced stages. CASES: We report on successful completion of two singleton pregnancies and deliveries of normal infants in two young women with juvenile granulosa cell tumor diagnosed and treated during pregnancy. This tumor has rarely been described in association with pregnancy. The presence of trisomy 12 as a single chromosomal abnormality was detected in these two tumors. Both tumors were localized strictly to the ovary, so conservative surgery was applied and proved sufficient to remove all tumor tissue. Follow-up showed no signs of recurrence 18 and 53 months after the interventions. CONCLUSION: These cases support the contention that trisomy 12 is a nonrandom chromosome abnormality in juvenile granulosa cell tumors and that pregnancy may affect nuclear stability in this tumor.

Epithelial mesothelioma with deciduoid features.

A rare case of malignant mesothelioma in a 15-year-old girl is described. The patient presented with secondary amenorrhoea and clinical symptoms resembling those of an ovarian cyst. One large and multiple small peritoneal nodules were found at laparoscopy. Histologically the tumour was characterised by an unusual pattern with a superficial resemblance to decidual reaction, but because of significant mitotic activity the diagnosis of a malignant tumour, epithelial mesothelioma with deciduoid features, was made. The patient died 11 months after diagnosis. Post-mortem examination revealed extensive extraperitoneal spread.

[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.