SEMINAR ONSEMINAR ON RECENT TRENDS RECENT TRENDS IN MANAGEMENT IN MANAGEMENT

OF BUERGERS OF BUERGERS DISEASEDISEASE

ModeratorModerator

Dr. Pawan AgrawalDr. Pawan Agrawal

SpeakerSpeaker

Dr. Sumeet JaiswalDr. Sumeet Jaiswal

ChairpersonChairperson

Dr. V.K. RainaDr. V.K. Raina

SPECIAL INVESTIGATIONSSPECIAL INVESTIGATIONS

1. Doppler ultrasound : Based on doppler effect. The 1. Doppler ultrasound : Based on doppler effect. The frequency shift is proportional to the velocity of the blood frequency shift is proportional to the velocity of the blood flow. It may be analysed audibly and may be recorded flow. It may be analysed audibly and may be recorded graphically. It gives quantitative information about the graphically. It gives quantitative information about the degree of stenosis.degree of stenosis.

2. Plethysmography : Method of assessing changes in 2. Plethysmography : Method of assessing changes in volume due to arterial supply to that particular part. volume due to arterial supply to that particular part. Recently, segmental plethysmography has been Recently, segmental plethysmography has been introduced by placing venous occlusion cuffs around the introduced by placing venous occlusion cuffs around the thigh, calf and ankle. The cuffs are inflated to 65 mmHg thigh, calf and ankle. The cuffs are inflated to 65 mmHg and the pulsation is the quantitative measure of the and the pulsation is the quantitative measure of the arterial diseases.arterial diseases.

3. Phonangiography – Vibrations of low frequently in the 3. Phonangiography – Vibrations of low frequently in the arterial wall due to disturbances in blood flow can be arterial wall due to disturbances in blood flow can be analysed audibly.analysed audibly.

4. Isotope technique – Xenon 133 injected 4. Isotope technique – Xenon 133 injected

Intramuscularly and its clearance is used Intramuscularly and its clearance is used

to study the blood flow in the calf muscles. to study the blood flow in the calf muscles.

Recently technetium has become the Recently technetium has become the

isotope of choice. Gamma camera is used isotope of choice. Gamma camera is used

to picturise the blood flow in a limb.to picturise the blood flow in a limb.

5. Arteriography : Most reliable method. Gives 5. Arteriography : Most reliable method. Gives

information about the size of the lumen, the information about the size of the lumen, the

course, constriction and dilatation of the arteries course, constriction and dilatation of the arteries

and collateral circulation. Hypaque 45 (sodium and collateral circulation. Hypaque 45 (sodium

diatrizoate) is the contrast medium often used. diatrizoate) is the contrast medium often used.

Method generally used : Retrograde percutaneous Method generally used : Retrograde percutaneous

catheterization.catheterization.

Retrograde percutaneous catheterizationRetrograde percutaneous catheterization - -

Needle and a cannula are introduced into common Needle and a cannula are introduced into common

femoral artery. Dangers (i) iodine sensitivity and (ii) femoral artery. Dangers (i) iodine sensitivity and (ii)

dissection of the arterial wall. Prevented by trial injection of 5 dissection of the arterial wall. Prevented by trial injection of 5

to 10 ml of 45% hypaque to ascertain the position.to 10 ml of 45% hypaque to ascertain the position.

Free flush arteriography : here tip of the catheter lies in Free flush arteriography : here tip of the catheter lies in

aorta. ‘Bolus’ of 30 ml. contrast medium is injected. Series of aorta. ‘Bolus’ of 30 ml. contrast medium is injected. Series of

X-rays are taken. X-rays are taken.

Selective angiogram : Tip of the catheter is introduced into Selective angiogram : Tip of the catheter is introduced into

the corresponding artery.the corresponding artery.

6. Magnetic resonance angiography (MRA): 6. Magnetic resonance angiography (MRA):

Advantage :Advantage :

(i)(i) Non invasiveNon invasive (ii) Contrast agent is non nephrotoxic(ii) Contrast agent is non nephrotoxic

Limitation :Limitation :

(i)(i) High costHigh cost (ii) Poor availability(ii) Poor availability (iii) Over (iii) Over estimation of degree of stenosisestimation of degree of stenosis

Uses bolus chasing methodUses bolus chasing method Images are obtained in coronal and sagittal plan Images are obtained in coronal and sagittal plan

adjustment can be done in bolus dose and time, infusion adjustment can be done in bolus dose and time, infusion rate, region of interestrate, region of interest

Time of flight (TOF) MRA : 2-D and 3-D TOF MRA detect Time of flight (TOF) MRA : 2-D and 3-D TOF MRA detect flow related phenomenon flow related phenomenon

Better than contrast enhanced MRA for evaluating Better than contrast enhanced MRA for evaluating infrapopliteal vesselsinfrapopliteal vessels

Treatment –Treatment –

1.1. Abstinence from tobacco Abstinence from tobacco

2.2. Drugs – (ilioprost)Drugs – (ilioprost)

3.3. Arterial surgery Arterial surgery

4.4. Omental transposition Omental transposition

5.5. Sympathectomy Sympathectomy

6.6. Neurostimulator devices Neurostimulator devices

7.7. Gene Therapy Gene Therapy

8.8. Ilizarov technique Ilizarov technique

1.1. Abstinence from tobacco – It is only proved treatment Abstinence from tobacco – It is only proved treatment guideline to present disease process. Treatment by any guideline to present disease process. Treatment by any modality is useless if smoking is continued. modality is useless if smoking is continued.

2.2. Drugs : Drugs :

(a) Prostaglandins – Prostaglandin I(a) Prostaglandins – Prostaglandin I22 (ilioprost) has (ilioprost) has

antiplatelet and vasodilator activity. Effective in both antiplatelet and vasodilator activity. Effective in both cutaneous and muscular vessels. Intraarterial infusion cutaneous and muscular vessels. Intraarterial infusion is done.is done.

Adminished in such a low dose that its effect is Adminished in such a low dose that its effect is restricted to target area onlyrestricted to target area only

Adverse effect is avoided because of extensive Adverse effect is avoided because of extensive degradation of PG Idegradation of PG I

2 2 during passage to pulmonary during passage to pulmonary

circulation.circulation.

Intraarterial route is effective more than I/V route (15 Intraarterial route is effective more than I/V route (15 mg/kg / min).mg/kg / min).

(b) Dextran –It Cause hemodilution, decrease (b) Dextran –It Cause hemodilution, decrease blood viscosity and improve microcirculation. blood viscosity and improve microcirculation.

(c) Intraarterial thrombolytic therapy – low (c) Intraarterial thrombolytic therapy – low dose streptokinase (1000 U bolus followed by dose streptokinase (1000 U bolus followed by 5000 U/m) can be used but results are 5000 U/m) can be used but results are variable.variable.

(d) Praxiline (Niftidrofuryloxalate) – It alter (d) Praxiline (Niftidrofuryloxalate) – It alter tissue metabolism, increase claudication tissue metabolism, increase claudication distance by allowing a greater Odistance by allowing a greater O22 supply to supply to

tissue no proved benefit.tissue no proved benefit.

(e) Trental (oxypentifylline) – It has effect on (e) Trental (oxypentifylline) – It has effect on whole blood viscosity by reducing rouleax whole blood viscosity by reducing rouleax formation. No proven benefit formation. No proven benefit

Arterial surgery (I) Surgical bypass or revascularisation

Various by pass procedures are attempted but none of them is convincing

(a)   Direct arterial reconstruction – Some time it is feasible inspite of multiple occluded distal arteries, if successful it provides the most effective healing of ischemic lesion.

(b)  If involvement of artery is above knee, by pass surgery may be possible

Synthetic graft are employed for aorto or ileo femoral by passes while autologus vein is graft of choice for infrainguinal bypass

(II) AV fistula –: If there is arterial involvement only with little pathology in veins. Arterialisation of veins by creating av fistula between artery proximal to site of block and adjacent veins

Omental transpositionOmental transposition

Pedical omental graft transfer can be used here Pedical omental graft transfer can be used here

because of its tremendous angiogenic properties.because of its tremendous angiogenic properties.

Omental pedical is based on right gastroepiploic Omental pedical is based on right gastroepiploic

artery (as it has longer length). For bilateral artery (as it has longer length). For bilateral

procedure both epiploics are used. A subfacial procedure both epiploics are used. A subfacial

tunnel is made from inferior end of laparotomy tunnel is made from inferior end of laparotomy

incision to inguinal and further down to ankle incision to inguinal and further down to ankle

medially. Omentum is lengthened and brought medially. Omentum is lengthened and brought

down to distal most portion of affected limb down to distal most portion of affected limb

through subcutaneous tunnel.through subcutaneous tunnel.

Improvement –Improvement –

- Ulcer healing Ulcer healing

- Rest pain Rest pain

- Claudication distance Claudication distance

Complication - Complication -

- Gastric devascularisation and necrosis in Gastric devascularisation and necrosis in bilateral cases bilateral cases

- Palalytic ileus Palalytic ileus

- Gastrichaemorrhage Gastrichaemorrhage

- Omental necrosis and wound infectionOmental necrosis and wound infection

SympathectomySympathectomy

It causes - It causes -

- VVasodilationasodilation

- Increase blood flow to skin and Increase blood flow to skin and

subcutaneous tissuesubcutaneous tissue

- Healing of superficial ischemic ulcerationHealing of superficial ischemic ulceration

- Abolish rest painAbolish rest pain

It is not beneficial in intermittent claudicationIt is not beneficial in intermittent claudication

Types Types (a) Surgical(a) Surgical (b) Chemical (b) Chemical

Surgical Sympathectomy Surgical Sympathectomy : lumbar sympathectomy : lumbar sympathectomy is done by extraperitoneal approach. Lis done by extraperitoneal approach. L11LL22LL33 and and

sometimes Lsometimes L44 symp ganglion is resected. symp ganglion is resected.

Complication – Paralytic ileus, injury to Complication – Paralytic ileus, injury to genitofemoral nerve, ureteric injury, Injury to major genitofemoral nerve, ureteric injury, Injury to major vessel (aorta, IVC), bowel injury. vessel (aorta, IVC), bowel injury.

Laproscopic sympathecomy :It is being used Laproscopic sympathecomy :It is being used recently. Here denervation is accomplished by recently. Here denervation is accomplished by endoscopic surgical retroperitoneal approachendoscopic surgical retroperitoneal approach

Advantage : (i) Much less operative traumaAdvantage : (i) Much less operative trauma

(ii) Less morbidity(ii) Less morbidity

(iii) Less chance of complication (iii) Less chance of complication

Chemical sympathectomy : Fluroscopic or Chemical sympathectomy : Fluroscopic or ultrasound guided injection of 5 ml of 6.7% phenol is ultrasound guided injection of 5 ml of 6.7% phenol is done by retroperitoneal route at Ldone by retroperitoneal route at L33LL44 level and level and require no anesthesia. require no anesthesia.

- Effects are temporary- Effects are temporaryPercutaneous chemical LS with alcohol with CT Percutaneous chemical LS with alcohol with CT controlcontrol- It is under evaluation and seems to be - It is under evaluation and seems to be better than traditional chemical L-S. better than traditional chemical L-S. Side effects : Side effects : (I) Injury to surrounding structures by needle (I) Injury to surrounding structures by needle (II) Post sympathetic neuralgia (II) Post sympathetic neuralgia Radiofrequency denervation : A new percutaneous Radiofrequency denervation : A new percutaneous approach for sympathectomy using radiofrequency approach for sympathectomy using radiofrequency as denervation source, have less post sympathetic as denervation source, have less post sympathetic neuralgia. neuralgia.

Neurostimulator devices : spinal cord Neurostimulator devices : spinal cord

stimulator are : neurostimulator device used stimulator are : neurostimulator device used

for pain management. They modify electrical for pain management. They modify electrical

nerve activety. Limitations of these devices nerve activety. Limitations of these devices

are :are :

-Data based on randomized control trials Data based on randomized control trials

not available not available

-Can be safely useful only in selected group Can be safely useful only in selected group

of patients of patients

-Lack of sufficient information Lack of sufficient information

Principles : Based on gate control theory of Principles : Based on gate control theory of

pain which explain the physiology of pain in pain which explain the physiology of pain in

terms of electrical conduction across nerve terms of electrical conduction across nerve

synapses, based on ionic changes in CM synapses, based on ionic changes in CM

and spaces between nerve cells. The flow of and spaces between nerve cells. The flow of

nerve impulse from peripheral to central nerve impulse from peripheral to central

nervous system is regulated by cells in nervous system is regulated by cells in

dorsalhorn of spinal cord. The location and dorsalhorn of spinal cord. The location and

type of ionic activity either open or close the type of ionic activity either open or close the

pain gate. pain gate.

Patient selection – Used as late treatment from Patient selection – Used as late treatment from chronic pain. Used only after other treatment chronic pain. Used only after other treatment modalities like pharmacological, surgical, physical, modalities like pharmacological, surgical, physical, psychological have been tried.psychological have been tried.

Procedure – Firstly Demonstration of pain relief Procedure – Firstly Demonstration of pain relief with temporary implanted electrod is made. with temporary implanted electrod is made. optimal electrod placement and pain response to optimal electrod placement and pain response to various frequency is determined. A device is various frequency is determined. A device is implanted by placing a multiple electrod lead in implanted by placing a multiple electrod lead in epidural space along the spinal column using a epidural space along the spinal column using a Tuohy needle. Some times a small laminectomy is Tuohy needle. Some times a small laminectomy is performed to insert a paddle type lead. After performed to insert a paddle type lead. After implantation a handheld programmer control implantation a handheld programmer control various leads of stimulation. various leads of stimulation.

Safety and efficacy :Safety and efficacy : More effective in neuropathic More effective in neuropathic pain rather than visceral/ muscular pain. pain rather than visceral/ muscular pain.

Provide a major benefit for lesion improvement is Provide a major benefit for lesion improvement is end stage patients. Patient having Tend stage patients. Patient having Tcc PO PO22 > 10 mg > 10 mg

(transcutaneous O(transcutaneous O22 (pressure) respond better. (pressure) respond better.

Improves ulcer healing and pain relief. Limb salvage Improves ulcer healing and pain relief. Limb salvage not improved.not improved.

Complication of SCS :Complication of SCS :

Infection in 3-5%Infection in 3-5%

Burning sensation at implantation siteBurning sensation at implantation site

SpasmSpasm

Urinary hesitancyUrinary hesitancy

Poor pain relief Poor pain relief

Gene Therapy :Gene Therapy :

Useful in persistent pain and ischemic Useful in persistent pain and ischemic ulcers.ulcers.

Based on hypothesis that sufficient Based on hypothesis that sufficient exposure of vascular bed to an angiogenic exposure of vascular bed to an angiogenic protein will stimulate neovascularisation. It protein will stimulate neovascularisation. It ensure continuous expression of angiogenic ensure continuous expression of angiogenic protein and prolonged exposure is targeted protein and prolonged exposure is targeted vascular bed.vascular bed.

Various angiogenic factors can be usedVarious angiogenic factors can be used

Such as VEGF, HGFSuch as VEGF, HGF11 del-1 etc. del-1 etc.

Gene therapy :Gene therapy :

VEGF - Most widely used. Stimulate collateral circulation. It VEGF - Most widely used. Stimulate collateral circulation. It is DNA fragment can be deposited on arterial wall. The is DNA fragment can be deposited on arterial wall. The hydrogel balloon operates like an angioplasty balloon hydrogel balloon operates like an angioplasty balloon covered with a hydrophillic layer which delivers the DNA covered with a hydrophillic layer which delivers the DNA fragment when inflated. A single intrarterial bolus of VEGF fragment when inflated. A single intrarterial bolus of VEGF recombinant human protein result in angiographic, recombinant human protein result in angiographic, hemodynamic, physiologic and histological evident hemodynamic, physiologic and histological evident augmentation of collateral circulation more recently I/M route augmentation of collateral circulation more recently I/M route has been used to take advantage of vascular distribution of has been used to take advantage of vascular distribution of this angiogenic cytokine. The peripheral muscle cells can this angiogenic cytokine. The peripheral muscle cells can perform the transcription and translation into human DNA perform the transcription and translation into human DNA protein.protein.

Indication – Can be used in – Indication – Can be used in –

Rest pain Ischemic ulcer Intermittent claudication Rest pain Ischemic ulcer Intermittent claudication

Hepatocyte growth factor – Potent angiogenicHepatocyte growth factor – Potent angiogenicI/M infusion of naked HGF plasmid DNA is performed in I/M infusion of naked HGF plasmid DNA is performed in ischemic limb.ischemic limb.Advantage – Severe complication and adverse side effect of Advantage – Severe complication and adverse side effect of gene transfer are absent. gene transfer are absent. Effects :Effects :

(1)   Reduction of pain related symptom(1)   Reduction of pain related symptom(2)   Increase in angle pressure index more than .1(2)   Increase in angle pressure index more than .1(3)   Diameter of ischemic ulcer reduced.(3)   Diameter of ischemic ulcer reduced.

Can be sole therapy for chronic limb ishcemia in future.Can be sole therapy for chronic limb ishcemia in future.(c) Extracellular matrix protein Del-1(c) Extracellular matrix protein Del-1The ECM protein Del-1 is ECM protein that accumulate The ECM protein Del-1 is ECM protein that accumulate around angiogenic vessel and promote angiogenesis. around angiogenic vessel and promote angiogenesis. restore muscle function. It bind to integrin alphabeta 5 on restore muscle function. It bind to integrin alphabeta 5 on resting endothelium, convert in to angiogenic endothelium by resting endothelium, convert in to angiogenic endothelium by inducing expression of proangiogenic molecules integrin inducing expression of proangiogenic molecules integrin alpha Balpha B33. .

Ilizarov Technique :- The physiological Ilizarov Technique :- The physiological basis is the law of Tension Stress. When basis is the law of Tension Stress. When living tissue are subjected to uniform living tissue are subjected to uniform planar distraction force after atraumatic planar distraction force after atraumatic corticotomy, in the presence in intact corticotomy, in the presence in intact functions, new tissue regenerate in the functions, new tissue regenerate in the limb. Not only does the new bone forms, limb. Not only does the new bone forms, but blood vessels, nerves, muscles, fascia but blood vessels, nerves, muscles, fascia and skin form as well. Thus, it is the and skin form as well. Thus, it is the phenomena of distruction phenomena of distruction neohistogenesis. neohistogenesis.

There is increase in the formation of There is increase in the formation of

capillaries in the zone of the ‘Regenerate capillaries in the zone of the ‘Regenerate

Bone Formation’ and in rest of the limb by Bone Formation’ and in rest of the limb by

an increase in the collateral circulation.an increase in the collateral circulation.

OPERATIVE TECHNIQUEOPERATIVE TECHNIQUE

-Widening of the bone is performed not lengthening. Widening of the bone is performed not lengthening.

-Longitudinal osteotomy is performed In the upper part of Longitudinal osteotomy is performed In the upper part of the tibia. the tibia.

-Osteotomy is very slowly distracted apart. Osteotomy is very slowly distracted apart.

-Gap would fill up with regenerative tissue (bone and Gap would fill up with regenerative tissue (bone and vascular tissue). vascular tissue).

Consists of two rings. One in each metaphysis. Consists of two rings. One in each metaphysis. Connected with a long rod. Longitudinal osteotomy is Connected with a long rod. Longitudinal osteotomy is made on the anteromedial face. Triangular fragment is made on the anteromedial face. Triangular fragment is about 12 to 15 cm long. The osteotomies have a width of about 12 to 15 cm long. The osteotomies have a width of only mm. Periosteum is not damaged.only mm. Periosteum is not damaged.

Distraction done with the help of olive wires or Distraction done with the help of olive wires or crossed plain wires at the rate of about 0.25 mm, three to crossed plain wires at the rate of about 0.25 mm, three to four times a day.four times a day.

OLIVE WIRE METHOD OLIVE WIRE METHOD • Olive wires are drilled in from the antero-Olive wires are drilled in from the antero-lateral crest of the tibia, passing through the lateral crest of the tibia, passing through the triangular fragment to exit from the postero-triangular fragment to exit from the postero-medial corner and the skin. medial corner and the skin. • Olive to pass through the holes. They rests Olive to pass through the holes. They rests against the inner cortex of the triangular against the inner cortex of the triangular fragment.fragment.• Olive wires connected to a long steel plate. Olive wires connected to a long steel plate. This steel. This steel. • When the nuts are turned, triangular When the nuts are turned, triangular fragment widened. fragment widened.

The Modified Crossed Wire Technique The Modified Crossed Wire Technique

•Achieves horizontal distraction simply and atraumatically.Achieves horizontal distraction simply and atraumatically.

• Plain K wires are inserted through the postero-medial Plain K wires are inserted through the postero-medial aspect into the triangular fragment. aspect into the triangular fragment.

• Four wires are inserted, angulated anteriorly to the mid-Four wires are inserted, angulated anteriorly to the mid-coronal plane. 4 wires are inserted in a plane angled coronal plane. 4 wires are inserted in a plane angled slightly posterior to the mid-coronal. slightly posterior to the mid-coronal.

• Wires stop within the triangular fragment. Wires stop within the triangular fragment.

• All the wires are connected to individual bolts and All the wires are connected to individual bolts and attached to a steel plate. attached to a steel plate.

• Wires do not cross physically, the resultant vector of Wires do not cross physically, the resultant vector of wires pull the triangular fragment horizontally. wires pull the triangular fragment horizontally.

• Advantage : No olive wires are needed, no incisions or Advantage : No olive wires are needed, no incisions or predrilling is required for insertion and removal, and the predrilling is required for insertion and removal, and the procedure is simple and atraumatic. procedure is simple and atraumatic.

Rate And Rhythm Of Distraction Rate And Rhythm Of Distraction

The ideal rate of distraction (widening) The ideal rate of distraction (widening)

is one mm per day in fractions of ¼ mm 4 is one mm per day in fractions of ¼ mm 4

times a day. It the entire 1 mm per day times a day. It the entire 1 mm per day

distraction is done in one step, the bone distraction is done in one step, the bone

formation may be poor. The lesser the range formation may be poor. The lesser the range

and more frequent the rhythm, better is the and more frequent the rhythm, better is the

bone and vessel formation.bone and vessel formation.

POSTOERATIVE COURSEPOSTOERATIVE COURSEFull weight bearing possible within a few Full weight bearing possible within a few

days. Total distraction is 1.5 to 2 cm. This much days. Total distraction is 1.5 to 2 cm. This much volume of ‘regenerate bone’ is sufficient to volume of ‘regenerate bone’ is sufficient to increase vascularity of the. increase vascularity of the.

The pain relief and appearance of warmth The pain relief and appearance of warmth commences after 15 to 20 days (coincides with the commences after 15 to 20 days (coincides with the formation of new blood vessels). The Ilizarov formation of new blood vessels). The Ilizarov apparatus is retained on the limb until the apparatus is retained on the limb until the regenerate bone matures and hardens which is regenerate bone matures and hardens which is usually 2.5 to 3 months.usually 2.5 to 3 months.RESULTS RESULTS • Dramatic pain relief Dramatic pain relief • Increased Claudication distanceIncreased Claudication distance• Limitation of gangreneous spreadLimitation of gangreneous spread