放射治疗在肝门部胆管癌综合治疗中的作用

肝门部胆管癌是少见的恶性肿瘤。根治性手术是肝门部胆管癌患者获得长期生存的惟一预后因素,但手术切除率很低,术后放射治疗可以提高姑息切除者的局部控制率和长期生存率。绝大多数肝门部胆管癌患者就诊时为不可切除的晚期肿瘤,并伴有不同程度的胆道梗阻症状,各种胆汁引流术可以有效地缓解胆道梗阻,但并不能延长生存期。回顾性临床分析结果表明,在胆汁引流基础上的放射治疗可以进一步缓解症状,延长生存期。放疗方式可以分为单纯外照射、外照射结合腔内放疗以及新的放射技术的应用。有效的肝门部胆管癌综合治疗手段还有待于前瞻性、随机对照的临床试验。     

肝门部胆管癌治疗方法演变与预后

目的探讨肝门部胆管癌治疗方法的变化及效果。方法回顾分析1990年1月─2009年8月收治的198例肝门部胆管癌的临床特点、诊断、分期、治疗方式及随访结果。结果梗阻性黄疸仍为肝门部胆管癌的首发临床表现,肝门部CT及核磁胆道成像（MRCP）均为诊断的有效方法 ,阳性率高。肿瘤分期：2000年以前（A组）和2000年以后（B组）病例进行比较,BismuthⅠ期病例数较前增加不明显;BismuthⅡ、Ⅲ期为主要病例,且病例数有明显增加;BismuthⅣ期则相反,病例数有所减少,但无统计学意义（P〉0.05）。治疗中,49例患者采取非手术内外引流;手术的149例中,单纯引流24例,手术探查＋胆肠吻合51例,姑息性局部切除42例,胆管癌切除＋肝部分切除30例,肝移植2例。按照时间节点分析,A组61例手术中手术切除率为34.4%（21/61）,且以姑息性切除为主（16例）;B组88例手术中手术切除率为60.2%（53/88）,其中姑息性切除与根治性切除分别为26例和27例,两组比较有统计学意义（P〈0.05）。A组仅8例行局部放疗,B组中89例行局部聚焦放疗。从治疗效果分析,非手术内外引流及手术内外引流效果均不好,5年生存为个案。手术切除患者中,BismuthⅠ、Ⅱ期生存率最高,5年生存率83.3%（10/12）;BismuthⅢ期手术切除效果好于非手术治疗;BismuthⅣ期手术切除与否效果均不好,两组手术切除后的预后无统计学意义（P〉0.05）。手术结合术后放疗（γ刀）可在一定程度上延长患者生存时间。影响患者预后的主要因素为肿瘤复发转移,其中局部淋巴结转移与肝内广泛转移最为多见。结论肝门部胆管癌Ⅰ期的诊断并未因为CT和MRI应用而提高,中期BismuthⅡ、Ⅲ期较前例数有所增多,晚期患者相对下降。手术切除率较前有所提高,根治性与姑息性切除均有利于延长患者生存时间,手术切除结合局部放疗可在一定程度上延长患者生命。影响患者长期存活的主要原因仍旧是肿瘤的局部与肝内广泛转移,更加有效的治疗手段有待进一步研究。     

经皮胆道支架联合近距内放疗治疗不能手术切除的肝门胆管癌

目的 探讨经皮胆道支架联合近距内放疗治疗不能手术切除的肝门胆管癌的可行性、安全性和有效性,以及联合治疗对患者黄疸复发和生存期的影响.方法 对2014年2月-2015年12月上海仁济医院肿瘤介入科收治的21例不能手术切除而接受经皮胆道支架联合近距内放疗的肝门胆管癌患者及该院同期单纯胆道引流或金属裸支架植入的患者28例进行回顾性分析.观察手术成功率、退黄效果及术后并发症发生率,比较两组患者生存期和黄疸复发时间的差异.结果 21例联合治疗患者共植入金属裸支架32枚,放射性12I粒子580颗,手术成功率100％,治疗有效率85.7％,术后早期并发症发生率9.5％,无手术相关死亡发生.联合治疗组患者术后中位黄疸复发时间为344 d而单纯胆道引流或金属裸支架植入患者的中位黄疸复发时间为193 d(P=0.035).联合治疗组患者中位生存期387 d明显长于单纯胆道引流或金属裸支架植入患者的256 d(P=0.022).结论 经皮胆道支架联合近距离内放疗作为不能手术切除的肝门胆管癌患者的姑息治疗方案安全有效可行,联合治疗能够推迟肝门胆管癌患者的黄疸复发及延长生存期.     

中晚期肝门部胆管癌15例手术切除体会

目的探讨中晚期肝门部胆管癌的外科治疗方式。方法对2002年12月—2005年10月收治的15例中晚期肝门部胆管癌的外科治疗方式和随访结果进行回顾性分析,其中中期7例(BismuthⅢa型4例,Ⅲb型3例),晚期(Ⅳ型)8例。结果手术切除10例,非手术胆道支架内引流5例(Ⅳ型5例)。随访14例(14/15,93.3%),手术切除组随访10例,中位生存期14.2月(16d～32.3月);非手术胆道支架内引流组随访4例,中位生存期3.8月(1.3～7.2月),两组中位生存期差异显著(t=2.802,P<0.05)。结论对于中晚期肝门部胆管癌,联合肝切除的姑息性肝门部胆管癌切除可显著延长患者生存期、提高生活质量,必要时,辅以“架桥式”肝管空肠内引流对提高手术切除率、降低术后胆漏发生率具有重要作用。     

肝门部胆管癌51例的外科治疗

目的探讨肝门部胆管癌的外科治疗方法和效果。方法对经手术和病理检查确定诊断的肝门部胆管癌51例的临床特征、手术方式和随访结果进行回顾性分析。结果肿瘤切除17例,其中根治性切除7例,姑息性切除10例。胆肠吻合15例,单纯探查活检6例,胆道支架置入13例。根治性切除组1,3,5年生存率分别为71%,42%和28%。姑息性切除、胆肠吻合和胆道支架置入组1年生存率分别为20%,0%和31%。结论应力争进行唯一能治愈肝门部胆管癌的根治性切除。如无法根治切除,以胆道支架置入为首选治疗方法。     

肝门部胆管癌126例临床分析

目的:分析肝门部胆管癌的诊断及手术治疗方法。方法:回顾分析2002-03~2007-03肝门部胆管癌手术治疗126例临床资料及随访结果。结果:按照Bismuth-Corlette分型法,Ⅰ型12例,Ⅱ型25例,Ⅲa型26例,Ⅲb型33例,Ⅳ型30例。B超、CT和磁共振胆胰管成像(MRCP)的确诊率分别为83.8%、92.1%及96.7%。126例中,根治性切除33例,姑息性切除22例,胆道引流46例,未手术25例。总手术率80.2%(101/126),根治性切除率32.7%(33/101)。根治性切除患者的1、3、5年生存率分别为81.8%、42.4%、24.2%,姑息性切除组分别为50.0%、18.2%、9.1%,单纯引流组分别为4.3%、0、0,未手术组分别为4.0%、0、0。根治性切除组和姑息性切除组生存率差异有统计学意义(P<0.05)。结论:提高手术切除率是改善肝门部胆管癌预后的唯一有效方法,肝十二指肠韧带骨骼化、肝部分切除可提高根治性切除率。     

恶性梗阻性黄疸的介入治疗临床价值

目的：经皮经肝穿刺放置引流管、内涵管或金属内支架作胆汁外引流、内外引流或内引流，可缓解黄疸，改善由于梗阻性黄疸引起的各种症状。提高患者的生存质量，为下一步治疗创造条件。方法：恶性梗阻性黄疸常由于胆管癌、胰头癌、原发性肝癌、肝脏转移瘤、肝门淋巴结转移等压迫和侵及胆管所致，外科手术切除率低。主要技术包括PTCD、胆管内外引流、胆管内涵管及内支架置入术。结论：可作为手术前辅助治疗，主要行经皮肝穿刺胆管引流术（PTCD）或姑息性内外引流治疗以解除黄疸。     

恶性胆道梗阻经皮肝穿综合治疗

<正>恶性胆道梗阻指因恶性肿瘤如胆管癌、胆囊癌、胰腺癌、肝癌、肝实质或肝门部的淋巴转移及其他转移性疾病引起的胆汁引流不良不畅~([1])。因起病隐匿、肿瘤进展迅速,大多数患者发现时已无手术指征,只能选择姑息性胆汁引流的减黄对症治疗。经皮肝穿刺胆道造影术(percutaneous transhepatic cholangiograpy,     

西宁地区老年胆道疾病82例临床分析

目的：了解西宁地区老年性胆道疾病的发病特点和临床表现,探讨其治疗方法。方法：总结2004年1月至2007年11月我院收治60岁以上老年胆道疾病。结果：82例中男38例,女44例,胆囊炎胆囊结石61例,重症急性胆管炎16例,胆管癌5例。微创治疗42例：治疗采用B超CT定位胆囊、胆管穿刺引流,EST（内镜下乳头切开术）,LC（腹腔镜胆囊切除）,死亡1例。手术治疗40例：均采用传统开腹手术,死亡4例,结论：西宁地区老年胆道疾病选用微创治疗可以降低术后并发症及死亡率。     

急性梗阻性化脓性胆管炎182例的内镜治疗

目的探讨内镜在急性梗阻性化脓性胆管炎治疗中应用的价值。方法回顾性分析182例急性梗阻性化脓性胆管炎患者治疗的临床资料。结果182例患者均经内镜治疗成功,在应用乳头括约肌切开术（EST）后,采用胆道内支架引流（ERBD）治疗25例,鼻胆管引流（ENBD）治疗140例,胆道金属支架引流（EMBD）治疗17例。治疗后所有病例临床症状均明显改善。结论急性梗阻性化脓性胆管炎的内镜治疗是一种快速、安全、有效和经济的治疗手段。     

Cholangiocarcinoma: An emerging indication for photodynamic therapy

Cholangiocarcinoma (CC) is emerging as an important treatment indication for photodynamic therapy. CCs are generally unresectable locally invasive tumors that occlude the biliary tree leading to fatal cholangitis and liver failure. Biliary decompression via stenting offers symptomatic relief but does not control tumor growth. Founded on an initial case study followed by ever more sophisticated clinical research, including randomized trials, photodynamic therapy has garnered enough momentum to be considered as part of the standard of care for these patients. Further, preliminary clinical data show the potential for benefit of the use of PDT in a neoadjuvant and adjuvant fashion to the minority of patients currently considered resectable or of border line resectability. PDT also impacts interleukin-6 levels and may form the basis for a targeted therapy approach to this disease. We review the clinical rationale, current studies and potential future directions of PDT for patients with CC.     

Randomised controlled trial of temoporfin photodynamic therapy plus chemotherapy in nonresectable biliary carcinoma—PCS Nordic study

BackgroundPhotodynamic therapy (PDT) in combination with stent have shown promising results in the treatment of biliary tract cancer (BTC) in patients not suitable for surgery. Chemotherapy has been shown to improve survival in patients with local advanced and metastatic BTC.Material and methodsIn the current randomized trial the combination of chemotherapy and stent with and without temoporfin (Foscan) photodynamic therapy (PDT), with a primary endpoint on feasibility and safety, has been performed. Ten patients in each group.ResultsNo serious, acute procedure-related complication related to PDT or the treatment combination was seen. The number of patients with cholangitis was equal in both groups. In the PDT group – arm A – two patients had cutaneous erythema after sun exposition, one of them with a localized blister. No neutropenic infection was seen. Quality of Life (QoL) was similar in both treatment groups. Progression free survival was numerically longer in the PDT group.ConclusionThe treatment combination was feasible. There was no serious complication related to PDT or the treatment combination. Number of cholangitis was equal in both groups, two abscesses were observed in the PDT group. Progression free survival was numerically longer in the PDT group.     

光动力疗法及其联合注射卡介苗对小鼠肝癌移植瘤的抑瘤作用与免疫反应

目的探讨光动力疗法(PDT)联合肿瘤局部注射卡介苗(BCG)的局部免疫反应及抑瘤效应。方法建立小鼠Heps肝癌移植瘤模型96只,随机分为对照组、PDT组、BCG组和PDT+BCG联合组。观测各组移植瘤体积的变化。以F4/80抗体为标记,采用免疫组化法计数肿瘤局部巨噬细胞(MΦ)数量。结果 1.各治疗组治疗后7 d的移植瘤体积较对照组均明显缩小(P<0.01)。联合组治疗后7 d的肿瘤体积较单纯PDT组明显缩小(P<0.05)。2.免疫组化染色结果显示,PDT组和联合组治疗后2、24 h和7 d肿瘤局部MΦ数量均明显高于对照组和BCG组(P<0.01)。上述时间点联合组肿瘤局部MΦ数量明显高于PDT组(P<0.05)。结论 PDT使小鼠肝癌移植瘤体积缩小,增强荷瘤宿主治疗局部的免疫力。PDT联合局部注射BCG的治疗方法的疗效优于单纯PDT和单纯BCG。     

Aminoleveulinate photodynamic therapy (ALA-PDT) for Bowen’s disease in a SLE patient: Case report and literature review

We reported a rare case of topical 5-aminolevulinic acid (ALA)–photodynamic therapy (PDT) in the treatment of a systemic lupus erythematosus (SLE) patient with lower limb multiple Bowen’s disease (BD). At the end of the treatment, an excellent clinical response was observed and no recurrence of rash after 2 months of treatment. The recovery time was prolonged only after the first treatment, however, no photosensitive phenomena were observed during and after the treatment. This is the first report to describe ALA-PDT for patient-confirmed photosensitivity in an Asian patient. Whether PDT is contraindicated for SLE remains to be discussed, although our findings show that PDT can be used as an alternative therapy for SLE patients with BD who cannot tolerate surgery.     

The influence of photodynamic therapy on the immune response

Photodynamic therapy (PDT) is a clinically approved therapeutic modality used for the management of several types of tumors as well as non-malignant diseases. Most of the effects of this treatment regimen result from direct action of singlet oxygen and reactive oxygen species. However, accumulating evidence indicates that antitumor effects are also mediated by indirect stimulation of inflammatory and immune responses. These responses include rapid local infiltration of tumors by neutrophils and macrophages accompanied by systemic release of inflammatory mediators. This early response can initiate and translate into a more precise immune reaction that involves activation of specific T lymphocytes that seem to be necessary for the ultimate control of residual tumor cells. Although still incompletely understood, PDT can not only activate but also suppress the immune response depending on several variables. This review summarizes the influence of PDT on the immune response and discusses its importance in the management of human diseases.     

Interstitial photodynamic laser therapy in interventional oncology

Photodynamic therapy (PDT) is a well-investigated locoregional cancer treatment in which a systemically administered photosensitizer is activated locally by illuminating the diseased tissue with light of a suitable wavelength. PDT offers various treatment strategies in oncology, especially palliative ones. This article focuses on the development and evaluation of interstitial PDT for the treatment of solid tumors, particularly liver tumors. The PDT is mostly used for superficial and endoluminal lesions like skin or bladder malignancies and also more frequently applied for the treatment of lung, esophageal, and head and neck cancer. With the help of specially designed application systems, PDT is now becoming a practicable option for solid lesions, including those in parenchymal organs such as the liver. After intravenous treatment with the photosensitizer followed by interstitial light activation, contrast-enhanced computed tomography shows the development of therapy-induced necrosis around the light-guiding device. With the use of multiple devices, ablation of liver tumors seems to be possible, and no severe side effects or toxicities related to the treatment are reported. PDT can become a clinically relevant adjunct in the locoregional therapy strategies.     

光动力疗法对荷瘤小鼠血清中TNF-α含量影响的实验研究

目的探讨光动力疗法（PDT）抑瘤效应的免疫机制,以及PDT联合肿瘤局部注射卡介苗（BCG）的治疗效果。方法建立小鼠Heps肝癌移植瘤模型72只,随机分为对照组、PDT组、BCG组和联合组,每组18只。观测各组移植瘤体积的变化。采用酶联免疫吸附实验（ELISA）,测定各组PDT治疗后2、24 h和7 d荷瘤小鼠血清中肿瘤坏死因子（TNF）-α的变化。结果 1.各治疗组治疗后7 d的移植瘤体积较对照组均明显缩小（P〈0.01）。治疗后7 d联合组的肿瘤体积较PDT组明显缩小（P〈0.05）。2.ELISA结果显示,治疗后2、24 h和7 dPDT组和联合组荷瘤小鼠血清中TNF-α的含量均明显高于对照组和BCG组（P〈0.01）,联合组荷瘤小鼠血清中TNF-α的含量明显高于PDT组（P〈0.05）。结论 PDT可增强荷瘤小鼠全身的免疫力,肝癌移植瘤体积明显缩小。PDT联合局部注射BCG的疗效优于单用PDT和单用BCG。     

PDT for Gastric Cancer — the view from China

The incidence rate and mortality of gastric cancer remain elevated. Traditionally, surgical treatment (including endoscopic surgery and traditional surgery), chemotherapy, targeted therapy, and immunotherapy were used for the treatment of gastric cancer. Although the emergence of targeted therapy and immunotherapy can effectively prolong the survival of some patients with gastric cancer and improve the quality of life of patients after chemotherapy or surgery, the overall survival rate of gastric cancer has not been significantly improved. Photodynamic therapy is a local photochemical therapy with the advantages of high safety, few adverse reactions, and repeatability, although it may cause some toxic reactions. There are some differences between East and West in the treatment of gastric cancer with PDT, and most earlier studies concentrated on using PDT alone. However, some studies have indicated that PDT may enhance the efficacy of chemotherapy and other medications. This paper summarizes the study on the use of PDT and its combination therapy in gastric cancer, which is anticipated to offer novel thoughts for the treatment of gastric cancer.     

Efficacy of photodynamic therapy in actinic cheilitis: A systematic review

BackgroundPhotodynamic therapy (PDT) has gradually developed into a promising modality for actinic cheilitis (AC), and many new PDT strategies are emerging. However, comprehensive reviews evaluating the efficacy of PDT strategies for AC are lacking.ObjectiveTo systematically review the safety and efficacy of PDT strategies for AC.MethodsA systematic review was conducted using three databases to compare several types of PDT for AC in terms of clinical response (CR), histopathology response (HR), cosmetic result, and adverse events.ResultsA total of 19 studies were included, and 292 subjects were finally enrolled. The complete CR rate of ALA-patch PDT, traditional photodynamic therapy (T-PDT), and daylight photodynamic therapy (DL-PDT) was 80.00% (24/30), 65.14% (114/179), and 76.74% (33/43), respectively. The rate of painless patients was 87.10% (27/31) in DL-PDT, whereas the rate was only 31.25% (15/48) in T-PDT. The rates of moderate and severe local phototoxicity were 47.78% (43/90) in T-PDT, 0.00% (0/23) in DL-PDT, and 21.05% (4/19) in ALA-patch PDT.ConclusionPublished literature suggests that ALA-patch PDT seem to achieve high complete CR rate. Besides, DL-PDT might be a well-tolerated therapy compared with T-PDT and ALA-patch PDT. However, these assumptions are made based on very limited data. It is necessary to conduct a long-term larger sample randomized controlled trial to further evaluate the efficacy and adverse events of various PDT schemes for AC.     

Benefits and safety of photodynamic therapy in patients with hilar cholangiocarcinoma: A meta-analysis

BackgroundPhotodynamic therapy (PDT) is a therapy evaluated for the treatment of cancers resistant to standard oncological treatments. PDT might be beneficial for the palliation of hilar cholangiocarcinoma.AimTo evaluate the efficacy and safety of PDT for treating hilar cholangiocarcinoma.MethodsPubMed, Embase, the Cochrane Library, and Web of Science were searched for articles published up to May 2021. The patients were grouped as PDT+stent vs. stent alone. The outcomes were survival, quality of life, and adverse events (AEs). Data were summarized using hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs).ResultsSix studies were included in this meta-analysis. There were 235 and 211 patients in the PDT+stent and stent groups, respectively. The 1-year survival rate of the PDT+stent group was 0.56, and that of the control group was 0.25. The 2-year survival rate of the PDT+stent group was 0.16, and that of the control group was 0.07. PDT significantly prolonged overall survival compared to the controls (P = 0.002). No differences were detected in the occurrence of cholangitis (P = 0.996) and all other AEs (early complications, stent malfunction, total AEs, acute pancreatitis, liver abscess, and biliary hemorrhage) between the two groups.ConclusionPDT in patients with hilar cholangiocarcinoma could improve survival without additional AEs. Large-scale randomized controlled trials are needed to confirm the findings.