Utility of bilateral inferior petrosal sinus sampling for diagnosis and lateralization of Cushing's disease in the pediatric population: case series and review of the literature.

OBJECTS: Cushing's disease (CD) is the most common cause of ACTH-dependent hypercortisolism in children age ≥ 7. The utility of bilateral inferior petrosal sinus sampling (BIPSS), an important test in adults, is less defined in children. We present a case series of children with ACTH-dependent hypercortisolemia and review the literature to assess the utility of BIPSS in the diagnosis and localization of CD. METHODS: We performed an IRB-approved chart review of patients aged ≤ 18 with ACTH-dependent hypercortisolism at MGH between 2000 and 2019 and collected clinical, laboratory, radiographic, BIPSS, surgical, and outcomes data. RESULTS: In our cohort (n = 21), BIPSS had a sensitivity of 93% and specificity of 100% for diagnosis of CD. Compared to surgery, successful BIPSS correctly predicted adenoma laterality in 69% of cases vs. 70% by MRI. Among patients with lesions ≥ 4 mm (n = 9), BIPSS correctly lateralized in 50% vs. 100% by MRI. In patients with subtle lesions (< 4 mm, n = 7), BIPSS correctly lateralized in 80% vs. 71% by MRI. In patients (n = 4) with CD and negative MRIs, BIPSS correctly lateralized in 75% cases. Surgical cure was achieved in 90% of patients and 95% of patients had long-term disease control. CONCLUSIONS: In our cohort (n = 21; n = 20 CD, n = 1 ectopic ACTH secretion), BIPSS was sensitive and specific for the diagnosis of CD. Compared to MRI, BIPSS was not additionally helpful for lateralization in patients with lesions ≥ 4 mm on MRI. BIPSS was helpful in guiding surgical exploration and achieving immediate postoperative remission among patients with subtle and negative MRI findings.

The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are prognostic factors for various types of cancer. In this study, we assessed the association of NLR and PLR with the prognosis of small-cell lung cancer (SCLC) in patients who received the standard treatment. METHODS: We retrospectively reviewed patients who were diagnosed with SCLC and treated with platinum-based chemotherapy between July 2006 and October 2013 in Gyeongsang National University Hospital Regional Cancer Center and Changwon Samsung Hospital. RESULTS: In total, 187 patients were evaluated. Compared with low NLR (<4), high NLR (⩾4) at diagnosis was associated with poor performance status, advanced stage, and lower response rate. Median overall survival (OS) and progression-free survival (PFS) were worse in the high-NLR group (high vs low, 11.17 vs 9.20 months, P=0.019 and 6.90 vs 5.49 months, P=0.005, respectively). In contrast, PLR at diagnosis was not associated with OS or PFS (P=0.467 and P=0.205, respectively). In multivariate analysis, stage, lactate dehydrogenase, and NLR at diagnosis were independent prognostic factors for OS and PFS. CONCLUSIONS: NLR is easily measurable and reflects the SCLC prognosis. A future prospective study is warranted to confirm our results.

Cluster Analysis of DSC MRI, Dynamic Contrast-Enhanced MRI, and DWI Parameters Associated with Prognosis in Patients with Glioblastoma after Removal of the Contrast-Enhancing Component: A Preliminary Study.

BACKGROUND AND PURPOSE: No report has been published on the use of DSC MR imaging, DCE MR imaging, and DWI parameters in combination to create a prognostic prediction model in glioblastoma patients. The aim of this study was to develop a machine learning-based model to find preoperative multiparametric MR imaging parameters associated with prognosis in patients with glioblastoma. Normalized CBV, volume transfer constant, and ADC of the nonenhancing T2 high-signal-intensity lesions were evaluated using K-means clustering. MATERIALS AND METHODS: A total of 142 patients with glioblastoma who underwent preoperative MR imaging and total resection were included in this retrospective study. From the normalized CBV, volume transfer constant, and ADC maps, the parametric data were sorted using the K-means clustering method. Patients were divided into training and test sets (ratio, 1:1), and the optimal number of clusters was determined using receiver operating characteristic analysis. Kaplan-Meier survival analysis and log-rank tests were performed to identify potential parametric predictors. A multivariate Cox proportional hazard model was conducted to adjust for clinical predictors. RESULTS: The nonenhancing T2 high-signal-intensity lesions were divided into 6 clusters. The cluster (class 4) with the relatively low normalized CBV and volume transfer constant value and the lowest ADC values was most associated with predicting glioblastoma prognosis. The optimal cutoff of the class 4 volume fraction of nonenhancing T2 high-signal-intensity lesions predicting 1-year progression-free survival was 9.70%, below which the cutoff was associated with longer progression-free survival. Two Kaplan-Meier curves based on the cutoff value showed a statistically significant difference (P = .037). When we adjusted for all clinical predictors, the cluster with the relatively low normalized CBV and volume transfer constant values and the lowest ADC value was an independent prognostic marker (hazard ratio, 3.04; P = .048). The multivariate Cox proportional hazard model showed a concordance index of 0.699 for progression-free survival. CONCLUSIONS: Our model showed that nonenhancing T2 high-signal-intensity lesions with the relatively low normalized CBV, low volume transfer constant values, and the lowest ADC values could serve as useful prognostic imaging markers for predicting survival outcomes in patients with glioblastoma.

MGMT Promoter Methylation Status in Initial and Recurrent Glioblastoma: Correlation Study with DWI and DSC PWI Features.

BACKGROUND AND PURPOSE: O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in primary and recurrent glioblastoma may change during treatment. The purpose of this study was to correlate MGMT promoter methylation status changes with DWI and DSC PWI features in patients with recurrent glioblastoma after standard treatment. MATERIALS AND METHODS: Between January 2008 and November 2016, forty patients with histologically confirmed recurrent glioblastoma were enrolled. Patients were divided into 3 groups according to the MGMT promoter methylation status for the initial and recurrent tumors: 2 groups whose MGMT promoter methylation status remained, group methylated (n = 13) or group unmethylated (n = 18), and 1 group whose MGMT promoter methylation status changed from methylated to unmethylated (n = 9). Normalized ADC and normalized relative CBV values were obtained from both the enhancing and nonenhancing regions, from which histogram parameters were calculated. The ANOVA and the Kruskal-Wallis test followed by post hoc tests were performed to compare histogram parameters among the 3 groups. The t test and Mann-Whitney U test were used to compare parameters between group methylated and group methylated to unmethylated. Receiver operating characteristic curve analysis was used to measure the predictive performance of the normalized relative CBV values between the 2 groups. RESULTS: Group methylated to unmethylated showed significantly higher means and 90th and 95th percentiles of the cumulative normalized relative CBV values of the nonenhancing region of the initial tumor than group methylated and group unmethylated (all P < .05). The mean normalized relative CBV value of the nonenhancing region of the initial tumor was the best predictor of methylation status change (P < .001), with a sensitivity of 77.78% and specificity of 92.31% at a cutoff value of 2.594. CONCLUSIONS: MGMT promoter methylation status might change in recurrent glioblastoma after standard treatment. The normalized relative CBV values of the nonenhancing region at the first preoperative MR imaging were higher in the MGMT promoter methylation change group from methylation to unmethylation in recurrent glioblastoma.

Dynamic Contrast-Enhanced MR Imaging of Nonenhancing T2 High-Signal-Intensity Lesions in Baseline and Posttreatment Glioblastoma: Temporal Change and Prognostic Value.

BACKGROUND AND PURPOSE: The prognostic value of dynamic contrast-enhanced MR imaging on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma has not been thoroughly elucidated to date. We evaluated the temporal change and prognostic value for progression-free survival of dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma before and after standard treatment, including gross total surgical resection. MATERIALS AND METHODS: This retrospective study included 33 patients who were newly diagnosed with glioblastoma and treated with gross total surgical resection followed by concurrent chemoradiation therapy and adjuvant chemotherapy with temozolomide in a single institution. All patients underwent dynamic contrast-enhanced MR imaging before surgery as a baseline and after completion of maximal surgical resection and concurrent chemoradiation therapy. On the whole nonenhancing T2 high-signal-intensity lesion, dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters (volume transfer constant [K trans], volume of extravascular extracellular space [v e], and blood plasma volume [vp ]) were calculated. The Cox proportional hazards regression model analysis was performed to determine the histogram features or percentage changes of pharmacokinetic parameters related to progression-free survival. RESULTS: Baseline median K trans, baseline first quartile K trans, and posttreatment median K trans were significant independent variables, as determined by univariate analysis (P < .05). By multivariate Cox regression analysis including methylation status of O6-methylguanine-DNA methyltransferase, baseline median K trans was determined to be the significant independent variable and was negatively related to progression-free survival (hazard ratio = 1.48, P = .003). CONCLUSIONS: Baseline median K trans from nonenhancing T2 high-signal-intensity lesions could be a potential prognostic imaging biomarker in patients undergoing gross total surgical resection followed by standard therapy for glioblastoma.

Can Arterial Spin-Labeling with Multiple Postlabeling Delays Predict Cerebrovascular Reserve?

BACKGROUND AND PURPOSE: The effect of delayed transit time is the main source of error in the quantitative measurement of CBF in arterial spin-labeling. In the present study, we evaluated the usefulness of the transit time-corrected CBF and arterial transit time delay from multiple postlabeling delays arterial spin-labeling compared with basal/acetazolamide stress technetium Tc99m-hexamethylpropylene amineoxime (Tc99m-HMPAO) SPECT in predicting impairment in the cerebrovascular reserve. MATERIALS AND METHODS: Transit time-corrected CBF maps and arterial transit time maps were acquired in 30 consecutive patients with unilateral ICA or MCA steno-occlusive disease (severe stenosis or occlusion). Internal carotid artery territory-based ROIs were applied to both perfusion maps. Additionally, impairment in the cerebrovascular reserve was evaluated according to both qualitative and quantitative analyses of the ROIs on basal/acetazolamide stress Tc99m-HMPAO SPECT using a previously described method. The area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of arterial spin-labeling in depicting impairment of the cerebrovascular reserve. The correlation between arterial spin-labeling and cerebrovascular reserve was evaluated. RESULTS: The affected hemisphere had a decreased transit time-corrected CBF and increased arterial transit time compared with the corresponding values of the contralateral normal hemisphere, which were statistically significant (P < .001). The percentage change of transit time-corrected CBF and the percentage change of arterial transit time were independently differentiating variables (P < .001) for predicting cerebrovascular reserve impairment. The correlation coefficient between the arterial transit time and cerebrovascular reserve index ratio was -0.511. CONCLUSIONS: Our results demonstrate that the transit time-corrected CBF and arterial transit time based on arterial spin-labeling perfusion MR imaging can predict cerebrovascular reserve impairment.

Neutrophil-lymphocyte ratio predicts response to chemotherapy in triple-negative breast cancer.

Background: The neutrophil-lymphocyte ratio (nlr) has been reported to correlate with patient outcome in several cancers, including breast cancer. We evaluated whether the nlr can be a predictive factor for pathologic complete response (pcr) after neoadjuvant chemotherapy (nac) in patients with triple-negative breast cancer (tnbc). Methods: We analyzed the correlation between response to nac and various factors, including the nlr, in 87 patients with tnbc who underwent nac. In addition, we analyzed the association between the nlr and recurrence-free survival (rfs) in patients with tnbc. Results: Of the 87 patients, 25 (28.7%) achieved a pcr. A high Ki-67 index and a low nlr were significantly associated with pcr. The pcr rate was higher in patients having a high Ki-67 index (≥15%) than in those having a low Ki-67 index (35.7% vs. 0%, p = 0.002) and higher in patients having a low nlr (≤1.7) than in those having a high nlr (42.1% vs. 18.4%, p = 0.018). In multiple logistic analysis, a low nlr remained the only predictive factor for pcr (odds ratio: 4.274; p = 0.008). In the survival analysis, the rfs was significantly higher in the low nlr group than in the high nlr group (5-year rfs rate: 83.7% vs. 66.9%; log-rank p = 0.016). Conclusions: Our findings that the nlr is a predictor of pcr to nac and also a prognosticator of recurrence suggest an association between response to chemotherapy and inflammation in patients with tnbc. The pretreatment nlr can be a useful predictive and prognostic marker in patients with tnbc scheduled for nac.

Application of 3D Fast Spin-Echo T1 Black-Blood Imaging in the Diagnosis and Prognostic Prediction of Patients with Leptomeningeal Carcinomatosis.

BACKGROUND AND PURPOSE: Contrast-enhanced 3D fast spin-echo T1 black-blood imaging selectively suppresses the signal of blood flow and could provide a higher contrast-to-noise ratio compared with contrast-enhanced 3D ultrafast gradient recalled echo (contrast-enhanced gradient recalled echo) and 2D spin-echo T1WI (contrast-enhanced spin-echo). The purpose of our study was to evaluate whether black-blood imaging can improve the diagnostic accuracy for leptomeningeal carcinomatosis compared with contrast-enhanced gradient recalled-echo and contrast-enhanced spin-echo and, furthermore, to determine whether the grade of leptomeningeal carcinomatosis evaluated on black-blood imaging is a significant predictor of progression-free survival. MATERIALS AND METHODS: Leptomeningeal carcinomatosis (n = 78) and healthy (n = 31) groups were enrolled. Contrast-enhanced gradient recalled-echo, contrast-enhanced spin-echo, and black-blood imaging were separately reviewed, and a diagnostic rating (positive, indeterminate, or negative) and grading of leptomeningeal carcinomatosis were assigned. The diagnostic accuracies of the 3 imaging sequences were compared in terms of leptomeningeal carcinomatosis detection. The Kaplan-Meier and the Cox proportional hazards model analyses were performed to determine the relationship between the leptomeningeal carcinomatosis grade evaluated on black-blood imaging and progression-free survival. RESULTS: Black-blood imaging showed a significantly higher sensitivity (97.43%) than contrast-enhanced gradient recalled-echo (64.1%) and contrast-enhanced spin-echo (66.67%) (P < .05). In terms of specificities, we did not find any significant differences among contrast-enhanced gradient recalled-echo (90.32%), contrast-enhanced spin-echo (90.32%), and black-blood imaging (96.77%) (P > .05). A Cox proportional hazards model identified the time to metastasis, Karnofsky Performance Scale status, and a combination of the leptomeningeal carcinomatosis grade with a linear pattern as independent predictors of progression-free survival (P < .05). CONCLUSIONS: Black-blood imaging can improve the diagnostic accuracy and predict progression-free survival in patients with leptomeningeal carcinomatosis.

Added Value of Arterial Spin-Labeling MR Imaging for the Differentiation of Cerebellar Hemangioblastoma from Metastasis.

BACKGROUND AND PURPOSE: In adults with only cerebellar masses, hemangioblastoma and metastasis are the 2 most important differential diagnoses. Our aim was to investigate the added value of arterial spin-labeling MR imaging for differentiating hemangioblastoma from metastasis in patients with only cerebellar masses. MATERIALS AND METHODS: This retrospective study included a homogeneous cohort comprising patients with only cerebellar masses, including 16 hemangioblastomas and 14 metastases. All patients underwent enhanced MR imaging, including arterial spin-labeling. First, the presence or absence of a hyperperfused mass was determined. Next, in the hyperperfused mass, relative tumor blood flow (mean blood flow in the tumor divided by blood flow measured in normal-appearing cerebellar tissue) and the size ratio (size in the arterial spin-labeling images divided by size in the postcontrast T1WI) were measured. To validate the arterial spin-labeling findings, 2 observers independently evaluated the conventional MR images and the combined set of arterial spin-labeling images. RESULTS: All patients with hemangioblastomas and half of the patients with metastases presented with a hyperperfused mass (P < .001). The size ratio and relative tumor blood flow were significantly larger for hemangioblastomas than for metastases (P < .001 and P = .039, respectively). The size ratio revealed excellent diagnostic power (area under the curve = 0.991), and the relative tumor blood flow demonstrated moderate diagnostic power (area under the curve = 0.777). The diagnostic accuracy of both observers was significantly improved after the addition of arterial spin-labeling; the area under the curve improved from 0.574 to 0.969 (P < .001) for observer 2 and from 0.683 to 1 (P < .001) for observer 2. CONCLUSIONS: Arterial spin-labeling imaging can aid in distinguishing hemangioblastoma from metastasis in patients with only cerebellar masses.

Comparison between the Prebolus T1 Measurement and the Fixed T1 Value in Dynamic Contrast-Enhanced MR Imaging for the Differentiation of True Progression from Pseudoprogression in Glioblastoma Treated with Concurrent Radiation Therapy and Temozolomide Chemotherapy.

BACKGROUND AND PURPOSE: Glioblastoma is the most common primary brain malignancy and differentiation of true progression from pseudoprogression is clinically important. Our purpose was to compare the diagnostic performance of dynamic contrast-enhanced pharmacokinetic parameters using the fixed T1 and measured T1 on differentiating true from pseudoprogression of glioblastoma after chemoradiation with temozolomide. MATERIALS AND METHODS: This retrospective study included 37 patients with histopathologically confirmed glioblastoma with new enhancing lesions after temozolomide chemoradiation defined as true progression (n = 15) or pseudoprogression (n = 22). Dynamic contrast-enhanced pharmacokinetic parameters, including the volume transfer constant, the rate transfer constant, the blood plasma volume per unit volume, and the extravascular extracellular space per unit volume, were calculated by using both the fixed T1 of 1000 ms and measured T1 by using the multiple flip-angle method. Intra- and interobserver reproducibility was assessed by using the intraclass correlation coefficient. Dynamic contrast-enhanced pharmacokinetic parameters were compared between the 2 groups by using univariate and multivariate analysis. The diagnostic performance was evaluated by receiver operating characteristic analysis and leave-one-out cross validation. RESULTS: The intraclass correlation coefficients of all the parameters from both T1 values were fair to excellent (0.689-0.999). The volume transfer constant and rate transfer constant from the fixed T1 were significantly higher in patients with true progression (P = .048 and .010, respectively). Multivariate analysis revealed that the rate transfer constant from the fixed T1 was the only independent variable (OR, 1.77 × 105) and showed substantial diagnostic power on receiver operating characteristic analysis (area under the curve, 0.752; P = .002). The sensitivity and specificity on leave-one-out cross validation were 73.3% (11/15) and 59.1% (13/20), respectively. CONCLUSIONS: The dynamic contrast-enhanced parameter of rate transfer constant from the fixed T1 acted as a preferable marker to differentiate true progression from pseudoprogression.

Differentiation of Parkinsonism-Predominant Multiple System Atrophy from Idiopathic Parkinson Disease Using 3T Susceptibility-Weighted MR Imaging, Focusing on Putaminal Change and Lesion Asymmetry.

BACKGROUND AND PURPOSE: Asymmetric presentation of clinical feature in parkinsonism is common, but correlatable radiologic feature is not clearly defined. Our aim was to evaluate 3T susceptibility-weighted imaging findings for differentiating parkinsonism-predominant multiple system atrophy from idiopathic Parkinson disease, focusing on putaminal changes and lesion asymmetry. MATERIALS AND METHODS: This retrospective cohort study included 27 patients with parkinsonism-predominant multiple system atrophy and 50 patients with idiopathic Parkinson disease diagnosed clinically. Twenty-seven age-matched subjects without evidence of movement disorders who underwent SWI were included as the control group. A consensus was reached by 2 radiologists who visually assessed SWI for the presence of putaminal atrophy and marked signal hypointensity on each side of the posterolateral putamen. We also quantitatively measured putaminal width and phase-shift values. RESULTS: The mean disease duration was 4.7 years for the patients with parkinsonism-predominant multiple system atrophy and 7.8 years for the patients with idiopathic Parkinson disease. In the patients with parkinsonism-predominant multiple system atrophy, putaminal atrophy was frequently observed (14/27, 51.9%) and was most commonly found in the unilateral putamen (13/14). Marked signal hypointensity was observed in 12 patients with parkinsonism-predominant multiple system atrophy (44.4%). No patients with idiopathic Parkinson disease or healthy controls showed putaminal atrophy or marked signal hypointensity. Quantitatively measured putaminal width, phase-shift values, and the ratio of mean phase-shift values for the dominant and nondominant sides were significantly different between the parkinsonism-predominant multiple system atrophy group and the idiopathic Parkinson disease and healthy control groups (P < .001). CONCLUSIONS: 3T SWI can visualize putaminal atrophy and marked signal hypointensity in patients with parkinsonism-predominant multiple system atrophy with high specificity. Furthermore, it clearly demonstrates the dominant side of putaminal changes, which correlate with the contralateral symptomatic side of patients.

Correlation of Asymmetry Indices Measured by Arterial Spin-Labeling MR Imaging and SPECT in Patients with Crossed Cerebellar Diaschisis.

BACKGROUND AND PURPOSE: Crossed cerebellar diaschisis, not only a secondary result of supratentorial infarction but also an indicator of clinical outcomes, has frequently been reported on PET and SPECT but has been rarely described with arterial spin-labeling MR imaging. The purpose of this study was to determine the ability of arterial spin-labeling MR imaging to evaluate crossed cerebellar diaschisis compared with that of SPECT. To our knowledge, this is the first study to validate arterial spin-labeling in crossed cerebellar diaschisis by using SPECT as a reference standard. MATERIALS AND METHODS: This study included 16 patients in whom crossed cerebellar diaschisis was shown on SPECT and 10 control subjects in whom crossed cerebellar diaschisis was not shown on SPECT. During the qualitative analysis, asymmetric cerebellar perfusion on arterial spin-labeling was divided into 1 of the following 3 grades by 2 blinded observers: the affected cerebellum was isointense compared with the unaffected cerebellum (grade I), it was slightly hypointense (grade II), or it was markedly hypointense (grade III). In the quantitative analysis, asymmetry indices were calculated by using SPECT and arterial spin-labeling images. For statistical analysis, κ statistics, the interobserver correlation coefficient, the independent t test, Pearson correlation, and linear regression analysis were used. RESULTS: Almost all the diagnoses of crossed cerebellar diaschisis on SPECT were noted on arterial spin-labeling in both qualitative and quantitative analyses with good interobserver agreement (κ = 0.961; interobserver correlation coefficient, 0.806). The mean asymmetry index of arterial spin-labeling (26.06 ± 9.00) was significantly larger than that for SPECT (15.28 ± 5.34; P < .001). There was a significant positive correlation between the asymmetry indices obtained for SPECT and those for arterial spin-labeling (r = 0.77 [95% CI, 0.443-0.916]; P < .001). The relationship of asymmetry indices between SPECT and arterial spin-labeling (x, y) was calculated as y = 6.2131 + 1.2986x (R(2) = 0.592; P < .001). CONCLUSIONS: Arterial spin-labeling can be a noninvasive alternative to SPECT for evaluating crossed cerebellar diaschisis.

Clinical utility of arterial spin-labeling as a confirmatory test for suspected brain death.

Diagnosis of brain death is made on the basis of 3 essential findings: coma, absence of brain stem reflexes, and apnea. Although confirmatory tests are not mandatory in most situations, additional testing may be necessary to declare brain death in patients in whom results of specific components of clinical testing cannot be reliably evaluated. Recently, arterial spin-labeling has been incorporated as part of MR imaging to evaluate cerebral perfusion. Advantages of arterial spin-labeling include being completely noninvasive and providing information about absolute CBF. We retrospectively reviewed arterial spin-labeling findings according to the following modified criteria based on previously established confirmatory tests to determine brain death: 1) extremely decreased perfusion in the whole brain, 2) bright vessel signal intensity around the entry of the carotid artery to the skull, 3) patent external carotid circulation, and 4) "hollow skull sign" in a series of 5 patients. Arterial spin-labeling findings satisfied the criteria for brain death in all patients. Arterial spin-labeling imaging has the potential to be a completely noninvasive confirmatory test to provide additional information to assist in the diagnosis of brain death.

Global gene expression changes induced in the human placenta during labor.

OBJECTIVES: To gain insight into the process of labor and the effects of labor on placental gene expression, we performed a microarray analysis to identify the differentially expressed transcripts that may participate in labor onset and progression. METHODS: We compared expression profiles in placentas from 16 women who underwent elective non-labored cesarean section and from seven women who underwent vaginal delivery. Oligonucleotide probes representing 55,000 genes were used to measure gene expression. Differential gene expression was evaluated using the Student's t-test and fold change assessment and reverse transcription PCR was used to validate the differentially expressed genes. RESULTS: A total of 351 genes were found to be differentially expressed between the two groups. Among these differentially expressed genes, 344 genes were up-regulated and seven were down-regulated. These differentially expressed genes involved 15 categories including genes involved in stress response, immune response, cell death, coagulation, and blood vessel development which are considered to be most closely associated with the inflammatory response that characterizes labor. CONCLUSION: A total of 351 differentially expressed genes of 15 categories were found in the placentas of the vaginal delivery group, indicating a diversity of gene expression alteration and complexity in the labor process. These gene expression changes could be a cause of labor onset and progress or simply an effect of labor.