目的 从局部创面毛囊干细胞激活的角度,探讨胫骨横向骨搬移技术促进重度糖尿病足溃疡创面再生、愈合修复的机制.方法 选取2014年6月至2018年1月在广西医科大学第一附属医院骨关节外科行胫骨横向骨搬移的126例重度糖尿病足患者,其中男94例,女32例,年龄39～86岁,中位数年龄61岁.Wagner分级构成:3级67例,4级57例,5级2例;TEXAS分级构成:2B级50例,2C级6例,2D级9例,3B级17例,3C级1例,3D级43例.针对患者进行创面愈合情况临床观察,并在治疗前后取创面边缘组织,进行HE染色观察创面组织学变化,还采用免疫组织化学染色观察富含亮氨酸重复序列的G蛋白偶联受体5(leucine-rich repeat-containing G protein-coupled re-ceptor 5,LGR5)、角蛋白19(cytokeratin 19,CK19)蛋白表达与分布情况.结果 126例重度糖尿病足患者平均愈合时间为(143.5±86.4)d,愈合过程基本呈现炎性期、增殖修复期等阶段特点,即搬移后早期出现创面边缘收缩,表面覆盖较多黄色纤维素样炎性渗出物;换药后逐渐出现鲜红肉芽组织,且边缘上皮组织向中心部位移行增生而基本覆盖创面,仅存线性或条状瘢痕.术后取移行修复创面边缘皮肤组织检测,发现有完整分层结构的表皮,可见大量微血管、胶原纤维和腺体结构,与术前对比,坏死组织减少,真皮有炎细胞浸润减少.治疗后LGR5与和CK19阳性细胞面积比分别为(6.781±1.889)％与(9.095±2.926)％,均显著高于术前创面组织中LGR5和CK19阳性面积比的(1.398±0.620)％与(1.834±0.772)％(P＜0.05).结论 胫骨横向骨搬移技术能促进糖尿病足溃疡创面再生愈合,其机制可能是通过LGR5和CK19等阳性细胞的活化,调控皮肤干细胞,参与创面过程.

Objective To investigate the effectiveness of tibial transverse transport (TTT) combined with nose ring drain (NRD) in the treatment of severe diabetic foot ulcer. Methods The clinical data of 60 patients with severe diabetic foot (Wagner grade 3 or 4) ulcer who were admitted between April 2017 and August 2020 and met the selection criteria were retrospectively analyzed. Among them, 30 cases were treated with TTT combined with NRD (TTT+NRD group), and 30 cases were treated with TTT (TTT group). There was no significant difference in gender, age, diabetes duration, preoperative glycated hemoglobin, comorbidities, wound area, and duration, side, and grade of diabetic foot ( P>0.05). The wound healing time, wound healing rate, amputation rate, recurrence rate, duration of antibiotic therapy, hospital stay, number of hospitalizations, and number of operations were recoreded and compared between the two groups. Results No obvious surgical complications occurred in the two groups. Patients in both groups were followed up 3-13 months, with an average of 5.7 months. The duration of antibiotic therapy and hospital stay in the TTT+NRD group were significantly shorter than those in the TTT group ( P<0.05). There was no significant difference in wound healing time, wound healing rate, number of hospitalizations, and number of operations between the two groups ( P>0.05). During follow-up, there was no recurrence of ulcer in the TTT+NRD group while 2 recurrent cases (6.7%) in the TTT group. The difference in recurrence rate was not significant ( P=0.492). One case (3.3%) in the TTT+NRD group underwent amputation due to acute lower extremity vascular embolism, and 1 case (3.3%) in the TTT group underwent amputation due to secondary necrosis. The difference in amputation rate was not significant between the two groups ( P=1.000). Conclusion TTT combined with NRD is an effective method for the treatment of severe diabetic foot ulcers with deep infections or relatively closed cavities or sinuses. It can shorten the time of antibiotic use and the length of hospitalization; and the NRD has a good drainage effect without obvious comorbidities, procedure and the postoperative care are simple and easy to obtain materials.

The treatment of lower extremity chronic refractory ulcers requires a long time but with poor prognosis. Thus, many patients end up with amputations. The treatment of lower extremity chronic and recalcitrant ulcers and limb salvage has been a challenge worldwide. The Ilizarov technique based on the law of "tension-stress" brings a new hope in treating lower limb chronic and recalcitrant ulcers. The Ilizarov technique and distraction osteogenesis not only induce bone formation but also lead to angiogenesis and improved microcirculation. The Ilizarov technique consists of longitudinal distraction of long bone and tibia trans-verse transport (TTT) (proximal tibial corticotomy followed by transverse distraction). These two techniques have their own advantages and disadvantages with different indications in clinical application. Longitudinal distraction of long bone is mainly used for bone formation, such as large bone defects, osteonecrosis or bone infection (with or without soft tissue loss or ulcers). Because of only a partial osteotomy in TTT, the trauma is minor and their effects on limb instability are limited. Moreover, the procedure is simple with only a few minor complications. Thus, it is ideal in treating lower limb ischemic ulcers, such as diabetic foot ulcers, thromboangiitis obliterans (Buerger's disease), ulcers caused by atherosclerotic occlusion, arterial or venous ulcers, and trauma wounds. Several studies reported that TTT achieved high healing and limb salvage rates in treating severe diabetic foot ulcer. However, TTT could achieve lower recurrent rate. Thus, it is the most successful application in treatment of chronic ulcers. TTT also improves healing and limb salvage in treatment of thromboangiitis obliterans. However, the overall effects are limited than those in treating diabetic foot ulcer. For lower limb atherosclerosis occlusion, TTT induces regeneration of microvessles and consequently leads to ulcer healing. The effects are better than other conventional treatments. A combination therapy with vascularization is emphasized to attain the optimal long-term effects. The effects of TTT on lower limb recalcitrant ulcers still need to be validated in randomized control trial with larger sample size. Further, the mechanism of treatment needs to be explored by pilot studies which could show that this may be related to the formation of pro-angiogenetic factors and a rebalance of the inflammatory microenvironment during TTT.

Chronic limb ischemic diseases are characterized by symptomatic reduced blood supply to the limbs and can develop into limb-threatening ischemia which is difficult to manage. Distraction osteogenesis induces a large volume of new bone and neovascularization in the surrounding tissues. Consequently, the transverse distraction of tibia has been applied to the management of thromboangiitis obliterans, a chronic limb ischemic disease. However, the application of this technique is still infrequent. Recently, we developed a new technique and coined the term tibial cortex transverse transport (TTT) for it and applied it to severe and recalcitrant diabetic foot ulcers and atherosclerosis obligation and attained excellent clinical outcomes. This review discusses recent advances in the technique of TTT, its application to chronic limb ischemia, the underlying mechanisms, and its potential new clinical applications. The translational potential of this article: TTT has shown promise for the treatment of chronic limb diseases such as diabetic foot ulcer, Buerger’s disease, and arthrosclerosis obliterans in retrospective clinical studies. Its new clinical applications are probably to be extended into the management of other chronic limb diseases such as ulcers of venous, traumatic, embolic, or nonatherosclerotic etiologies, wounds left after tumor resection, radiation, or chemotherapy therapy, or infectious or inflammatory diseases. The surgical procedure is relatively simple and the complications are few and minor. Nevertheless, its effectiveness and safety needs to be confirmed in large population-based trials, and its indications and contraindications are also to be clarified. Additionally, more basic and clinical studies are required to illustrate the underlying mechanisms.

目的:观察胫骨横向骨搬移术治疗下肢血栓闭塞性脉管炎的临床疗效及安全性.方法:2014年2月至2018年9月,采用胫骨横向骨搬移术治疗下肢血栓闭塞性脉管炎患者20例,均为男性.年龄31～56岁,中位数38岁.左侧12例,右侧8例.均有吸烟史,吸烟时间5～33年,中位数21年;吸烟量每日5～60支,中位数35支.均经正规非手术或其他手术治疗无效.均有下肢静息痛和间歇性跛行.下肢单纯溃疡6例,单纯坏疽9例,溃疡和坏疽5例.病程1～7年,中位数3年.记录创面愈合时间,测量跛行距离、足趾皮肤温度及踝肱指数,采用疼痛视觉模拟量表(visual analogue scale,VAS)评分评价患者平卧位休息1 h后患肢静息痛程度,术后随访观察并发症发生情况.结果:所有患者均获随访,随访时间14～69个月,中位数40个月.术后1个月,患者的跛行距离较术前增加[(120±20)m,(1320±531)m,t=10.053,P=0.001]、足趾皮肤温度较术前增高[(28.79±0.58)℃,(32.22±1.01)℃,t=15.188,P=0.001]、踝肱指数较术前增大(0.44±0.03,0.84±0.09,t=23.150,P=0.001)、患肢静息痛VAS评分较术前降低[(5.30±1.78)分,(1.30±1.21)分,t=10.066,P=0.001].20例患者中17例创面愈合,愈合时间(3.6±2.7)个月;3例创面未愈合,其中1例经加强换药后创面最终愈合,1例术后3个月因足部缺血症状加重行小腿中上段截肢术,1例因截骨块感染自行在其他医院摘除骨块后行截肢术.至末次随访时,所有已愈合的溃疡或坏疽均未复发,均未出现胫骨骨折、钉道感染、截骨块延迟愈合、下肢深静脉血栓等并发症.结论:胫骨横向骨搬移术治疗下肢血栓闭塞性脉管炎,可以减轻患肢疼痛症状、增加跛行距离、提高足趾皮肤温度及踝肱指数,有利于创面愈合,且安全性较高.

OBJECTIVE:The treatment of recalcitrant not-diabetic leg ulcers remains challenging. Distraction osteogenesis is accompanying by angiogenesis and neovascularization in the surrounding tissues. We previously applied tibial cortex transverse transport (TTT) to patients with recalcitrant diabetic foot ulcers and found neovascularization and increased perfusion in the foot and consequently enhanced healing and limb salvage and reduced recurrence. However, the effects of TTT on recalcitrant non-diabetic leg ulcer remains largely unknown. METHODS:Consecutive patients (n ​= ​85) with recalcitrant non-diabetic leg ulcers (University of Texas Grade 2-B to 3-D, ie, wound penetrating to the tendon, capsule, bone, or joint with infection and/or ischemia) were recruited and divided into TTT (n ​= ​42) and control (n ​= ​43) groups based on the treatment they received. There were 36 (85.7%) arterial ulcers, 4 (9.5%) venous ulcers and 2 (4.8%) mixed ulcers in the TTT group and 32 (74.4%) arterial ulcers, 7 (16.7%) venous ulcers and 4 (9.3%) mixed ulcers in the control group (p ​> ​0.05). The two groups were matched on demographic and clinical characteristics. Patients in the TTT group underwent tibial corticotomy followed by 4 weeks of distraction medially then laterally, while those in the control group received conventional surgeries (debridements, revascularization, reconstruction with flaps, or skin grafts or equivalents). Ulcer healing and healing time, limb salvage, recurrence, and patient death were evaluated at a 1-year follow-up. Changes in leg small vessels were assessed in the TTT group using computed tomography angiography (CTA). RESULTS:TTT group had higher healing rates at 1-year follow-up than the control group (78.6% [33/42] vs. 58.1% [25/43], OR 2.64 [95% CI 1.10 to 6.85], p ​= ​0.04). The healing time of the TTT group was shorter than the control group (4.5 vs. 6.1 months, mean difference -1.60 [95% CI -2.93 to -0.26], p ​= ​0.02). There were no significant differences in rates of major amputation, reulceration, or mortality between the groups (p ​> ​0.05). TTT group displayed more small vessels 4 weeks postoperatively at the wound area, the foot, and the calf of the ipsilateral side in CTA. All patients in the TTT group achieved good union at the osteotomy site and had no skin or soft tissue necrosis or infection around the incision area. CONCLUSION:The findings showed that TTT facilitated the healing of recalcitrant non-diabetic leg ulcers and reduced the healing time compared with conventional surgeries. They suggest that TTT is an effective procedure to treat recalcitrant non-diabetic foot ulcers compared with standard surgical therapy. The procedure of TTT is relatively simple. Randomized controlled trials are required to confirm these findings. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE:TTT can be used as an effective treatment for recalcitrant non-diabetic leg ulcers in patients. The mechanism may be associated with the neovascularization in the ulcerated foot induced by TTT and consequently increased perfusion. Together with previous findings from recalcitrant diabetic leg ulcers, the findings suggest TTT as an effective procedure to treat recalcitrant chronic leg ulcers.

Category: Diabetes; Diabetes Introduction/Purpose: The management of severe and recalcitrant diabetic foot ulcers is challenging. Distraction osteogenesis is accompanied by vascularization and regeneration of the surrounding tissues. The longitudinal distraction of the proximal tibia stimulates increased and prolonged blood flow to the distal tibia. However, the effects of the transverse distraction of the proximal tibia cortex on severe and recalcitrant diabetic foot ulcers are largely unknown. Methods: Between July 2014 and March 2017, we treated 136 patients with diabetes and severe ulcers (University of Texas Grade 2B to 3D) that had not responded to treatment for at least 6 months. and their ulcers had a mean ± SD area of 44 cm 2 ± 10 cm 2 . All 136 patients underwent tibial cortex transverse distraction. We compared these patients with the last 136 consecutive patients we treated with standard surgical treatment between May 2011 and June 2013; All patients received standard off-loading and wound care. We compared the groups with respect to ulcer healing (complete epithelialization without discharge, maintained for at least 2 weeks) in a 2-year follow-up, the proportion of ulcers that healed by 6 months, major amputation, recurrence, and complications in the 2-year follow-up. Foot arterial status and perfusion were assessed in the TCTD group using CT angiography and perfusion imaging. Results: The tibial cortex transverse distraction group had a higher proportion of ulcers that healed in the 2-year follow-up than the control group (96% versus 68% ; p < 0.001). By 6 months, a higher proportion of ulcers healed in the TCTD group than in the control group (93% versus 41% ; p < 0.001). Lower proportions of patients in the TCTD group underwent major amputation (2.9% versus 23%; p < 0.001) or had recurrences 2.9% versus 17%, OR 0.20 [95% CI 0.05 to 0.45]; p < 0.001) than the control group in 2-year follow-up. In the feet of the patients in the TCTD group, there was a higher density of small vessels and higher blood flow and blood volume 12 weeks postoperatively than preoperatively. Conclusion: Proximal tibial cortex transverse distraction substantially facilitated healing and limb salvage and decreased the recurrence of severe and recalcitrant diabetic foot ulcers. The surgical techniques were relatively straightforward although the treatment was unorthodox, and the complications were few and minor. These findings suggest that tibial cortex transverse distraction is an effective procedure to treat severe and recalcitrant diabetic foot ulcers compared with standard surgical therapy. Randomized controlled trials are required to confirm these findings.

目的:探讨重度糖尿病足胫骨横向骨搬移术治疗后创面愈合方式及机制.方法:2014年12月至2018年6月收治136例重度糖尿病足患者.按照Wagner分级标准,3级66例、4级60例、5级10例.按照TEXAS分级标准,2B级32例、2C级2例、2D级11例、3B级13例、3D级78例.均采用胫骨横向骨搬移术治疗.对创面愈合过程进行大体观察,同时分别于术前及术后1个月复诊时切取创面边缘组织,HE染色观察创面组织形态,免疫组织化学染色观察Ki-67、CD31和血管内皮生长因子(vascular en-dothelial growth factor,VEGF)表达情况.结果:①创面大体观察结果.术后初期创面处于炎性期,有炎性细胞浸润,创面黄白;随后有新鲜肉芽组织形成,肉芽组织由创面周围向创面中心移行,创面红润,进入增生期;肉芽组织覆盖创面的过程中,上皮组织逐渐由创面四周向中心移行,1～3个月时创面愈合50%左右,上皮组织最终覆盖创面,仅留线性瘢痕.②创面组织形态观察结果.术前创面边缘组织表皮结构不完整,坏死结构较多.术后1个月创面边缘组织可清晰地观察到完整表皮结构,分为角质层、颗粒层、棘层和基底层;真皮层结缔组织中可观察到血管及胶原纤维,纤维结构少见.术前、术后创面边缘组织表皮均有大量炎性细胞浸润.③术后1个月时,创面边缘组织中 Ki -67、CD31、VEGF染色阳性细胞面积百分比均大于术前[(1.850 ± 1.287)%, (7.480 ± 5.272)%,Z＝3.292,P＝0.001;(0.395 ± 0.139)%,(1.082 ± 0.636)%,Z＝3.403,P＝0.001;(0.341 ± 0.217)%,(2.428 ± 1.502)%,Z＝3.780,P＝0.000].结论:胫骨横向骨搬移术能有效促进重度糖尿病足创面愈合,治疗后创面愈合方式为再生愈合,其机制可能是该手术能促进创面组织细胞增殖与毛细血管再生.