葡萄酒色斑（鲜红斑痣）的血管异构性及临床激光治疗探究

发布时间：2018-01-04 03:17

本文关键词：葡萄酒色斑（鲜红斑痣）的血管异构性及临床激光治疗探究　出处：《上海交通大学》2015年博士论文　论文类型：学位论文

【摘要】：第一部分葡萄酒色斑的临床前瞻性自身对照治疗研究1.1第一节59 5 n m脉冲染料激光对葡萄酒色斑的前瞻性自身对照研究目的脉冲染料激光的出现成为治疗毛细血管畸形(Capillary Malformation,CM)-葡萄酒色斑(Port-Wine Stain,PWS)的主要手段,然而,大部分的患者在多次激光治疗后仍无法达到病灶的完全清除。临床上,目前以Vbeam及Cynergy为名的脉冲染料激光(Pulsed Dye Laser,PDL)广泛应用于葡萄酒色斑的治疗,不过,至今并无相关研究对两台设备的疗效进行比较。本研究通过临床上脉冲染料激光前瞻性自身研究为切入点对临床治疗葡萄酒色斑进行疗效评估;探讨两台设备对葡萄酒色斑治疗的疗效及安全性进行评价。方法22例葡萄酒色斑患者纳入本研究,每位患者接受Vbeam和Cynergy的治疗,总共接受三次治疗。治疗使用的参数如下:(1)Cynergy?,Cynosure公司,595 nm波长,11 J/cm2的辐射能量,脉冲持续时间为2毫秒,7毫米光斑大小,冷空气冷却系统三级。(2)Vbeam?,Candela公司,595 nm波长,辐射能量11 J/cm2,脉冲持续时间为1.5毫秒,7毫米光斑大小,动态冷却系统:冰雾冷却(20毫秒延迟,冷却30毫秒)。术后两个月的临床疗效评价采用光度计和视觉评估。结果所有患者在病灶的相邻部位分别接受Vbeam和Cynergy治疗。光度计评估显示,Vbeam及Cynergy治疗区平均病灶消退率分别为为36.42%及21.24%。两者差异具有统计学意义(P0.05),这表明PWS对Vbeam的治疗反应优于Cynergy。没有患者出现疤痕或永久性色素改变。结论相对于Cynergy,Vbeam可能对PWS的治疗更加有效。尽管同样应用为595 nm波长及相同的辐照能量,不能保证相同的临床结果。1.2第二节缩短治疗间隔时间有助于提高脉冲染料激光治疗葡萄酒色斑的疗效?-前瞻性自身对照研究目的以往学说认为缩短脉冲染料激光(Pulsed Dye Laser,PDL)的治疗间隔时间可能提高葡萄酒色斑(Port-Wine Stain,PWS)治疗疗效,然而,缩短治疗间隔时间是否对能提高葡萄酒色斑疗效尚未明确定论。本研究探讨PDL采用3周及6周治疗间隔比较两者间对葡萄酒色斑疗效的影响。方法39例未经治疗的葡萄酒色斑患者加入本研究,对每个病人挑选相邻的病灶区域,分别在相邻部位接受3周及6周治疗间隔的PDL治疗,共三次。在末次激光治疗术后两个月进行视觉评估及光度计评估疗效。结果光度计评价表明,间隔3周及6周治疗组中,PWS平均消退率分别为40.27%和44.17%(P?0.05),认为两者无明显差异性。没有患者出现疤痕或永久性色素改变。结论三周间隔的PDL治疗疗效与常规6周间隔治疗葡萄酒色斑疗效相似。另外,三周治疗间隔具有良好耐受性,这意味着缩短治疗间隔的安全性佳,也大大减少治疗过程总时间。第二部分葡萄酒色斑(鲜红斑痣)其血管异构性及血管生成的探究2.1第一节面部不同亚解剖区域葡萄酒色斑激光治疗疗效差异的病理学基础目的探讨面部不同亚解剖区域葡萄酒色斑(Port-Wine Stain,PWS)脉冲染料激光(Pulsed Dye Laser,PDL)治疗疗效差异的病理学基础。方法所有PWS患者接受面部不同亚解剖区域(面内侧及面外侧区)PWS的病理活检,对PWS血管的管径及深度进行测量,后进行脉冲染料激光治疗,对激光术后2月不同亚解剖区域的PWS通过光度计(ΔE和Δa*值)测量进行疗效评估。结果全部患者皆接受面部不同亚解剖区域(面内侧及面外侧区)病灶的脉冲染料激光治疗,光度计测量示面外侧区PWS的平均Δa*及ΔE值分别为4.63及8.81,而面内侧区PWS的平均Δa*及ΔE值分别为-0.19及3.55,两者差别具有统计学意义(P0.05)。组织学表现示面外侧区PWS扩张的血管主要分布于真皮浅层,而面内侧区PWS扩张的血管分布于真皮浅层至深层,部分累及皮下。皮尔森相关系数显示PWS血管深度、血管管径与PDL疗效呈负相关。结论对同一位患者,相比于面部偏中心区域PWS,PDL对偏外周区域PWS具有更佳疗效;PWS血管的组织学差异特别是血管深度可能是面部不同亚解剖区域PWS疗效差异的重要原因之一。2.2第二节上肢部位葡萄酒色斑的组织病理学表现目的目前被广泛认为不同解剖部位的葡萄酒色斑(Port-Wine Stain,PWS)其对脉冲染料激光(Pulsed Dye Laser,PDL)疗效反应是不一致的。先前的研究认为肢体部位PWS对PDL疗效反应不如面部部位PWS。本研究通过上肢区域PWS的血管组织形态学及解剖学特点为切入点探讨造成临床激光疗效差异的原因。方法11例上肢葡萄酒色斑患者及11例正常皮肤对照加入本研究,每位患者分别于手部,前臂部,上臂部位的病灶区进行活检,测量上肢不同亚解剖区域的PWS平均血管管径及平均血管深度,最大血管深度。结果正常皮肤,手部,前臂,上臂PWS的平均血管管径分别为18.75μm,22.49μm,20.48μm,35.15μm,上臂PWS较其他各组具有较粗大的血管管径(P0.05)。正常皮肤,手部,前臂,上臂PWS的最大血管深度分别为0.335mm,0.572mm,0.447mm,0.448mm,手部PWS相比其他组具有较深的血管最大深度(P0.05)。正常皮肤,手部,前臂,上臂PWS的平均血管深度分别0.172mm,0.312mm,0.256mm,0.224mm,手部PWS与正常皮肤及上臂PWS相比其平均血管深度较深;前臂PWS相比于正常皮肤,其平均血管深度较深(P0.05)。结论上肢部位PWS随着解剖位置越远端,其血管口径逐渐变得越小。手部区域PWS其血管细小,血管深度较深,血管容积小,可能是造成激光疗效反应差的重要原因。2.3第三节不同葡萄酒色斑组织中血管生长因子的表达目的观察血管生长因子VEGF,MMP-9,ANG-2及FGF-2在葡萄酒色斑(Port-Wine Stain,PWS)中的表达。方法对62例未接受过治疗的PWS患者进行活检,所有标本采用常规免疫组化染色(IHC)检测VEGF,MMP-9,Ang-2和FGF-2的表达。结果62例PWS列入本研究,11例正常人类皮肤为对照组;47例PWS位于面部而15例PWS位于肢体部。其中29例病灶为平坦型PWS,21例为弥漫增厚型PWS和12例局部结节型PWS,所有增厚及结节型PWS皆位于面部区域。葡萄酒色斑的病理表现为真皮层大小不一的畸形血管腔聚集成团或散落分布,管壁厚薄不均,内皮细胞多呈扁平状排列紊乱,部分管腔可见红细胞充盈及血栓,多无内皮细胞增生。于局部结节型葡萄酒色斑可见病灶内大量新生毛细血管增生呈团块状分布。VEGF,MMP-9,Ang-2和FGF-2在正常皮肤组织无表达,在葡萄酒色斑病灶中见不同程度表达(P0.05),而在细胞增殖旺盛的局部结节型葡萄酒色斑中阳性表达上调最显著(P0.05)。结论和正常皮肤对照相比,VEGF,MMP-9,ANG-2,FGF-2在不同的葡萄酒色斑病灶中有不同程度的表达上调,特别是在细胞增殖旺盛的局部结节型葡萄酒色斑表达上调最为明显,这种在毛细血管畸形基础上发生的毛细血管瘤增生可能与血管生成因子的调控有一定关联。血管生成因子可能与葡萄酒色斑的发生发展有一定关系。
[Abstract]:The first part of a prospective self controlled study Wine stain treatment of 1.1 first section of the 595 n m pulsed dye laser on Wine stain prospective self control study purpose of pulsed dye laser treatment of capillary malformation (Capillary becomes Malformation, CM) - wine stains (Port-Wine, Stain, PWS) of the main means, however, most in many patients after laser therapy is still unable to meet the complete removal of lesions. Clinically, the Vbeam and Cynergy in the name of the pulsed dye laser (Pulsed Dye Laser, PDL) treatment, widely used in wine stain but compared to two sets of equipment related research no effect through the clinical research so far. On the pulsed dye laser prospective studies as a starting point to evaluate the curative effect of clinical treatment of Wine stain; two sets of equipment for wine spot therapy To evaluate the effect and safety. Methods: We studied 22 patients Wine stain patients, each patient received the treatment of Vbeam and Cynergy, received a total of three treatments. The following parameters: (1) for use in Cynergy?, Cynosure, 595 nm wavelength, the radiation energy of 11 J/cm2, pulse duration of 2 milliseconds. 7 mm spot size, the cold air cooling system three. (2), Vbeam? Candela, 595 nm wavelength, the radiation energy of 11 J/cm2, pulse duration of 1.5 ms, 7 mm spot size, dynamic cooling system: pogonip cooling (20 millisecond delayed cooling, 30 ms). Clinical evaluation of two months the photometer and visual evaluation after operation. Results all the patients in the adjacent lesions were respectively treated with Vbeam and Cynergy treatment. The photometric evaluation showed that the average Vbeam lesions and Cynergy treatment respectively for the two regions the extinction rate of 36.42% and 21.24%. with statistical difference Significance (P0.05), which indicated that PWS treatment of Vbeam reaction is better than that of Cynergy. patients had no permanent scarring or pigmentation. Conclusion compared with Cynergy, Vbeam treatment of PWS more effective. Although the same application for 595 nm wavelength and the same irradiation energy, the clinical results can not be guaranteed the same.1.2 second day shorter therapy the time interval is helpful to improve the curative effect of pulsed dye laser treatment of Wine stain? - self contrast study to the previous theories suggested that shorter pulsed dye laser (Pulsed Dye Laser PDL, prospective) treatment can improve the time interval Wine stain (Port-Wine Stain, PWS) curative effect, however, shorten the treatment time interval on whether can improve Wine stain efficacy has not been clear conclusion. This study used PDL 3 weeks and 6 weeks of treatment interval comparison between the two of Wine stain curative effect. Methods 39 cases without This study with Wine stain patients, lesions of each patient selected adjacent, respectively received PDL treatment for 3 weeks and 6 weeks of treatment interval in the adjacent area, a total of three times. In the last two months after laser treatment for visual assessment and evaluation. The results of photometric photometer evaluation show that the interval of 3 weeks and 6 weeks in the treatment group, the average extinction rate of PWS were 40.27% and 44.17% (P? 0.05), that no significant difference between the two. None of the patients had permanent scarring or pigmentation. Conclusion three week intervals PDL therapy and conventional treatment 6 week interval Wine stain curative effect is similar. In addition three weeks, the treatment interval has a good tolerance, which means the safety of shortening the treatment interval, greatly reduce the total time of treatment process. The second part Wine stain (PWS) on the vascular heterogeneity and angiogenesis in the first section 2.1 To explore the different facial anatomical region based Wine stain to sub sub regional differences in different pathological anatomy of facial pigmentation Wine laser treatment study (Port-Wine Stain PWS) pulsed dye laser (Pulsed Dye Laser, PDL) and pathological foundation treatment differences study. All PWS patients received different facial anatomical regions (sub outer surface and inner surface biopsy of PWS area), the diameter and depth of PWS vessels were measured after pulsed dye laser treatment, laser surgery on February different anatomic region of PWS by spectrophotometer (E and a*) measurement to evaluate the curative effect. Results all the patients received different facial anatomical regions (outer surface of Asia the medial surface area) and pulsed dye laser in the treatment of lesions, mean a a* and a E surface lateral region of PWS measuring the photometric values were 4.63 and 8.81, and the average PWS surface of the medial region of delta a* and delta E respectively. For -0.19 and 3.55, the difference was statistically significant (P0.05). Histological findings showed dilated blood vessels outside surface area of PWS is mainly distributed in the superficial dermis, while the surface of the medial region of PWS dilated blood vessels distributed in the shallow and deep dermis, involving the subcutaneous. Pearson correlation coefficient shows PWS vascular depth, vascular diameter was negative related to the same conclusion. The curative effect of PDL patients, compared to the partial face area of PWS, PDL on partial peripheral region PWS has better curative effect; PWS vascular tissue differentiation especially vascular depth may be the pathological facial anatomical regions of different sub PWS curative effect difference is one of the important reasons.2.2 second upper limbs Wine the findings of the purpose of the stain is widely considered in different anatomical parts Wine stain (Port-Wine Stain, PWS) of the pulsed dye laser (Pulsed Dye Laser, PDL) response is not identical to the previous. Study on the effect of PDL PWS. PWS limbs was inferior to facial parts on the vascular morphology and anatomy of the upper region of PWS as the starting point to explore the causes of the difference of clinical curative effects of laser treatment. Methods 11 cases of upper limb Wine stain patients and 11 cases of normal skin were enrolled in this study, all patients were on hand, forearm the upper parts of the lesion, biopsy, measurement of upper sub anatomical region PWS average vascular diameter and average vessel depth, maximum depth of blood vessels. The results of normal skin, hand, forearm, upper arm PWS the average blood vessel diameter were 18.75 m, 22.49 m, 20.48 m, 35.15 m, arm PWS compared with the other groups with relatively large vascular diameter (P0.05). Normal skin, hand, forearm, upper arm PWS maximum vessel depth were 0.335mm, 0.572mm, 0.447mm, 0.448mm, PWS compared to the other group with the hand The maximal depth (P0.05). Normal skin, hand, forearm, upper arm mean vessels depth of PWS were 0.172mm, 0.312mm, 0.256mm, 0.224mm, PWS and normal skin of hand and arm PWS compared to the average blood vessels deep; forearm PWS compared to normal skin, the average vessel depth (P0.05). Conclusion the upper limbs with PWS anatomical position more distal, the caliber of the vessel became smaller. The hand area PWS the small vessel, vessel depth, vascular volume small, may be caused by the objective to observe the expression of vascular endothelial growth factor VEGF, vascular endothelial growth factor of the laser response difference of third different.2.3 important reasons Wine stain tissue MMP-9, ANG-2 and FGF-2 in Wine stain (Port-Wine Stain, PWS) in the expression. Methods 62 cases of untreated PWS patients with biopsy, all specimens were collected by routine immunohistochemical staining (IHC). VEGF, MMP-9, expression of Ang-2 and FGF-2. The results of 62 cases of PWS included in this study, 11 cases of normal human skin as control group; 47 cases of PWS and 15 cases of PWS located in the face of limbs. Among them 29 cases were flat type PWS, 21 cases were diffuse thickening of type PWS and 12 cases of focal nodular type PWS all, thickening and nodular type PWS are located in the facial area. The pathological Wine stain showed dermal vascular malformation cavity size of the clustered or scattered distribution, tube wall is uneven, endothelial cells were flat and disorganized, visible red blood cell filling and lumen thrombosis, without endothelial cell proliferation. Local nodular Wine stain visible lesions within a large number of the number of capillaries with mass distribution of.VEGF, MMP-9, Ang-2 and FGF-2 had no expression in normal skin tissue, in Wine stain lesions of different degrees of expression (P0.05), and the cell proliferation of the The most significant positive expression of focal nodular type Wine spots up-regulated (P0.05) and normal skin. Conclusion compared to the control, VEGF, MMP-9, ANG-2, FGF-2 increased in a different degree in different Wine stain lesions, especially in the vigorous cell proliferation of local nodular type Wine spots up-regulated the expression of the most obvious, there is a certain related regulation of capillary hemangioma hyperplasia and angiogenesis factors that may occur in the capillary malformation on the basis of. There is a certain relationship between the occurrence and development of angiogenesis may be related to Wine stain factor.

【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R751.05

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