Outcome prediction by extranodal involvement,IPI, R‐IPI,and NCCN‐IPI in the PET/CT and rituximab era: A Danish–Canadian study of 443 patients with diffuse‐large B‐cell lymphoma

18F‐fluorodeoxyglucose PET/CT (PET/CT) is the current state‐of‐the‐art in the staging of diffuse large B‐cell lymphoma (DLBCL) and has a high sensitivity for extranodal involvement. Therefore, reassessment of extranodal involvement and the current prognostic indices in the PET/CT era is warranted. We screened patients with newly diagnosed DLBCL seen at the academic centers of Aalborg, Copenhagen, and British Columbia for eligibility. Patients that had been staged with PET/CT and treated with R‐CHOP(‐like) 1^st line treatment were retrospectively included. In total 443 patients met the inclusion criteria. With a median follow‐up of 2.4 years, the 3‐year overall (OS) and progression‐free survival (PFS) were 73% and 69%, respectively. The Ann Arbor classification had no prognostic impact in itself with the exception of stage IV disease (HR 2.14 for PFS, P<0.01). Extranodal involvement was associated with a worse outcome in general, and in particular for patients with involvement of >2 extranodal sites, including HR 7.81 (P < 0.001) for PFS for >3 sites. Bone/bone marrow involvement was the most commonly involved extranodal site identified by PET/CT (29%) and was associated with an inferior PFS and OS. The IPI, R‐IPI, and NCCN‐IPI were predictive of PFS and OS, and the two latter could identify a very good prognostic subgroup with 3‐year PFS and OS of 100%. PET/CT‐ascertained extranodal involvement in DLBCL is common and involvement of >2 extranodal sites is associated with a dismal outcome. The IPI, R‐IPI, and NCCN‐IPI predict outcome with high accuracy. Am. J. Hematol. 90:1041–1046, 2015. © 2015 Wiley Periodicals, Inc.     

Multimodality Hyperpolarized C-13 MRS/PET/Multiparametric MR Imaging for Detection and Image-Guided Biopsy of Prostate Cancer: First Experience in a Canine Prostate Cancer Model

Molecular Imaging and Biology - To assess whether simultaneous hyperpolarized C-13 magnetic resonance spectroscopy (MRS)/positron emission tomography (PET)/multiparametric magnetic resonance (mpMR)...     

Metronidazole pharmacokinetics in patients with hepatic encephalopathy

The pharmacokinetics of metronidazole and its major metabolites was investigated in eight patients with liver cirrhosis and coma of grade 2 to 4 and in eight healthy controls. In the coma patients the systemic clearance of metronidazole was reduced (29 +/- 10 versus 83 +/- 14 ml/min, mean +/- SD; p less than 0.001) and the elimination half-life prolonged (20 +/- 9 versus 7.3 +/- 0.9 h; p less than 0.001), whereas the volume of distribution at steady state was unchanged (44 +/- 9 versus 48 +/- 7 l) as compared with the healthy controls. Investigation of the major elimination pathways of metronidazole showed that the decreased rate of elimination in the patients was mainly due to impaired hepatic drug oxidation. In four patients therapeutic plasma concentrations were achieved during 6 days' treatment with 500 mg metronidazole per 24 or 48 h.     

Long-term effects of vitamin E, vitamin C, and combined supplementation on urinary 7-hydro-8-oxo-2'-deoxyguanosine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men

We studied the long-term effects of vitamins E and C and their combination on lipid peroxidation in vivo and in vitro. The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) trial is a double-masked placebo-controlled randomized clinical trial to study the effects of vitamin C (500 mg of slow release ascorbate per day), vitamin E (182 mg of RRR-alpha-tocopherol acetate per day), and the combination of both antioxidants. Lipid peroxidation measurements were carried out for 48 male participants at entry and at 12 and 36 months. Compared with placebo, vitamin E and the vitamin combination increased plasma lipid-standardized alpha-tocopherol during the first 12 months by 68.2% and 65.2% (P:<0. 001 for both), respectively, and reduced serum 7beta-hydroxycholesterol by 50.4% (P:=0.013) and 44.0% (P:=0.041), respectively. The net change of lipid standardized alpha-tocopherol was 63.8% after 36 months of vitamin E supplementation and 43.3% for the combination. Vitamin C supplementation elevated plasma total ascorbate level by 30.1% (P:=0.043) in 12 months and by 91.1% (P:=0. 001) in 36 months. Neither vitamin E, vitamin C, nor the combination influenced the urinary excretion rate of 7-hydro-8-oxo-2'-deoxyguanosine or the antioxidative capacity of plasma. Vitamin E and the combination of vitamins E and C enhanced the oxidation resistance of isolated lipoproteins and total serum lipids. Our data indicate that long-term supplementation of nondepleted men with a reasonable dose of vitamin E alone or in combination with slow release vitamin C reduces lipid peroxidation in vitro and in vivo, whereas a relatively high dose of vitamin C alone does not.     

18F-FDG PET/CT as a diagnostic tool in patients with extracervical carcinoma of unknown primary site: a literature review

Background.

Carcinoma of unknown primary (CUP) represents a heterogeneous group of metastatic malignancies for which no primary tumor site can be identified after extensive diagnostic workup. Failure to identify the primary site may negatively influence patient management. The aim of this review was to evaluate ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) as a diagnostic tool in patients with extracervical CUP.

Materials and Methods.

A comprehensive literature search was performed and four publications were identified (involving 152 patients) evaluating ¹⁸F-FDG PET/CT in CUP patients with extracervical metastases. All studies were retrospective and heterogeneous in inclusion criteria, study design, and diagnostic workup prior to ¹⁸F-FDG PET/CT.

Results.

¹⁸F-FDG PET/CT detected the primary tumor in 39.5% of patients with extracervical CUP. The lung was the most commonly detected primary tumor site (∼50%). The pooled estimates of sensitivity, specificity, and accuracy of ¹⁸F-FDG PET/CT in the detection of the primary tumor site were 87%, 88%, and 87.5%, respectively.

Conclusions.

The present review of currently available data indicates that ¹⁸F-FDG PET/CT might contribute to the identification of the primary tumor site in extracervical CUP. However, prospective studies with more uniform inclusion criteria are required to evaluate the exact value of this diagnostic tool.     

Reduced serum testosterone levels in infant boys conceived by intracytoplasmic sperm injection

CONTEXT: Concern has been raised for the health of the offspring conceived by assisted reproduction technologies. Basal reproductive hormones around 3 months of age reflect the pituitary-testicular axis, which is transiently active at this age. OBJECTIVES: We tested the hypothesis that transmission of impaired testicular function from father to son could be detected at 3 months of age in boys conceived by intracytoplasmic sperm injection (ICSI), which is predominantly used in the management of male infertility. DESIGN: We conducted a longitudinal prospective cohort study, including 125 boys conceived by ICSI, 124 boys conceived by in vitro fertilization (IVF), and 933 naturally conceived (NC) boys. INTERVENTION: Anthropometrical measurements were performed at birth and at 3 months of age; 58, 67, and 64% of ICSI, IVF, and NC boys, respectively, had a blood sample taken at 3 months. MAIN OUTCOME MEASURES: We measured serum levels of LH, FSH, SHBG, inhibin B, testosterone, as well as penile length. RESULTS: Serum testosterone levels were significantly lower in boys conceived by ICSI (2.4 nmol/liter; 0.2-4.9 nmol/liter) (median; 2.5th-97.5th percentiles) compared with NC boys (3.3 nmol/liter; 0.6-7.6 nmol/liter; P < 0.001), and the LH to testosterone ratio was increased (0.8; 0.2-7.9 vs. 0.5; 0.2-2.3, respectively; P = 0.001). Boys conceived by IVF because of female infertility factors had a normal serum testosterone and LH to testosterone ratio compared with controls. Adjusted analyses for confounders did not alter the results. CONCLUSIONS: Our results point toward a subtle impairment of Leydig cell function in boys conceived by ICSI, possibly inherited from their fathers. The clinical significance of our findings is uncertain. However, our findings should raise concern because ICSI is increasingly used to overcome male infertility.     

Prospective study of 18FDG-PET in the detection and management of patients with lymph node metastases to the neck from an unknown primary tumor. Results from the DAHANCA-13 study

BACKGROUND: The benefit of a complementary fluorodeoxyglucose-positron emission tomography (FDG-PET) scan to standard workup for carcinoma of unknown primary (CUP) and metastatic neck lesions was prospectively studied. METHODS: Sixty-seven patients underwent standardized diagnostic workup according to national guidelines including panendoscopies, multiple mucosal biopsies, and diagnostic CT/MRI scans. Median follow-up was 40 months (range, 2-65 months). RESULTS: In 60 eligible patients, FDG-PET indicated a primary tumor or metastatic disease in 30 patients (50%). Additional investigations confirmed a primary tumor in 18 patients: hypopharynx in 5, oropharynx in 5, nasopharynx in 2, lung in 1, axilla in 1, bone in 1, rectum in 1, as well as multiple metastatic lesions from CUP in 2 patients. In retrospect, MRI was able to detect 1 of the PET-detected primaries, leading to an overall detection rate of PET of 29% in CUP. A therapeutic change of treatment was made in 25% as a consequence of FDG-PET. PET before panendoscopy demonstrated fewer false-positive pathological foci. CONCLUSION: FDG-PET is a valuable tool in addition to conventional extensive workup in CUP and neck metastases. Consequently, FDG-PET is now recommended as an early diagnostic modality in the workup of these patients.     

Size-resolved respiratory-tract deposition of fine and ultrafine hydrophobic and hygroscopic aerosol particles during rest and exercise

Airborne ultrafine particles (diameter <100 nm) are ubiquitous in the environment and have been associated with adverse health effects. The respiratory-tract deposition of these particles is fundamentally influenced by their hygroscopicity: their ability to grow by condensation of water in the humid respiratory system. Ambient particles are typically hygroscopic, to varying degrees. This article investigates the influence of hygroscopicity, exercise level, gender, and intersubject variability on size-dependent deposition of fine and ultrafine particles during spontaneous breathing. Using a novel and well-characterized setup, respiratory-tract deposition in the range 12-320 nm has been measured for 29 healthy adults (20 men, 9 women). Each subject completed four sessions: rest and light exercise on an ergometer bicycle while inhaling both hydrophobic (diethylhexylsebacate) and hygroscopic (NaCl) particles. The deposited fraction (DF) based on dry diameters was two to four times higher for the hydrophobic ultrafine particles than for the hygroscopic. The DF of hygroscopic ultrafine particles could be estimated by calculating their equilibrium size at 99.5% relative humidity. The differences in average DF due to exercise level and gender were essentially less than 0.03. However, the minute ventilation increased fourfold during exercise and was 18-46% higher for the men than for the women. Consequently the deposited dose of particles was fourfold higher during exercise and considerably increased for the male subjects. Some individuals consistently had a high DF in all four sessions. As an example, the results show that an average person exposed to 100-nm hydrophobic particles during exercise will receive a 16 times higher dose than a relaxed person exposed to an equal amount of hygroscopic (NaCl) particles.     

Nasopharyngeal carcinoma. Treatment planning with IMRT and 3D conformal radiotherapy

The study was undertaken in order to compare dose plans for intensity-modulated radiotherapy (IMRT) with 3D conformal radiotherapy (3D-CRT) dose plans in patients with nasopharyngeal carcinoma (NPC). Clinical data from 20 consecutive patients treated with IMRT are presented. For 11 patients 3D-CRT plans were made and compared to the IMRT plans with respect to doses to the planning target volumes (PTVs) and to organs at risk (OARs). For comparison of the conformation of dose to defined target volumes the conformity index (CI) was used. Target volume coverage and critical organ protection were significantly improved with IMRT compared to 3D-CRT. One-year loco-regional control, distant metastasis-free survival, and overall survival were 79%, 72%, and 80%. Two patients have had recurrence in the clinical target volume (CTV) only and seven patients have relapsed in distant organs and/or in head-and-neck areas outside the target areas. The study confirms that IMRT is superior to 3D-CRT in the treatment of NPC. As locoregional control of NPC improves we are facing an increasing number of recurrences outside the irradiated area.