高强度聚焦超声联合术前新辅助化疗治疗乳腺癌的疗效观察

目的对乳腺癌术前做新辅助化疗的病人进行低能量的高强度聚焦超声(HIFU)治疗,探讨HIFU联合化疗药物治疗乳腺肿瘤的有效性和安全性。方法选取同期经病理确诊可手术的女性乳腺癌患者40例,分为HIFU治疗组和对照组各20例,HIFU治疗组患者术前接受化疗的同时进行一次HIFU治疗,对照组术前只接受化疗,两组患者均行乳腺癌改良根治性手术,并于治疗前后及手术前进行血常规、肝功能、肾功能和超声检查。化疗期间观察药物的不良反应。结果治疗后HIFU治疗组肿瘤原发灶的大小较对照组明显缩小(P<0.05),血流明显减少,临床分期明显降低。两组患者的不良反应比较差异无统计学意义(P>0.05)。结论HIFU联合化疗药物治疗乳腺肿瘤是安全和有效的。     

High-intensity focused ultrasound treatment for intra-abdominal desmoid tumors: a report of four cases

Desmoid tumors are rare clonal fibroblastic proliferations that can arise at abdominal or extra-abdominal sites. Complete surgical resection is the primary treatment for resectable desmoid tumors, but a high rate of local recurrence has been reported even after complete resection. For patients with a recurrent tumor, the goals of treatment are to control the recurrence, maintain quality of life, and prolong survival. Radiofrequency ablation, radiotherapy, chemotherapy, and other medical therapies can be used as alternative methods, but there are considerable controversies over the roles of these methods in the management of desmoid tumors. High-intensity focused ultrasound (HIFU) is a minimally invasive and effective method for treatment of solid tumors. We used HIFU to treat four patients with intra-abdominal desmoid tumors from June 2011 to September 2013. Post-procedural pain was seen in all patients. One patient had an intra-abdominal abscess and another suffered a slight injury to the femoral nerve. The patients were followed up for 19–46 months (mean 34 months) until April 2015. The tumor in one patient disappeared, and no tumor progression was observed in the other patients.     

Percutaneous image-guided radiofrequency ablation of liver tumors

The development of image-guided percutaneous techniques for local tumor ablation has been one of the major advances in the treatment of liver malignancies. Over the past two decades, several methods for chemical or thermal tumor destruction have been clinically tested. Among these methods, radiofrequency (RF) ablation is currently established as the primary ablative modality at most institutions. RF ablation is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma (HCC) when liver transplantation or surgical resection are not suitable options. In addition, RF ablation is emerging as a viable alternate to surgery for inoperable patients with limited hepatic metastatic disease, especially from colorectal cancer. Several series have shown that RF ablation can result in complete tumor eradication in properly selected candidates, and have provided indirect evidence that the treatment improves survival. In this article, we review technique, indications, and clinical results of percutaneous RF ablation in the treatment of HCC and colorectal hepatic metastases.     

Neoadjuvant Chemotherapy in breast cancer

Neoadjuvant chemotherapy for breast cancer was originally used in locally advanced inoperable disease in order to achieve surgical resection. It was then extended to operable breast cancer with a view to downstaging tumors to facilitate breast-conserving surgery. Long-term results from randomized studies have shown no difference in disease-free or overall survival between neoadjuvant and adjuvant chemotherapy. The main benefit of neoadjuvant chemotherapy is its ability to downstage large tumors with a view to treatment by breast-conserving surgery. Since pathological complete response is thought to be main factor to achieve long-term survival, development of new agent or novel combination treatment is needed.     

躯干和肢体软组织肉瘤的围手术期化疗与放疗

虽然手术是肢体和躯干原发软组织肉瘤的根治性治疗手段,但对于高危患者单纯手术常难以获得疾病的长期控制。治疗失败的主要原因为远处转移,其次为局部复发。一些局部进展期的患者可能面临无法手术切除,或仅边缘可切除,因此预后很差。围手术期的系统治疗和放疗可提高手术疗效。如何确立围手术期系统治疗的价值颇具挑战。系统治疗可以缩小肿瘤。但要证明其对局部控制的价值从而促进实施更为保守的外科手术的证据仍不充分。对于那些原发肿瘤被认定为难以或不可能切除的患者,新辅助化疗可能为疾病的局部控制提供一种选择。围手术期的系统治疗也可以避免远处转移的发生。近期的研究表明,以蒽环类药物/异环磷酰胺为基础的辅助治疗能够使患者获益,虽然证据来自于对一项大型研究的再次分析。一项新辅助化疗的随机研究提示,对某些经过选择的肉瘤组织学亚型,以蒽环类药物/异环磷酰胺为基础的系统化疗可能改善患者无病生存和总生存期。其疗效的获得主要是通过改善远处无转移生存而不是局控率的提高。这两项研究所采用的方法均存在一定的局限性,因此需要进一步探索。尽管如此,我们相信这些结果支持在局部进展期、肢体和躯干原发的软组织肉瘤患者中进行新辅助化疗。放疗与手术结合在软组织肉瘤的治疗中有确切的疗效。虽然预后并不因放疗和手术的先后顺序而异,但不良反应却存在差异。辅助放疗较新辅助放疗有更低的围手术期伤口并发症,但相对于新辅助放疗而言,辅助放疗需要更高的放射剂量,对长期功能的预后差于新辅助放疗。因此,我们相信围手术期放疗与化疗一样,在可能的情况下,应尽可能在术前进行。     

高强度聚焦超声治疗晚期恶性胸腹壁肿瘤

目的 探讨高强度聚焦超声(HIFU)对复发、转移晚期恶性胸腹壁肿瘤的治疗疗效。方法 对10例患者常规抗肿瘤治疗后晚期胸腹壁恶性病灶进行15次HIFU治疗。结果 10例患者中肿瘤大小在3～5cm3例，5～8cm3例，8cm以上4例。其中多发性病灶7例，进行过手术治疗7例，放疗6例，化疗6例。HIFU治疗后部分缓解2例，稳定5例，进展2例，失访1例。3例合并肋间神经痛术后消失，1例合并肋骨转移术后骨转移信号消失。死亡2例。结论 HIFU对手术、放化疗后复发、转移性胸腹壁恶性肿瘤是可以选择的、有效的局部治疗手段之一。     

Tumor vessel destruction resulting from high-intensity focused ultrasound in patients with solid malignancies

The purpose of this study was to explore the sequential imaging and histologic alterations of tumor blood vessels in the patient with solid malignancies after extracorporeal treatment of high-intensity focused ultrasound (HIFU). A total of 164 patients underwent extracorporeal HIFU ablation of malignant solid tumors. After HIFU treatment, enhanced magnetic resonance imaging (MRI), color Doppler ultrasound (US) imaging, dynamic radionuclide scanning, digital subtraction angiography, and histologic study were performed to monitor the response of tumor vessels to HIFU ablation. Compared with tumor images in the patients before HIFU, clinical images showed an abrupt interruption, followed by the cessation of blood flow within the tumor vessels after HIFU treatment. The histologic examination indicated that not only the treated tumor cells showed coagulative necrosis, but also small tumor vessels were severely damaged by the HIFU treatment. The results strongly imply that the damaged tumor vessels might play a critical role in secondary tumor cell death, and then indirectly strengthen the destructive force of focused US beams on tumor tissue. It is concluded that tumor vessel damage can be induced by HIFU, which may be a promising strategy in the treatment of patients with solid malignancies.     

新辅助化疗联合腹腔镜下中低位直肠癌保肛手术的临床效果

目的 探讨新辅助化疗联合腹腔镜手术在中低位直肠癌保肛治疗中的应用价值.方法 选择我院2007年1月-2012年12月收治的可切除的中低位直肠癌54例,分为辅助化疗组24例和对照组30例,两组均行腹腔镜下直肠癌手术治疗,辅助化疗组术前行3周期FOLFOX4方案（奥沙利铂＋亚叶酸钙＋氟尿嘧啶）新辅助化疗,对照组不行任何放化疗.结果 辅助化疗组41.6％的病例肿瘤体积缩小、变软,肿瘤距肛缘距离增加,保肛率为75.0％;对照组保肛率为46.7％,差异有统计学意义（P＜0.05）;经腹直肠前切除术比例、淋巴结转移比例与对照组比较,差异均有统计学意义（P＜0.05）.结论 术前新辅助化疗联合腹腔镜手术可显著提高中低位直肠癌的根治率及保肛率.     

Extracorporeal high intensity focused ultrasound in the treatment of patients with solid malignancy.

The ideal treatment of localized cancer should cause the complete death of tumor cells without damage to surrounding normal tissue. High intensity focused ultrasound (HIFU) is such a potential treatment, which can induce complete coagulation necrosis of a targeted tumor, at depth, through the intact skin. The concept of using HIFU as a non-invasive therapy has attracted attention in medicine for 60 years. Recently, it has received increasing interest as a promising modality for the treatment of localized solid malignancies. The goal of this article is to introduce recent clinical developments in the use of extracorporeal HIFU ablation for solid tumors, including those of liver, breast, bone, kidney, pancreas, soft tissue, and uterus. It describes the physical principles and ablative mechanisms, three-dimensional therapeutic regimes, and medical imaging used in HIFU. Currently, large numbers of patients with solid malignancy are already treated using HIFU, and short-term clinical results are very encouraging. However, large-scale randomized clinical trials are necessary to evaluate long-term efficacy of HIFU treatment for solid malignancies. It is concluded that this non-invasive ablation can be considered as a conventional therapy for widespread clinical use only when the results from prospective, randomized clinical trials worldwide are available.     

Preclinical in vivo Evaluation of an Extracorporeal HIFU Device for Ablation of Pancreatic Tumors

Extracorporeal high-intensity focused ultrasound (HIFU) can be used to ablate tissue noninvasively by delivering focused ultrasound energy from an external source. HIFU for clinical treatment of pancreatic cancer has been reported; however, systematic evaluation of the safety and efficacy of pancreatic ablation with HIFU has not been performed. The objectives of this in vivo study are as follows: (1) assess the safety and feasibility of targeting and ablating pancreatic tissue using the FEP-BY02 HIFU system (Yuande Bio-Medical Engineering, Beijing, China); (2) evaluate a method for estimating in situ acoustic treatment energy in an in vivo setting; and (3) identify the optimal treatment parameters that result in safe and effective ablation of the pancreas. The pancreata of 12 common swine were treated in vivo. Prior to therapy, blood was drawn for laboratory analysis. Animals were then treated with extracorporeal HIFU at three different acoustic treatment energies (750, 1000 and 1250 J). Endoscopy was performed prior to and immediately following HIFU therapy to assess for gastric injury. Blood was drawn after completion of the treatment and on days 2 and 7 following treatment to assess for biochemical evidence of pancreatitis. Animals were then euthanized 7 d following treatment and a necropsy was performed to assess for unintended injury and to obtain pancreatic tissue for histology to assess efficacy of HIFU ablation. Histologic scoring of pancreatic tissue changes was performed by a pathologist blinded to the treatment energy delivered. The degree of ablation identified on histology correlated with the treatment energy. No collateral tissue damage was seen at treatment energies of 750 and 1000 J. At 1250 J, thermal injury to the abdominal muscles and gastric ulcers were observed. There were no premature deaths, serious illnesses, skin burns or evidence of pancreatitis on biochemical analysis. HIFU treatment of the pancreas is feasible, safe and can be used to ablate tissue noninvasively. A clinical trial in humans examining the use of extracorporeal HIFU for palliation of pain related to pancreatic cancer is planned. (E-mail: jooha@u.washington.edu)     

高强度聚焦超声治疗放疗后残留肝癌的初步临床观察

目的 探讨高强度聚焦超声(HIFU)治疗放疗后残留肝癌的安全性和有效性.方法 HIFU治疗20例三维适形、立体定向放疗后25个肝癌残留病灶,比较HIFU治疗前、治疗后1周肝功能和血细胞变化,及治疗前、治疗后2周MRI、AFP变化,并行生存分析.结果 平均随访(12.6±8.0)个月,中位生存时间、1年生存率分别为22个月、87.5%.所有患者无皮肤烧伤.白蛋白、谷丙转氨酶、谷草转氨酶、总胆红素、直接胆红素、红细胞、白细胞、血小板HIFU治疗前与治疗后1周比较,差异无统计学意义(P=0.156、0.356、0.203、0.659、0.531、0.519、0.310、0.346).AFP(9例阳性)HIFU治疗前与治疗后2周比较,差异有统计学意义(P=0.030).MRI示16个病灶完整消融,6个消融体积≥80%.结论 HIFU可能是一种安全、有效治疗适形、立体定向放疗后残留肝癌的新方法.

Abstract：

Objective To investigate the safety and effect of high intensity focused ultrasound ablation(HIFU) on residual liver cancer in patients after radiotherapy. Methods Twenty liver cancer patients with twenty five residual tumors after three-dimensional conformal radiotherapy or stereotactic radiotherapy received HIFU ablation. Liver function and periphery blood cell counts were performed before HIFU and at 1 week after HIFU in all patients. Enhanced MRI and α-fetoprotein (AFP) level were performed before HIFU and at 2 weeks after HIFU to evaluate the effect of HIFU ablation. The survival of all patients was assessed by the Kaplan-Meier method. Results The mean follow-up time was (12.6 ± 8.0)months. The median survival time and 1-year survival rate were 22 months and 87.5% respectively. No skin burns were observed in all patients. As compared with before HIFU,there were no significant differences in the levels of albumin,alanine transarninase, aspartate transarninase, total bilirubin, direct bilirubin, blood red cell counts,blood white cell counts and blood platelet counts at 1 week after HIFU (paired t test, P =0. 156,0. 356,0. 203,0.659,0. 531,0. 519,0. 310,0. 346, respectively). Significant difference in AFP level of 9 patients with AFP＞20 μg/L was observed before HIFU and 2 weeks after HIFU (paired t test, P =0.030). Among 25 residual liver tumors,sixteen with complete ablation and six with ablation volume of ≥80% were observed by enhanced MRI at 2 weeks after HIFU. Conclusions HIFU may be a safe and effective new method to ablate residual liver cancer after three-dimensional conformal radiotherapy or stereotactic radiotherapy.     

新辅助化疗联合高-低氧吸入放射治疗浸润性膀胱癌的研究

目的 评估新辅助化疗联合高-低氧吸入放射治疗浸润性膀胱癌的疗效及安全性.方法 对31例无法耐受或拒绝接受膀胱全切手术的浸润性膀胱癌患者进行保留膀胱治疗,先给予新辅助化疗2周期,然后给予盆腔适形放疗,放疗过程中先后吸入高低浓度氧.对肿瘤部分缓解及复发患者行保留膀胱的手术.结果 肿瘤完全缓解率为71.0%(22/31),部分缓解率29.0%(9/31).9例部分缓解的患者接受了保留膀胱的手术治疗,4例复发患者接受了再次手术治疗.结论 新辅助化疗联合高-低氧吸入放疗为部分无法耐受或拒绝接受膀胱全切术的浸润性膀胱癌患者提供了一种有效的治疗方法.     

新辅助化疗联合高-低氧吸入放射治疗浸润性膀胱癌的研究

目的评估新辅助化疗联合高-低氧吸入放射治疗浸润性膀胱癌的疗效及安全性。方法对31例无法耐受或拒绝接受膀胱全切手术的浸润性膀胱癌患者进行保留膀胱治疗,先给予新辅助化疗2周期,然后给予盆腔适形放疗,放疗过程中先后吸入高低浓度氧。对肿瘤部分缓解及复发患者行保留膀胱的手术。结果肿瘤完全缓解率为71．0％（22／31）,部分缓解率29．0％（9／31）。9例部分缓解的患者接受了保留膀胱的手术治疗,4例复发患者接受了再次手术治疗。结论新辅助化疗联合高-低氧吸入放疗为部分无法耐受或拒绝接受膀胱全切术的浸润性膀胱癌患者提供了一种有效的治疗方法。     

新辅助化疗联合高-低氧吸入放射治疗浸润性膀胱癌的研究

目的 评估新辅助化疗联合高-低氧吸入放射治疗浸润性膀胱癌的疗效及安全性.方法 对31例无法耐受或拒绝接受膀胱全切手术的浸润性膀胱癌患者进行保留膀胱治疗,先给予新辅助化疗2周期,然后给予盆腔适形放疗,放疗过程中先后吸入高低浓度氧.对肿瘤部分缓解及复发患者行保留膀胱的手术.结果 肿瘤完全缓解率为71.0%(22/31),部分缓解率29.0%(9/31).9例部分缓解的患者接受了保留膀胱的手术治疗,4例复发患者接受了再次手术治疗.结论 新辅助化疗联合高-低氧吸入放疗为部分无法耐受或拒绝接受膀胱全切术的浸润性膀胱癌患者提供了一种有效的治疗方法.     

Primary hepatic follicular dendritic cell sarcoma: A case report

BACKGROUND Follicular dendritic cell sarcoma(FDCS) is an uncommon type of tumor with low incidence. To date,no standard treatment for the disease has been established.Surgery remains the main treatment. Adjuvant chemotherapy and radiotherapy are optional approaches. Metastatic cases require multidisciplinary collaborative treatments. However,the choice of chemotherapeutic drugs is controversial.CASE SUMMARY A 66-year-old Chinese woman presented to our hospital complaining of intermittent pain of right upper quadrant. An enhanced computed tomography(CT) scan of the abdomen revealed hepatocellular carcinoma. Subsequently,the patient underwent a radical partial hepatectomy. Primary FDCS of the liver was diagnosed pathologically. Except for regular follow-up examinations,the patient did not receive adjuvant chemotherapy or radiotherapy. However,fluorine-18-fluorodeoxyglucose positron emission tomography/CT(PET/CT) confirmed lymph node metastases in the space of ligamentum hepatogastricum and pancreatic head,as well as the portacaval space. The patient was given systemic chemotherapy with gemcitabine and docetaxel for she was unsuitable for surgery. Satisfactorily,the metastatic lymph nodes were significantly reduced to clinical complete remission after eight cycles of chemotherapy. Then,strengthened radiotherapy was followed when the patient rejected the opportunity of surgery. Eventually,the carcinoma got better control and the patient was free of progression.CONCLUSION This case highlights the importance of making suitable chemotherapy regimens for the rare tumor. The combination of gemcitabine,docetaxel,and consolidated radiotherapy may offer a new promising option for the treatment of metastatic hepatic FDCS in the future.     

高强度聚焦超声治疗子宫平滑肌瘤的病理变化及其超声随访研究

目的通过病理穿刺及超声随访探讨高强度聚焦超声（HIFU）治疗子宫肌瘤的有效性。方法62例经HIFU治疗的子宫肌瘤患者，术前、术后1周分别进行超声引导下穿刺活检，标本行光镜和电镜观察。并分别在术后1、3、6和12个月进行超声检查，计算瘤体均径并与治疗前均径比较。结果光镜和电镜显示HIFU治疗后子宫肌瘤组织明显的细胞坏死、核固缩浓染、核碎裂溶解以及细胞器的破坏；同时可见血管的破坏以及空泡的形成。超声随访显示治疗后1个月肌瘤出现缩小，治疗后3个月瘤体明显缩小，与治疗前相比有显著差异（P〈0．05）。结论病理检查和超声随访证实HIFU治疗子宫平滑肌瘤明确有效。     

Fast and Selective Ablation of Liver Tumors by High-Intensity Focused Ultrasound Using a Toroidal Transducer Guided by Ultrasound Imaging: The Results of Animal Experiments

This study demonstrated that high-intensity focused ultrasound (HIFU) produced with an intra-operative toroidal-shaped transducer causes fast, selective liver tumor ablations in an animal model. The HIFU device is composed of 256 emitters working at 3 MHz. A 7.5 MHz ultrasound imaging probe centered on the HIFU transducer guided treatment. VX2 tumor segments (25 mg) were implanted into the right lateral liver lobes of 45 New Zealand rabbits. The animals were evenly divided into groups 1 (toroidal HIFU ablation), 2 (surgical resection) and 3 (untreated control). Therapeutic responses were evaluated with gross pathology and histology 11 d post-treatment. Toroidal transducer-produced HIFU ablation (average ablation rate 10.5 cc/min) allowed fast and homogeneous tumor treatment. Sonograms showed all ablations. VX2 tumors were completely coagulated and surrounded by safety margins without surrounding-organ secondary HIFU lesions. HIFU group tumor volumes at autopsy (39 mm³) were significantly lower than control group volumes (2610 mm³, p < 0.0001). HIFU group tumor metastasis (27%) was lower than resected (33%) and control (67%) group metastasis. Ultrasound imaging, gross pathology and histology results supported these outcomes. HIFU procedures had no complications. Rabbit liver tumor ablation using a toroidal HIFU transducer under ultrasound imaging guidance might therefore be an effective intra-operative treatment for localized liver metastases.     

High-Intensity Focused Ultrasound– and Radiation Therapy–Induced Immuno-Modulation: Comparison and Potential Opportunities

In recent years, high-intensity focused ultrasound (HIFU) has emerged as a new and promising non-invasive and non-ionizing ablative technique for the treatment of localized solid tumors. Extensive pre-clinical and clinical studies have evidenced that, in addition to direct destruction of the primary tumor, HIFU-thermoablation may elicit long-term systemic host anti-tumor immunity. In particular, an important consequence of HIFU treatment includes the release of tumor-associated antigens (TAAs), the secretion of immuno-suppressing factors by cancer cells and the induction of cytotoxic T lymphocyte (CTL) activity. Radiation therapy (RT) is the main treatment modality used for many types of tumors and about 50% of all cancer patients receive RT, often used in combination with surgery and chemotherapy. It is well known that RT can modulate anti-tumor immune responses, modifying micro-environment and stimulating inflammatory factors that can greatly affect cell invasion, bystander effects, radiation tissue complications (such as fibrosis), genomic instability and thus, intrinsic cellular radio-sensitivity. To date, various combined therapeutic strategies (such as immuno-therapy) have been performed in order to enhance RT success in treating locally advanced and recurrent tumors. Recent works suggested the combined use of HIFU and RT treatments to increase the tumor cell radio-sensitivity, in order to synergize the effects reaching the maximum results with minimal doses of ionizing radiation (IR). Here, we highlight the opposite immuno-modulation roles of RT and HIFU, providing scientific reasons to test, by experimental approaches, the use of HIFU immune-stimulatory capacity to improve tumor radio-sensitivity, to reduce the RT induced inflammatory response and to decrease the dose-correlated side effects in normal tissues.     

局限期小细胞肺癌综合治疗及预后影响因素分析

目的探讨分析局限期小细胞肺癌(L-SCLC)的综合治疗疗效及影响预后的临床病理因素。方法回顾性分析96例于2003年1月至2010年12月行手术切除的L-SCLC患者的临床相关资料,分析手术为主,包括辅助放化疗在内的综合治疗疗效及预后的影响因素。结果 L-SCLC总体5年生存率为32.0%。单因素分析结果显示性别、年龄、吸烟史、肿瘤部位等因素对患者生存率的影响均无明显统计学差异(P0.05)。而手术切缘、手术方式、T分期、N分期、TNM分期及LDH水平对患者生存率的影响有明显统计学差异(P0.05)。关于综合治疗模式,发现新辅助化疗、术后辅助化疗及术后放疗均不是预后的影响因素,只有术后联合放化疗才能使患者的生存真正获益(P0.05)。多因素分析,TNM分期(P=0.000)、术后联合放化疗(P=0.022)以及LDH水平(P=0.010)都是L-SCLC预后的独立影响因素。结论与非手术相比,L-SCLC患者手术生存更优。TNM分期、术后联合放化疗以及LDH水平都是影响L-SCLC预后的独立因素,推荐对L-SCLC给予手术为主联合术后放化疗的综合治疗模式。     

Digital angiography of bone sarcoma in the child

The authors analyze the results of 50 computed angiographies made for osteosarcoma and Ewing's sarcoma. Better tolerated than conventional angiography computed angiography is also more sensitive in preoperative evaluation of effectiveness of neoadjuvant chemotherapy. Automatic subtraction, direct measuring of tumor size and vascularization density give to angiographic changes after chemotherapy the most predictive value. After conservative surgery or radiotherapy digital angiography provides most reliable local follow up.