Clinical observation of local resection or enucleation for uveal melanoma

Backround Local resection is an effective method for treating the uveal melanoma. The aim of this study is to evaluate the survival and clinical outcomes of patients with uveal melanoma treated by local resection or enucleation. Methods Totally, 167 consecutive patients with uveal melanoma were recruited for the study, of whom 57 patients were treated with local resection and 110 patients were treated with enucleation. The main outcome was measured by the visual acuity, local recurrence, eye retention, metastases, and melanoma-related mortality. Results There were statistically significant differences in the largest basal diameter of the tumor （t=-3.441）, the tumor thickness （t=-4.140）, the ciliary body infiltration （X2=8.391）, and the duration of follow-up （Z=3.995） between the two groups （P 〈0.05）. The univariate survival analysis showed that the method of treatment was not significantly associated with metastases. The Cox proportion hazard analysis showed that the risk factors for metastasis involved the age at the time of diagnosis （RR=1.752, 95% CI 1.066- 2.880, P=0.027）, the largest basal diameter of the tumor （RR=3.508, 95% CI 1.934-6.336, P=0.000）, and the histological type （RR=2.444, 95% CI 1.106-5.877, P=0.046）. The 5-year metastases rate was 18.60% for the group with local resection and 27.81% for enucleation （X2=1.214, P 〉0.05）; the 5-year melanoma-related mortality was 16.27% for the group with local resection and 25.33% for enucleation （X2=1.304, P 〉0.05）. The 5-year local tumor recurrence rate was 29.50% and the 5-year accumulated eye retention rate was 69.00% after local resection. The visual acuity which light perception or better of 60 months after local resection was observed in 25 （92.60%） among persons retaining eye. Conclusions The survival outcomes of the patients with local resection were not worse than that of the patients with enucleation, and local resection could make the patient retain eye and partial visual functions. Hence, local res     

Repeat resection of liver metastases from gastrointestinal stromal tumor

A 44-year-old man, who was diagnosed with a gastrointestinal stromal tumor incidentally during emergency laparotomy for treatment of acute obstruction of small intestine at another hospital in 1999, was referred to our hospital due to a solitary metastasis in the liver in November 2002. A right segmentectomy (Segment 6, Couinaud‘s system) of liver was carried out. Half and one years later, a recurrent metastasis with involvement of the inferior vena cava was detected in posterior region of the liver. He underwent the third surgery in May 2004. Three another small metastases in greater omentum were found and removed. The tumor in posterior sector of the liver was en bloc resected with portion of involved inferior vena cava and diaphragm. The resected vena cava is repaired primarily through a lateral venorraphy.However, local recurrence was detected one year later, he recieved the fourth surgery in July 2005. He is now in Gleevec therapy. At present, he is in good health and free of recurrence.     

结直肠癌肝转移及合并肝外转移手术治疗现状

目前,结直肠癌已成为一种常见疾病,并逐渐朝着年轻化的趋势发展。结直肠癌远处转移最常见的部位为肝脏,占50％以上,原因是结直肠静脉血通常是经过门静脉进入肝脏,癌细胞极易转移至肝脏。手术切除是结直肠癌肝转移（ colorectal liver metastases ,CRLM）最有效的治疗方法。此外,随着手术观念和技术的革新以及综合治疗手段的不断完善,初始不可切除的CRLM、CRLM同时合并肝外转移（肝门淋巴结、肺、骨、腹腔转移等）已经不再是绝对的手术禁忌证。本文将对初始可切除CRLM、初始不可切除CRLM、CRLM同时合并肝外转移三种情形的手术治疗及相关问题分别进行综述。     

氩氦刀治疗结直肠癌肝转移临床获益分析

目的评估氩氦刀治疗不适合再次手术切除结直肠癌肝转移患者的临床获益。方法 68例患者随机分为A、B两组,比较应用氩氦刀组(A组)与未用组(B组)在2年生存率、瘤负荷减小和生活质量等方面的差别。结果用氩氦刀组与未用组相比两年生存率分别为71.88%和51.61%,血清CEA降至正常分别为57.14%和22.22%,病灶坏死或缩小分别为62.5%和22.6%,差异均有显著意义(P值分别为0.048、0.049和0.002)。结论氩氦刀治疗大肠癌肝转移瘤是一种微创、相对安全、疗效可靠的新方法,对于失去外科手术治疗机会的晚期结直肠癌肝转移患者氩氦刀联合化疗是一种有效的综合治疗模式。     

MicroRNA 145 may play an important role in uveal melanoma cell growth by potentially targeting insulin receptor substrate-1

Background MicroRNAs （miRNAs） contribute to tumorigenesis by acting as either oncogenes or tumor suppressor genes. In this study, we investigated the role of miR-145 in the pathogenesis of uveal melanoma. Methods Expression profiles of miRNAs in uveal melanoma were performed using Agilent miRNA array. Quantitative real-time polymerase chain reaction was used to screen the expression levels of miR-145 in normal uveal tissue, uveal melanoma tissue, and uveal melanoma cell lines. Lenti-virus expression system was used to construct MUM-2B and OCM-1 cell lines with stable overexpression of miR-145. Cell proliferation, cell cycle, and cell apoptosis of these miR-145 overexpression cell lines were examined by MTT assay and flow cytometry respectively. The target genes of miR-145 were predicted by bioinformatics and confirmed using a luciferase reporter assay. The expression of insulin-like growth factor-1 receptor （IGF-1R）, insulin receptor substrate-1 （IRS-1） proteins was determined by Western blotting analysis. IRS- 1 was knocked down in OCM-1 cells. TUNEL, BrdU, and flow cytometry assay were performed in IRS-1 knocked down OCM-1 cell lines to analyze its function. Results Forty-seven miRNAs were up regulated in uveal melanoma and 61 were down regulated, miR-145 expression was significantly lower in uveal melanoma sample and the cell lines were compared with normal uveal sample. Overexpression of miR-145 suppressed cell proliferation by blocking the G1 phase entering S phase in uveal melanoma cells, and promoted uveal melanoma cell apoptosis. IRS-1 was identified as a potential target of miR-145 by dual luciferase reporter assay. Knocking down of IRS-1 had similar effect as overexpression of miR-145. Conclusion miR-145 might act as a tumor suppressor in uveal melanoma, and downregulation of the target IRS-1 might be a potential mechanism.     

肝转移性眼底恶性黑素瘤的治疗探讨(附5例剖腹探查经验)

目的 探讨肝脏转移性黑素瘤手术切除的指征和可行性.方法和结果 回顾2005年1月至2010年12月期间在我院行剖腹探查的5例肝脏转移性恶性黑素瘤患者的临床资料,并结合文献进行分析.5例眼底恶性黑素瘤转移至肝脏的患者,均行激进性手术治疗,术中发现腹腔和肝脏多发转移1例(仅行剖腹探查、肝脏活检术),肝内多发病灶4例(均行姑息性肝脏转移病灶切除术).3例患者同期行围术期肝动脉栓塞化疗治疗.5例患者的预后均不佳,术后的平均生存时间为9.6(3～26)个月.结论 肝脏转移性眼底恶性黑素瘤无法早期发现,且手术指征不明,预后较差,仍是临床上的一项治疗难题.     

CIK细胞治疗黑色素瘤肝转移的临床效果观察

目的探讨黑色素瘤肝转移患者CIK细胞治疗的疗效及对生存期的影响。方法选取2009年6月至2011年10月郑州大学附属肿瘤医院生物治疗科进行CIK细胞治疗的10例黑色素瘤肝转移患者,给予CIK细胞回输,同时应用白细胞介素2和胸腺肽进行治疗,15~20 d为1周期。疗效评价采用RECIST标准。结果 10例患者中无完全缓解与部分缓解患者,疾病稳定患者8例,疾病控制率为80%(8/10);全组患者中位至疾病进展时间为3个月(1~11个月),中位生存期为4.5个月(1~13个月)。不良反应轻微。结论 CIK细胞过继免疫治疗是黑色素瘤肝转移患者的有效治疗方案。     

靶向SF3B1突变型葡萄膜黑色素瘤的药物筛选

目的 构建SF3B1突变等位基因敲除的人葡萄膜黑色素瘤细胞模型,筛选靶向抑制SF3B1突变型葡萄膜黑色素瘤的药物。方法 通过主成分分析法对来自TCGA数据库的葡萄膜黑色素瘤患者分成SF3B1野生型和突变型两组进行转录组可变剪接分析,研究SF3B1突变对可变剪接的影响。通过CRISPR-Cas9技术敲除Mel202细胞株的SF3B1突变等位基因,Sanger测序明确基因编辑的序列。MTT法和克隆形成实验检测Mel202细胞株和基因敲除mut-KO细胞株的增殖,RT-PCR琼脂糖电泳结合Sanger测序检测Mel202细胞株和基因敲除mut-KO细胞株的可变剪接事件。MTT法从上市药物库和生物活性化合物库筛选对SF3B1突变细胞具有选择性抑制活性的药物。结果 选择性敲除Mel202细胞SF3B1突变等位基因促进了细胞的增殖（5.47±0.32 vs 10.17±0.27）,改变了ZDHHC16和DYNLL1转录本的可变剪接。化合物库筛选结果显示13个化合物对SF3B1突变的Mel202细胞具有选择性的抑制活性（Fold change≥2）,其中上市药物tetrandrine和lapatinib显示了较好的量效曲线。结论 本研究为SF3B1突变的葡萄膜黑色素瘤患者提供了细胞筛选模型和潜在的个体化治疗药物。     

大肠癌肝脏转移患者同期切除效果与相关因素研究

目的  探讨同期手术切除治疗大肠癌肝转移患者的疗效,并分析其相关影响因素。方法  收集2007年3月-2009年12月西安交通大学医学部附属红会医院行同期切除治疗的86例同时性结直肠癌肝转移患者的临床资料,观察患者术后的近期及远期疗效,采用Logistic回归分析与预后相关的危险因素。结果  86例患者围手术期无死亡病例,术后5例患者出现切口感染,2例吻合口瘘,1例吻合口出血,3例发生胆漏。术后并发症发生率为12.79%（11/86）,经腹腔引流和抗感染等对症支持治疗后获得治愈或明显缓解。至随访结束共42例患者死亡,中位生存时间为60个月,51例患者出现肿瘤复发或远处转移,其中肝内复发38例,肺内转移7例,其他部位转移者6例。患者1、3及5年总生存率分别为93.84%、75.58%及50.74%,无瘤生存率分别为88.37%、61.10%及31.80%。Logistic多因素回归模型结果显示：淋巴结转移阳性、肝脏转移灶数≥4个、肝切缘阳性及术前癌胚抗原水平≥100μg/L是影响患者预后的主要危险因素;术前新辅助化疗可以改善患者的预后。结论  采用同期切除治疗大肠癌肝脏转移患者安全可行,淋巴结转移阳性、肝脏转移灶数≥4个、肝切缘阳性及术前癌胚抗原水平≥100μg/L是影响患者长期预后的主要因素,术前给予新辅助化疗对提高患者生存率有一定积极作用。

     

肝转移瘤立体定向适形放疗临床分析

目的探讨立体定向适形放疗对肝转移瘤的疗效。方法对63例共121个转移病灶实施立体定向适形放疗，肿瘤中心剂量30～68GY，每次5～8GY，分6～8次，每周2、3次，疗程2～4周，计划靶区体积1．8～130．0cm3，设伊8个非共面照射野，利用同步铅挡块，80％等剂量线包括靶区边界。结果肿瘤消退有效率（CR＋PR）86．8％（105／121），其中CR33．1％（40／121），PR53．7％（65／121），NC10．7％（13／121），PD2．5％（3／121）。肿瘤剂量30-45GY组：CR14．3％（3／21），50-58GY组：CR29．4％（20／68）（P〈O．05）；60-68GY组，CR53．2％（17／32）（P〈0．05）。原发灶病理学类型为鳞癌CR73．3％（11／15）；病理学类型为软组织来源CR12．5％（1／8）（P〈0．05）。低分化组CR47．2％（17／36）、中高分化组CR27．1％（23／85）（P〈0．05）。肿瘤直径〈2．0cm组CR75．9％（22／29）；肿瘤直径2．0-5．0cm组CR24．2％（15／62）（P〈0．05）；肿瘤直径〉5．0cmCR10．0％（3／30）（P〈0．05）。结论立体定向适行放疗为肝转移瘤治疗的有效手段，疗效与肿瘤剂量、原发灶病理学类型及肿瘤体积大小关系密切。     

妊娠滋养细胞肿瘤肝转移的诊断和处理

评估对滋养细胞肿瘤肝转移患者的治疗方法及临床预后。方法回顾性分析１９８５－１９９８年收治的滋养细胞肿瘤肝转移患者１６例。所有患者均接受以５－氟尿嘧啶为主的联合化疗或ＥＭＡ／ＣＯ（氨甲蝶呤、更生霉素、足叶乙甙／长春新碱,环磷酰胺）化疗,其中８例进行选择性肝动脉持管局部灌注化疗。通过监测血β－人绒毛膜促性腺激素（β－ＨＣＧ）水平,超声及ＣＴ等检查判断治疗效果。结果１６例患者经以上治疗４例完全缓解,２例     

肝转移癌的超声造影表现及其临床应用价值

目的观察肝转移癌超声造影表现并探讨其临床应用价值。方法采用低机械指数实时灰阶谐波反相超声造影技术对21例共21个肝转移癌病灶进行超声造影,分析研究其造影增强各时相的特征。结果21个肝转移癌中,19个(90.5%)超声造影表现为快进快出,动脉相21个病灶均可见增强,12个(57.1%)为快速弥漫增强,8个(38.1%)为快速环状增强,余1个较大的病灶呈缓慢不均匀轻度增强;延迟相20个病灶(95.2%)呈边界清晰的低回声,3个(14.3%)发现更多的肝内病灶。结论肝转移癌的超声造影有特征性表现,可将其作为筛查及诊断的可靠依据。     

大肠癌肝转移24例外科治疗

目的探讨大肠癌肝转移的手术治疗效果。方法对24例大肠癌肝转移患者施行手术切除,结合文献对手术适应证、手术方式以及随访结果进行分析。结果全组无手术死亡。1,3,5年生存率分别为95.8%,58.3%和16.7%。结论手术切除是治疗大肠癌肝转移的有效方法。     

Folfox4 regimen administered through combined hepatic arterial and systemic infusion for treatment of colorectal cancer with unresectable liver metastases

Background  Hepatic arterial infusion chemotherapy for liver metastases is under evaluation because of the high target dose and low general toxicity. To investigate the efficacy and safety of a Folfox4 regimen administered through a combined hepatic arterial and systemic infusion for the first-line treatment of colorectal cancer (CRC) with unresectable liver metastases.

Methods  Twenty-seven CRC patients with unresectable hepatic metastases and no prior chemotherapy were enrolled into the study. They received a Folfox4 regimen; 1st day: HAI of oxaliplatin 85 mg/m² and L-folinic acid 200 mg/m², followed by a bolus hepatic arterial injection of 5-fluorouracil 400 mg/m², then continuous HAI of 5-FU 600 mg/m²; 2nd day: infusion of L-folinic acid 200 mg/m² i.v. followed by an intravenous bolus injection of 5-Fluorouracil 400 mg/m², then continuous infusion of 5-fluorouracil 600 mg/m² i.v. The patients received HAI during the odd cycles, and the intravenous administration of the same Folfox4 regimen during the even cycles.

Results  A total of 236 treatment cycles were given with a median of 10 cycles. The therapy generated the following results after six treatment cycles: complete response (CR) 1/27 (3.7%), partial response (PR) 17/27 (63.0%), stable disease (SD) 6/27 (22.2%), and progress disease (PD) 3/27 (11.1%). Five patients had hepatectomy. The serum levels of both carcinoembryonic antigen (CEA) and CA19-9 were significantly reduced (P<0.05). A median time to progression of 11 months and a median overall survival of 24 months were documented. The major adverse events included grade 1/2 nausea/vomiting, upper abdominal pain, peripheral neuropathy, and neutropenia/ thrombocytopenia.

Conclusions  The Folfox4 regimen administered through combined hepatic arterial and systemic infusions is efficacious and safe for the treatment of CRC with unresectable liver metastases, and it facilitates the control of local lesions.

     

动脉介入化疗加手术治疗四肢软组织肿瘤

目的　探讨动脉介入化疗加手术治疗四肢软组织肿瘤的方法与临床价值。方法　 18例肢体软组织肿瘤 ,其中 11例 ( 61% )术前影像学检查显示肿瘤与大血管及神经粘连侵犯。分别采用股动脉或肱动脉插管 ,介入化疗 2至 3周后 ,施行肿瘤广泛切除并保存患肢功能。结果　动脉介入后病理学检查 ,肿瘤均有不同程度坏死 ,体积缩小 ,周围水肿浸润带明显减少 ,肿瘤与邻近组织尤其大血管及神经间隙增宽 ,术中得以分离切除并保存患肢 ,术后随访 10～ 5 2个月 ,患肢基本功能正常。结论　对四肢软组织肿瘤 ,影像学检查大血管与神经受累但有保肢可能者 ,术前动脉介入化疗对提高切除率、降低局部复发与远处转移特别是保存患肢与功能起到积极作用。     

Predictive factors improving survival after gastric and hepatic surgical treatment in gastric cancer patients with synchronous liver metastases

Background  The prognosis for patients with gastric cancer and synchronous liver metastases is very poor. However, a standard therapeutic strategy has not been well established. The clinical benefit and prognostic factors after hepatic surgical treatment for liver metastases from gastric cancer remain controversial.

Methods  Records of 105 patients who underwent gastrectomy regardless of hepatic surgical treatment for gastric cancer with synchronous liver-only metastases in our center between 1995 and 2010 were retrospectively reviewed.

Results  The overall survival rate for the 105 patients was 42.1%, 17.2%, and 10.6% at 1, 2, and 3 years, respectively, with a median survival time of 11 months. Multivariate survival analysis revealed that the extent of lymphadenectomy (D) (P <0.001), lymph node metastases (P <0.001), extent of liver metastases (H) (P=0.008), and lymphovascular invasion (P=0.002) were significant independent prognostic factors for survival. Among patients who underwent D2 lymphadenectomy, those who underwent hepatic surgical treatment had a significantly improved survival compared with those who underwent gastrectomy alone (median survival, 24 vs. 12 months; P <0.001). However, hepatic surgical treatment was not a prognostic factor for patients who underwent D1 lymphadenectomy (median survival, 8 vs. 8 months; P=0.495). For the 35 patients who underwent gastrectomy plus hepatic surgical treatment, D2 lymphadenectomy (P <0.001), lymph node metastases (P=0.015), and extent of liver metastases (H1 vs. H2 and H3) (P=0.017) were independent significant prognostic factors for survival.

Conclusions  D2 lymphadenectomy plus hepatic surgical treatment may provide hope for long-term survival of judiciously selected patients with hepatic metastases from gastric cancer. Patients with a low degree of lymph node metastases and H1 liver metastases would make the most appropriate candidates. However, if D2 dissection cannot be achieved, hepatic surgical treatment is not recommended.

     

西妥昔单抗转化性治疗大肠癌肝转移患者的临床观察

目的观察西妥昔单抗联合化疗转化性治疗初始不可切除KRAS基因野生型结直肠癌肝转移患者的疗效及安全性,探讨与预后可能相关的因素。方法收集2007年5月-2012年5月我院仅有肝转移的KRAS野生型结直肠癌患者,外科评估无法行手术治疗,经西妥昔单抗联合化疗转化治疗后疗效评价为CR＋PR＋SD,并接受原发肿瘤病灶根治术,同时行或不行转移灶手术治疗的患者18例。总结评估其转化治疗疗效和安全性,回顾性分析各临床病理因素与预后关系。结果西妥昔单抗中位治疗时间12周,其中CR0例,PR11例。18例经过转化性治疗后,均接受了手术治疗,原发灶切缘无癌细胞（RO）切除18例;肝转移病灶RO切除11例,局部治疗7例。生存分析显示：18例中,12例出现复发转移,5例死亡。中位无进展生存期（progression free survival,PFS）为20．80个月,总生存时间（overall survival,OS）为9．59～37．13个月。单因素分析显示：肝转移病灶数目、大小、治疗前的CEA状态、治疗后早期肿瘤缓解与患者PFS相关,差异有统计学意义（P〈0．05）。结论对于KRAS野生型大肠癌肝转移患者,西妥昔单抗联合多种化疗方案转化性治疗安全有效,提高了肝转移灶RO切除率,使其生存获益。     

133例胃癌肝转移患者的预后分析

 目的  探讨影响胃癌肝转移患者预后的相关因素。方法  回顾性分析2009年5月至2014年3月复旦大学附属中山医院收治的133例胃癌肝转移患者的临床病理资料。Kaplan-Meier法行单因素生存分析,COX比例风险模型对影响预后的因素进行多因素分析。结果  133例胃癌肝转移患者总体中位生存期9.9个月(95%CI:8.1~11.7个月),1年、2年、3年生存率分别为51.6%、21.0%及11.2%。单因素分析显示,原发肿瘤分化程度、肝转移癌程度、确诊肝转移时的白蛋白水平均与预后相关,而性别、年龄、发生肝转移时间、原发肿瘤部位、是否合并肝外转移、确诊肝转移时的血红蛋白、肿瘤标志物、Her-2状态均与预后无关。多因素分析显示,原发肿瘤分化程度、肝转移癌程度是影响胃癌肝转移预后的独立因素。在治疗上,133例患者中,24例患者采取了最佳支持治疗(best supportive care,BSC),109例患者接受了姑息化疗。接受BSC的患者生存期明显短于接受姑息化疗的患者(12.0个月vs. 2.8个月,P=0.000)。接受多线化疗的患者的生存期明显长于仅接受单线姑息化疗的患者(14.7个月 vs. 8.0个月,P=0.000)。在姑息化疗的基础上加用局部治疗未取得更长的总生存时间。结论  姑息化疗能显著延长胃癌肝转移患者的总生存时间,针对胃癌肝转移患者应尽量让其获得多线化疗的机会。     

经皮左锁骨下动脉埋置药盒治疗肝转移性肿瘤

目的 评价经皮左锁骨下动脉穿刺导管药盒系统植入术治疗肝转移性肿瘤的作用。方法 22例肝转移性肿瘤,其中来源于胃肠道转移的14例,来源于其它脏器转移8例。行经皮左锁骨下动脉穿刺导管药盒系统植入术。术后经导管药盒系统灌注化疗药物。结果 导管药盒系统植入术技术成功率100％。生存期：6个月生存率79%,1年生存率58％,2年生存率30.4%,3年生存率17%。术后1－3个月CT复查,肿瘤体积缩小 大于50％者占27.27％,无变化者占36.36%,增大者占9.1%。手术并发症有;少量气胸1例,左锁骨下区药盒附近感染,拔除导管药盒1例,导管移位至右肾动脉经再次插管调整导管于靶动脉1例。结论 经皮导管药盒系统植入术适用于肝转移瘤的长期动脉内灌注化疗,疗效满意,并发症少,值得推广应用。     

5-Fu区域化疗对大肠癌手术后肝转移影响的临床研究

目的 探讨5－FU区域化疗是否可以减少大肠癌手术后肝转移的发生率。方法 1994年4月至1998年7月我们将符合研究标准的117例患进行了研究，手术中按随机分组，治疗组57例，对照组60例。治疗组5－FU 500mg/m2，连续7d，对照组不插管。所有患至少随访4年。结果 门静脉插管化疗的不良反应与全身化疗一样，主要是消化道症状和造血功能抑制，但都较轻微，可以耐受。对照组肝转移13（13／60）例，治疗组肝转移3（3／57）例（X^=5．1，P＜0．05）。结论 大肠癌手术后门静脉插管化疗可减少肝转移的发生率，其不良反应是可以忍受的，它是值得广泛推广的治疗手段。