The role of positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) in early-stage cervical cancer is unclear. We aimed to investigate the clinical benefit of FDG-PET in primary ...staging before radical hysterectomy and pelvic lymphadenectomy (RH-PLND).
Patients with untreated stage IA2 to IIA adenocarcinoma (AD) or adenosquamous carcinoma (ASC) or nonbulky (< or = 4 cm) squamous cell carcinoma cervical cancer with magnetic resonance imaging (MRI) -defined negative nodal metastasis were enrolled onto a prospective study with a two-stage design. All patients had a preoperative dual-phase FDG-PET, technetium-99m-sulfur colloid lymphoscintigraphy, and intraoperative sentinel lymph node (LN) detection at RH-PLND. The gold standard of LN metastasis is histologic. A sample size of 120 patients was calculated to fit study aims (diagnostic efficacy of PET and sentinel LN sampling). An interim analysis was performed when 60 patients were accrued, which led to the current report.
There were 36 SCCs, 20 ADs, and four ASCs. Of the 60 patients, 10 (16.7%) had pelvic LN metastases, and one (1.7%) had para-aortic LN (PALN) metastasis histologically. FDG-PET detected the single PALN metastasis (one of one patient) but detected only one (10%) of the 10 pelvic LN metastases. The PET false-negative pelvic LN micrometastases measured a median of 4.0 x 3.0 mm (range, 0.5 x 0.5 to 7 x 6 mm). The second stage of this trial will be continued without PET.
This study shows that dual-phase FDG-PET has little value in primary, nonbulky, stage IA2 to IIA and MRI-defined, LN-negative cervical cancer.
Cervical cancer patients with histologically documented re-recurrence after curative salvage therapy or unexplained tumor marker elevation (negative computed tomography and/or magnetic resonance ...imaging CT-MRI) proven to be a re-recurrence when a further attempt for cure (or control of cancer) appeared feasible were enrolled. Lesion status was determined from pathology or clinical follow-up for at least 12 months. Management decisions were recorded with CT-MRI alone and incorporating 18Ffluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), respectively. The benefits calculated were based on clinical impact because of the FDG-PET findings. Cox proportional hazards model was used to select independent prognostic covariates. Of the 26 patients who were eligible for analysis, 12 (46.2%) patients had positive impacts due to PET. Squamous cell carcinoma (SCC, P = 0.029), re-recurrence at distant metastasis only (P = 0.012), and level of SCC antigen < or = 4 ng/mL (P = 0.005) were significantly associated with better survival. A scoring system using these covariates defined three distinct prognostic groups (P = 0.0001). Patients with score 0 had a 36-month cumulative survival rate of 80%. Using this prognostic scoring system, FDG-PET may facilitate selecting appropriate management for the individual patient with re-recurrent cervical cancer.
Bone metastasis occurs frequently in patients with endemic nasopharyngeal carcinoma (NPC). The main objective of this study is to evaluate positron emission tomography (PET) using fluorine-18-labeled ...fluorodeoxyglucose (18FFDG) and conventional skeletal scintigraphy (SS) for detecting bone metastasis at initial staging. Auxiliary objectives are to identify risk factors for bone metastasis and features associated with poor survival in patients with bone metastasis.
Patients with endemic NPC before initiation of treatment were enrolled. PET and SS were performed at initial staging and compared using McNemar's paired-sample test. Bone metastasis was considered to be present if there was any reliable evidence identified within 1 year after primary diagnosis. Multiple logistic regression and Cox's proportional hazards models were used for auxiliary objectives.
Thirty (15%) of 202 eligible patients were found to have bone metastasis. 18FFDG PET was found to be more sensitive than SS in the patient-based analysis (P = .006) and in the region-based analysis at the spine (P = .001). Advanced N stage was the only significant risk factor (P < .0001), and the coexistence of hepatic metastasis was a prognosticator of poor survival (P = .017). The survival was not significantly better for patients with bone metastasis undetected at primary staging than for those with initially detectable bone metastasis (P = .620).
18FFDG PET is more sensitive than SS for detecting bone metastasis in endemic NPC at initial staging, whereas SS can be considered as supplementary in this setting.
Aims Glucose transporter 10 (GLUT10), encoded by the SLC2A10 gene, is a member of the class III facilitative glucose transporter family. Mutations in the SLC2A10 gene cause arterial tortuosity ...syndrome (ATS) in humans. To further study the pathogenesis of the disease, we generated mice carrying GLUT10 mutations. Methods and results Using a gene-driven N-ethyl-N-nitrosourea (ENU)-mutagenesis approach, we generated mice carrying GLUT10 mutations c.383G>A and c.449C>T, which resulted in missense mutations of glycine to glutamic acid (p.G128E) and serine to phenylalanine (p.S150F), respectively. Both mutant strains appeared normal at birth, gained weight appropriately and survived to adulthood (>18 months). Blood and urine glucose were normal. Echocardiogram and electrocardiogram were also normal and brain magnetic resonance angiography revealed normal cerebral arteries without tortuosity, stenosis/dilatation, or aneurysm. Histopathology revealed thickening and irregular vessel wall shape of large and medium size arteries characterized by markedly increased elastic fibres, both in number and size. There was also intima endothelial hypertrophy and deranged elastic fibres that resulted in disruption of internal elastic lamina in the aorta of older mice. Conclusion Abnormal elastogenesis with early elastic fibre proliferation provides a clue to the pathogenesis of arterial tortuosity in human ATS. Availability of this mouse model will allow testing of the relationship between diabetes and its vascular complications, including diabetic retinopathy, nephropathy and peripheral vascular disease.
Nasopharyngeal carcinoma (NPC) is treated by radiotherapy with or without chemotherapy. It is not uncommon to find the residual/recurrent lesion in the skull base area. For patients who had received ...radiotherapy, it is difficult to differentiate the skull base tumour from post-treatment change in the CT or MRI. (18)F-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) provides an alternative diagnostic choice in this situation for head and neck cancer including NPC especially when there is inconclusive CT/MRI finding. This report of an NPC patient who received radiotherapy 18 months previously, describes the misdiagnosis of tumour recurrence at the skull base found in both MRI and FDG PET scan. Histopathological studies showed osteoradionecrosis of the debrided tissue and follow-up PET showed complete regression of the skull base lesion. Therefore, a false positive result in FDG PET caused by osteoradionecrosis was confirmed. To the best of our knowledge, this is the first case report in the literature.
Spectroscopic + photometric redshifts, stellar mass estimates, and rest-frame colors from the 3D-HST survey are combined with structural parameter measurements from CANDELS imaging to determine the ...galaxy size-mass distribution over the redshift range 0 < z < 3. Separating early- and late-type galaxies on the basis of star-formation activity, we confirm that early-type galaxies are on average smaller than late-type galaxies at all redshifts, and we find a significantly different rate of average size evolution at fixed galaxy mass, with fast evolution for the early-type population, R sub(eff) is proportional to (1 + z) super(-1.48), and moderate evolution for the late-type population, R sub(eff) is proportional to (1 + z) super(-0.75). The intrinsic scatter is lap0.2 dex for all galaxy types and redshifts. For late-type galaxies, the logarithmic size distribution is not symmetric but is skewed toward small sizes: at all redshifts and masses, a tail of small late-type galaxies exists that overlaps in size with the early-type galaxy population.
Precise assessment of the extent of nasopharyngeal carcinoma (NPC) represents the basic step towards optimal treatment. We compared the capacity of CT and MRI in assessing the extent of NPC in 67 ...patients. MRI was superior to CT in demonstrating lesions in the retropharyngeal node, skull base, intracranial area, carotid space, longus colli muscle and levator palatini muscle. Of 25 cases in which retropharyngeal adenopathy was recognised only on MRI, seven had been reported as showing oropharyngeal involvement and 18 as primary extension to the carotid space on CT. MRI showed skull-base involvement in 40 patients compared with 27 on CT and intracranial involvement in 38 patients versus 24 on CT. There was not a single case in which skull base invasion was seen on CT but not on MRI. MRI enabled improved recognition of tumour infiltration of longus colli muscles (34 cases compared with 15 on CT). It allowed us to clarify 12 questionable sinonasal opacities on CT. Overall, T-staging was changed in 18 of 67 patients (26.9%), including upstaging in 15 cases and down-staging in 3 cases, after comparing CT with MRI. The nodel status was changed from negative on CT to positive on MRI in 4 of 67 patients (6%). We believe that MRI allows more accurate evaluation of the extent of NPC than CT and should be the primary mode of investigation.
There are limited data comparing the clinical outcomes between telbivudine and entecavir. We consecutively enrolled 115 telbivudine-naive and 115 entecavir-naive chronic hepatitis B patients, who ...were matched for age, sex, hepatitis B e antigen (HBeAg) status and cirrhosis, and treated for at least 2 years or less than 2 years but had developed resistance. Except for the rate of HBeAg seroconversion, which was similar, patients in the entecavir group had better clinical outcomes than those in the telbivudine group for alanine aminotransferase normalization (85.2% vs 78.4%, p <0.048), undetectable HBV DNA (96.5% vs 74.8%, p <0.001), and viral resistance (0.9% vs 21.7%, p <0.001) after 2 years of treatment, After applying roadmap or super-responders concepts, entecavir still had better outcomes than telbivudine in undetectable HBV DNA and viral resistance. The cumulative incidence of hepatocellular carcinoma development was similar between telbivudine-naive and entecavir-naive patients (p 0.565). In renal function analysis, there were significantly more patients with estimated glomerular filtration rate (eGFR) category improvement in both the telbivudine and entecavir groups at year 1 (p 0.006 and p 0.047, respectively). The rate of virological improvement was significantly higher with entecavir than with telbivudine after 2 years of treatment, whether applying the concepts of roadmap or super-responders. The incidence of hepatocellular carcinoma was similar between telbivudine and entecavir. Both telbivudine and entecavir were associated with eGFR improvement, especially in patients with renal insufficiency.
The SuperCDMS experiment is designed to directly detect weakly interacting massive particles (WIMPs) that may constitute the dark matter in our Galaxy. During its operation at the Soudan Underground ...Laboratory, germanium detectors were run in the CDMSlite mode to gather data sets with sensitivity specifically for WIMPs with masses <10 GeV/c2. In this mode, a higher detector-bias voltage is applied to amplify the phonon signals produced by drifting charges. This paper presents studies of the experimental noise and its effect on the achievable energy threshold, which is demonstrated to be as low as 56 eVee (electron equivalent energy). The detector-biasing configuration is described in detail, with analysis corrections for voltage variations to the level of a few percent. Detailed studies of the electric-field geometry, and the resulting successful development of a fiducial parameter, eliminate poorly measured events, yielding an energy resolution ranging from ∼9 eVee at 0 keV to 101 eVee at ∼10 keVee. New results are derived for astrophysical uncertainties relevant to the WIMP-search limits, specifically examining how they are affected by variations in the most probable WIMP velocity and the Galactic escape velocity. These variations become more important for WIMP masses below 10 GeV/c2. Finally, new limits on spin-dependent low-mass WIMP-nucleon interactions are derived, with new parameter space excluded for WIMP masses ≲3 GeV/c2.
Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence.
In a double-blind, phase ...3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year). The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point.
A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval CI, 0.53 to 0.87; P = 0.002 two-sided). The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96). Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred.
Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.).
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