RANKL在骨巨细胞瘤发病及诊治中作用的研究进展

骨巨细胞瘤(giant cell tumor of bone,GCTB)是一种好发于长骨干骺端的局部侵袭性生长的原发性骨肿瘤,是交界性肿瘤,极少发生转移,但有恶变可能,常会导致严重骨质破坏,治疗难点是手术后极易复发。细胞核因子κB受体活化因子配体(receptor activator of NF-κB ligand,RANKL)是蚀骨细胞初成、发挥功能所必需的跨膜及可溶性蛋白。RANKL过表达引发骨质溶解破坏,导致GCTB瘤体逐步膨胀性、局部侵袭性生长。     

脊柱骨巨细胞瘤的诊断与治疗进展

脊柱骨巨细胞瘤（giant cell tumor of bone,GCTB）较为少见,诊断依靠临床、影像和病理三结合原则。脊柱GCTB的治疗难度较大,目前还没有基于循证医学的治疗流程和共识,因而具有很强的挑战性。手术仍然是脊柱GCTB治疗的首选方法,术前选择性动脉栓塞、完整切除肿瘤及术后辅助使用地诺单抗（denosumab）是目前推荐的综合治疗方法。整块切除是脊柱GCTB的理想治疗方式,但手术方法的选择需要遵循个体化原则,根据不同的部位制定不同的手术方案。地诺赛麦对于手术无法完全切除、复发及转移性GCTB的治疗具有一定的优势,术前使用能够有效降低GCTB外科分期,并为整块切除手术创造条件,具有广泛的应用前景。     

结直肠癌肝转移的治疗进展

结直肠癌是威胁人类健康的重要疾病之一,世界范围每年有超过1百万的新发病例,将近50万的患者死于该病。其发病率位于欧美发达国家恶性肿瘤第3位,死亡率位于第2位[1]。我国结直肠癌发病率呈上升趋势,发病率位于恶性肿瘤的第3位,而病死率位于第5位[2]。约有25%的患者在确诊结直肠癌时发现肝转移,另有25%在疾病进展过程中出现肝转移,最终约2/3的患者死于肝转移[3]。以往结直肠癌出现肝转移被认为是晚期的表现,无积极治疗的价     

肢体骨肉瘤的诊断和治疗进展

骨肉瘤(Osteosarcoma)是起源于骨骼的恶性肿瘤,好发于青少年的长骨干骺端,最多见于膝关节上下,发病率约为2～3例/百万人口[1,2].其恶性程度高,不仅局部侵袭性强,而且易于发生转移.在过去近百年时间里,单纯截肢一直是标准治疗,然而疗效非常差[2～4].最近30年,骨肉瘤的诊断和治疗都取得了很大的进展,诊断技术手段增多,疗效大为改善,并且截肢术逐渐被保肢术取代.本文就骨肉瘤的诊疗进展和现状综述如下.     

食管癌放化疗相关进展

2008年全球新诊断食管癌约482 300例,死亡约406 800例[1]。我国食管癌发病率居世界之首,欧美等西方国家食管癌患者中腺癌发病率逐年升高,而在我国等东方国家食管鳞癌为主要病理类型,占90%以上。目前手术仍然是食管癌的主要治疗手段,但ⅡA~Ⅲ期食管鳞癌单纯手术的5年生存率仅为20.6%~34.0%。对临床分期较晚的食管癌,目前推荐采用手术、放疗、化疗相结合的综合治疗模式。     

CD133和Ki-67在骨巨细胞瘤中的表达及其临床意义

目的 探讨CD133和Ki-67在骨巨细胞瘤（GCTB）中的表达及其与预后的关系,为临床判断其生物学行为及评估预后提供有力的证据。方法 采用用免疫组织化学染色检测CD133和Ki-67蛋白在80例GCTB组织中的表达,并分析2种蛋白的表达与GCTB临床病理特征及预后的关系。结果 GCTB组织中CD133阳性表达率为43.8％ （35／80）,Ki-67阳性表达率为57.5％（46／80）。CD133表达与肿瘤直径、肿瘤复发、Jaffe分级、Campanacci分期及手术方式有关（P＜0.05）;Ki-67表达与肿瘤直径、Jaffe分级和Campanacci分期有关（P＜0.05）。全组GCTB患者1、3、5年无复发生存率分别为93.0％、88.0％和80.0％。CD133阳性和阴性表达者的1、3、5年无复发生存率分别为89.0％、83.0％、75.0％和99.0％、91.0％、91.0％,差异有统计学意义（P＜0.05）。Ki-67阳性和阴性表达者的1、3、5年无复发生存率分别为89.0％、75.0％、68.0％和 97.0％、93.0％、90.0％,差异亦有统计学意义（P＜0.05）。结论 CD133和Ki-67表达与GCTB患者的预后密切相关,是评估其恶性程度以及预后的重要指标。     

Smac蛋白表达与骨巨细胞瘤恶性程度负相关

目的：研究GCTB组织中Smac分子表达的变化及其与x线Campanacci分期的关系。方法：应用免疫组织化学方法观察GCTB标本及各个X线Campanacci分期中Smac分子表达的变化。结果：GCTB标本中Smac分子表达显著降低（P〈0．001），其阳性率在各个X线Campanacci分期中分别为84．8％、56．1％和34．3％。结论：Smac分子表达在GCTB组织中显著降低，并与恶性程度负相关。     

直肠癌辅助治疗新进展

结肠直肠癌是世界范围常见恶性肿瘤,在发达国家,结肠直肠癌发病率和死亡率均位居所有癌症的前2～3位（第1位为肺癌）。虽然近年来由于早期诊断和治疗的进步使美国和欧洲癌症死亡率得以缓慢下降,但是在国内,癌症的发病率和死亡率目前正呈快速上升趋势,预计包括结肠直肠癌在内的常见恶性肿瘤的发病率和死亡率将接近或达到欧美目前水平。     

晚期非小细胞肺癌化疗和靶向治疗的现状

肺癌是一种恶性程度极高且易复发、转移的恶性肿瘤,Rivera[1]报道在新诊断的肺癌中,非小细胞肺癌(NSCLC)占80%～85%,而其中1/3初诊时已为局部晚期,不能手术的中晚期NSCLC约占全部NSCLC的3/4.治疗必须采用针对全身兼顾局部的多学科治疗方法(包括手术、化疗、放疗等).我国肺癌的发病率与死亡率逐年增长[2],发病率已居各种恶性肿瘤的首位,晚期NSCLC失去了手术根治的机会,化疗成为主要的治疗方法.     

黑色素瘤临床研究进展

黑色素瘤是一类高侵袭、高转移,预后极差的皮肤恶性肿瘤,发病率在全球各地区均成持续增长趋势。2012年据美国估计约76250人诊断为黑色素瘤,死亡约9180例。尽管我国黑色素瘤发病率低于欧美等西方国家,但其危害却不容轻视,发病率逐年增长,估计每年新发病例约2万例,     

Current status and unanswered questions on the use of Denosumab in giant cell tumor of bone

Denosumab is a monoclonal antibody to RANK ligand approved for use in giant cell tumour (GCT) of bone. Due to its efficacy, Denosumab is recommended as the first option in inoperable or metastatic GCT. Denosumab has also been used pre-operatively to downstage tumours with large soft tissue extension to allow for less morbid surgery. The role of Denosumab for conventional limb GCT of bone is yet to be defined. Further studies are required to determine whether local recurrence rates will be decreased with the adjuvant use of Denosumab along with surgery. The long term use and toxicity of this agent is unknown as is the proportion of patients with primary or secondary resistance. It is advised that complicated cases of GCT requiring Denosumab treatment should be referred and followed up at expert centres. Collaborative studies involving further clinical trials and rigorous data collection are strongly recommended to identify the optimum use of this drug.     

84例肝内胆管细胞癌患者预后因素分析

背景与目的：肝内胆管细胞癌（intrahepatic cholangiocarcinoma,ICC）发病率低,治疗效果不理想。本研究旨在分析可手术治疗和无法手术治疗ICC患者的预后相关因素和生存情况。方法：回顾性收集1997年1月至2007年12月在中山大学肿瘤防治中心经病理诊断并治疗的84例ICC患者的临床资料,采用Kaplan—Meier法进行单因素生存分析,用Cox模型进行多因素分析。结果：84例患者中采用手术治疗者56例（66．7％）,非手术治疗者28例（33．3％）;手术治疗者中根治性切除者27例（48．2％）,姑息性切除者29例（51．8％）。无法手术治疗患者、姑息手术治疗患者及根治性手术治疗患者的2年总生存率分别是3．1％、16．0％及49．2％．根治性切除患者的2年生存率明显高于姑息性切除患者（P〈0．01）。对手术患者进行单因素生存分析,结果显示。手术方式、病理类型、肿块大小、肿块数目、淋巴结侵犯、肝脏侵犯、门脉癌栓、术后血清白蛋白水平和术前血清CEA、CA199、TBIL、ALT、AST水平与预后相关;多因素生存分析结果显示。手术方式、病理类型和术前血清CEA、CA199、TBIL水平是手术患者的独立预后因素。未手术患者的单因素生存分析结果显示病理类型和血清CA199水平与预后相关。多因素生存分析结果显示只有病理类型为独立预后因素。化疗在手术患者组和非手术患者组均未显示生存优势（P=0．30和P=0．78）。结论：根治性切除是ICC患者获得长期生存的主要有效治疗手段。术前血清CEA、CA199、TBIL水平是手术患者重要的预后因素。     

Hepatectomy for colorectal liver metastases after neoadjuvant chemotherapy

The majority of patients with colorectal liver metastases receive systemic chemotherapy. In the context of unresectable liver metastases, the objective of chemotherapy based on new and more effective regimens is not only to prolong survival, but also to induce enough response and shrinkage of the tumor to render resectable patients initially not deemed to be surgical candidates. In patients with resectable liver metastases, the goal of chemotherapy is to improve the outcome after surgery and especially to decrease the risk of recurrence. Although the principles of combined modality treatment become widely accepted, this therapeutic strategy is also associated with potential risks related to the preoperative use of chemotherapy.     

Histopathological effects of intraoperative radiotherapy on pancreas and adjacent tissues: a postmortem analysis

Intraoperative radiotherapy (IORT) has been utilized in the treatment of resectable and unresectable pancreatic carcinoma at the National Cancer Institute. Detailed autopsy analyses of the radiation effects on the pancreas and adjacent tissues were performed on 13 patients dying at various times following therapy. IORT can induce a progressive retroperitoneal fibrosis and fibrosis of the porta hepatis in patients with resectable pancreatic carcinoma. In unresectable pancreatic carcinoma, the major expression of intraoperative irradiation with external beam irradiation is a progressive fibrosis of the pancreas with vascular sclerosis, nerve degeneration, atrophy of acinar cells, and atypical changes in the ducts of the pancreas, as well as degenerative changes of the pancreatic tumor.     

Treatment strategy for marginally resectable gastric cancer

It has been postulated that preoperative chemotherapy might promote tumor regression, eradicate nodal metastases, and improve resectability in patients with marginally resectable gastric cancer.For a marginally resectable tumor of gastric cancer, we selected the advanced gastric cancer patients with metastases and recurrences to the abdominal para-aortic lymph node (PAN), liver and invasion to the pancreas head and/or the duodenum.Patients with positive peritoneal cytology(P0, CY1)or localized peritoneal metastasis(P1), and Stage IV gastric cancer patients, were also considered candidates in this category. The strategy and results of surgical treatment for marginally resectable gastric cancer were explained as the dissection of PAN, hepatic resection, pancreaticoduodenectomy, perioperative chemotherapy for P0CY1 or P1, and neoadjuvant chemotherapy for Stage IV gastric cancer, which was still considered an experimental approach, although its use may be justified in unresectable or marginally resectable GC.The result of the resection of a marginally resectable gastric cancer is poor, but when there are no other non-curative factors, extended surgical resection should be performed because complete response is difficult at present with chemotherapy alone.In conclusion, there was no evidence suggesting that extended surgical procedures are effective, but a strategy of multidisciplinary treatment including extended surgical approach should be verified based on randomized controlled trials.     

Systemic therapy for hepatocellular carcinoma (HCC): from bench to bedside

Primary liver cancer is the fifth most common cancer worldwide and the third most common cause of cancer mortality. For patients with early resectable disease, surgical resection or transplantation is considered a potentially curative modality for hepatocellular carcinoma (HCC); on the other hand, for patients with unresectable or metastatic disease, treatment is essentially palliative and prior to the approval of sorafenib, there was no globally approved systemic treatment for patients presenting with unresectable or metastatic HCC. Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit in a large phase III trial. Thus, novel systemic approaches represent a high unmet medical need in advanced HCC. In this review article, we will try to take a journey through the history of systemic therapeutic options for HCC passing through the current standard options and exploring the potential new systemic options for this disease.     

Radioimmunotherapy in treatment of unresectable hepatoma—A report of 43 cases

Forty-three patients with surgically verified unresectable hepatoma had been treated by radioimmunotherapy (RIT) using¹³¹I antiferritin antibidy as a part of multimodality treatment during 1985–1990. The short-and long-term responses were compared with those in control group of 39 patients with unresectable hepatoma receiving conventional multimodality treatment in the same period. The rates of the tumor ahrinkage, serum AFP decline and sequence resection were 67.4% (29/43), 69.6% (16/23) and 30.2% (13/43) respectively, which were significantly higher than those in control group [23.1% (15/39), 40.0% (8/20) and 10.3% (4/39), respectively]. The 1-, 3- and 5-year survival rates were 61.5%, 40.4% and 35.4%, respectively, for the RIT group, and 51.2%, 20.1% and 15.5%, respectrely, for the control group. The tumor size, dose of RIT and sequence resection were identified as significant factors (P=0.005, 0.025 and 0.006, respectively, with Cox analysis model in 13 influencing factors. The results indicate that RIT was an effective one in multimodality treatment, particularly in the conversion of unresectable to resectable tumor.     

The impact of postoperative morbidity on survival in patients with metastatic colon and rectal cancer

Introduction: Avoiding postoperative morbidity is essential in patients with advanced cancer. To further improve treatment in stage IV colorectal cancer, knowledge about risk factors which effect short- and long-term outcomes is important. Methods: All stage IV colon and rectal cancer who underwent elective surgery between 2004 and 2015 were included (n = 345). We compared resectable colon and rectal patients, and unresectable colon and rectal cancer patients. Results: Median follow-up duration was 22.2 (unresectable) and 56.7 months (resectable) with no difference in tumor location. Colon cancer patients were more often considered unresectable (P < .001). Rectal procedures were correlated with a higher morbidity rate and a longer surgical duration (P < .001). In the resectable cohort, obese patients, open procedures and prolonged surgery were independently associated with postoperative complications. Considering the palliative group, neoadjuvant treatment and age were correlated with worse outcomes. Morbidity was not associated with long-term outcomes in the resectable cohort. However, unresectable patients who developed respiratory (hazard ratio [HR]: 7.53) or cardiac (HR: 3.75) complications and patients with an American Society of Anesthesiologists—score III to IV (HR: 1.51) had an impaired survival. Conclusion: Our results emphasize the need for an adequate preoperative assessment to identify patients at risk for postoperative complications and impaired survival.     

Optimizing the management of locally advanced pancreatic cancer with a focus on induction chemotherapy: Expert opinion based on a review of current evidence

Surgical resection of pancreatic cancer offers a chance of cure, but currently only 15–20% of patients are diagnosed with resectable disease, while 30–40% are diagnosed with non-metastatic, unresectable locally advanced pancreatic cancer (LAPC). Treatment for LAPC usually involves systemic chemotherapy, with the aim of controlling disease progression, reducing symptoms and maintaining quality of life. In a small proportion of patients with LAPC, primary chemotherapy may successfully convert unresectable tumours to resectable tumours. In this setting, primary chemotherapy is termed ‘induction therapy’ rather than ‘neoadjuvant’. There is currently a lack of data from randomized studies to thoroughly evaluate the benefits of induction chemotherapy in LAPC, but Phase II and retrospective data have shown improved survival and high R0 resection rates. New chemotherapy regimens such as nab–paclitaxel + gemcitabine and FOLFIRINOX have demonstrated improvement in overall survival for metastatic disease and shown promise as neoadjuvant treatment in patients with resectable and borderline resectable disease. Prospective trials are underway to evaluate these regimens further as induction therapy in LAPC and preliminary data indicate a beneficial effect of FOLFIRINOX in this setting. Further research into optimal induction schedules is needed, as well as guidance on the patients who are most suitable for induction therapy. In this expert opinion article, a panel of surgeons, medical oncologists and gastrointestinal oncologists review the available evidence on management strategies for LAPC and provide their recommendations for patient care, with a particular focus on the use of induction chemotherapy.     

挽救性手术治愈降低分级后的肝癌患者的可行性

联合运用非手术治疗模式能有效降低不能切除肝痛患者的分级,从而使一部分患者的肝癌变为可切除的。对这些降低分级后的患者实施挽救性手术可使其得到治愈。