The role of vascular resistance in BOLD responses to progressive hypercapnia

The ability of the cerebral vasculature to regulate vascular diameter, hence resistance and cerebral blood flow (CBF), in response to metabolic demands (neurovascular coupling), and perfusion pressure changes (autoregulation) may be assessed by measuring the CBF response to carbon dioxide (CO₂). In healthy individuals, the CBF response to a ramp CO₂ stimulus from hypocapnia to hypercapnia is assumed sigmoidal or linear. However, other response patterns commonly occur, especially in individuals with cerebrovascular disease, and these remain unexplained. CBF responses to CO₂ in a vascular region are determined by the combined effects of the innate vascular responses to CO₂ and the local perfusion pressure; the latter ensuing from pressure‐flow interactions within the cerebral vascular network. We modeled this situation as two vascular beds perfused in parallel from a fixed resistance source. Our premise is that all vascular beds have a sigmoidal reduction of resistance in response to a progressive rise in CO₂. Surrogate CBF data to test the model was provided by magnetic resonance imaging of blood oxygen level‐dependent (BOLD) signals. The model successfully generated all the various BOLD‐CO₂ response patterns, providing a physiological explanation of CBF distribution as relative differences in the network of vascular bed resistance responses to CO₂. Hum Brain Mapp 38:5590–5602, 2017. © 2017 Wiley Periodicals, Inc.     

Evidence-based review of the utility of radiation therapy in the treatment of endometrial cancer

Endometrial cancer is the most common cancer of the female genital tract in the USA and usually presents at an early stage. Most women are cured with surgery, however, some patients may require adjuvant therapy including radiation and/or chemotherapy. Risk factors determine the need for adjuvant treatment and, based on these risk factors, patients are categorized as being at low, intermediate or high risk for recurrence. In this article we will review the best level of evidence available for the use of radiation therapy within each risk stratum. The most controversy and debate is associated with patients stratified to the intermediate-risk group.     

Outcomes in 24 selected patients with stage IVB cervical cancer and excellent performance status treated with radiotherapy and chemotherapy

Purpose We sought to review outcomes in patients with stage IVB carcinoma of the cervix treated with irradiation in combination with chemotherapy. Materials and methods We report outcomes of 24 consecutive patients with good performance status treated from 1998 to 2005. Most of these patients underwent concurrent irradiation with platinum-based chemotherapy. Some patients received subsequent systemic chemotherapy. Results All patients underwent external beam radiotherapy; 7 patients (29%) had additional high-dose-rate and 12 (50%) low-dose-rate brachytherapy. Two patients (8%) received an IMRT boost instead of brachytherapy. The mean dose to point A was variable (73.9 ± 19.2 Gy). Twenty patients (83%) received radio-sensitizing platinum-based chemotherapy, and the remaining had radiotherapy alone. Seven patients (29%) had further combination chemotherapy. Therapy was well tolerated. The overall survival was 44% at 36 months and 22% at 5 years. Conclusion Patients with stage IVB cervical cancer have mostly been treated with palliative intent. With the advent of concurrent chemoradiation, we have treated many of these cases with aggressive combination therapy. In this series, the use of radiotherapy and multiagent chemotherapy in patients with stage IVB cervical carcinoma and good performance status was well tolerated and resulted in higher survival rates than previously reported. This study was presented at the 37th annual meeting of the Society of Gynecologic Oncologists, Palm Springs, CA, March 2006     

Frequent mutations in the RPL22 gene and its clinical and functional implications

ObjectiveTo determine the frequency and spectrum of mutations in RPL22 a gene identified by The Cancer Genome Atlas (TCGA) as mutated in endometrioid endometrial cancer, and determine the relationship between RPL22 defects and clinicopathologic features.MethodsDirect sequencing of the entire coding region of the RPL22 cDNA and exons 2/4 was performed in tumors with/without microsatellite instability (MSI). RPL22 expression was assessed by immunofluorescence microscopy in the KLE, RL952 and AN3CA cell lines, wildtype, heterozygous and homozygous mutants, respectively. Relationships between RPL22 mutation and clinicopathological features were assessed using Chi-squared analysis and Student's t test. Progression-free survival (PFS) was calculated from the date of diagnosis to the date of recurrence.ResultsA single nucleotide deletion in an A8 coding repeat was identified in exon 2 of the RPL22 gene in 116/226 (52%) of MSI-high tumors. No mutations were identified in MSI-stable tumors. Only 2% of the tumors expressed a homozygous A deletion. RPL22 mutation was not associated with stage, grade, race and lymphovascular space invasion. Women whose tumors harbored RPL22 mutations were significantly older (67 vs. 63 years, p = 0.005). There was no difference in PFS between patients with the wildtype and mutant genotypes.ConclusionsRPL22 is frequently mutated in MSI-high endometrioid endometrial cancers. The A8 mutation identified was not reported in the whole exome sequences analyzed by the TCGA. The demonstration of frequent mutation in RPL22 may point to a limitation of the exome capture and next generation sequencing analysis methods for some mononucleotide string mutations. Functional assessment of the RPL22 knockdown may be warranted.     

Epithelial ovarian tumors of low malignant potential: the role of microinvasion.

OBJECTIVE: To identify prognostic factors that may be used to predict an aggressive disease course and poor outcome in patients with epithelial ovarian tumors of low malignant potential (borderline tumors). METHODS: Data on 126 patients with ovarian borderline tumors were analyzed with regard to demographic characteristics, staging, presence of microinvasion, duration of follow-up, recurrence rate, rate of recurrence as invasive disease, mortality rate, preoperative and postoperative CA-125, and treatment. Chi-square and Fisher exact tests were used to evaluate proportions for statistical significance. Disease-free and overall survival was calculated by using the Kaplan-Meier method and log-rank test. RESULTS: Patients were followed for a median of 39.0 months (mean 47.8 months). Seven patients (5.6%) had recurrent disease. Advanced stage disease and microinvasion were associated with significantly higher recurrence and mortality rates than were stage I/II disease and borderline tumors without microinvasion, respectively. Two of 13 (15%, 95% CI 8.7, 21.3) patients with microinvasion died of recurrent invasive cancer, whereas only 1 out of 113 patients without microinvasion died of recurrent borderline tumor (OR 20.4, 95% CI 1.2, 239). All 3 patients with an aggressive disease course and poor outcome had increasing CA 125 levels at the time of recurrence. CONCLUSION: Certain patients with microinvasion may be at higher risk for recurrence as invasive disease and may require different treatment strategies. CA 125 monitoring may have a role in early detection of recurrence in patients with aggressive disease.     

A Case Report Demonstrating Unambiguous Clinical Utility of Pet/CT Scanning in Recurrent Ovarian Cancer

There has been discussion and debate in the medical literature regarding the clinical value of PET/CT scans in ovarian cancer, particularly focusing on evidence whether the technology is of predictive versus solely prognostic utility. In the somewhat unusual case reported here, the results of the PET/CT scan were extremely helpful in developing a rational management strategy. The case emphasizes the critical need to specifically address the issue of whether data generated from an expensive diagnostic test will be useful in an individual patient''s management before it is obtained.Key Words: PET/CT scan, Recurrent ovarian cancer, Predictive utility, Prognostic utility