Clinical Application of Argon Plasma Coagulation in Gastrointestinal Endoscopy: Has the Time Come to Replace the Laser?

Argon plasma coagulation (APC) is a recently introduced treatment in digestive endoscopy. Since the first description of this technique [1], and of early endoscopic experience with it [2], it has become more and more widely used, so that the question arises of whether it should replace the laser in some of its indications, or in most of them, or even in all of them. In fact, its expected advantages are numerous and have been recently reiterated [3] [4] . The main ones are the following: effective and safe coagulation; noncontact mode (2 - 10 mm); axial, radial, and retrograde application; controllable depth of coagulation (0.5 - 3 mm); marked desiccation; no destruction of metal stents; little smoke or vapor; mobile handy apparatus; steerable, robust, and cheap applicators; low cost in purchase, use, and maintenance and no extended safety precautions. In this review we sum up the situation regarding the published data on the main indications of APC in gastrointestinal diseases, and to compare the results in medical literature with our own experience in, up to now, more than 300 patients.

The best results were expected to be found in hemorrhagic lesions. Four kinds of lesions have been treated: angiomata, watermelon stomach, radiation proctitis, and bleeding peptic ulcers. The results are summarized in Table [1], compared with those of the laser in a recent review [5]. At first sight, the clinical impression is that the efficiency of APC is equal or even superior to that of the laser, with a lower complication rate. However, it should be noted that most of the studies were published only in abstract form and results were given for all indications collectively, without results for each specific indication, so that the data in Table [1] are often extrapolations. Moreover, follow-up is often insufficient, practical details of the procedure are not given (i. e.: power setting, gas flow, frequency of sessions), and efficacy criteria (clinical, endoscopic, biological) vary from one study to another and are often not specified. In the case of digestive angiomata, the number of patients treated and the follow-up are sufficient to conclude that APC is an effective and safe method compared with laser [6] [7] [8] [9] [10] . Although perforation is rare - about 0.31 % according to Grund, cited by Hoyer et al. [11] it is still possible. One case has been described after treatment of cecal angiodysplasia, without need for laparotomy [12]. In various indications, other side effects have been reported, such as submucosal emphysema which is classic but mild, and inflammatory polyp which is rare and mild [12]. One bowel gas explosion has been reported, during a palliative treatment of a colonic cancer [13].

Table 1Comparison of results of argon plasma coagulation (APC) and laser treatment in hemorrhagic lesions Indications Angiodysplasia Watermelon stomach Radiation proctitis Bleeding ulcers References 6 7 8 9 10 5 2 6 7 8 22 5 14 15 16 17 18 19 20 21 5 23 Technique APC Laser APC Laser APC Laser APC Number of patients treated > 65 205 > 16 45 129 47 27 Success 68 - 100 % 78 - 82 % 75 % 86 % 91 % 87 % 93 % Recurrence ND 15 - 47 % ND ND 0 ND 15 % Complications 2.5 % 2 - 5 % 4 % ND 7 % ND 0 Number of sessions 1 - 3 1 - 3 1 - 8 ND 1 - 4 ND 1 - 3 MNS 1.3 - 2 1 2 2 - 5 2.24 2 ND Follow-up (months) 1.5 - 14 11.5 - 19.5 1 - 14 3 1 - 48 14 ND ND: no data. MNS: mean number of sessions.

With regard to treatment of radiation proctitis by APC, eight studies have been published, in which 129 patients have been treated [14] [15] [16] [17] [18] [19] [20] [21] . We published the largest one (30 patients) with the longest follow-up (mean follow-up 23 months, range 9 - 48) [19]. Results are promising, since the effectiveness of APC seems to be superior to that of the laser, with some patients cured by APC while laser treatment was ineffective. In our experience, clinical success is achieved in 94 % of patients, with complete disappearance of bleeding in 86 %. This is a little superior to the results of other authors, who find improvement in 90 % with complete disappearance of bleeding in 81 %. However, we must point out that complications are not rare, (14 % in our series) even though most complications were asymptomatic stenosis and pain, for which patients were treated using the usual analgesics. However, we observed one perforation and one extensive necrosis. Our results suggest (and this is a crucial point) that the incidence of complications depends on the power setting. According to our experience, a power of less than 45 Watts should be used, in order not to cause injuries to a fragile rectal wall thinned by previous irradiation.

With regard to watermelon stomach, APC seems to be as efficient as laser treatment [2] [6] [7] [8] [22] . Perhaps reduction in the need for transfusion chosen as an efficiency criterion for laser treatment is not sufficient to prove the superiority of APC in this case, and clinical criteria should be preferred. In fact, in our experience, we observed the disappearance of bleeding and more than 90 % regression in endoscopic lesions following the first session in most of the patients (5/6). So it seems that no further evidence is required to allow the use of APC in watermelon stomach.

In bleeding ulcers, according to the only study on use of APC for this indication, it is as safe and effective as the heater probe [23].

From the beginning, APC has been experimented with for the treatment of benign and malignant tumors of the upper and lower digestive tract. Results for each indication, except esophageal cancer, compared with those of laser treatment are summarized in Table [2]. In the main indications, the number of patients treated by APC is lower than the number of patients treated by laser, and follow-up duration is not always specified; furthermore, follow-up is most often shorter than in laser studies. Moreover, the same reservations can be expressed as with the publications on APC in hemorrhagic lesions. Furthermore, tumor characteristics in most cases are not given. Efficacy criteria, details of the procedure, and tumor characteristics are of special relevance when assessing efficiency in large tumors and comparing the results in different studies.

Table 2Comparison of results of argon plasma coagulation (APC) and laser treatment in benign and malignant tumors and in preneoplastic lesions Indication Rectal cancer Dysplasiaand super-ficical cancer Residues after polypectomy and multiple polyps Large villous adenoma Gastriccancer Barrett's esophagus References 6 7 5 6 25 26 6 9 27 5 6 5 6 28 29 30 5 Technique APC Laser APC APC Laser APC Laser APC APC Laser Number of patients treated 6 63 16 72 21 28 244 10 57 19 Success 6/6 75 - 82 %* 94 % 100 % 100 % 100 % 84 - 92 % 80 % 38/57 complete endoscopic eradication 59 % Recurrence 0 85 % at 12 mo 0 ND 0 ND 26 - 29 % ND ND ND Complication 0 16 % 0 17 % ND 0 5.6 % 0 5/57 0 Number of sessions 1 - 5 ND 1 - 2 1 - 9 ND 1 - 5 ND 1 - 21 1 - 7 1 - 6 MNS 2.7 3/2 ND 1 - 3 5 1.5 - 3 3.6 - 6.7 4.9 2.2 ND Follow-up (months) ND ND 5 - 14 1 - 12 60 3 - 18 17 - 57 ND 6 ND *results in subocclusion-bleeding. ND: no data, MNS: mean number of sessions.

Rectal cancers have been treated by Wahab et al. [6]. Effectiveness was good in patients with 1 - 5 sessions (mean number of sessions [MNS] = 2.7) without complications. We treated 21 patients for rectal cancers, with excellent results in 19/21 patients [24]. Six were treated before surgery during radiotherapy; in the other 15, APC was used only as a palliative treatment. In the six patients treated during radiotherapy, the tumor was circumferential and stenosing. We observed no occlusion syndrome, and complete disappearance of bleeding in the six patients. In the 15 patients in whom APC was used only in a palliative role, five had a stenosing tumor, eight had bleeding, and two had bleeding and stenosis. In two patients APC was not sufficient and surgery or stenting was required. Thus APC seems to be very useful during radiotherapy, allowing a delay before surgery, avoiding occlusion and reducing rectal syndrome. A specific study is necessary for this indication with details on procedure, tumor characteristics, and efficiency criteria. For gastric cancers, as for rectal cancers, a specific study would be welcome, with the same precision as for the other cancers. APC has also been successfully used by many authors in dysplasia, superficial cancers [6] [25] [26] , large villous adenomas [6], and multiple adenomas [27]. Ten patients were treated by Sessler et al. for T1 tumors, with complete response in 9/10 patients [26]. However it seems the best treatment is certainly mucosectomy, APC being used only for residues or for lesions located behind a fold or on both sides of a fold.

APC may be used to treat Barrett’s esophagus. In our experience we observed complete endoscopic eradication without complication in eight patients. In contrast, the complication rate in three other studies is rather surprising, about 7.5 to 10 % [28] [29] [30] . In the largest study, including 31 patients [29], complete eradication of Barrett’s esophagus, with histological assessment, was achieved in 61 %, while in another study [30] the success rate was 100 % with a mean number of sessions (MNS) of 2.4 (range 1 - 4). Interestingly, in 30 % of cases the new squamous epithelium covered areas of underlying metaplasia [30]. This could result in deep dysplasia in glandular structures under the squamous epithelium, so it is not certain that such an endoscopic treatment can result in a decreased incidence of and mortality from adenocarcinoma. Therefore, since the endoscopic treatment of Barrett’s esophagus is not yet established for the moment, APC should be used only in prospective studies in this indication.

In spite of the characteristics of APC, which at first would seem to make it unsuitable for large esophageal or cardial tumors, this is one of the indications most investigated by specific studies. Nine reports concern the treatment of dysphagia, three are heterogenous studies [2] [6] [9] , but six focus on this indication [31] [32] [33] [34] [35] [36] , one of them concerning mainly neoplasic overgrowth at the upper or lower part of a plastic prosthesis [36]. Detailed results of APC and laser in the treatment of neoplasic dysphagia are given in Table [3]. They do not seem to be very different, with an improvement of dysphagia score in 66 - 96 % of patients undergoing laser treatment and in 88 % of patients undergoing APC, of whom 40 - 86 % had a normal diet following laser treatment and 66 % following APC. In fact, it is not really possible to draw conclusions, as APC was sometimes used in association with another treatment, such as dilation or radiotherapy, sometimes combined with chemotherapy [31] [34] or just before stent placement [9] [34] . Our experience [35] indicates that good results can be obtained by means of an intensive initial treatment. We achieved complete release from dysphagia and normal diet in 11 patients with tumors involving 75 - 100 % of the circumference (mean 95 %), and 3 to 8 cm in length. The first two sessions were performed 3 to 6 days apart, at settings of 65 - 80 Watts. The MNS was 1.5 (range 1 - 3). The mean follow-up was 5 months (range 1 - 13). A randomized comparative study of laser treatment and APC, with details on procedure and tumor characteristics is required. Two studies have examined tumor overgrowth between the mesh of metallic self-expanding stents. One is only an experimental study [36]. The other one reports use of APC in debulking tumor ingrowth in stents. According to this experience in 75 patients, APC could be considered the best treatment because it does not cause damage to the metallic mesh [37].

Table 3Comparison of results of argon plasma coagulation (APC) and laser treatment of malignant dysphagia Technique APC Laser References 6 31 32 33 34 35 5 Number of patients treated > 152 116 Success 87.5 % (66 %)* 66 - 96 % (40 - 86 %) Recurrence ND 78 % in 6 mo Complications 7 % 1.4 - 9.5 % Death related to endoscopic treatment 0.7 % 0 - 6 % ND: no data*Decrease in dysphagia (normal diet).

In conclusion, we can distinguish three types of indication. Firstly, there were indications in which APC can be preferred to laser treatment without reservation. APC is suitable in angiodysplasia, watermelon stomach, radiation proctitis, bleeding peptic ulcers and ulcers with high risk of rebleeding, obstructed stents, multiple polyps and residues after polypectomy and mucosectomy. Indeed, several facts strongly suggest that, in these indications, APC has a better advantage - risk ratio than laser treatment. Ease of learning, low cost, and the mobility of the apparatus are additional arguments for choosing APC rather than laser treatment. Thus, for these indications, it seems there is no obstacle to the expanded use of APC; it is after all a simple question of common sense. However, details about the technical procedure used should be specified for some of these indications.

Secondly, on the other hand, for treatment of neoplasic dysphagia it would be more advisable to perform further APC studies. Randomized studies comparing APC with laser treatment, analyzed with regard to intention to treat, would be of particular relevance in this case. Such studies should detail the procedure used (number and frequency of sessions, power setting and tumour characteristics, initial grade of dysphagia, T staging, percentage of esophageal circumference invaded, etc.).

Thirdly, between these two situations we find several indications in which APC can still be used, though a more precise evaluation of results would be welcome; specifically large villous adenoma, rectal and gastric cancer. In rectal and gastric cancer and large villous adenoma, it seems that APC could be safer than laser treatment but with a possibly lower efficiency.

The use of APC has recently been greatly developed, and this will probably continue. Though such a development is justified, there is still a place for rigorous studies in order to refine assessment of results and optimize the technical details of the procedure.

References

• 1 Farin G, Grund K E. Technology of argon plasma coagulation with particular regard to endoscopic applications.  End Surg. 1994;  2 71-77
• 2 Grund K E, Storek D, Farin G. Endoscopic argon plasma coagulation (APC). First clinical experiences in flexible endoscopy.  End Surg. 1994;  2 42-46
• 3 Grund K E. Argon plasma coagulation (APC): ballyhoo or breakthrough?.  Endoscopy. 1997;  29 196-198
• 4 Farin G, Grund K E. Principes de l’éléctrochirurgie. In: Canard JM, Palazzo L (eds). Endoscopie digestive.  Paris; Laboratoires Glaxo, 2001: in press
• 5 Belda E, Naveau S, Borotto E, Chaput J C. Traitement des lésions digestives par laser. Encycl Med Chir Gastro Entérologie. Elsevier, Paris; 1997
• 6 Wahab P, Mulder C, den Hartog G, Thies J. Argon plasma coagulation in flexible gastrointestinal endoscopy: pilot experiences.  Endoscopy. 1997;  29 176-181
• 7 Waye J D, Grund K E, Farin G. Argon plasma coagulation (APC) - clinical usefulness in flexible endoscopy.  Gastrointest Endosc. 1996;  43 306
• 8 Cohen J, Abedi M, Haber G, et al. Argon plasma coagulation: a new effective technique of non-contact thermal coagulation. Experience in 44 cases of GI angiomata.  Gastrointest Endosc. 1996;  43 293
• 9 Johanns W, Luis W, Janssen J, et al. Argon plasma coagulation (APC) in gastroenterology: experimental and clinical experiences.  Eur J Gastroenterol Hepatol. 1997;  9 581-587
• 10 Cipolletta L, Bianco M A, Rotondano G, et al. Argon plasma coagulation (APC) in gastrointestinal endoscopy: a pilot experience in Italy.  ltal J Gastroenterol. 1996;  28 (Suppl. 2) 80-81
• 11 Hoyer N, Thouet R, Zellweger U. Massive pneumoperitoneum after endoscopic argon plasma coagulation.  Endoscopy. 1998;  30 S44-S45
• 12 Schmek-Lindenau H J, Kurtz W, Heine M. Inflammatory polyps: an unreported side effect of argon plasma coagulation.  Endoscopy. 1998;  30 S93-S94
• 13 Zinsser E, Will U, Gottschalk P, Bosseckert H. Bowel gas explosion during argon plasma coagulation.  Endoscopy. 1999;  31 S26
• 14 Fantin A, Binek J, Suter W, Meyenberger C. Argon beam coagulation for treatment of symptomatic radiation induced proctitis.  Gastrointest Endosc. 1999;  49 515-518
• 15 Silva R, Correia A, Moreira Dias L, Lamba Viana H. Argon plasma coagulation therapy for hemorrhagic radiation proctosigmoiditis.  Gastrointest Endosc. 1999;  50 221-224
• 16 Rolachon A, Papillon E, Fournet J. Coagulation au plasma d’argon des malformations digestives et des rectites radiques: à propos d’une étude prospective.  Acta Endoscopica. 1999;  29 (3) 440
• 17 Chutkan R, Lipp A, Waye J. The argon plasma coagulator: a new and effective modality for treatment of radiation proctitis.  Gastrointest Endosc. 1997;  45 AB27
• 18 Saurin J C, Coehlo J, Leprêtre J, et al. Rectite radique ou ectasies vasculaires antrales: effet de la coagulation au plasma d’argon.  Gastroenterol Clin Biol. 1999;  23 A54
• 19 Védrenne B, Canard J M, Bader R, et al. Traitement des rectites radiques par la coagulation au plasma argon (CPA).  Gastroenterol Clin Biol. 2000;  24 A2
• 20 Tam W, Moore J, Schoeman M. Treatment of radiation proctitis with argon plasma coagulation.  Endoscopy. 2000;  32 667-672
• 21 Kaassis M, Oberti F, Burtin P, Boyer J. Argon plasma coagulation for the treatment of hemorrhagic radiation proctitis.  Endoscopy. 2000;  32 673-676
• 22 Abedi M, Haber G B. Watermelon stomach.  Gastroenterologist. 1997;  5 179-184
• 23 Cipoletta L, Bianco M A, Rotondano G, et al. Prospective comparison of argon plasma coagulator and heater probe in the endoscopic treatment of or peptic ulcer bleeding.  Gastrointest Endosc. 1998;  48 191-195
• 24 Védrenne B, Canard J M, Bader R, et al. Traitement symptomatique des cancers du rectum par coagulation au plasma d’argon.  Gastroenterol Clin Biol. 2000;  24 A35
• 25 Byrne J P, Armstrong G R, Attwood S E. Endoscopic argon beam plasma coagulation and “cure” of early upper gastrointestinal malignancy.  Endoscopy. 1997;  29 E32
• 26 Sessler M, Becker H D, Flesch I, Grund K E. Therapeutic effect of argon plasma coagulation on small malignant gastrointestinal tumors.  J Cancer Res Clin Oncol. 1995;  121 235-238
• 27 Regula J, Wronska E, Polkowski M, et al. Argon plasma coagulation (APC) after piecemeal polypectomy for colorectal adenomas.  Endoscopy. 1996;  28 S61
• 28 Dumoulin F L, Terjung B, Neubrand M, et al. Treatment of Barrett’s esophagus by endoscopic argon plasma coagulation.  Endoscopy. 1997;  29 751-753
• 29 Van Laethem J L, Cremer M, Peny M O, et al. Eradication of Barrett’s mucosa with argon plasma coagulation and acid suppression: immediate and mid term results.  Gut. 1998;  43 747-751
• 30 Byrne J, Armstrong G, Attwood S. Restoration of the normal squamous lining in Barrett’s esophagus by argon beam plasma coagulation.  Am J Gastroenterol. 1998;  93 1810-1815
• 31 Niezychowski W, Regula J, Fijuth J, et al. Argon plasma coagulation in palliative treatment of malignant dysphagia.  Gut. 1996;  39 (Suppl. 3) A5
• 32 Robertson G SM, Thomas M, Jamieson J, et al. Palliation of esophageal carcinoma using the argon beam coagulator.  Br J Surg. 1996;  83 1769-1771
• 33 Watson J P, Jowett S, Oppong K, et al. Endoscopic argon plasma coagulation: a better treatment for malignant dysphagia than laser therapy?.  Endoscopy. 1997;  29 E32-E33
• 34 Heindorff H, Wojdemann M, Bisgaard T, Svendsen L B. Endoscopic palliation of inoperable cancer of the oesophagus or cardia by argon electrocoagulation.  .  Scand J Gastroenterol. 1998;  33 21-23
• 35 Védrenne B, Canard J M, Bader R, et al. Traitement de la dysphagie d’origine néoplasique par coagulation au plasma d’argon.  Gastroenterol Clin Biol. 2000;  24 A35
• 36 May A, Gossner L, Hahn E G, Ell C. Treatment of tumor in-overgrowth in metal stents: a comparison of the argon beamer, KTP and Nd:Yag laser.  Gastrointest Endosc. 1996;  43 300
• 37 Grund K E, Storek D, Becker H D. Highly flexible self expanding meshed metal stents palliation of malignant esophagogastric obstruction.  Endoscopy. . 1995;  27 486-494