Computerized tomography texture analysis of pheochromocytoma: relationship with hormonal and histopathological data.

OBJECTIVES: Pheochromocytomas are rare tumors which can present with heterogeneous secretion profiles, clinical manifestations, and radiologic appearance. Under a histopathological point of view, they can be characterized as more or less aggressive with the Pheochromocytoma of the Adrenal gland Scaled Score (PASS) and the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) score. The aim of this study is to analyze the texture analysis characteristics of pheochromocytoma and identify whether the texture analysis can yield information aiding in the diagnosis and the characterization of those tumors. METHODS: Radiological, biochemical, and histopathological data regarding 30 consecutive patients with histologically confirmed pheochromocytoma were analyzed. Images obtained in the unenhanced, late arterial, venous, and delayed phases were used for the texture analysis. RESULTS: Urinary epinephrine and metanephrine levels showed a significant correlation (R2 = 0.946; R2 = 699) in the multivariate linear model with texture features, as well as Ki-67 (R2 = 0.397), PASS score (R2 = 0.182), GAPP score (R2 = 0.705), and cellularity showed a significant correlation (R2 = 0.389). The cluster analysis based on radiomic features resulted in 2 clusters, with significative differences in terms of systolic and diastolic blood pressure values at the time of diagnosis (p = 0.025), GAPP score (4 vs 6, p = 0.05), histological pattern (1-2, p = 0.039), and comedonecrosis (0% vs 50%, p = 0.013). CONCLUSION: In conclusion, our study provides the proof of concept for the use of texture analysis on contrast-enhanced CT images as a noninvasive, quantitative tool for helping in the characterization of the clinical, biochemical, and histopathological features of pheochromocytoma.

Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients?

The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm(2)) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8-13), median survival was 18 years (95 % CI 9-28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0-97.2 %) and 60.2 % (95 % CI 36.9-83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group).

Agreement between two- and three-dimensional transperineal ultrasound methods for assessment of fetal head-symphysis distance in active labor.

OBJECTIVES: To assess the intermethod agreement between two-dimensional (2D) and three-dimensional (3D) transperineal ultrasound methods in measuring a new index of fetal head station (the fetal head-symphysis distance (HSD)) in active labor, and to assess potential factors that may affect their agreement. METHODS: HSD was measured by transperineal ultrasound in 86 women in active labor, once using a 2D and once using a 3D technique. 2D images were acquired first in 43 cases and 3D images were acquired first in the other 43 women. Intermethod agreement between 2D and 3D methods was analyzed by means of intraclass correlation coefficient (ICC) and Bland-Altman analysis. In addition, potential factors affecting the intermethod reproducibility were investigated including fetal occiput position, order of acquisition, fetal head station, stage of labor, maternal body mass index and use of epidural analgesia, using the ANOVA test to check for systematic bias and Levene's test for homoscedasticity. RESULTS: Good agreement was demonstrated between 2D and 3D measurements of HSD (ICC, 0.949 (95% CI, 0.914-0.984)). No evidence of systematic difference was shown between the two methods (average difference ± SD = 0.03 ± 2.29 mm; P = 0.888). The only factor that had a significant effect on systematic difference between 2D and 3D methods was order of acquisition (P = 0.042); the first observation was higher regardless of the method used. Fetal head station had a significant effect on the homogeneity between the two methods (P = 0.004) with a better 2D-3D agreement obtained at lower head stations (SD of differences: 1.63 vs 2.59 mm). CONCLUSIONS: There is very good agreement between 2D and 3D methods of assessing HSD. Agreement is better in lower fetal head stations.

Sonographic pattern of fetal head descent: relationship with duration of active second stage of labor and occiput position at delivery.

OBJECTIVES: The objectives of this study were firstly to assess the longitudinal changes of various sonographic parameters of fetal head progression in relation to length of active second stage of labor, and secondly to compare ultrasound findings obtained longitudinally among fetuses with persistent occiput posterior (OP) vs those with persistent occiput anterior (OA) position. METHODS: From a series of nulliparous low-risk women at term attending the labor ward of our university hospital, transperineal ultrasound volumes were prospectively acquired at the beginning of the active second stage (T1) and at 40-min intervals thereafter until delivery (T2, T3). Sonographic parameters were derived from offline analysis of each volume, including the angle of progression (AoP), progression distance (PD), head-symphysis distance (HSD), head direction (HD) and midline angle. These parameters were compared between patients who delivered within 60 min from the beginning of the active second stage of labor (early delivery) and those who remained undelivered by that time (late delivery). Fetal head position was determined from stored digital images of transabdominal examinations performed at the beginning of the active second stage. Comparison was performed between fetuses with OA and those with persistent OP position at delivery. RESULTS: Spontaneous vaginal delivery was achieved in 58 (81.7%) cases, whereas vacuum extraction and Cesarean section were performed in eight (11.3%) and five (7.0%) cases, respectively. Delivery was achieved within 60 min from the beginning of the active second stage in 44 (62.0%) patients. In the early vs late delivery groups, measurements of AoP, HSD and PD at T1 were significantly different (AoP, 143.9 ± 20.5° vs 125.3 ± 15.0°, P < 0.001; HSD, 14.8 ± 4.5 mm vs 20.9 ± 5.8 mm, P < 0.001; PD, 44.0 ± 14.1 vs 35.0 ± 13.1 mm, P = 0.008). On logistic regression analysis of data obtained at T1, maternal body mass index, oxytocin administration, neonatal birth weight and HSD appeared to predict independently duration of the active second stage. Among fetuses delivering in the OP position (n = 10, 13.5%), Cesarean delivery was significantly more common than in those delivering in the OA position (n = 5 (50.0%) vs n = 2 (3.1%), P = 0.001). Women with persistent OP position compared with OA showed a significantly different AoP at T1 (122 ± 17° vs 138 ± 20°, P = 0.016), HD and HSD at T1 (HD, 112 ± 17 mm vs 86 ± 19 mm, P < 0.001; HSD, 16.5 ± 5.4 mm vs 22.8 ± 6.6 mm, P = 0.008) and at T2 (HD, 120 ± 16 vs 82 ± 27 mm, P = 0.008; HSD, 12.6 ± 3.4 mm vs 18.5 ± 5.4 mm, P = 0.038). CONCLUSIONS: AoP, PD and HSD are significantly different between patients undergoing delivery before or after 60 min from the beginning of the active second stage of labor. Ultrasound parameters are among the significant predictors of duration of the active second stage. Moreover, in fetuses persisting in the OP position vs those delivering in the OA position, fetal head progression seems to differ at early phases of the active second stage.

A prospective study on the early evaluation of response to androgen receptor-targeted agents with 11C-Choline, 68Ga-PSMA, and 18F-FACBC PET in metastatic castration-resistant prostate cancer: a single-center experience.

BACKGROUND: The early identification of responsive and resistant patients to androgen receptor-targeting agents (ARTA) in metastatic castration-resistant prostate cancer (mCRPC) is not completely possible with prostate-specific antigen (PSA) assessment and conventional imaging. Considering its ability to determine metabolic activity of lesions, positron emission tomography (PET) assessment might be a promising tool. PATIENTS AND METHODS: We carried out a monocentric prospective study in patients with mCRPC treated with ARTA to evaluate the role of different PET radiotracers: 49 patients were randomized to receive 11C-Choline, Fluorine 18 fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid - FACBC) (18F-FACBC), or Gallium-68-prostate-specific-membrane-antigen (68Ga-PSMA) PET, one scan before therapy and one 2 months later. The primary aim was to investigate the performance of three novel PET radiotracers for the early evaluation of response to ARTA in metastatic CRPC patients; the outcome evaluated was biochemical response (PSA reduction ≥50%). The secondary aim was to investigate the prognostic role of several semiquantitative PET parameters and their variations with the different radiotracers in terms of biochemical progression-free survival (bPFS) and overall survival (OS). The study was promoted by the Italian Department of Health (code RF-2016-02364809). RESULTS: Regarding the primary endpoint, at log-rank test a statistically significant correlation was found between metabolic tumor volume (MTV) (P = 0.018) and total lesion activity (TLA) (P = 0.025) percentage variation among the two scans with 68Ga-PSMA PET and biochemical response. As for the secondary endpoints, significant correlations with bPFS were found for 68Ga-PSMA total MTV and TLA at the first scan (P = 0.001 and P = 0.025, respectively), and MTV percentage variation (P = 0.031). For OS, statistically significant correlations were found for different 68Ga-PSMA and 18F-FACBC parameters and for major maximum standardized uptake value at the first 11C-Choline PET scan. CONCLUSIONS: Our study highlighted that 11C-Choline, 68Ga-PSMA, and 18F-FACBC semiquantitative PET parameters and their variations present a prognostic value in terms of OS and bPFS, and MTV and TLA variations with 68Ga-PSMA PET a correlation with biochemical response, which could help to assess the response to ARTA.

Fetal head-symphysis distance: a simple and reliable ultrasound index of fetal head station in labor.

OBJECTIVES: To assess the reproducibility of measurement of a new sonographic index of fetal head station in labor, the fetal head-symphysis distance (HSD), using three-dimensional ultrasound, and its correlation with digital assessment of fetal head descent and with the angle of progression (AoP). METHODS: Three-dimensional (3D) ultrasound volumes were acquired from 47 nulliparous women in active labor following assessment of fetal head station with digital examination. The HSD (the distance between the lower edge of the pubic symphysis and the nearest point of the fetal skull) was measured independently by two operators in order to evaluate intra- and interobserver reproducibility. The correlation between HSD, AoP and fetal head station was evaluated using regression analysis. Using 3D tomographic ultrasound imaging (TUI), measurements of the HSD were obtained in different parasagittal planes to evaluate the influence of inaccurate alignment of the probe with the midline of the pelvis. RESULTS: Measurement of HSD showed high intraobserver (intraclass correlation coefficient (ICC) = 0.995; 95% CI, 0.991-0.997) and interobserver (ICC = 0.991; 95% CI, 0.984-0.995) reliability. In addition, a high correlation was demonstrated between mid-sagittal and parasagittal HSD measurements. HSD showed significant negative correlation with both fetal head station and AoP. CONCLUSION: Fetal HSD is a simple and reliable method for the assessment of fetal head descent in labor.

Intrapartum transperineal ultrasound assessment of fetal head progression in active second stage of labor and mode of delivery.

OBJECTIVE: To compare longitudinal changes in angle of progression (AoP) and midline angle (MLA) during the active second stage of labor according to the mode of delivery. METHODS: A three-dimensional transperineal ultrasound volume was acquired in a series of nulliparous women at the beginning of the active second stage (T1) and every 20 min thereafter (T2, T3, T4, T5 and T6). Following delivery, all ultrasound volumes were analyzed and AoP and MLA were measured. RESULTS: Among 71 women included in the study, 58 underwent spontaneous vaginal delivery (group A) and 13 underwent operative delivery (group B) (eight by vacuum extraction and five by Cesarean section). When compared with Group B, Group A had a wider AoP only at T1 (140.0 ± 20.2° vs. 122.9 ± 16.7°; P = 0.010) and T2 (149.7 ± 20.7° vs. 126.9 ± 17.5°; P = 0.006). MLA was narrower in group A only at T3 (21.2 ± 11.7° vs. 40.8 ± 27.9°; P = 0.043), T4 (18.2 ± 15.0° vs. 47.4 ± 29.6°; P = 0.020) and T5 (18.3 ± 6.0° vs. 34.7 ± 4.2°; P = 0.034). On stepwise forward multiple logistic regression analysis, both AoP and MLA were independently associated with operative delivery (OR = 0.955 and OR = 1.018, respectively). CONCLUSION: Ultrasonographic assessment of fetal head descent in the second stage of labor may play a role in the prediction of the mode of delivery.

Treatment of malignant gliomas: a new approach.

The aim of this study is to describe the authors' experience with intra-arterial ACNU chemotherapy of malignant gliomas. The prognosis of cerebral malignant gliomas remains poor, whatever traditional therapy is applied. ACNU is a well tolerated nitrosourea with a strong antimitotic effect on neurogenic cells both in vitro and in vivo; this drug has enhanced efficacy when used at high concentrations, particularly as an intraarterial infusion. Seventy-six patients have been studied to date, 68 of whom are evaluable; these patients were treated by intra-arterial infusion of ACNU (100 mg/m2) every 6 weeks, with a mean of 2.5 courses per patient. The objective response (OR) was 28% and analysis of pretreatment factors revealed that survival was influenced by histological grade, other types of therapy applied, and age. In general IAC is well tolerated and the response and survival appear to be better than with systemic chemotherapy.

Twice-daily dosing of temozolomide in combination with fotemustine for the treatment of patients with refractory glioblastoma.

Alkylating agents, such as temozolomide (TMZ) and fotemustine (FTM) are widely used in recurrent glioblastoma (GBM) regimes. Several strategies have been proposed to prevent resistance to these agents, by combining or sequencing them. We report the results of a pilot study of patients with refractory GBM receiving a regime of twice-daily dosing of temozolomide administered on day 1, (with an initial oral dose of 200 mg/m(2) and a second oral dose of 75 mg/m(2) 12 h later), followed by fotemustine in a single i.v. infusion at 75 mg/m(2) on day 2, repeated every four weeks. Enrolment was stopped at 15 patients due to lack of effectiveness of this schedule for patients with GBM. Toxicity was mild, with no grade 4 side effects reported. Results indicate that our temozolomide -FTM combined schedule is not effective, although well tolerated, in non responsive patients with GBM. Further strategies are required to improve the outcome of these patients.

Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons.

BACKGROUND: Mediators released in the mucosal milieu have been suggested to be involved in visceral hypersensitivity and abdominal pain in patients with irritable bowel syndrome (IBS). However, their impact on myenteric neurons remains unsettled. METHODS: Mucosal biopsies were obtained from the descending colon of patients with IBS and controls. Mucosal mast cells were identified immunohistochemically. The impact of spontaneously released mucosal mediators on guinea pig electrically stimulated longitudinal muscle myenteric plexus (LMMP) preparations was assessed in vitro by means of selective receptor antagonists and inhibitors. KEY RESULTS: Patients with IBS showed an increased mast cell count compared with controls. Application of mucosal mediators of IBS to LMMPs potentiated cholinergic twitch contractions, an effect directly correlated with mast cell counts. Enhanced contractions were inhibited by 50.3% with the prostaglandin D2 antagonist BW A868C, by 31.3% and 39% with the TRPV1 antagonists capsazepine and HC-030031, respectively, and by 60.5% with purinergic P2X antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid. Conversely, the serotonin1-4, histamine1-3, tachykinin1-3 receptor blockade, and serine protease inhibition had no significant effect. CONCLUSIONS & INFERENCES: Colonic mucosal mediators from patients with IBS excite myenteric cholinergic motor neurons. These effects were correlated with mast cell counts and mediated by activation of prostanoid receptors, TRPV1, and P2X receptors. These results support the role of mucosal inflammatory mediators and mast cell activation in altered motor function of IBS.