Contrast enhanced ultrasound versus MRI for response assessment of extra-abdominal desmoid Fibromatosis- A feasibility study.

Objective To evaluate the contrast-enhanced ultrasound (CEUS) features and related biological behaviors of endometrial cancer (EC) . Methods Eighty patients with EC confirmed by surgical pathology between January 2017 and December 2018 in our hospital were enrolled as the EC group. A contemporary cohort of 80 non-EC patients were recruited as the control group. All patients underwent CEUS examination. The CEUS features, the mean transit time (MTT) , peak intensity (Peak) , and time to peak (TTP) of the contrast agent in the region of interest during the CEUS examination were compared between groups. The CEUS features of EC at different stages, consistency between CEUS-identified myometrial invasion and pathological findings, expression of proliferating apoptotic proteins (Beclin1, Bax, Survivin, Bcl-2, CDK4, and CDK6) were examined. The correlation between MTT, Peak, TTP and proliferating apoptotic proteins was analyzed. Results The CEUS in EC group was mainly of fast filling pattern, with shorter filling time and quicker regression in the lesions compared with the surrounding muscle wall, showing hyperenhancement in most of cases. The CEUS in the control group was mainly of eccentric filling pattern, with longer filling time but earlier or similar regression in the lesions compared with the surrounding muscle wall, showing hypo-or isoenhencement in most of cases. The EC group presented more MTT and Peak but less TTP compared with the control group (P<0.05) . Features of EC identified on CEUS were: (1) 41 cases of stage Ⅰa, showing uneven, moderate enhancement or hyperenhancement (n=27) , and isoenhancement or uneven, hypoenhancement (n=14) of endometrium. The contrast agent appeared earlier in endometrium than in the myometrium. The EC lesions presented disrupted and thickened vessels inside and invaded <50% of the muscle layer with a clear boundary with the latter. The muscle layer was evenly enhanced, showing short rod-like, patchy blood flow signals. (2) 30 cases of stage Ⅰb, showing moderate or hyperenhancement of the endometrium, invading ≥50% of the muscle layer with blurred demarcation. The muslce layer showed uneven hyperenhancement, with thickened and tortuous blood vessels, and earlier regression of the contrast agent compared with adjacent unaffected muscle tissue and normal endometrium. (3) 9 case of stage Ⅱ, showing fast filling of contrast agent in the supplying blood vessels, rapid moderate or hyperenhancement of the cervix and endometrial lesion. The time to enhancement and regression was shorter for the EC-affected muscle layer, endometrium and cervis compared with adjacent normal muscle or the endometrium. Using pathological findings as the gold standard, the accuracy of CEUS in diagnosing stages Ⅰa, Ⅰb, ⅡEC was 94.12%, 75.68%, and 77.78%, respectively. For the consistency with pathology, the Kappa index of CEUS was 0.727 (P<0.001, 95% CI 0.557~0.898) ; EC group showed lower levels of Beclin1 and Bax, and higher levels of Survivin, Bcl-2, CDK4, and CDK6, compared with the control group (P<0.05) . The levels of Beclin1 and Bax were negatively correlated with MTT and Peak, and positively correlated with TTP (P<0.05) . The levels of Survivin, Bcl-2, CDK4 and CDK6 were positively correlated with MMT and Peak, and negatively correlated with TTP (P<0.05) . Conclusion On CEUS, EC patients may show filling patterns, filling time, enhancement intensity and regression pattern of contrast agents that are different from as found for normal individuals. In these patients, CEUS features combined with the tumor biological behavior of myometrial invasion may help identify different clinical stages with good consistency with clinical pathology. MTT, Peak, and TTP may be useful to reflect the expression of cell proliferation and apoptosis proteins, and thereby offer clues for evaluation of the disease. Key words: Biological behavior; CEUS; Endometrial cancer; Signs; Consistency

Determination of rat cerebral cortical blood volume changes by capillary mean transit time analysis during hypoxia, hypercapnia and hyperventilation

We read with great interest the article by Mir and colleagues that evaluated the efficacy and safety of oral vinorelbine in patients with advanced desmoid fibromatosis (ref. 1). However, we believe that there may yet be some questions left unanswered.A flat dose of vinorelbine lower than the dose routinely used in other solid tumors was chosen to balance the efficacy of drug use against toxic side effects (2). The authors demonstrated that if the tumor-related pain did not remit in the therapeutic period, treatment prolongation until symptomatic improvement was considered. While the authors did not describe the time to best response in each patient, rendering it challenging to evaluate the optimal duration of vinorelbine administration. For the patients who were initially stable on oral vinorelbine but had tumor growth after discontinuation, reinstitution of vinorelbine was again effective to control disease progression, indicating these patients benefited from the prolongated treatment duration. Thus, the appropriate duration of oral vinorelbine for patients with progressive desmoid fibromatosis warrants further elaboration. In addition, the authors did not describe whether the patients with progressive disease under the treatment of a dose of 90 mg would obtain disease stabilization by escalating the dosage to a standard dose of 60–80 mg/m2, although it might be accompanied by more adverse events.Second, the use of RECIST-defined responses to define outcomes among patients with solid tumors remains controversial. Although Mir and colleagues mentioned the potential limitations of RECIST, the interpretation of their results merits further discussion. Assessment of treatment response to systemic therapy for desmoid fibromatosis relying on unidimensional measurement may underestimate patient benefit (3). Because of its unique histologic components, desmoid fibromatosis exhibiting a biologic response to systemic treatment may not shrink (4). Collagenization usually indicates maturation and biological quiescence, presenting a low T2-weighted signal on MRI. In contrast, high T2-weighted signal intensity denotes more aggressive behavior. Thus, the T2-weighted signal intensity can early reflect the biological response of desmoid fibromatosis to systemic therapy. The authors described that the decreased imaging density was observed in several patients who initially achieved stable disease but subsequently experienced partial response during the follow-up. Presumably, these patients had partial response under vinorelbine treatment using the criterion of T2 signal intensity change. More recently, the Choi criteria and revised Choi criteria were shown to be more strongly associated with progression-free survival of patients with desmoid fibromatosis than RECIST 1.1 (5). At the same time, quantitatively analyzing the early change in intralesional heterogeneity through a radiomics score for desmoid fibromatosis under chemotherapy could improve the prediction of dimensional progression (5). However, the use of T2 signal intensity change to assess early response to systemic treatment in desmoid fibromatosis requires further investigation.We commend the authors for their work, and expect that exploration of the issues mentioned above could provide more information to help manage advanced desmoid fibromatosis, and emphasize the necessity for a consistent radiological standard to evaluate the treatment response of desmoid fibromatosis to systemic therapy.No disclosures were reported by the authors.See the Response, p. 2120This work was supported by the National Natural Science Foundation of China (grant nos. 81702664 and 81801852) and the National Key Research and Development Program of China (grant nos. 2016YFC1102003 and 2017YFB0702604).

Desmoid fibromatosis is a rare tumor of locally aggressive nature and associated with a high risk of recurrence. Although it possesses benign morphologies such as the absence of necrosis and atypical mitoses, it is classified as an intermediate malignant neoplasm due to its potential of infiltrating into the adjacent structures and the high rate of local recurrence even after excision. A 22-year-old unmarried female came with the complaint of abdominal pain and lump. The preoperative diagnosis was in favor of ovarian leiomyosarcoma but to the surprise intraoperative, tumor was found to be arising from mesentery of ileum. Following the complete resection, tumor was sent for histopathology. The histopathology examination report along with immunohistochemistry was suggestive of desmoids fibromatosis. Mesenteric desmoids fibromatosis is a rare tumor. It should be differentiated from gastrointestinal stromal tumor, leiomyoma, leiomyosarcoma, neurofibroma, and solitary fibrous tumor because of its completely different management and outcome. Histopathology and immunohistochemistry is the key for its diagnosis.

Gray-scale Contrast-enhanced Ultrasonography for Quantitative Evaluation of the Blood Perfusion of the Sciatic Nerves with Crush Injury

11513 Background: Desmoid fibromatosis (DF) often occurs during pregnancy/peripartum. Guidance for planning new pregnancies during active surveillance or following DF resection has been limited. Thus, we sought to evaluate outcomes and decision making in the peripartum. Methods: Women of child-bearing age with DF diagnosed between 2000 and 2020 were interviewed about procreation decisions, in a multicenter retrospective observational study (NCT05284305). Pregnancies simultaneous or after diagnosis were analyzed. Primary outcome was DF progression/recurrence within 1 yr postpartum. Secondary outcomes were spontaneous regression, switch to active treatment, and obstetric risks. To estimate probability of progression, a random intercept logistic model was fit to account for correlation of progression in multiple pregnancies in the same patient. Results: Of 483 pts interviewed, 120 (24.8%) postponed, 32 (6.6%) interrupted, and/or 232 (48%) avoided pregnancy (in 93.3%, 50%, and 72.9% of cases because of DF), respectively. 147 pregnancies in 131 pts were concurrent with or after diagnosis: 26 (17.7%, Group A) concurrent with diagnosis, 48 (32.7%, B) after DF resection, and 73 (49.7%, C) with DF on surveillance. Estimated probability of progression was 12.0% (CI 2.0 – 48.4) during pregnancy and 15.8% (5.6 – 37.5) postpartum; for pregnancies after diagnosis (Groups B and C), these rates were 5.1% (0.4 – 40.0) and 9.0% (1.8 – 35.0). On multivariate analysis, age at pregnancy and size of primary DF were significant risk factors for progression (Table). Estimated probability of spontaneous regression was 3.6% (CI 0.2-40.7) during pregnancy and 7.1% (CI 0.3 – 67.2) postpartum. 7/38 (18.4%) spontaneously regressed after pregnancy-related PD, 4/23 (17.4%) in Groups B and C. Treatment for progression was needed in 9/79 (11.4%) postpartum, in 4/63 (6.3%) in Groups B and C. Obstetric complications were comparable to population data in developed countries. Conclusions: After DF diagnosis, pregnancy is safe with a risk of progression of 5% during pregnancy and 9% postpartum. Treatment is needed in only 6%. Spontaneous regression is less common but occurs even after initial progression. Patients decision making about procreation appeared to be influenced by their DF diagnosis. This study supports counseling that fertility options should be fully explored with expert guidance as intervention rates are low. [Table: see text]

The thermodilution curve assessed by transpulmonary thermodilution is the basis for calculation of global end-diastolic volume index (GEDI) and extravascular lung water index (EVLWI). Until now, it was unclear whether the method is affected by 1-lung ventilation. Therefore, aim of our study was to evaluate the impact of 1-lung ventilation on the thermodilution curve and assessment of GEDI and EVLWI. In 23 pigs, mean transit time, down slope time, and difference in blood temperature (ΔTb) were assessed by transpulmonary thermodilution. "Gold standard" cardiac output was measured by pulmonary artery flowprobe (PAFP) and used for GEDIPAFP and EVLWIPAFP calculations. Measurements were performed during normovolemia during double-lung ventilation (M1), 15 minutes after 1-lung ventilation (M2) and during hypovolemia (blood withdrawal 20 mL/kg) during double-lung ventilation (M3) and again 15 minutes after 1-lung ventilation (M4). Configuration of the thermodilution curve was significantly affected by 1-lung ventilation demonstrated by an increase in ΔTb and a decrease in mean transit time and down slope time (all P < 0.04) during normovolemia and hypovolemia. GEDIPAFP was lower after 1-lung ventilation during normovolemia (M1: 459.9 ± 67.5 mL/m(2); M2: 397.0 ± 54.8 mL/m(2); P = 0.001) and hypovolemia (M3: 300.6 ± 40.9 mL/m(2); M4: 275.2 ± 37.6 mL/m(2); P = 0.03). EVLWIPAFP also decreased after 1-lung ventilation in normovolemia (M1: 9.0 [7.3, 10.1] mL/kg; M2: 7.4 [5.8, 8.3] mL/kg; P = 0.01) and hypovolemia (M3: 7.4 [6.3, 9.7] mL/kg; M4: 5.8 [5.2, 7.4]) mL/kg; P = 0.0009). Configuration of the thermodilution curve and therefore assessment of GEDI and EVLWI are significantly affected by 1-lung ventilation.

Quantification of flow rates using harmonic grey-scale imaging and an ultrasound contrast agent: an in vitro and in vivo study

PurposeInvestigate the involvement of vascular endothelial growth factor receptor 1 (VEGFR1) in vasculogenic mimicry (VM) formation in ocular melanoma, as well as whether or not VEGFR1-targeted contrast-enhanced ultrasound (CEUS) can evaluate and quantify VM perfusion and function in the ocular melanoma model.MethodsThe expression of VEGFR1 was examined using immunofluorescence, western blot, and quantitative polymerase chain reaction. VM networks were analyzed with tube formation and periodic acid Schiff staining. Targeted microbubbles (MBs) were constructed and used for targeted CEUS imaging in vivo. Comparisons were made in perfusion parameters of tumors between targeted and non-targeted CEUS imaging.ResultsVEGFR1 was highly expressed, and knockdown of VEGFR1 significantly decreased VM protein expression and disrupted VM formation in MUM-2B melanoma. VEGFR1-targeted MBs specifically bind to MUM-2B cell surfaces. CEUS with VEGFR1-targeted MBs showed significant imaging enhancement throughout the entire perfusion phase compared with CEUS with IgG MBs. VEGFR1-targeted imaging was able to detect a decrease in maximum intensity and mean transit time in VEGFR1 knockdown melanoma compared with control melanoma. The pathological VM patterns were consistent with VEGFR1-targeted CEUS findings.ConclusionsVEGFR1 was responsible for VM network formation and was required for efficient choroidal melanoma tumor growth. This study shows that VEGFR1-targeted CEUS can track VM levels in animal models of ocular melanoma at morphological levels in vivo. This experiment is noninvasive and reproducible and indicates the possibility of real-time in vivo imaging technology for VM evaluation.Translational RelevanceBased on our study results, VEGFR1 could prove to be a promising treatment that targets VM formation in choroidal melanoma. Our findings also suggest the potential use of VEGFR1-targeted CEUS for quantitative monitoring of VM processes at the molecular level in the future.

Background: Desmoid fibromatosis (DF) is a rare, locally aggressive soft tissue tumour with unpredictable clinical behaviour. Historically, treatment has involved surgery; however, contemporary guidelines, such as those from the Desmoid Tumour Working Group, advocate active surveillance. This article reviews current perspectives on DF, focusing on epidemiology, pathogenesis, treatment strategies, emerging research directions and cost effectiveness based on our experience at the West of Scotland Musculoskeletal Oncology Service, Glasgow Royal Infirmary (GRI). Methodology: We reviewed 101 patients diagnosed with desmoid fibromatosis between 2010 and 2024. A review of patient records was conducted to gather information on demographics, date of diagnosis, prior treatment, treatment initiation, intervention types, imaging intervals, follow-up duration, recurrence rate for surgery and other intervention, and discharge timelines. All data was systematically organized and analyzed to assess our outcomes. Results: Out of 101 patients with DF in the study, 66% were females. The most common site of primary tumour was lower extremity (39.6%) followed by near equal distribution in upper extremity and trunk. Out of the total cases, 72 (71.2%) were successfully managed with active surveillance involving serial imaging and clinical reviews in accordance with European guidelines. A total of 22 patients (21%) received treatment: 10 underwent surgery alone, 2 had surgery combined with radiotherapy, 8 received only radiotherapy, 1 was treated with hormonal therapy and 1 participated in a trial with Nirogacestat. Of the seven remaining patients, six had unplanned surgery outside followed by active surveillance at GRI. One patient was on alternative treatment modality, homeopathy. The average number of MRI scans per patient was 3.11, with many patients requiring significantly more imaging. MRI surveillance varies significantly in desmoid tumours due to their heterogeneous behaviour. Active or symptomatic tumours often require more frequent scans (every 3–6 months), while stable cases may need only imaging annually or just clinical monitoring. Recurrence was noted in eight patients, all of which were related to prior surgery. The total combined cost of imaging and appointments exceeds £6500 per patient in active surveillance. Conclusions: We conclude that most patients with desmoid fibromatosis in our cohort were effectively treated with active surveillance, consistent with current European guidelines. Surgical management of desmoid fibromatosis in our cohort is historic and has shown a significant recurrence risk. Our study proposes a revised follow-up protocol that significantly reduces costs without compromising on patient care. We suggest a two-year surveillance period for stable disease with patient-initiated return to reduce unnecessary clinic visits, imaging and healthcare costs.

To evaluate the utility of gray scale harmonic ultrasonography with a microbubble contrast agent in the early assessment of the therapeutic response to radio frequency ablation for hepatocellular carcinoma. Seventy-five patients with 81 nodular hepatocellular carcinomas (1.3-4.8 cm) treated with percutaneous radio frequency ablation were evaluated with contrast-enhanced gray scale harmonic ultrasonography after intravenous bolus injection of a galactose-based microbubble contrast agent. The vascularity within the ablation zones was evaluated with a continuous scan for 3 to 5 seconds between 15 and 30 seconds after initiation of contrast agent injection. To evaluate the perfusion of the ablation zones, intermittent stimulated acoustic emission imaging was performed with a rapid sweeping technique from the end of the continuous scan. All patients underwent follow-up 3-phase helical computed tomography at 1 month after radio frequency ablation and were followed for at least 1 year. The results of contrast-enhanced ultrasonography were compared with those of follow-up computed tomography in terms of the presence or absence of residual unablated tumors. In 10 (12%) of the 81 treated hepatocellular carcinomas, contrast-enhanced ultrasonography showed either nodular or crescentic enhancing foci at the margins of ablation zones, suggesting residual unablated tumors. Contrast-enhanced computed tomography obtained 1 month after radio frequency ablation confirmed the residual unablated tumors in the same 10 lesions. Diagnostic agreement between 1-month follow-up computed tomography and contrast-enhanced ultrasonography was achieved in all 81 cases (100%). Contrast-enhanced gray scale harmonic ultrasonography can be a reliable alternative to contrast-enhanced computed tomography in the early assessment of the therapeutic response to radio frequency ablation for hepatocellular carcinoma.

Evaluation of Postoperative Acute Kidney Injury Through Contrast-Enhanced Ultrasound in Patients With Aortic Dissection: An Observational Cohort Study.

What is the best front-line approach in patients with desmoid fibromatosis? – A retrospective analysis from a reference center

Refractory ischemic symptoms in moyamoya disease are a challenging problem, particularly in situations in which multiple direct and indirect revascularization techniques have already been employed. In addition, revascularization of the parietal lobes is difficult, as this area is a watershed between the middle cerebral artery and posterior cerebral artery distributions. This is the case of a 50-yr-old woman with hemibody sensorimotor deficits, who had previously undergone bilateral arterial bypass and temporalis myosynangiosis. A method for indirect surgical cerebral revascularization is described, utilizing a rotated and tunneled sternocleidomastoid flap. The perfused muscle is approximated to the cortical surface, with adjacent sulci dissected to expose the underlying vasculature. After sternocleidomastoid encephalomyosynangiosis, the patient experienced symptomatic improvement, along with the appearance of new pial collateral vasculature on diagnostic cerebral angiography. Pre- and postoperative dynamic perfusion computed tomography with acetazolamide challenge demonstrate an increase in cerebral blood flow and decrease in mean transit time, as well as improved cerebrovascular reserve. Sternocleidomastoid encephalomyosynangiosis using a tunneled muscle flap is a useful method for revascularization of the parietal and occipital lobes, particularly for refractory moyamoya in cases where a variety of other options have been exhausted.

Hyperpolarized carbon-13 magnetic resonance imaging is a promising technique for in vivo metabolic interrogation of alterations between health and disease. This study introduces a formalism for quantifying the metabolic information in hyperpolarized imaging. This study investigated a novel perfusion formalism and metabolic clearance rate (MCR) model in pre-clinical stroke and in the healthy human brain. Simulations showed that the proposed model was robust to perturbations in T1, transmit B1, and kPL. A significant difference in ipsilateral vs contralateral pyruvate derived cerebral blood flow (CBF) was detected in rats (140 ± 2 vs 89 ± 6 mL/100 g/min, p < 0.01, respectively) and pigs (139 ± 12 vs 95 ± 5 mL/100 g/min, p = 0.04, respectively), along with an increase in fractional metabolism (26 ± 5 vs 4 ± 2%, p < 0.01, respectively) in the rodent brain. In addition, a significant increase in ipsilateral vs contralateral MCR (0.034 ± 0.007 vs 0.017 ± 0.02/s, p = 0.03, respectively) and a decrease in mean transit time (31 ± 8 vs 60 ± 2 s, p = 0.04, respectively) was observed in the porcine brain. In conclusion, MCR mapping is a simple and robust approach to the post-processing of hyperpolarized magnetic resonance imaging.