Cutaneous metastases from adenocarcinoma of unknown primary

Cutaneous manifestations of malignancy are not uncommon, especially in advanced disease. They may also occur early in malignant disease or they may even signify recurrence particularly if they are paraneoplastic in nature. Clinical diagnosis can be difficult because of the wide spectrum of appearance of these lesions, and, in many cases, because of the lack of an identifiable underlying primary. Presented here is the case of a 65-year-old woman with multiple inflammatory cutaneous metastases, which were sclerodermoid in nature. These appeared 14 months after initial diagnosis of adenocarcinoma of unknown primary (ACUP) and signified the beginning of a rapid deterioration in her condition. The coexistence of limited systemic sclerosis (scleroderma) and ACUP initially raised several interesting diagnostic possibilities. Adenocarcinoma of unknown primary and the sclerodermoid reaction in malignancy are discussed.     

Evidence that Tamoxifen Preserves Bone Density in Late Postmenopausal Women with Breast Cancer

Tamoxifen, which is used for treating breast cancer, exhibits estrogenic and antiestrogenic characteristics, depending on the tissue. In the human breast it acts as an antiestrogen, whereas estrogenic effects have been reported on endometrium and bone. The purpose of this study was to determine whether tamoxifen (TAM) prevents bone loss in elderly, postmenopausal women. Bone mineral density of the lumbar spine (SBD) was measured in elderly women (at least 10 years after menopause) 5 years after stage I or II breast cancer (n=111). The results showed that SBD in untreated patients (n=74) was significantly lower (p0.05) than SBD in patients (n=37) treated with TAM over 5 years. In a subgroup of patients (n=24) with positive estrogen receptor status, changes in SBD 12 months after discontinuation of 5-year TAM therapy were measured and compared with the changes of extended TAM treatment over a sixth year. Twelve months after withdrawal of 5-year TAM medication (n     

Daily CT localization for correcting portal errors in the treatment of prostate cancer

Introduction: Improved prostate localization techniques should allow the reduction of margins around the target to facilitate dose escalation in high-risk patients while minimizing the risk of normal tissue morbidity. A daily CT simulation technique is presented to assess setup variations in portal placement and organ motion for the treatment of localized prostate cancer.

Methods and Materials: Six patients who consented to this study underwent supine position CT simulation with an alpha cradle cast, intravenous contrast, and urethrogram. Patients received 46 Gy to the initial Planning Treatment Volume (PTV₁) in a four-field conformal technique that included the prostate, seminal vesicles, and lymph nodes as the Gross Tumor Volume (GTV₁). The prostate or prostate and seminal vesicles (GTV₂) then received 56 Gy to PTV₂. All doses were delivered in 2-Gy fractions.

After 5 weeks of treatment (50 Gy), a second CT simulation was performed. The alpha cradle was secured to a specially designed rigid sliding board. The prostate was contoured and a new isocenter was generated with appropriate surface markers. Prostate-only treatment portals for the final conedown (GTV₃) were created with a 0.25-cm margin from the GTV to PTV. On each subsequent treatment day, the patient was placed in his cast on the sliding board for a repeat CT simulation. The daily isocenter was recalculated in the anterior/posterior (A/P) and lateral dimension and compared to the 50-Gy CT simulation isocenter. Couch and surface marker shifts were calculated to produce portal alignment. To maintain proper positioning, the patients were transferred to a stretcher while on the sliding board in the cast and transported to the treatment room where they were then transferred to the treatment couch. The patients were then treated to the corrected isocenter. Portal films and electronic portal images were obtained for each field.

Results: Utilizing CT–CT image registration (fusion) of the daily and 50-Gy baseline CT scans, the isocenter changes were quantified to reflect the contribution of positional (surface marker shifts) error and absolute prostate motion relative to the bony pelvis. The maximum daily A/P shift was 7.3 mm. Motion was less than 5 mm in the remaining patients and the overall mean magnitude change was 2.9 mm. The overall variability was quantified by a pooled standard deviation of 1.7 mm. The maximum lateral shifts were less than 3 mm for all patients. With careful attention to patient positioning, maximal portal placement error was reduced to 3 mm.

Conclusion: In our experience, prostate motion after 50 Gy was significantly less than previously reported. This may reflect early physiologic changes due to radiation, which restrict prostate motion. This observation is being tested in a separate study. Intrapatient and overall population variance was minimal. With daily isocenter correction of setup and organ motion errors by CT imaging, PTV margins can be significantly reduced or eliminated. We believe this will facilitate further dose escalation in high-risk patients with minimal risk of increased morbidity. This technique may also be beneficial in low-risk patients by sparing more normal surrounding tissue.     

Influence of intratumoral basic fibroblast growth factor concentration on survival in ovarian cancer patients

Since basic fibroblast growth factor (bFGF) is considered as a potent mitogen that stimulates the growth of ovarian cancer cells, we evaluated the role of bFGF as a prognostic marker in patients with epithelial ovarian cancer. bFGF was quantified from the tumor cytoplasm of 76 patients with FIGO stage I–III ovarian cancer by a human FGF basic immunoassay (R&D Systems). After a mean follow-up period of 42 months, 50 patients were found to be free of tumor while 26 patients had died of the disease. The median bFGF concentration was 352.9 pg/mg (range 27.4–26 600 pg/mg). After dichotomization cytoplasmic expression of bFGF was found to be low in 44 tumors (≤500 pg/mg) and high in 32 tumors (>500 pg/mg). The probability of overall survival was 38.8 and 58.5% in the low bFGF and high bFGF groups, respectively (log-rank P=0.0066). In multivariate analysis, residual tumor after initial surgery and bFGF, but not histologic grade or stage of the disease, independently influenced the overall survival probability. Furthermore, tumors with high cytoplasmic expression of bFGF revealed a much greater stromal content. Therefore, we hypothesize that bFGF may induce a fibroblastic response which causes tumors with a high bFGF to be less aggressive than those with less stromal tissue.     

Fatal shoulder dystocia: a review of 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy

Objective To use information collected by the Confidential Enquiry into Stillbirths and Deaths in Infancy to help obstetric, midwifery and paediatric practice in the management of shoulder dystocia.
Design Review of casenotes by a multidisciplinary focus group.
Sample All 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy from England, Wales and Northern Ireland in 1994 and 1995, where stillbirth or neonatal death was attributed to shoulder dystocia.
Main outcome measures Case notes were reviewed with respect to a range of perinatal variables. Comparisons were made with normative data from other studies when appropriate.
Results Maternal obesity and big babies were over-represented in pregnancies complicated by fatal shoulder dystocia. Fetal compromise was recorded in 26% of labours. The median time interval between delivery of the head and the rest of the body was only five minutes. The lead professional at the time the head was delivered was a midwife in 65% of cases. Middle grade or senior obstetric staff were supervising 47% of cases by the time the body was delivered.
Conclusions Antenatal prediction of shoulder dystocia is imprecise, and the majority of deliveries are attended by midwives. A relatively brief delay in delivery of the shoulders may be associated with a fatal outcome.     

Promoting and sustaining health through increased vegetable and fruit consumption among European schoolchildren: The Pro Children Project

Aim The Pro Children consortium consists of the following partners: Knut-Inge Klepp (Coordinator), Department of Nutrition, University of Oslo, Norway; Carmen Perez Rodrigo, Unidad de Nutricion Comunitaria, Bilbao, Spain; Inga Thorsdottir, Unit for Nutrition Research, Landspitali University Hospital, Reykjavik, Iceland; Pernille Due, Department of Social Medicine, University of Copenhagen, Denmark; Maria Daniel Vaz de Almeida, Faculdade de Ciências da Nutrição e Alimentação da Universidade do Porto, Portugal; Ibrahim Elmadfa and Alexandra Wolf, Institute of Nutrition, University of Vienna, Austria; Jóhanna Haraldsdóttir, Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Copenhagen, Denmark; Johannes Brug, Erasmus Medical Center Rotterdam, Department of Public Health, The Netherlands; Michael Sjöström and Agneta Yngve, Unit for Preventive Nutrition, Karolinska Institutet, Stockholm, Sweden; Ilse De Bourdeaudhuij, Department of Movement and Sport Sciences, Ghent University, Belgium.The Pro Children study is designed to assess vegetable and fruit consumption and determinants of the consumption patterns among European school children and their parents. A second objective is to develop and test strategies for promoting increased consumption of vegetables and fruits among school children and their parents.Subjects and methods Surveys of national, representative samples of 11-year-old school children and their parents were conducted in nine countries during October–November 2003, i.e. in Austria, Belgium, Denmark, Iceland, The Netherlands, Norway, Portugal, Spain and Sweden. Comprehensive school-based educational programmes were developed and tested in three settings, i.e. in the Bilbao region, Spain, in Rotterdam, The Netherlands, and in Buskerud county of Norway. A 24-h recall format and frequency items assessing regular intake were used to assess vegetable and fruit consumption. Determinants were assessed employing the theoretical framework of the ASE model (Attitudes, Social Influences and Self-Efficacy), including cognitive factors, normative influences, skills and environmental barriers related to vegetable and fruit consumption. The intervention programmes were tested employing a group-randomized trial design where schools were randomly allocated to an intervention arm and a delayed intervention arm. Surveys among all participating children and their parents were conducted prior to the initiation of the intervention (September 2003; month 0), immediately after the end of the intervention (at month 8) and at the end of the subsequent school year (month 20).Results Preliminary data from the project indicate that girls eat vegetables and fruit significantly more often than do boys across all participating countries. There are no sex differences, however, with respect to perceived availability of vegetables and fruit at home and outside the home setting. In all countries, perceived availability appears to be significantly associated with reported frequency of both vegetable and fruit consumption.Conclusion Experience so far indicates that the Pro Children Project will succeed in producing valid and reliable research instruments for assessing vegetable and fruit consumption among school children and their parents and that comparable, comprehensive intervention programmes can be implemented across geographic and cultural settings within Europe.     

Prevalence of potentially severe drug-drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy.

BACKGROUND: Drug-drug interactions (DDIs) are a well known risk factor for adverse drug reactions. HMG-CoA reductase inhibitors ('statins') are a cornerstone in the treatment of dyslipidaemia and patients with dyslipidaemia are concomitantly treated with a variety of additional drugs. Since DDIs are associated with adverse reactions, we performed a cross-sectional study to assess the prevalence of potentially critical drug-drug and drug-statin interactions in an outpatient adult population with dyslipidaemia. METHODS: Data from patients with dyslipidaemia treated with a statin were collected from 242 practitioners from different parts of Switzerland. The medication list was screened for potentially harmful DDIs with statins or other drugs using an interactive electronic drug interaction program. RESULTS: We included 2742 ambulatory statin-treated patients (mean age +/- SD 65.1 +/- 11.1 years; 61.6% males) with (mean +/- SD) 3.2 +/- 1.6 diagnoses and 4.9 +/- 2.4 drugs prescribed. Of those, 190 patients (6.9%) had a total of 198 potentially harmful drug-statin interactions. Interacting drugs were fibrates or nicotinic acid (9.5% of patients with drug-statin interactions), cytochrome P450 (CYP) 3A4 inhibitors (70.5%), digoxin (22.6%) or ciclosporin (cyclosporine) [1.6%]. The proportion of patients with a potential drug-statin interaction was 12.1% for simvastatin, 10.0% for atorvastatin, 3.8% for fluvastatin and 0.3% for pravastatin. Additionally, the program identified 393 potentially critical non-statin DDIs in 288 patients. CONCLUSIONS: CYP3A4 inhibitors are the most frequent cause of potential drug interactions with statins. As the risk for developing rhabdomyolysis is increased in patients with drug-statin interactions, clinicians should be aware of the most frequently observed drug-statin interactions and how these interactions can be avoided.     

Calidad de vida relacionada con la salud informada por los padres en preescolares españoles: propiedades psicométricas del Kiddy-KINDL-R

IntroductionAlthough several tools have been developed to assess general HRQoL in children, parental reports are required to supplement this information, especially in very young children. The parents version of the Kiddy-KINDL-R was developed to assess HRQoL in children aged 3 to 7 years through the reports of their parents or legal guardians.ObjectiveThe aim of this study was to validate the parents version of the Kiddy-KINDL-R questionnaire and assess its psychometric properties in a sample of Spanish preschool-aged children.MethodCross-sectional study in 283 parents or legal guardians of children aged 3 to 6 years that completed the Kiddy-KINDL-R questionnaire and an additional scale to assess anxiety problems. We performed confirmatory factor analysis to assess whether the original Kiddy-KINDL-R version fit the Spanish data; we assessed internal consistency by means of the ordinal alpha and the discriminant validity by means of the Preschool Anxiety Scale.ResultsAlthough the original six-factor model showed a good fit, we propose a model consisting of 22 items and the same 6 factors for the Spanish version. The reliability was excellent, and the internal consistency values were adequate. Our results showed significant negative correlations between the Kiddy-KINDL-R and the external anxiety measure, which was evidence of discriminant validity.ConclusionWe demonstrated that the Spanish version of the Kiddy-KINDL-R had good psychometric properties and that this questionnaire is an adequate assessment tool that could be useful in clinical practice.     

In-Hospital Patient Education Markedly Reduces Alcohol Consumption after Alcohol-Induced Acute Pancreatitis

Although excessive alcohol consumption is by far the most frequent cause of recurrent acute pancreatitis (AP) cases, specific therapy is still not well established to prevent recurrence. Generally, psychological therapy (e.g., brief intervention (BI)) is the cornerstone of cessation programs; however, it is not yet widely used in everyday practice. We conducted a post-hoc analysis of a prospectively collected database. Patients suffering from alcohol-induced AP between 2016 and 2021 received 30 min BI by a physician. Patient-reported alcohol consumption, serum gamma-glutamyl-transferase (GGT) level, and mean corpuscular volume (MCV) of red blood cells were collected on admission and at the 1-month follow-up visit to monitor patients’ drinking habits. Ninety-nine patients with alcohol-induced AP were enrolled in the study (mean age: 50 ± 11, 89% male). A significant decrease was detected both in mean GGT value (294 ± 251 U/L vs. 103 ± 113 U/L, p < 0.001) and in MCV level (93.7 ± 5.3 U/L vs. 92.1 ± 5.1 U/L, p < 0.001) in patients with elevated on-admission GGT levels. Notably, 79% of the patients (78/99) reported alcohol abstinence at the 1-month control visit. Brief intervention is an effective tool to reduce alcohol consumption and to prevent recurrent AP. Longitudinal randomized clinical studies are needed to identify the adequate structure and frequency of BIs in alcohol-induced AP.