Use of the Needs Evaluation Questionnaire with cancer outpatients.

PURPOSE: The Needs Evaluation Questionnaire (NEQ) is a self-administered instrument with 23 dichotomous items that is used both in oncology clinical practice and in research. It was originally developed for use in setting of hospitalization. The aim of the present study was to assess the factor structure of the NEQ in an outpatient oncology sample and to compare the unmet needs of inpatients and outpatients in the Italian context. METHODS: In 6 Italian oncology departments, 783 patients completed the NEQ. Patients included in the study had different primary tumor sites and were in different phases of the disease and care process. There were 195 inpatients and 588 outpatients total. RESULTS: Confirmatory factor analysis (CFA) showed that, with outpatients, the NEQ retained the distribution of the items in five main areas previously described with inpatients. Cancer outpatients expressed high percentages of unmet needs primarily concerning "material needs" and "needs for psycho-emotional support." Our survey also suggested that, in addition to the 23 original items, four new items could be tested for specific use with outpatients. CONCLUSIONS: Our findings highlight the importance of establishing routine assessment of unmet needs also in clinical oncology settings different from wards-such as day hospitals, ambulatory rehabilitation, or follow-up ambulatory care-where, at least in the Italian context, the rate of unmet needs is currently considerably high. The NEQ could be an effective tool for this assessment.

Complementary needs behind complementary therapies in cancer patients.

OBJECTIVE: Although many studies indicate that the use of complementary and alternative medicine by cancer patients is common and widespread, few studies have focused on unmet needs of patients using complementary therapies (CTs). The aim of the present study was to evaluate, through a quantitative approach, possible associations between the use of CTs and the presence of specific unmet needs in cancer patients. METHODS: In six Italian oncology departments, 783 patients were interviewed about CTs use and completed the Needs Evaluation Questionnaire. Patients included in the study had different primary tumor sites and were in different phases of the disease and care process. RESULTS: At the time of the survey, 38.3% of patients were using one or more types of CTs. According to Needs Evaluation Questionnaire, the use of CTs was associated (p < .05) with the need to be more involved in therapeutic choices (40% vs. 31.7%), the need to have a better dialogue with clinicians (44.4% vs. 37.2%), and the need to have more economic-insurance information in relation to their illness (46.1% vs. 36.4%). Statistical significance was confirmed with multivariable analysis for the last two items, whereas three more needs were associated with the use of CTs after adjustment: to receive more explanation on treatments (46.8% vs. 41.0%), to receive more comprehensible information (38% vs. 31.9%), and to receive more attention from nurses (16% vs. 12.1%). CONCLUSIONS: Our study shows interesting differences regarding perceived needs between cancer patients who use and who do not use CTs. Unmet needs that are more expressed in CTs users should be known and, when possible, could be taken into account to improve both psychosocial interventions in the context of conventional care process and the quality of the relationship between patient and medical and nursing staff.

An experimental therapy to improve skeletal growth and prevent bone loss in a mouse model overexpressing IL-6.

UNLABELLED: Premature osteoporosis and stunted growth are common complications of childhood chronic inflammatory disease. Presently, no treatment regimens are available for these defects in juvenile diseases. We identified the sequential Fc-OPG/hPTH treatment as an experimental therapy that improves the skeletal growth and prevents the bone loss in a mouse model overexpressing IL-6. INTRODUCTION: Premature osteoporosis and stunted growth are common complications of childhood chronic inflammatory diseases and have a significant impact on patients' quality of life. Presently, no treatment regimens are available for these defects in juvenile diseases. To test a new therapeutic approach, we used growing mice overexpressing the pro-inflammatory cytokine IL-6 (TG), which show a generalized bone loss and stunted growth. METHODS: Since TG mice present increased bone resorption and impaired bone formation, we tested a combined therapy with the antiresorptive modified osteoprotegerin, Fc-OPG, and the anabolic PTH. We injected TG mice with Fc-OPG once at the 4th day of life and with hPTH(1-34) everyday from the 16th to the 30th day of age. RESULTS: A complete prevention of growth and bone defects was observed in treated mice due to normalization of osteoclast and osteoblast parameters. Re-establishment of normal bone turnover was confirmed by RT-PCR analysis and by in vitro experiments that revealed the full rescue of osteoclast and osteoblast functions. The phenotypic recovery of TG mice was due to the sequential treatment, because TG mice treated with Fc-OPG or hPTH alone showed an increase of body weight, tibia length, and bone volume to intermediate levels between those observed in vehicle-treated WT and TG mice. CONCLUSIONS: Our results identified the sequential Fc-OPG/hPTH treatment as an experimental therapy that improves the skeletal growth and prevents the bone loss in IL-6 overexpressing mice, thus providing the proof of principle for a therapeutic approach to correct these defects in juvenile inflammatory diseases.

A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study.

BACKGROUND: Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies. METHODS: We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence. RESULTS: After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen. CONCLUSIONS: The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.

Microbial tracking of multidrug-resistant Klebsiella pneumoniae isolates in a pediatric hospital setting.

We investigated the clonal relatedness of seven multi-drug-resistant (MDR) Klebsiella pneumoniae isolates, as well as three susceptible K. pneumoniae isolates collected during hospital outbreaks and outbreak-related microbiological surveillance, respectively. The relatedness among K. pneumoniae isolates was assessed by pulsed field gel electrophoresis (PFGE) and automated repetitive-sequence-based PCR (rep-PCR) genotyping and the results were compared to a proteomic phenotyping performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). All typing methods agreed on the generation of three different clusters of K. pneumoniae isogenetic/related MDR strains. After strengthening hospital infection control measures, no other spreading events involving MDR-K. pneumoniae were reported until the end of the observation period. This preliminary investigation suggests that, in a hierarchical approach to bacterial typing, MALDI-TOF MS proteome profiling might offer a fast and valuable preliminary screening tool able to support microbiologists during nosocomial outbreak surveys.

Bilirubin, a physiological antioxidant, can improve cryopreservation of human hepatocytes.

The availability of cryopreserved hepatocytes is required for a more widespread use of hepatocyte transplantation, but human hepatocytes are easily damaged during freezing-thawing. Here, preincubation with unconjugated bilirubin, a physiological antioxidant, resulted in increased viability and function of hepatocytes (as determined by trypan blue exclusion, mitochondrial succinate dehydrogenases activity, urea synthesis, and cytochrome P450 1A/2) compared with cells incubated without the pigment. These findings suggest that unconjugated bilirubin may be used as cryoprotectant in clinical hepatocyte transplantation.

Stem and progenitor cells for liver repopulation: can we standardise the process from bench to bedside?

There has been recent progress in the isolation and characterisation of stem/progenitor cells that may differentiate towards the hepatic lineage. This has raised expectations that therapy of genetic or acquired liver disease might be possible by transplanting stem/progenitor cells or their liver-committed progeny. However, it is currently impossible to determine from the many documented studies which of the stem/progenitor cell populations are the best for therapy of a given disease. This is largely because of the great variability in methods used to characterise cells and their differentiation ability, variability in transplantation models and inconsistent methods to determine the effect of cell grafting in vivo. This manuscript represents a first proposal, created by a group of investigators ranging from basic biologists to clinical hepatologists. It aims to define standardised methods to assess stem/progenitor cells or their hepatic lineage-committed progeny that could be used for cell therapy in liver disease. Furthermore standardisation is suggested both for preclinical animal models to evaluate the ability of such cells to repopulate the liver functionally, and for the ongoing clinical trials using mature hepatocytes. Only when these measures have been put in place will the promise of stem/progenitor-derived hepatocyte-based therapies become reality.

Liver repopulation with bone marrow derived cells improves the metabolic disorder in the Gunn rat.

BACKGROUND: Reversible ischaemia/reperfusion (I/R) liver injury has been used to induce engraftment and hepatic parenchymal differentiation of exogenous beta2-microglubulin(-)/Thy1(+) bone marrow derived cells. AIM: To test the ability of this method of hepatic parenchymal repopulation, theoretically applicable to clinical practice, to correct the metabolic disorder in a rat model of congenital hyperbilirubinaemia. METHODS AND RESULTS: Analysis by confocal laser microscopy of fluorescence labelled cells and by immunohistochemistry for beta2-microglubulin, 72 hours after intraportal delivery, showed engraftment of infused cells in liver parenchyma of rats with I/R, but not in control animals with non-injured liver. Transplantation of bone marrow derived cells obtained from GFP-transgenic rats into Lewis rats resulted in the presence of up to 20% of GFP positive hepatocytes in I/R liver lobes after one month. The repopulation rate was proportional to the number of transplanted cells. Infusion of GFP negative bone marrow derived cells into GFP positive transgenic rats resulted in the appearance of GFP negative hepatocytes, suggesting that the main mechanism underlying parenchymal repopulation was differentiation rather than cell fusion. Transplantation of wild type bone marrow derived cells into hyperbilirubinaemic Gunn rats with deficient bilirubin conjugation after I/R damage resulted in 30% decrease in serum bilirubin, the appearance of bilirubin conjugates in bile, and the expression of normal UDP-glucuronyltransferase enzyme evaluated by polymerase chain reaction. CONCLUSIONS: I/R injury induced hepatic parenchymal engraftment and differentiation into hepatocyte-like cells of bone marrow derived cells. Transplantation of bone marrow derived cells from non-affected animals resulted in the partial correction of hyperbilirubinaemia in the Gunn rat.

Regenerative medicine: an insight.

Regenerative Medicine is a rapidly evolving field of therapy integrating different scientific and technological areas, including cell biology, biomedical and computer engineering, and clinical medicine, thus creating an interdisciplinary exchange network of skill, ideas, materials and efforts between basic and clinical research. Even if significant achievements have been obtained particularly in Plastic Surgery, Ophthalmology and Orthopedics, the field is still experimental and so far has failed to meet the expectations. The present article reviews the major hurdles that are still hampering the translational "bench to bedside" process and limiting the availability of these innovative therapeutic tools.

Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer.

BACKGROUND: Fenretinide, a vitamin A analogue, has been shown to inhibit breast carcinogenesis in preclinical studies. We determined the efficacy of fenretinide in preventing a second breast malignancy in women with breast cancer. METHODS: We randomly assigned 2972 women, aged 30-70 years, with surgically removed stage I breast cancer or ductal carcinoma in situ to receive for 5 years either fenretinide orally (200 mg/day) or no treatment. The primary end point was the incidence of contralateral breast cancer or ipsilateral breast cancer 7 years after randomization. Other end points considered post hoc were the same outcomes stratified by menopausal status, incidence of distant metastases, overall mortality, and tumors in other organs. The hazards of breast cancer occurrence were determined by Cox proportional hazards regression analysis. Statistical tests were two-sided. RESULTS: At a median observation time of 97 months, there were no statistically significant differences in the occurrence of contralateral breast cancer (P =.642) or ipsilateral breast cancer (P =.177) between the two arms. However, an interaction was detected between fenretinide treatment and menopausal status in both outcomes (P for interaction in both outcomes =.045), with a possible beneficial effect in premenopausal women (contralateral breast cancer: adjusted hazard ratio [HR] = 0.66, and 95% confidence interval [CI] = 0.41-1.07; ipsilateral breast cancer: adjusted HR = 0.65, and 95% CI = 0.46-0. 92) and an opposite effect in postmenopausal women (contralateral breast cancer: adjusted HR = 1.32, and 95% CI = 0.82-2.15; ipsilateral breast cancer: adjusted HR = 1.19, and 95% CI = 0.75-1. 89). There were no statistically significant differences between the two arms in tumors in other organs, incidence of distant metastasis, and all-cause mortality. CONCLUSIONS: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women. These studies, particularly the post hoc analyses, are considered exploratory and need to be confirmed.

Neonatal bilirubin production-conjugation imbalance: effect of glucose-6-phosphate dehydrogenase deficiency and borderline prematurity.

OBJECTIVE: To evaluate relations between production and conjugation of bilirubin in the pathophysiology of jaundice in glucose-6-phosophate dehydrogenase (G6PD) deficient neonates. METHODS: Term and borderline premature (35-37 weeks gestational age), healthy, male, G6PD deficient neonates were studied close to the beginning of the 3rd day. Blood carboxyhaemogobin corrected for inspired CO (COHbc; an index of bilirubin production) and serum total conjugated bilirubin (TCB; a reflection of bilirubin conjugation) were measured in simultaneously drawn blood samples by gas chromatography and reverse phase high performance liquid chromatography respectively. A bilirubin production-conjugation index comprising COHbc/TCB was determined; a high index reflects imbalance between the bilirubin production and conjugation processes. COHbc and TCB individually and the production-conjugation index were studied in relation to serum total bilirubin (STB) concentration. RESULTS: Fifty one G6PD deficient neonates were sampled at 51 (8) hours. COHbc values did not correlate with STB (r=0.22, p=0.15). TCB did correlate inversely with STB (r=-0.42, p=0.004), and there was a positive correlation between the production-conjugation index and STB (r=0.45, p=0.002). The production-conjugation index (median (interquartile range)) was higher in the premature (n=8) than term neonates (2.31 (2.12-3.08) v 1.05 (0.53-1.81), p=0.003). This difference was the result of changes in TCB. CONCLUSIONS: The data show that jaundice in G6PD deficient neonates is the result of an imbalance between production and conjugation of bilirubin with a tendency for inefficient bilirubin conjugation over increased haemolysis in its pathogenesis. Borderline premature infants are at special risk of bilirubin production-conjugation imbalance.

Olive-oil-enriched diet: effect on serum lipoprotein levels and biliary cholesterol saturation.

The effect of diet enriched with a monounsaturated fatty acid (olive oil) on serum lipoproteins, biliary cholesterol saturation index, and gallbladder motility compared with a standard low-fat diet was evaluated in 11 young volunteers admitted to a metabolic ward. A significant decrease of mean total cholesterol (-9.5%), total apo B (-7.4%), LDL cholesterol (-12.2%), and total triglycerides (-25.5%) was observed after the olive-oil-enriched diet. Total HDL- and HDL-subfractions-cholesterol levels as well as serum apo A-I mean levels remained unchanged. Cholesterol saturation index of the bile and fasting and after-meal gallbladder volumes were unaffected by the enriched diet as compared with the low-fat diet. Olive oil may be a natural fat that can be used for the control of plasma and LDL cholesterol as a valid alternative to polyunsaturated fatty acids.

Effect of withdrawal of pravastatin on biliary lipid composition in humans.

Abrupt withdrawal of HMG-CoA reductase inhibitors is associated with increased excretion of cholesterol into bile, but this phenomenon has not been investigated in humans. In order to evaluate whether patients interrupting these hypolipidemic drugs are at increased risk of forming gallstones, pravastatin (40 mg twice a day) or placebo was randomly administered to 16 bile fistula patients for 5 days. Biliary lipid composition was determined in basal conditions and for 5 consecutive days after drug withdrawal. Both biliary cholesterol concentration and saturation increased significantly on the second day after pravastatin withdrawal, but tended to decrease thereafter. Biliary bile acids and phospholipids were not affected. This short-lasting effect on biliary cholesterol excretion was probably the result of a transient increase of hepatic cholesterol synthesis by the up-regulated HMG-CoA reductase in the absence of the inhibitory drug. These results are consistent with the hypothesis that, also in humans, biliary cholesterol excretion could be dependent on the hepatic free cholesterol pool.

Serum and bile bilirubin pigments in the differential diagnosis of Crigler-Najjar disease.

OBJECTIVE: To differentiate between Crigler-Najjar (CN) disease types 1 and 2. DESIGN: The patterns of serum bilirubins, bile pigment composition, and phenobarbital response were studied. PATIENTS: Three infants, affected by high serum unconjugated bilirubin concentrations, previously classified as type 1 CN. METHODS: Serum and bile bilirubin pigment composition, both before and after phenobarbital (PB) treatment, were determined by alkaline methanolysis and high-pressure liquid chromatography. PB was given for at least 3 weeks by oral administration (5 mg/kg bw per day). RESULTS: No diconjugated bilirubin was found either before or after PB treatment in the serum of the three studied infants. In two patients traces of monoconjugated bilirubin were detected before PB therapy, and the ratio of conjugated/total bilirubin (percent) was increased by the PB response. In the third patient, traces of monoconjugated bilirubin appeared only after PB administration. However, the serum unconjugated bilirubin concentration decreased significantly only in the second patient, following the second cycle of PB treatment, leading to the diagnosis of type 2 CN. The analysis of the methyl ester derivatives of bile pigments was also performed on bile samples obtained in two patients by Entero-Test (R) both before and after PB treatment. An absolute increment in monoesterified bilirubin concentration was found after PB administration, although the percent concentration increased in one case and decreased in the other. No diesterified bilirubin was detected in the bile samples. CONCLUSIONS: The present results show that in types 1 and 2 CN disease it is possible to detect traces of monoconjugated but not diconjugated bilirubin both in serum and in bile. Whereas PB treatment is effective in slightly increasing the serum monoconjugated bilirubin concentration even in type 1 CN disease, the diagnosis of type 1 or 2 is based on finding a substantial decrease of serum unconjugated bilirubin following PB administration.

The effect of drugs on bile flow and composition. An overview.

Many drugs are eliminated via the hepatobiliary route, after biotransformation in the liver. Some of them may affect bile flow and/or the hepatic secretion of biliary lipids such as bile acids, cholesterol and phospholipids. Bile acids are the most potent agents which increase bile flow, especially unconjugated bile acids. Other drugs which increase bile flow include phenobarbitone (phenobarbital), theophylline, glucagon and insulin. In contrast, ethacrynic acid, amiloride, ouabain, oestrogens and chlorpromazine are among those agents which decrease bile flow. Biliary bile acid secretion is altered by a variety of drugs, including cheno- and ursodeoxycholic acids (CDCA and UCDA), the bile acid sequestrants cholestyramine and colestipol, and ethinyloestradiol. The composition of bile can also be altered by drug therapy. Thus, clofibrate increases biliary cholesterol secretion, and reduces bile acid concentrations, without altering biliary phospholipid concentrations. However, other clofibrate derivatives may produce changes of a different pattern, suggesting that the risk of developing gallstones may differ for each derivative. Nicotinic acid and d-thyroxine also increase biliary cholesterol saturation, while CDCA and UDCA reduce biliary cholesterol concentration. The potential consequences of drug-induced changes in bile flow and composition extend to the liver, the gallbladder and the intestine. If adverse effects are to be avoided, further study in this often overlooked area is required.

Serum bile acids in patients with liver failure supported with a bioartificial liver.

BACKGROUND: Serum bile acids are increased in liver failure, but the composition of the bile acid pool in this condition has not been studied in detail. This information is of interest because of dihydroxy bile acid toxicity. METHODS: We measured serum bile acids by gas chromatography-mass spectrometry in 13 patients with fulminant liver failure and five patients with acute-on-chronic liver failure. Furthermore, serum bile acids were analysed in the same patients after 6 h of treatment with a bioartificial liver, consisting of a hollow-fibre cartridge with microcarrier-attached porcine hepatocytes and a charcoal column. RESULTS: Pre-bioartificial liver serum bile acids demonstrated a high dihydroxy/trihydroxy ratio and were higher in patients with acute-on-chronic liver failure than in those with fulminant liver failure (452.8 +/- 98.6 vs. 182.1 +/- 39.7 micro mol/L; P < 0.05). Bioartificial liver treatment decreased significantly serum bile acids in patients with fulminant liver failure (-38.8%) and acute-on-chronic liver failure (-35.8%), with a decreased dihydroxy/trihydroxy ratio. In vitro, porcine hepatocytes in the bioreactor cleared most conjugated bile acid species from pooled patient plasma. CONCLUSIONS: Acute liver failure is associated with very high serum levels of toxic bile acids that could contribute to the pathogenesis of the syndrome. Bioartificial liver treatment reduces both serum bile acid concentrations and the hydrophobicity of the bile acid pool.

Standards for diagnosis of gastrointestinal motility disorders. Section: ultrasonography. A position statement from the Gruppo Italiano di Studio Motilità Apparato Digerente.

Ultrasonography is a non-invasive, relatively easy, validated and reproducible technique. We assessed the usefulness of functional ultrasonography to study disorders of gastro-oesophageal tract, gallbladder and pancreatic duct. Oesophagus Oesophagus and the gastro-oesophageal junction can be visualized in children up to 5 years old. Ultrasonography shows 100% sensitivity and 87.5% specificity compared to ambulatory pH-metry for gastro-oesophageal reflux disease diagnosis. Stomach Ultrasonography can be used to estimate whole gastric volume, antral area or diameters, antro-pyloric volume, transpyloric flow in fasting state and in response to test meal. Gallbladder Ultrasonography is reliable to estimate volume in fasting state and in response to test meal or exogenous stimulus. For both stomach and gallbladder, indications might include the study of healthy subjects and of pathophysiologically relevant conditions such as dysmotility-like dyspepsia, suspicion of delayed gastric emptying, diabetes mellitus, gallstone disease and effect of drugs either delaying or accelerating motility. Common bile duct Ultrasonography can be used to estimate interprandial and postprandial common bile duct diameter in patients with clinical suspicion of common bile duct obstruction in fasting state and in response to test meal or exogenous stimuli. Although functional ultrasonography is used mainly for research purposes, its simplicity makes it appealing for clinical use to assess gastrointestinal motility in health and disease.

Effect of tauroursodeoxycholic acid on biliary lipid composition. A dose-response study.

Tauroursodeoxycholic acid has been proposed for the treatment of hepatobiliary disease, but data on the enrichment of biliary tauroursodeoxycholic acid pool and on changes of biliary lipids after administration of the compound are scarce. We studied the composition of biliary lipids in a series of 33 patients with radiolucent stones, before and after treatment with tauroursodeoxycholic acid, 3.5 - 16.6 mg/kg/day for 4 - 6 weeks. Duodenal bile was collected with the Entero-Test after gallbladder contraction. Tauroursodeoxycholic acid administration produced the following dose-dependent effects: a linear decrease of cholesterol saturation (r = 0.59, p < 0.001); a non-linear increase of the percent of ursodeoxycholic acid in bile (r = 0.59, p < 0.001); a non-linear increase of the fraction of ursodeoxycholate conjugated with taurine. At the dose of 11 mg/kg per day, cholesterol saturation was 80%, ursodeoxycholic acid represented about 45% of biliary bile acids, and about half of UDCA was conjugated with taurine. Biliary bile acids were repeatedly measured in 6 patients during long-term treatment with 9.7 - 12.1 mg/kg. The fraction of tauroursodeoxycholic acid decreased progressively from 67.6% +/- 10.5 to 29.1% +/- 5. Tauroursodeoxycholic acid is as effective as ursodeoxycholic acid on a molar basis in reducing biliary cholesterol saturation and in enriching bile with ursodeoxycholate. Moreover, tauroursodeoxycholic acid administration is associated with higher concentrations of tauroconjugates in the bile than those previously reported by feeding the free bile acid.

Is there a place for medical treatment in children with gallstones?

BACKGROUND: Medical treatment of gallstones with ursodeoxycholic acid (UDCA) or chenodeoxycholic acid (CDCA) has not been evaluated in children. AIM: The purpose of this study was to assess the effectiveness of UDCA in the treatment of gallstones in children. METHODS: UDCA was used to treat 15 patients, (7 boys and 8 girls; mean age, 7.8 years; range, 3 months to 15 years) for 1 year. All had radiolucent stones with a maximum diameter of 10 mm and a normally contractile gallbladder. RESULTS: The stones disappeared completely in two children but returned later. All symptomatic patients became symptom free. CONCLUSION: UDCA is ineffective in the treatment of gallstones in children except in terms of relieving symptoms while on treatment.

Risk of endometrial cancer in breast cancer patients under long-term adjuvant treatment with tamoxifen.

AIMS: To evaluate the relative risk of endometrial cancer with respect to the expected underlying incidence in breast cancer patients undergoing long-term adjuvant tamoxifen therapy. METHODS: A total of 1010 postmenopausal breast cancer patients receiving adjuvant tamoxifen and with a first negative endometrial ultrasonography (cutoff for abnormal endometrial thickness >5 mm) were followed by annual transvaginal ultrasonography. Abnormal endometrial thickness prompted an outpatient endometrial biopsy or curettage under anesthesia in the case of cervical stenosis and increasing endometrial thickness. The standardized incidence ratio (SIR) with respect to underlying incidence was determined. RESULTS: A total of 1,010 eligible subjects who had been receiving tamoxifen for an average of 51 months were enrolled and followed for a total of 2,361 patient-years between January 1993 and December 1996. Five cases of endometrial cancer were observed in the study period: 1 was detected at screening, and 4 were diagnosed for vaginal bleeding in the interval between screening examinations. SIR was 4.0 (95% confidence interval, 1.3-9.4) and increased to 4.8 (CI, 1.6-10.5) when the single cancer detected at first screening was considered as incident. CONCLUSIONS: This study adds evidence to the hypothesis that long-term tamoxifen treatment may be responsible for a relevant increase in the risk of developing endometrial cancer. Surveillance based on endometrial ultrasonography was poorly sensitive, but the favorable stage at diagnosis of screen-detected or interval endometrial cancers does not support a more aggressive screening approach.