Unfavorable Parameters Research Articles

Unfavourable Outcome and Heterogeneity of Partner Chromosomes in Chronic Lymphocytic Leukemia with 14q32/IGH Translocations.

Translocations of 14q32/IgH have a low incidence in CLL. Partner chromosomes and the prognostic significance are poorly defined. Four hundred thirty cases of CLL seen at the Hospitals of Ferrara, Salamanca and Siena between 1992 and 2006 were studied. Inclusion criteria were:a.diagnosis of CD5/CD19+ CLL with k/λ restriction,b.cytogenetic/FISH data,c.immunophenotypic data,d.complete hematological and clinical data. Lymphomas in leukemic phase were excluded.FISH was performed for 17p13/TP53, 11q22.3/ATM, 6q21, chr 12 centromere, 13q14 and 14q32/IGH. Patients with no detectable aberration or isolated 13q− were included into a favourable cytogenetic group (group 1), those with +12, 6q− or 1–2 aberrations into an intermediate risk group (group 2) and those with 17p−, 11q−, ≥ 3 aberrations into an unfavourable group (group 3). Cases with 14q32/IGH translocation as primary chromosome change represented a specific category (group 4) and were studied with FISH probes for the detection of partners (BCL1, BCL2, BCL3, BCL6, c-MYC, BCL11A, PAX5, CCND3, CDK6). One hundred eighty-six cases were allocated into group 1; 158 into group 2; 64 into group 3, and 22 into group 4. Additional aberrations were found in a minority of cells in 8 patients in group 4. Being the aim of the study to assess whether the 14q32/IGH translocation represented an unfavourable parameter as compared with cases in the favourable or intermediate cytogenetic risk groups, cases within group 3 were excluded from the analysis and the data presented here will refer to 366 patients belonging to groups 1,2 and 4. Translocation partners of 14q32/IGH were identified in 9/22 cases: 2p13/BCL11A, (n 1); 6p21/CCND3 (n 1); 7q21/CDK6 (n 1); 18q21/BCL2 (n 6). Thirteen cases did not show involvement of the loci studied. Cases with 14q32/IGH translocations were characterized by typical morphology and classical immunophenotype (score 4–5 in 92% of the cases). Unmutated IGVH genes were found in 11/18 cases tested (61%); ZAP-70 was positive in 3/5 cases tested. Median age was 63.5 years (range 18–97), male:female ratio 240/126; 345 patients were in Rai stage 0-II, 21 were in stage 3–4; CD38 was positive in 137/366 cases. There was no difference between groups 1,2 and 4 for age, stage, male:female ratio, hematological parameters at diagnosis, IGVH mutations and ZAP70. CD38 was more positive in group 4 than in group 1 (p=0.028). There was no difference in survival and treatment free interval (TFI) when comparing cases in group 4 with and without additional aberrations. Cases in group 4 had a shorter TFI and a shorter survival when compared with group 1 (p=0.02) and group 2 (p=0.02). The difference maintained its statistical significance at multivariate analysis for TFI (p=0.02) along with stage (p<0.0001) and CD38 positivity (p<0.0001) and for survival (p=0.02) along with sex (p=0.006) and stage (p=0.0001). In conclusion, the 14q32/IGH translocation in CLL shows heterogeneity of partner chromosomes and it represents a cytogenetic marker predicting for an evolutive form of CLL.

Factors Associated with Low Incidence of Exclusive Breastfeeding for the First 6 Months

The identification of factors that are associated with early cessation of exclusive breastfeeding is important for defining strategies for the promotion of exclusive breastfeeding. The objective of this study was to identify the determinants of exclusive breastfeeding cessation before 6 months, including variables that generally receive little attention, such as the influence of grandmothers, breastfeeding technique, and sore nipples. This prospective study follows a cohort of 220 healthy mother-baby pairs from birth to 6 months, living in Porto Alegre, Brazil. Data were collected at the maternity unit, during a home visit at 30 days, and by telephone interview at 60, 120, and 180 days. Breastfeeding technique was assessed and breasts examined at the maternity unit and during home visits. Cox regression was employed to estimate the degree of association between the variables and the outcome. The following factors were associated with cessation of exclusive breastfeeding before 6 months: adolescent mother (hazard ratio [HR] = 1.48, 95% CI 1.01-2.17), fewer than six prenatal visits (HR = 1.60, 95% CI 1.10-2.33), use of a pacifier within the first month (HR = 1.53, 95% CI 1.12-2.11), and poor latch-on (HR = 1.29, 95% CI 1.06-1.58 for each unfavorable parameter). Activities to promote exclusive breastfeeding should be intensified for adolescent mothers and for those whose prenatal care was less than ideal. These activities should reinforce the ill effects of pacifiers and should also include appropriate instruction for these mothers in correct breastfeeding technique.

Magnetic Resonance Imaging in Multiple Myeloma: Diagnostic and Clinical Implications

Magnetic resonance imaging (MRI) permits the detection of diffuse and focal bone marrow infiltration in the absence of osteopenia or focal osteolysis on standard metastatic bone surveys (MBSs). Both baseline MBS and MRI were available in 611 of 668 myeloma patients who were treated uniformly with a tandem autologous transplantation-based protocol and were evaluated to determine their respective merits for disease staging, response assessment, and outcome prediction. MRI detected focal lesions (FLs) in 74% and MBS in 56% of imaged anatomic sites; 52% of 267 patients with normal MBS results and 20% of 160 with normal MRI results had FL on MRI and MBS, respectively. MRI- but not MBS-defined FL independently affected survival. Cytogenetic abnormalities (CAs) and more than seven FLs on MRI (MRI-FLs) distinguished three risk groups: 5-year survival was 76% in the absence of both more than seven MRI-FLs and CA (n = 276), 61% in the presence of one MRI-FL (n = 262), and 37% in the presence of both unfavorable parameters (n = 67). MRI-FL correlated with low albumin and elevated levels of C-reactive protein, lactate dehydrogenase, and creatinine, but did not correlate with age, beta-2-microglobulin, and CA. Resolution of MRI-FL, occurring in 60% of cases and not seen with MBS-defined FL, conferred superior survival. MRI is a more powerful tool for detection of FLs than is MBS. MRI-FL number had independent prognostic implications; additionally, MRI-FL resolution identified a subgroup with superior survival. We therefore recommend that, in addition to MBS, MRI be used routinely for staging, prognosis, and response assessment in myeloma.

Pathological stage: pronostic factors

Most of prostatic malignancies are adenocarcinomas. Nomograms using pretreatment clinical or pathological features predict the probability of biochemical or clinical relapse after radical prostatectomy. These predictive tools must not be used in decision making for the anticancer treatment. The accurate pathological stage can only be assessed after examination of the radical prostatectomy specimens. Postoperative nomograms can be also used to predict the probability of survival without progression on the basis of pretreatment PSA level, the Gleason score of the biopsy and prostatectomy samples, the histological grading, the presence or absence of positive surgical margins, involvement of seminal vesicles, capsular penetration and lymph-node metastases. Retrospective studies have confirmed that these pathological post-treatment parameters are risk factors for clinical and biochemical progression. These unfavourable parameters, along with the PSA velocity during the year before radical prostatectomy, predict the risk of local relapse and distant dissemination. Scientific consensus exists for prescribing an adjuvant therapy after the initial local treatment for this population of patients with carcinoma of the prostate who are considered at high risk of progression.

Influência da técnica de amamentação nas freqüências de aleitamento materno exclusivo e lesões mamilares no primeiro mês de lactação

To investigate the influence of breastfeeding technique on the frequencies of exclusive breastfeeding and nipple trauma in the first month of lactation. We searched for unfavorable parameters of breastfeeding (five related to mother/baby positioning and three related to baby's latch on) in 211 mother-baby pairs in the maternity ward and at day 30, at home. We compared the frequencies of these parameters between mothers practicing or not exclusive breastfeeding at days 7 and 30, and between mothers with or without nipple trauma at the hospital. The number of unfavorable parameters in the maternity ward was similar for mother-baby pairs practicing or not exclusive breastfeeding at day 7 and 30. However, at day 30, it was, on average, lower among those under exclusive breastfeeding, regarding positioning (1.7+/-1.2 vs 2.2+/-1.1; p = 0.009) as well as latch on (1.0+/-0.6 vs 1.4+/-0.6; p < 0.001). The number of unfavorable parameters related to latch on in the maternity ward was similar for women with or without nipple trauma, but women without trauma presented a higher number of unfavorable parameters related to positioning. (2.0+/-1.4 vs 1.4+/-1.2; p = 0.04). The frequencies of exclusive breastfeeding in the first month and of nipple trauma were not influenced by the breastfeeding technique in the maternity ward, but there was an association between a better technique at day 30 and the practice of exclusive breastfeeding. New studies may help to elucidate whether an improvement in breastfeeding practices over time helps the maintenance of exclusive breastfeeding or whether the introduction of bottle-feeding determines a negative effect on breastfeeding.

Influence of overall treatment time and radiobiological parameters on biologically effective doses in cervical cancer patients treated with radiation therapy alone

The aim of the study was to examine the influence of overall treatment time (OTT) on the value of calculated biological effective doses (BEDs) for different biological variables. These variables were: tumour proliferation rate, different cell radiosensitivity (α=0.2, 0.3, and 0.4 /Gy), and different start time for repopulation (Tk=21, 28, and 35 days). Also the influence of age (≤50 years >), Hb level (≤116 g/l>), tumor proliferation rate (bromodeoxyuridine labelling index; BrdUrdLI), and DNA ploidy on survival after shorter (≤60 days) or longer (>60 days) OTT was investigated. The study included 229 patients with cervix carcinoma treated entirely by standard radiotherapy (RT) (external beam RT plus low-medium dose-rate (LDR/MDR) brachytherapy (BT) at the Center of Oncology in Krakow. The linear quadratic equation was used to calculate BED, which is proportional to log cell kill. BEDs 10 (for tumours) were calculated with consideration of OTT for each patient and tumour proliferation rate (standardized potential doubling time; standardized Tpot) based on BrdUrdLI assessed on biopsy material before RT. Median OTT was 90 days (range 30–210). The mean calculated total BED for point A for tumour and ‘early reactions’ was equal to 103.0 Gy10. The longest median survival time—52 months—was seen for patients treated with OTT ≤60 days. If OTT exceeded 90 days to more than 120 days, loss in BED10 for relatively radiosensitive tumours (α=0.3–0.4/Gy and Tk=28 days) was equal to 0.37–0.26 Gy/day. However, for radioresistant tumours (α=0.2/Gy) it was 0.6 Gy/day. For fast proliferating tumours (BrdUrdLI >8.8%) BED loss was 1.4 Gy/day and for slowly proliferating tumours (BrdUrdLI ≤8.8%) it was 0.2 Gy/day. Assuming shorter (21 days) or longer (35 days) periods for Tk and relatively radiosensitive tumours similar BED loss of 0.38 Gy/day was observed. Kaplan–Meier analysis revealed that OTT ≤60 days was a significant prognostic factor for overall survival (OS) (p=0.019), disease-free survival (DFS) (p=0.0173), and local control (LC) (p=0.011). BED10 had significant influence on survival (p=0.047). Cox multivariate analysis revealed that for OTT shorter than 60 days the only favourable significant parameters were: age >50 years (p=0.003) and high Hb level (>116 g/l) (p=0.041). For longer treatments (OTT >60 days) the unfavourable parameters were: age ≤50 years (p=0.037), BrdUrdLI ≤8.8% (p=0.003), tumour aneuploidy (p=0.043), and BED10 ≤103 Gy (p=0.017). The examined tumour biological parameters should be taken into account for RT and provide a basis for adjuvant RT.

Coal inclusions in sedimentary rocks: a geochemical phenomenon. A review

In many coal-bearing basins, there are numerous coalified fragments of ancient plants (coal-precursors) enclosed in host rocks. Such fragments occur in isolated positions out of the coal beds. In the Russian literature, these coal fragments are named coal inclusions. Coal inclusions are mostly the remains of stems, trunks, and branches, as well as the roots of trees. The review presented covers: (a) definition and classification of fossil woods; (b) relations between coalification and mineralization of fossil woods; (c) some special topics dealing with different and even zonal coalification degree of coal inclusions embedded different host rocks; (d) some historical data on geochemistry of coal inclusions; (e) basic empirical regularities in geochemistry, observed world-wide; (f) some data about chemical nature of humin substance—a precursor of lignite and vitrain matter in coalified wood; (g) results of calculations modelling the Ge enrichment in coal inclusions; (h) economic importance of Ge in coal inclusions; and (j) use of coal inclusion geochemistry for indication of some diagenetic and catagenetic processes, and as a tool for stratigraphic correlation. The most part of the above studies performed during 1934–1972 were outlined in the monograph “Geochemistry of coal inclusions in sedimentary rocks” [Yudovich, Ya.E., 1972. Geochemistry of coal inclusions in sedimentary rocks. L.: Nauka [Leningrad: “Science” Pub. House], 84 pp.]. These materials are added to some recent work by Bulgarian and Russian geologists, performed with use of modern analytical methods. It has been shown that: (a) coalified wood may contain very exotic micro-mineral phases, sometimes far unexpected; (b) apart from Ge, coalified wood may contain high concentrations of some other trace elements, which were earlier not detected because of analytical limitations (REE, As, etc.). These special peculiarities can be partly contributed by epigenetic hydrothermal processes. As a summary, the review shows that coal inclusions are unique geochemical phenomenon, sharply different from even neighboring coal beds in trace element content. Among the most extreme elements is germanium, its mean concentration in the ash of coal inclusions being up to 220 times higher than in the ash of coal beds. The most important peculiarity of the coalified wood is the good preservation of the original lignin structures, which may effectively scavenge Ge from solutions, whereas peat-born coals (in beds) contained such structures in far fewer amounts. In addition, a reservoir of dissolved germanium in peat bog waters was of lower concentration than in sediments, which buried the coal inclusions. Finally, the peat bog acidic environment may act as an unfavorable factor. Ge-enrichment can be completed in a time ranging from a few thousand years up to tens of million years. However, if the waters are enriched in Ge, the process can proceed more rapidly and would be completed even under the most unfavorable parameters (compared to the model conditions). This implies that enrichment can take place during the early diagenetic stage. Such a scenario was supported by geologic considerations. Some Canadian and Soviet works performed from 1950 to 1960 along with some recent Russian studies show that Ge in coal inclusions can be of economic interest. Geochemistry and mineralogy of coal inclusions are of great interest and need further detailed study.

Foliar nutrient status and tree growth response of young Pseudotsuga menziesii Mirb. (Franco) to nitrogen, phosphorus and potassium fertilization in Galicia (Northwest Spain)

The nutritional status of 14 young Pseudotsuga menziesii plantations on abandoned agricultural land in Galicia (Northwest Spain) was studied and related to growth response to N, P and K fertilization. Nutritional status was assessed using macronutrient foliar analysis followed by the critical levels method and foliar nutrient ratios interpretation. Douglas fir showed high N levels in control foliage samples. Foliar N:P and N:K ratios were greatly unbalanced in many sites. Foliar Mg concentrations were below the satisfactory levels in all cases and P, K and Ca were deficient in several cases. Height growth of untreated plants correlated positively with foliar P, K and Ca concentrations and negatively with total soil N in the surface soil. Thus, P, K and Ca were classified as favorable parameters for Douglas fir growth, whereas N was classified as an unfavorable parameter. According to this, the application of urea significantly reduced the Douglas fir growth in several trials. However, there was a lack of consistence between the foliar diagnosis and the growth response to superphosphate and potassium sulphate applications at the end of the first growing season following fertilization. This response was much lower than expected after the foliar diagnosis. The low fertilization rates used, the short time passed between fertilization and response measurements or other factors such as Mg nutrition and other nutrient interactions, could be the cause. In conclusion, N fertilization is not recommended in young P. menziesii plantations on abandoned agricultural land in Galicia whereas further research is needed to generate a fertilization recommendation for the other nutrients.

Trust in the Shadow of the Courts

If contract enforcers must be randomly selected from the same population and thus are as opportunistic as ordinary traders could a system of adjudication nevertheless increase the degree to which contractual obligations on large anonymous markets are fulfilled? Adopting an indirect evolutionary approach with endogenous preference formation it can be shown that without superior behaviour of adjudicators an adjudication system can induce untrustworthy traders to behave as if trustworthy. However, in the presence of occasional mistakes adjudication will merely slow down but not fully eliminate the evolutionary advantage of untrustworthy types. Only if arbitrators become judges who receive a fixed income occasional mistakes will not favour untrustworthy types. But even then under non-optimal court politics and unfavourable parameter constellations in a low trust environment the introduction of courts may in fact contribute to the crowding out of the trustworthy.

Histologic indices in biopsy specimens for estimating the probability of extended local spread in patients with rectal carcinoma.

Although precise preoperative assessment of the extent of local cancer spread is important to determine the appropriate treatment strategy, imaging modalities have not been sufficient. The aim of this study was to establish effective preoperative indices that would predict the degree of local spread in patients with rectal carcinoma. In specimens from 437 patients with advanced rectal carcinoma, the submucosal horizontal invasive frontal region was examined histologically with reference to three unfavorable characteristics: 1) tumor "budding", 2) poor differentiation, and 3) vascular invasion. In addition, a transanal submucosal biopsy, which targets the tumor edge, was performed on 85 patients to verify the utility of preoperative evaluation of these parameters. Multivariate logistic analysis showed that three unfavorable parameters had independent impact on the degree of nodal involvement. These parameters related significantly to the number of lymph nodes involved, the development of extranodal tumor deposits, circumferential surgical margin involvement, and lateral pelvic lymph node metastases. Regarding patients without unfavorable parameters as a standard, the odds ratio of pelvic recurrence was 1.8 (0.9-3.4) in patients with one unfavorable parameter and 5.3 (2.7-10.2) in patients with multiple unfavorable parameters. Based on the transanal biopsy, the submucosal invasive frontal region could be estimated in 73 patients (85.9%). Among these cases, the multiple unfavorable parameters were relevant to an increased risk of extensive local spread. In addition, pelvic recurrence developed in 36% of patients with multiple unfavorable parameters (no-risk patients, 5%; single-risk patients, 13%). Histology in the submucosal invasive frontal region reflects the extent of local spread and can be evaluated preoperatively by transanal biopsy, which should become a useful tool for therapy selection for patients with advanced rectal carcinoma.

Foliar nutrient status and nutritional relationships of young Pinus radiata D. Don plantations in northwest Spain

Fifty-four plots of young Pinus radiata D. Don plantations on abandoned agricultural land in Galicia (northwest Spain) were selected for nutritional diagnosis. Nutritional status was assessed by foliar analysis using the critical levels method. The relationships between foliar nutrient concentrations and the plantation’s growth and survival and the topsoil physical and chemical properties were also analyzed. The most common deficiencies among plots were P and Mg. Foliar N concentrations were relatively high and generally they were above the critical level. Foliar N:P, N:K and N:Mg ratios were significantly unbalanced in 31, 44 and 17 out of 54 studied plots. Foliar P levels were significantly higher on sites with previous herbaceous land use and on soils with a finer texture, whereas foliar Mg levels were higher at low altitudes. Foliar nutrient levels were not significantly correlated with their respective soil levels except in the case of K. Foliar Ca and Mg concentrations correlated positively with topsoil pH. Growth correlated positively with foliar K and Mg concentrations and negatively with foliar N:P, N:K and N:Mg ratios. Percentage of dead and poor state plants were negatively correlated with foliar P, K and Ca levels and positively correlated with foliar N:P and N:Mg ratios. These results suggested that nitrogen may be in excess and may condition the uptake of other nutrients. Foliar N level was considered as an unfavorable parameter, whereas foliar P, K, Ca and Mg concentrations were considered as favorable parameters for P. radiata establishment in Galicia.

Maximum likelihood estimation of a migration matrix and effective population sizes in n subpopulations by using a coalescent approach.

A maximum likelihood estimator based on the coalescent for unequal migration rates and different subpopulation sizes is developed. The method uses a Markov chain Monte Carlo approach to investigate possible genealogies with branch lengths and with migration events. Properties of the new method are shown by using simulated data from a four-population n-island model and a source-sink population model. Our estimation method as coded in migrate is tested against genetree; both programs deliver a very similar likelihood surface. The algorithm converges to the estimates fairly quickly, even when the Markov chain is started from unfavorable parameters. The method was used to estimate gene flow in the Nile valley by using mtDNA data from three human populations.

Amplification of cyclin D1 gene in multiple myeloma: clinical and prognostic relevance.

Approximately 30% of myeloma patients express cyclin D1 RNA and protein. The low incidence of translocation t(11; 14) detected by conventional cytogenetics suggests that the up-regulation of cyclin D1 protein might result from other mechanisms as well as from gene amplification. Therefore, the frequency and the clinical and prognostic implications of cyclin D1 amplification were examined. We highly purified myeloma cells from bone marrow by magnetic cell sorting and analysed 50 myelomas by fluorescence in situ hybridization (FISH) using probes specific for cyclin D1 and 20 samples by immunoblotting to detect cyclin D1 expression. The amplification of cyclin D1 gene was found in 19 of 50 analysed patients and was associated with expression of cyclin D1 protein. The amplification correlated significantly with the bone marrow infiltration, plasma cell morphology and labelling index as well as serum beta2-microglobulin, C-reactive protein (CRP) and creatinine levels. In univariate analysis, the amplification of the cyclin D1 gene was a significantly unfavourable parameter with regard to overall survival (P = 0.0064) and progression-free survival (P = 0. 0005). In multivariate analysis, cyclin D1 amplification and serum beta2-microglobulin were independent and well-suited parameters for predicting survival. The detection of cyclin D1 amplification seems to be of promising prognostic value in multiple myeloma.

Management of malignant mucinous adenomas.

Malignant polyps are defined as adenoma with cancerous tissue penetrating into or through the muscolaris mucosae in the submucosa, and endoscopic removal is the most common treatment for such polyps. In the presence of malignant mucinous adenoma, defined as a malignant adenoma in which a significant amount of mucus is present in the stroma, the therapeutic approach is controversial and authors have performed surgical resection in all cases. The purpose of the study was to demonstrate that malignant mucinous adenoma is not a condition suggesting by itself a bowel resection. Ten patients with malignant mucinous adenoma were enrolled in the study: endoscopic treatment alone was performed in 4 cases, and polypectomy was followed by surgical resection in 6 cases. At a median follow-up of 74.2 months no distant metastases had occurred in any of the patients treated with endoscopic polypectomy alone; during the follow-up, 1 patient had a local recurrence and surgical resection was performed. Only one case of residual disease was found at histology among the patients in which endoscopic polypectomy was followed by surgical resection. No complications occurred after endoscopic treatment in any case. In the absence of unfavorable histologic parameters, malignant mucinous adenomas should be managed with the same criteria of other malignant adenomas, and endoscopic polypectomy is considered as a safe and effective treatment when radicality criteria are fulfilled.

Therapy of CNS metastases

Brain metastases occur in 20-30% of patients with systemic cancer and represent one of the most unfavourable prognostic parameters. In the majority of cases brain metastases are multiple and are usually treated with whole brain irradiation. The treatment of single brain metastases often includes surgery, followed by whole brain radiotherapy. Although the goal of treatment of both single and brain metastases is almost always palliation and not cure, it is important that several modes of treatment are carefully compared. In comparing different treatment regimens it should be emphasised that not only duration of survival time and time until tumour recurrence are used as outcome parameters but also the quality of life. The only way in which the results of different therapies can be compared is by means of randomised trials. As long as high quality studies are not available, any definitive assessment of the relative effectiveness of radiosurgery to standard treatment for brain cannot be defined. Radiosurgery can be used to treat patients, whose metastases recur after traditional therapies. As with other definitive therapies for patients with brain metastases, highly functional patients with well-controlled systemic cancers derive the greatest benefit from treatment with radiosurgery.

Effects of Tamoxifen on Steroid Hormone Receptors and Hormone Concentration and the Results of DNA Analysis by Flow Cytometry in Endometrial Carcinoma

Objectives.Tamoxifen is a nonsteroidal triphenylethylene derivate with a predominant antiestrogen activity, used in the endocrine treatment of breast and endometrial cancer. It is not known which endometrial carcinomas will respond favorably to tamoxifen and which ones will not. The aim of this study was to find out whether tamoxifen has an effect on hormone steroid receptors, hormone concentration, DNA content, and proliferative activity in endometrial cancer and to correlate the tamoxifen-induced changes with pathologic parameters such as clinical stage, tumor differentiation, depth of invasion, and histologic type.Methods.Thirty postmenopausal women with endometrial carcinoma were treated with 30 mg of tamoxifen daily for 7–10 days after curettage. Steroid hormone receptors (estrogen and progesterone receptors), levels of follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, progesterone, testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, and DNA ploidy and proliferative activity were determined before and after therapy. The patients were also divided into favorable and unfavorable prognosis groups according to classical histological parameters. The patients in the favorable group consisted of patients with stage I disease, well and moderately differentiated tumors, favorable histologic type, and a depth of myometrial invasion of less than 13. The patients with only one of the unfavorable parameters (clinical stage II or III, poorly differentiated tumors, unfavorable histologic types, and deeper invasion of myometrium) were included in the unfavorable prognosis group.Results.After the treatment, there was a net increase in the progesterone receptors and sex hormone binding globulin and a significant decrease in the estrogen receptors. The increase in progesterone receptors and decrease in estrogen receptors occurred in the patient group with favorable prognosis regarding histologic type, degree of differentiation, and clinical stage, but also in the unfavorable prognosis group regarding the depth of myometrial invasion. Statistically significant decrease in the follicle-stimulating hormone concentration was observed in the groups with favorable prognosis regarding histologic type, depth of myometrial invasion, and grade of differentiation. Concentration of sex hormone binding globulin was significantly increased in groups with favorable prognosis if histologic type and grade of differentiation were taken into account. On the other hand, there was a significant decrease in the concentration of luteinizing hormone in the group with unfavorable histologic type and also a decrease in progesterone concentration in patients with unfavorable prognosis regarding the grade of differentiation. There was no statistical significance either in the concentrations of other hormones measured or in the DNA analysis by flow cytometry.Conclusions.Our results revealed that tamoxifen can increase progesterone receptors and decrease estrogen receptors in endometrial cancer. The effect was most pronounced in tumors with favorable clinicopathologic parameters. We conclude that tamoxifen therapy can induce progesterone receptor synthesis even in tumors with low initial progesterone receptor levels, making such tumors potentially responsive to additional hormonal therapy with progesterone.

Treatment of hairy cell leukaemia (HCL) with 2-chlorodeoxyadenosine (2-CdA): identification of parameters predictive of adverse effects.

2-chlorodeoxyadenosine (2-CdA) induces high complete remission (CR) rates in hairy cell leukaemia (HCL), but is associated with serious toxicities. Therefore we reviewed our experience with 2-CdA in 16 HCL patients, with special attention to adverse effects. One-third of patients presented severe neutropenic infections and/or required prolonged blood support. Patients with low tumour mass and moderate cytopenias were more likely to achieve CR, whereas those with high tumour burden and severe bone marrow impairment were at increased risk of severe infection and blood product requirements. All these unfavourable parameters may be corrected by short-term alpha-interferon (IFN) therapy. Therefore we suggest that patients with unfavourable presenting features might benefit from IFN therapy before 2-CdA.

Clinicopathological study of superficial-type invasive carcinoma of the colorectum

We investigated the relationship between histological parameters such as the level of invasion (scanty submucosal invasion, sm-s or massive submucosal invasion, sm-m), histologic grade (presence or absence of grade III carcinoma), lymphatic invasion, venous invasion, budding and lymph node metastasis in 33 lesions of superficial-type invasive colorectal carcinoma. On statistical analysis, there was no definite influence of any histological parameter on lymph node metastasis. None of 6 sm-s lesions showed lymph node metastasis, however, 7 sm-m lesions were found to have lymph node metastasis (25.9%). Whereas only 16.7% (1/6) of the lesions showing sm-s had one or more unfavorable histological parameters, 85.2% (23/27) of the lesions showing sm-m had one or more of unfavorable histological parameters. There was a significant difference between the two types of lesions (p<0.003). Consequently, in the treatment of superficial-type invasive carcinoma, sm-s lesions without unfavorable histological parameters could be radically cured by endoscopic mucosal resection alone.

Prognostic value of cardiotocography in pregnancy with pathologic Doppler findings

Absent (absent-EDF) or reversed (RF) end-diastolic flow in Doppler velocimetry in the umbilical artery and fetal aorta indicates highly disturbed fetoplacental perfusion, which often occurs early in pregnancy. Perinatal mortality and morbidity is very high. In this situation it is not clear how long pregnancy can be continued to achieve better conditions for the preterm fetus. This study was performed to investigate the value of fetal heart rate recordings (FHR) in patients with absent EDF or RF as a parameter to determine the optimum time of delivery. 25 pregnancies with absent (n = 21) or reversed end-diastolic velocity (n = 4) were analysed. Gestational age was between 24 and 34 weeks. 17 children showed compensatory dilatation of the middle cerebral artery (68%). 15 (60%) were growth retarded, 8 of them below the 3% percentile, while 3 had normal weight. Maximum time interval until delivery was 18 days, median was 2 days. Five children died before, 2 during delivery. As none died after delivery, perinatal mortality was 28%. 4 of the survivers (22%) showed arterial acidosis. Only three children had completely normal fetal heart rate recordings on the day of diagnosis of absent EDF or RF. All others showed at least suspicious FHR (according to Hammacher), 8 of them (32%) even pathological FHR, including all children who died later. Early suspicious changes in FHR were the reduction in frequency and amplitude of oscillation, while decelerations occurred later. Additional unfavourable parameters in FHR were roundings of the oscillatory inversions as well as missing reactivity to fetal movements. Fetal heart rate monitoring is a reliable tool for determination of the optimum time of delivery in children with absent EDF or RF. The decision has to be made in relation to the gestational age. If possible, the fetus should be born before FHR becomes pathological. In this manner perinatal mortality and morbidity should be kept at a low level even in high-risk patients with absent EDF or RF.

Neuroblastoma mass screening: The arguments for and against

Neuroblastoma is the second commonest malignancy in childhood. The prognosis of the disease is largely dependent on the extension of the tumour at diagnosis. For disseminated disease the survival rate is very low. The question as to whether mass screening in infants can improve the prognosis of the disease was first addressed in Japan more than 20 years ago. Since then, more than 7 million children have been screened in Japan and over 650 cases of neuroblastoma have been detected. However, the available data are compromised by an inadequate cancer registry and conclude that screening at 6 months of age seems to double the incidence of neuroblastoma. This result has been verified by a Canadian study conducted from 1989 to 1994 in the province of Quebec. The incidence of neuroblastoma appeared to have tripled, and there was no decrease in the rate of advanced disease. Mass screening pilot studies have also been conducted in the U.K., France, Austria, Australia, U.S.A., Italy, Norway and Germany. Analysis of the results shows that neuroblastoma screening before the age of 6 months is feasible, but no significant reduction in mortality could be shown until now. Moreover, most of the cases diagnosed by screening have favourable biological markers. Only a few with unfavourable parameters, such as amplification of proto-oncogene MYCN, diploidy and/or del 1p36 could be detected. A screening programme that includes 1.25-2 million screened and unscreened children at 1 year of age monitored by an almost complete national cancer registry should show whether mass screening for early detection of neuroblastoma is worthwhile.