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New haemostatic techniques: argon plasma coagulation
BEST
Baillière’s Clinical Gastroenterology Vol. 13, No. 1, pp 67–84, 1999
B A I L L I È R E ’ S
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PRACTICE & RESEARCH
New haemostatic techniques: argon plasma coagulation Karl E. Grund
MD
Professor of Surgery
T. Straub
MD
Resident Physician Department of Surgical Endoscopy, University Hospital, Hoppe-Seyler Strasse 3, D-72076 Tuebingen, Germany
G. Farin
Dipl. Ing.
Chief Engineer Medical Research Center, Eberhards-Karls University, Waldhoernlestrasse 22, D-72072 Tuebingen, Germany
Bleeding is one of the main challenges for endoscopists. Despite a large number of methods for haemostasis, several types of haemorrhage lack an adequate therapeutic remedy. Argon plasmacoagulation (APC), a new method for the non-contact application of high-frequency current, promises to solve many of these problems. Among 1164 patients treated in 2349 sessions using APC, the indication was bleeding (due to tumour, intervention, angiodysplasia or coagulation disorders) in 305 patients (26%). The primary success rate was over 99%, the rebleeding rate 1.6% and the complication rate less than 1%, with zero mortality. Physical principles, indications, application parameters and results are discussed, especially in comparison with the Nd:YAG laser. APC is a new, efficacious, safe and easy-to-use method for the devitalization of tissue and haemostasis, especially in problematic cases. Key words: haemostasis; bleeding; argon plasma coagulation; laser; endoscopy.
Haemostasis represents one of the most important problems in endoscopy. Many different endoscopic methods have been developed during the last 20 years (Friedman 1993, 1994; Soehendra et al, 1997), resulting in a revolution in treatment of different types of bleeding (Table 1). No single method, however, covers all kinds and sources of haemorrhage. All the currently used methods are insufficient in the treatment of some difficult types of bleeding: diffuse bleeding arising from large areas, bleeding as a result of coagulation disorders (e.g. drug-induced, non-steroidal-antiphlogistic drug (NSAPD), etc.) or a haemorrhage from a tumour which is diffuse and difficult to control (Fleischer 1986; Lee and Liebermann, 1996). To achieve haemostasis in these problematic lesions, argon plasma coagulation (APC), a new method of electrocoagulation using the non-contact application of electrical energy to the lesion, was taken into consideration. According to experiences in open surgery, where APC has proved to be an efficient method for haemorrhage from the liver, spleen or kidney, we modified the method to 1521–6918/99/010067 + 18 $12.00/00
© 1999, Baillière Tindall
Peptic ulcer (visible vessel) Spurting Oozing Varices Tumour Post-intervention Inflammation Post-irradiation Angiodysplasia Coagulation disorder
Type of bleeding + ? – – ? – – ? –
Clip – – + – ? – – – –
Rubber band ligation + + (+) (+) (+) – – (+) –
Injection techniques – – + – – – – (+) –
Sclerosants
? (+) – ? ? – – ? –
Heater probe
? (+) – ? ? – – ? –
HF-surgery
? ? – (+) ? ? (+) ? ?
Nd:YAG laser
Table 1. Conventional methods of haemostasis compared with argon plasma coagulation (APC) in different types of haemorrhage.
– + ? + + + + + +
APC
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be applied in flexible endoscopy by developing flexible probes and optimizing generators and gas sources. The following paper describes the physics, equipment and clinical experiences related to this new method. PHYSICAL PRINCIPLES OF ARGON PLASMA COAGULATION APC is a new modality to apply high-frequency (HF) electric current to tissue in order to cause defined thermal effects that can be used for the thermal devitalization of pathological tissue as well as for haemostasis. In principle, APC is a special mode of HF surgery. The most important prerequisite for the effective and safe use of APC is the understanding of its physical principles (Farin and Grund, 1997, 1998). In contrast to conventional HF surgery, the HF current is not conducted to the target tissue via monopolar, bipolar or multipolar active electrodes in direct contact, but via ionized and thus electrically conductive argon (which is called ‘argon plasma’). APC requires an APC applicator suited to the intended task, an argon source and a HF current source (Figure 1). APC applicators consist principally of a tube (R) whose distal end contains an electrode (E) (Figure 2). When adequately high HF voltage (UHF) is applied between the electrode and the tissue (G), the argon (Ar) flowing out of the tube becomes ionized in the electric field between the electrode and the tissue. In this way, electrically conductive argon plasma beams are created through which a HF current (IHF) can flow into the tissue and back to the HF current source (HF) via a neutral electrode (NE). The HF current generates heat in the tissue, causing different thermal effects such as devitalization (zone 1), coagulation (zone 2), desiccation (zone 3) and tissue shrinking (zone 4) (Figure 2). As soon as a location on the tissue surface loses its electric conductivity as a result of desiccation, the plasma beams automatically change the direction to locations at the surface that are still electrically conductive. This process continues until the entire surface in the area close to the distal end of the APC applicator has been desiccated. As a result of these characteristics, APC creates uniformly deep zones of devitalization (1) coagulation (2) and desiccation (3); even in large-area applications, these are automatically limited to at most 3(–4) mm,
Figure 1. Schematic depiction of the equipment for argon plasma coagulation.
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Figure 2. Schematic depiction of the principle of argon plasma coagulation.
depending mainly on application time. Another result of these characteristics is that the direction of the plasma beam is independent of the direction of the argon flow. Hence the APC applicator can be used in nearly all directions in relation to the tissue (Figure 3). In addition, APC does not cause carbonization or vaporization and therefore does not generate smoke, so it is well suited for endoscopic applications. The automatically limited depth of the thermal effects, as well as the absence of the vaporization effect, predestine APC for applications in flexible endoscopy, where perforation of thinwalled organs is a serious complication. In its simplest version, an argon source consists of a gas cylinder and a valve for reducing the pressure from the gas cylinder to a value appropriate to the intended application. For APC in endoscopy, the argon source should, for safety reasons, be provided with automatically controlled flow rates and maximum gas pressure limitations. A relatively low argon flow rate or velocity is sufficient to produce plasma beams. The HF current source must provide both a sufficiently high HF voltage for the ionization of the argon and a sufficiently large HF current to generate adequate heat within the target tissue. An electric field strength of approximately 500 V/mm is
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Figure 3. Argon plasma coagulation can be applicated axially, laterally and radially.
needed to ionize the argon. The voltage (UHF) needed for ignition is determined by the required electric field strength and the distance (d) between the electrode and the tissue. A distance of, for example, 10 mm thus requires a HF voltage with a peak value of approximately 5000 V. The HF current needed for APC is comparable to that required for conventional contact coagulation. Measurements in vitro and in vivo have shown that the depth of the thermal effects depends upon the power setting and duration of application (Figure 4) but is limited to 3 mm using the equipment described below with reasonable application time (Farin and Grund, 1997; Grund, 1997; Grund and Farin, 1997). Although APC had been used in open surgery for 20 years to perform haemostasis, mainly of the liver, spleen and kidney tissue, its application in flexible endoscopy was not possible until special APC applicators for this purpose, which can be used through the working channel of flexible endoscopes, had been developed, designed and clinically tested (Farin and Grund, 1994; Grund and Farin, 1997).
Figure 4. Depth of coagulation versus duration of application in different power settings.
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EQUIPMENT After several years of development and clinical tests, standard APC equipment for endoscopy consists of different flexible APC-applicators matched to the various flexible endoscopes, an automatically controlled argon source (APC 300 ERBE Electromedizin GmbH, Tuebingen, Germany) and a HF generator (Erbotom ICC 350, or Erbotom ICC 200, ERBE Elektromedizin GmbH). The APC applicators consist of a flexible PTFE tube, containing a lumen for the flow of argon from the argon source to the distal end of the tube, and a wire to conduct HF current from the HF generator to the electrode within the end of the tube. These flexible APC applicators can be introduced into the working channel of flexible endoscopes in a range from paediatric bronchoscopes (working channel diameter 2.0 mm) up to therapeutic colonoscopes (working channel diameter 3.5–4.0 mm). The generator and argon source are combined on a trolley as a mobile unit (Figure 5). The documentation of therapeutic sessions is performed audiovisually from start to finish using a VCR, electrical and pneumatic parameters being registered automatically. Because of such complete documentation, a work-up of the sessions is possible in detail by reviewing the audiovisual recordings. CLINICAL APPLICATION Patients and indications Our experiences with APC are based on experimental and clinical work from 1991 to 1998. In a prospective study, 1164 consecutive patients—644 men and 520 women
(A)
(B)
Figure 5. Equipment for argon plasma coagulation (A), consisting of an automatically controlled argon source (APC 300), a high-frequency current source (ICC 350) installed on a mobile trolley and argon plasma coagulation applicators for flexible endoscopes (B).
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with a mean age of 67 years (range 3 months–97 years)—underwent treatment with APC in the upper or lower gastrointestinal tract or the tracheobronchial system in 2.349 sessions. The primary indications for treatment are listed in Table 2. Without the availability of APC, these patients would all have been treated with the Nd:YAG Laser or by conventional electrosurgery, many of them being candidates for an operation. Three hundred and five of these patients were treated in 410 sessions because of acute or chronic haemorrhage. The most relevant sources of the bleeding were tumours, post-interventional bleeding, angiodysplasia, post-irradiation lesions and inflammatory sources (Table 3). For each patient the defined goal of therapy had to be reached in a maximum of 2–3 sessions: reliable haemostasis according to endoscopic (and clinical) criteria without recurrent bleeding. In all cases, follow-up endoscopies were performed to confirm haemostasis and to judge the state of the bleeding source. In arteriovenous abnormalities (angiodysplasia or watermelon stomach), the goal was haemostasis and the eradication of pathological lesions, with no recurrence of the haemorrhage and pathological tissue, controlled by biopsy and histology. After the successful development of a reliable endoscopic Doppler system in 1995 (Grund et al,
Table 2. Indications for treatment with APC (partly overlapping). Tumour Malignant Benign Bleeding Stent (in-/overgrowth) Adenomas Others
Patients
Applications
665 581 84 305 140 168 115
1399 1236 163 410 385 220 166
Table 3. Distribution of sources of haemorrhage in 305 patients and 410 episodes of treatment. The majority of tumors were malignant exulcerating tumours with relevant bleeding activity, about one-third of the cases referred from other hospitals after unsuccessful trials of haemostasis. Tumours Oesophagus Stomach Duodenum/small bowel Colon Rectum Other (pharyngeal, tracheobronchial)
65 18 8 15 26 14
Other Angiodysplasia/watermelon stomach Post-irradiation lesion Mallory–Weiss lesion Dieulafoy’s ulcer Other
44 14 8 8 8
Post-interventional Dilatation/bougienage Incision Snare manoeuvre (polypectomy, mucosal resection) Post-biopsy Other
19 4 16 8 9
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1999), the bleeding lesions were objectively checked for their origin (arterial, venous or arteriovenous), the presence of a bleeding vessel, its diameter and its depth in the wall (Grund et al, 1999). Localization The sources of the bleeding were mainly located in the upper (52%) and lower (32%) gastrointestinal tract and in the tracheobronchial system (16%). Application Patients were on average treated for 2 or 3 applications (range 1–18) (Table 4), the duration of application reaching 1 minute. Because of the nearly unrestricted access to the target area with the APC probe, the application technique could easily be adapted to the underlying lesion. Applications were preferably carried out by drawing back the probe either longitudinally or laterally in a brush-like manner. The ‘ten commandments for APC’, the power settings and the safety instructions (see discussion below) were maintained in order to achieve a high level of security.
Table 4. Application data. Parameter
Value (range)
Number of patients Applications Applications per patient Duration of application Argon gas volume Electric power Electric energy
1164 2349 2 (1–18) 60 (0.5–600) seconds 1.3 (0.2–18.0) litres 79 (10–100) W 6.8 (0.08–30.0) kJ
Results The data acquired for all interventions were evaluated with regard to the previously defined goals of treatment. In all but one patient (99.7%), haemostasis was achieved. In this latter case, because of strong arterial bleeding from a gastric cancer, APC was tried after the unsuccessful application of clips and injection. Bleeding was reduced but not stopped, so the patient underwent an emergency operation. Only in five patients out of 305 (1.6%) was recurrent bleeding observed; two of these patients needed surgery, and three others additional haemostatic endoscopic procedures (additional injection therapy, more than three APC sessions). Compared with other indications for APC, (especially palliative tumour therapy with a very low complication rate and mortality (Grund and Farin, 1997; Grund et al, 1998)), in the group of haemostatic procedures even a zero rate of severe side-effects, complications and mortality was noticed. Intestinal emphysema occurred in three sessions (1.3%) because of accidental activation of the HF generator during contact between the tip of the probe and the wall; this remained asymptomatic in all cases and was endoscopically no longer visible during follow-up examinations. No further serious method-related
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complications or side-effects were found immediately or later during a mean followup period of 26 (range 1–75) months. Approximately 30% of the patients complained of intermittent pain arising from distension, and rarely from thermal effects. The surgeons and the assisting staff assessed the practicability and ergonomics of the unit and the probes as superior, particularly in comparison to laser. These characteristics are now undergoing further analysis in multicentre studies.
DISCUSSION Ideally, the endoscopic treatment of bleeding in the gastrointestinal tract should fulfil the conditions of maximal efficaciousness paired with minimal mechanical or thermal lesions of the unaffected neighbouring tissue (Lee and Liebermann, 1996; Morgan and Clamp, 1988; Rollhauser and Fleischer, 1998). Perforation, deep necrosis and the disturbance of re-epithelialization and healing should be strictly avoided. Not one of the established methods (except fibrin glue injection) can fulfil the requirements to stop bleeding and simultaneously preserve the underlying or adjacent healthy tissue. In relation to the vast diversity of different methods for endoscopic haemostasis, it has to be stressed that diffuse bleeding from tumours or from wide-area lesions, as well as haemorrhage as a result of bleeding disorders, is still an unsolved problem. Conventional electrosurgery and the Nd:YAG laser, usually mentioned as the most suitable methods for this purpose (Fleischer, 1986; Mathus–Vliegen, 1997), have indisputable disadvantages: ● ● ● ● ● ●
a penetration depth that cannot be estimated using visual control, and hence a remarkable risk of perforation occurs; a high absorption of energy in liquid and/or coagulated blood, leading to difficulty controlling the thermal effect; substantial problems in ergonomics and practicability with the probes, leading to an impairment of intervention and rising stress; difficult or impossible application in certain anatomical cases and situations demanding lateral application (caecum or oesophagus) or inversion (gastric cardia), making the target inaccessible; the tip of the probes easily becoming encrusted, necessitating a repeated pull-out for cleaning; the absorption of energy depending on the colour of the tissue (white tissue reflecting 90% of the laser energy). The tissue, however, changes its colour during activation.
APC versus other methods, especially the Nd:YAG laser The decisive difference between these two methods depends on the transfer of energy to the tissue. The Nd:YAG laser (Mathus–Vliegen, 1997; Soehendra et al, 1997) may lead to coagulation (under certain conditions), otherwise it removes tissue by vaporization, but these effects are difficult to control. The physical principles governing APC, on the other hand, allow good control and manoeuvrability for devitalization, coagulation and desiccation, with a homogeneous penetration depth over wide areas. The maximum penetration depth is physically limited and can be controlled by the parameters of application (Farin and Grund, 1997; Grund and Farin, 1997). On the
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other hand, APC allows effective tissue ablation in palliative tumour therapy as a result of its pronounced desiccation and tissue shrinkage effects. Table 5 lists these characteristics of APC. APC combines the advantages of conventional electrosurgery with those of the Nd:YAG laser, but without their drawbacks. It combines non-contact application with a controllable, constant coagulation depth in an uncomplicated technique, managing apparently contradictory characteristics—effective coagulation, especially of larger areas, with shallow but well-controlled and uniform coagulation depth. Neither conventional electrosurgical methods nor the Nd:YAG laser permit such a well-defined and visually easily controlled discharge of energy at target structures as does APC. Since APC can be applied in a brushwork fashion over large areas, it is particularly well suited for treating diffuse bleeding, broad tumours and adenomatous tissue. The plasma beam can be applied in an orthograde fashion, radially and even ‘round corners’. This is highly advantageous in difficult anatomical areas, for stenotic tumours, in the colorectum, at high inversion angles in the gastric cardia, and in the tracheobronchial system. A sturdy, flexible and easily controlled applicator is a must for use in clinical practice. The APC probe avoids previously unsolved problems with laser probes (i.e. the limited flexing radius, the fixed angle of divergence, the limited lifespan of the probe tip, the
Table 5. Advantages and disadvantages of argon plasma coagulation seen in experimental and clinical experience. Advantages
Disadvantages
Effective and safe coagulation Non-contact mode (2–10 mm) Axial, radial and retrograde applications Controllable depth of coagulation (0.5–3.0 mm) Marked desiccation No destruction of metal stents* Low smoke and vapour production Mobile, handy equipment Applicators steerable, robust and cheap Low cost of purchase, use and maintenance No extended safety precautions needed
Intestinal distension by argon flow No ‘real’ vapourization* Bowel wall emphysema possible Radiofrequency interference with video
* Not relevant for haemostasis.
(B) (A)
Plate 12. Cervical oesophageal cancer with stenosis and haemorrhage during (A) and after (B) 8 kJ argon plasma coagulation. Effective haemostasis and recanalization. Please see Appendix for colour figure.
New haemostatic techniques: argon plasma coagulation (A)
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Plate 13. Duodenojejunal invasion of a sarcoma before (A) and during (B) argon plasma coagulation therapy for palliation. Please see Appendix for colour figure. (A)
(B)
(C)
Plate 14. Recurrently bleeding watermelon stomach (A), after intensive 6 kJ argon plasma coagulation (B), and the healing stage 3 weeks later (C). Haemoglebin level is now constant at over 12; no symptoms. Please see Appendix for colour figure.
(A)
(B)
(C)
Plate 15. Extended angiodysplastic lesion (MB stained) in the stomach before (A) and after (B) extensive argon plasma coagulation, and the healing stage 25 days later (C). Please see Appendix for colour figure.
(A)
(B)
(C)
Plate 16. Post-irradiation ‘proctocolitis’ after 60 Gy with recurrent, severe bleeding episodes (A), after superficial argon plasma coagulation with 4.8 kJ (B), and healing with fibrin after 10 days (C) Please see Appendix for colour figure.
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(A)
Plate 17. Haemostasis with argon plasma coagulation in a superficial heavily bleeding laceration after dilatation (A) and in a Dieulafoy’s ulcer (B), typically located. Perfect haemostasis. Please see Appendix for colour figure.
rapid build-up of crusts, the high costs and its clumsiness in use). A further advantage of the unit is its mobility: it can—in contrast to laser—be employed quickly and carried to any place at any time. The acquisition and operating costs of an APC system are only a fraction of those of an Nd:YAG laser. No special safety precautions are required to prepare, operate or service the APC unit. For haemostasis in endoscopy, deep coagulation and the production of smoke and vapours should be avoided, especially in the tracheobronchial system. For precisely targeted applications, it should be possible to view the coagulation process clearly through the endoscope. Most of these requirements are fulfilled by APC. In contrast to alternative methods, the bright plasma jet is easily kept in view and can be used to pass brush-like over the tissue; thus wide area, diffuse haemorrhages are the special domain of APC. In spite of all the euphoria, however, certain disadvantages must also be clearly recognized (Table 5). As with carbon dioxide-cooled laser probes, argon insufflation during APC must be carefully monitored, and precautions must be taken to avoid distension. Wall emphysema, which may extend as far as to become intestinal pneumatosis (Wahab et al, 1997), has been observed but appears to be reversible. Finally, even the limited penetration depth of APC cannot, of course, provide absolute protection against possible complications such as the perforation of very thin-walled structures or inadequate application. In both absolute and relative terms, however, the complication rates of APC remain very low (Johanns et al, 1996; Grund and Farin, 1997; Wahab et al, 1997; Grund et al, 1998). To achieve the best results, it is essential to follow certain recommendations (Farin and Grund, 1998). Application With the increasing use of APC as a method for haemostasis and devitalization in flexible endoscopy, technical details for the correct application and use of the probe in special situations, the dosage of energy for different indications and, last but not least, safety aspects have to be clearly outlined. The basic information is given in Table 6 and in the ‘ten commandments for APC’ (Farin and Grund, 1998). The ignition and electric arc must be properly tested outside the endoscope before advancing the probe into the working channel. Correct positioning of the probe during application in order to carry out APC in full view is also absolutely necessary.
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Table 6. Setting of argon plasma coagulation (APC) parameters.
Normal settings for oesophagus, duodenum, small bowel and rectum Stomach Stent in/overgrowth Conditioning of fistulae Tracheobronchial system Thin probe (1.5 mm) Normal probe (2.0 mm) Large tumours (diameter > 15 mm) Medium-sized tumours (diameter = 5–15 mm) Small tumours Right colon Remaining colon
Power limitation (setting) (W)
Activation time (seconds)
60–80
1–3
60–80 60 40–60
1–3 3–5 0.3–1.0
40 50–60 99 80 60 (!)40(!) 40–50
1–5 1–5 3–10 3–5 1–5 (!)0.1–0.5(!) 1–3
Recommended dosages of APC energy in practice. The recommended values refer to the standard equipment (ICC 200 or ICC 350, APC 300 and flexible APC probes, all manufactured by ERBE Elektromedizin GmbH, Tuebingen, Germany).
This may be generally difficult in some situations with bleeding, but effective suction/irrigation equipment and some rules of positioning the patient to reach the site of bleeding under vision may help to identify the source exactly. The APC probe should be moved close enough to the target to ensure ignition, but one should avoid touching the organ wall. In order to avoid emphysema or wall damage, the tip of the APC probe should never be pressed against the tissue during activation. HF output power should be limited according to the values given in Table 6, which are relevant for haemostatic indications as well as tumour destruction. A series of brief activations is superior to few prolonged activations in haemostasis with APC, as well as in the technique’s more general use. Indications The characteristics of APC are especially beneficial for the above-mentioned problematic situations of profuse wide area haemorrhage, tumour bleeding and angiodysplastic lesions. The plasma stream always automatically seeks the best path to the tissue regardless of the angle at which the APC probe is directed toward the tissue. As soon as a location on the tissue surface loses its electric conductivity as a result of desiccation, the plasma stream automatically redirects itself to locations that are still electrically conductive, this process continuing until the entire surface in the area of the APC probe is desiccated. As interventional procedures become more and more relevant, postinterventional bleedings have to be managed during and after the endoscopic manoeuvre. Bougienage, balloon dilatation, removal of tumours, adenomas and polyps can be associated with haemorrhage. In all these cases, APC proved to be effective, quick and easy to apply, especially in critical cases. In haemorrhages out of—mostly malignant—often exulcerated tumours with clefts and fissures, APC has the unique characteristic that the electrical beams can ‘dive down’ into the clefts, leading to thermal effects at an otherwise inaccessible site.
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Nevertheless, the effective penetration depth runs from the tissue surface to only the level defined by the electrical parameters and the duration of application. With the correct use of these parameters, this depth can be ‘adjusted’ between 0.5 and 3.0 mm, thus ideally fulfilling the demands of the indications mentioned above. Angiodysplastic changes, such as watermelon stomach, require a controlled and very superficial application of energy, spread over a wide area. A reliable and reproducible restriction of penetration depth to less than 1 mm appears absolutely necessary in the case of arteriovenous malformations. In addition, contact-free application is desirable to prevent adhesions to the probe. All these demands are completely met by APC. In principle, the underlying technique of APC also permits the treatment of isolated punctate haemorrhages (e.g. from an ulcer). For arterial haemorrhage and spurting vessels (e.g. in peptic ulceration), injection methods with highly diluted epinephrine and/or fibrin glue or the application of a clip seem to be the standard procedure (see Table 1 above). Experiences with APC in such indications are rare; in our own series, only five patients with strong arterial haemorrhage were treated this way, four of them with a successful haemostatic result. Due to the fact that APC is a thermal method causing relatively slight but indisputable thermal injury to the surrounding and underlying tissue, APC is thought not to be the first choice for such indications. An exception seems to exist in Dieulafoy’s ‘ulcer’, which does not have the characteristics of a peptic ulcer. For this indication, APC has proved to be a promising therapeutic method. All of our eight patients were cured with a single APC session. Results A rate of primary haemostasis of 99.3%, a recurrence rate of 1.6%, zero mortality and a complication rate less than 1% in a big clinical series are undoubtedly promising (Lee and Liebermann, 1996; Grund, 1997; Grund et al, 1998). This holds especially true for the fact that mainly problematic haemorrhages, for which no standard therapy has been established, were treated. Additionally, relatively hard criteria have been used to evaluate and control the effect. As with every new method, however, results may depend on the physician’s experience. On the other hand, the initial results from other clinical groups using APC confirm our own findings (Elhasani et al, 1996; Johanns et al, 1996; Cipolletta et al, 1997; Mulder and Wahab, 1997; Wahab et al, 1997). All the authors describe successful haemostasis in all (or nearly all) patients undergoing APC therapy. The complication rate for haemostatic indications is very low in all reports in the literature; APC is estimated to be an effective, safe and cost-effective method Bergler et al, 1997; Cipoletta et al, 1996; Fleischer et al, 1997; Grund et al, 1997; Heindorf et al, 1998; Van Laethem et al, 1997; Niezychowski et al, 1996; Regula et al, 1996; Robertson et al, 1996; Vreeburg et al, 1997). Endoscopic haemostasis in the tracheobronchial system presents a special problem because of the anatomical restrictions and the production of smoke and vapour. These manoeuvres are technically very demanding and sometimes impossible with commonly used methods, but APC seems to be ideal (Grund et al, 1998). Future aspects In summary, even a critical appraisal clearly shows that APC is not merely a modification of previous electrosurgical techniques but represents a new, trendsetting development in haemostasis. It should also be remembered that plasma surgery in
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general is at present only in the initial stages of its development, and that APC in its present form has taken only the first step in its clinical career. Controlled, multicentre studies with large numbers of patients will be needed to test APC in different indications, including different types of haemorrhage, comparing the results with those of already established methods. Further fundamental research in plasma physics is on the way to elucidate the phenomenon of the interaction between plasma and tissue. The physical characteristics of APC pave the way for wide-ranging future developments, opening up the horizon of treatment of many previously challenging conditions. REFERENCES Bergler W, Hönig M, Götte K et al (1997) Treatment of recurrent respiratory papillomatosis with argon plasma coagulation. Journal of Laryngology and Otology 111: 381–384. Cipolletta L, Bianco MA, Rotondano G et al (1996) Argon plasma coagulation (APC) in gastrointestinal endoscopy: a pilot experience in Italy. Italian Journal of Gastroenterology 28 (supplement 2): 80–81. Cipolletta L, Bianco MA, Rotondano G et al (1997) Argon plasma coagulation (APC) vs. heat probe (HP) for bleeding peptic ulcers: a prospective, randomized trial. Digestive Disease Week p A-442 (abstract). Elhasani S, Hodson RM, Tsai HH et al (1996) Use of argon beamer electrocoagulation in a UK endoscopy unit. Endoscopy 28: 1172. Farin G & Grund KE (1994) Technology of argon plasma coagulation with particular regard to endoscopic application. Endoscopic Surgery 2: 71–77. Farin G & Grund KE (1997) Basic principles of electrosurgery in flexible endoscopy. In Tytgat GNJ, Mulder CJJ (eds) Procedures in Hepatogastroenterology, vol. 15, pp 415–437 Dordrecht: Kluwer Academic. Farin G & Grund KE (1998) Argon plasma coagulation in flexible endoscopy—the physical principle. Endoscopia Digestiva (Japan) 10: 1521–1527. Fleischer D (1986) Endoscopic therapy of upper gastrointestinal bleeding in humans. Gastroenterology 90: 217–234 (review). Fleischer DE, Wang GQ, Dawsey SM et al (1997) Endoscopic therapy for esophageal dysplasia (ED) and early esophageal cancer (EEC) in Linxian, China. Digestive Disease Week p A-34 (abstract). Friedman LS (1993) Gastrointestinal bleeding I. Gastroenterology Clinics of North America 22(4): 717–891. Friedman LS (1994) Gastrointestinal bleeding II. Gastroenterology Clinics of North America 23(1): 1–183. Grund KE (1997) Argon plasma coagulation (APC): ballyhoo or breakthrough. Endoscopy 29: 196–198. Grund KE & Farin G (1997) New principles and applications of high-frequency surgery, including argon plasma coagulation. In Cotton PB, Tytgat GNJ & Williams CB (eds) Annual of Gastrointestinal Endoscopy, pp 15–23. London: Rapid Science. Grund KE, Zindel C & Farin G (1996) Argon plasma coagulation (APC)—a new and innovative tool for flexible endoscopy. Endoscopia Digestive (Japan) 9: 1209–1212. Grund KE, Zindel C & Farin G (1997) Argonplasmakoagulation in der flexiblen Endoskopie—Bewertung eines neuen therapeutischen Verfahrens nach 1606 Anwendungen. Deutsche Medizin Wochenschrift 122: 432–438. Grund KE, Straub T & Farin G (1998) Clinical application of argon plasma coagulation (APC) in flexible endoscopy. Endoscopia Digestiva (Japan) 10: 1543–1554. Grund KE, Straub T & Kayalar A (in press) Doppler sonography in flexible endoscopy. Digestive Disease Week. Heindorff H, Wojdemann M, Bisgaard T & Svendsen LB (1998) Endoscopic palliation of inoperable cancer of the oesophagus or cardia by argon electrocoagulation. Scandinavian Journal of Gastroenterology 33: 21–23. Johanns W, Janssen J, Jakobeit C & Greiner L (1996) Argon plasma coagulation in flexible endoscopy of the gastro-intestinal tract: initial clinical experience. Endoscopy 28: 1174. Van Laethem JL, Deviere J, Peny MO et al (1997) Complete eradication of Barrett’s mucosa using argon beam coagulation combined with omeprazole. DDW, 10–16 May, Washington, DC, A-432 (abstract). Lee JG & Liebermann DA (1996) Complications of endoscopic hemostasis techniques. Gastrointestinal Endoscopy Clinics of North America 6: 305–332. Mathus-Vliegen EMH (1997) Laser coagulation In Tytgat GNJ & Mulder CJJ (eds) Procedures in Hepatogastroenterology, vol. 15, pp 437–465. Dordrecht: Kluwer Academic. Morgan AG & Clamp SE (1988) OMGE international upper gastrointestinal bleeding survey, 1978–1986. Scandinavian Journal of Gastroenterology 144 (supplement): 51–58.
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Mulder CJJ & Wahab PJ (1997) Argon plasma coagulation in endoscopy. In Tytgat GNJ & Mulder CJJ (eds) Procedures in Hepatogastroenterology, vol. 15, pp 465–473. Dordrecht: Kluwer Academic. Niezychowski W, Regula J, Fijuth J et al (1996) Argon plasma coagulation in palliative treatment of malignant dysphagia. Gut 39 (supplement 3): A5. Regula J, Wronska E, Polkowsky M et al (1996) Argon plasma coagulation (APC) after piecemeal polypectomy for colorectal adenomas. Endoscopy 28: S61 (1274). Robertson GSM, Thomas M, Jamieson J et al (1996) Palliation of oesophageal carcinoma using argon beam coagulator. British Journal of Surgery 83: 1769–1771. Rollhauser C & Fleischer DE (1998) Upper gastrointestinal nonvariceal bleeding: a review covering the years 1996–1997. Endoscopy 30: 114–125. Soehendra N, Bohnacker S & Binmoeller KF (1997) New and alternative hemostatic techniques. Gastrointestinal Endoscopy Clinics of North America 7: 641–657. Vreeburg EM, Snel P & Tytgat GNJ (1997) Diagnostic and therapeutic management of gastrointestinal bleeding. In Tytgat GNJ & Mulder CJJ (eds) Procedures in Hepatogastroenterology vol. 115, pp 31–49. Drodrecht: Kluwer Academic. Wahab PJ, Mulder CJJ, den Hartog G & Thies JE (1997) Argon plasma coagulation in flexible gastrointestinal endoscopy. Pilot experiences. Endoscopy 29: 176–181.
Baillière’s Clinical Gastroenterology Vol. 13, No. 1, pp 67–84, 1999
B A I L L I È R E ’ S
7
PRACTICE & RESEARCH
New haemostatic techniques: argon plasma coagulation Karl E. Grund
MD
Professor of Surgery
T. Straub
MD
Resident Physician Department of Surgical Endoscopy, University Hospital, Hoppe-Seyler Strasse 3, D-72076 Tuebingen, Germany
G. Farin
Dipl. Ing.
Chief Engineer Medical Research Center, Eberhards-Karls University, Waldhoernlestrasse 22, D-72072 Tuebingen, Germany
Bleeding is one of the main challenges for endoscopists. Despite a large number of methods for haemostasis, several types of haemorrhage lack an adequate therapeutic remedy. Argon plasmacoagulation (APC), a new method for the non-contact application of high-frequency current, promises to solve many of these problems. Among 1164 patients treated in 2349 sessions using APC, the indication was bleeding (due to tumour, intervention, angiodysplasia or coagulation disorders) in 305 patients (26%). The primary success rate was over 99%, the rebleeding rate 1.6% and the complication rate less than 1%, with zero mortality. Physical principles, indications, application parameters and results are discussed, especially in comparison with the Nd:YAG laser. APC is a new, efficacious, safe and easy-to-use method for the devitalization of tissue and haemostasis, especially in problematic cases. Key words: haemostasis; bleeding; argon plasma coagulation; laser; endoscopy.
Haemostasis represents one of the most important problems in endoscopy. Many different endoscopic methods have been developed during the last 20 years (Friedman 1993, 1994; Soehendra et al, 1997), resulting in a revolution in treatment of different types of bleeding (Table 1). No single method, however, covers all kinds and sources of haemorrhage. All the currently used methods are insufficient in the treatment of some difficult types of bleeding: diffuse bleeding arising from large areas, bleeding as a result of coagulation disorders (e.g. drug-induced, non-steroidal-antiphlogistic drug (NSAPD), etc.) or a haemorrhage from a tumour which is diffuse and difficult to control (Fleischer 1986; Lee and Liebermann, 1996). To achieve haemostasis in these problematic lesions, argon plasma coagulation (APC), a new method of electrocoagulation using the non-contact application of electrical energy to the lesion, was taken into consideration. According to experiences in open surgery, where APC has proved to be an efficient method for haemorrhage from the liver, spleen or kidney, we modified the method to 1521–6918/99/010067 + 18 $12.00/00
© 1999, Baillière Tindall
Peptic ulcer (visible vessel) Spurting Oozing Varices Tumour Post-intervention Inflammation Post-irradiation Angiodysplasia Coagulation disorder
Type of bleeding + ? – – ? – – ? –
Clip – – + – ? – – – –
Rubber band ligation + + (+) (+) (+) – – (+) –
Injection techniques – – + – – – – (+) –
Sclerosants
? (+) – ? ? – – ? –
Heater probe
? (+) – ? ? – – ? –
HF-surgery
? ? – (+) ? ? (+) ? ?
Nd:YAG laser
Table 1. Conventional methods of haemostasis compared with argon plasma coagulation (APC) in different types of haemorrhage.
– + ? + + + + + +
APC
68 K. E. Grund et al
New haemostatic techniques: argon plasma coagulation
69
be applied in flexible endoscopy by developing flexible probes and optimizing generators and gas sources. The following paper describes the physics, equipment and clinical experiences related to this new method. PHYSICAL PRINCIPLES OF ARGON PLASMA COAGULATION APC is a new modality to apply high-frequency (HF) electric current to tissue in order to cause defined thermal effects that can be used for the thermal devitalization of pathological tissue as well as for haemostasis. In principle, APC is a special mode of HF surgery. The most important prerequisite for the effective and safe use of APC is the understanding of its physical principles (Farin and Grund, 1997, 1998). In contrast to conventional HF surgery, the HF current is not conducted to the target tissue via monopolar, bipolar or multipolar active electrodes in direct contact, but via ionized and thus electrically conductive argon (which is called ‘argon plasma’). APC requires an APC applicator suited to the intended task, an argon source and a HF current source (Figure 1). APC applicators consist principally of a tube (R) whose distal end contains an electrode (E) (Figure 2). When adequately high HF voltage (UHF) is applied between the electrode and the tissue (G), the argon (Ar) flowing out of the tube becomes ionized in the electric field between the electrode and the tissue. In this way, electrically conductive argon plasma beams are created through which a HF current (IHF) can flow into the tissue and back to the HF current source (HF) via a neutral electrode (NE). The HF current generates heat in the tissue, causing different thermal effects such as devitalization (zone 1), coagulation (zone 2), desiccation (zone 3) and tissue shrinking (zone 4) (Figure 2). As soon as a location on the tissue surface loses its electric conductivity as a result of desiccation, the plasma beams automatically change the direction to locations at the surface that are still electrically conductive. This process continues until the entire surface in the area close to the distal end of the APC applicator has been desiccated. As a result of these characteristics, APC creates uniformly deep zones of devitalization (1) coagulation (2) and desiccation (3); even in large-area applications, these are automatically limited to at most 3(–4) mm,
Figure 1. Schematic depiction of the equipment for argon plasma coagulation.
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Figure 2. Schematic depiction of the principle of argon plasma coagulation.
depending mainly on application time. Another result of these characteristics is that the direction of the plasma beam is independent of the direction of the argon flow. Hence the APC applicator can be used in nearly all directions in relation to the tissue (Figure 3). In addition, APC does not cause carbonization or vaporization and therefore does not generate smoke, so it is well suited for endoscopic applications. The automatically limited depth of the thermal effects, as well as the absence of the vaporization effect, predestine APC for applications in flexible endoscopy, where perforation of thinwalled organs is a serious complication. In its simplest version, an argon source consists of a gas cylinder and a valve for reducing the pressure from the gas cylinder to a value appropriate to the intended application. For APC in endoscopy, the argon source should, for safety reasons, be provided with automatically controlled flow rates and maximum gas pressure limitations. A relatively low argon flow rate or velocity is sufficient to produce plasma beams. The HF current source must provide both a sufficiently high HF voltage for the ionization of the argon and a sufficiently large HF current to generate adequate heat within the target tissue. An electric field strength of approximately 500 V/mm is
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Figure 3. Argon plasma coagulation can be applicated axially, laterally and radially.
needed to ionize the argon. The voltage (UHF) needed for ignition is determined by the required electric field strength and the distance (d) between the electrode and the tissue. A distance of, for example, 10 mm thus requires a HF voltage with a peak value of approximately 5000 V. The HF current needed for APC is comparable to that required for conventional contact coagulation. Measurements in vitro and in vivo have shown that the depth of the thermal effects depends upon the power setting and duration of application (Figure 4) but is limited to 3 mm using the equipment described below with reasonable application time (Farin and Grund, 1997; Grund, 1997; Grund and Farin, 1997). Although APC had been used in open surgery for 20 years to perform haemostasis, mainly of the liver, spleen and kidney tissue, its application in flexible endoscopy was not possible until special APC applicators for this purpose, which can be used through the working channel of flexible endoscopes, had been developed, designed and clinically tested (Farin and Grund, 1994; Grund and Farin, 1997).
Figure 4. Depth of coagulation versus duration of application in different power settings.
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EQUIPMENT After several years of development and clinical tests, standard APC equipment for endoscopy consists of different flexible APC-applicators matched to the various flexible endoscopes, an automatically controlled argon source (APC 300 ERBE Electromedizin GmbH, Tuebingen, Germany) and a HF generator (Erbotom ICC 350, or Erbotom ICC 200, ERBE Elektromedizin GmbH). The APC applicators consist of a flexible PTFE tube, containing a lumen for the flow of argon from the argon source to the distal end of the tube, and a wire to conduct HF current from the HF generator to the electrode within the end of the tube. These flexible APC applicators can be introduced into the working channel of flexible endoscopes in a range from paediatric bronchoscopes (working channel diameter 2.0 mm) up to therapeutic colonoscopes (working channel diameter 3.5–4.0 mm). The generator and argon source are combined on a trolley as a mobile unit (Figure 5). The documentation of therapeutic sessions is performed audiovisually from start to finish using a VCR, electrical and pneumatic parameters being registered automatically. Because of such complete documentation, a work-up of the sessions is possible in detail by reviewing the audiovisual recordings. CLINICAL APPLICATION Patients and indications Our experiences with APC are based on experimental and clinical work from 1991 to 1998. In a prospective study, 1164 consecutive patients—644 men and 520 women
(A)
(B)
Figure 5. Equipment for argon plasma coagulation (A), consisting of an automatically controlled argon source (APC 300), a high-frequency current source (ICC 350) installed on a mobile trolley and argon plasma coagulation applicators for flexible endoscopes (B).
New haemostatic techniques: argon plasma coagulation
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with a mean age of 67 years (range 3 months–97 years)—underwent treatment with APC in the upper or lower gastrointestinal tract or the tracheobronchial system in 2.349 sessions. The primary indications for treatment are listed in Table 2. Without the availability of APC, these patients would all have been treated with the Nd:YAG Laser or by conventional electrosurgery, many of them being candidates for an operation. Three hundred and five of these patients were treated in 410 sessions because of acute or chronic haemorrhage. The most relevant sources of the bleeding were tumours, post-interventional bleeding, angiodysplasia, post-irradiation lesions and inflammatory sources (Table 3). For each patient the defined goal of therapy had to be reached in a maximum of 2–3 sessions: reliable haemostasis according to endoscopic (and clinical) criteria without recurrent bleeding. In all cases, follow-up endoscopies were performed to confirm haemostasis and to judge the state of the bleeding source. In arteriovenous abnormalities (angiodysplasia or watermelon stomach), the goal was haemostasis and the eradication of pathological lesions, with no recurrence of the haemorrhage and pathological tissue, controlled by biopsy and histology. After the successful development of a reliable endoscopic Doppler system in 1995 (Grund et al,
Table 2. Indications for treatment with APC (partly overlapping). Tumour Malignant Benign Bleeding Stent (in-/overgrowth) Adenomas Others
Patients
Applications
665 581 84 305 140 168 115
1399 1236 163 410 385 220 166
Table 3. Distribution of sources of haemorrhage in 305 patients and 410 episodes of treatment. The majority of tumors were malignant exulcerating tumours with relevant bleeding activity, about one-third of the cases referred from other hospitals after unsuccessful trials of haemostasis. Tumours Oesophagus Stomach Duodenum/small bowel Colon Rectum Other (pharyngeal, tracheobronchial)
65 18 8 15 26 14
Other Angiodysplasia/watermelon stomach Post-irradiation lesion Mallory–Weiss lesion Dieulafoy’s ulcer Other
44 14 8 8 8
Post-interventional Dilatation/bougienage Incision Snare manoeuvre (polypectomy, mucosal resection) Post-biopsy Other
19 4 16 8 9
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1999), the bleeding lesions were objectively checked for their origin (arterial, venous or arteriovenous), the presence of a bleeding vessel, its diameter and its depth in the wall (Grund et al, 1999). Localization The sources of the bleeding were mainly located in the upper (52%) and lower (32%) gastrointestinal tract and in the tracheobronchial system (16%). Application Patients were on average treated for 2 or 3 applications (range 1–18) (Table 4), the duration of application reaching 1 minute. Because of the nearly unrestricted access to the target area with the APC probe, the application technique could easily be adapted to the underlying lesion. Applications were preferably carried out by drawing back the probe either longitudinally or laterally in a brush-like manner. The ‘ten commandments for APC’, the power settings and the safety instructions (see discussion below) were maintained in order to achieve a high level of security.
Table 4. Application data. Parameter
Value (range)
Number of patients Applications Applications per patient Duration of application Argon gas volume Electric power Electric energy
1164 2349 2 (1–18) 60 (0.5–600) seconds 1.3 (0.2–18.0) litres 79 (10–100) W 6.8 (0.08–30.0) kJ
Results The data acquired for all interventions were evaluated with regard to the previously defined goals of treatment. In all but one patient (99.7%), haemostasis was achieved. In this latter case, because of strong arterial bleeding from a gastric cancer, APC was tried after the unsuccessful application of clips and injection. Bleeding was reduced but not stopped, so the patient underwent an emergency operation. Only in five patients out of 305 (1.6%) was recurrent bleeding observed; two of these patients needed surgery, and three others additional haemostatic endoscopic procedures (additional injection therapy, more than three APC sessions). Compared with other indications for APC, (especially palliative tumour therapy with a very low complication rate and mortality (Grund and Farin, 1997; Grund et al, 1998)), in the group of haemostatic procedures even a zero rate of severe side-effects, complications and mortality was noticed. Intestinal emphysema occurred in three sessions (1.3%) because of accidental activation of the HF generator during contact between the tip of the probe and the wall; this remained asymptomatic in all cases and was endoscopically no longer visible during follow-up examinations. No further serious method-related
New haemostatic techniques: argon plasma coagulation
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complications or side-effects were found immediately or later during a mean followup period of 26 (range 1–75) months. Approximately 30% of the patients complained of intermittent pain arising from distension, and rarely from thermal effects. The surgeons and the assisting staff assessed the practicability and ergonomics of the unit and the probes as superior, particularly in comparison to laser. These characteristics are now undergoing further analysis in multicentre studies.
DISCUSSION Ideally, the endoscopic treatment of bleeding in the gastrointestinal tract should fulfil the conditions of maximal efficaciousness paired with minimal mechanical or thermal lesions of the unaffected neighbouring tissue (Lee and Liebermann, 1996; Morgan and Clamp, 1988; Rollhauser and Fleischer, 1998). Perforation, deep necrosis and the disturbance of re-epithelialization and healing should be strictly avoided. Not one of the established methods (except fibrin glue injection) can fulfil the requirements to stop bleeding and simultaneously preserve the underlying or adjacent healthy tissue. In relation to the vast diversity of different methods for endoscopic haemostasis, it has to be stressed that diffuse bleeding from tumours or from wide-area lesions, as well as haemorrhage as a result of bleeding disorders, is still an unsolved problem. Conventional electrosurgery and the Nd:YAG laser, usually mentioned as the most suitable methods for this purpose (Fleischer, 1986; Mathus–Vliegen, 1997), have indisputable disadvantages: ● ● ● ● ● ●
a penetration depth that cannot be estimated using visual control, and hence a remarkable risk of perforation occurs; a high absorption of energy in liquid and/or coagulated blood, leading to difficulty controlling the thermal effect; substantial problems in ergonomics and practicability with the probes, leading to an impairment of intervention and rising stress; difficult or impossible application in certain anatomical cases and situations demanding lateral application (caecum or oesophagus) or inversion (gastric cardia), making the target inaccessible; the tip of the probes easily becoming encrusted, necessitating a repeated pull-out for cleaning; the absorption of energy depending on the colour of the tissue (white tissue reflecting 90% of the laser energy). The tissue, however, changes its colour during activation.
APC versus other methods, especially the Nd:YAG laser The decisive difference between these two methods depends on the transfer of energy to the tissue. The Nd:YAG laser (Mathus–Vliegen, 1997; Soehendra et al, 1997) may lead to coagulation (under certain conditions), otherwise it removes tissue by vaporization, but these effects are difficult to control. The physical principles governing APC, on the other hand, allow good control and manoeuvrability for devitalization, coagulation and desiccation, with a homogeneous penetration depth over wide areas. The maximum penetration depth is physically limited and can be controlled by the parameters of application (Farin and Grund, 1997; Grund and Farin, 1997). On the
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other hand, APC allows effective tissue ablation in palliative tumour therapy as a result of its pronounced desiccation and tissue shrinkage effects. Table 5 lists these characteristics of APC. APC combines the advantages of conventional electrosurgery with those of the Nd:YAG laser, but without their drawbacks. It combines non-contact application with a controllable, constant coagulation depth in an uncomplicated technique, managing apparently contradictory characteristics—effective coagulation, especially of larger areas, with shallow but well-controlled and uniform coagulation depth. Neither conventional electrosurgical methods nor the Nd:YAG laser permit such a well-defined and visually easily controlled discharge of energy at target structures as does APC. Since APC can be applied in a brushwork fashion over large areas, it is particularly well suited for treating diffuse bleeding, broad tumours and adenomatous tissue. The plasma beam can be applied in an orthograde fashion, radially and even ‘round corners’. This is highly advantageous in difficult anatomical areas, for stenotic tumours, in the colorectum, at high inversion angles in the gastric cardia, and in the tracheobronchial system. A sturdy, flexible and easily controlled applicator is a must for use in clinical practice. The APC probe avoids previously unsolved problems with laser probes (i.e. the limited flexing radius, the fixed angle of divergence, the limited lifespan of the probe tip, the
Table 5. Advantages and disadvantages of argon plasma coagulation seen in experimental and clinical experience. Advantages
Disadvantages
Effective and safe coagulation Non-contact mode (2–10 mm) Axial, radial and retrograde applications Controllable depth of coagulation (0.5–3.0 mm) Marked desiccation No destruction of metal stents* Low smoke and vapour production Mobile, handy equipment Applicators steerable, robust and cheap Low cost of purchase, use and maintenance No extended safety precautions needed
Intestinal distension by argon flow No ‘real’ vapourization* Bowel wall emphysema possible Radiofrequency interference with video
* Not relevant for haemostasis.
(B) (A)
Plate 12. Cervical oesophageal cancer with stenosis and haemorrhage during (A) and after (B) 8 kJ argon plasma coagulation. Effective haemostasis and recanalization. Please see Appendix for colour figure.
New haemostatic techniques: argon plasma coagulation (A)
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Plate 13. Duodenojejunal invasion of a sarcoma before (A) and during (B) argon plasma coagulation therapy for palliation. Please see Appendix for colour figure. (A)
(B)
(C)
Plate 14. Recurrently bleeding watermelon stomach (A), after intensive 6 kJ argon plasma coagulation (B), and the healing stage 3 weeks later (C). Haemoglebin level is now constant at over 12; no symptoms. Please see Appendix for colour figure.
(A)
(B)
(C)
Plate 15. Extended angiodysplastic lesion (MB stained) in the stomach before (A) and after (B) extensive argon plasma coagulation, and the healing stage 25 days later (C). Please see Appendix for colour figure.
(A)
(B)
(C)
Plate 16. Post-irradiation ‘proctocolitis’ after 60 Gy with recurrent, severe bleeding episodes (A), after superficial argon plasma coagulation with 4.8 kJ (B), and healing with fibrin after 10 days (C) Please see Appendix for colour figure.
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(A)
Plate 17. Haemostasis with argon plasma coagulation in a superficial heavily bleeding laceration after dilatation (A) and in a Dieulafoy’s ulcer (B), typically located. Perfect haemostasis. Please see Appendix for colour figure.
rapid build-up of crusts, the high costs and its clumsiness in use). A further advantage of the unit is its mobility: it can—in contrast to laser—be employed quickly and carried to any place at any time. The acquisition and operating costs of an APC system are only a fraction of those of an Nd:YAG laser. No special safety precautions are required to prepare, operate or service the APC unit. For haemostasis in endoscopy, deep coagulation and the production of smoke and vapours should be avoided, especially in the tracheobronchial system. For precisely targeted applications, it should be possible to view the coagulation process clearly through the endoscope. Most of these requirements are fulfilled by APC. In contrast to alternative methods, the bright plasma jet is easily kept in view and can be used to pass brush-like over the tissue; thus wide area, diffuse haemorrhages are the special domain of APC. In spite of all the euphoria, however, certain disadvantages must also be clearly recognized (Table 5). As with carbon dioxide-cooled laser probes, argon insufflation during APC must be carefully monitored, and precautions must be taken to avoid distension. Wall emphysema, which may extend as far as to become intestinal pneumatosis (Wahab et al, 1997), has been observed but appears to be reversible. Finally, even the limited penetration depth of APC cannot, of course, provide absolute protection against possible complications such as the perforation of very thin-walled structures or inadequate application. In both absolute and relative terms, however, the complication rates of APC remain very low (Johanns et al, 1996; Grund and Farin, 1997; Wahab et al, 1997; Grund et al, 1998). To achieve the best results, it is essential to follow certain recommendations (Farin and Grund, 1998). Application With the increasing use of APC as a method for haemostasis and devitalization in flexible endoscopy, technical details for the correct application and use of the probe in special situations, the dosage of energy for different indications and, last but not least, safety aspects have to be clearly outlined. The basic information is given in Table 6 and in the ‘ten commandments for APC’ (Farin and Grund, 1998). The ignition and electric arc must be properly tested outside the endoscope before advancing the probe into the working channel. Correct positioning of the probe during application in order to carry out APC in full view is also absolutely necessary.
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Table 6. Setting of argon plasma coagulation (APC) parameters.
Normal settings for oesophagus, duodenum, small bowel and rectum Stomach Stent in/overgrowth Conditioning of fistulae Tracheobronchial system Thin probe (1.5 mm) Normal probe (2.0 mm) Large tumours (diameter > 15 mm) Medium-sized tumours (diameter = 5–15 mm) Small tumours Right colon Remaining colon
Power limitation (setting) (W)
Activation time (seconds)
60–80
1–3
60–80 60 40–60
1–3 3–5 0.3–1.0
40 50–60 99 80 60 (!)40(!) 40–50
1–5 1–5 3–10 3–5 1–5 (!)0.1–0.5(!) 1–3
Recommended dosages of APC energy in practice. The recommended values refer to the standard equipment (ICC 200 or ICC 350, APC 300 and flexible APC probes, all manufactured by ERBE Elektromedizin GmbH, Tuebingen, Germany).
This may be generally difficult in some situations with bleeding, but effective suction/irrigation equipment and some rules of positioning the patient to reach the site of bleeding under vision may help to identify the source exactly. The APC probe should be moved close enough to the target to ensure ignition, but one should avoid touching the organ wall. In order to avoid emphysema or wall damage, the tip of the APC probe should never be pressed against the tissue during activation. HF output power should be limited according to the values given in Table 6, which are relevant for haemostatic indications as well as tumour destruction. A series of brief activations is superior to few prolonged activations in haemostasis with APC, as well as in the technique’s more general use. Indications The characteristics of APC are especially beneficial for the above-mentioned problematic situations of profuse wide area haemorrhage, tumour bleeding and angiodysplastic lesions. The plasma stream always automatically seeks the best path to the tissue regardless of the angle at which the APC probe is directed toward the tissue. As soon as a location on the tissue surface loses its electric conductivity as a result of desiccation, the plasma stream automatically redirects itself to locations that are still electrically conductive, this process continuing until the entire surface in the area of the APC probe is desiccated. As interventional procedures become more and more relevant, postinterventional bleedings have to be managed during and after the endoscopic manoeuvre. Bougienage, balloon dilatation, removal of tumours, adenomas and polyps can be associated with haemorrhage. In all these cases, APC proved to be effective, quick and easy to apply, especially in critical cases. In haemorrhages out of—mostly malignant—often exulcerated tumours with clefts and fissures, APC has the unique characteristic that the electrical beams can ‘dive down’ into the clefts, leading to thermal effects at an otherwise inaccessible site.
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Nevertheless, the effective penetration depth runs from the tissue surface to only the level defined by the electrical parameters and the duration of application. With the correct use of these parameters, this depth can be ‘adjusted’ between 0.5 and 3.0 mm, thus ideally fulfilling the demands of the indications mentioned above. Angiodysplastic changes, such as watermelon stomach, require a controlled and very superficial application of energy, spread over a wide area. A reliable and reproducible restriction of penetration depth to less than 1 mm appears absolutely necessary in the case of arteriovenous malformations. In addition, contact-free application is desirable to prevent adhesions to the probe. All these demands are completely met by APC. In principle, the underlying technique of APC also permits the treatment of isolated punctate haemorrhages (e.g. from an ulcer). For arterial haemorrhage and spurting vessels (e.g. in peptic ulceration), injection methods with highly diluted epinephrine and/or fibrin glue or the application of a clip seem to be the standard procedure (see Table 1 above). Experiences with APC in such indications are rare; in our own series, only five patients with strong arterial haemorrhage were treated this way, four of them with a successful haemostatic result. Due to the fact that APC is a thermal method causing relatively slight but indisputable thermal injury to the surrounding and underlying tissue, APC is thought not to be the first choice for such indications. An exception seems to exist in Dieulafoy’s ‘ulcer’, which does not have the characteristics of a peptic ulcer. For this indication, APC has proved to be a promising therapeutic method. All of our eight patients were cured with a single APC session. Results A rate of primary haemostasis of 99.3%, a recurrence rate of 1.6%, zero mortality and a complication rate less than 1% in a big clinical series are undoubtedly promising (Lee and Liebermann, 1996; Grund, 1997; Grund et al, 1998). This holds especially true for the fact that mainly problematic haemorrhages, for which no standard therapy has been established, were treated. Additionally, relatively hard criteria have been used to evaluate and control the effect. As with every new method, however, results may depend on the physician’s experience. On the other hand, the initial results from other clinical groups using APC confirm our own findings (Elhasani et al, 1996; Johanns et al, 1996; Cipolletta et al, 1997; Mulder and Wahab, 1997; Wahab et al, 1997). All the authors describe successful haemostasis in all (or nearly all) patients undergoing APC therapy. The complication rate for haemostatic indications is very low in all reports in the literature; APC is estimated to be an effective, safe and cost-effective method Bergler et al, 1997; Cipoletta et al, 1996; Fleischer et al, 1997; Grund et al, 1997; Heindorf et al, 1998; Van Laethem et al, 1997; Niezychowski et al, 1996; Regula et al, 1996; Robertson et al, 1996; Vreeburg et al, 1997). Endoscopic haemostasis in the tracheobronchial system presents a special problem because of the anatomical restrictions and the production of smoke and vapour. These manoeuvres are technically very demanding and sometimes impossible with commonly used methods, but APC seems to be ideal (Grund et al, 1998). Future aspects In summary, even a critical appraisal clearly shows that APC is not merely a modification of previous electrosurgical techniques but represents a new, trendsetting development in haemostasis. It should also be remembered that plasma surgery in
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general is at present only in the initial stages of its development, and that APC in its present form has taken only the first step in its clinical career. Controlled, multicentre studies with large numbers of patients will be needed to test APC in different indications, including different types of haemorrhage, comparing the results with those of already established methods. Further fundamental research in plasma physics is on the way to elucidate the phenomenon of the interaction between plasma and tissue. The physical characteristics of APC pave the way for wide-ranging future developments, opening up the horizon of treatment of many previously challenging conditions. REFERENCES Bergler W, Hönig M, Götte K et al (1997) Treatment of recurrent respiratory papillomatosis with argon plasma coagulation. Journal of Laryngology and Otology 111: 381–384. Cipolletta L, Bianco MA, Rotondano G et al (1996) Argon plasma coagulation (APC) in gastrointestinal endoscopy: a pilot experience in Italy. Italian Journal of Gastroenterology 28 (supplement 2): 80–81. Cipolletta L, Bianco MA, Rotondano G et al (1997) Argon plasma coagulation (APC) vs. heat probe (HP) for bleeding peptic ulcers: a prospective, randomized trial. Digestive Disease Week p A-442 (abstract). Elhasani S, Hodson RM, Tsai HH et al (1996) Use of argon beamer electrocoagulation in a UK endoscopy unit. Endoscopy 28: 1172. Farin G & Grund KE (1994) Technology of argon plasma coagulation with particular regard to endoscopic application. Endoscopic Surgery 2: 71–77. Farin G & Grund KE (1997) Basic principles of electrosurgery in flexible endoscopy. In Tytgat GNJ, Mulder CJJ (eds) Procedures in Hepatogastroenterology, vol. 15, pp 415–437 Dordrecht: Kluwer Academic. Farin G & Grund KE (1998) Argon plasma coagulation in flexible endoscopy—the physical principle. Endoscopia Digestiva (Japan) 10: 1521–1527. Fleischer D (1986) Endoscopic therapy of upper gastrointestinal bleeding in humans. Gastroenterology 90: 217–234 (review). Fleischer DE, Wang GQ, Dawsey SM et al (1997) Endoscopic therapy for esophageal dysplasia (ED) and early esophageal cancer (EEC) in Linxian, China. Digestive Disease Week p A-34 (abstract). Friedman LS (1993) Gastrointestinal bleeding I. Gastroenterology Clinics of North America 22(4): 717–891. Friedman LS (1994) Gastrointestinal bleeding II. Gastroenterology Clinics of North America 23(1): 1–183. Grund KE (1997) Argon plasma coagulation (APC): ballyhoo or breakthrough. Endoscopy 29: 196–198. Grund KE & Farin G (1997) New principles and applications of high-frequency surgery, including argon plasma coagulation. In Cotton PB, Tytgat GNJ & Williams CB (eds) Annual of Gastrointestinal Endoscopy, pp 15–23. London: Rapid Science. Grund KE, Zindel C & Farin G (1996) Argon plasma coagulation (APC)—a new and innovative tool for flexible endoscopy. Endoscopia Digestive (Japan) 9: 1209–1212. Grund KE, Zindel C & Farin G (1997) Argonplasmakoagulation in der flexiblen Endoskopie—Bewertung eines neuen therapeutischen Verfahrens nach 1606 Anwendungen. Deutsche Medizin Wochenschrift 122: 432–438. Grund KE, Straub T & Farin G (1998) Clinical application of argon plasma coagulation (APC) in flexible endoscopy. Endoscopia Digestiva (Japan) 10: 1543–1554. Grund KE, Straub T & Kayalar A (in press) Doppler sonography in flexible endoscopy. Digestive Disease Week. Heindorff H, Wojdemann M, Bisgaard T & Svendsen LB (1998) Endoscopic palliation of inoperable cancer of the oesophagus or cardia by argon electrocoagulation. Scandinavian Journal of Gastroenterology 33: 21–23. Johanns W, Janssen J, Jakobeit C & Greiner L (1996) Argon plasma coagulation in flexible endoscopy of the gastro-intestinal tract: initial clinical experience. Endoscopy 28: 1174. Van Laethem JL, Deviere J, Peny MO et al (1997) Complete eradication of Barrett’s mucosa using argon beam coagulation combined with omeprazole. DDW, 10–16 May, Washington, DC, A-432 (abstract). Lee JG & Liebermann DA (1996) Complications of endoscopic hemostasis techniques. Gastrointestinal Endoscopy Clinics of North America 6: 305–332. Mathus-Vliegen EMH (1997) Laser coagulation In Tytgat GNJ & Mulder CJJ (eds) Procedures in Hepatogastroenterology, vol. 15, pp 437–465. Dordrecht: Kluwer Academic. Morgan AG & Clamp SE (1988) OMGE international upper gastrointestinal bleeding survey, 1978–1986. Scandinavian Journal of Gastroenterology 144 (supplement): 51–58.
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