Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-Müllerian hormone, inhibin B and ovarian ultrasound.

BACKGROUND: Treatment of cancer during childhood may result in loss of primordial follicles from the ovary. METHODS: Ten cancer survivors and 11 controls with regular menstrual cycles, in addition to 10 cancer survivors and 10 controls taking the combined oral contraceptive pill (COCP) were recruited. Subjects were investigated on days 3-5 of a menstrual cycle, or week 3 of COCP administration before and 24 h after administration of 225 IU FSH. RESULTS: Serum FSH levels were elevated in cancer survivors with regular menstrual cycles (7.5 +/- 1.4 versus 4.2 +/- 0.3 IU/l; P = 0.02), while anti-Müllerian hormone (AMH) levels were lower (13.0 +/- 3.0 versus 21.0 +/- 3.4 pmol/l; P < 0.05). Other hormone levels were unchanged. Ovarian volume was smaller in cancer survivors than controls (3.0 +/- 0.5 versus 5.0 +/- 0.8 ml; P < 0.05), but antral follicle count (AFC) was similar. During COCP administration, inhibin B remained undetectable in six cancer survivors after FSH administration, whereas all controls showed a rise in inhibin B levels. The AFC was lower in cancer survivors than in controls (4.2 +/- 0.8 versus 7.2 +/- 0.8; P = 0.02). Ovarian volume was low in both groups, but did not differ between them. CONCLUSIONS: The study results demonstrate both hormonal and biophysical evidence of partial loss of the ovarian reserve in young cancer survivors. This was detected both in women with normal menstrual cycles and during COCP administration.

Barium enema and endoscopy for the detection of colorectal neoplasia: sensitivity, specificity, complications and its determinants.

AIM: To analyse sensitivity, specificity and complication rate of endoscopy, and barium enema for the detection of colorectal neoplasia. MATERIALS AND METHODS: A MEDLINE search was performed (1980-2000) directed at the endoscopic and radiologic literature on barium enema. Articles were selected based on the type of study, availability of sensitivity and specificity values in sizeable patient groups, and reports on complications. Sixty articles were included in the analysis. RESULTS: Endoscopy proved to have superior sensitivity for polyps in patients at high-risk for colorectal neoplasia. The role of endoscopy and radiology in average-risk screening populations is not known. Sensitivity and specificity rates ranged widely, probably due to bias. For the detection of small polyps endoscopy has superior performance, whereas sensitivity is similar for endoscopy and barium enema for the detection of larger (>1 cm) polyps and tumours. Overall, endoscopy is associated with a higher complication rate. CONCLUSION: Endoscopy is the preferred detection method in high-risk patients. The role of endoscopy and radiology in a screening setting requires evaluation. This review provides the test characteristics of endoscopy and radiology which are relevant for a cost-effectiveness analysis. Double-contrast barium enema may play an important role for screening purposes, owing to its good sensitivity for detecting larger (>1 cm) polyps and its lack of major complications. de Zwart, I. M.et al. (2001). Clinical Radiology56, 401-409.

Structure of the macrocycle thiostrepton solved using the anomalous dispersion contribution of sulfur.

The structure of a tetragonal crystal form of thiostrepton has been solved using the anomalous dispersive effects of five S atoms from high-redundancy data collected to 1.33 A resolution at the Cu Kalpha wavelength. Data measured to 1.02 A resolution with a synchrotron source were used for refinement. Details of the molecular structure, intramolecular and intermolecular interactions are given.

Obesity in leukemia survivors: the familial contribution.

A high prevalence of obesity in survivors of acute lymphoblastic leukemia (ALL) has been described, but genetic and social influence in obesity has not been analyzed in this group of patients. The authors studied a population of 33 long-term (25 females, 8 males) in first remission who had reached their final height. All patients received cranial irradiation as part of their central nervous system (CNS)-directed therapy and no patient received growth hormone. The body mass index (BMI: weight/height2) of patients and their biological parents was calculated and submitted to statistical analysis. Obesity was defined as BMI greater than the 85th centile. No excessive obesity was found among the males at final height. Fifty-six percent of the females were obese. In this group of 14 obese female survivors 59% had obese mother, but only 14% had obese fathers. The results indicate a significant maternal predisposition to obesity.

Totally implantable central venous access devices for paediatric oncology patients.

BACKGROUND: Totally implantable central venous access devices (ports) have been available for over 10 years but have not achieved widespread use in paediatric oncology patients. We reviewed our experience with these devices over 9 years to assess their safety and acceptability. PROCEDURE: We conducted a retrospective review of insertion technique and reasons for removal of all ports placed in paediatric oncology patients in this hospital between 1989 and 1996, with follow-up until 1998. Acceptability of both ports and external catheters was assessed by a questionnaire in a subgroup of families attending the oncology clinic. RESULTS: One hundred forty-nine ports were inserted during the study period. The median catheter life was 399 days (4-1,406), with a total of 69,342 catheter days. Sixty-nine percent of ports were removed electively at the end of treatment; 8% required removal because of infection and 5% because of blockage. No ports were accidentally dislodged or damaged. Children experienced significantly less restriction of activity with a port compared to an external catheter and greatly preferred the cosmetic appearance. The need for needle insertion to access the port was not seen as a disadvantage by most families. CONCLUSIONS: Ports can provide satisfactory central venous access for the majority of paediatric oncology patients, with a low risk of line-related complications and a high degree of acceptability to children and their parents.

A comparison of patient dose for examinations of the upper gastrointestinal tract at 11 conventional and digital X-ray units in The Netherlands.

The objective of this study was to derive the effective dose to patients from examinations of the upper gastrointestinal (GI) tract at 11 X-ray units in 10 Dutch hospitals. Entrance dose and entrance dose rate were measured at the surface of a homogeneous PMMA phantom and at the entrance surface of the image intensifier. Dose-area products (DAPs) were assessed during examinations of patients. The patients (334 females and 256 males) ages were 18-95 years (average 52 years). Effective dose was assessed from DAP using Monte Carlo computer calculations for male and female mathematical anthropomorphic phantoms. The DAPs measured during the survey showed substantial variations, i.e. an overall average value of 21 Gy cm2 and a range of average DAP per X-ray unit varying from 7 to 56 Gy cm2. Variations in the number of images (8-28) and the fluoroscopy time (1.7 min-7.0 min) were also large. A DAP to effective dose conversion factor of 0.32 mSv Gy cm-2 was derived for upper GI studies. The dose survey yielded an overall average effective dose of 6.7 mSv. At one location an examination involving as many as 28 projections was performed, whilst maintaining a DAP well below 15 Gy cm2 and an effective dose below 6 mSv. This was achieved using modern equipment (i.e. high frequency generator, digital spot films) with 0.2 mm additional copper filtration and a relatively high tube voltage. For examinations of the upper GI tract, the application of a reference value of 30 Gy cm2 for the DAP will ensure that, in general, the effective dose to individual patients will not exceed 15 mSv.

Patient dose due to colon examination: dose assessment and results from a survey in The Netherlands.

PURPOSE: To determine the effective dose to the patient during radiographic colon examination. MATERIALS AND METHODS: The integral dose-area product was measured during colon examination in 1,733 patients aged 18-94 years. The effective dose was estimated from the dose-area product through computer simulations of radiation transport in anthropomorphic phantoms. The relation between patient dose and imaging or radiographic technique was considered. Patient dose from a biphasic colon examination was compared to that from a double-contrast examination. RESULTS: The factors for converting dose-area product to effective dose were 0.29 mSv x Gy(-1) x cm(-2) and 0.27 mSv x Gy(-1) x cm(-2) for the biphasic and the double-contrast studies, respectively. The average dose-area product for the biphasic colon examination was 21 Gy x cm2, of which 13 Gy x cm2 was attributed to the double-contrast views. The average dose-area product was 29 Gy x cm2 (range, 18-53 Gy x cm2); the average effective dose was 4.7 mSv (range, 2.7-8.4 mSv). CONCLUSION: Careful selection of the radiologic technique resulted in a surprisingly low dose during the biphasic colon examination. It is recommended that additional filtration of at least 0.1-mm copper be applied and that a screen-film combination with a speed class of at least 400 be used. Dose reduction when using digital techniques is often not realized in clinical practice.

Spindle cell carcinoma of the tongue in a long-term survivor of childhood acute lymphoblastic leukemia.

A 25-year-old male previously treated (age 9 years) for acute lymphoblastic leukemia developed a spindle cell carcinoma of the tongue. Possible causes for the development of his second malignancy are discussed. A combination of scatter from cranial irradiation, poor oral hygiene, alcohol consumption, and cigarette smoking is likely to be contributory. Genetic predisposition can never be fully excluded.

Gastric outlet obstruction as a presenting manifestation of systemic lupus erythematosus.

A patient with nausea and vomiting who subsequently proved to have systemic lupus erythematosus is described. Although gastrointestinal involvement is common in systemic lupus erythematosus it is rare as an initial manifestation. Gastric outlet obstruction was shown on the air contrast examination while the mucosa at endoscopy was normal. The gastric symptoms regressed after treatment with high dose corticosteroids and a repeat air contrast examination of the stomach was normal. This stricturing process may have been caused by a local peritonitis.

Children under two years treated according to the Medical Research Council UKALL VIII study and trial 1980-1984 (on behalf of the Medical Research Council Working Party on Leukaemia in Childhood).

Ten per cent of children entered into the national leukaemia study UKALL VIII were under 2 years at diagnosis. The 6 year event-free survival of this cohort was 39%. Specific adverse features were age under 1 year, high initial white cell count and null cell ALL. Those with common ALL, WBC 10-50 x 10(9) 1-1 and especially those aged 18 months or older did not have an adverse prognosis compared with the whole trial entrants. Overall, however there was a doubling of CNS relapse rate and of both induction and remission deaths. Those with a WBC under 10 x 10(9) 1-1 had a high haematological relapse rate. The type of leukaemia and method of management rather than specifically the age appeared to be the predictor for poor outcome.

Acute lymphoblastic leukemia and Klinefelter's syndrome.

We report two children with acute lymphoblastic leukemia (ALL) who in initial cytogenetic investigation were coincidently found to have a 47, XXY karyotype. In one patient 100% of peripheral blood lymphocytes showed a 47,XXY complement, but in the other only 30% of cells had such a complement, the remainder having a normal male karyotype (46, XY). In neither case was the diagnosis of Klinefelter's syndrome clinically obvious. Antileukemic therapy may exacerbate both the hypogonadism and the learning difficulties seen in this condition. Routine cytogenetic investigations on peripheral blood and bone marrow should be performed in all new cases of leukemia. Cytogenetic analysis of cultured fibroblasts is essential in all cases in which the abnormal X line did not disappear after initial therapy. Evidence of an increased risk of leukemia in association with Klinefelter's is beginning to accumulate.

Results of Medical Research Council Childhood Leukaemia Trial UKALL VIII (report to the Medical Research Council on behalf of the Working Party on Leukaemia in Childhood).

During the 1970s, despite apparently similar treatment, the prognosis for children with lymphoblastic leukaemia (ALL) improved more in some countries, notably the United States and West Germany, than in others. To find out why, the first phase of the United Kingdom (UK) Medical Research Council (MRC) childhood ALL trial, UKALL VIII, was designed to see whether similar results to the United States Children's Cancer Study Group (CCSG) could be obtained in the U.K. using an identical protocol (CCG 162). Protocol 162 was one of a series of regimens devised by the American Children's Cancer Study Group in the 1970s and was used specifically for their average risk patients (all children with ALL with an initial white cell count up to 50 x 10(9)/l except those aged 3-6 years with white cell counts under 10 x 10(9)/l). One arm (1A) of their study was adopted by the MRC for all children in the U.K. aged 0-14 years with confirmed ALL. Eight hundred and twenty-nine consecutive patients were entered between 1980 and 1984. The first 199 patients formed a single arm study as per the original protocol 162 (arm 1A), but the subsequent 630 children were randomized to receive or not two doses of daunorubicin on the first 2 d of induction. This randomization was an attempt to answer the important question as to whether event-free survival was influenced by the use of four rather than three induction agents. A second randomization between 2 and 3 years continuing therapy was also introduced at this stage as it had been by the CCSG in their protocol. With a minimum follow up period of more than 5 years, disease-free survival for the whole group is 55%, a considerable improvement on all previous UKALL trials. Results for patients directly comparable with those in CCSG 162 ('average risk' patients) and their American counterparts were similar. Daunorubicin was associated with more early deaths but improved disease-free survival for those achieving remission. More children relapsed who stopped treatment after 2 years than those who continued for 3, but this was balanced by increased treatment mortality in the third year. The fact that for UKALL VIII the results were similar to those of the CCSG suggests that previous MRC protocols were not sufficiently sustained and intensive, particularly during the maintenance phase of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

[Comparison of biphasic radiologic stomach and duodenum studies with fiber endoscopy for the diagnosis of peptic ulcer and stomach carcinoma]. / Vergelijking van bifasisch radiologisch maag-en duodenumonderzoek met fiberendoscopie voor de diagnostiek van peptische zweren en maagcarcinomen.

In a prospective, blind study of 385 patients with dyspepsia, the diagnostic value of biphasic radiological examination of stomach and duodenum was compared with endoscopy. The patients were examined for presence of peptic ulcers and gastric carcinomas. No golden standard being available, kappa values were calculated for the comparison. The kappa values were 0.67 and 0.77 for gastric and duodenal ulcers, respectively; for gastric carcinomas the value was 0.91. These values indicate good agreement. The sensitivity and specificity of both methods were high; a lower sensitivity of radiological examination for duodenal ulcers was accounted for by ulcers smaller than 5 mm; for larger ulcers, the sensitivity and specificity of both methods were practically the same. It is concluded that the two methods are of equal value for the diagnosis of peptic ulcers and gastric carcinomas. Endoscopy offers the major advantage that biopsy samples can be taken for histological examination or culturing. The biphasic radiological examination, on the other hand, is cheaper and often better tolerated by the patient.

Non-randomised study comparing toxicity of Escherichia coli and Erwinia asparaginase in children with leukaemia.

Seven hundred fifty-eight unselected children entered into the United Kingdom Medical Research Council acute lymphoblastic leukaemia UKALL VIII Study and Trial were studied for differences in early treatment-related toxicity according to the type of intramuscular L-asparaginase received. Two hundred seventy-five received a product obtained from Escherichia coli and 483 the enzyme from Erwinia chrysanthemi. The E. coli patients had a significantly higher incidence of neurotoxicity, pancreatitis, and life-threatening sepsis (4%, 2%, and 20%, respectively) when compared with the Erwinia group (2%, 0%, and 18%). Severe hypersensitivity was seen in one patient from both groups and the incidence of glucose intolerance was not significantly different. These findings indicate that E. coli asparaginase may be more toxic. With a minimum follow up of 4 1/2 years there is no evidence that either product has made a significantly different contribution to disease-free survival.

Anaphylaxis as a rare complication of a barium enema examination.

A patient is described who developed anaphylaxis with respiratory and circulatory arrest after a single contrast barium enema examination. Since barium sulphate is an inert substance, the reaction must have been caused by additives present in the barium suspension.

Medical Research Council Childhood Leukaemia Trial VIII compared with trials II-VII: lessons for future management.

This improvement in medium disease-free survival is probably a result of sustained early cell kill, and UKALL VIII has enabled us to define risk categories requiring even further continuous intensification, as now introduced in MRC UKALL X. Thanks to the greater availability of blood products, for example, the rational use of antibiotics and the development of expertise amongst nurses and doctors, such sustained therapy can now be delivered on a multi-centre basis, but only in experienced centres. The monitoring and removal of morbidity are essential if the advantages of this more sustained chemotherapy are to be realised. All elements of therapy require controlling and patients, parents and, above all, doctors must comply with protocol requirements in order to build further upon these initial promising results.