Amyloid precursor-like protein 2 suppresses irradiation-induced apoptosis in Ewing sarcoma cells and is elevated in immune-evasive Ewing sarcoma cells

Despite surgery, chemotherapy, and radiotherapy treatments, the children, adolescents, and young adults who are diagnosed with metastasized Ewing sarcoma face a dismal prognosis. Amyloid precursor-like protein 2 (APLP2) has recently been implicated in the survival of cancer cells and in our current study, APLP2’s contribution to the survival of Ewing sarcoma cells was examined. APLP2 was readily detected in all Ewing sarcoma cell lines analyzed by western blotting, with the TC71 Ewing sarcoma cells expressing the lowest level of APLP2 among the lines. While irradiation induces apoptosis in TC71 Ewing sarcoma cells (as we determined by quantifying the proportion of cells in the sub-G₁ population), transfection of additional APLP2 into TC71 decreased irradiation-induced apoptosis. Consistent with these findings, in parallel studies, we noted that isolates of the TC71 cell line that survived co-culture with lymphokine-activated killer (LAK) cells (which kill by inducing apoptosis in target cells) displayed increased expression of APLP2, in addition to smaller sub-G₁ cell populations after irradiation. Together, these findings suggest that APLP2 lowers the sensitivity of Ewing sarcoma cells to radiotherapy-induced apoptosis and that APLP2 expression is increased in Ewing sarcoma cells able to survive exposure to cytotoxic immune cells.     

Risk factors for thyroid cancer: an epidemiological review focused on nutritional factors

Objectives  The present review summarizes epidemiological evidence on risk factors for thyroid cancer (TC), in particular, nutritional factors. Methods  Searches of articles on the issue were conducted using MEDLINE. Results  Exposure to ionizing radiation, particularly during childhood, is the best-established risk factor for TC. There is also a strong association with history of benign nodules/adenoma or goiter. Iodine deficiency may induce an increasing incidence of benign thyroid conditions, but very high iodine intake also affects thyroid function and, possibly, TC risk. Among dietary factors, fish—the major natural source of iodine in human diet—is not consistently related to TC risk. High intake of cruciferous vegetables shows a weak inverse association with TC. Among other food groups, vegetables other than cruciferous are the only food group showing a favorable effect on TC, with an approximate 20% reduction in risk for subjects with the highest consumption. No effect on TC risk of alcohol, coffee, or other food-groups/nutrients emerged. Height and weight at diagnosis show a moderate positive association with TC risk. Conclusion  At present, the only recognized measures for reducing TC risk is to avoid ionizing radiation and iodine deficiency, particularly in childhood and young women, and to increase vegetable consumption.     

Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study

Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C‐reactive protein, interleukin (IL)‐6, IL‐10 and tumor necrosis factor (TNF)‐α and the risk of TC. A case‐control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer‐free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (OR_T3vs.T1 = 0.69, 95% CI: 0.49–0.98, P_trend = 0.04) but not among men (OR_T3vs.T1 = 1.36, 95% CI: 0.67–2.76, P_trend = 0.37). Increasing levels of IL‐10 were positively associated with TC risk in both genders and significantly so in women (OR_T3vs.T1 = 1.59, 95% CI: 1.13–2.25, P_trend = 0.01) but not in men (OR_T3vs.T1 = 1.78, 95% CI: 0.80–3.98, P_trend = 0.17). Leptin, CRP, IL‐6 and TNF‐α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL‐10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight.     

腘窝瘤样钙化症一例

患者,女,75岁,于2012年10月31日以“发现右胭窝包块1周”为主诉来我院就诊,该患者入院1周前因右足跟疼痛1个月并出现右膝关节轻微疼痛,到外院就诊,膝关节X线片（图1A）发现右胭窝外下部4cm×3cm不均匀高密度影,为求进一步诊治,来我院就诊并住院。     

Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HR_{Q4 vs. Q1} = 0.99, 95% confidence interval [CI] 0.77–1.29), papillary (HR_{Q4 vs. Q1} = 1.06, 95% CI 0.80–1.41) or follicular TC (HR_{Q4 vs. Q1} = 1.10, 95% CI 0.55–2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.     

Cadmium‐coordinated supramolecule suppresses tumor growth of T‐cell leukemia in mice

Cadmium is a toxic pollutant with occupational and environmental significance, due to its diverse toxic effects. Supramolecules that conjugate and decontaminate toxic metals have potential for use in treatment of cadmium intoxication. In addition, metal‐coordinating ability has been postulated to contribute to the cytotoxic effects of anti‐tumor agents such as cisplatin or bleomycin. Thiacalixarenes, cyclic oligomers of p‐alkylphenol bridged by sulfur atoms, are supramolecules known to have potent coordinating ability to metal ions. In this study, we show that cadmium‐coordinated thiacalix[4]arene tetrasulfate (TC4ATS‐Cd) exhibits an anti‐proliferative effect against T‐cell leukemia cells. Cadmium exhibited cytotoxicity with IC₅₀ values ranging from 36 to 129 μM against epithelia‐derived cancer cell lines, while TC4ATS‐Cd elicited no significant cytotoxicity (IC₅₀ > 947 μM). However, a number of T‐cell leukemia cell lines exhibited marked sensitivity to TC4ATS‐Cd. In Jurkat cells, toxicity of TC4ATS‐Cd occurred with an IC₅₀ of 6.9 μM, which is comparable to that of 6.5 μM observed for cadmium alone. TC4ATS‐Cd induced apoptotic cell death through activation of caspase‐3 in Jurkat cells. In a xenograft model, TC4ATS‐Cd (13 mg/kg) treatment significantly suppressed the tumor growth of Jurkat cells in mice. In addition, TC4ATS‐Cd‐treated mice exhibited significantly less cadmium accumulation in liver and kidney compared to equimolar cadmium‐treated mice. These results suggest that cadmium‐coordinated supramolecules may have therapeutic potential for treatment of T‐cell leukemia.     

Testicular Cancer Awareness and Knowledge: Is It the Same? Exploratory Study in a Mixed-Gender Population

Testicular cancer (TC) is among the most common malignancies in the young male. Awareness plays an important role, because delay in diagnosis affects outcome. Testicular self-examination (TSE) is controversial, but recent evidence shows some cost benefits in performing this exam versus a late-stage diagnosis. The aims of this study are to determine and compare awareness for TC and TSE in males and females with the actual knowledge to this disease in an academic population. An exploratory study using an online questionnaire about TC and TSE was performed in a public university. Answers were collected and submitted to statistical analysis. A total of 815 participants—507 males (62.2 %) and 308 females (37.7 %)—answered the survey. The participants that responded that they were aware of TC were 399/507 (78.7 %) males and 275/308 (89.3 %) females. About half (48.9 %) of male and 42.2 % of female respondents did not answered correctly to most common symptom, and only 15 % of males and 25 % of females answered to the question on age at diagnosis. Both gender subjects rated TSE as very important, and the majority of females were motivated to advise male partners or friends to perform TSE. This study reported a good awareness on TC and TSE, but comparing to the correct knowledge about this disease, results are disappointing. The actual knowledge about TC is low and comparable in men and women. Women revealed a better understanding of this disease and importance of TSE, suggesting that they can assume an important role in promoting health behaviors in men.     

Circulating endogenous sex steroids and risk of differentiated thyroid carcinoma in men and women

Thyroid cancer (TC) is substantially more common in women than in men, pointing to a possible role of sex steroid hormones. We investigated the association between circulating sex steroid hormones, sex hormone binding globulin (SHBG) and the risk of differentiated TC in men and women within the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. During follow-up, we identified 333 first primary incident cases of differentiated TC (152 in pre/peri-menopausal women, 111 in post-menopausal women, and 70 in men) and 706 cancer-free controls. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre-menopausal women only) were performed using liquid chromatography/mass spectrometry method. SHBG concentrations were measured by immunoassay. Odds ratios (ORs) were estimated using conditional logistic regression models adjusted for possible confounders. No significant associations were observed in men and postmenopausal women, while a borderline significant increase in differentiated TC risk was observed with increasing testosterone (adjusted OR T3 vs T1: 1.68, 95% CI: 0.96–2.92, p_trend = .06) and androstenedione concentrations in pre/perimenopausal women (adjusted OR T3 vs T1: 1.78, 95% CI: 0.96–3.30, p_trend = .06, respectively). A borderline decrease in risk was observed for the highest progesterone/estradiol ratio (adjusted OR T3 vs T1: 0.54, 95% CI: 0.28–1.05, p_trend = .07). Overall, our results do not support a major role of circulating sex steroids in the etiology of differentiated TC in post-menopausal women and men but may suggest an involvement of altered sex steroid production in pre-menopausal women.     

Predictive value of SAR based quality indicators for head and neck hyperthermia treatment quality

Purpose: Hyperthermia treatment quality determines treatment effectiveness as shown by the clinically derived thermal-dose effect relations. SAR based optimization factors are used as possible surrogate for temperature, since they are not affected by thermal tissue properties uncertainty and variations. Previously, target coverage (TC) at the 25% and 50% iso-SAR level was shown predictive for treatment outcome in superficial hyperthermia and the target-to-hot-spot-quotient (THQ) was shown to highly correlate with predictive temperature in deep pelvic hyperthermia. Here, we investigate the correlation with temperature for THQ and TC using an ‘intermediate’ scenario: semi-deep hyperthermia in the head & neck region using the HYPERcollar3D.

Methods: Fifteen patient-specific models and two different planning approaches were used, including random perturbations to circumvent optimization bias. The predicted SAR indicators were compared to predicted target temperature distribution indicators T50 and T90, i.e., the median and 90th percentile temperature respectively.

Results: The intra-patient analysis identified THQ, TC25 and TC50 as good temperature surrogates: with a mean correlation coefficient R²_T50?=?0.72 and R²_T90=0.66. The inter-patient analysis identified the highest correlation with TC25 (R²_T50?=?0.76, R²_T90=0.54) and TC50 (R²_T50?=?0.74, R²_T90?=?0.56).

Conclusion: Our investigation confirmed the validity of our current strategy for deep hyperthermia in the head & neck based on a combination of THQ and TC25. TC50 was identified as the best surrogate since it enables optimization and patient inclusion decision making using one single parameter.     

Incidence of thyroid cancer in Italy, 1991–2005: time trends and age–period–cohort effects

BackgroundIn Italy, some of the highest incidence rates (IRs) of thyroid cancer (TC) worldwide have been reported.Patients and methodsTC cases <85 years of age reported to Italian cancer registries during 1991–2005 were included. Age-standardized IRs were computed for all TC and age–period–cohort effects were estimated for papillary TC.ResultsIRs of TC were twofold higher in 2001–2005 than in 1991–1995 (18 and 8 per 100 000 women, 6 and 3 per 100 000 men, respectively). Increases were similar in the two sexes and nearly exclusively due to papillary TC. Increases of papillary TC by birth cohort were found in both sexes and among all age groups between 20 and 79 years. Age–period–cohort models showed a strong period effect in both sexes (rate ratio for 2001–2009 versus 1991–1995 = 2.5 in women and 2.3 in men), although IRs peaked at an earlier age in women (45–49 years) than men (65–69 years).ConclusionThe strength of the period effect in both sexes and the earlier onset in women than men strongly implicated increased medical surveillance in the upward trends of papillary TC incidence in Italy. The consequences of the current intense search for TC on morbidity and possible overtreatment, especially among young women, should be carefully evaluated.     

Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study

Incidence rates of differentiated thyroid carcinoma (TC) have increased in many countries. Adiposity and dietary risk factors may play a role, but little is known on the influence of energy intake and macronutrient composition. The aim of this study was to investigate the associations between TC and the intake of energy, macronutrients, glycemic index (GI) and glycemic load in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,274 middle‐age participants (70.2% women) from ten European countries. Dietary data were collected using country‐specific validated dietary questionnaires. Total carbohydrates, proteins, fats, saturated, monounsaturated and polyunsaturated fats (PUFA), starch, sugar, and fiber were computed as g/1,000 kcal. Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence interval (CI) by intake quartile (Q). After a mean follow‐up time of 11 years, differentiated TC was diagnosed in 556 participants (90% women). Overall, we found significant associations only with total energy (HR_Q4vs.Q1, 1.29; 95% CI, 1.00–1.68) and PUFA intakes (HR_Q4vs.Q1, 0.74; 95% CI, 0.57–0.95). However, the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index (BMI) groups, i.e., positive associations with starch and GI were found in participants with a BMI ≥ 25 and with sugar intake in those with BMI < 25. Moreover, inverse associations with starch and GI were observed in subjects with BMI < 25. In conclusion, our results suggest that high total energy and low PUFA intakes may increase the risk of differentiated TC. Positive associations with starch intake and GI in participants with BMI ≥ 25 suggest that those persons may have a greater insulin response to high starch intake and GI than lean people.     

The Radiographic Changes of Scleroderma in the Hands

Hand radiographs from 160 patients with scleroderma were reviewed. The presence of calcinosis distal to the metacarpophalangeal joints was significantly associated with the female sex, disease duration over 10 years, digital ulceration, telangiectasia, tuft erosion and the presence of anticentromere antibodies. The presence of calcinosis proximal to the metacarpophalangeal joints was significantly associated with tuft erosions and erosions involving all joints. The lack of distal calcinosis was significantly associated with anti Scl 70 and antinucleolar antibodies. The prevalence of other radiological manifestations of scleroderma such as osteoarthritis, erosions and dorsal tuft modelling was documented. Specific radiological findings correlate with certain clinical and serological characteristics in scleroderma.     

Intestinal uptake of bile acids: Effect of external abdominal irradiation

Abdominal irradiation has recently been shown to influence the uptake of hexoses, amino acids, fatty acids and cholesterol into the jejunum of rats. The present studies were undertaken with a previously validated in vitro technique to determine the effect of abdominal irradiation from a cesium¹³⁷ source on the rates of uptake of six bile acids into the jejunum, ileum, and colon. In the ileum of control rats, there were marked differences in the value of the apparent Michaelis constant (Km¹), maximal transport rate (J_d^m), and apparent passive permeability coefficient (Pd¹) between cholic (C), glycocholic (GC), taurocholic (TC), chenodeoxycholic (CDC), and glycochenodeoxycholic (GCDC), and deoxycholic (DC) acid. The Km¹ for each bile acid except. DC was lower three and 14 days after 600 rad, whereas the J_d^m for GC fell, but rose for TC, CDC, GCDC and DC and was unchanged for C. The Pd¹ rose for C, GC, and DC, fell for TC and CDC, but remained unchanged for GCDC 14 days after irradiation. After 600 rad the value of Pd¹ in the colon was increased at day 3 and 14 for CDC and GCDC, but was unchanged for GC and TC and was decreased for C. The uptake of bile acids was also affected by 300 rad and by 900 rad, but the direction and magnitude of the change was influenced by the intestinal site, the dose of irradiation, and the type of bile acid. The results show that: 1) there likely are multiple ileal carriers for bile acids; 2) abdominal irradiation has a variable effect on these carriers; 3) the passive permeability to bile acids varies with the bile acid and with the site along the intestine; and 4) abdominal irradiation is associated with a rise in the colonic permeability to only some bile acids.     

A Phase II Study of Pemetrexed in Patients with Recurrent Thymoma and Thymic Carcinoma

Introduction

Thymoma and thymic carcinoma (TC) are neoplastic diseases with reported chemosensitivity to a broad range of agents. However, because of the rarity of these diseases, few prospective trials have been conducted in patients with advanced thymic malignancies. We conducted a prospective phase II trial to evaluate the clinical activity of pemetrexed, a multitargeted antifolate agent, in previously treated patients with thymoma and TC.

Molecular Classification of Neuroendocrine Tumors of the Thymus

IntroductionThe WHO classification of pulmonary neuroendocrine tumors (PNETs) is also used to classify thymic NETs (TNETs) into typical and atypical carcinoid (TC and AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC), but little is known about the usability of alternative classification systems.MethodsOne hundred seven TNET (22 TC, 51 AC, 28 LCNEC, and 6 SCC) from 103 patients were classified according to the WHO, the European Neuroendocrine Tumor Society, and a grading-related PNET classification. Low coverage whole-genome sequencing and immunohistochemical studies were performed in 63 cases. A copy number instability (CNI) score was applied to compare tumors. Eleven LCNEC were further analyzed using targeted next-generation sequencing. Morphologic classifications were tested against molecular features.ResultsWhole-genome sequencing data fell into three clusters: CNI_low, CNI_int, and CNI_high. CNI_low and CNI_int comprised not only TC and AC, but also six LCNECs. CNI_high contained all SCC and nine LCNEC, but also three AC. No morphologic classification was able to predict the CNI cluster. Cases where primary tumors and metastases were available showed progression from low-grade to higher-grade histologies. Analysis of LCNEC revealed a subgroup of intermediate NET G3 tumors that differed from LCNEC by carcinoid morphology, expression of chromogranin, and negativity for enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2).ConclusionsTNETs fall into three molecular subgroups that are not reflected by the current WHO classification. Given the large overlap between TC and AC on the one hand, and AC and LCNEC on the other, we propose a morphomolecular grading system, Thy-NET G1-G3, instead of histologic classification for patient stratification and prognostication.     

Latency Period until the Development of Thyroid Cancer in Young Patients Submitted to Radiotherapy: Report of 10 Cases

Background

Radiotherapy increases the risk of thyroid cancer (TC); patients submitted to this treatment should undergo a long-term follow-up. Our aim is to describe the features and outcomes of young patients who developed TC after radiotherapy.

Methods

At our center, patients undergoing radiotherapy directly or indirectly involving the thyroid are regularly followed up in order to detect early dysfunction or nodules. Herein, we report the cases of 10 patients who were submitted to radiotherapy and developed TC.

Clinical Findings

Seven patients were irradiated in the neck and 3 in nearby regions. The mean age at the last radiotherapy session was 10 ± 5.5 years. The average time until the appearance of the first thyroid nodule was 14 ± 4.7 years. The mean size increment of the nodules was 2.4 ± 1.6 mm/year. On the first cytology, only 2 results were suspicious of papillary thyroid cancer (PTC). All patients presented a histology of PTC. Eight were in stage I and 2 in stage II. The median follow-up from primary diagnosis to TC and beyond was 20 and 3 years, respectively.

Conclusions

In these patients, cytologies may be difficult to interpret due to persistent benign results. The threshold for surgical indication may be anticipated, considering the increased risk of TC. We report the evolution of these nodules over time, from the end of primary oncological treatment.Key words: Cancer survivors, Radiotherapy, Radiation-related cancer, Thyroid cancer     

The Prevalence of Thyroid Cancer and Benign Thyroid Disease in Patients With Familial Adenomatous Polyposis May Be Higher Than Previously Recognized

PurposePatients with familial adenomatous polyposis (FAP) are at increased risk for colorectal cancer and extracolonic neoplasms. The prevalence of thyroid cancer (TC) and benign thyroid disease in this patient population is unclear, and guidelines for screening for TC in these patients are not well established. The purpose of this study was to report the prevalence of TC and benign thyroid disease in patients with FAP.MethodsThe prospectively maintained Hereditary Colorectal Cancer Family Registry at Memorial Sloan-Kettering Cancer Center was queried to identify patients with FAP and with TC and/or benign thyroid disease.ResultsSixty-six patients with FAP were identified. There were 30 men and 36 women, with a median age of 38.6 years. Four (6.1%) patients had a history of TC. All were women, with a mean age at TC diagnosis of 36.5 years. Three of the 4 TCs were papillary thyroid cancer. Two patients with TC presented with palpable nodules. An additional 6 (9.1%) patients with FAP had a history of benign thyroid disease, including nodules (3), hypothyroidism (2), cysts (2), goiter (1), and thyroiditis (1). Three of 4 patients with TC and all 6 patients with benign thyroid disease had other extracolonic manifestations associated with FAP.ConclusionsThe prevalences of TC (6.1%) and benign thyroid disease (9.1%) are increased in our patients with FAP and are higher than noted in some previous reports. Periodic thyroid ultrasound screening should be considered in patients with FAP to further elucidate the prevalence and for possible early detection of TC and benign thyroid disease in this population.     

Independent and joint associations of blood lipids and lipoproteins with lung cancer risk in Chinese males: A prospective cohort study

To investigate the independent and joint associations of blood lipids and lipoproteins with lung cancer risk in Chinese males, a prospective cohort study was conducted. A total of 109,798 males with baseline information on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and non-HDL were prospectively observed from 2006 to 2015 for cancer incidence. Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a 9-year follow-up, a total of 986 lung cancer cases were identified. Multivariable analyses showed that both males with low TC (HR_Q1vs.Q2 = 1.27, 95%CI: 1.02–1.60) and males with high TC (HR_Q5vs.Q2 = 1.30, 95%CI: 1.04–1.63) had an increased lung cancer risk, and the U-shaped association was also revealed in the RCS analysis (p_overall = 0.013, p_nonlinear = 0.006). Furthermore, both low TG (HR_Q1vs.Q2 = 1.24, 95%CI: 0.99–1.54) and high TG (HR_Q5vs.Q2 = 1.27, 95%CI: 1.01–1.59) were associated with increased lung cancer risk, while low LDL-C (HR_Q1vs.Q2 = 1.38, 95%CI: 1.11–1.72) was associated with increased lung cancer risk. When TC, TG and LDL-C were considered jointly, the number of abnormal indicators was linearly associated with an increased risk of lung cancer (p_trend < 0.001), as subjects with three abnormal indicators had a twofold higher risk of developing lung cancer (HR = 2.02, 95%CI: 1.62–2.54). Notably, these associations were statistically significant among never smokers, never drinkers and overweight/obese males. These findings suggest that dyslipidemia may potentially be a modifiable risk factor that has key scientific and clinical significance for lung cancer prevention.     

Sperm count in Swedish clinical stage I testicular cancer patients following adjuvant treatment

BackgroundLittle is known regarding sperm production following adjuvant treatment in testicular cancer (TC) clinical stage I (CS I) patients.Patients and methodsA total of 182 TC patients aged 18–50 years were prospectively included during 2001–2006 at any given time within 5 years of orchiectomy. Semen samples were delivered postorchiectomy but before further treatment, 6, 12, 24, 36 and 60 months (T₀–T₆₀) after completed therapy. Total sperm number (TSN) and sperm concentration (SC) were used as measurements of testicular function. Four groups according to treatment modality were identified; Radiotherapy; To a total dose of 25.2 Gy to the infradiaphragmal paraaortic and ipsilateral iliac lymph nodes (RT, N = 70), one cycle of adjuvant BEP (bleomycin, etoposide, cisplatin, 5 day regimen) (BEP, N = 62), one cycle of adjuvant carboplatin AUC 7 (Carbo, N = 22), and patients managed by surveillance (SURV, N = 28).ResultsIn the cross-sectional analysis, a significant but transient drop in mean TSN and mean SC (T₀–T₆₀) was seen at T₆ after radiotherapy. Apart from a significant increase in mean SC at T₁₂ compared with baseline, no significant differences were observed in the other treatment groups. In 119 patients delivering 3 or more samples, values in TSN and SC were rather stable over time. Azoospermic patients (N = 11) were observed in most treatment groups except for in the BEP group. During follow-up, one azoospermic patient belonging to the Carbo group became normospermic.ConclusionsNo clinically significant long-term effect on TSN or SC associated with adjuvant treatment in TC CSI patients was found. However, as patients may have low sperm counts before orchiectomy as well as after adjuvant treatment, we offer sperm banking before orchiectomy as assisted reproductive measures may be necessary regardless of treatment given.     

Prostate cancer risk in the Swedish AMORIS study: the interplay among triglycerides, total cholesterol, and glucose

BACKGROUND:

In a cohort including 5112 prostate cancer (pCa) patients, the authors investigated associations among triglycerides (TG), total cholesterol (TC), and pCa while taking into account glucose.

METHODS:

A cohort (n = 200,660) based on 4 groups of men, according to age at cohort entry, with TG, TC, and glucose measurements was selected from the Apolipoprotein MOrtality RISk (AMORIS) database. Of these, 5112 men developed pCa. Multivariate Cox proportional hazard models were used to analyze associations among TG, TC, and pCa. Competing risks were assessed graphically.

RESULTS:

Age‐stratified analyses for quartiles of TG, TC, and glucose showed a negative association between glucose and pCa risk (HR, 0.93; 95% CI, 0.86‐1.01), 0.93 (0.86‐1.01), 0.87 (0.81‐0.94) for the second, third, and fourth quartiles compared with the first (P_trend = .001). Stratified analysis by glucose levels (<6.11 or ≥6.11 mmol/L) showed a positive association between hypertriglyceridemia (TG≥1.71 mmol/L) and pCa risk, when there were high glucose levels (HR, 1.23; 95% CI, 1.01‐1.48). No association was found for hypercholesterolemia (TC≥6.50 mmol/L). Competing risk analysis showed that protective effects of glucose were overestimated in conventional Cox proportional hazard models and strengthened positive findings between TG and pCa risk.

CONCLUSIONS:

The authors'; findings supported the hypothesis that factors of the glucose and lipid metabolism influence pCa risk. Competing risk assessment showed that it is important to take into account the long natural history and age distribution of pCa when interpreting results. The authors'; findings indicate another reason to fight the increasing prevalence of obesity and dyslipidemia. Cancer 2011. © 2010 American Cancer Society.