Differential Diagnosis of Central Neurocytoma: Two Cases.

Central neurocytoma are rare primary brain tumors of the young and middle-aged adult, typically located in the lateral ventricles. Diagnosis has historically been difficult due to histomorphologic similarities to oligodendroglioma and ependymal tumors and remains a challenge even today. We present two cases of intraventricular central neurocytoma in which careful consideration of the clinical and radiological findings led to reevaluation of the preliminary histological interpretation, highlighting the importance of a meticulous differential diagnosis.

Epidermal growth factor receptor and anaplastic lymphoma kinase testing and mutation prevalence in patients with advanced non-small cell lung cancer in Switzerland: A comprehensive evaluation of real world practices.

In order to improve outcomes, identification of the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genes has become crucial in advanced non-small-cell lung cancer (NSCLC). The aim of the present study is to analyse time trends and frequency of testing, factors affecting testing as well as prevalence of mutations in the Swiss population. We analysed EGFR and ALK testing in a cohort of patients with newly diagnosed metastasised non-squamous NSCLC in the catchment area of the cancer registry Eastern Switzerland in the years 2008-2014. We analysed prevalence of mutations and studied clinicopathological characteristics and survival of tested and non-tested patients and of patients with and without mutations. Among 718 patients identified, 11% (51/447) harboured an EGFR mutation in the exons 18, 19 or 21 and further 12% (31/265) showed a positive test result for ALK rearrangements. In non-smokers the proportions of mutations were 31% and 23% respectively. Testing rates increased over time and reached 79% in 2014. We observed significantly lower testing rates and poorer survival in elderly, patients with limited life expectancy and patients treated at hospitals not involved in clinical research. Outcomes can be further improved in a considerable proportion of patients with advanced non-squamous NSCLC.

Treatment of breast cancer in the elderly: a prospective, population-based Swiss study.

OBJECTIVES: The primary objective of this population-based study is to describe the patterns of care of elderly patients with breast cancer (BC), and evaluate potential causative factors for the decrease in BC-specific survival (BCSS) in the elderly. PATIENTS AND METHODS: We included all or representative samples of patients with newly diagnosed BC from seven Swiss cancer registries between 2003 and 2005 (n=4820). Surgical and non-surgical BC treatment was analyzed over 5 age groups (<65, 65 to <70, 70 to <75, 75 to <80 and ≥80years), and the predictive impact of patient age on specific treatments was calculated using multivariate logistic regression analysis. RESULTS: The proportion of locally advanced, metastatic and incompletely staged BC increased with age. The odds ratio for performing breast-conserving surgery (BCS) in stages I-II BC (0.37), sentinel lymph node dissection (SLND) in patients with no palpable adenopathy (0.58), post-BCS radiotherapy (0.04) and adjuvant endocrine treatment (0.23) were all in disfavor of patients ≥80years of age compared to their younger peers. Only 36% of patients ≥80years of age with no palpable adenopathy underwent SLND. In the adjusted model, higher age was a significant risk factor for omitting post-BCS radiotherapy, SLND and adjuvant endocrine treatment. CONCLUSIONS: This study found an increase in incomplete diagnostic assessment, and a substantial underuse of BCS, post-BCS radiotherapy, SLND and adjuvant endocrine treatment in elderly patients with BC. There is a need for improved management of early BC in the elderly even in a system with universal access to health care services.

Predictors of state-of-the-art management of early breast cancer in Switzerland.

BACKGROUND: The aim of this study was to investigate predictors of state-of-the-art management of early breast cancer in Switzerland. PATIENTS AND METHODS: The study included 3499 women aged 25-79 years diagnosed with invasive breast cancer stages I-IIIA in 2003-2005. Patients were identified through population-based cancer registries and treated in all kinds of settings. Concordance with national and international recommendations was assessed for 10 items covering surgery, radiotherapy, systemic adjuvant therapy and histopathology reporting. We used multivariate logistic regression to identify independent predictors of high (10 points) and low (≤7 points) concordance. RESULTS: In one-third of the patients, management met guidelines in all items, whereas in about one-fifth, three or more items did not comply. Treatment by a surgeon with caseload in the upper tercile and team involved in clinical research were independent predictors of a high score, whereas treatment by a surgeon with a caseload in the lower tercile was associated with a low score. Socioeconomic characteristics such as income and education were not independent predictors, but patient's place of residence and age independently predicted management according to recommendations. CONCLUSION: Specialization and involvement in clinical research seem to be key elements for enhancing the quality of early breast cancer management at population level.

Changing patterns of cancer incidence in the early- and late-HAART periods: the Swiss HIV Cohort Study.

BACKGROUND: The advent of highly active antiretroviral therapy (HAART) in 1996 led to a decrease in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), but not of other cancers, among people with HIV or AIDS (PWHA). It also led to marked increases in their life expectancy. METHODS: We conducted a record-linkage study between the Swiss HIV Cohort Study and nine Swiss cantonal cancer registries. In total, 9429 PWHA provided 20,615, 17,690, and 15,410 person-years in the pre-, early-, and late-HAART periods, respectively. Standardised incidence ratios in PWHA vs the general population, as well as age-standardised, and age-specific incidence rates were computed for different periods. RESULTS: Incidence of KS and NHL decreased by several fold between the pre- and early-HAART periods, and additionally declined from the early- to the late-HAART period. Incidence of cancers of the anus, liver, non-melanomatous skin, and Hodgkin's lymphoma increased in the early- compared with the pre-HAART period, but not during the late-HAART period. The incidence of all non-AIDS-defining cancers (NADCs) combined was similar in all periods, and approximately double that in the general population. CONCLUSIONS: Increases in the incidence of selected NADCs after the introduction of HAART were largely accounted for by the ageing of PWHA.

Geographic variation in breast cancer care in Switzerland.

PURPOSE: Regional disparities in breast cancer outcomes have been reported in Switzerland. The purpose of this study is to investigate geographic variation in early diagnosis and management of breast cancer. METHODS: We used data from a representative sample of 4820 women diagnosed with invasive breast cancer between January 1, 2003 and December 31, 2005 identified by seven Swiss population based cancer registries. We collected retrospectively detailed information on mode of detection, tumor characteristics and treatments. Differences across geographic regions were tested for statistical significance using chi-square tests and uni- and multivariate logistic regression. RESULTS: Considerable disparities in early detection and management of early breast cancer were found across regions. In particular, the proportion of early detected cancer varied from 43% in Valais to 27% in St. Gallen-Appenzell. Mastectomy rates varied from 24% in Geneva to 38% in St. Gallen-Appenzell and Grisons-Glarus. Higher reconstruction rates were observed in regions with lower rates of mastectomy. The use of sentinel node procedure in patients with nodal negative disease was high in Geneva and low in Eastern Switzerland. Differences in compliance with recommendations on the use of endocrine therapy and chemotherapy were less pronounced but statistically significant. CONCLUSIONS: This analysis shows considerable geographic variation in breast cancer care in a health system characterized by high expenditures, universal access to services and high decentralization. Further study into the causes and effects of this variation on short- and long term patient outcomes is needed.

Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients.

BACKGROUND: Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy. METHODS: Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status. RESULTS: In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01). CONCLUSIONS: TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30-40% of CRC patients, may represent a new avenue of investigation for targeted therapy.

Variation in survival after diagnosis of breast cancer in Switzerland.

BACKGROUND: Survival after diagnosis of cancer is a key criterion for cancer control. Major survival differences between time periods and countries have been reported by the EUROCARE studies. We investigated whether similar differences by period and region existed in Switzerland. METHODS: Survival of 11,376 cases of primary invasive female breast cancer diagnosed between 1988 and 1997 and registered in seven Swiss cancer registries covering a population of 3.5 million was analysed. RESULTS: Comparing the two periods 1988-1992 and 1993-1997, age-standardized 5 year relative survival improved globally from 77% to 81%. Furthermore, multivariate analysis adjusting for age, tumour size and nodal involvement identified regional survival differences. Survival was lowest in the rural parts of German-speaking eastern Switzerland and highest in urbanised regions of the Latin- and German-speaking northwestern parts of the country. CONCLUSIONS: This study confirms that survival differences are present even in a small and affluent, but culturally diverse, country like Switzerland, raising the issue of heterogeneity in access to care and quality of treatment.

Photodynamic detection of diseased axillary sentinel lymph node after oral application of aminolevulinic acid in patients with breast cancer.

Benign as well as malignant tumour tissues of the breast demonstrate higher fluorescence intensity (FI) than normal breast tissue after application of a photosensitiser. As a follow-up study, we evaluated the FI of metastatic sentinel lymph nodes and metastatic axillary lymph nodes compared to nonmetastatic sentinel and axillary lymph nodes in patients with breast cancer. In all, 11 patients received 30 mg 5-aminolevulinic acid (ALA) kg(-1) bodyweight orally 3 h prior to surgery. The sentinel lymph node was marked with Nanocoll preoperatively and with a blue dye intraoperatively. Tumour excision, excision of the sentinel lymph node and an axillary lymph node dissection were performed during the same surgical session. The operation site was illuminated with blue light (400 nm) to obtain macroscopic tissue characterisation of fluorescence. Tissue samples were stored protected from light, and analysed using a fluorescence microscope. Results were correlated with histopathology. In all, 14 sentinel lymph nodes, seven axillary lymph nodes and seven primary tumours were analysed. Metastatic sentinel lymph nodes demonstrated a statistically significant higher FI than nonmetastatic sentinel lymph nodes (2630 vs 526, P<0.0001). The FI of metastatic sentinel lymph nodes, of metastatic axillary lymph nodes and of the primary tumour were comparably high, and were statistically significantly higher compared to the normal mammary tissue. Intraoperatively, only in a few cases, it was possible to recognise the metastatic sentinel lymph node macroscopically with blue light. Our study indicates that photodynamic diagnosis with ALA has a potential in the diagnosis and detection of the sentinel lymph node in patients with breast cancer, and is worth to be further investigated and developed for intraoperative photodynamic diagnosis and possibly therapy.

International business travel: impact on families and travellers.

OBJECTIVES: Spouses and staff of the World Bank Group (WBG) were questioned about the impact of international business travel on families and travellers. Dependent variables were self reported stress, concern about the health of the traveller, and negative impact on the family. We hypothesised that several travel factors (independent variables) would be associated with these impacts. These travel factors had to do with the frequency, duration, and predictability of travel and its interference with family activities. METHODS: Survey forms were developed and distributed to all spouses of travelling staff as well as a small sample of operational staff. Kendall's tau b correlation coefficients of response frequencies were computed with the data from scaled items. Written responses to open ended questions were categorised. RESULTS: Response rates for spouses and staff were 24% and 36%, respectively. Half the spouse sample (n=533) and almost 75% of the staff sample (n=102) reported high or very high stress due to business travel. Self reported spouse stress was associated with six out of eight travel factors. Female spouses, those with children, and younger spouses reported greater stress. Self reported staff stress was significantly associated with four out of nine travel factors. Further insight into how business travel affects families and staff (including children's behavioural changes) and how families cope was gained through responses to written questions. CONCLUSIONS: The findings support the notion that lengthy and frequent travel and frequent changes in travel dates which affect family plans, all characteristic of WBG missions, negatively affects many spouses and children (particularly young children) and that the strain on families contributes significantly to the stress staff feel about their travel. Policies or management practices that take into consideration family activities and give staff greater leeway in controlling and refusing travel may help relieve stress.

[Neurosyphilis 12 years after treatment of primary infection in a meanwhile HIV infected patient]. / Neurolues 12 Jahre nach Behandlung eines Primäraffekts bei einem inzwischen HIV-infizierten Patienten.

A 33-year-old male HIV-positive patient developed pure right motor hemiplegia due to meningovascular neurosyphilis. 12 years ago he was successfully treated for early syphilis with a single dose of 2.4 million units penicillin G benzathine without subsequent evidence of new infection or disease progression. Repeated HIV tests remained negative until 1993 when the HIV infection was diagnosed. It is well known that Treponema pallidum, the etiologic agent of syphilis, may be detected in the cerebrospinal fluid during early infection. Thus the former recommended regimen of single-dose penicillin G benzathine may not reliably eradicate T. pallidum from the CNS. Residual organisms may serve as a reservoir for relapse and dissemination in an immunocompromised host.

Hypoplastic thymus and T-cell reduction in EECUT syndrome.

We report on a patient with EEC/EECUT syndrome and concomitant hypoplasia of the thymus and reduction of T cells in secondary lymphatic organs. The patient was born prematurely at 35 weeks of gestational age and exhibited ectodermal dysplasia, ectrodactyly, cleft palate and urinary tract abnormalities. On the left side, a large ureterocele was present. On the right side, an atretic ureter was found. Both conditions had led to intrauterine hydronephrosis, renal dysplasia, oligohydramnios, pulmonary hypoplasia, and death of the child. Ureteral malformations are thought to be of epithelial origin. Autopsy showed only small rudiments of thymic tissue containing single epithelial cells, but were completely devoid of Hassall corpuscules. Again, this clearly points to an ectodermal defect. Although there was severe reduction of T cells in secondary lymphatic organs, the thymic defect would not have necessarily led to immunological deficiency; perhaps this is the reason that an epithelial defect in the thymus of patients with EEC syndrome has not yet been reported. With regard to an updating of the diagnosis of the EEC/EECUT syndrome, an "EEC/EECUT plus" syndrome is suggested.

The substrate specificity of tocopherol cyclase.

The substrate specificity of the enzyme tocopherol cyclase from the blue-green algae Anabaena variabilis (Cyanobacteria) was investigated with 11 substrate analogues revealing the significance of three major recognition sites: (i) the OH group at C(1) of the hydroquinone, (ii) the (E) configuration of the double bond, and (iii) the length of the lipophilic side chain. Experiments with two affinity matrices suggest that substrates approach the enzyme's active site with the hydrophobic tail.

[Diffuse cholangiofibromatosis--incidental findings in sonography, ERCP and laparoscopy]. / Die diffuse Cholangiofibromatose--Zufallsbefunde bei Sonographie, ERCP und Laparoskopie.

Diffuse cholangiofibromatosis is a rare and asymptomatic abnormality. Its clinical significance results from problems that occur in differential diagnosis to granulomatous hepatitis, sclerosing cholangitis, multiple microabscesses or diffuse tumour infiltration of the liver, when it is incidentally found in ultrasound, ERCP or laparoscopy. The characteristic findings in these examinations are described in two case reports. The ultrasonic pattern of multiple intrahepatic double structures, microcystic areas and surrounding hyperechoic reflexes are in accordance with multiple intrahepatic microcystic and hazy areas in ERCP x-rays and multiple white-yellowish areas that retract liver surface in laparoscopy. Final diagnosis is confined by the characteristical microscopic finding of von Meyenburg-complexes in liver biopsy.

DNA polymorphisms of apolipoprotein B and AI/CIII genes and response to gemfibrozil treatment.

Apolipoprotein B XbaI polymorphism and apolipoprotein AI/CIII SstI polymorphism have been found to be associated with variations in serum lipoprotein levels. We investigated whether these gene polymorphisms are involved in determining the lipid-modulating action of gemfibrozil. Of the 221 male subjects with hyperlipidemia studied, 121 responded well to the treatment with more than a 25% reduction in the non-high-density lipoprotein cholesterol level, whereas 100 were nonresponders. Among responders, but not nonresponders, homozygosity for the apolipoprotein B X2 allele (XbaI site present) and heterozygosity for the apolipoprotein AI/CIII S2 allele (SstI site present) were associated with elevated baseline serum low-density lipoprotein cholesterol and triglyceride levels, respectively. However, the hypolipidemic effect of gemfibrozil among the responders was independent of these gene polymorphisms. These data indicate that common polymorphisms of the apolipoprotein B and apolipoprotein AI/CIII gene loci influence serum lipid levels by mechanisms that are amenable to an intervention with gemfibrozil.

Predictive value for coronary heart disease of baseline high-density and low-density lipoprotein cholesterol among Fredrickson type IIa subjects in the Helsinki Heart Study.

In the Helsinki Heart Study 2,590 subjects (63.5% of total) had a type IIa hyperlipoproteinemia at screening. Baseline low-density lipoprotein (LDL) cholesterol (mean 193 mg/dl; 5 mmol/liter) and high-density lipoprotein (HDL) cholesterol (mean 50.2 mg/dl; 1.3 mmol/liter) showed no statistical correlation (r = 0.046). Both the placebo (1,293 patients) and gemfibrozil groups (1,297 patients) were divided into tertiles by baseline HDL and LDL cholesterol to determine the relative predictive risk of developing coronary artery disease. In a population with elevated LDL cholesterol, it is significant that the lipoprotein fraction with the greatest predictive value was HDL cholesterol. The severity of LDL cholesterol elevation did not provide any differential predictive value for coronary artery disease.

Modification of membrane protein expression and protein secretion in LLC-PK1 cultures grown on different carbohydrates.

Membrane glycoproteins and glycolipids play an important role in epithelial organization, transport and function. To study the effects of exogenous carbohydrates on the expression of glycoproteins, cells of the renal epithelial line LLC-PK1 were cultured on different nutritive carbohydrate sources and on uridine, which is, despite striking differences, known to substitute all essential nutritive functions of glucose. LLC-PK1 cultures were long-term adapted to growth in culture medium containing 0.5, 5, 10 and 25 mM glucose, and 5 mM fructose, galactose and uridine, respectively, as the sole carbohydrate source. These growth conditions elicited adaptive changes in the expression of enzyme activities of alkaline phosphatase and gamma-glutamyltranspeptidase, integral membrane glycoproteins exclusively localized in the apical membrane of LLC-PK1 cells. SDS-PAGE of membrane preparations of adapted LLC-PK1 cells revealed a strong induction of several protein bands between 13.5 and 47 kD in fructose-grown cells, while in plasma membranes of cells grown in galactose several protein bands between 62 and 70 kD decreased. Changes in the secretion pattern of proteins into the culture medium were most prominent in uridine-grown cells compared to controls grown on 25 mM glucose.

Histochemistry of mucosubstances in Brunner's-gland cells and duodenal goblet cells of two New World monkey species (Saimiri sciureus and Saguinus fuscicollis).

Duodenal goblet cells and Brunner's-gland cells obtained from two species of New World monkeys (Saimiri sciureus and Saguinus fuscicollis) were studied using conventional histochemical methods and by applying a panel of 17 labelled lectins. The secretions of both goblet and Brunner's-gland cells were found to contain neutral mucosubstances, while those of goblet cells also exhibit acid and sulphated carbohydrate components. Lectin binding studies allowed a more detailed analysis of the mucus glycoproteins. Marked differences between the two examined species were not detected. N-Acetyl-galactosamine, galactose, fucose and N-Acetyl-glucosamine were found to be the predominant sugar residues in Brunner's-glands glycoproteins, with mannose and glucose being only minor components.