Interventional oncological treatment of breast cancer liver metastasis (BCLM): single center long-term evaluation over 26 years using thermoablation techniques like LITT, MWA and TACE in a multimodal application.

The purpose of the study is to retrospectively evaluate the development and technological progress in local oncological treatments of patients with breast cancer liver metastasis (BCLM) using LITT (laser interstitial thermotherapy), MWA (microwave ablation) and TACE (transarterial chemoembolization) ablation techniques in a multimodal application. The study uses data generated between 1993 and 2020. Therapy results were evaluated using the Kaplan-Meier survival estimate, Cox proportional hazard regression and log-rank test. Cox regression analysis showed that the different treatment methods are statistically significant predictors of survival of patients. Median survival times for groups treated with LITT (212 patients) and LITT + TACE (215 patients) were 2.2 years and 2.1 years respectively; median survival times for groups treated with MWA (17 patients) and MWA + TACE (143 patients) were 5.6 and 2.4 years respectively. For LITT only treatments, the 1-, 3- and 5-year survival probability scored 80%, 37%, 22%. Results for combined LITT + TACE treatments were 76%, 34% and 15%. In group MWA, the 1-/3-/5-year survival probability rates were calculated as 89%, 89%, 89% (however, they should be interpreted carefully due to a relatively small sample size of n = 17 patients). Group MWA + TACE offered values of 77%, 38% and 22%. A separate group of 549 patients was analyzed with TACE monotherapy treatment. The estimated median survival time in this group was 0.8 years. The 1-/3-/5-year survival probability rates were 37%, 8% and 4%. Treatments with combined MWA and MWA + TACE resulted in the best median survival time estimations in this study.

Health innovations in response to the COVID-19 pandemic: perspectives from the Eastern Mediterranean Region.

BACKGROUND: This paper aims to document the numerous health innovations developed in response to the COVID-19 crisis in the Eastern Mediterranean Region (EMR) using a scoping review approach. METHODS: A literature search was conducted using PubMed, the Eastern Mediterranean Health Journal, the Index Medicus for EMR to identify peer-reviewed articles between December 2019 and November 2020 and WHO and ministries of health websites for grey literature. Following an initial review, full-text screening identified studies reporting on health innovations in response to the COVID-19 pandemic in the region. RESULTS: This review describes 82 health innovations reported from 20 countries across the region: 80% (n = 66) were digital and technology-based products and services including health care delivery (n = 25), public health informatics (n = 24) and prevention (n = 17); 20% (n = 16) were innovative processes including health care delivery (n = 8), educational programmes (n = 6) and community engagement (n = 2). CONCLUSION: The speed with which these technologies were deployed in different contexts demonstrates their ease of adoption and manageability and thus can be considered as the most scalable. Strengthened frameworks to protect users' privacy, documentation and evaluation of impact of innovations, and training of health care professionals are fundamental for promoting health innovations in the EMR.

Feasibility of diffusion-weighted magnetic resonance imaging in evaluation of early therapeutic response after CT-guided microwave ablation of inoperable lung neoplasms.

OBJECTIVE: To determine the early treatment response after microwave ablation (MWA) of inoperable lung neoplasms using the apparent diffusion coefficient (ADC) value calculated 24 h after the ablation. MATERIALS AND METHODS: This retrospective study included 47 patients with 68 lung lesions, who underwent percutaneous MWA from January 2008 to December 2017. Evaluation of the lesions was done using MRI including DWI sequence with ADC value calculation pre-ablation and 24 h post-ablation. DWI-MR was performed with b values (50, 400, 800 mm2/s). The post-ablation follow-up was performed using chest CT and/or MRI within 24 h following the procedure; after 3, 6, 9, and 12 months; and every 6 months onwards to determine the local tumor response. The post-ablation ADC value changes were compared to the end response of the lesions. RESULTS: Forty-seven patients (mean age: 63.8 ± 14.2 years, 25 women) with 68 lesions having a mean tumor size of 1.5 ± 0.9 cm (range: 0.7-5 cm) were evaluated. Sixty-one lesions (89.7%) showed a complete treatment response, and the remaining 7 lesions (10.3%) showed a local progression (residual activity). There was a statistically significant difference regarding the ADC value measured 24 h after the ablation between the responding (1.7 ± 0.3 × 10-3 mm2/s) and non-responding groups (1.4 ± 0.3 × 10-3 mm2/s) with significantly higher values in the responding group (p = 0.001). A suggested ADC cut-off value of 1.42 could be used as a reference point for the post-ablation response prediction (sensitivity: 66.67%, specificity: 84.21%, PPV: 66.7%, and NPV: 84.2%). No significant difference was reported regarding the ADC value performed before the ablation as a factor for the prognosis of treatment response (p = 0.86). CONCLUSION: ADC value assessment following ablation may allow the early prediction of treatment efficacy after MWA of inoperable lung neoplasms. KEY POINTS: • ADC value calculated 24 h post-treatment may allow the early prediction of MWA efficacy as a treatment of pulmonary tumors and can be used in the early immediate post-ablation imaging follow-up. • The pre-treatment ADC value of lung neoplasms is not different between the responding and non-responding tumors.

Postoperative radiological assessment of the mastoid facial canal in cochlear implant patients in correlation with facial nerve stimulation.

OBJECTIVES: To correlate the radiological assessment of the mastoid facial canal in postoperative cochlear implant (CI) cone-beam CT (CBCT) and other possible contributing clinical or implant-related factors with postoperative facial nerve stimulation (FNS) occurrence. METHODS: Two experienced radiologists evaluated retrospectively 215 postoperative post-CI CBCT examinations. The mastoid facial canal diameter, wall thickness, distance between the electrode cable and mastoid facial canal, and facial-chorda tympani angle were assessed. Additionally, the intracochlear position and the insertion angle and depth of electrodes were evaluated. Clinical data were analyzed for postoperative FNS within 1.5-year follow-up, CI type, onset, and causes for hearing loss such as otosclerosis, meningitis, and history of previous ear surgeries. Postoperative FNS was correlated with the measurements and clinical data using logistic regression. RESULTS: Within the study population (mean age: 56 ± 18 years), ten patients presented with FNS. The correlations between FNS and facial canal diameter (p = 0.09), wall thickness (p = 0.27), distance to CI cable (p = 0.44), and angle with chorda tympani (p = 0.75) were statistically non-significant. There were statistical significances for previous history of meningitis/encephalitis (p = 0.001), extracochlear-electrode-contacts (p = 0.002), scala-vestibuli position (p = 0.02), younger patients' age (p = 0.03), lateral-wall-electrode type (p = 0.04), and early/childhood onset hearing loss (p = 0.04). Histories of meningitis/encephalitis and extracochlear-electrode-contacts were included in the first two steps of the multivariate logistic regression. CONCLUSION: The mastoid-facial canal radiological assessment and the positional relationship with the CI electrode provide no predictor of postoperative FNS. Histories of meningitis/encephalitis and extracochlear-electrode-contacts are important risk factors. KEY POINTS: • Post-operative radiological assessment of the mastoid facial canal and the positional relationship with the CI electrode provide no predictor of post-cochlear implant facial nerve stimulation. • Radiological detection of extracochlear electrode contacts and the previous clinical history of meningitis/encephalitis are two important risk factors for postoperative facial nerve stimulation in cochlear implant patients. • The presence of scala vestibuli electrode insertion as well as the lateral wall electrode type, the younger patient's age, and early onset of SNHL can play important role in the prediction of post-cochlear implant facial nerve stimulation.

Long-term outcomes following percutaneous microwave ablation for colorectal cancer liver metastases.

PURPOSE: To evaluate the overall survival (OS), local progression-free survival (PFS) and prognostic factors of patients with colorectal cancer liver metastases (CRLM) undergoing microwave ablation (MWA). METHOD: A total of 132 patients were retrospectively enrolled who had been treated between 2010 and 2018. For the evaluation of survival rates, all patients were divided according to their indications (curative n = 57 and debulking (patients with additional non-target extrahepatic metastases) n = 75). In total, 257 ablations were evaluated for prognostic factors: number of liver metastases, primary tumor origin (PTO), diameter and volume of metastases, duration and energy of ablation. RESULTS: The OS was 32.1 months with 93.2% of patients free from recurrence at 28.3 months (median follow-up time). The one- year and three-year OS were 82.72% and 41.66%, respectively. The OS and recurrence-free survival of the curative group were statistically significantly higher than the debulking group (p < .001). Statistically significant prognostic factors for OS included the location of the primary tumor (p < .038) and the number of metastases (all p < .017). Metastasis diameter and volume and ablation duration and energy had no significant correlation with survival (p > .05). CONCLUSIONS: Satisfactory OS and local tumor PFS can be achieved in patients with CRLM using MWA with the number of metastases and the location of the primary tumor influencing the outcome of patients. The metastasis's size and the duration and energy used for ablation were not of significant prognostic value.

Endurance training-induced cardiac remodeling in a guinea pig athlete's heart model.

Besides the health benefits of regular exercise, high-level training-above an optimal level-may have adverse effects. In this study, we investigated the effects of long-term vigorous training and its potentially detrimental structural-functional changes in a small animal athlete's heart model. Thirty-eight 4-month-old male guinea pigs were randomized into sedentary and exercised groups. The latter underwent a 15-week-long endurance-training program. To investigate the effects of the intense long-term exercise, in vivo (echocardiography, electrocardiography), ex vivo, and in vitro (histopathology, patch-clamp) measurements were performed. Following the training protocol, the exercised animals exhibited structural left ventricular enlargement and a significantly higher degree of myocardial fibrosis. Furthermore, resting bradycardia accompanied by elevated heart rate variability occurred, representing increased parasympathetic activity in the exercised hearts. The observed prolonged QTc intervals and increased repolarization variability parameters may raise the risk of electrical instability in exercised animals. Complex arrhythmias did not occur in either group, and there were no differences between the groups in ex vivo or cellular electrophysiological experiments. Accordingly, the high parasympathetic activity may promote impaired repolarization in conscious exercised animals. The detected structural-functional changes share similarities with the human athlete's heart; therefore, this model might be useful for investigations on cardiac remodeling.

Transarterial chemoembolization of colorectal cancer liver metastasis: improved tumor response by DSM-TACE versus conventional TACE, a prospective, randomized, single-center trial.

OBJECTIVES: To prospectively evaluate the therapy response of third-line TACE with DSM or lipiodol in the treatment of CRLM using MRI. METHODS: In this prospective, randomized, single-center trial, patients were randomly assigned to receive TACE therapy with either lipiodol or DSM as the embolization agent. Therapy response was evaluated using MRI. Local tumor response was determined according to RECIST 1.1, and survival data was analyzed using the Kaplan-Meier estimator. RESULTS: Fifty patients (35 male, 15 female) were randomized and included in the survival analysis, whereas 31 patients completed therapy and were considered for evaluation of tumor responses (cTACE: n = 13, DSM-TACE: n = 18). In the cTACE group, PR was observed in 23%, SD in 15%, and PD in 62%. In the DSM-TACE-group, PR was observed in 22% of patients, SD in 56%, and PD in 22% (p = 0.047). In addition, the DSM-TACE group showed statistically significant tumor volume reduction (p = 0.006). Median apparent diffusion coefficient values were not significantly different between both groups at baseline (p = 0.26) and study endpoint (p = 0.83). Median survival in the cTACE group was 13 months (95% confidence interval, range 5-40 months) compared to 16 months (95% confidence interval, range 1-48 months) in the DSM-TACE group, exhibiting no statistically significant difference (p = 0.75). CONCLUSION: DSM-TACE showed a significant difference reducing tumor volume and in tumor response according to RECIST 1.1 compared to cTACE. Thus, patients with CRLM might not only benefit from short embolization effect of DSM-TACE but also from better tumor responses. Apparent diffusion coefficients were not significantly different between both groups and cannot be used as a biomarker for monitoring for therapeutic effect of TACE. KEY POINTS: • To our knowledge, this is the first prospective study that directly compared cTACE and DSM-TACE in patients with CRLM. • DSM-TACE showed a significant difference reducing tumor volume (p = 0.006) and in tumor response according to RECIST 1.1 (p = 0.047) compared to cTACE. • Survival analysis showed a median survival of 13 months in the cTACE group compared to 16 months in the DSM-TACE group (p = 0.75).

Identification of putative genetic modifying factors that influence the development of Papillon-Lefévre or Haim-Munk syndrome phenotypes.

BACKGROUND: Papillon-Lefévre syndrome (PLS; OMIM 245000) and Haim-Munk syndrome (HMS; OMIM 245010), which are both characterized by palmoplantar hyperkeratosis and periodontitis, are phenotypic variants of the same disease caused by mutations of the cathepsin C (CTSC) gene. AIM: To identify putative genetic modifying factors responsible for the differential development of the PLS or HMS phenotypes, we investigated two Hungarian patients with different phenotypic variants (PLS and HMS) but carrying the same homozygous nonsense CTSC mutation (c.748C/T; p.Arg250X). METHODS: To gain insights into phenotype-modifying associations, whole exome sequencing (WES) was performed for both patients, and the results were compared to identify potentially relevant genetic modifying factors. RESULTS: WES revealed two putative phenotype-modifying variants: (i) a missense mutation (rs34608771) of the SH2 domain containing 4A (SH2D4A) gene encoding an adaptor protein involved in intracellular signalling of cystatin F, a known inhibitor of the cathepsin protein, and (ii) a missense variant (rs55695858) of the odorant binding protein 2A (OBP2A) gene, influencing the function of the cathepsin protein through the glycosyltransferase 6 domain containing 1 (GLT6D1) protein. CONCLUSION: Our study contributes to the accumulating evidence supporting the clinical importance of phenotype-modifying genetic factors, which have high potential to aid the elucidation of genotype-phenotype correlations and disease prognosis.

Transvenous pulmonary chemoembolization (TPCE) for palliative or neoadjuvant treatment of lung metastases.

PURPOSE: To retrospectively evaluate tumor response, local tumor control, and patient survival after the treatment of pulmonary metastases using transpulmonary chemoembolization (TPCE) in palliative and neoadjuvant intent. MATERIALS AND METHODS: One hundred forty-three patients (mean age 56.7 ± 13.4 years) underwent repetitive TPCE (mean number of sessions 5.8 ± 2.9) between June 2005 and April 2017 for the treatment of unresectable lung metastases, not responding to systemic chemotherapy. Patients had predominant lung metastases with bilateral lung involvement in 80.4% of the cases. Regional delivery of the chemotherapeutic agents was performed through selective catheterization of the tumor-supplying pulmonary arteries with subsequent injection of iodized oil and microspheres. Patients, who underwent subsequent ablation (n = 51), either for all lesions (complete) or dominant lesions (incomplete), constituted the neoadjuvant group, and those who underwent TPCE alone represented the palliative treatment intent (n = 92). The response was assessed according to the revised Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Partial response was achieved in 11.9% (n = 17), stable disease in 66.4% (n = 95), and progressive disease in 21.7% (n = 31). The mean survival time and time to progression were 24.5 ± 1.7 and 7.5 ± 0.5 months, respectively. The mean survival time was shorter for the palliative group (19.7 ± 2), compared to the neoadjuvant group (30.1 ± 2.6 months). The use of TPCE alone or with incomplete ablation had a significantly increased hazard of death of 4.6- (p = 0.002) and 3.1-fold (p = 0.027), respectively, in comparison with TPCE with subsequent complete ablation. CONCLUSION: TPCE has the potential to improve local tumor control and to prolong survival with a neoadjuvant potential when combined with ablation therapy. KEY POINTS: • Transpulmonary chemoembolization (TPCE) is a locoregional technique for delivering chemotherapy in higher intratumoral concentrations and with reduced systemic toxicity. • TPCE can be an alternative treatment for patients with pulmonary metastases who failed prior systemic chemotherapy or with post-operative recurrence. • The current retrospective study revealed that TPCE is a feasible treatment option for patients with unrespectable lung secondaries in both palliative and neoadjuvant intent and has the potential of improving local control and prolonging survival.

Microwave Ablation (MWA) of Pulmonary Neoplasms: Clinical Performance of High-Frequency MWA With Spatial Energy Control Versus Conventional Low-Frequency MWA.

OBJECTIVE. The objective of our study was to evaluate the clinical performance of a new high-frequency (HF) microwave ablation (MWA) technology with spatial energy control for treatment of lung malignancies in comparison with a conventional low-frequency (LF) MWA technology. MATERIALS AND METHODS. In this retrospective study, 59 consecutive patients (mean age, 58.9 ± 12.6 [SD] years) were treated in 71 sessions using HF spatial-energy-control MWA. Parameters collected were technical success and efficacy, tumor diameter, tumor and ablation volumes, ablation time, output energy, complication rate, 90-day mortality, local tumor progression (LTP), ablative margin size, and ablation zone sphericity. Results were compared with the same parameters retrospectively collected from the last 71 conventional LF-MWA sessions. This group consisted of 56 patients (mean age, 60.3 ± 10.8 years). Statistical comparisons were performed using the Wilcoxon-Mann-Whitney test. RESULTS. Technical success was 98.6% for both technologies; technical efficacy was 97.2% for HF spatial-energy-control MWA and 95.8% for LF-MWA. The 90-day mortality rate was 5.1% (3/59) in the HF spatial-energy-control MWA group and 5.4% (3/56) in the LF-MWA group; for both groups, there were zero intraprocedural deaths. The median ablation time was 8.0 minutes for HF spatial-energy-control MWA and 10.0 minutes for LF-MWA (p < 0.0001). Complications were recorded in 21.1% (15/71) of HF spatial-energy-control MWA sessions and in 31.0% (22/71) of LF-MWA sessions (p = 0.182); of these complications, 4.2% (3/71) were major complications in the HF spatial-energy-control MWA group, and 9.9% (7/71) were major complications in the LF-MWA group. The median deviation from ideal sphericity (1.0) was 0.195 in the HF spatial-energy-control MWA group versus 0.376 in the LF-MWA group (p < 0.0001). Absolute minimal ablative margins per ablation were 7.5 ± 3.6 mm (mean ± SD) in the HF spatial-energy-control MWA group versus 4.2 ± 3.0 mm in the LF-MWA group (p < 0.0001). In the HF spatial-energy-control MWA group, LTP at 12 months was 6.5% (4/62). LTP at 12 months in the LF-MWA group was 12.5% (7/56). Differences in LTP rate (p = 0.137) and time point (p = 0.833) were not significant. CONCLUSION. HF spatial-energy-control MWA technology and conventional LFMWA technology are safe and effective for the treatment of lung malignancies independent of the MWA system used. However, HF spatial-energy-control MWA as an HF and high-energy MWA technique achieves ablation zones that are closer to an ideal sphere and achieves larger ablative margins than LF-MWA (p < 0.0001).

The management and genetic background of pityriasis rubra pilaris: a single-centre experience.

BACKGROUND: Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory dermatosis with multifactorial aetiology. It is known that particular caspase recruitment domain family member 14 (CARD14) gene mutations are associated with familial PRP and certain forms of psoriasis. Additionally, few data are available about the role of CARD14 gene variants in sporadic PRP. The clinical picture is variable for the different types of PRP, therefore choosing the adequate treatment is often difficult, furthermore there are no specific guidelines for therapy. OBJECTIVE: Our aim was to survey the efficacy of the applied therapies and to screen the CARD14 gene variants in our PRP patients. METHODS: In this retrospective study, patients diagnosed with PRP between 2006 and 2016 at our clinic were involved. Besides the follow-up study of the treatments, the genetic analysis of CARD14 gene was performed. RESULTS: We analysed 19 patients, among whom 17 were diagnosed with type I, one with type III, and one with type V PRP. The majority of the patients were successfully treated with acitretin in combination with systemic corticosteroids, and the remaining patients were treated with other systemic therapies with diverse effects. The genetic screening of CARD14 gene revealed two previously described mutations (rs114688446, rs117918077) and six polymorphisms (rs28674001, rs2066964, rs34367357, rs11653893, rs11652075, rs2289541). Ten of 19 patients carried different CARD14 genetic variants either alone or in combination. CONCLUSION: Based on our experience, we propose that acitretin and an initial combination of short-term systemic corticosteroid therapy could be a successful treatment option for PRP. Although we identified several CARD14 variants in almost half of our cases, we did not find a correlation between the therapeutic response and the genetic background. Our data support the previous observation that CARD14 genetic variants are not specific to PRP, although they may indicate chronic inflammation.

[Urachal Cancer: an update of current molecular findings]. / Das Urachuskarzinom: Ein Update aktueller molekularer Ergebnisse.

BACKGROUND: Urachal cancer is a rare type of cancer, often following a clinically aggressive course. Due to its rarity, knowledge about its molecular background is still limited. In addition, no sufficiently reliable diagnostic markers are available. OBJECTIVES: The aim of the present study is to give an overview of our recent molecular projects on urachal cancer and to connect it with current literature in the field. MATERIALS AND METHODS: Three projects are introduced. The first project identified and validated diagnostic biomarkers in urachal adenocarcinomas compared to colorectal adenocarcinomas and primary adenocarcinomas of the bladder using various proteomic methods. In the second project, the most relevant differential diagnostic markers between urachal adenocarcinomas and colorectal adenocarcinomas compared to normal tissue (urachal remnants) were determined by analyzing a miRNA panel. Sequence analyses were performed in the third project. The focus was on molecular differences to colorectal adenocarcinomas and urothelial carcinomas. RESULTS AND CONCLUSIONS: We detected potential biomarker candidates for the immunohistochemical differential-diagnosis and generated a miRNA-based diagnostic scoring system with a potentially high differential-diagnostic significance. The sequence analyses data confirm the molecular autonomy of the urachal adenocarcinomas compared to other entities.

Transarterial chemoembolization (TACE) using mitomycin and lipiodol with or without degradable starch microspheres for hepatocellular carcinoma: comparative study.

BACKGROUND: To evaluate survival data and local tumor control after transarterial chemoembolization in two groups with different embolization protocols for the treatment of HCC patients. METHODS: Ninty-nine patients (mean age: 63.6 years), 78 male (78.8%) with HCC were repeatedly treated with chemoembolization in 4-week-intervals. Eighty-eight patients had BCLC-Stage-B and in 11 patients, chemoembolization was performed for bridging (BCLC-Stage-A). In total, 667 chemoembolization treatments were performed (mean 6.7 treatments/patient). The administered chemotherapeutic agent included mitomycin. For embolization, lipiodol only (n = 51;51.5%; mean age 63.8 years; 38 male), or lipiodol plus degradable starch microspheres (DSM) (n = 48; 48.5%; mean age 63.4 years; 40 male) were used. The local tumor response was assessed by MRI using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). Patient survival times were evaluated using Kaplan-Meier curves and log-rank tests. RESULTS: The local tumor control in the lipiodol-group was: PR (partial response) in 11 (21.6%), SD (stable disease) in 32 (62.7%) and PD (progressive disease) in 8 cases (15.7%). In the lipiodol-DSM-group, PR was seen in 14 (29.2%), SD in 22 (45.8%), and PD in 12 (25.0%) individuals (p = 0.211). The median survival of patients after chemoembolization with lipiodol was 25 months and in the lipiodol-DSM-group 28 months (p = 0.845). CONCLUSION: Our data suggest a slight benefit of the use of lipiodol and DSM in comparison of using lipiodol only for chemoembolization of HCC in terms of local tumor control and survival data, this trend did not reach the level of significance.

Transarterial chemoembolization in pancreatic adenocarcinoma with liver metastases: MR-based tumor response evaluation, apparent diffusion coefficient (ADC) patterns, and survival rates.

PURPOSE: To retrospectively investigate the effectiveness of triple drug combination transarterial chemoembolization (TACE) on local tumor response and survival in patients with liver metastases from pancreatic cancer. Also, this study will evaluate the variances in response regarding the number of metastases, assess the correlation between tumor response and the changes in the apparent diffusion coefficients (ADC) in diffusion weighted (DW) MRI. MATERIALS AND METHODS: One hundred and twelve patients (58 men and 54 women; mean age 57) with malignant liver metastases from pancreatic adenocarcinoma underwent at least one session of TACE with a chemotherapeutic combination of mitomycin C, cisplatin, and gemcitabine. A size-based evaluation of tumor response (response evaluation criteria in solid tumors (RECIST)) was conducted, along with ADC values, and survival indices as related to treatment pattern. RESULTS: Four weeks following the end of the treatment, 78.26% of patients showed stable disease and 11.59% showed partial response. The median survival time was 19 months and for the stable disease group, 26 months. Low pretreatment ADC values showed no significant correlation to poor response to treatment (r = 0.347,p = 0.146). CONCLUSION: The triple drug TACE technique showed improvements in median survival times in patients with hepatic metastases from pancreatic carcinoma and helped control disease progression, whereas the number of hepatic lesions was not a statistically significant factor in patients' response to TACE. The data suggest that pre-treatment ADC values in DW-MRI have no statistical correlation with tumor response.

The role of MRI in the early evaluation of lung microwave ablation.

PURPOSE: To retrospectively investigate the role of a contrast enhanced MRI (ceMRI) performed 24 h after a microwave ablation (MWA) of the lung, in predicting local tumour progression (LTP) and detecting complications compared to an unenhanced CT. MATERIAL AND METHODS: Forty-nine patients who underwent MWA of 77 lung metastases between 2008 and 2015 were included. All patients received an unenhanced chest CT and a ceMRI (including T2 and ceT1) 24 h after MWA. The conspicuities of the peripheral rim and the ablated tumour were scored using 1-3 scales and compared between examinations. The safety margin was measured directly (both scores ≥2) and indirectly using a subtraction method. The ability of each imaging modality to predict LTP based on safety margin width was analysed using receiver operating characteristic curves. The MRI ability to detect a pneumothorax was compared to CT. RESULTS: The peripheral rim was best visualised on T2 followed by T1 and CT. The tumour was best visualised on CT, followed by T1 and T2. Direct safety margin measurement was possible on CT, ceT1 and T2 in 68.8%, 64.9% and 27.3% of cases, respectively. Direct CT (AUC = 0.77) and ceT1 (AUC = 0.76) measurements had better diagnostic performance than indirect CT (AUC = 0.72), ceT1 (AUC = 0.70) and T2 (AUC = 0.69) measurements. The MRI sensitivity and specificity for pneumothorax were 60.8% and 87.0%, respectively. Only one pneumothorax >1 cm was missed. CONCLUSIONS: A ceMRI performed 24 h after MWA of lung tumours has a similar ability to predict LTP and detect important complications as a CT has.

Evaluation of microwave ablation of liver malignancy with enabled constant spatial energy control to achieve a predictable spherical ablation zone.

OBJECTIVES: To evaluate the clinical performance of a new microwave ablation (MWA) system with enabled constant spatial energy control (ECSEC) to achieve spherical ablation zones in the treatment of liver malignancies. MATERIALS AND METHODS: In this retrospective study, 56 hepatic tumours in 48 patients (23 men, 25 women; mean age: 59.6 years) were treated using a new high-frequency MWA-system with ECSEC. Parameters evaluated were technical success, technical efficacy, tumour diameter, tumour and ablation volume, complication rate, 90-day mortality, local tumour progression (LTP) at the 12-month follow-up, ablative margin and ablation zone sphericity. These parameters were compared using the Kruskal-Wallis test with the same parameters collected retrospectively from cohorts of patients treated with conventional high-frequency (HF) MWA (n = 20) or low-frequency (LF) MWA (n = 20). RESULTS: Technical success was achieved in all interventions. The technical efficacy was 100% (ECSEC) vs. 100% (LF-MWA) vs. 95% (HF-MWA). There were no intra-procedural deaths or major complications. Minor complications occurred in 3.57% (2/56), 0% (0/20) and 0% (0/20) of the patients, respectively. The one-year mortality rate was 16.1% (9/56), 15% (3/20) and 10% (2/20), respectively. The LTP was 3.57% (2/56), 5% (1/20) and 5% (1/20), respectively. The median deviation from ideal sphericity (1.0) was 0.135 (ECSEC) vs. 0.344 (LF-MWA) vs. 0.314 (HF-MWA) (p < 0.001). The absolute minimal ablative margin was 8.1 vs. 2.3 vs. 3.1 mm (p < 0.001). CONCLUSIONS: Microwave ablation of liver malignancies is a safe and efficient treatment independent of the system used. Hepatic MWA with ECSEC achieves significantly more spherical ablation zones and higher minimal ablative margins.

Ablation therapy of non-colorectal cancer lung metastases: retrospective analysis of tumour response post-laser-induced interstitial thermotherapy (LITT), radiofrequency ablation (RFA) and microwave ablation (MWA).

PURPOSE: To retrospectively compare the local tumour response and survival rates in patients with non-colorectal cancer lung metastases post-ablation therapy using laser-induced thermotherapy (LITT), radiofrequency ablation (RFA) and microwave ablation (MWA). MATERIAL AND METHODS: Retrospective analysis of 175 computed tomography (CT)-guided ablation sessions performed on 109 patients (43 males and 66 females, mean age: 56.6 years). Seventeen patients with 22 lesions underwent LITT treatment (tumour size: 1.2-4.8 cm), 29 patients with 49 lesions underwent RFA (tumour size: 0.8-4.5 cm) and 63 patients with 104 lesions underwent MWA treatment (tumour size: 0.6-5 cm). CT scans were performed 24-h post-therapy and on follow-up at 3, 6, 12, 18 and 24 months. RESULTS: The overall-survival rates at 1-, 2-, 3- and 4-year were 93.8, 56.3, 50.0 and 31.3% for patients treated with LITT; 81.5, 50.0, 45.5 and 24.2% for patients treated with RFA and 97.6, 79.9, 62.3 and 45.4% for patients treated with MWA, respectively. The mean survival time was 34.14 months for MWA, 34.79 months for RFA and 35.32 months for LITT. In paired comparison, a significant difference could be detected between MWA versus RFA (p = 0.032). The progression-free survival showed a median of 23.49 ± 0.62 months for MWA,19.88 ± 2.17 months for LITT and 16.66 ± 0.66 months for RFA (p = 0.048). The lowest recurrence rate was detected in lesions ablated with MWA (7.7%; 8 of 104 lesions) followed by RFA (20.4%; 10 of 49 lesions) and LITT (27.3%; 6 of 22 lesions) p value of 0.012. Pneumothorax was detected in 22.16% of MWA ablations, 22.73% of LITT ablations and 14.23% of RFA ablations. CONCLUSION: LITT, RFA and MWA may provide an effective therapeutic option for non-colorectal cancer lung metastases with an advantage for MWA regarding local tumour control and progression-free survival rate.

Atypical neurofibromatosis type 1 with unilateral limb hypertrophy mimicking overgrowth syndrome.

Neurofibromatosis type 1 (NF1; OMIM 162200), a dominantly inherited multitumor syndrome, results from mutations in the Neurofibromin 1 (NF1) gene. We present the case of a Hungarian woman with the clinical phenotype of NF1 over her whole body and the clinical features of unilateral overgrowth involving her entire left leg. This unusual phenotype suggested either the atypical form of NF1 or the coexistence of NF1 and overgrowth syndrome. Direct sequencing of the genomic DNA isolated from peripheral blood revealed a novel frameshift mutation (c.5727insT, p.V1909fsX1912) in the NF1 gene. Next-generation sequencing of 50 oncogenes and tumour suppressor genes, performed on the genomic DNAs isolated from tissue samples and peripheral blood, detected only wild-type sequences. Based on these results, we concluded that the patient is affected by an unusual phenotype of NF1, and that the observed unilateral overgrowth of the left leg might be a rare consequence of the identified c.5727insT mutation.

The pharmacokinetics and dosing of oral 4-methylumbelliferone for inhibition of hyaluronan synthesis in mice.

Recently, there has been considerable interest in using 4-methylumbelliferone (4-MU) to inhibit hyaluronan (HA) synthesis in mouse models of cancer, autoimmunity and a variety of other inflammatory disorders where HA has been implicated in disease pathogenesis. In order to facilitate future studies in this area, we have examined the dosing, treatment route, treatment duration and metabolism of 4-MU in both C57BL/6 and BALB/c mice. Mice fed chow containing 5% 4-MU, a dose calculated to deliver 250 mg/mouse/day, initially lose substantial weight but typically resume normal weight gain after 1 week. It also takes up to a week to see a reduction in serum HA in these animals, indicating that at least a 1-week loading period on the drug is required for most protocols. At steady state, more than 90% of the drug is present in plasma as the glucuronidated metabolite 4-methylumbelliferyl glucuronide (4-MUG), with the sulphated metabolite, 4-methylumbelliferyl sulphate (4-MUS) comprising most of the remainder. Chow containing 5% but not 0·65% 4-MU was effective at preventing disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis, as well as in the DORmO mouse model of autoimmune diabetes. While oral 4-MU was effective at preventing EAE, daily intraperitoneal injections of 4-MU were not. Factors potentially affecting 4-MU uptake and plasma concentrations in mice include its taste, short half-life and low bioavailability. These studies provide a practical resource for implementing oral 4-MU treatment protocols in mice.

Intraprocedural blood volume measurement using C-arm CT as a predictor for treatment response of malignant liver tumours undergoing repetitive transarterial chemoembolization (TACE).

PURPOSE: To evaluate feasibility of measuring parenchymal blood volume (PBV) of malignant hepatic tumours using C-arm CT, test the changes in PBV following repeated transarterial chemoembolization (TACE) and correlate these changes with the change in tumour size in MRI. METHODS: 111 patients with liver malignancy were included. Patients underwent MRI and TACE in a 4- to 6-week interval. During intervention C-arm CT was performed. Images were post-processed to generate PBV maps. Blood volume data in C-arm CT and change in size in MRI were evaluated. The correlation between PBV and size was tested using Spearman rank test. RESULTS: Pre-interventional PBV maps showed a mean blood volume of 84.5 ml/1000 ml ± 62.0, follow-up PBV maps after multiple TACE demonstrated 61.1 ml/1000 ml ± 57.5. The change in PBV was statistically significant (p = 0.02). Patients with initial tumour blood volume >100 ml/1000 ml dropped 7.1% in size and 47.2% in blood volume; 50-100 ml/1000 ml dropped 4.6% in size and 25.7% in blood volume; and <50 ml/1000 ml decreased 2.8% in size and increased 82.2% in blood volume. CONCLUSION: PBV measurement of malignant liver tumours using C-arm CT is feasible. Following TACE PBV decreased significantly. Patients with low initial PBV show low local response rates and further increase in blood volume, whereas high initial tumour PBV showed better response to TACE. KEY POINTS: Parenchymal blood volume assessment of malignant hepatic lesions using C-arm CT is feasible. The parenchymal blood volume is reduced significantly following transarterial chemoembolization. Parenchymal blood volume can monitor the response of tumours after transarterial chemoembolization. Although not significant, high initial parenchymal blood volume yields better response to TACE.