Long-term benefit of lurbinectedin as palliative chemotherapy in progressive malignant pleural mesothelioma (MPM): final efficacy and translational data of the SAKK 17/16 study.

BACKGROUND: The SAKK 17/16 study showed promising efficacy data with lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma. Here, we evaluated long-term outcome and analyzed the impact of lurbinectedin monotherapy on the tumor microenvironment at the cellular and molecular level to predict outcomes. MATERIAL AND METHODS: Forty-two patients were treated with lurbinectedin in this single-arm study. Twenty-nine samples were available at baseline, and seven additional matched samples at day one of cycle two of treatment. Survival curves and rates between groups were compared using the log-rank test and Kaplan-Meier method. Statistical significance was set at P value <0.05. RESULTS: Updated median overall survival (OS) was slightly increased to 11.5 months [95% confidence interval (CI) 8.8-13.8 months]. Thirty-six patients (85%) had died. The OS rate at 12 and 18 months was 47% (95% CI 32.1% to 61.6%) and 31% (95% CI 17.8% to 45.0%), respectively. Median progression-free survival was 4.1 months (95% CI 2.6-5.5 months). No new safety signals were observed. Patients with lower frequencies of regulatory T cells, as well as lower tumor-associated macrophages (TAMs) at baseline, had a better OS. Comparing matched biopsies, a decrease of M2 macrophages was observed in five out of seven patients after exposure to lurbinectedin, and two out of four patients showed increased CD8+ T-cell infiltrates in tumor. DISCUSSION: Lurbinectedin continues to be active in patients with progressing malignant pleural mesothelioma. According to our very small sample size, we hypothesize that baseline TAMs and regulatory T cells are associated with survival. Lurbinectedin seems to inhibit conversion of TAMs to M2 phenotype in humans.

WITHDRAWN: The benefit of adopting Microultrasound in the prostate cancer imaging pathway : A lesion-by-lesion analysis

INTRODUCTION: Microultrasound (MicroUS) is a novel imaging modality relying on a high-frequency transducer which confers a three-fold improvement in spatial resolution as compared with conventional transrectal ultrasound. We evaluated the diagnostic value of MRI-MicroUS fusion biopsy and determined the additional benefit of employing MicroUS. METHODS: Retrospective analysis of consecutive treatment-naïve men undergoing MRI-MicroUS fusion biopsy between May 2018 and March 2019. Pre-biopsy MRI was systematically reviewed in a dedicated meeting where suspicious lesions PIRADS≥3 were registered and uploaded in the ExactVu MicroUS device. MRI and MicroUS lesions were individually marked in a PIRADS v2 scheme. The biopsy protocol included MRI-MicroUS fusion and MicroUS targeted biopsies; systematic biopsies were performed at clinician's discretion. The diagnostic value was evaluated in terms of detection rate of clinically significant prostate cancer, defined as Gleason pattern≥4 at histology. RESULTS: In all, 148 patients with a median age of 69 years (IQR 63-74) and median PSA density of 0.16ng/ml/cc (0.10-0.23) were included. Clinically significant cancer was detected in 42.5% (63/148) patients. MRI detected 89 lesions in the peripheral zone; 73% (65/89) were visible on MicroUS. Clinically significant cancer was detected in 46.1% (30/65) MRI and MicroUS visible lesions, and in 4.2% (1/24) lesions only visible on mpMRI. MicroUS additionally identified 35 suspicious lesions non-visible on MRI of which clinically significant cancer was present in 25.7% (9/35). CONCLUSION: Adding MicroUS to the conventional pathway seems to increase the detection rate of clinically significant disease in unselected men undergoing biopsy.

The benefit of adopting Microultrasound in the prostate cancer imaging pathway: A lesion-by-lesion analysis: Biopsies prostatiques guidée par micro-échographie, quel bénéfice ? Une analyse lésion par lésion.

INTRODUCTION: - Microultrasound (MicroUS) is a novel imaging modality relying on a high-frequency transducer which confers a three-fold improvement in spatial resolution as compared with conventional transrectal ultrasound. We evaluated the diagnostic value of MRI-MicroUS fusion biopsy and determined the additional benefit of employing MicroUS. METHODS: - Retrospective analysis of consecutive treatment-naïve men undergoing MRI-MicroUS fusion biopsy between May 2018 and March 2019. Pre-biopsy MRI was systematically reviewed in a dedicated meeting where suspicious lesions PIRADS ≥ 3 were registered and uploaded in the ExactVu MicroUS device. MRI and MicroUS lesions were individually marked in a PIRADS v2 scheme. The biopsy protocol included MRI-MicroUS fusion and MicroUS targeted biopsies; systematic biopsies were performed at clinician's discretion. The diagnostic value was evaluated in terms of detection rate of clinically significant prostate cancer, defined as Gleason pattern ≥ 4 at histology. RESULTS: - In all, 148 patients with a median age of 69 years (IQR 63-74) and median PSA density of 0.16 ng/ml/cc (0.10-0.23) were included. Clinically significant cancer was detected in 42.5% (63/148) patients. MRI detected 89 lesions in the peripheral zone; 73% (65/89) were visible on MicroUS. Clinically significant cancer was detected in 46.1% (30/65) MRI and MicroUS visible lesions, and in 4.2% (1/24) lesions only visible on mpMRI. MicroUS additionally identified 35 suspicious lesions non-visible on MRI of which clinically significant cancer was present in 25.7% (9/35). CONCLUSION: - Adding MicroUS to the conventional pathway seems to increase the detection rate of clinically significant disease in unselected men undergoing biopsy. © 2022 Elsevier Masson SAS. All rights reserved.

Maximum AmbiGuity Distance for Phase Imaging in Detection of Traumatic Cerebral Microbleeds: An Improvement over Current Imaging Practice.

BACKGROUND AND PURPOSE: Developed using a rigorous mathematic framework, Maximum AmbiGuity distance for Phase Imaging (MAGPI) is a promising phase-imaging technique that provides optimal phase SNR and reduced susceptibility artifacts. We aimed to test the potential of MAGPI over routinely used SWI in the detection of traumatic cerebral microbleeds in athletes diagnosed with mild traumatic brain injury. MATERIALS AND METHODS: In this prospective study, 10 athletes (18-22 years of age, 3 women/7 men) diagnosed with mild traumatic brain injury were enrolled. Brain MRIs were performed using 3T MR imaging at 2 days, 2 weeks, and 2 months after head trauma. The imaging protocol included whole-brain T1 MPRAGE, T2 FLAIR, conventional SWI, and the MAGPI multiecho sequence. Phase images from MAGPI were put through a previously described SWI process to generate MAGPI-SWI. Conventional and MAGPI-SWI were assessed independently by a board-certified neuroradiologist for the presence of contusions and cerebral microbleeds. All participants had routine neuropsychological assessment and Visuo-Motor Tests. RESULTS: At initial assessment, 4 of the participants had visuo-motor performance indicative of mild traumatic brain injury, and 4 participants had a Post-Concussion Symptom Scale score of >21, a threshold that has been used to define moderate impairment. Cerebral microbleeds were identified in 6 participants on MAGPI-SWI, 4 of whom had evidence of concurrent contusions on FLAIR imaging. None of these cerebral microbleeds were identified confidently on conventional SWI due to substantial distortion and susceptibility artifacts. CONCLUSIONS: Optimal phase unwrapping with reduced susceptibility in MAGPI-SWI can clarify small microbleeds that can go undetected with routinely used conventional SWI.

Impact of a risk-stratified thromboprophylaxis protocol on the incidence of postoperative venous thromboembolism and bleeding.

Efforts to reduce postoperative venous thromboembolism are challenging due to heterogeneity in thromboprophylaxis practice. As a result, a 'one-size-fits-all' approach that accounts for surgery-specific risk, but fails to account for patient-level variation, is often adopted by healthcare networks. Updated clinical practice guidelines have advocated an individualised risk-stratified approach that balances the risk:benefit ratio associated with thromboprophylaxis; however, there are limited data confirming effectiveness of these recommendations on the incidence of postoperative venous thromboembolism and bleeding. We developed the surgical-thrombo-embolism-prevention protocol, a novel risk-stratified algorithm that classified patients into low-, intermediate-, and high-risk profiles according to surgical procedure and patient baseline medical risk. Expert-endorsed risk-specific thromboprophylaxis strategies were then applied. A staged quality improvement program was developed to implement the protocol. We postulated that compliance with the protocol would reduce postoperative venous thromboembolism rates without increasing the incidence of postoperative bleeding. Between June 2013 and March 2018, we evaluated the efficacy, safety and sustainability of this risk-stratified approach in 24,953 surgical admissions at a dedicated cancer centre. By final implementation, program compliance was 91%. Postoperative venous thromboembolism rates reduced from 3.1 per 1000 surgical admissions to 0.6 per 1000 surgical admissions (relative risk reduction 79%; p < 0.005). Postoperative bleeding rates also declined from 10.0 per 1000 surgical admissions to 6.3 per 1000 surgical admissions (relative risk reduction 37%; p = 0.02). Sustained improvement was evident more than 3 years after implementation. Implementation of the surgical-thrombo-embolism-prevention protocol significantly reduced the incidence of postoperative venous thromboembolism supporting its validation at other institutions.

Reconsidering the role of pelvic lymph node dissection with radical prostatectomy for prostate cancer in an era of improving radiological staging techniques.

BACKGROUND: Performing an extended pelvic lymph node dissection (PLND) on all men with intermediate- and high-risk prostate cancer at the time of a radical prostatectomy (RP) remains controversial. The majority of patients PLND histology is benign, and the long-term cancer-free progression in men with positive lymph node metastasis is low. The objective is to investigate the probability of long-term biochemical freedom from recurrent disease (bNED) in men with lymph node metastasis identified at the time of radical prostatectomy (RP). SUBJECTS AND METHODS: A retrospective review of the pathology of 1184 pelvic lymph node dissections performed at the time of a radical prostatectomy by multiple surgeons referred to a single uro-pathology laboratory between 2008 and 2014 identified 61 men with node-positive prostate cancer. Of the men with positive nodes, 24 had a standard PLND and 37 an extended PLND (ePLND). bNED was defined as a post-operative serum PSA < 0.2 ng/ml. RESULTS: The median follow-up is 4 years (2-8). The median lymph node count was 7 (range 2-16) for PLND and 22 (range 6-46) for the ePLND. A single lymph node metastasis was identified in 56% of the 61 men. Only 10% of men with a positive lymph node metastasis remained free of biochemical recurrence of disease, and only 5% had undetectable serum PSA. There was no difference in bNED outcome between a PLND and ePLND. The number of men needed to be treated with a PLND at the time of RP (NNT) to result in an undetectable post-operative PSA at a median follow-up of 4 years is 395. CONCLUSIONS: In men with lymph node metastasis, the probability of long-term bNED is low and the NNT for cure is high. With emerging improved radiological imaging techniques increasing the detection of lymph node metastasis outside the extended lymph node dissection templates, more scientific investigation is required to evaluate which men will benefit from a PLND and which men can avoid an unnecessary PLND procedure.

Olfactory function in acute traumatic brain injury.

OBJECTIVE: Traumatic brain injury (TBI) represents a significant public health problem and is associated with a high rate of mortality and morbidity. Although TBI is amongst the most common causes of olfactory dysfunction the relationship between injury severity and olfactory problems has not yet been investigated with validated and standardized methods in the first days following the TBI. METHODS: We measured olfactory function in 63 patients admitted with TBI within the first 12 days following the trauma by means of the Sniffin' Sticks identification test (quantitative assessment) and a parosmia questionnaire (qualitative assessment). TBI severity was determined by means of the Glasgow Coma Scale (GCS) and by duration of post-traumatic amnesia (PTA) as measured by the Galveston Orientation and Amnesia Test. RESULTS: Poor olfactory scores correlated with a longer amnesia period, but not with GCS scores. Further, we observed higher parosmia scores in assault victims than in victims of falls or motor vehicle collisions. CONCLUSIONS: We show that PTA is intimately related to olfactory problems following a TBI. Thus, a thorough evaluation of olfaction is essential in order to detect posttraumatic olfactory dysfunction and to take appropriate actions early on to help the individual deal with this impairment.

Bayesian estimation of cerebral perfusion using reduced-contrast-dose dynamic susceptibility contrast perfusion at 3T.

BACKGROUND AND PURPOSE: DSC perfusion has been increasingly used in conjunction with other contrast-enhanced MR applications and therefore there is need for contrast-dose reduction when feasible. The purpose of this study was to establish the feasibility of reduced-contrast-dose brain DSC perfusion by using a probabilistic Bayesian method and to compare the results with the commonly used singular value decomposition technique. MATERIALS AND METHODS: Half-dose (0.05-mmol/kg) and full-dose (0.1-mmol/kg) DSC perfusion studies were prospectively performed in 20 patients (12 men; 34-70 years of age) by using a 3T MR imaging scanner and a gradient-EPI sequence (TR/TE, 1450/22 ms; flip angle, 90°). All DSC scans were processed with block circulant singular value decomposition and Bayesian probabilistic methods. SNR analysis was performed in both half-dose and full-dose groups. The CBF, CBV, and MTT maps from both full-dose and half-dose scans were evaluated qualitatively and quantitatively in both WM and GM on coregistered perfusion maps. Statistical analysis was performed by using a t test, regression, and Bland-Altman analysis. RESULTS: The SNR was significantly (P < .0001) lower in the half-dose group with 32% and 40% reduction in GM and WM, respectively. In the half-dose group, the image-quality scores were significantly higher in Bayesian-derived CBV (P = .02) and MTT (P = .004) maps in comparison with block circulant singular value decomposition. Quantitative values of CBF, CBV, and MTT in Bayesian-processed data were comparable and without a statistically significant difference between the half-dose and full-dose groups. The block circulant singular value decomposition-derived half-dose perfusion values were significantly different from those of the full-dose group both in GM (CBF, P < .001; CBV, P = .02; MTT, P = .02) and WM (CBF, P < .001; CBV, P = .003; MTT, P = .01). CONCLUSIONS: Reduced-contrast-dose (0.05-mmol/kg) DSC perfusion of the brain is feasible at 3T by using the Bayesian probabilistic method with quantitative results comparable with those of the full-dose protocol.

Transforaminal versus intra-articular facet corticosteroid injections for the treatment of cervical radiculopathy: a randomized, double-blind, controlled study.

BACKGROUND AND PURPOSE: Transforaminal corticosteroid injections can be performed in the management of cervical radiculopathy but carry the risk of catastrophic complications. This study compares the efficacy of transforaminal and facet corticosteroid injections at 4 weeks' follow-up. MATERIALS AND METHODS: We randomly assigned 56 subjects to receive CT-guided transforaminal (15 men, 13 women; mean age, 52 years; range, 28-72 years) or facet (8 men, 20 women; mean, 44 years; range, 26-60 years) injections. The primary outcome was pain severity rated on a Visual Analog Scale (0-100). Secondary outcomes were the Neck Disability Index and the Medication Quantitative Scale. RESULTS: In the intention-to-treat and as-treated analyses, for a mean baseline score, facet injections demonstrated a significant pain score reduction of 45.3% (95% CI, 21.4-69.2) and 37.0% (95% CI, 9.2-64.7), while transforaminal injections showed a nonsignificant pain score reduction of 9.8% (95% CI, +11.5-31.2) and 17.8% (95% CI, +6.6-42.2). While facet injections demonstrated an improvement in the Neck Disability Index score of 24.3% (95% CI, +2.9-51.5) and 20.7% (95% CI, +6.2-47.6) as opposed to transforaminal injections of 9.6% (95% CI, +15.2-34.4) and 12.8% (95% CI, +11.2-36.7), the results were not statistically significant. Noninferiority of facet to transforaminal injections was demonstrated for baseline pain scores of ≤60, while noninferiority analysis was inconclusive for baseline pain scores of ≥80 and for the Neck Disability Index. Neither intervention showed a significant medication-intake score reduction with time. CONCLUSIONS: Facet injections are effective for the treatment of cervical radiculopathy and represent a valid and safer alternative to transforaminal injections.

[Cytogenetics profiles of renal carcinoma]. / Cytogénétique des carcinomes rénaux.

Renal carcinomas are histologically and prognostically heterogeneous. Genomic as well as chromosomal studies of these tumors have permitted a better comprehension of molecular mechanisms implicated in their development and progression. The most frequent histological subtypes are characterized by recurrent cytogenetic abnormalities, such as the loss of the chromosome 3 short arm involving a VHL gene copy in clear cell renal carcinomas, or trisomies 7 and 17 in papillary renal cell carcinomas. New histological subtypes like renal carcinomas associated with Xp11.2 translocations have also been individualized. Besides diagnosis, some chromosomal aberrations like the loss of a short arm of chromosome 9 in different renal carcinoma histological subtypes have a worse prognostic impact. The identification of chromosomal shuffles contributes in backing histological diagnosis and in precising the individual prognosis of patients. This review describes chromosomal abnormalities associated to renal carcinomas and their impact for an accurate classification of these tumors and the evaluation of their prognosis.