Long-term prevention of bladder cancer progression by alpha1-oleate alone or in combination with chemotherapy

Bladder cancer is common and one of the most costly cancer forms, due to a lack of curative therapies. Recently, clinical safety and efficacy of the alpha1-oleate complex was demonstrated in a placebo-controlled study of nonmuscle invasive bladder cancer. Our study investigated if long-term therapeutic efficacy is improved by repeated treatment cycles and by combining alpha1-oleate with low-dose chemotherapy. Rapidly growing bladder tumors were treated by intravesical instillation of alpha1-oleate, Epirubicin or Mitomycin C alone or in combination. One treatment cycle arrested tumor growth, with a protective effect lasting at least 4 weeks in mice receiving 8.5 mM of alpha1-oleate alone or 1.7 mM of alpha-oleate combined with Epirubicin or Mitomycin C. Repeated treatment cycles extended protection, defined by a lack of bladder pathology and a virtual absence of bladder cancer-specific gene expression. Synergy with Epirubicin was detected at the lower alpha1-oleate concentration and in vitro, alpha1-oleate was shown to enhance the uptake and nuclear translocation of Epirubicin, by tumor cells. Effects at the chromatin level affecting cell proliferation were further suggested by reduced BrdU incorporation. In addition, alpha1-oleate triggered DNA fragmentation, defined by the TUNEL assay. The results suggest that bladder cancer development may be prevented long-term in the murine model, by alpha1-oleate alone or in combination with low-dose Epirubicin. In addition, the combination of alpha1-oleate and Epirubicin reduced the size of established tumors. Exploring these potent preventive and therapeutic effects will be of immediate interest in patients with bladder cancer.     

Sélection de patientes et tolérance précoce de l’irradiation mammaire selon le protocole « Fast Forward » : résultats préliminaires

PurposeModerate hypofractionated radiotherapy has become routine practice for a selected population of patients treated for early-stage breast cancer. In April 2020, the Fast Forward (FF) study was published which introduced another extreme hypofractionated radiotherapy regimen in five sessions over a week. The aim of this work is to evaluate the population of first patients in whom this regimen was used in our department, as well as the results in terms of early toxicity.Material and methodsWe retrospectively analysed all the patients treated in our department according to the Fast Forward protocol after establishing an institutional consensus regarding the selection of patients with breast cancer without indication for lymph node irradiation. All patients received breast-only irradiation at a total dose of 26 Gy in five fractions according to protocol. All patients were treated by modern conformational techniques with planning large volume coverage between 95 and 100%. Acute toxicity of the treatment was assessed using the NCI CTC v4.0 scale and the general condition was assessed according to the WHO classification.ResultsBetween August 2020 and May 2021, 30 patients were included, treated on the breast alone without complement on the tumour bed or irradiation of the lymph node areas. The median age of the patients was 80 years (range: 60–85 years) with performance status 2 in 27 cases (89%). Only one patient had metastatic disease (3%), one patient presented locally advanced and 28 (94%) patients had early stage disease. Three patients (10%) were treated in dorsal decubitus according to the “field in the field” technique and 27 patients (90%) in isocentric lateral decubitus, which made it possible to avoid the organs at risk such as the heart (average dose of less than 1 Gy) and the lungs. The early toxicity observed was grade I radio dermatitis in 8 patients (27%). No grade 2 and 3 toxicity, as well as radiation-induced pain or lymphedema were observed.ConclusionsThe results of this series of patients treated with hypofractionated radiotherapy according to the Fast Forward protocol on the breast alone with adapted techniques show that the protocol is feasible, with little early toxicity but a greater follow-up is necessary to assess long-term toxicity.     

Segmentation of CT Lung Images Using FCM with Active Contour and CNN Classifier

Objective: Lung cancer is one of the unsafe diseases for human which reduces the patient life time. Generally, most of the lung cancers are identified after it has been spread into the lung parts and moreover it is difficult to find the lung cancer at the early stage. It requires radiologist and special doctors to find the tumoral tissue of the lung cancer. For this reason, the recommended work helps to segment the tumoral tissue of CT lung image in an effective way. Methods:  The research work uses hybrid segmentation technique to separate the lung cancer cells to diagnose the lung tumour. It is a technique which combines active contour along with Fuzzy c means to diagnose the tumoral tissue. Further the segmented portion was trained by Convolutional Neural Network (CNN) in order to classify the segmented region as normal or abnormal. Results: The evaluation of the proposed method was done by analyzing the results of test image with the ground truth image. Finally, the results of the implemented technique provided good accuracy, Peak signal to noise ratio (PSNR), Mean Square Error (MSE) value. In future the other techniques can be utilized to improve the details before segmentation. The proposed work provides 96.67 % accuracy. Conclusion: Hybrid segmentation technique involves several steps like preprocessing, binarization, thresholding, segmentation and feature extraction using GLCM.     

宫颈癌免疫治疗的耐药机制及应对措施

宫颈癌严重威胁全球女性的生命健康，晚期宫颈癌治疗手段有限，5年生存率不到20%，是妇科肿瘤的巨大挑战。免疫治疗是晚期宫颈癌患者的重要治疗手段之一，包括免疫检查点抑制剂、治疗性疫苗和过继性T细胞免疫疗法等，但免疫治疗耐药性使部分患者无应答而效果不佳。因此，迫切需要深入研究和探讨免疫耐药的机制从而改善耐药，现归纳总结了近年有关宫颈癌中免疫耐药机制的相关研究，主要分为肿瘤内在因素和外在免疫环境改变等因素，并介绍针对免疫耐药提出的应对措施及进展。     

Evaluation of Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) for the prevention of breast cancer-related lymphedema after axillary lymph node dissection using bioimpedance spectroscopy

BackgroundLymphedema is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 20%. Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) is a safe and relatively simple method, which decreases incidence of lymphedema dramatically. Our initial study showed an 88% decrease in clinical lymphedema rate. In the initial study, we used arm circumference measurement for the diagnosis of lymphedema and median follow up was 15 months. The aim of this study was to confirm these results after a long-term follow up period and by using bioimpedance spectroscopy (L-Dex) technology in detecting lymphedema.Study designAll patients, undergoing ALND with or without SLYMPHA between January 2014 and November 2020 were included in the study. Patients with no postoperative L-Dex measurements were excluded. A L-Dex score outside the normal range (±10 L-Dex unit) or ≥10 L-Dex unit increase above patient's baseline was considered as lymphedema. The incidence of lymphedema was compared between patients with and without SLYMPHA.Results194 patients were included in the study. 57% of cohort underwent SLYMPHA. Mean follow-up time was 47 ± 37 months. Patients, who underwent SLYMPHA, had a significantly lower rate of lymphedema (16% vs 32%; p = 0.01; OR 0.4 [0.2–0.8]).ConclusionSLYMPHA is a safe and relatively simple method, which continued its efficacy after a long-term follow up period. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.     

Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin

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Metastasis-directed Therapy in Prostate Cancer: Prognostic Significance of the ESTRO/EORTC Classification in Oligometastatic Bone Disease

AimsOligometastatic disease (OMD) represents a spectrum of clinical scenarios and various classification systems have been proposed. Bone-only OMD can occur in patients with advanced prostate cancer and validated decision-making tools are needed to assist patient selection for metastasis-directed therapy. The aim of the present study was to determine the prognostic utility of a classification system for OMD.Materials and methodsA retrospective review was conducted of all patients with bone-only oligometastatic prostate cancer treated with stereotactic body radiotherapy (SBRT) since November 2011. SBRT was delivered using CyberKnife® and gantry-based linear accelerator platforms. All patients were classified into oligometastatic states based on the European Society for Radiotherapy and Oncology/European Organisation for Research and Treatment of Cancer (ESTRO/EORTC) classification system. Kaplan–Meier and Cox regression analyses were carried out to determine the prognostic utility of this classification system.ResultsIn total, 105 patients with 145 osseous metastases were treated over 119 sessions. The median follow-up after SBRT was 23 months (interquartile range 10–39.8). Twelve patients had died after a median time of 31 months. The 3-year metastatic progression-free survival was 23% (95% confidence interval 13–32) and the 3-year overall survival was 88% (95% confidence interval 80–96). Patients in a metachronous oligometastatic state were 4.50 (95% confidence interval 1.19–17.10, P = 0.03) times more likely to experience metastatic progression compared with those with synchronous oligometastases, and 6.69 (95% confidence interval 1.05–42.50, P = 0.04) times more likely to experience any failure. Hazard ratio magnitudes increased for patients in a repeat oligometastatic state. The multivariate model for both metastatic progression-free survival and failure-free survival found prostate-specific antigen doubling time <4 months (P = 0.002; P = 0.05) to independently predict for progression.ConclusionThe ESTRO/EORTC classification of OMD predicts for progression in patients treated with SBRT for bone-only oligometastatic prostate cancer at our institution. Further validation in prospective series over multiple tumour sites is needed. These characterisation factors should be assessed in patients considered for metastasis-directed therapy together with established prognostic features.     

Robot-assisted-radical-cystectomy with total intracorporeal Y neobladder: Analysis of postoperative complications and functional outcomes with urodynamics findings

ObjectivesTo describe our robotic Y intracorporeal neobladder (ICNB) technique and to report its post-operative complications and urodynamics (UD) findings.Subjectsand Methods: In this prospective study we enrolled patients affected by MIBC (T1-T4N0–N1M0) from 01/2017 to 06/2021 at our Centers. All the patients underwent robotic radical cystectomy (RARC) with Y–ICNB reconfiguration. Early and late complications were collected and classified according to Clavien-Dindo. Continence and potency at 1, 3, 6 and 12 months were evaluated. At the 3rd month of follow-up patients underwent UD. Finally, in a retrospective match paired analysis the functional outcomes of Y RARC patients were compared with a cohort of open Y radical cystectomy.Results45 patients were enrolled. Overall 30-day complications were observed in 25 (55,5%) patients and 30 to 90-days complications in 4 (8,9%). 9 patients (20%) had Clavien ≥3 complications. UDs revealed median neobladder capacity of 268 cc, with a median compliance of 13 ml/cm H20; the voiding phase showed a voiding volume and a post void residual (PVR) of 154 cc and 105 cc respectively. At 12 months of follow-up 4.4%, 15.5% and 4.4% of the patients experienced urge, stress and mix urinary incontinence respectively. The comparison between Y RARC and Y open RC revealed a higher neobladder capacity with open approach (p = 0.049) with subsequent better findings during the voiding phase in terms of maximum flow (p = 0.002), voiding volume (p = 0.001) and PVR (p = 0.01). Focusing on continence recovery, a slight trend in favor of RARC was shown without reaching the statistical significance.ConclusionsRobotic Y–ICNB is feasible and safe as shown by the low rate of postoperative complications. Satisfying UD functional outcomes are achievable, both during filling and voiding phase.