Mean Volume Research Articles

Abstract TMP81: Effect of Post Thrombolytic Intracerebral Hemorrhage Volume on 90-day Outcomes in Acute Ischemic Stroke Patients

Background and Purpose: Post thrombolytic intracerebral hemorrhage (ICH) is associated with higher rate of death or disability in acute ischemic stroke patients. We investigated the relationship between post thrombolytic ICH volume and change in volume and death or disability at 90 days in acute ischemic stroke patients. Methods: We analyzed 110 patents recruited in the Safety Evaluation of 3K3A-APC in Ischemic Stroke (RHAPSODY) trial who received intravenous tissue plasminogen activator (tPA) followed by mechanical thrombectomy (if indicated) and 3K3A-APC or placebo. ICH volume was measured at Day 2 and Day 7 using susceptibility weighted sequence (SWI) on magnetic resonance imaging (MRI). We also calculated the post thrombolytic ICH volume change between Day 2 and Day 7. Outcomes were determined by using utility weighted modified Rankin scale (UW-mRs) at 90-days. We adjusted for age, gender, National Institute of Health Stroke Scale (NIHSS) score (<10,10-19 and ≥20), location of hemorrhage (single basal ganglia hemorrhage, single lobar, single cerebellum, and multiple sites hemorrhage) in multivariate regression analysis. Results: A total of 88 (80%) of 110 patients had post thrombolytic ICH (mean volume 28.3 ml ± SD 62ml). The strata of ICH volume were not associated with UW-mRs at 90 days: <20 cc (regression coefficient-0.05, p= 0.58), 20-39 cc (-0.23, p=0.15), or 40 cc (-0.33, p= 0.086) compared with no ICH after adjusting for potential confounders. Change in ICH volume mean volume 27.43ml ±59.01, 52 had increase in volume) between Day 2 and day 7 was not associated with UW-mRS at 90 days (regression coefficient -11.87, p= 0.796). Conclusions: We did not observe any independent effect of post thrombolytic ICH volume on death or disability in acute ischemic stroke patients. Strategies to prevent ICH expansion such as antifibrinolytic medications and reduction in ICH volume such as surgical evacuation may not reduce death or disability in acute ischemic stroke patients with post thrombolytic ICH.

Analysis of upfront resection or stereotactic radiosurgery for local control of solid and cystic cerebellar hemangioblastomas.

The purpose of this study was to identify rates of and risk factors for local tumor progression in patients who had undergone surgery or radiosurgery for the management of cerebellar hemangioblastoma and to describe treatments pursued following tumor progression. The authors conducted a retrospective single-center review of patients who had undergone treatment of a cerebellar hemangioblastoma with either surgery or stereotactic radiosurgery (SRS) between 1996 and 2019. Univariate and multivariate regression analyses were performed to examine factors associated with local tumor control. One hundred nine patients met the study inclusion criteria. Overall, these patients had a total of 577 hemangioblastomas, 229 of which were located in the cerebellum. The surgical and SRS cohorts consisted of 106 and 123 cerebellar hemangioblastomas, respectively. For patients undergoing surgery, tumors were treated with subtotal resection and gross-total resection in 5.7% and 94.3% of cases, respectively. For patients receiving SRS, the mean target volume was 0.71 cm3 and the mean margin dose was 18.0 Gy. Five-year freedom from lesion progression for the surgical and SRS groups was 99% and 82%, respectively. The surgical and SRS cohorts contained 32% versus 97% von Hippel-Lindau tumors, 78% versus 7% cystic hemangioblastomas, and 12.8- versus 0.56-cm3 mean tumor volumes, respectively. On multivariate analysis, factors associated with local tumor progression in the SRS group included older patient age (HR 1.06, 95% CI 1.03-1.09, p < 0.001) and a cystic component (HR 9.0, 95% CI 2.03-32.0, p = 0.001). Repeat SRS as salvage therapy was used more often for smaller tumor recurrences, and no tumor recurrences of < 1.0 cm3 required additional salvage surgery following repeat SRS. Both surgery and SRS achieve high rates of local control of hemangioblastomas. Age and cystic features are associated with local progression after SRS treatment for cerebellar hemangioblastomas. In cases of local tumor recurrence, salvage surgery and repeat SRS are valid forms of treatment to achieve local tumor control, although resection may be preferable for larger recurrences.

Equine grass sickness is associated with major abnormalities in the ultrastructure of skeletal neuromuscular junctions.

Equine grass sickness (EGS) is a frequently fatal multisystem neuropathy of equids. The aetiology is unknown; proposed causes include toxicoinfection with Clostridium botulinum and a mycotoxicosis. The effect of EGS on the organisation and structural integrity of the skeletal neuromuscular junction (NMJ), the target of botulinum neurotoxins (BoNTs), is unknown. To compare the organisation and structural integrity of skeletal NMJs from EGS horses, control horses and one horse with a presumptive diagnosis of botulism. Blinded, retrospective case control. NMJs in samples of diaphragm or intercostal muscle from six EGS horses, three control horses and one equine botulism case were compared using electron microscopy, morphometry and confocal light microscopy. A significantly higher percentage of EGS NMJs had abnormal morphology (EGS 72.2%, 95% CI 55.6-84.4; Controls 6.9%, 1.7-23.8; OR 35.1, 8.47-244.8; p < 0.001). EGS NMJs had a significantly lower mean volume fraction occupied by synaptic vesicles (SVs) (EGS 18.7%, 12.6-28.0; Controls 36.3%, 20.8-63.4; p = 0.024). EGS NMJs had evidence of accelerated SV exocytosis and SV depletion, accumulation of neurofilament-like material in terminal boutons and/or bouton degeneration. NMJs from the botulism horse had dense packing of SVs towards the presynaptic membrane active zone, consistent with BoNT intoxication, but had absence of the abnormalities identified in EGS NMJs. Group sizes were limited by difficulties obtaining suitably processed samples. Ages of control and EGS horses differed. Botulism was diagnosed based on clinical and post mortem findings. EGS is associated with major changes in skeletal NMJ ultrastructure that are inconsistent with the effects of BoNTs. SV depletion may reflect increased exocytosis coupled with reduced repopulation of SVs via anterograde axonal transport and endocytosis, consistent with the action of an excitatory presynaptic toxin and/or neurotransmitter reuptake inhibitor. Skeletal NMJs represent a previously unrecognised target for the toxin that causes EGS.

Effect of provenances on growth and stem form of 16-year Juniperus procera plantation in Injibara, Northwestern Ethiopia

Juniperus procera Hochst. ex Endl. is an evergreen highland tree species reaching 30–40 m high and restricted to some mountainous areas. This tree is a species of great ecological and economic significance in supporting biodiversity, preventing soil erosion, and providing valuable resources. The study aimed at comparing the provenances effect on growth and yield performance of a 16-years-old J. procera plantation. This long-term experiment included eleven provenances from different regions of Ethiopia. It was laid out in a randomized complete block design with four replicates. The plot size was 100 m2 with 2.5 m by 2.5 m spacing. Growth parameters such as height and diameter over a 1-m interval of standing trees were measured for sample trees. The results showed that the overall mean of basal area for 11 provenances was ranging from 4.4 ± 0.29 to 5.2 ± 0.33 m2 ha⁻1. The biggest (11.3 ± 0.14 m) and smallest (9.8 ± 0.16 m) mean height was obtained in the provenances of Kolobo and Dikisis, respectively. The mean volume of the stem ranges from 12.3 ± 0.93 to 17.9 ± 1.1 m3 ha⁻1. The highest and lowest form factor was obtained in the provenances of Gaynt (0.43 ± 0.02) and Hirna (0.32 ± 0.02), respectively. The generic form factor is 0.4 ± 0.01. Provenance Kolobo had the best growth rate in all growth stages with 1.4 m height greater than the poorest provenance Dikisis and 23% greater than the overall average volume (14.5 m3 ha⁻1) at age of 16 years. The variations in growth and yield performance among the provenances could be attributed to genetic differences and adaptation to the local environment. Provenances originating from similar altitude such as Kolobo's provenances showed better growth and yield performance, possibly due to their adaptation to the cooler and wetter conditions prevailing in the study area. Choosing provenances that are well-adapted to the local site conditions can lead to improved productivity and economic returns.

Magnetic Resonance Imaging-Guided Frameless Stereotactic Injections of the Bilateral Cerebellar Dentate Nuclei in Nonhuman Primates: Technical Note.

Nonhuman primates (NHPs) are important preclinical models for evaluating therapeutics because of their anatomophysiological similarities to humans, and can be especially useful for testing new delivery targets. With the growing promise of cell and gene therapies for the treatment of neurological diseases, it is important to ensure the accurate and safe delivery of these agents to target structures in the brain. However, a standard guideline or method has not been developed for stereotactic targeting in NHPs. In this article, we describe the safe use of a magnetic resonance imaging-guided frameless stereotactic system to target bilateral cerebellar dentate nuclei for accurate, real-time delivery of viral vector in NHPs. Seventeen rhesus macaques (Macaca mulatta) underwent stereotactic surgery under real-time MRI guidance using the ClearPoint® system. Bilateral cerebellar dentate nuclei were targeted through a single parietal entry point with a transtentorial approach. Fifty microliters of contrast-impregnated infusate was delivered to each dentate nucleus, and adjustments were made as necessary according to real-time MRI monitoring of delivery. Perioperative clinical outcomes and postoperative volumes of distribution were recorded. All macaques underwent bilateral surgery successfully. Superficial pin site infection occurred in 4/17 (23.5%) subjects, which resolved with antibiotics. Two episodes of transient neurological deficit (anisocoria and unilateral weakness) were recorded, which did not require additional postoperative treatment and resolved over time. Volume of distribution of infusate achieved satisfactory coverage of target dentate nuclei, and only 1 incidence (2.9%) of cerebrospinal fluid penetration was recorded. Mean volume of distribution was 161.22 ± 39.61 mm3 (left, 173.65 ± 48.29; right, 148.80 ± 23.98). MRI-guided frameless stereotactic injection of bilateral cerebellar dentate nuclei in NHPs is safe and feasible. The use of this technique enables real-time modification of the surgical plan to achieve adequate target coverage and can be readily translated to clinical use.

Dosimetric Comparison of Isodose Surface Volume and Total Reference Air Kerma (TRAK) based Volume in Cervical Cancer Brachytherapy.

We aim to compare TRAK & TPS based isodose volumes in cervical cancer brachytherapy and assess the feasibility, accuracy and potential future implications of TRAK in this regard and as a newer emerging tool to assess treatment intensity in cervical cancer brachytherapy. one hundred patients with histologically proven squamous cell carcinoma of cervix uteri were assessed for brachytherapy (after completion of external radiation) and prospectively enrolled for the study. 60 Gy, 75 Gy, and 85 Gy isodose volumes were obtained from the TPS (VTPS) for 50, 25 & 25 patients with Manchester, Fletcher & interstitial implant respectively, receiving various fractionation schedules by Ir192 HDR remote after-loading system. Using the formula Vpred=4965(TRAK/dref)3/2+170(TRAK/dref)-1.5 the TRAK based isodose surface volumes (Vpred) were derived. Reference doses (dref) were calculated based on accumulated EBRT and brachytherapy doses. The two sets of volume were compared with respect to applicator type, standard, and optimised plan. Surrogate point A dose was also correlated. VTPS - Vpred were 5.24 ± 2.7%, all volumes being predicted within 10%. Correlation of TRAK vs VTPS60/ VTPS75/ VTPS85 showed R2 of 0.994, 0.987 and 0.971 respectively. There was no significant difference in predicted volumes with respect to applicator type. The surrogate point A showed mean volume and standard deviation of 7.44 ± 13.4%, 17.63 ± 16.38 and 3.5 ± 0.95 for Manchester optimised, Fletcher optimised and standard plans respectively. TRAK with point A (R2=0.5632), bladder (R2=0.2015) and rectal doses (R2=0.121) yielded no correlation. Volumes calculated by TRAK correlate with TPS obtained volumes significantly and the formula predicting isodose surface volumes within 10% accuracy for ICBT applications and not for pure interstitial implants. However, TRAK fails to correlate with surrogate point A, bladder and rectal doses hence has questionable utility as a marker for biological response & treatment intensity.

Conversion to Autologous Breast Reconstruction with Latissimus Dorsi and Immediate Fat Grafting in Patients with Previous Implant Failure: An Efficient, Reproducible, and Safe Technique.

Introduction Implant-based breast reconstructions (IBBRs) increased last years despite the growing indications for radiotherapy in the treatment of breast cancer. As a result, complications and reconstructive failures associated to IBBR have increased. Autologous breast reconstruction (ABR) using fat-augmented latissimus dorsi (FALD) has become popular in recent years. Methods We aimed to evaluate conversion to ABR using latissimus dorsi and immediate fat grafting in 61 cases with IBBR failure. Results Immediate reconstruction was found significatively related with an increased number of surgeries resulting from IBBR complications ( p < 0.001). Note that 41% of the cases presented a grade III/IV Baker and Palmer capsular contracture, 29% implant extrusion, and 21% implant infection. Mean survival of the first implant was 16.95 months. ABR process was completed in 47% of cases with a single surgery. Statistically significant differences were observed between this fact and previous IBBR failure due to infection ( p = 0.03) or extrusion ( p = 0.01). Mean volume of fat graft was 429.61 mL, mean length of the surgical procedure was 3.17 hours, and the average length of hospital stay after surgery was 2.67 days. Only 3.3% of the cases developed some major complication. None of the cases presented reconstructive failure. Conclusion FALD is a very safe total ABR technique, an important fact in patients with previous reconstructive failures. The large volume of fat that can be grafted in a single surgery allows the reconstruction of breast in a reasonable size. The reduced length of surgery and hospital stay make the FALD technique an option to consider when an autologous but efficient and safe reconstruction is desired.

Holmium Laser Enucleation of Prostate: Is novel En Bloc Enucleation Technique Better Than the Traditional 2-Lobe Technique-A Prospective Randomized Study.

To compare the safety and efficacy of the en bloc technique with the standard 2-lobe technique for holmium laser enucleation of the prostate (HoLEP). This prospective study included patients with benign prostatic hyperplasia (BPH) who underwent HoLEP from September 2020 to March 2022, by en bloc or 2-lobe technique. Patient demographics, prostate volume, enucleation, morcellation and operative time, and incidence of postoperative incontinence were compared between the 2 groups. We included 64 patients (30 en bloc and 34 2-lobe techniques) who underwent HoLEP in this study. The mean age, prostate volume, creatinine, and PSA of patients were comparable in both groups [(68.53 vs. 67.55 years; P=.62), (79.43 vs. 79.88 g, P=.92), (1.08 mg/dL vs. 1.20 mg/dL, P=.35), (3.78 vs. 4.63 ng/mL; P=.376), respectively]. The enucleation time was significantly shorter in the en bloc group than in the 2-lobe group (54.2 vs. 61.67; P=.03). Additionally, the mean operative time was also comparatively shorter in the en bloc group than the 2-lobe group (72.36 vs. 80.50; P=.057). The improvement in the quality-of-life (QoL) score was significantly better with en bloc than the 2-lobe group (3.80 vs. 2.11; P=.01). There was a significant difference in stress urinary incontinence on days 1, 7, and 30 (P .001) with en bloc compared to the two-lobe technique. Although the outcomes of en bloc and 2-lobe endoscopic enucleation of prostate techniques were comparable, the en bloc technique seems to be a better option in most patients undergoing HoLEP due to less enucleation and operative time and lowered stress urinary incontinence incidence.

Availability of Mean Platelet Volume and Neutrophil/Lymphocyte Ratio in Control of Helicobacter Pylori Eradication

Aim: The most common chronic bacterial infection in humans is Helicobacter pylori (HP) and has been proven to cause gastritis, recurrent peptic ulcers, duodenal ulcers, and gastric cancer. We investigated the neutrophil-lymphocyte ratio (NLR) and the mean platelet volume (MPV) in the control of HP infection eradication success.&#x0D; Material and Method: Patients with HP infection in endoscopic biopsy performed due to dyspeptic complaints were included in this retrospective analysis. Quadruple antibiotic eradication therapy was given to the patients for 14 days. Pre- and post-treatment complete blood count parameters of 217 patients whose eradication treatment was successful were evaluated.&#x0D; Results: There was a statistically significant decrease in the neutrophil count after treatment compared to before treatment (p

An exploratory prospective phase II study of preoperative neoadjuvant bevacizumab and temozolomide for newly diagnosed glioblastoma

PurposeThis multi-institutional phase I/II study was conducted to confirm the safety and explore the clinical utility of preoperative Bevacizumab (Bev) for newly diagnosed glioblastoma (GB).MethodsPatients were enrolled based on magnetic resonance imaging (MRI) findings typically suggestive of GB. Preoperative Bev and temozolomide (TMZ) were administered at doses of 10 mg/kg on day 0 and 150 mg/m2 on days 1–5, respectively. Surgical resection was performed between days 21 and 30, inclusive. The safety and efficacy were evaluated in a total of 15 cases by progression-free survival (PFS), changes in tumor volume, Karnofsky Performance Scale (KPS) and Mini-Mental State Examination (MMSE) scores after preoperative therapy.ResultsTumor resection was performed on a mean of day 23.7. Pathological diagnosis was GB, isocitrate dehydrogenase (IDH)-wildtype in 14 cases and GB, IDH-mutant in 1 case. Severe adverse events possibly related to preoperative Bev and TMZ were observed in 2 of the 15 patients, as wound infection and postoperative hematoma and thrombocytopenia. KPS and MMSE scores were significantly improved with preoperative therapy. Tumor volume was decreased in all but one case on T1-weighted imaging with contrast-enhancement (T1CE) and in all cases on fluid-attenuated inversion recovery, with mean volume decrease rates of 36.2% and 54.0%, respectively. Median PFS and overall survival were 9.5 months and 16.5 months, respectively.ConclusionPreoperative Bev and TMZ is safe as long as the instructions are followed. The strategy might be useful for GB in some patients, not only reducing tumor burden, but also improving patient KPS preoperatively.Trial Registration Number: UMIN000025579, jRCT1031180233 https://jrct.niph.go.jp/latest-detail/jRCT1031180233. Registration Date: Jan. 16, 2017

A follicular volume of >0.56 cm3 at trigger is the cutoff to predict oocyte maturity: a starting point for novel volume-based triggering criteria

ObjectiveTo determine the minimum follicular volume on the day of trigger that will correspond to a mature oocyte at egg retrieval by individualized follicular puncture and to calculate the mean follicular growth from ovulation induction to egg retrieval by SonoAVC™follicle. DesignProspective observational study of 53 women undergoing IVF, in which it was possible to identify unequivocally one or more follicles at trigger and at egg retrieval by three-dimensional ultrasound. SettingUniversity-affiliated private IVF center. PatientsThe final sample included 206 follicles from 14 oocyte donors and 39 patients. InterventionsA three-dimensional ultrasound with SonoAVC™follicle was performed at trigger and at egg retrieval. The same operator selected follicles that were easily identified on both scans and verified that they were apt to be aspirated individually. Follicles were punctured individually, recording the real aspirated volume and the maturity stage of the oocyte. Main outcome measuresThe primary outcome was the relationship between follicular volume on the day of trigger and oocyte maturity stage. The secondary outcome was the rate of follicular growth from the day of trigger to the day of oocyte retrieval as measured by SonoAVC™follicle. ResultsOn the day of trigger 206 follicles were selected. Of these, 5 could not be identified on the day of oocyte retrieval, probably due to follicular rupture (mean volume 4 cm3, range 2-7) and in 48 an oocyte was not obtained. The relationship between follicular volume and oocyte maturity was studied in 153 follicles, 125(82%) mature and 28(18%) immature. ROC curves show an area under the curve of 0.73 (95%CI:0.65-0.80, p<0.001). A follicular volume of >0.56 cm3 is the cut point with the highest Youden index having a sensitivity of 85% and a specificity of 64% to predict oocyte maturity. The mean follicular growth from trigger to egg retrieval was 26-50% in 53% of cases. ConclusionA follicular volume of >0.56 cm3 at trigger is the cut-off point with the optimal balance between sensitivity and specificity for oocyte maturity. Follicles >2-3 cm3 may undergo spontaneous rupture before egg retrieval. Given these findings, we propose new volume-based criteria for trigger: 70% of follicles >0.6 cm3 with dominant follicles between 2 and 3 cm3. These need validation by randomized controlled trials.

Spatiotemporal Distribution of Antarctic Silverfish in the Ross Sea, Antarctica

Antarctic silverfish (Pleuragramma antarcticum) play a crucial intermediary role in connecting top predators and krill in the food web of the Antarctic Ocean. Despite their crucial role, research on their abundance is lacking. In this study, we estimated the abundance of juvenile Antarctic silverfish as foundational data for predicting their abundance. The density of juvenile Antarctic silverfish was estimated using an acoustic backscattering theoretical model. The mean volume backscattering strength was used to investigate the vertical and horizontal distributions of juvenile Antarctic silverfish in the Antarctic Ross Sea. The survey area was located near Cape Hallett, Antarctica, where Antarctic krill (Euphausia superba), ice krill (E. crystallorophias), and Antarctic silverfish coexist. The survey was performed four times using the Korean Antarctic research ship, RV Araon (R/V, 7507 GT). Frame trawls were conducted to identify the length and weight of the target fish species in the survey area. Captured Antarctic silverfish captured measured 3–9 cm. The maximum target strength (TS) was −92.93 dB at 38 kHz, −86.63 dB at 120 kHz, and 85.89 dB at 200 kHz. The average TS was −100.00 dB at 38 kHz, −93.00 dB at 120 kHz, and −106.90 dB at 200 kHz. Most juvenile Antarctic silverfish were found at a depth of 100 m and were distributed closer to sea ice. Between nearshore and polynya waters, the fish demonstrated a proclivity for polynya waters.

Predesigned chimeric deep inferior epigastric perforator and inguinal lymph node flap for combined breast and lymphedema reconstruction: A comprehensive algorithmic approach

The combined use of a deep inferior epigastric perforator (DIEP) flap coupled with vascularized inguinal lymph nodes (VILNs) for simultaneous breast and lymphedema reconstruction has already been well established, and promising results have been reported. However, a standardized approach for the planning and shaping of this combined flap is still lacking. We aimed to propose a comprehensive algorithmic approach for delayed unilateral breast and lymphedema reconstruction using a predesigned abdominal flap associated with inguinal lymph node transfer. We present in detail the preoperative measurements and surgical technique of the chimeric flap, which combines a predesigned DIEP template and a preselected inguinal lymph node flap, based on the preoperative computed tomography angiography and SPEC-CT findings, respectively; four different flap types are described according to the location of the pedicles of the two flap components. Our results of a series of 34 consecutive female patients with unilateral mastectomy and arm lymphedema, who underwent this combined predesigned reconstructive procedure, are retrospectively analyzed and reported. We recorded a high survival rate of the chimeric flaps in our series, with only one case of partial ischemic loss of a DIEP skin island. In the majority of our patients, the pedicles of the combined flaps were located in opposite positions. After a mean 35-month follow-up, we recorded a 47% mean volume difference reduction of the lymphedematous compared to the unaffected arm; no donor-site lymphedema was documented. Self-evaluation questionnaires showed high patient satisfaction rates regarding breast reconstruction. This algorithmic approach provides standardized guidance for accurate design and transfer of the DIEP-VILN chimeric flap while achieving highly satisfactory outcomes for both breast and lymphedema reconstruction.

Clinical assessment of deep learning-based uncertainty maps in lung cancer segmentation.

Objective. Prior to radiation therapy planning, accurate delineation of gross tumour volume (GTVs) and organs at risk (OARs) is crucial. In the current clinical practice, tumour delineation is performed manually by radiation oncologists, which is time-consuming and prone to large inter-observer variability. With the advent of deep learning (DL) models, automated contouring has become possible, speeding up procedures and assisting clinicians. However, these tools are currently used in the clinic mostly for contouring OARs, since these systems are not reliable yet for contouring GTVs. To improve the reliability of these systems, researchers have started exploring the topic of probabilistic neural networks. However, there is still limited knowledge of the practical implementation of such networks in real clinical settings.Approach. In this work, we developed a 3D probabilistic system that generates DL-based uncertainty maps for lung cancer CT segmentations. We employed the Monte Carlo (MC) dropout technique to generate probabilistic and uncertainty maps, while the model calibration was evaluated by using reliability diagrams. A clinical validation was conducted in collaboration with a radiation oncologist to qualitatively assess the value of the uncertainty estimates. We also proposed two novel metrics, namely mean uncertainty (MU) and relative uncertainty volume (RUV), as potential indicators for clinicians to assess the need for independent visual checks of the DL-based segmentation. Main results. Our study showed that uncertainty mapping effectively identified cases of under or over-contouring. Although the overconfidence of the model, a strong correlation was observed between the clinical opinion and MU metric. Moreover, both MU and RUV revealed high AUC values in discretising between low and high uncertainty cases.Significance. Our study is one of the first attempts to clinically validate uncertainty estimates in DL-based contouring. The two proposed metrics exhibited promising potential as indicators for clinicians to independently assess the quality of tumour delineation.

Volumetric and geometric changes in the parotid glands and target volume during image-guided radiotherapy for locally advanced oropharyngeal cancers.

This study aimed to evaluate the volumetric and geometric changes in the parotid glands and target volume during image-guided radiotherapy (IGRT) for locally advanced oropharyngeal cancers. Twenty patients receiving radiotherapy using IGRT at a dose of 70 Gy/35 fractions/7 weeks for locally advanced oropharyngeal cancers were accrued. Radiotherapy planning computed tomography (CT) scans were performed at pre-radiotherapy (RT), 20, 40, and 60 Gy for each patient. Volume changes in target and parotids along with shifts of parotids were assessed with respect to pre-RT scan after co-registration. In study scans, GTVp and GTVn were recontoured as per particular CT. CTV and PTV were copied from planning CT to study CT. CTV was edited from anatomical barriers, and PTV was edited only from the skin in the study CT. The parotids were recontoured on each study scan. The center of mass (COM) of C2 vertebral body was considered as the reference to evaluate its shifts. There was a statistically significant percentage regression of ipsilateral and contralateral parotid mean volumes at the rate of 0.85%/0.207 cc and 0.98%/0.26 cc per day, respectively. We observed the mean medial shift of center of mass of ipsilateral parotid of 2.23 mm (p = 0.011) and contralateral parotid of 2.67 mm (p = 0.069) at the end of 60 Gy. GTVp (mean) reduced from 41.87 cc at 0 Gy to 31.13 cc (25.65%) at 60 Gy (p = 0.003), while GTVn (mean) reduced from 19.98 cc at 0 Gy to 10.79 cc (45.99%) at 60 Gy (p = 0.003). There was a statistically significant reduction in CTV and PTV volumes at 60 Gy. Statistically significant volumetric and geometric changes occurred during intensity-modulated radiation (IMRT), which were most prominent after 40 Gy and were maximum at 60 Gy. There was a medial shift of parotid glands toward the high-dose region. This study can be useful to devise an adaptive radiotherapy strategy.

Effect of sitravatinib combined with PD-1 blockade on cytotoxic T-cell infiltration by M2 to M1 tumor macrophage repolarization in esophageal adenocarcinoma.

383 Background: Esophageal adenocarcinoma (EAC) is a deadly cancer with a low survival rate and limited treatment options. Receptor tyrosine kinase inhibitor, sitravatinib, selectively targets tumor associated macrophage (TAM) family receptors, AXL, TYRO3 and MERTK, and split family receptors, VEGFR, PDGFR, KIT and MET. In solid tumors, sitravatinib has been shown to potentiate PD-1 blockade by production of pro-inflammatory cytokines and reducing MDSCs, Tregs and TAMs, in the tumor microenvironment (TME). Methods: End-to-side esophagojejunostomy was performed on a cohort of 96 rats to induce gastroesophageal reflux, leading to EAC carcinogenesis. At 32 weeks post-operative, all surviving animals underwent endoscopic examination with biopsy and a pre-treatment MRI. All tumor bearing animals were randomized to a dose of 10mg/kg of sitravatinib (S) or vehicle control (VC) for three cycles, and PD-1 inhibitor, AUNP-12 (IO), was administered on day 12 of each 14 day cycle, at a dose of 3mg/kg. At 38 weeks post-operative, animals received a post-treatment MRI and were euthanized. Safety and efficacy were evaluated by on-treatment mortality, pre- and post-treatment MRI, immunohistochemistry, immunofluorescence and real-time PCR. Results: The S+/-IO groups demonstrated a higher on-treatment mortality when compared to the VC+/-IO groups (p=&lt;0.001). Pre- to post-treatment, mean MRI tumor volume decreased by 32% and 73% in the S-IO and S+IO animals and increased by 90% and 160% in the VC+IO and VC-IO animals, respectively (p=&lt;0.001). Increased apoptosis and decreased proliferation were confirmed through Cas-3 and Ki-67 immunohistochemistry, respectively, in both S treatment groups (p=&lt;0.001). CD8+ T-cell infiltration was upregulated, and M2 to M1 macrophage phenotype repolarization was demonstrated in all treatment groups by immunofluorescence (p&lt;0.01). Downstream gene expression demonstrated upregulation of pro-inflammatory cytokines including TNF-α, IFN-γ, IL-1β, IL-6, IL-12 and downregulation of anti-inflammatory cytokines including TGF-β, IL-4, IL-10, and IL-13 in S treatment groups compared to VC treatment groups (p&lt;0.05). There was no significant difference in pre-treatment PD-L1 levels between any of the treatment groups (p=0.09). Pre- to post-treatment qRT-PCR demonstrated significant inhibition of pathway genes AXL, AKT, MERTK and PI3K in the treatment animals (p=&lt;0.001). Additionally, pre-treatment AXL and PD-L1 levels were significantly higher in major responders (&gt;80% tumor reduction) when compared to the non-responders (&lt;25% tumor reduction or progression), in the combined S+/-IO groups (p&lt;0.05). Conclusions: This study establishes a favorable combinational strategy using sitravatinib to overcome immunosuppression in the TME, providing strong rationale for future clinical strategies in the treatment of EAC.

Lateral-type posterior fossa ependymomas in pediatric population

BackgroundLateral-type posterior fossa ependymomas are a well-defined subtype of tumours both clinically and pathologically, with a poor prognosis. Their incidence is low and surgical management is challenging. The objective of the present work is to review our series of lateral-tye posterior fossa ependymomas and compare our results with those of previous series. MethodsAmong 30 cases of ependymoma operated in our paediatric department in the last ten years, we identified seven cases of lateral-type posterior fossa ependymomas. We then performed a retrospective, descriptive study. ResultsMean age of our patients was 3.75 years. 6 cases presented with hydrocephalus. Mean tumour volume at diagnosis was 61 cc. A complete resection was achieved in six cases and a near-total resection in one patient. 5 patients transiently required a gastrostomy and a tracheostomy. Mean follow-up was 58 months. One case progressed along this period and eventually died. 4 cases of hydrocephalus required a ventriculoperitoneal CSF shunt and two were managed with a third ventriculostomy. At last follow-up 4 patients carried a normal life and two displayed a mild restriction according to Lansky´s scale. ConclusionsThe aim of surgical treatment in lateral-type posterior fossa ependymomas is complete resection. Neurological deficits associated to lower cranial nerve dysfunction are common but transient. Deeper genetic characterization of these tumours may identify risk factors that guide stratification of adjuvant therapies.

Comparison of the efficacy and safety of ultrasound-guided radiofrequency ablation and microwave ablation for the treatment of unifocal papillary thyroid microcarcinoma: a retrospective study

Purpose This study aimed to compare the efficacy and safety of ultrasound-guided RFA and MWA in the treatment of unifocal PTMC. Methods This retrospective study included 512 patients with 512 unifocal papillary thyroid microcarcinomas (PTMCs) who underwent RFA (n = 346) and MWA (n = 166) between January 2021 and December 2021. The volumes of the ablation areas were measured during follow-up, and the volume reduction rates were evaluated. The ablation duration, volume of hydrodissection, and ablation-related complications were also compared between the groups. Results All lesions received complete ablation and no local or distant recurrences were observed in the two groups. A larger volume of isolation liquid was used for RFA than for MWA (p = 0.000). Hoarseness occurred in seven patients who underwent RFA (p = 0.102). At the 1-week follow-up, the mean volume of the areas ablated by RFA was smaller than that of the areas ablated by MWA (p = 0.049). During follow-ups at months 3, 9, 12, 15, and 18, the mean volumes of the ablated areas were larger in the RFA group than in the MWA group (all, p < 0.05). The mean volume of the ablated lesions increased slightly at the 1-week follow-up and then decreased at 1 month after ablation in both groups. The absorption curve of the ablated lesions in the RFA group was similar to that in the MWA group. Conclusions RFA and MWA are both efficient and safe methods for treating unifocal PTMC. They may be alternative techniques for patients who are not eligible or are unwilling to undergo surgery.

Intracystic injection of large surface area microparticle paclitaxel for chemoablation of intraductal papillary mucinous neoplasms: Insights from an expanded access protocol

AimsA novel large surface area microparticle paclitaxel (LSAM-PTX) has unique properties of long retention in cystic spaces while maintaining high drug concentration. We prospectively evaluated the safety and response of EUS-guided fine needle injection (EUS-FNI) of LSAM-PTX to chemoablate branch duct (BD)-IPMNs. MethodsSubjects diagnosed with BD-IPMNs exhibiting at least one worrisome criteria and considered non-surgical were enrolled in a multicenter clinical trial (NCT03188991) and subsequently included in an Expanded Access Protocol (EAP) where they received EUS-FNI of LSAM-PTX (15 mg/mL). ResultsSix BD-IPMNs measuring (mean ± SD) 3.18 ± 0.76 cm in diameter among 5 subjects (mean age: 66 years) were treated by EUS-FNI of LSAM-PTX. A mean of 4 doses of LSAM-PTX (mean dose/cyst: 73 ± 31 mg) were administered, and subjects were followed for up to 32 months. The mean volume reduction/cyst ranged from 42 to 89% (9.58 ± 5.1 ml to 2.2 ± 1.1 ml (p = 0.016)). The mean surface area reduction ranged from 31 to 83% (21.9 ± 8.7 cm2 to 5.7 ± 2.5 cm2 (p = 0.009)). Higher dosing-frequency of EUS-FNI of LSAM-PTX significantly correlated with a reduction in cyst volume (R2 = 0.87, p = 0.03) and surface area (R2 = 0.83, p = 0.04). Comparing pre- and post-ablation samples, molecular analysis of the cyst fluid revealed a loss of IPMN-associated mutations in 5 cases (83.3%), while reemergence was observed in 1 case and persistence in 1 case. Intracystic changes (fibrosis/calcification) were observed in 83.3% (n = 5). One subject developed mild acute pancreatitis (1 of 22 EUS-FNIs of LSAM-PTX). ConclusionIn this EAP, EUS-FNI of LSAM-PTX into BD-IPMNs was safe and resulted in volume and surface area reduction, morphological changes, and loss of pathogenic mutations.

A microcomputed tomography analysis of adaptation in premolars with flared root canals restored with different digitally custom fabricated post materials

Statement of problemPreserving and strengthening the remaining tooth structure of compromised flared root canals after endodontic treatment is challenging. PurposeThe purpose of this in vitro study was to compare the adaptation of milled polymer- infiltrated ceramic, fiber-reinforced composite resin, and high-performance semicrystalline thermoplastic resin posts as used to restore mandibular premolars with flared root canals. Material and methodsForty sound mandibular premolars were randomly divided into 4 groups: custom Vita Enamic (CV), custom fiber-reinforced composite resin (CF), custom polyetherketoneketone (CP), and prefabricated fiber (RF) posts. After endodontic treatment, each tooth was sectioned 1.5 mm occlusal to the cementoenamel junction. Then, the post space was prepared and flared, except the RF group, to a depth of 9 mm. The post space in RF group was prepared with a post drill. For the CV, CF, and CP groups, the posts were milled, finished, and cemented to their corresponding teeth. Each tooth was scanned using a microcomputed tomography device, and the reconstructed images were analyzed in mesiodistal, buccolingual, and horizontal planes. The cement thickness, cement volume, and volume of voids were measured. The data were analyzed using 3-way ANOVA (cement thickness) and 2-way ANOVA (cement volume and voids volume) tests followed by the post hoc Tukey test (α=.05). ResultsThe 3-way ANOVA test revealed a significant interaction (P<.001) between material type, section, and surface on the cement thickness. The mean cement thickness in the RF group was significantly higher than in the CV group (P=.001) and CF group (P=.005). The least mean cement thickness was at the apical section followed by the cervical and middle sections. Regarding cement volume, the 2-way ANOVA test showed statistically significant interaction between material type and section. The mean cement volume in the RF group was significantly lower than in the CV group (P=.001), CF group (P=.001), and CP group (P=.001). The highest mean cement volume was in the cervical section followed by the middle and apical sections. The 2-way ANOVA test showed statistically significant interaction (P<.001) between material type and section on the volume of voids. Significant differences were found between the mean volume of voids at the cervical and middle sections (P=.001) and the cervical and apical sections (P=.002). ConclusionsCompared with prefabricated fiber posts, digitally fabricated polymer-infiltrated ceramic and fiber-reinforced composite resin posts had a thinner cement layer with minimal thickness at the apical section. The digitally fabricated posts had higher cement volume, especially at the cervical section, than prefabricated fiber posts. High volumes of voids were related to the cervical section of all tested posts.