ORIGINAL PAPERS

 

Endoscopic band ligation without resection in selected patients for small and superficial upper gastrointestinal tract lesions

 

 

Gemma Ibáñez-Sanz¹, Joan B. Gornals¹, Laura Rivas¹, Sílvia Salord¹, María J. Paúles², Josep M. Botargues¹ and Maica Galán³

¹ Endoscopy Unit. Department of Digestive Diseases. Hospital Universitari de Bellvitge-IDIBELL. L'Hospitalet de Llobregat, Barcelona. Spain.
² Department of Pathological Anatomy. Hospital Universitari de Bellvitge-IDIBELL. L'Hospitalet de Llobregat, Barcelona. Spain.
³ Department of Medical Oncology. Institut Català d'Oncologia DiR-IDIBELL. L'Hospitalet de Llobregat, Barcelona. Spain

Correspondence

 

 

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ABSTRACT

Background and aim: The aim of this study was to evaluate the efficacy of endoscopic band ligation (EBL) in carefully selected patients who would benefit from this method of resection.
Methods: Patients with early upper gastrointestinal and small (< 15 mm) lesions treated with EBL (Duette^® Multi-Band Mucosectomy) were prospectively recruited and retrospectively analyzed between 2010 and 2015. All cases were discussed in a multidisciplinary cancer committee and it was concluded that, owing to patient conditions, surgery was not possible and that not conducting histology would not change the clinical management. A first endoscopic control with biopsies was planned at 4-8 weeks. If there was no persistence of the lesion, new controls were programmed at 6 and 12 months.
Results: The group (n = 12) included 5 esophagus lesions (adenosquamous carcinoma, n = 1; carcinoma squamous, n = 2; adenocarcinoma, n = 2); 4 gastric lesions (high grade dysplasia, n = 1; adenocarcinoma, n = 2; neuroendocrine tumor [NET], n = 1), and 3 duodenal lesions (NETs) (n = 3). The mean tumor diameter was 9.6 ± 2.8 mm (range 4-15). Only one minor adverse event was described. At first follow-up (4-8 weeks), there was 91.6% and 75% of endoscopic and histological remission, respectively. At 6-month follow-up there was 70% of both endoscopic remission and negative biopsies. And at 12 months, there was 100% and 75% of endoscopic and histological remission, respectively. Persisting lesions were T1 cancers. The median follow-up was 30.6 months.
Conclusion: EBL without resection is an easy and safe technique that should be considered in patients with multiple morbidities and small superficial UGI lesions.

Key words: Endoscopic band ligation. Autoamputation. Early lesions. Superficial lesions. Small upper GI-lesions. Endoscopic mucosal resection. Duette mucosectomy.

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Introduction

Nowadays, new endoscopic techniques that can avoid invasive surgery in the treatment of small superficial upper gastrointestinal (UGI) lesions are emerging. Endoscopic mucosal resection (EMR) using electrocautery is the most common technique, but it has potential complications such as perforation (1-20%) and hemorrhage (7-30%), especially in duodenum (1).

The use of endoscopic band ligation (EBL) without electrocautery has been described for removal of Barrett's esophagus without dysplasia (2), duodenal carcinoids (3,4), duodenal gastrinoma (5), and leiomyomas of the upper gastrointestinal (UGI) tract (6). In fact, Schrerer et al. (4) suggest that this method would be the best option to treat neuroendocrine tumors (NET) located in the duodenum. Our group (7) has already published a successful case report of the application of this treatment in T1 esophageal squamous cell cancer in a patient with multimorbidities. That successful case is what led us to carry out the present case series.

We report our single-center experience evaluating the use of EBL with autoamputation as a treatment for small superficial lesions of the UGI tract in patients in whom surgery was contraindicated. The aim of this study waws to evaluate the efficacy of EBL in carefully selected patients who would benefit from this new variant method of endoscopic treatment which we considered to be associated with fewer adverse events.

 

Material and Methods

Study subjects

Our study was conducted between May 2010 and May 2015 at Hospital Universitari de Bellvitge-IDIBELL, a tertiary university hospital in the Barcelona area. Twelve consecutive patients who had small (< 15 mm) and superficial lesions (high-grade dysplasia, T1a-b and well-differentiated NET) in the upper gastrointestinal tract and for whom surgery was contraindicated were included. Before EBL, all lesions were diagnosed by biopsy to identify histologic characteristics of the lesion, and computed tomography (CT) and/or endoscopic ultrasound (EUS) were performed for staging.

Patients were excluded if surgery could be offered or if performing an endoscopic mucosal resection was an acceptable risk. All cases were discussed in a multidisciplinary committee and it was concluded that surgery was contraindicated owing to the presence of multimorbidities (Table I). Moreover, the absence of histology was accepted by the committee as it would not change future management and, more importantly, it would protect them from adverse events.

 

 

Data collection

A retrospective analysis of our prospective patients' recollection was performed. The following variables were collected from a specific endoscopic therapeutic database system: sex, age, comorbidities, upper endoscopy, CT and EUS findings, pathology results, adverse events and findings on endoscopic and histological surveillance.

Patients and their families were informed of the multidisciplinary team's decision and they gave oral informed consent before their participation.

Endoscopic procedure

Using a standard upper endoscope (GIF-Q165, Olympus, Hamburg, Germany), the procedure was performed under conscious sedation by an anesthesiologist. The same endoscopist (J.G.) performed or supervised all endoscopic procedures. Before the treatment, an EUS, using a radial echoendoscope (GF-UE160-AL5; Olympus), was performed to evaluate the depth of invasion which could determine the feasibility of endoscopic treatment, and to exclude a T2 grade.

In flat lesions (Paris Classification: Is-IIa), chromoendoscopy using a spray catheter (EMR Olympus) with methylene blue covering the lesions, and argon plasma coagulation (40W) to delimit the margins were used before the banding. With a Duette^® Multi-Band Mucosectomy Device (Cook Medical, Bloomington, Indiana) the lesions were aspirated into the cap and rubber bands were deployed in order to surround the complete lesion. No submucosal injection was performed. The ligated mucosa was left in place and was not removed with a snare. Examples of cases #10, #8, #1 are shown in figures 1, 2, and 3 respectively.

 

 

 

 

After the procedure, patients were in clinical observation for eight hours and then discharged if there were no complications. All study subjects provided written informed consent.

Follow-up evaluation

After initial treatment, follow-up endoscopies with biopsies were planned at 4-8 weeks, 6 months and 12 months. Only when biopsies showed histological persistence a second session of EBL was considered.

 

Results

The median age of the patients was 74 (range 59-83 years), and the male/female ratio was 0.5 (6/6). The mean tumor diameter was 9.6 ± 2.8 mm (range 4-15). Among the twelve patients, an EUS was performed in 9 cases (75%), a CT in 8 cases (67%) and a PET-CT in 2 cases of esophageal lesion (17%). The patients showed neither lymph nodes nor metastasis. Lesion classifications are summarized in table II.

 

 

Therapeutic outcome

Lesions were aspirated into the cap and 1-4 rubber bands (mean 1.83) were applied. It was possible to include the whole lesion within the bands in all patients. Immediate endoscopic homeostasis was not necessary in any case and no patient showed clinically apparent signs of bleeding. Only one patient had an adverse effect which was mild chest pain after the procedure that resolved with acetaminophen. In two cases, an admission of 24 hours was necessary for reasons not related to the procedure. The rest were only in observation for 8 hours.

Regarding the outcomes (success of eradication vs. persistence of lesions), table III summarizes all the results at each control. At the first follow-up (a median of 7 weeks), there was 91.6% (n = 11/12) of endoscopic remission and 75% (n = 9/12) of negative biopsies (histological remission). At 6-month follow-up, there was 70% (n = 7/10) of both endoscopic remission and negative biopsies. And at 12 months, there was 100% (n = 8/8) of endoscopic remission and 75% (n = 6/8) of negative biopsies and two cases of downgrading to low grade dysplasia.

 

 

As shown in table IV, in the first surveillance endoscopy, performed at a median of 7 weeks (range 4-70 weeks) after EBL, there were three patients with persistent T1 cancer lesions (n = 1 stomach, n = 2 esophagus). Endoscopic treatment was planned in the three cases. In two of them, it was possible to perform a second EBL (Table III). In one T1 of esophagus (#2), banding was impossible to repeat because of the width of an upper esophageal stricture and trismus. For this reason, in this case APC at high potency (70 W) was applied but the next control resulted in persistence of the tumor. In this particular case, it was decided not to apply another treatment, because the lung cancer worsened and palliative treatment was considered. In another case, a T1 of stomach (#11), after two EBLs there was macro- and microscopic persistence. Due to the patient's cognitive disorder it was decided not to perform any kind of treatment.

 

 

In the second control, at 6 months there were three cases with lesion persistence. Surprisingly, an esophageal intramucosal adenocarcinoma with negative first biopsies had microscopic persistence. In this case (#5), a second EBL was performed and then the histology was normal (Table IV).

In the third control, at 12 months, there were two cases (28%), with high grade dysplasia and gastric T1, that became to low-grade dysplasia (downgrading). In both, it was decided to carry out a strict follow up. In contrast, six patients (75%) had endoscopic and histological remission.

There are a few patients without a second or third control (NA: not applied, in table IV) because of the characteristics of the patients, elderly and with multiple comorbidities requiring postponement of some procedures. During follow-up (mean 30.61, range 15.10-69.17 months), one patient was lost to controls.

 

Discussion

EBL is not a new technique; it has been used in esophageal varices, Dielafoy's lesions and hemorrhoids, among other lesions. Autoamputation is a new effective technique described in UGI lesions such as subepithelial lesions (6,15), NETs (3-5) and Barrett esophagus without dysplasia (2). Endoscopic treatment in duodenal NETs with a size < 1 cm has been recommended (8), due to the low risk of metastasis. Regarding UGI submucosal lesions, there are a few reports suggesting that endoscopic management may be a useful alternative to surgery (6,9). However, in the treatment of cancer it is always accompanied by electrocautery in order to obtain a sample for histological study. Our group was the first to publish a case of applying EBL without resection in a selected patient with esophageal squamous cell cancer (7). In fact, this patient has been included in the case series and after 61 months he is still in remission. So, in this case, we may conclude that the technique has been a success as a cancer treatment, with no complications or morbidity. This case is what led us to consider the possibility of applying EBL in carefully selected patients.

The main advantage of this technique is that complications are almost nil. Scherer et al. (4) compared EMR to autoamputation with EBL in small duodenal carcinoids and found 18.8% adverse events in the EMR versus none in EBL. Du Jeong et al. (10) evaluated endoscopic resection of gastric subepithelial tumors arising from the muscularis propria layer and described perforation in 12% successfully managed by the endoscopic application of clips; and Young-MiPark et al. (11) carried out a meta-analysis of endoscopic submucosal dissection and EMR which showed that bleeding occurs in 7% and perforation in 1% with EMR.

Another advantage of EBL without resection is that it is an easy and inexpensive technique compared to other endoscopic procedures. Although it can be more challenging in flat lesions of the esophagus or fundus.

However, barring further evidence, we should not recommend autoamputation for the treatment of small and superficial UGI lesions as this technique has not yet been validated as a routine treatment for tumors. For this reason, this technique was associated with planned surveillance. If we had the certainty that applying a rubber band is an effective treatment, we could skip endoscopic follow-up. However, the indication of this endoscopic treatment has not yet been validated. In the future, with an accurate analysis of criteria of persistence (size, histology, grade, etc.), we will learn in which cases it is not necessary to perform surveillance. In case of persistence, a new session of EBL or other endoscopic techniques may need to be considered.

We also want to highlight that macroscopic endoscopic image can underestimate the persistence of the lesion as only two cases out of six were detected macroscopically by endoscopic image (Table III).

Despite the fact that all patients had surgery contraindicated due to multiple morbidities, it is a heterogeneous group of patients in terms of their individual comorbidity, survival and type of upper gastrointestinal lesion. Each treatment and follow-up was discussed individually with the multidisciplinary team. Furthermore, we would like to highlight that although patients had a very high risk for surgery, most of them have an acceptable quality of life and the risk of a surveillance endoscopy was an acceptable one.

This study has several limitations. First, we defined a complete resection as the absence of remnant tumor with biopsies after EBL. It was not possible to carry out an examination of surgical specimens to confirm the completeness of the resection. Moreover, with this technique, as with EMR, it is difficult to assure a sufficiently safe margin. Second, an obvious drawback of this technique is not having a histological piece, which would indicate the degree of T1 tumor involvement (m or sm; T1a or T1b, respectively) and, consequently, the need for a lymphadenectomy in a patient with no surgical risk. In esophageal cancer the lymph node metastasis rate is known to be 6% (T1m) and 29% (T1sm) (12); in gastric cancer 3.3% (T1m) and 23.5% (T1sm) (13); and in duodenal NET 4% (T1m) and 28% (T2) (14). For this reason, each patient was discussed among the members of the UGI multidisciplinary cancer committee and in each case it was decided that, owing to the patient's condition, histology would not change clinical management, and so the procedure was carried out. Third, it is a case series with a prospective inclusion but retrospective analysis, and the mean follow-up period is relatively short for determining complete histological remission. Furthermore, this study takes in different kinds of tumors (T1, high grade dysplasia and NET) with differing carcinogenesis behavior in order to draw some conclusions regarding the necessity of follow-up, but with our case series we may deduce that autoamputation might be especially effective for NET. Finally, because this case series reports the endoscopic experience of a single center, it may not be valid to extrapolate the results to other centers, where endoscopists may have varying levels of skill and familiarity with EBL. However, the fact that all procedures were carried out by the same endoscopist means that the procedure and surveillance were more standardized.

In conclusion, management of early small lesions in UGI with EBL without use of electrocautery appears to be a safe, effective, simple and widely available technique in patients who are not good candidates for surgery. We found that it would be especially useful as a treatment option in HGD and NETs. Furthermore, we are conscious of the limitations of this case series, and prospective studies with more cases and longer follow-up are needed. In practice, we suggest performing control endoscopy with biopsies at 1 month, 6 months, and then yearly after EBL.

 

References

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Correspondence:
Joan B. Gornals.
Endoscopy Unit.
Department of Digestive Diseases.
Hospital Universitari de Bellvitge-IDIBELL
(Bellvitge Biomedical Research Institute).
Feixa Llarga, s/n.
08907 L'Hospitalet de Llobregat, Barcelona, Spain
e-mail: jgornals@bellvitgehospital.cat

Received: 11-10-2015
Accepted: 18-03-2016