Demographic Traits, Clinical Status, and Comorbidities of Patients With Thromboangiitis Obliterans in Japan.

BACKGROUND: The latest demographics, clinical and living conditions, and comorbidities of patients with thromboangiitis obliterans (TAO) in Japan are unknown.Methods and Results: We conducted a retrospective cross-sectional survey using the annual database of the Japanese Ministry of Health, Labour and Welfare medical support system for patients with TAO between April 2013 and March 2014. This study included 3,220 patients (87.6% male), with current age ≥60 years in 2,155 patients (66.9%), including 306 (9.5%) patients aged ≥80 years. Overall, 546 (17.0%) had undergone extremity amputation. The median interval from onset to amputation was 3 years. Compared with never smokers (n=400), 2,715 patients with a smoking history had a higher amputation rate (17.7% vs. 13.0%, P=0.02, odds ratio [OR]=1.437, 95% confidence interval [CI]=1.058-1.953). A lower proportion of workers and students was seen among patients after amputation than among amputation-free patients (37.9% vs. 53.0%, P<0.0001, OR=0.542, 95% CI=0.449-0.654). Comorbidities, including arteriosclerosis-related diseases, were found even in patients in their 20-30 s. CONCLUSIONS: This large survey confirmed that TAO is not a life-threatening but an extremity-threatening disease that threatens patients' professional lives. Smoking history worsens patients' condition and extremity prognosis. Long-term total health support is required, including care of extremities and arteriosclerosis-related diseases, social life support, and smoking cessation.

Endovascular Treatment of Critical Limb Ischemia in Buerger Disease (Thromboangiitis Obliterans) With Midterm Follow-Up: A Viable Option When Bypass Surgery Is Not Feasible.

OBJECTIVE. Thromboangiitis obliterans (TAO) is an occlusive inflammatory disease affecting small- and medium-sized vessels that causes decrease in life quality and eventually limb loss. The only proven treatment method is smoking cessation, but it may be insufficient for limb salvage in patients with critical limb ischemia. In this single-center retrospective study, the feasibility and efficiency of endovascular treatment in TAO were evaluated. MATERIALS AND METHODS. After approval of the local institutional review board, 41 patients who underwent endovascular treatment of TAO between January 2014 and June 2019 were evaluated retrospectively. Technical success and procedure-related complications were recorded. Decrease in Rutherford classification score, relief of pain, and wound healing were evaluated to determine clinical success. Primary patency, limb salvage rate, and amputation-free survival were also evaluated. RESULTS. A total of 45 limbs were treated during the study period. Technical success was achieved in 82.2% of procedures. Mean follow-up was 29.8 months. Clinical improvement was achieved in 35 limbs. Three patients underwent major amputation and 12 patients underwent minor amputation. Amputation-free survival and limb salvage were both 93.3% at both 1 and 2 years. Reintervention was performed in 14 patients because of occlusion and clinical relapsing of the symptoms. CONCLUSION. Endovascular treatment of TAO is feasible, has a potential to prevent limb amputation in patients with critical limb ischemia, and has acceptable technical success and limb salvage rates. Because there is no consensus in treatment of TAO, prospective comparative studies are needed to determine the effectiveness of an endovascular approach.

Long-Term Clinical Outcomes of Autologous Bone Marrow Mononuclear Cell Implantation in Patients With Severe Thromboangiitis Obliterans.

BACKGROUND: Patients with severe Buerger disease, also known as thromboangiitis obliterans (TAO), are at risk of major limb amputation. It has been shown that autologous bone marrow mononuclear cell (BM-MNC) implantation improves the condition of critical limb ischemia in TAO patients. This study was conducted to further clarify the long-term (>10 years) results of autologous BM-MNC implantation in patients with TAO.Methods and Results:An observational study was conducted of the long-term results of BM-MNC implantation in 47 lower limbs of 27 patients with TAO. The mean (±SD) follow-up period was 12.0±8.6 years. There was no major amputation event up to 10 years of follow-up in patients treated with BM-MNC implantation. The overall amputation-free survival rates were significantly higher in patients who underwent BM-MNC implantation than in internal controls and historical controls. There was no significant difference in amputation-free survival rates between the historical and internal controls. There was also no significant difference in overall survival between patients who underwent BM-MNC implantation and the historical controls. CONCLUSIONS: BM-MNC transplantation successfully prevented major limb amputation over a period of >10 years in patients with severe TAO who had no other therapeutic options.

Pharmacological treatment for Buerger's disease.

BACKGROUND: Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The aetiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularisation to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain.This is an update of the review first published in 2016. OBJECTIVES: To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 15 October 2019. The review authors searched LILACS, ISRCTN, Australian New Zealand Clinical Trials Registry, EU Clinical Trials Register, clincialtrials.gov and the OpenGrey Database to 5 January 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. DATA COLLECTION AND ANALYSIS: Two review authors, independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS: No new studies were identified for this update. Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid. Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; 1 study; moderate-certainty evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; 1 study; moderate-certainty evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; 1 study; moderate-certainty evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; 2 studies; I² = 0%; very low-certainty evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; 1 study; low-certainty evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; 1 study; moderate-certainty evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; 1 study; moderate-certainty evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; 1 study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; 1 study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low-certainty evidence). Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study. Overall, the certainty of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information (for example regarding baseline tobacco exposure). AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Very low and low-certainty evidence suggests there is no clear difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very low-certainty evidence suggests there is no clear difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. Further well designed RCTs assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.

[Early outcomes of therapy and indirect revascularization surgery in patients with critical ischemia of lower extremities]. / Blizhaishie rezul'taty konservativnogo lecheniya i operatsii nepryamoi revaskulyarizatsii u bol'nykh s kriticheskoi ishemiei nizhnikh konechnostei na fone distal'noi okklyuzii arterii.

OBJECTIVE: To study the immediate results of therapy and indirect revascularization in patients with critical ischemia of the lower limbs. MATERIAL AND METHODS: The results of medication and surgical treatment were analyzed in 210 patients with critical ischemia of the lower limbs. Atherosclerosis obliterans was diagnosed in 142 patients, thromboangiitis obliterans - in 68 patients. Lesion of femoropopliteal segment was observed in 32 (15.2%) cases, popliteal-tibial segment - 68 (32.8%) patients, tibial and foot segment - 62 (29.5%) cases, foot - 31 (14.8%) cases, multiple-level lesion - 17 (8.1%) cases. Survey consisted of Doppler ultrasound, CT angiography, rheovasography with analysis of rheographic index (RI) and pulse oximetry. Circulatory parameters were compared with identical values in 48 almost healthy persons ("reference group"). The results of medication and surgical treatment were evaluated by using of the scale of Rutherford R.B. et al. (1997). RESULTS: Conservative treatment was performed in 48 patients (control group). The following types of indirect revascularization operations were performed to stimulate regional circulation: bone trepanation in 42 patients, lumbar sympathectomy in 51 patients, bone trepanation + lumbar sympathectomy in 38 patients, bone trepanation with intraosseous irradiation in 31 cases. CONCLUSION: Indirect revascularization improves early postoperative outcomes, ensures maintaining support function of the limb and active lifestyle in patients with critical ischemia of the lower limbs. Technical simplicity of these procedures facilitates widespread introduction of indirect revascularization in multi-field hospitals.

Successful Fat Grafting in a Patient With Thromboangiitis Obliterans.

Thromboangiitis obliterans, or Buerger disease, is a rare nonatherosclerotic segmental inflammatory vasculitis that generally affects young tobacco smokers. Although no surgical treatment is available, the most effective way to halt the disease's progress is smoking cessation. In this case report, a 29-year-old smoker showed up to emergency department with gangrene of his fifth left toe and extensive plantar ulceration. After investigative angiography, he was diagnosed with Buerger disease. On November 2017, he underwent fifth left toe amputation and hyperbaric therapy. Five months after amputation, the patient was rehospitalized because of surgical wound dehiscence, wide ulceration, and pain. He was treated with lipofilling using the Coleman technique. Two weeks after the fat grafting procedure, the patient suspended pain control medication, and after 2 months, the surgical wound was almost healed. Fat grafting (lipofilling) is mostly used in plastic surgery; it offers regenerative effects, with minimal discomfort for the patient. This case report demonstrates a successful alternative use of lipofilling for this unique condition and opens up new options for use of this technique in other fields.

Immediate and late outcomes of endovascular therapy for lower extremity arteries in Buerger disease.

OBJECTIVE: Buerger disease is a rare inflammatory vasculopathy presenting with severe claudication or critical limb ischemia. In this study, we sought to evaluate the feasibility and clinical outcomes of endovascular therapy for Buerger disease involving arteries in the lower extremities. METHODS: Between January 2006 and May 2016, there were 44 Buerger disease patients (43 men; mean age, 40.4 ± 9.6 years) with 50 target limbs treated by endovascular therapy at the Severance Cardiovascular Hospital. Baseline characteristics as well as both immediate and late clinical outcomes were retrospectively analyzed. RESULTS: The majority (86.4%) of patients presented with critical limb ischemia. A total of 88 target lesions in 50 limbs were treated with endovascular procedures. All limbs showed infrapopliteal artery occlusions, and multilevel diseases involving the iliac or femoropopliteal artery were found in 31 patients (62%). Technical success was achieved in 80% of subjects. We found that a lower serum level of C-reactive protein, specifically the log C-reactive protein value (odds ratio, 0.03; 95% confidence interval [CI], 0.00-0.71; P = .030), was an independent predictor of technical failure. The median follow-up duration was 29 months. Major adverse limb event-free survival and reintervention- and amputation-free survival were 83.3% and 67.9% at 3 years, respectively. In a multivariate Cox proportional hazards analysis, previous endovascular treatment (hazard ratio, 3.70; 95% CI, 1.20-11.31; P = .022) and previous amputation (hazard ratio, 4.68; 95% CI, 1.37-15.96; P = .014) were identified as independent risk factors for reintervention- and amputation-free survival. CONCLUSIONS: In patients with Buerger disease, endovascular treatment achieved technical success in the majority of the cases and was associated with favorable immediate and late clinical outcomes. These findings indicate that endovascular therapy may be considered a first-line treatment option for severe symptomatic patients with Buerger disease.

Chronic Nonatherosclerotic Occlusive Popliteal Artery Disease.

BACKGROUND: The outcomes of revascularization of nonatherosclerotic occlusive popliteal artery disease are unknown. Therefore, the objective of this study was to analyze the outcomes of recanalization of nonatherosclerotic occlusive popliteal artery disease, the results of which would be useful in creating surgical strategies for such cases. METHODS: From January 2000 to December 2015, a total of 22 patients with nonatherosclerotic occlusive popliteal artery disease underwent open surgical repair. We retrospectively analyzed the data of these patients. Thrombectomy with angioplasty on the occluded popliteal artery, graft interposition, and bypass surgery were conducted for revascularization of the affected region. We analyzed the overall primary patency rate, type of graft, and surgical approach. Furthermore, we compared the primary patency rate after surgical treatment. RESULTS: Of 22 patients, 3 (13.6%) had cystic adventitial disease, 16 (72.7%) had popliteal artery entrapment syndrome, and 3 (13.6%) were diagnosed as having thromboangiitis obliterans. Five patients (22.7%) underwent thrombectomy with patch angioplasty, 8 (36.3%) underwent bypass surgery, and 9 (40.9%) underwent graft interposition of the popliteal artery. All graft interpositions and thrombectomies with patch angioplasty were performed through a posterior approach, whereas all bypass surgeries were performed through a medial approach except in 1 case. The mean follow-up period was 54.95 ± 42.99 months. The overall primary patency rate at 1, 3, and 10 years was 100%, 86.9%, and 69.5%, respectively. In the bypass group, the primary patency rate at 1, 3, and 10 years was 100%, 66.7%, and 44.4%, respectively. In the other groups, the primary patency rate was 100% during the follow-up period. The difference in primary patency rate was statistically significant (P ≤ 0.05). CONCLUSIONS: The result of surgical treatment for nonatherosclerotic occlusive popliteal artery disease was better than that of atherosclerotic popliteal artery disease. Direct popliteal artery reconstruction, such as graft interposition or thrombectomy with patch angioplasty, showed better short- and long-term patency than did bypass surgery.

How to Treat a Patient with Thromboangiitis Obliterans: A Systematic Review.

To date, there is still no treatment protocol for patients with thromboangiitis obliterans (TAO) who are also afflicted with critical limb ischemia (CLI). Smoking cessation on its own cannot be considered a treatment for the purposes of salvaging a limb of a TAO patient with CLI. The aim of this review was to evaluate different studies of various treatment protocols for avoiding amputation in TAO patients. A systematic search for relevant studies dating from 1990 to the end of 2016 was performed on the PubMed, SCOPUS, and Science Direct databases. Only 24 studies fulfilled the inclusion criteria, of which only one was a randomized controlled trial (RCT). The remaining studies were quasi-experimental with various treatments and follow-up durations. Therefore, meta-analysis was not performed. Judging from the major amputation rates after the suggested treatments were performed, no treatment was particularly effective. This review demonstrated that more standard RCTs are needed to resolve this treatment issue involved in TAO. In addition, because health insurance coverage for TAO patients differs by country, regional cost-benefit and cost-efficacy studies of the suggested treatments for TAO are highly recommended.

Efficacy of Endovascular Radiofrequency Ablation for Thromboangiitis Obliterans (Buerger's Disease).

BACKGROUND: This study aimed to evaluate the efficacy of endovascular radiofrequency ablation (RFA) for the treatment of thromboangiitis obliterans (TAO). METHODS: Total 30 males (median age: 46.00 years, interquartile range: 42.00-51.25 years) with unilateral TAO in the lower extremity underwent RFA were retrospectively enrolled from January 2013 and October 2013. The pre-operative and post-operative digital subtraction angiographic (DSA) images were recorded. Pain scores preoperatively and postoperatively were assessed according to the World Health Organization Pain Guideline. The values of ankle brachial index (ABI) at pre-operation, post-operation, 2 weeks and 2 years after surgery were all recorded and analyzed. Additionally, a 2-year follow up was performed by a computed tomographic angiography (CTA) image. RESULTS: The DSA images indicated that occlusion of femoral artery was improved after surgery. Moreover, there was no recurrence of TAO at 2 years of follow-up based on the CTA images. The pain score (P < 0.001) was significantly deceased after surgery. The values of ABI at postoperation, 2 weeks after surgery, and 2 years after surgery were all significantly higher than the preoperative ABI (P < 0.001). Furthermore, the values of ABI at 2 weeks after surgery and 2 years after surgery were all significantly higher than the postoperative ABI (P < 0.001). CONCLUSIONS: These results supported the application of endovascular RFA for treating TAO.

Very distal vein bypass in patients with thromboangiitis obliterans.

BACKGROUND: Surgical revascularization for chronic critical limb ischaemia in patients with thromboangiitis obliterans (TAO) still remains controversial. Generally, besides cessation of smoking, conservative treatment supported by intravenous administration of vasoactive agents is regarded as the treatment of choice, in combination with local wound therapy or minor amputation. PATIENTS AND METHODS: In four male patients (42-47 years) surgical revascularization was chosen as therapy for established gangrene or non-healing ulceration after unsuccessful conservative treatment and cessation of smoking. Angiography was able to identify a suitable distal arterial segment for the bypass which was revascularized by means of an autologous vein graft. Grafts were followed with repetitive duplex ultrasound. Revision of the bypass graft was initiated if indicated by pathological duplex findings. RESULTS: In all cases a bypass could be constructed with either the ipsilateral greater saphenous vein or arm veins. A distal origin configuration was possible in three cases with popliteo-pedal or cruro-pedal bypasses. In the fourth case the distal superficial femoral artery was used for inflow. Two early graft thromboses underwent successful revision. During follow-up, duplex ultrasound identified graft stenoses in three bypasses which were successfully treated with endovascular techniques. All grafts are patent with complete resolution of ischaemic symptoms after 46, 42, 32, and 29 months. The patients remained non-smokers and returned to a professional life. CONCLUSIONS: Surgical therapy with distal vein bypass for persistent ischaemic symptoms after definitive cessation of smoking seems feasible in selected cases with TAO and a suitable distal artery. Close follow-ups of the patients with duplex ultrasound are necessary to identify developing vein graft stenoses. Angioplasty seems to be an important part of the long-term therapeutic concept.

Pharmacological treatment for Buerger's disease.

BACKGROUND: Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain. OBJECTIVES: To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. SEARCH METHODS: The Cochrane Vascular Trials Search Co-ordinator searched their Specialised Register (last searched in April 2015) and the Cochrane Register of Studies (Issue 3, 2015). The review authors searched trial registers and the European grey literature; screened reference lists of relevant studies, and contacted study authors and major pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. DATA COLLECTION AND ANALYSIS: Two review authors, independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS: Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid.Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; one study; moderate quality evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; one study; moderate quality evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; one study; moderate quality evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; two studies; I² = 0%; very low quality evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; one study; low quality evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; one study; moderate quality evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; one study; moderate quality evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; one study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; one study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low quality evidence).Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study.Overall, the quality of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information regarding for example baseline tobacco exposure. AUTHORS' CONCLUSIONS: Moderate quality evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Verylow and low quality evidence suggests there is no difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. High quality trials assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.

Pharmacological treatment for Buerger's disease.

BACKGROUND: Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain. OBJECTIVES: To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. SEARCH METHODS: The Cochrane Vascular Trials Search Co-ordinator searched their Specialised Register (last searched in April 2015) and the Cochrane Register of Studies (Issue 3, 2015). The review authors searched trial registers and the European grey literature; screened reference lists of relevant studies, and contacted study authors and major pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. DATA COLLECTION AND ANALYSIS: Two review authors, independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS: Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid.Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; one study; moderate quality evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; one study; moderate quality evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; one study; moderate quality evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; two studies; I² = 0%; very low quality evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; one study; low quality evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; one study; moderate quality evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; one study; moderate quality evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; one study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; one study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low quality evidence).Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study.Overall, the quality of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information regarding for example baseline tobacco exposure. AUTHORS' CONCLUSIONS: Moderate quality evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Verylow and low quality evidence suggests there is no difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. High quality trials assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.

The Epidemiologic and Clinical Findings of Patients with Buerger Disease.

BACKGROUND: Buerger disease is a nonatherosclerotic peripheral arterial disease, which is mostly observed in young male smokers. Buerger disease is characterized by the observation of peripheral arterial occlusion by angiography. The condition may be caused by microembolization in the small-sized arteries of the distal extremities. Buerger disease is diagnosed based on the Shionoya's clinical diagnostic criteria, which include: (1) a history of smoking, (2) onset before the age of 50 years, (3) the presence of infrapopliteal arterial occlusions, (4) either upper limb involvement or phlebitis migrans, and (5) the absence of atherosclerotic risk factors other than smoking. Several studies have reported that oral bacterial infections (periodontitis) could activate the onset of Buerger disease. In this study, we report the epidemiologic and clinical manifestations of patients with Buerger disease. METHODS: Fifty-eight patients who were surgically treated between July 1989 and June 2014 at Tokyo Medical and Dental University Hospital were enrolled in this study. All of the patients clinically diagnosed with Buerger disease based on Shionoya's clinical diagnostic criteria. Fifty-five male and 3 female patients were treated. The mean age of the patients was 48 years (range, 21-73 years). RESULTS: All of the patients were either smokers or had a history of smoking. The mean Brinkman index score was 780 (range, 150-1,640). Their mean age at the onset of Buerger disease was 38 years (range, 21-50). The arterial lesions extended to the femoral arteries in 25% of cases, to the iliac arteries in 8% and to the abdominal aorta and/or visceral arteries in 6% of cases. Upper limb involvement, including cyanosis, paleness, and gangrene, was obvious in 84% of patients, and phlebitis migrans was recognized in 34%. The lower extremities symptoms involved intermittent claudication in 23% of the patients, rest pain in 13% of the patients, and ulceration or gangrene in 64% of the patients. Fifteen patients had undergone surgical arterial reconstruction, 4 patients had received endovascular therapy, 33 patients had undergone lumbar sympathectomy and 8 patients had undergone thoracic sympathectomy. Twenty percent of the patients needed minor limb amputations, and 4% required major limb amputations. In the patients who were examined for their oral conditions, periodontitis corresponding to grades B (moderate periodontitis), C (severe periodontitis), and D (edentulous patients) was revealed in 31%, 56%, and 13% of the patients, respectively. CONCLUSIONS: More than half of the Buerger disease patients in this study were suffering from severe periodontitis. It is possible that not only the cessation of smoking, but also the improvement of periodontal care could improve the clinical symptoms related to Buerger disease.

Repeated small bowel resection in a patient with Buerger's disease and intestinal involvement.

Buerger's disease, also called thromboangiitis obliterans, is a recurrent and an uncommon vaso-occlusive inflammatory disease, which typically affects small and medium-sized arteries, veins and nerves of the upper and lower extremities. Mesenteric and multisystem involvement of two or more organs is extremely rare. Here we report the case of a 39-year-old male heavy smoker who had undergone four repetitive laparotomies and multiple small bowel resections for ischaemic involvement of Buerger's disease. He had below-the-knee amputation of the right leg and finger of the left hand because of that disease before bowel involvement. Histopathological findings revealed that the arteries and veins of the resected small intestine were occluded with organised thrombi. Inflammatory cell infiltration was recognised mainly in the intima of distal branches of mesenteric artery. These findings were compatible with previous findings in histopathological examinations of amputated extremities.

Extreme distal bypass to improve wound healing in Buerger's disease.

Thromboangiitis obliterans or Buerger's disease is a rare non-atherosclerotic segmental inflammatory vasculitis that most commonly involves small and medium-sized arteries, veins and nerves of the extremities, and generally affects young tobacco smokers. A 53-year-old man was found to have critical ischaemia of his left lower limb with foot gangrene. He underwent extremely distal surgical revascularisation using a great saphenous vein bypass graft. The choice of a very distal artery as run-off vessel promoted a faster wound healing and pain relief, with improvement in quality of life.

[Lumbar sympathectomy literature review over the past 15 years]. / Lumbálna sympatektómia prehlad svetovej literatúry za posledných 15 rokov.

INTRODUCTION: Lumbar sympathectomy (LS) irreversibly damages a part of the sympathetic trunk and adjacent ganglia between L1 and L5, typically between L2 and L4. The first LS was performed in 1923. Initially, it used to be performed very often; however, with the progress of vascular and endovascular surgery its importance gradually continues to decline. The aim of the paper is to present literature review focusing on LS over the past 15 years. METHOD: Literature review of 113 academic articles found in academic journal databases. PATHOPHYSIOLOGY: Irreversible interruption of the efferent innervation leads to relative vasodilation of small vessels in lower extremities (α1-receptors blockade), and it reduces the volume of sweat due to inactivation of eccrine glands and nociception from lower limbs. INDICATION: Raynaud´s phenomenon, thromboangitis obliterans, non-revascularizable peripheral arterial disease (PAD) (Fontain grade III-IV), hyperhidrosis, persistent pain in lower extremities, chronic pain of amputation stump, frostbites, chilblains.Effect: The three largest studies showed a positive effect in 63.6-93.4% cases of PAD and in 97%100% cases of hyperhidrosis. The positive effect was defined as warmer lower extremities, increased blood flow, acceleration of chronic defects healing, sweating disappearance and pain reduction. CONCLUSION: Lumbar sympathectomy still remains a useful method in the treatment of above mentioned diseases if properly indicated. KEY WORDS: lumbar sympathectomy - Raynaud´s phenomenon - thromboangitis obliterans -peripheral arterial disease - hyperhidrosis.

[The results of combined surgical treatment of thromboangiitis obliterans and critical lower limb ischemia using prolonged epidural analgesia and autohemotherapy with ozone]. / Rezul'taty kombinirovannogo khirurgicheskogo lecheniya bol'nykh obliteriruyushchim trombangiitom i kriticheskoi ishemiei nizhnikh konechnostei.

AIM: to evaluate the results of combined treatment of thromboangiitis obliterans with severe lower limb ischemia using prolonged epidural anaesthesia and autohemotherapy with ozone. MATERIAL AND METHODS: It was analyzed treatment of 125 patients with thromboangiitis obliterans and severe lower limb ischemia. Patients were divided into 2 groups. Control group consisted of 60 patients who underwent conventional perioperative therapy with anticoagulants, antiplatelet agents, dextrans, metabolic drugs, glucocorticoids, angioprotectors, narcotic and non-narcotic analgesics. Study group included 65 patients in whom prolonged epidural anaesthesia and autohemotherapy with ozone was applied additionally. RESULTS: In early postoperative period (up to 30 days) the incidence of secondary lower leg amputation was 10% and 1.5% in both groups respectively (p<0.05). Primary healing after limited foot amputation was achieved in 63.6% and 83.3% in control and stugy groups respectively (p<0.05). Ulcerative defect recovery was observed in 62.2% and 76.2% in both groups respectively (p<0.01). Satisfactory result of treatment was obtained in 61.7% and 80.0% of patients. CONCLUSION: Restoration of magistral and collateral blood flow combined with prolonged epidural anaesthesia and autohemotherapy with ozone improves surgical outcomes and rehabilitation of patients with thromboangiitis obliterans and severe lower limb ischemia.

Buerger's disease in the northeast of Iran: Epidemiology and clinical features.

BACKGROUND: The aim of this study is to present our long-term clinical experience in describing a clinical picture of Buerger's disease in our region. MATERIALS AND METHODS: In a retrospective study, files of 225 patients who were admitted to the hospital with diagnosis of thromboangiitis obliterans in a 10 year period from 2000 to 2010 were reviewed. All data including demographic, signs and symptoms, history of previous illness, history of smoking, medications, laboratory tests, angiography, and details of surgical operation were obtained. RESULTS: A total of 222 (98.7%) and 3 (1.3%) of patients were male and female, respectively. Average age of hospitalized patients was 40.7 ± 8.5 (20-62) years. A total of 200 patients (88.9%) were active cigarette smokers while 168 (74.7%) of them were opium addicts. The most prevalent symptoms were chronic ulcers (80%) and claudication (63.6%). Minor and major amputation was required in 113 (50.2%) and 41 (18.4%) patients, respectively. Amputation was carried out on the lower limb (80%), upper limb (4.1%), or on both (15.1%). Also, four patients underwent revascularization through surgical bypass procedures. CONCLUSIONS: The diagnosis and treatment of Buerger's Disease is still a challenge in those communities where the disease is endemic. Therefore, identifying the natural course of the disease can play a pivotal role in the diagnosis and treatment of these patients.

Pregnancy management for a patient with graft occlusion after right iliac artery bypass surgery.

We describe an extremely rare case of a pregnant woman who had a successful delivery despite developing bypass graft occlusion after right external iliac bypass surgery. External and common iliac artery bypass surgery is often performed when arteriosclerosis obliterans or thromboangiitis obliterans result in iliac artery occlusion or when revascularization is required because of iliac artery injury. Because arteriosclerosis obliterans and thromboangiitis obliterans rarely develop in young women or girls, most physicians have little experience with graft occlusion after iliac artery bypass surgery. Here we describe and discuss the published work pertaining to this extremely rare case.