本文關(guān)鍵詞：葡萄酒色斑（鮮紅斑痣）的血管異構(gòu)性及臨床激光治療探究　出處：《上海交通大學(xué)》2015年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 毛細(xì)血管畸形 葡萄酒色斑 鮮紅斑痣 療效 病理 血管生成 VEGF MMP-9 ANG-9 FGF-2 部位 肢體 脈沖染料激光 595nm Vbeam Cynergy 治療間隔

【摘要】：第一部分葡萄酒色斑的臨床前瞻性自身對照治療研究1.1第一節(jié)59 5 n m脈沖染料激光對葡萄酒色斑的前瞻性自身對照研究目的脈沖染料激光的出現(xiàn)成為治療毛細(xì)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療后仍無法達(dá)到病灶的完全清除。臨床上,目前以Vbeam及Cynergy為名的脈沖染料激光(Pulsed Dye Laser,PDL)廣泛應(yīng)用于葡萄酒色斑的治療,不過,至今并無相關(guān)研究對兩臺設(shè)備的療效進(jìn)行比較。本研究通過臨床上脈沖染料激光前瞻性自身研究為切入點(diǎn)對臨床治療葡萄酒色斑進(jìn)行療效評估;探討兩臺設(shè)備對葡萄酒色斑治療的療效及安全性進(jìn)行評價(jià)。方法22例葡萄酒色斑患者納入本研究,每位患者接受Vbeam和Cynergy的治療,總共接受三次治療。治療使用的參數(shù)如下:(1)Cynergy?,Cynosure公司,595 nm波長,11 J/cm2的輻射能量,脈沖持續(xù)時(shí)間為2毫秒,7毫米光斑大小,冷空氣冷卻系統(tǒng)三級。(2)Vbeam?,Candela公司,595 nm波長,輻射能量11 J/cm2,脈沖持續(xù)時(shí)間為1.5毫秒,7毫米光斑大小,動(dòng)態(tài)冷卻系統(tǒng):冰霧冷卻(20毫秒延遲,冷卻30毫秒)。術(shù)后兩個(gè)月的臨床療效評價(jià)采用光度計(jì)和視覺評估。結(jié)果所有患者在病灶的相鄰部位分別接受Vbeam和Cynergy治療。光度計(jì)評估顯示,Vbeam及Cynergy治療區(qū)平均病灶消退率分別為為36.42%及21.24%。兩者差異具有統(tǒng)計(jì)學(xué)意義(P0.05),這表明PWS對Vbeam的治療反應(yīng)優(yōu)于Cynergy。沒有患者出現(xiàn)疤痕或永久性色素改變。結(jié)論相對于Cynergy,Vbeam可能對PWS的治療更加有效。盡管同樣應(yīng)用為595 nm波長及相同的輻照能量,不能保證相同的臨床結(jié)果。1.2第二節(jié)縮短治療間隔時(shí)間有助于提高脈沖染料激光治療葡萄酒色斑的療效?-前瞻性自身對照研究目的以往學(xué)說認(rèn)為縮短脈沖染料激光(Pulsed Dye Laser,PDL)的治療間隔時(shí)間可能提高葡萄酒色斑(Port-Wine Stain,PWS)治療療效,然而,縮短治療間隔時(shí)間是否對能提高葡萄酒色斑療效尚未明確定論。本研究探討PDL采用3周及6周治療間隔比較兩者間對葡萄酒色斑療效的影響。方法39例未經(jīng)治療的葡萄酒色斑患者加入本研究,對每個(gè)病人挑選相鄰的病灶區(qū)域,分別在相鄰部位接受3周及6周治療間隔的PDL治療,共三次。在末次激光治療術(shù)后兩個(gè)月進(jìn)行視覺評估及光度計(jì)評估療效。結(jié)果光度計(jì)評價(jià)表明,間隔3周及6周治療組中,PWS平均消退率分別為40.27%和44.17%(P?0.05),認(rèn)為兩者無明顯差異性。沒有患者出現(xiàn)疤痕或永久性色素改變。結(jié)論三周間隔的PDL治療療效與常規(guī)6周間隔治療葡萄酒色斑療效相似。另外,三周治療間隔具有良好耐受性,這意味著縮短治療間隔的安全性佳,也大大減少治療過程總時(shí)間。第二部分葡萄酒色斑(鮮紅斑痣)其血管異構(gòu)性及血管生成的探究2.1第一節(jié)面部不同亞解剖區(qū)域葡萄酒色斑激光治療療效差異的病理學(xué)基礎(chǔ)目的探討面部不同亞解剖區(qū)域葡萄酒色斑(Port-Wine Stain,PWS)脈沖染料激光(Pulsed Dye Laser,PDL)治療療效差異的病理學(xué)基礎(chǔ)。方法所有PWS患者接受面部不同亞解剖區(qū)域(面內(nèi)側(cè)及面外側(cè)區(qū))PWS的病理活檢,對PWS血管的管徑及深度進(jìn)行測量,后進(jìn)行脈沖染料激光治療,對激光術(shù)后2月不同亞解剖區(qū)域的PWS通過光度計(jì)(ΔE和Δa*值)測量進(jìn)行療效評估。結(jié)果全部患者皆接受面部不同亞解剖區(qū)域(面內(nèi)側(cè)及面外側(cè)區(qū))病灶的脈沖染料激光治療,光度計(jì)測量示面外側(cè)區(qū)PWS的平均Δa*及ΔE值分別為4.63及8.81,而面內(nèi)側(cè)區(qū)PWS的平均Δa*及ΔE值分別為-0.19及3.55,兩者差別具有統(tǒng)計(jì)學(xué)意義(P0.05)。組織學(xué)表現(xiàn)示面外側(cè)區(qū)PWS擴(kuò)張的血管主要分布于真皮淺層,而面內(nèi)側(cè)區(qū)PWS擴(kuò)張的血管分布于真皮淺層至深層,部分累及皮下。皮爾森相關(guān)系數(shù)顯示PWS血管深度、血管管徑與PDL療效呈負(fù)相關(guān)。結(jié)論對同一位患者,相比于面部偏中心區(qū)域PWS,PDL對偏外周區(qū)域PWS具有更佳療效;PWS血管的組織學(xué)差異特別是血管深度可能是面部不同亞解剖區(qū)域PWS療效差異的重要原因之一。2.2第二節(jié)上肢部位葡萄酒色斑的組織病理學(xué)表現(xiàn)目的目前被廣泛認(rèn)為不同解剖部位的葡萄酒色斑(Port-Wine Stain,PWS)其對脈沖染料激光(Pulsed Dye Laser,PDL)療效反應(yīng)是不一致的。先前的研究認(rèn)為肢體部位PWS對PDL療效反應(yīng)不如面部部位PWS。本研究通過上肢區(qū)域PWS的血管組織形態(tài)學(xué)及解剖學(xué)特點(diǎn)為切入點(diǎn)探討造成臨床激光療效差異的原因。方法11例上肢葡萄酒色斑患者及11例正常皮膚對照加入本研究,每位患者分別于手部,前臂部,上臂部位的病灶區(qū)進(jìn)行活檢,測量上肢不同亞解剖區(qū)域的PWS平均血管管徑及平均血管深度,最大血管深度。結(jié)果正常皮膚,手部,前臂,上臂PWS的平均血管管徑分別為18.75μm,22.49μm,20.48μm,35.15μm,上臂PWS較其他各組具有較粗大的血管管徑(P0.05)。正常皮膚,手部,前臂,上臂PWS的最大血管深度分別為0.335mm,0.572mm,0.447mm,0.448mm,手部PWS相比其他組具有較深的血管最大深度(P0.05)。正常皮膚,手部,前臂,上臂PWS的平均血管深度分別0.172mm,0.312mm,0.256mm,0.224mm,手部PWS與正常皮膚及上臂PWS相比其平均血管深度較深;前臂PWS相比于正常皮膚,其平均血管深度較深(P0.05)。結(jié)論上肢部位PWS隨著解剖位置越遠(yuǎn)端,其血管口徑逐漸變得越小。手部區(qū)域PWS其血管細(xì)小,血管深度較深,血管容積小,可能是造成激光療效反應(yīng)差的重要原因。2.3第三節(jié)不同葡萄酒色斑組織中血管生長因子的表達(dá)目的觀察血管生長因子VEGF,MMP-9,ANG-2及FGF-2在葡萄酒色斑(Port-Wine Stain,PWS)中的表達(dá)。方法對62例未接受過治療的PWS患者進(jìn)行活檢,所有標(biāo)本采用常規(guī)免疫組化染色(IHC)檢測VEGF,MMP-9,Ang-2和FGF-2的表達(dá)。結(jié)果62例PWS列入本研究,11例正常人類皮膚為對照組;47例PWS位于面部而15例PWS位于肢體部。其中29例病灶為平坦型PWS,21例為彌漫增厚型PWS和12例局部結(jié)節(jié)型PWS,所有增厚及結(jié)節(jié)型PWS皆位于面部區(qū)域。葡萄酒色斑的病理表現(xiàn)為真皮層大小不一的畸形血管腔聚集成團(tuán)或散落分布,管壁厚薄不均,內(nèi)皮細(xì)胞多呈扁平狀排列紊亂,部分管腔可見紅細(xì)胞充盈及血栓,多無內(nèi)皮細(xì)胞增生。于局部結(jié)節(jié)型葡萄酒色斑可見病灶內(nèi)大量新生毛細(xì)血管增生呈團(tuán)塊狀分布。VEGF,MMP-9,Ang-2和FGF-2在正常皮膚組織無表達(dá),在葡萄酒色斑病灶中見不同程度表達(dá)(P0.05),而在細(xì)胞增殖旺盛的局部結(jié)節(jié)型葡萄酒色斑中陽性表達(dá)上調(diào)最顯著(P0.05)。結(jié)論和正常皮膚對照相比,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達(dá)上調(diào),特別是在細(xì)胞增殖旺盛的局部結(jié)節(jié)型葡萄酒色斑表達(dá)上調(diào)最為明顯,這種在毛細(xì)血管畸形基礎(chǔ)上發(fā)生的毛細(xì)血管瘤增生可能與血管生成因子的調(diào)控有一定關(guān)聯(lián)。血管生成因子可能與葡萄酒色斑的發(fā)生發(fā)展有一定關(guān)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.

【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R751.05

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