Financial difficulties in breast cancer survivors with and without migration background in Germany-results from the prospective multicentre cohort study BRENDA II.

PURPOSE: We aimed to explore the trajectory of financial difficulties among breast cancer survivors in the German health system and its association with migration background. METHODS: In a multicentre prospective study, breast cancer survivors were approached four times (before surgery, before and after adjuvant therapy, five years after surgery) and asked about their migration history and financial difficulties. Migrants were defined as born/resided outside Germany or having citizenship/nationality other than German. Financial difficulties were ascertained with the financial difficulties item of the European Organisation for Research and Treatment of Cancer Core Instrument (EORTC QLQ-C30) at each time-point (cut-off > 17). Financial difficulties were classified in trajectories: always (every time-point), never (no time-point), initial (first, not fourth), delayed (only fourth), and acquired (second and/or third, not first). A logistic regression was conducted with the trajectories of financial difficulties as outcome and migration background as exposure. Age, trends in partnership status, and educational level were considered as confounders. RESULTS: Of the 363 participants included, 49% reported financial difficulties at at least one time-point. Financial difficulties were reported always by 7% of the participants, initially by 5%, delayed by 10%, and acquired by 21%. Migrants were almost four times more likely to report delayed (odds ratio [OR] = 3.7; 95% confidence interval [CI] 1.3, 10.5) or acquired (OR = 3.6; 95% CI 1.6, 8.4) financial difficulties compared to non-migrant participants. CONCLUSION: Survivors with a migration background are more likely to suffer from financial difficulties, especially in later stages of the follow-up. A linguistically/culturally competent active enquiry about financial difficulties and information material regarding supporting services/insurances should be considered.

To which extent do breast cancer survivors feel well informed about disease and treatment 5 years after diagnosis?

OBJECTIVE: In this study, we investigated to which extent patients feel well informed about their disease and treatment, which areas they wish more or less information and which variables are associated with a need for information about the disease, medical tests and treatment. METHODS: In a German multi-centre prospective study, we enrolled 759 female breast cancer patients at the time of cancer diagnosis (baseline). Data on information were captured at 5 years after diagnosis with the European Organisation for Research and Treatment of Cancer (EORTC) Information Module (EORTC QLQ-INFO24). Good information predictors were analysed using linear regression models. RESULTS: There were 456 patients who participated at the 5-year follow-up. They reported to feel well informed about medical tests (mean score 78.5) and the disease itself (69.3) but relatively poorly about other services (44.3) and about different places of care (31.3). The survivors expressed a need for more information concerning: side effects and long-term consequences of therapy, more information in general, information about aftercare, prognosis, complementary medicine, disease and therapy. Patients with higher incomes were better informed about medical tests (ß 0.26, p 0.04) and worse informed with increasing levels of fear of treatment (ß - 0.11, p 0.02). Information about treatment was reported to be worse by survivors > 70 years old (ß -0.34, p 0.03) and by immigrants (ß -0.11, p 0.02). Survivors who had received additional written information felt better informed about disease, medical tests, treatment and other services (ß 0.19/0.19/0.20/0.25; each p < 0.01). CONCLUSION: Health care providers have to reconsider how and what kind of information they provide. Providing written information, in addition to oral information, may improve meeting those information needs.

Carbon tattooing for targeted lymph node biopsy after primary systemic therapy in breast cancer: prospective multicentre TATTOO trial.

BACKGROUND: Several techniques for targeted lymph node biopsy in patients with node-positive breast cancer receiving primary systemic therapy are in use, each with their inherent advantages and disadvantages. The aim of the TATTOO trial was to evaluate the feasibility and accuracy of carbon tattooing of positive lymph nodes as a method for targeted lymph node biopsy avoiding radiation exposure, high costs, and preoperative localization procedures. METHODS: Patients with initially cT1-4c cN1-3 cM0 invasive breast cancer were included in this prospective multicentre trial. Before initiation of primary systemic therapy, a carbon suspension was injected into the most suspicious axillary lymph node. Targeted lymph node biopsy was performed in all patients after completion of primary systemic therapy. Additional sentinel lymph node biopsy was done in those with axillary downstaging, and completion axillary lymph node dissection in patients still presenting with suspicious lymph nodes. RESULTS: A total of 118 patients were included and 110 were eligible for data analysis. The detection rate for the targeted lymph node was 93.6 per cent (103 of 110), and the sentinel lymph node was identical to the targeted lymph node in 60 per cent. The false-negative rate for the combination of targeted and sentinel node lymph node biopsy (targeted axillary dissection) was 9 per cent. CONCLUSION: Targeted axillary dissection after carbon tattooing is associated with a high detection rate, an acceptable false-negative rate, and appears feasible for clinical use even in healthcare settings with limited resources.

Femtosecond Transfer and Manipulation of Persistent Hot-Trion Coherence in a Single CdSe/ZnSe Quantum Dot.

Ultrafast transmission changes around the fundamental trion resonance are studied after exciting a p-shell exciton in a negatively charged II-VI quantum dot. The biexcitonic induced absorption reveals quantum beats between hot-trion states at 133 GHz. While interband dephasing is dominated by relaxation of the P-shell hole within 390 fs, trionic coherence remains stored in the spin system for 85 ps due to Pauli blocking of the triplet electron. The complex spectrotemporal evolution of transmission is explained analytically by solving the Maxwell-Liouville equations. Pump and probe polarizations provide full control over amplitude and phase of the quantum beats.

Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults.

PURPOSE: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up. METHODS: A total of 255,170 participants aged 25-70 years were recruited in ten European countries (1992-2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC-MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. RESULTS: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087-0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041-0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. CONCLUSION: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.

Phonon-Induced Enhancement of Photon Entanglement in Quantum Dot-Cavity Systems.

We report on simulations of the degree of polarization entanglement of photon pairs simultaneously emitted from a quantum dot-cavity system that demand revisiting the role of phonons. Since coherence is a fundamental precondition for entanglement and phonons are known to be a major source of decoherence, it seems unavoidable that phonons can only degrade entanglement. In contrast, we demonstrate that phonons can cause a degree of entanglement that even surpasses the corresponding value for the phonon-free case. In particular, we consider the situation of comparatively small biexciton binding energies and either finite exciton or cavity mode splitting. In both cases, combinations of the splitting and the dot-cavity coupling strength are found where the entanglement exhibits a nonmonotonic temperature dependence which enables entanglement above the phonon-free level in a finite parameter range. This unusual behavior can be explained by phonon-induced renormalizations of the dot-cavity coupling g in combination with a nonmonotonic dependence of the entanglement on g that is present already without phonons.

Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort.

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41-0.98; ptrend = 0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 = 0.60; 95%CI = 0.39-0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3-T1 = 0.52; 95%CI = 0.32-0.85; ptrend = 0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 = 3.00; 95%CI = 1.13-7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 = 0.37; 95%CI = 0.17-0.81; ptrend = 0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 = 3.40; 95%CI = 1.39-8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking.

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients.

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

A life cycle assessment of liquid pig manure transport in line with EU regulations: A case study from Germany.

The transport of excess manure to crop farming systems is a core measure of livestock farmers to comply with environmental regulations like the EU Nitrates Directive. The German implementation of the directive has recently been revised and will lead to a distinct increase of manure transport. We quantify the environmental impact of 1 m3 of pig manure excreted in scenarios with and without manure transport by life cycle assessment, focusing on farming systems in North-West Germany. Furthermore, we assess how the environmental impact is linked to the regulation which is causing the transport. Compared to a reference scenario without transport, manure transport lowers all assessed impact categories and no trade-off between environmental impacts is found. Major reductions are realized for global warming (39%), freshwater (61%) and marine eutrophication (54%) as well as particulate matter formation (10%). Furthermore, the depletion of fossil fuels and phosphate is lowered. Reductions are mainly caused by an increase of nutrient use efficiency and the savings in chemical fertilizer. However, in a scenario where manure transport is caused by strict regulations regarding phosphate, needed nitrogen leaves the exporting farm likewise and chemical fertilizer use rises at the exporting farm. Caused by the increased fertilizer use, the positive environmental effect of manure transport diminishes, even leading to a rise of fossil fuel depletion by 20% and slight rise of global warming potential by 3%. However, we find that the use of lorries which combine manure and grain transport and, thereby, reduce empty drives, can prevent this trade-off. Our results show the potential of manure transport to reduce the environmental burden caused by the geographical concentration of livestock production. However, the impact of manure transport on global warming and fossil fuel depletion highly depends on the transport distance. Agronomic measures are needed to prevent the increase of chemical N fertilizer use on the exporting farms and policy makers should be aware of possible trade-offs between strict regulations regarding phosphorus and fossil fuel depletion.

Alcohol consumption and risk of urothelial cell bladder cancer in the European prospective investigation into cancer and nutrition cohort.

Findings on the association between alcohol consumption and bladder cancer are inconsistent. We investigated that association in the European Prospective Investigation into Cancer and Nutrition cohort. We included 476,160 individuals mostly aged 35-70 years, enrolled in ten countries and followed for 13.9 years on average. Hazard ratios (HR) for developing urothelial cell carcinoma (UCC; 1,802 incident cases) were calculated using Cox proportional hazards models. Alcohol consumption at baseline and over the life course was analyzed, as well as different types of beverages (beer, wine, spirits). Baseline alcohol intake was associated with a statistically nonsignificant increased risk of UCC (HR 1.03; 95% confidence interval (CI) 1.00-1.06 for each additional 12 g/day). HR in smokers was 1.04 (95% CI 1.01-1.07). Men reporting high baseline intakes of alcohol (>96 g/day) had an increased risk of UCC (HR 1.57; 95% CI 1.03-2.40) compared to those reporting moderate intakes (<6 g/day), but no dose-response relationship emerged. In men, an increased risk of aggressive forms of UCC was observed even at lower doses (>6 to 24 g/day). Average lifelong alcohol intake was not associated with the risk of UCC, however intakes of spirits > 24 g/day were associated with an increased risk of UCC in men (1.38; 95% CI 1.01-1.91) and smokers (1.39; 95% CI 1.01-1.92), compared to moderate intakes. We found no association between alcohol and UCC in women and never smokers. In conclusion, we observed some associations between alcohol and UCC in men and in smokers, possibly because of residual confounding by tobacco smoking.

A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study.

BACKGROUND: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting. MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours. RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor. CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.

Stationary Phonon Squeezing by Optical Polaron Excitation.

We demonstrate that a stationary squeezed phonon state can be prepared by a pulsed optical excitation of a semiconductor quantum well. Unlike previously discussed scenarios for generating squeezed phonons, the corresponding uncertainties become stationary after the excitation and do not oscillate in time. The effect is caused by two-phonon correlations within the excited polaron. We demonstrate by quantum kinetic simulations and by a perturbation analysis that the energetically lowest polaron state comprises two-phonon correlations which, after the pulse, result in an uncertainty of the lattice momentum that is continuously lower than in the ground state of the semiconductor. The simulations show the dynamics of the polaron formation process and the resulting time-dependent lattice uncertainties.

Picosecond Control of Quantum Dot Laser Emission by Coherent Phonons.

A picosecond acoustic pulse can be used to control the lasing emission from semiconductor nanostructures by shifting their electronic transitions. When the active medium, here an ensemble of (In,Ga)As quantum dots, is shifted into or out of resonance with the cavity mode, a large enhancement or suppression of the lasing emission can dynamically be achieved. Most interesting, even in the case when gain medium and cavity mode are in resonance, we observe an enhancement of the lasing due to shaking by coherent phonons. In order to understand the interactions of the nonlinearly coupled photon-exciton-phonon subsystems, we develop a semiclassical model and find an excellent agreement between theory and experiment.

[Multimodal therapy of fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Multimodale Therapie des Fibromyalgiesyndroms : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n = 8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A search of the literature for systematic reviews on randomized controlled trials of multimodal therapy from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: The use of multimodal therapy (combination of aerobic exercise with at least one psychological therapy) with a duration of at least 24 h is strongly recommended for patients with severe forms of fibromyalgia.

[General treatment principles, coordination of care and patient education in fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Allgemeine Behandlungsgrundsätze, Versorgungskoordination und Patientenschulung beim Fibromyalgiesyndrom : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A search of the literature for systematic reviews on randomized, controlled trials on patient education and shared decision-making from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences, clinical and practical applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: The diagnosis of fibromyalgia syndrome should be explicitly communicated to the affected individual. Shared decision-making with the patient on the therapeutic options based on individual preferences of the patient, comorbidities and the success of previous treatment is recommended. A step-wise treatment approach depending on the severity of fibromyalgia syndrome and the response to therapeutic measures is recommended.

Coulomb Mediated Hybridization of Excitons in Coupled Quantum Dots.

We report Coulomb mediated hybridization of excitonic states in optically active InGaAs quantum dot molecules. By probing the optical response of an individual quantum dot molecule as a function of the static electric field applied along the molecular axis, we observe unexpected avoided level crossings that do not arise from the dominant single-particle tunnel coupling. We identify a new few-particle coupling mechanism stemming from Coulomb interactions between different neutral exciton states. Such Coulomb resonances hybridize the exciton wave function over four different electron and hole single-particle orbitals. Comparisons of experimental observations with microscopic eight-band k·p calculations taking into account a realistic quantum dot geometry show good agreement and reveal that the Coulomb resonances arise from broken symmetry in the artificial semiconductor molecule.

Evidence for a Strong Topological Insulator Phase in ZrTe_{5}.

The complex electronic properties of ZrTe_{5} have recently stimulated in-depth investigations that assigned this material to either a topological insulator or a 3D Dirac semimetal phase. Here we report a comprehensive experimental and theoretical study of both electronic and structural properties of ZrTe_{5}, revealing that the bulk material is a strong topological insulator (STI). By means of angle-resolved photoelectron spectroscopy, we identify at the top of the valence band both a surface and a bulk state. The dispersion of these bands is well captured by ab initio calculations for the STI case, for the specific interlayer distance measured in our x-ray diffraction study. Furthermore, these findings are supported by scanning tunneling spectroscopy revealing the metallic character of the sample surface, thus confirming the strong topological nature of ZrTe_{5}.

Meal patterns across ten European countries - results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study.

OBJECTIVE: To characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study. DESIGN: Cross-sectional study utilizing dietary data collected through a standardized 24 h diet recall during 1995-2000. Eleven predefined intake occasions across a 24 h period were assessed during the interview. In the present descriptive report, meal patterns were analysed in terms of daily number of intake occasions, the proportion reporting each intake occasion and the energy contributions from each intake occasion. SETTING: Twenty-seven centres across ten European countries. SUBJECTS: Women (64 %) and men (36 %) aged 35-74 years (n 36 020). RESULTS: Pronounced differences in meal patterns emerged both across centres within the same country and across different countries, with a trend for fewer intake occasions per day in Mediterranean countries compared with central and northern Europe. Differences were also found for daily energy intake provided by lunch, with 38-43 % for women and 41-45 % for men within Mediterranean countries compared with 16-27 % for women and 20-26 % for men in central and northern European countries. Likewise, a south-north gradient was found for daily energy intake from snacks, with 13-20 % (women) and 10-17 % (men) in Mediterranean countries compared with 24-34 % (women) and 23-35 % (men) in central/northern Europe. CONCLUSIONS: We found distinct differences in meal patterns with marked diversity for intake frequency and lunch and snack consumption between Mediterranean and central/northern European countries. Monitoring of meal patterns across various cultures and populations could provide critical context to the research efforts to characterize relationships between dietary intake and health.

Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study.

BACKGROUND: Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations. METHODS: In 486,799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes. RESULTS: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11. CONCLUSIONS: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.

Long-term ovarian function in women treated with CHOP or CHOP plus etoposide for aggressive lymphoma.

BACKGROUND: Chemotherapy-associated ovarian damage comprises not only infertility, but also premature menopause. The latter has been reported as a consequence of alkylating chemotherapy for breast cancer or Hodgkin's lymphoma. In this study, we assessed the long-term impact of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimens on ovarian function in patients with aggressive non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: Long-term survivors after CHOP or CHOP plus etoposide (CHOEP) treatment within the Mabthera International Trial or the NHL-B1 trial of the German NHL Study Group were requested to respond to a questionnaire and to consent to blood sampling for hormone assessment. RESULTS: A total of 46 of 81 contacted patients with a median age of 32.5 years at the time of enrolment into the aforementioned clinical trials responded to the questionnaire. The median follow-up after completion of treatment was 14 years. Last menstrual bleeding occurred significantly earlier in patients compared with the general population (47 versus 51 years, P < 0.0001). In comparison to the distribution of menopausal symptoms in the general population, the percentage of women with moderate or severe menopausal symptoms was increased. In 23 patients who agreed to participate in laboratory analyses, anti-Muller hormone as a marker of ovarian reserve was decreased when compared with correspondent age groups of the general population. CONCLUSION: Although most female patients regain fertility after CHOP-like chemotherapy, late ovarian impairment occurs frequently. Therefore, awareness of such delayed side-effects at the time of counselling is of importance.