光动力和冷冻治疗非黑色素瘤性皮肤癌的疗效观察

目的探讨光动力+冷冻治疗非黑色素瘤性皮肤癌(NMSC)患者的临床效果。方法选取2019年8月至2020年8月间锦州市中心医院收治的82例NMSC患者,采用随机数表法分为研究组和对照组,每组41例。对照组患者采用光动力治疗,研究组患者以光动力+冷冻治疗,比较两组患者的临床效果、视觉模拟评分量表(VAS)评分、不良反应和外观满意度。结果研究组患者客观有效率为95.1%,高于对照组的78.0%,差异有统计学意义(P <0.05)。治疗前,两组患者VAS评分比较,差异无统计学意义(P> 0.05)。治疗后,研究组患者VAS评分低于对照组,差异有统计学意义(P <0.05)。研究组患者不良反应发生率为4.9%,低于对照组的22.0%,差异有统计学意义(P <0.05)。研究组患者总满意度为97.6%,高于对照组的80.5%,差异有统计学意义(P <0.05)。结论光动力+冷冻治疗NMSC患者临床效果较好,不良反应少,患者疼痛缓解明显,外观满意度较高,建议临床推广。     

New frontiers in focal therapy for prostate cancer: Prostate-specific membrane antigen positron emission tomography/magnetic resonance imaging

Imaging has a central role in the context of focal therapy (FT) for prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) positron emission tomography/magnetic resonance imaging (PET/MRI) is a novel imaging modality that combines the morpho-functional information of MRI with the molecular characterization of PET. Some papers reported the potential advantages of PSMA PET/MRI in different clinical scenarios. Limited evidence on PSMA PET/MRI is available in the setting of FT. PSMA PET/MRI can be an effective imaging modality for detecting primary PCa and seems to provide accurate local staging of primary PCa. PSMA PET/MRI also shows high performance for restaging and detecting tumor recurrence. The higher soft-tissue contrast and the reduction of ionizing radiation are the main advantages reported in the literature compared to PET/computed tomography. PSMA PET/MRI could represent a turning point in the management of patients with PCa in the context of FT. Further studies are needed to confirm its applications in this specific clinical setting.     

高强度聚焦超声治疗前列腺癌的研究现状

 作为常见肿瘤的前列腺癌，其发病率逐年上升。手术是局限性病变的主要治疗手段，但仍然有一定的并发症和死亡率。放化疗等传统治疗手段也有其适应证和疗效的局限性，迫切需要有效的微创治疗方法。近年发展起来的高强度聚焦超声（HIFU）正日益受到人们的关注，对其作用机制、设备原理、适应证、治疗效果和局限性等问题作综述。     

高强度聚焦超声对中晚期前列腺癌患者去势治疗后机体免疫指标的影响

背景与目的：高强度聚焦超声(high intensity focused ultrasound,HIFU)可以有效治疗前列腺癌,但肿瘤是一种全身性的疾病,理想的肿瘤治疗方法是能够在不损伤正常组织的同时进行局部肿瘤切除,还能够激活全身的抗肿瘤免疫反应。本研究旨在探讨HIFU治疗对去势治疗后中晚期前列腺癌患者机体免疫指标的影响。方法：行去势治疗的中晚期前列腺癌患者40例,随机分为2组,HIFU组为去势治疗后2周行HIFU治疗(n=20),对照组为单纯去势治疗(n=20),全部经直肠前列腺穿刺病理检查确诊,均为晚期前列腺癌患者,即前列腺特异性抗原(prostate specific antigen,PSA)>20 ng/mL。患者自愿接受HIFU治疗并签署知情同意书。HIFU组与对照组患者平均年龄(72.56±12.38)岁、(75.23±9.35)岁(P=0.446 3);初始PSA为(105.22±20.55)ng/mL、(100.53±18.38)ng/mL(P=0.451 5)。分别取治疗前和治疗后2周前列腺癌患者外周血6 d,检测T淋巴细胞亚群(CD4⁺、CD8⁺、CD4⁺/CD8⁺)和外周血Th细胞因子(IFN-γ、IL-2、IL-4、IL-10)。结果：HIFU组患者治疗后CD4⁺百分比及CD4⁺/CD8⁺比值明显升高;细胞因子IFN-γ、IL-2水平明显增高,而IL-4、IL-10水平明显降低,与治疗前相比差异有统计学意义(P＜0.05),Th1/Th2平衡向Th1漂移。而对照组患者治疗前、后各项免疫指标差异无统计学意义(P＞0.05)。HIFU组与对照组前、后各项免疫指标差值比较差异有统计学意义(P＜0.05)。结论：HIFU治疗可在近期内改善去势治疗后中晚期前列腺癌患者机体免疫功能。     

CBCT和超声技术在HIFU与IMRT联合治疗胰腺癌中的应用价值

目的 探讨千伏级锥形束CT（CBCT）与超声技术在高强度聚焦超声（HIFU）联合调强放疗（IMRT）治疗胰腺癌中的应用价值。方法 2010年12月至2012年6月收治的21例胰腺癌患者均采用HIFU联合IMRT治疗模式。应用超声多普勒评估治疗情况,调整HIFU治疗剂量和治疗次数;CBCT引导下行IMRT,2 Gy／次,5次／周,6～7周,DT 58～70Gy。分析IMRT在CBCT引导后的摆位误差及PTV外扩边界。评价患者治疗前、后的疼痛缓解情况和KPS评分。结果 本组21例患者共实施6～18次HIFU治疗。IMRT在CBCT引导后平均误差小于2 mm。21例患者中疼痛完全缓解12例,部分缓解8例,无效1例,总有效率为95.0％。无1例发生严重并发症。治疗前KPS评分为 （46.8±9.1）分,治疗后为（87.1±8.3）分,差异有统计学意义（P＜0.01）。全组3例患者死亡,平均生存期10个月。结论 将CBCT图像引导技术与超声技术应用于HIFU联合IMRT治疗胰腺癌,能有效降低危及器官的受照射量,增强肿瘤的局部控制,减少并发症,提高患者的生存质量。     

"Wide local ablation" of localized breast cancer using high intensity focused ultrasound

BACKGROUND AND OBJECTIVE: High intensity focused ultrasound (HIFU) is a non-invasive technique for tumor ablation. The goal of this study was to investigate the feasibility of performing wide local ablation using ultrasound-guided HIFU in the treatment of patients with localized breast cancer. METHODS: Twenty-three patients with histologically proven breast cancer were enrolled in this prospective clinical trial. They underwent HIFU treatment for breast cancer including the tumor and 1.5-2.0 cm normal breast tissue surrounding the tumor, followed by modified mastectomy 1-2 weeks after HIFU. Radiological examination, histological, and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) methods were performed to evaluate therapeutic effects in the treated region. RESULTS: Thermal ablation was confirmed in all 23 patients. It included tumor and normal breast tissue surrounding the tumor. Mean values of the largest parallel and perpendicular dimensions, and volume of HIFU lesions in excised breasts were significantly larger than those of the targeted tumors respectively (P < 0.001). Hematoxylin and eosin (H & E) staining showed clear evidence of complete coagulation necrosis in the treated regions. However, no apoptotic cells were detected in either treated tumor or normal breast tissue. CONCLUSION: As a non-invasive therapy, ultrasound-guided HIFU can induce wide local ablation in the treatment of patients with localized breast cancer.     

Novel Therapeutic Method for Unresectable Pancreatic Cancer—The Impact of the Long-Term Research in Therapeutic Effect of High-Intensity Focused Ultrasound (HIFU) Therapy

High-intensity focused ultrasound (HIFU) is a novel advanced therapy for unresectable pancreatic cancer (PC). HIFU therapy with chemotherapy is being promoted as a novel method to control local advancement by tumor ablation. We evaluated the therapeutic effects of HIFU therapy in locally advanced and metastatic PC. PC patients were treated with HIFU as an optional local therapy and systemic chemotherapy. The FEP-BY02 (Yuande Bio-Medical Engineering) HIFU device was used under ultrasound guidance. Of 176 PC patients, 89 cases were Stage III and 87 were Stage IV. The rate of complete tumor ablation was 90.3%, while that of symptom relief was 66.7%. The effectiveness on the primary lesions were as follows: complete response (CR): n = 0, partial response (PR): n = 21, stable disease (SD): n = 106, and progressive disease (PD): n = 49; the primary disease control rate was 72.2%. Eight patients underwent surgery. The median survival time (MST) after diagnosis for HIFU with chemotherapy compared to chemotherapy alone (100 patients in our hospital) was 648 vs. 288 days (p < 0.001). Compared with chemotherapy alone, the combination of HIFU therapy and chemotherapy demonstrated significant prolongation of prognosis. This study suggests that HIFU therapy has the potential to be a novel combination therapy for unresectable PC.     

Focal therapy in prostate cancer: A review of seven common controversies

Radical treatments such as prostatectomy and radiotherapy have demonstrated success in terms of biochemical and disease-specific survival for localised prostate cancer. However, whilst the end goal of any cancer treatment is to control or cure disease it must also do so by minimising any side effects that may be experienced by the patient. Focal therapy as a concept aims to redress this established therapeutic ratio by treating areas of the prostate affected by significant disease as opposed to treating the entire gland. However, there are a number of common criticisms of focal therapy – we deem the seven sins – that require further interrogation.     

High intensity focused ultrasound (HIFU) for prostate cancer: Current clinical status,outcomes and future perspectives

Two devices are currently available for the treatment of prostate cancer with HIFU: Sonablate® and Ablatherm®. The outcomes achieved for primary-care patient are very promissing with mid- and long-term progression-free survival rates around 70%, negative postoperative prostate biopsies almost 85%, and an excellent morbidity profile. Moreover, HIFU has a considerable potential for local recurrence after radiation failure. Recently, some early experiences on focal therapy suggest that HIFU could be an excellent option for highly selected patient.     

Factors influencing thermal injury to skin and abdominal wall structures in HIFU ablation of uterine fibroids

Objective: To investigate the factors which may cause thermal injury of abdominal wall structures in ultrasound-guided high-intensity focussed ultrasound (USgHIFU) ablation of uterine fibroids.

Method: A total of 892 patients with uterine fibroids diagnosed on contrast-enhanced magnetic resonance imaging (MRI) scans received HIFU ablation and follow-up MRI scanning. After therapy, thermal injury to the skin was assessed via measurement of skin redness, blisters, subcutaneous nodules and to the abdominal wall structures via measurement of signal intensity on T2-weighted MRI images. A total of 151 patients were assigned to the injury group, 741 patients were assigned to the non-injury group. The relationship between patient and treatment parameters and injury were analysed using univariate and multiple logistic regression analyses.

Results: Univariate logistic regression revealed that sonication time, sonication time per hour, total energy deposited, distance from uterine fibroid ventral side to skin, volume of uterine fibroids, abdominal wall scar, abdominal wall thickness and body mass index (BMI) all affected whether thermal injury occurred (p?p?=?0.000, OR?=?2.228, 95% CI 1.831–2.712), abdominal wall scar (p?=?0.019, OR?=?1.639, 95% CI 1.085–2.477) and abdominal wall thickness (p?=?0.000, OR?=?1.562, 95% CI 1.313–1.857) were significantly correlated with thermal injury.

Conclusion: Multiple logistic regression analysis revealed that abdominal wall thickness, total energy and abdominal wall scar were the most significant influencing factors that influenced minimal thermal injury of abdominal wall structures in USgHIFU ablation of uterine fibroids.     

Pro-survival and pro-growth effects of stress-induced nitric oxide in a prostate cancer photodynamic therapy model

We discovered recently that human breast cancer cells subjected to photodynamic therapy (PDT)-like oxidative stress localized in mitochondria rapidly upregulated nitric oxide synthase-2 (NOS2) and nitric oxide (NO), which increased resistance to apoptotic photokilling. In this study, we asked whether human prostate cancer PC-3 cells would exploit NOS2/NO similarly and, if so, how proliferation of surviving cells might be affected. Irradiation of photosensitized PC-3 cells resulted in a rapid (<1 h), robust (∼12-fold), and prolonged (∼20 h) post-irradiation upregulation of NOS2. Caspase-3/7 activation and apoptosis were stimulated by NOS2 inhibitors and a NO scavenger, implying that induced NO was acting cytoprotectively. Cyclic GMP involvement was ruled out, whereas suppression of pro-apoptotic JNK and p38 MAPK activation was clearly implicated. Cells surviving photostress grew back ∼2-times faster than controls. NOS2 inhibition prevented this and the large increase in cell cycle S-phase occupancy observed after irradiation. Thus, photostress upregulation of NOS/NO elicited both a pro-survival and pro-growth response, both of which could compromise clinical PDT efficacy unless suppressed, e.g. by pharmacological intervention with a NOS2 inhibitor.     

The role of androgen deprivation therapy plus radiation therapy in patients with non-metastatic prostate cancer

Introduction: Androgen deprivation therapy (ADT) has a long and illustrious history in the treatment for prostate cancer and continues to be a mainstay treatment for locally advanced and high-risk patients. Because the survival for even high-risk prostate patients is lengthy, details of treatment such as duration and timing must be considered carefully and weighed against the various side effects.

Areas covered: In the following article, we discuss the evolution of ADT from its initial applications in metastatic prostate cancer to its more recent incorporation into front line treatment in conjunction with radiation therapy (RT) for intermediate and high risk disease. We emphasize the results of phase III trials, which have defined the role of ADT in combination with RT in this patient population. We emphasize not only the potential benefits of ADT with RT, but also the potential risks, and underscore the need to consider both in order to maximize the therapeutic ration for each patient. Studies were identified via a search of PubMed as well as the bibliographies of articles discussed herein.

Expert commentary: Even with advanced radiation techniques and dose escalation, adjuvant ADT continues to confer an overall survival benefit in intermediate and high-risk patients, although some evidence suggest that duration of treatment may be shortened, particularly for the high-risk group. The coming years will shed further information on this complicated topic with maturing of results from several ongoing trials.     

慢性前列腺炎及多灶型HGPIN患者再次穿刺时发展为前列腺癌风险的研究

目的 探讨伴有慢性前列腺炎及多灶型高级别前列腺上皮内瘤(Widespread high grade prostatic intraepithelial neoplasia,wHGPIN)患者再次活检,发展为前列腺癌风险的研究。方法2006年7月—2014年12月收集前列腺再次穿刺活检者172例,均为初次活检病理诊断为HGPIN者,穿刺为经直肠超声引导下前列腺12点穿刺法。再次穿刺均是在初次穿刺6个月后进行的。多灶型HGPIN界定为在前列腺活检中有2针及以上检出高级别前列腺上皮内瘤,孤立型HGPIN界定为在前列腺活检中有1针检出高级别前列腺上皮内瘤。结果 初次活检172例HGPIN患者,孤立型HGPIN 102例,伴有慢性前列腺炎患者17例;多灶型HGPIN 70例,伴有慢性前列腺炎患者54例;172例HGPIN患者再次活检病理为前列腺腺癌者48例,多灶型HGPIN组检出率52.86%(37/70),孤立型HGPIN组检出率为10.78%(11/102),差异有统计学意义(P＜0.001);多灶型HGPIN伴有慢性前列腺炎组前列腺腺癌检出率高于不伴有慢性前列腺炎组,差异有统计学意义(P=0.011)。经Logistic回归模型分析,慢性前列腺炎和多灶型HGPIN是再次活检为前列腺癌的独立风险因素。结论 首次活检为慢性前列腺炎与多灶型HGPIN患者是再次活检为前列腺腺癌的高风险因素,建议超声引导下经直肠前列腺再次活检。     

Salvage focal cryosurgery may delay use of androgen deprivation therapy in cryotherapy and radiation recurrent prostate cancer patients

Introduction: Salvage treatment options for recurrent unilateral prostate cancer (PCa) after primary radiation are limited and associated with severe complications and poor quality of life measures. Salvage focal cryotherapy (SFC) has shown success in biochemical recurrence (BCR) free survival. We aim to determine if SFC can delay use of androgen deprivation therapy (ADT) in recurrent PCa with low morbidity.

Methods: A retrospective review of patients who underwent SFC at our institution from 2007 to 2015 was performed. Patients with?<2 follow-up prostate-specific antigen (PSA) values, metastatic disease, and a history of radical prostatectomy were excluded. Age at treatment, prior treatment history, PSA nadir, complications, BCR status (nadir?+2?ng/ml), and follow-up data were obtained/analysed. ADT was commenced if patient experienced BCR and had a PSA doubling time?<6?months or positive confirmatory biopsy or positive imaging. Cox regression and survival analysis were used to assess confounding and time to BCR respectively.

Results: A total of 65 patients were included and followed for a median of 26.6 (8.0–99.0) months. Thirty-one (47.7%) patients did not experience BCR. An even higher number of patients (52/65, 80.0%) are yet to receive ADT. Of those who experienced BCR [median time to BCR, 17.1 [interquartile range (IQR):11.4–23.3] months], 22/34 (64.7%) are currently carefully monitored without ADT. Survival analysis showed a biochemical recurrence-free survival of 48.1 at 1- and 3-year follow up. No patient died/experienced major complications.

Conclusions: SFC may be used to delay the use of ADT. Further assessment of our findings with high-powered studies and longer follow-up is required.     

Volumetric modulated arc therapy (VMAT) vs. serial tomotherapy, step-and-shoot IMRT and 3D-conformal RT for treatment of prostate cancer

Introduction

Volumetric modulated arc therapy (VMAT), a complex treatment strategy for intensity-modulated radiation therapy, may increase treatment efficiency and has recently been established clinically. This analysis compares VMAT against established IMRT and 3D-conformal radiation therapy (3D-CRT) delivery techniques.

Methods

Based on CT datasets of 9 patients treated for prostate cancer step-and-shoot IMRT, serial tomotherapy (MIMiC), 3D-CRT and VMAT were compared with regard to plan quality and treatment efficiency. Two VMAT approaches (one rotation (VMAT1x) and one rotation plus a second 200° rotation (VMAT2x)) were calculated for the plan comparison. Plan quality was assessed by calculating homogeneity and conformity index (HI and CI), dose to normal tissue (non-target) and D_95% (dose encompassing 95% of the target volume). For plan efficiency evaluation, treatment time and number of monitor units (MU) were considered.

Results

For MIMiC/IMRT_MLC/VMAT2x/VMAT1x/3D-CRT, mean CI was 1.5/1.23/1.45/1.51/1.46 and HI was 1.19/1.1/1.09/1.11/1.04. For a prescribed dose of 76 Gy, mean doses to organs-at-risk (OAR) were 50.69 Gy/53.99 Gy/60.29 Gy/61.59 Gy/66.33 Gy for the anterior half of the rectum and 31.85 Gy/34.89 Gy/38.75 Gy/38.57 Gy/55.43 Gy for the posterior rectum. Volumes of non-target normal tissue receiving ?70% of prescribed dose (53 Gy) were 337 ml/284 ml/482 ml/505 ml/414 ml, for ? 50% (38 Gy) 869 ml/933 ml/1155 ml/1231 ml/1993 ml and for ? 30% (23 Gy) 2819 ml/3414 ml/3340 ml/3438 ml /3061 ml. D_95% was 69.79 Gy/70.51 Gy/71,7 Gy/71.59 Gy/73.42 Gy. Mean treatment time was 12 min/6 min/3.7 min/1.8 min/2.5 min.

Conclusion

All approaches yield treatment plans of improved quality when compared to 3D-conformal treatments, with serial tomotherapy providing best OAR sparing and VMAT being the most efficient treatment option in our comparison. Plans which were calculated with 3D-CRT provided good target coverage but resulted in higher dose to the rectum.     

The role of galectin-1 in in vitro and in vivo photodynamic therapy with a galactodendritic porphyrin

Conventional photodynamic agents used in clinic are porphyrin-based photosensitizers. However, they have low tumour selectivity, which may induce unwanted side-effects and damage to healthy tissues. In this study, we used a porphyrin with dendritic units of galactose (PorGal₈) developed by us, which can target the galactose-binding protein, galectin-1, known to be overexpressed in many tumour tissues. In vitro and in vivo studies had been conducted for the validation of PorGal₈ effectiveness. We showed a specific uptake of PorGal₈ and induction of apoptotic cell death by generating oxidative stress and alterations in the cytoskeleton of bladder cancer cells overexpressing galectin-1. We further validated the photodynamic efficiency of PorGal₈ in athymic nude mice (Balb/c nu/nu) bearing subcutaneously implanted luciferase-positive bladder cancer xenografts, overexpressing galectin-1 protein. PorGal₈ (5 μmol/kg, intraperitoneal), injected 24 h before light delivery (50.4 J/cm²), inhibited tumour growth. We conclude that the use of PorGal₈ enables selective target and cytotoxicity by photodynamic therapy in cancer cells overexpressing galectin-1, preventing undesired phototoxicity in the surrounding healthy tissues.     

Evaluation of image-guided radiation therapy (IGRT) technologies and their impact on the outcomes of hypofractionated prostate cancer treatments: a radiobiologic analysis

PURPOSE: To quantify the mitigation of geometric uncertainties achieved with the application of various patient setup techniques during the delivery of hypofractionated prostate cancer treatments, using tumor control probability (TCP) and normal tissue complication probability. METHODS AND MATERIALS: Five prostate cancer patients with approximately 16 treatment CT studies, taken during the course of their radiation therapy (77 total), were analyzed. All patients were planned twice with an 18 MV six-field conformal technique, with 10- and 5-mm margin sizes, with various hypofractionation schedules (5 to 35 fractions). Subsequently, four clinically relevant patient setup techniques (laser guided and image guided) were simulated to deliver such schedules. RESULTS: As hypothesized, the impact of geometric uncertainties on clinical outcomes increased with more hypofractionated schedules. However, the absolute gain in TCP due to hypofractionation (up to 21.8% increase) was significantly higher compared with the losses due to geometric uncertainties (up to 8.6% decrease). CONCLUSIONS: The results of this study suggest that, although the impact of geometric uncertainties on the treatment outcomes increases as the number of fractions decrease, the reduction in TCP due to the uncertainties does not significantly offset the expected theoretical gain in TCP by hypofractionation.     

自噬在前列腺癌发生发展和治疗中的研究进展

自噬是真核细胞通过溶酶体对其自身生物大分子和细胞器回收再利用的过程,其在维持细胞稳态中发挥重要作用,并参与多种病理生理过程。在肿瘤的发病过程中,自噬发挥“双面作用”,既可以抗癌也能促癌。前列腺癌是老年男性最常见的恶性肿瘤,研究表明前列腺癌的发生发展与自噬作用密切相关,放化疗、内分泌治疗等对肿瘤细胞造成的应激可通过自噬得以缓解,抵抗治疗,因而自噬抑制剂对于放化疗等具有协同促进作用。本文就自噬在前列腺癌中发病和治疗进行综述,以期为前列腺癌的诊治提供一些新的思路。