Nd:YAG laser versus polidocanol injection for palliation of esophageal malignancy: a prospective, randomized study

0016-5107/91/3706-0607$03.00 GASTROINTESTINAL ENDOSCOPY Copyright © 1991 by the American Society for Gastrointestinal Endoscopy

Nd:YAG laser versus polidocanol injection for palliation of esophageal malignancy: a prospective, randomized study G. Angelini, MD, A. Fratta Pasini, MD A. Ederle, MD, A. Castagnini, MD G. Talamini, MD, G. Bulighin, MD Verona, Italy

Palliation is often the only treatment that can be offered to patients affected by esophageal malignancy. This prospective study was carried out in order to compare two endoscopic palliative treatments: Nd:YAG laser and local injection of 3% polidocanol. We randomized 34 patients with inoperable malignancies to one of the two treatments. After the first course, 88.8% of the patients in the laser group and 81.5% in the polidocanol group were able to swallow a normal oral caloric intake. Only one major complication (esophageal perforation) was observed (polidocanol group) and was successfully treated with endoscopic placement of a prosthesis. We believe that both techniques are safe and effective for the palliation of esophageal malignant strictures but that polidocanol injection is cheap, simple, and more widely available. (Gastrointest Endosc 1991;37:607610)

The endoscopic management of non-resectable esophageal cancer includes balloon or mechanical dilation, prosthesis, bipolar or monopolar electrocoagulation, Nd:YAG or argon dye lasers, and chemical necrolysis. 1- 4 Nd:YAG laser has probably become the most widely employed technique in spite of its high cost. In our own experience, Nd:YAG laser proved to be effective in relieving dysphagia in a group of 28 subjects treated between 1984 and 1986.5 ,6 Nevertheless, a superiority of Nd:YAG laser compared with other endoscopic devices has not yet been proven, and no one endoscopic treatment has been shown to be clearly better than the others. 7 This consideration prompted us to compare the safety and efficacy of the Nd:YAG laser with that of a much cheaper method: tumor necrolysis by means of local injection of a chemical agent. PATIENTS AND METHODS

Between January 1986 and June 1989, 37 consecutive patients referred to our endoscopy service because of obstruction due to esophageal cancer have been allocated by Received June 16, 1990. For revision August 7, 1990. Accepted June 25,1991.

From the Institute of Medical Clinic, University of Verona, Verona, Italy and the Endoscopy Center U.S.L. 33, Verona, Italy. Reprint requests: G. Angelini, MD, Institute of Medical Clinic, Policlinico Borgo Lorna, Verona 37134, Italy. VOLUME 37, NO.6, 1991

the random numbers table of Fisher and Yates to endoscopic laser treatment (ELT, group A) or local injection of 3% polidocanol (PLI, group B). Surgical treatment was excluded due to advanced carcinoma or poor general condition in all patients. Three patients (one of group A and two of group B) submitted to the first treatment and thereafter were lost to follow-up, and were considered to have dropped out. No other patients were excluded from the study. Twenty-eight of the remaining 34 patients were men (17 in group A and 11 in group B) and 6 were women (1 in group A and 5 in group B). The mean age of the patients was 67.3 years (range, 52 to 80 years) in group A and 72 years (range, 49 to 86 years) in group B. Adenocarcinoma of the gastric cardia was diagnosed in 6 patients allocated to ELT and in 7 submitted to PLI; squamous cell carcinoma was found in 21 subjects (12 in group A and 9 in group B). The cancer was exophytic in all cases. No other therapy was given with the endoscopic treatment. The site and extension of the neoplastic strictures in the two groups are summarized in Table 1. The dysphagia was graded as follows: grade 0, absent; grade 1, mild (only for rough foods); grade 2, moderate (free ingestion of liquids); and grade 3, severe (impossible or difficult swallowing also of liquids). ELT was carried out using a Medilas-2 Nd:YAG laser, set at a power of 80 to 95 watts with a I-sec pulse duration. The flexible quartz fiber with coaxial CO 2 was passed through the biopsy channel of the endoscope (Olympus IT-la, XQ10, and XQ-20). The ELT was carried out in a "retrograde" manner in patients with an esophageal lumen patent to the endoscope, while the antegrade approach was used in the 607

other patients. A retrograde approach after bouginage (balloons or Savary dilators) was employed in two patients. The sessions were spaced at I-week intervals. This wide interval was chosen to allow a complete slough of the necrotic tissue, to minimize the complication rate and for organizational reasons. Laser sessions were repeated until patients were able to swallow at least some solids (grade 1 dysphagia) and to have a normal oral caloric intake. The course was interrupted if no improvement of dysphagia was achieved within three to four sessions. Further sessions were scheduled in patients with relief of dysphagia according to recurrent symptoms. Three percent polidocanol was injected via a sclerotherapy needle with an operative length of 10 to 12 mm. Multiple 1- to 2-ml injections into the neoplastic mass were done. The needle was inserted parallel to the esophageal wall and a distance of 0.5 cm was left between injection sites. No injection was done closer than 0.5 cm to the wall. The retrograde approach was preferred when possible (previous dilation was carried out in four patients). The sessions were spaced at I-week intervals; after the first course further treatments were scheduled as needed. The efficacy of the Table 1. Site and extension of malignancy Group A (18 patients)

Group B (16 patients)

N

%

N

%

1 11 6

5.5 61.1 33.4

3 5 8

18.7 31.3 50

11 7

61.1 38.9

12 4

Site a Cervical Middle Distal Length (em) <8 >8 a

75 25

Cervical, 15 to 22 em; middle, 23 to 34 em; and distal, >34 em.

treatment was judged by the same criteria adopted for ELT. Statistical evaluation was carried out by means of the Fisher's exact test (two sided). RESULTS

Each patient underwent a mean of 5.16 ± 1.94 sessions with a mean dose of 2,671 ± 1,373 joules (from 1,130 to 4,839 joules) per session and a total mean dose of 13,071 ± 7,226 joules (from 5,985 to 33,878 joules) (Table 2). A satisfying result (at least grade 1 dysphagia and normal oral caloric intake) was reached in 16 of 18 patients (88.8%) after 3.31 ± 1.29 sessions. Both the patients with poor results had a stricture less than 8 em long (6 and 5 em, respectively). In our experience, the histologic type, the site of the cancer, and the length of the stricture had no influence on the effectiveness of the treatment. Further laser treatments were carried out when dysphagia worsened during the follow-up period that ranged from 3 to 24 months. The mean free interval after the first course was 7.7 weeks. Ten patients required a total of 47 sessions to maintain the patency of the esophageal lumen. The remaining six patients did not request any further laser treatment during follow-up. Prostheses were placed in the two patients with unsuccessful ELT. In this group no major complication was recorded. After treatment a slight and transient retrosternal pain, never requiring analgesic drugs, was observed in 7 of 18 (38.8%) patients and in 11 of 108 total sessions (10.2%). Each patient underwent a mean of 3.68 ± 2.41 sessions with injection of a mean dose of 10.1 ± 4.9

Table 2. Results of laser treatment N

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Site (em) 28-32 27-30 30-36 30-38 26-31 39-42 30-40 25-31 25-28 30-34 26-30 26-38 36-41 32-42 26-36 17-28 35-42 35-43

Histology

Total sessions (N)

Squamous Adeno Squamous Squamous Squamous Adeno Adeno Squamous Squamous Squamous Squamous Squamous Adeno Adeno Squamous Squamous Adeno Adeno

5 8 3 6 4 5 4 4 9 6 7 7 12 4 7 11 3 3

Total joules 14,606 9,045 5,985 8,205 7,440 7,964 17,566 9,088 14,293 12,820 20,518 21,441 10,625 16,654 33,878 11,283 14,000 12,940

Joules! session (mean) 2,921 1,130 1,995 1,367 1,860 1,592 4,391 2,272 1,588 2,136 2,931 3,063 1,770 4,163 4,839 3,760 4,666 4,313

Grade of dysphagia

Ba

A

2 2 2 2 3 3 3 2 2 3 3 2 2 2 3 2 3 2

3 1 3 1 3 1 1 1 0 1 1 1 0 1 1 1 1 1

Follow-up (months) 10 14 b 4b

6 3b 4 8b 3 4 4

7b 3 24 b

3 7 12 b

7 3

aB, before laser treatment and A, after laser treatment. bDeath.

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Table 3. Results of polidocanol treatment

N

1 2 3 4 5 6 7 8 9 10

11 12 13 14 15 16

Site (em)

32-40 22-33 25-30 38-40 27-32 28-31 25-29 28-35 25-40 35-42 32-39 22-28 35-40 21-27 30-38 35-42

Histology

Total sessions (N)

Squamous Adeno Squamous Adeno Squamous Squamous Squamous Squamous Adeno Adeno Adeno Squamous Adeno Squamous Adeno Adeno

11 3 5 2 3 4 6 2 3 5 3 3 3 3 4 4

Total ml

123 30 40 17 21 23 37 25 35 113 37 28 34 40 46 21

ml/session (mean)

11.2 10 8 8.5 7 5.7 6.1 12.5 11.6 22.6 12.3 9.3 11.3 13.3 11.5 5.2

Grade of dysphagia

Ba

A

3 3 3 3 2 3 2 3 2 2 3 3 3 2 2 3

1 0 3 3 1 0 0 1 1 1 3 1 1 1 0 1

Follow-up (months) 11 b

3 8b 3b

3 2 3 21 b

4b

3 2 2 2 4b 6b 16

aB, before polidoeanol treatment and A, after polidoeanol treatment. b Death.

mlftreatment (from 5.2 to 22.6 ml) and a total mean dose of 39.4 ± 31.5 ml (from 21 to 123 ml) (Table 3). An improvement of the dysphagia, at least grade 1 with normal oral caloric intake, was achieved in 13 of 16 (81.2%) of the cases after 3.2 ± 1.2 sessions. This result was obtained in 9 of 12 (75%) of the patients with stricture length less than 8 cm and in 4 of 4 (100%) of those with strictures longer than 8 cm. Again, the length of the stricture has no influence on the effectiveness of the treatment. Also, the histologic type and the site of the malignancy did not influence the results. In this group, the follow-up ranged from 2 to 21 months. After a 4-week free interval, 10 further sessions were carried out in two patients, due to a worsening of dysphagia. No other treatment was required for 10 patients during a mean follow-up period of 6.4 (from 2 to 21) months. The last patient, who complained of worsening of dysphagia 6 weeks after the end of the first course, was erroneously changed to laser treatment with relief of the symptoms. In this group, we observed one major complication (mediastinal fistula in patient 3) successfully treated by endoscopic placement of a prosthesis. Prostheses were placed also in two of the three patients with unsuccessful chemical treatment; the last patient received TPN on admission because of complete esophageal stenosis and died after three sessions without any improvement of dysphagia. In this group, only one patient complained of mild post-procedure retrosternal pain (6.2%) that did not require analgesic drugs. The statistical comparison between the two groups pointed out that the need for further sessions after the first course was significantly lower in the PLI VOLUME 37, NO.6, 1991

group (p < 0.02), while no difference was found as far as the efficacy of the two treatments is concerned. DISCUSSION

Palliation is often the only possible therapy in esophageal cancer, due to the late occurrence of dysphagia. 3,8 Endoscopy seems to offer the best alternative because of its effectiveness and low incidence of complications. 9- 13 Among the treatment options offered by endoscopy, laser has become the first choice in many gastroenterologic centers since clinical experience and prospective studies have shown its effectiveness and safety.14-2o Nevertheless, there is still a lack of clinical trials prospectively designed to compare laser with the other endoscopic palliative treatments. Moreover, laser devices have the disadvantage of expense and limited availability. This prospective, randomized study compares the effectiveness of Nd:YAG laser with that of tumor necrolysis induced by the local injection of 3% polidocanol. These techniques aim at relieving dysphagia by a reduction of obstructing malignant tissue by thermal and chemical injury, respectively. We chose Nd:YAG laser because it is the most widely used, and because of our 3-year experience with this treatment. Among chemical agents, we selected polidocanol because of our previous experience with its use for the treatment of esophageal varices, and because of the good results reported by Soehendra et al. l for the relief of malignant dysphagia. In our study, as in the work of others, we found that both Nd:YAG laser and polidocanol proved to be safe. A single complication was observed after a total of 609

172 sessions in 34 patients. It was a fistula in the PLI group, successfully treated by the endoscopic placement of a prosthesis. The fistula was likely due to a too deep injection of the drug. Our frequency of complications is comparable to that reported in the literature, ranging from 1 to 10%,7 for perforation during laser treatment. The duration of the procedure was roughly the same in the two groups but the discomfort was greater during laser treatments related to gastric distension from gas insufflation during laser activation. It was our experience that injection therapy was easily carried out, whereas the use of Nd:YAG laser was sometimes difficult in cancers of the cervical esophagus due to lack of room between the endoscope and the malignancy. Many patients in the ELT group but only one in the PLI group complained of mild post-procedure pain that did not require administration of analgesic drugs. The effectiveness of the two techniques was statistically the same from many points of view: length of treatment, number of sessions, relief of dysphagia, and possibility of treatment on an outpatient basis. It was of great advantage to perform a dilation (with Savary-Gilliard dilators or other endoscopic devices) before treatment, as suggested by Pietrafitta and Dwyer 21 for laser therapy, in patients with an esophageallumen less than the caliber of the endoscope, in order to allow the treatment of the entire cancer and to give immediate relief of dysphagia. On the basis of these data, it is our opinion that both thermal and chemical methods are safe and effective for the palliative treatment of esophageal cancer. If these results can be confirmed in a larger number of patients, the use of polidocanol may be preferred because of its low expense, availability, technical simplicity, and good tolerance.

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