Endoscopic Resection

Endoscopic resection (ER) has become the most important endoscopic treatment method of early cancers of the upper GI tract. ER serves as a therapeutic but also as a diagnostic tool by providing a specimen for histologic assessment. In expert hands ER is easy to performa and has a very low complication rate. Long-term results in early esophageal and gastric cancer are excellent.

Endoscopic resection (ER) of early neoplastic lesions has become increasingly important in recent years, both as a diagnostic tool for the staging of esophageal carcinoma and as a method of performing definitive treatment when the cancer meets certain criteria in which the risk of lymph node metastasis is negligible. For many years, surgery was considered to be the treatment of choice, even in patients with high-grade intraepithelial neoplasia (HGIN) or mucosal carcinoma, but it is associated with a 30-day mortality of 2% to 5% and with significant morbidity in 30% to 50% of cases, even in high-volume centers.

Because of these alarming data, local treatment methods have been introduced and investigated in several studies on early Barrett’s neoplasia. In contrast to ablative treatment methods, such as photodynamic therapy (PDT), argon plasma coagulation (APC), cryotherapy, and radiofrequency ablation (RFA), ER allows histologic assessment of the resected specimen to assess the depth of infiltration of the tumor (pT1m1–4; pT1sm1–3) and whether an infiltration of lymph (L-status) or blood vessels (V-status) is present. In addition, the pathologist can provide important information about the freedom from neoplasia at the lateral and (more importantly) basal margins, imitating the surgical situation. These significant advantages of ER are the main reason why ER should be preferred over all ablative treatment methods whenever possible, especially keeping in mind the low accuracy of endoscopic ultrasound regarding local tumor staging.

ER techniques

“Endoscopic resection” is the general term for the different resection techniques used to treat neoplastic and uncertain lesions in the gastrointestinal tract. The aim of ER must always be complete resection of the mucosal and submucosal layer down to the lamina muscularis propria. The term “endoscopic mucosal resection” or “mucosectomy” is also widely used; however, it is misleading because significant proportions of the submucosal layer are also resected, which is important in the case of submucosal infiltration of the tumor.

ER with a Ligation Device

A widely used method is ER with a ligation device, also used for ligation of esophageal varices. With this method, the target lesion is sucked into the cylinder of the ligation device and a rubber band is then released to create a pseudopolyp that has the rubber band at its base. Prior submucosal injection of saline is usually not necessary. After this, the endoscope is withdrawn to remove the ligation cylinder. Afterward, the endoscope is reintroduced and the pseudopolyp is resected with a reusable snare underneath the rubber band to achieve larger resection specimens.

Several ligation devices are available. In addition to single-use devices, available ligation devices include a reusable ligator, with which similar results can be achieved at reduced cost. Ligation devices with multiple rubber bands are also available to allow several ligations to be performed in a single session without having to withdraw the endoscope. Another useful development is a ligation cylinder that has six rubber bands and a facility for advancing a snare through the working channel of a regular endoscope. This enables the endoscopist to perform up to six resections without having to withdraw and reintroduce the endoscope. This device is widely used for piecemeal resections of larger neoplastic lesions.

ER with a Transparent Cap

The cap technique was introduced by Inoue and Endo almost 20 years ago for resection of early neoplastic lesions. In ER with the cap technique, a specially developed transparent plastic cap is attached to the end of the endoscope. After submucosal injection under the target lesion, usually with a saline–epinephrine solution, the lesion is sucked into the cap and resected with a diathermy snare that has previously been loaded onto a specially designed groove on the lower edge of the cap. Preloading of the snare can be done in the gastric antrum by applying slight suction to the mucosa and carefully advancing the snare until it is placed exactly in the rim at the distal margin of the cap. Prior marking of the borders of the lesion either with electrocautery using the tip of the snare or an APC probe is recommended, because injecting underneath a discrete neoplastic lesion often makes it difficult to identify the borders of the target lesion afterward.

ER with a ligation device and ER with the cap can be performed in the esophagus with similar results and complication rates. A prospective randomized trial with 100 consecutive ERs in 70 patients comparing ER with a reusable ligation device with ER with the cap was able to demonstrate that there is no difference regarding size of the resection specimens, the resection area, and complication rate. One minor bleeding incident occurred in each group, but no severe complications were seen. However, another retrospective study from the Amsterdam group showed that ER with a multiband ligator was faster and safer than cap resection. Mild bleeding occurred significantly more often after cap ER (20% vs 6%).

The major drawback of ER with the suck-and-cut technique seems to be that only small lesions with a diameter of less than 20 mm can be resected en bloc with tumor-free lateral margins. Ulcerated lesions often have fibrosis attaching the submucosa to the lamina muscularis propria, often resulting in failure of the lesion to lift. In these cases, ER is not advisable, or should only be performed with caution. Larger lesions can usually be resected completely with the piecemeal technique, but this method seems to be associated with a higher recurrence rate probably because of small neoplastic residues resulting from insufficient overlapping of the resection areas. For piecemeal ER the ligation device or cap has to be placed at the margin of the prior resection area and careful suction has to be applied ( Fig. 1 ). The endoscopist has to be very careful to avoid small neoplastic remnants between the resection areas. On the other side, there is a danger of sucking the proper muscle layer of the previous resection into the pseudopolyp leading to a perforation. To minimize the risk of complications and of insufficient resection, only experienced endoscopists in high-volume centers should perform this procedure. En bloc resection allows more accurate histologic evaluation of the neoplastic lesion, especially of the lateral and basal margins. A new resection technique, endoscopic submucosal dissection (ESD), was therefore developed.

ESD

The ESD procedure in the treatment of early gastric cancer was first described by Hosokawa and Yoshida and Ono and colleagues with a method using an insulated-tip knife to obtain a large resection specimen with the neoplasm resected en bloc ( Fig. 2 ). Once the borders of a neoplastic lesion have been adequately visualized the borders are marked with electrocautery at a distance of 5 to 10 mm from the margin of the carcinoma. After this, submucosal injection of fluid is performed to elevate the lesion from the muscular layer, and the mucosa surrounding the lesion is circumferentially cut outside the markings. Finally, the submucosal connective tissue is dissected with a dedicated knife. Visible vessels can be coagulated to prevent bleeding. The fluid used for submucosal injection can be isotonic saline solution, a solution of hyaluronic acid with or without glycerol, or 20% glucose or hypertonic saline with epinephrine. Some endoscopists add a dye, such as indigo carmine, to the solution to facilitate discrimination of the submucosal from the proper muscle layer.

A wide variety of different knives are used for ESD, including the insulated-tip knife, hook knife, flex knife, needle-knife, triangle-tip knife, flush knife, and hybrid knife. With the flush and hybrid knife submucosal injection and dissection can be performed at the same time without changing the instruments.

ESD is not only used for gastric cancers but also for esophageal, colorectal, and duodenal neoplastic lesions. The size of the resected specimen obtained with ESD can extend to more than 10 cm in diameter, but this fascinating new method is associated with a substantial complication rate, including perforations requiring surgery, long procedure times of up to several hours, a slow learning curve, and a high degree of operator dependency. The endoscopist should first start to practice ESD in models to become familiar with this technique. Afterward, they should start with ESD procedures in the stomach, then in the rectum, before this method is used for esophageal lesions.

Indications and results of ER in HGIN and early Barrett’s cancer

ER is the treatment of choice in high-grade dysplasia (HGD) and early mucosal cancer in Barrett’s esophagus because the risk for lymph node and distant metastasis is almost absent. Large series from several groups demonstrate the safety and efficacy of this treatment approach even after long-term follow-up. Risk stratification should be performed in accordance with known risk factors, such as grade of differentiation, lymph vessel or venous infiltration, and the infiltration depth of the carcinoma (m1–m3/m4). From the authors’ center’s experience with 899 patients with mucosal Barrett’s cancer treated endoscopically only 0.34% have developed lymph node metastasis. Those patients usually had lymph vessel invasion on histology (L1 status). Thirty-eight patients with mucosal Barrett’s cancer have been referred to the surgical unit for esophageal resection because of unfavorable conditions for ER or high-risk situation after diagnostic ER. Among those negatively selected patients three (7.8%) were found to have metastatic nodes. The overall risk for lymph node metastasis in mucosal Barrett’s cancer in the authors’ center was 0.6%. However, a strong predictor for lymphatic spread was lymph vessel infiltration. Therefore, all patients should be referred for esophageal resection in case of a L1 situation.

Submucosal invasion goes along with a significantly increased lymph node risk of up to 41% and it strongly correlates with the infiltration depth. Cancer invading the upper third of the submucosa (pT1sm1) has a risk varying between 0% and 21%. Cancer invading the mid and lower submucosa (pT1sm2/3) goes along with metastatic lymph nodes in 36% to 54%. These data are mainly from older retrospective surgical series in a time when exact determination of the tumor infiltration depth had little clinical relevance. In contrast to ER specimen that are sliced every 1 to 2 mm, surgical resection specimens were routinely cut in 5-mm slices. This explains that deeper infiltrating parts of the tumor might have been missed, underestimating invasion depth. Reported rates of lymph node metastasis might have corresponded with deeper invading cancers. Further important risk factors, such as differentiation grade and lymphatic and vascular invasion, were usually not reported making it impossible to draw final conclusions from these series. Some data are suggesting that ER can safely be performed in so-called “low-risk” submucosal cancer (sm1-cancer, G1/2, L0, V0) but larger series are awaited to generally recommend ER in these patients.

Clinical Outcome of ER

The relevant publications on ER of early Barrett’s neoplasia are summarized in Table 1 . The first report on ER in 64 patients with early carcinoma or HGIN arising in Barrett’s esophagus was published in 2000. Complete remission was achieved with ER in 82.5% of cases (97% in the low-risk group and 59% in the high-risk group) in the study. During a mean follow-up period of 12 months, recurrences or metachronous lesions were observed in 14% of patients, who underwent successful endoscopic retreatment.

Table 1

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