BACKGROUND: To investigate the feasibility of strain elastography imaging in early detecting and predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for locally advanced cervical cancer. METHODS: Between January 2015 and June 2016, 47 patients with locally advanced cervical cancer were enrolled in a feasibility study approved by the institutional review board. All patients underwent CCRT and received strain elastography examinations at 4 time points: pre-therapy (baseline), 1 week and 2 weeks during, as well as immediately post CCRT. Treatment response was evaluated by MRI at the time of diagnosis and immediately after CCRT. Based on the MRI findings, the treatment outcome was characterized as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Strain ratio of the normal parametrial tissue vs. cervical tumor was calculated and compared with the clinical outcome.
RESULTS: Out of the 47 patients, 36 patients who completed all 4 examinations were included in the analyses: 25 were classified as CR, 11 as PR, and 0 in the SD/PD groups. Strain ratios were significantly different among the time points in both the CR group (F = 87.004, p < 0.001) and PR group (F = 38.317, p < 0.001). Strain ratios were significantly difference between the CR and PR groups (F = 7.203 p = 0.011). Strain ratios between the CR group and PR group were significantly different at 1 week after treatment initiation (p < 0.05). Compared to the baseline, a significant decrease in the CR group was observed at week 1, week 2 and post treatment (all p < 0.001), while a significant decrease in the PR group was shown in week 2 and post treatment (both p < 0.05), but not at week 1 during CCRT (p = 0.084). CONCLUSIONS: We have conducted a prospective longitudinal study to evaluate tumor response in women receiving CCRT for cervical cancers. This study has demonstrated the potential of strain elastography imaging in monitoring and early predicting tumor response induced by CCRT.
The STK11/LKB1 gene encodes a ubiquitously expressed serine/threonine kinase that is mutated in multiple sporadic cancers including non-small cell lung carcinomas, pancreatic cancers, and melanomas. LKB1 affects multiple cellular functions including cell growth, cell cycle progression, metabolism, cell polarity and migration. To date, only a limited number of studies have assessed the status of LKB1 in cervical cancers. Herein, we investigate DNA methylation, DNA mutation, and transcription at the LKB1 locus in cervical cancer cell lines. We identified homozygous deletions of 25–85kb in the HeLa and SiHa cell lines. Deletion breakpoint analysis in HeLa cells revealed that the deletion resulted from an Alu-recombination mediated deletion (ARMD) and generated a novel LKB1 fusion transcript driven by an uncharacterized CpG island promoter located ~11kb upstream of LKB1. Although the homozygous deletion in SiHa cells removes the entire LKB1 gene and portions of the neighboring genes SBNO2 and c19orf26, this deletion also generates a fusion transcript driven by the c19orf26 promoter and comprised of both c19orf26 and SBNO2 sequences. Further analyses of public gene expression and mutation databases suggest that LKB1 and its neighboring genes are frequently dysregulated in primary cervical cancers. Thus, homozygous deletions affecting LKB1 in cervical cancers may generate multiple fusion transcripts involving LKB1, SBNO2, and c19orf26.
Background: Cervical cancer is a leading cause of morbidity and mortality in women, but cerebral metastasis from cervical carcinoma is a rare event with a reported incidence of 0.57%. Case Report: We describe a case of brain metastasis from primary cervical adenocarcinoma with several distinct features. This case illustrates uncommon presenting neurologic symptoms, a rare combination of histopathologic features, and atypical findings on radiographic evaluation. Conclusion: Clinicians must maintain a high index of suspicion for cerebral metastasis to make an accurate diagnosis and initiate appropriate management of advanced cervical cancer.
by
Joseph Chao;
Timothy W. Synold;
Robert J. Morgan Jr.;
Charles Kunos;
Jeff Longmate;
Heinz-Josef Lenz;
Dean Lim;
Stephen Shibata;
Vincent Chung;
Ronald G. Stoller;
Chandra P. Belani;
David R. Gandara;
Mark McNamara;
Barbara J. Gitlitz;
Derick H. Lau;
Suresh S Ramalingam;
Angela Davies;
Igor Espinoza-Delgado;
Edward M. Newman;
Yun Yen
Background: 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) is a novel small-molecule ribonucleotide reductase inhibitor. This study was designed to estimate the maximum tolerated dose (MTD) and oral bioavailability of 3-AP in patients with advanced-stage solid tumors.
Methods: Twenty patients received one dose of intravenous and subsequent cycles of oral 3-AP following a 3 + 3 patient dose escalation. Intravenous 3-AP was administered to every patient at a fixed dose of 100 mg over a 2-h infusion 1 week prior to the first oral cycle. Oral 3-AP was administered every 12 h for 5 consecutive doses on days 1-3, days 8-10, and days 15-17 of every 28-day cycle. 3-AP was started at 50 mg with a planned dose escalation to 100, 150, and 200 mg. Dose-limiting toxicities (DLT) and bioavailability were evaluated.
Results: Twenty patients were enrolled. For dose level 1 (50 mg), the second of three treated patients had a DLT of grade 3 hypertension. In the dose level 1 expansion cohort, three patients had no DLTs. No further DLTs were encountered during escalation until the 200-mg dose was reached. At the 200 mg 3-AP dose level, two treated patients had DLTs of grade 3 hypoxia. One additional DLT of grade 4 febrile neutropenia was subsequently observed at the de-escalated 150 mg dose. One DLT in 6 evaluable patients established the MTD as 150 mg per dose on this dosing schedule. Responses in the form of stable disease occurred in 5 (25%) of 20 patients. The oral bioavailability of 3-AP was 67 ± 29% and was consistent with the finding that the MTD by the oral route was 33% higher than by the intravenous route.
Conclusions: Oral 3-AP is well tolerated and has an MTD similar to its intravenous form after accounting for the oral bioavailability. Oral 3-AP is associated with a modest clinical benefit rate of 25% in our treated patient population with advanced solid tumors.
BACKGROUND: Intravoxel incoherent motion (IVIM) MR imaging has been applied in researches of various diseases, however its potential in cervical cancer patients has not been fully explored. The purpose of this study was to investigate the feasibility of IVIM MR imaging to monitor early treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancers.
METHODS: Twenty-one patients receiving CCRT for advanced cervical cancer were prospectively enrolled. MR examinations including IVIM imaging (with 14 b values, 0 ~ 1000 s/mm(2)) were performed at 4 time points: 1-week prior to, 2-week and 4-week during, as well as immediately post CCRT (within 1 week). The apparent diffusion coefficient (ADC) maps were derived from the mono-exponential model, while the diffusion coefficient (D), perfusion fraction (f) and pseudo-diffusion coefficient (D*) maps were calculated from the bi-exponential model. Dynamic changes of ADC, D, f and D* in cervical cancers were investigated as early surrogate markers for treatment response.
RESULTS: ADC and D values increased throughout the CCRT course. Both f and D* increased in the first 2 to 3 weeks of CCRT and started to decrease around 4 weeks of CCRT. Significant increase of f value was observed from prior to CCRT (f 1 = 0.12 ± 0.52) to two-week during CCRT (f 2 = 0.20 ± 0.90, p = 0.002).
CONCLUSIONS: IVIM MR imaging has the potential in monitoring early tumor response induced by CCRT in patients with cervical cancers.
by
Jacqueline Casillas;
Sharon M. Castellino;
Melissa M. Hudson;
Ann Mertens;
Isac S. F. Lima;
Qi Liu;
Lonnie K. Zeltzer;
Yutaka Yasui;
Leslie L. Robison;
Kevin C. Oeffinger
BACKGROUND: Lack of health insurance is a key barrier to accessing care for chronic conditions and cancer screening. The influence of insurance type (private, public, none) on survivor-focused and general preventive health care in adult survivors of childhood cancer was examined. METHODS: The Childhood Cancer Survivor Study is a retrospective cohort study of childhood cancer survivors diagnosed between 1970 and 1986. Among 8425 adult survivors, the relative risk (RR) and 95% confidence interval (CI) of receiving survivor-focused and general preventive health care were estimated for uninsured (n = 1390) and publicly insured (n = 640), compared with for the privately insured (n = 6395) RESULTS: Uninsured survivors were less likely than those privately insured to report a cancer-related visit (adjusted RR, 0.83; 95% CI, 0.75-0.91) or a cancer center visit (adjusted RR, 0.83; 95% CI, 0.71-0.98). Uninsured survivors had lower levels of utilization in all measures of care in comparison with privately insured. In contrast, publicly insured survivors were more likely to report a cancer-related visit (adjusted RR, 1.22; 95% CI, 1.11-1.35) or a cancer center visit (adjusted RR, 1.41; 95% CI, 1.18-1.70) than were privately insured survivors. Although publicly insured survivors had similar utilization of general health examinations, they were less likely to report a Papanicolaou test or a dental examinations CONCLUSIONS: Among this large, socioeconomically diverse cohort, publicly insured survivors utilize survivor-focused health care at rates at least as high as survivors with private insurance. Uninsured survivors have lower utilization of both survivor-focused and general preventive health care. Cancer 2011;117:1966-1975.
Study Objective: To describe the prevalence and correlates of vaginal douching among urban African American adolescents and to examine the association between douching and sexually transmitted infection (STI) status.
Design: Demographic, psychosocial, and behavioral data were collected through cross-sectional, self-administered surveys. Self-collected vaginal swabs were assayed using nucleic acid amplification tests for trichomoniasis, chlamydia, and gonorrhea. Setting: Sexual health clinic in a large metropolitan area of the southeastern United States.
Participants: African American females (N = 701), ages 14-20, participating in a human immunodeficiency virus prevention intervention.
Main Outcome Measure: The outcome of interest was the association between vaginal douching (lifetime, past 90 days, and past 7 days) with demographic characteristics (eg, age, education, and socioeconomic status), physical and mental health status, STI status, sexual behavior (eg, number of vaginal sexual partners, age of sex partners, consistent condom use in the past 90 days, sex while self/partner was high on drugs or alcohol), and psychosocial characteristics (eg, sexual adventurism, social support, peer norms, sexual satisfaction, self-efficacy for sex refusal, self-esteem, relationship power, risk avoidance). Results: Forty-three percent reported ever douching, and 29% reported douching in the past 90 days. In bivariate analyses, recent douching was associated with demographic, behavioral, and psychosocial variables, but not current STI status. In multivariate analyses, recent douching was associated with age (odds ratio [AOR] = 1.13, confidence interval [CI] = 1.02-1.25), lower socioeconomic status (AOR = 1.25, CI = 1.05-1.47), and having sex with much older partners (AOR = 1.87, CI = 1.22-2.86).
Conclusion: Increased age, lower socioeconomic status, and older partners may be salient risk factors for douching behavior among African American young women.
Dystonia is a neurological disorder characterized by involuntary twisting movements and postures. There are many different clinical manifestations, and many different causes. The neuroanatomical substrates for dystonia are only partly understood. Although the traditional view localizes dystonia to basal ganglia circuits, there is increasing recognition that this view is inadequate for accommodating a substantial portion of available clinical and experimental evidence. A model in which several brain regions play a role in a network better accommodates the evidence. This network model accommodates neuropathological and neuroimaging evidence that dystonia may be associated with abnormalities in multiple different brain regions. It also accommodates animal studies showing that dystonic movements arise with manipulations of different brain regions. It is consistent with neurophysiological evidence suggesting defects in neural inhibitory processes, sensorimotor integration, and maladaptive plasticity. Finally, it may explain neurosurgical experience showing that targeting the basal ganglia is effective only for certain subpopulations of dystonia. Most importantly, the network model provides many new and testable hypotheses with direct relevance for new treatment strategies that go beyond the basal ganglia. This article is part of a Special Issue entitled "Advances in dystonia".
We present the case of a 10-year-old boy with the sudden onset of a large, painless left neck mass. Findings on magnetic resonance imaging (MRI) and fine needle aspiration (FNA) biopsy suggest a cystic lesion, most likely of thymic origin. Cervical thymic cysts are a rare form of cervical mass, which are easily overlooked in the differential diagnosis of children presenting with painless neck masses. A combination of CT and MRI investigations can be helpful in differentiating thymic cysts from other congenital and neoplastic masses, but the definitive diagnosis of thymic cyst requires histopathological documentation of thymic tissue. Surgical excision is considered the management of choice for thymic cysts, and no cases of postoperative recurrence have been reported.
The dystonias are a group of disorders characterized by excessive muscle contractions leading to abnormal movements and postures. There are many different clinical manifestations and underlying causes. Deep brain stimulation (DBS) provides an effect treatment, but outcomes can vary considerably among the different subtypes of dystonia. Several variables are thought to contribute to this variation including age of onset and duration of dystonia, specific characteristics of the dystonic movements, location of stimulation and stimulator settings, and others. The potential contributions of genetic factors have received little attention. In this review, we summarize evidence that some of the variation in DBS outcomes for dystonia is due to genetic factors. The evidence suggests that more methodical genetic testing may provide useful information in the assessment of potential surgical candidates, and in advancing our understanding of the biological mechanisms that influence DBS outcomes.