Endoscopic mucosal resection of gastric tumors located in the lesser curvature of the upper third of the stomach

Endoscopic mucosal resection of gastric tumors located in the lesser curvature of the upper third of the stomach Mitsunobu Matsushita, Kiyoshi Hajiro, Kazuichi Okazaki, Hiroshi Takakuwa,

MD MD MD MD

Endoscopic m u c o s a l resection (EMR) is i n c r e a s i n g l y u s e d for the r e m o v a l of s m a l l gastric t u m o r s w i t h surr o u n d i n g m u c o s a 1 a n d is a useful t h e r a p e u t i c m e t h o d as well as a diagnostic a p p r o a c h to m u c o s a l lesions. E M R for e a r l y gastric cancers h a s b e e n widely accepted as a s t a n d a r d p r o c e d u r e b e c a u s e of its m i n i m a l i n v a s i v e n e s s a n d s a t i s f a c t o r y p o s t p r o c e d u r e r e s u l t s in m a i n t a i n i n g a good quality of life for patients. Several different E M R p r o c e d u r e s h a v e b e e n r e p o r t e d a n d t h e i r u s e f u l n e s s is well established. 2 Strip biopsy m e t h o d or lift-and-cut E M R (LC-EMR), i n t r o d u c e d by T a d a et al., 3 h a s b e e n u s e d m o s t widely in J a p a n . 4 I f the t a r g e t lesion is located in the lesser c u r v a t u r e of the u p p e r t h i r d of t h e stomach, L C - E M R u s i n g a double-channel endoscope is quite difficult to p e r f o r m because of the t a n g e n t i a l location of t h e t u m o r to t h e endoscope. 5 I n this article, we describe the u s e of a cutt i n g E M R (C-EMR) technique, b a s e d on t h e original p r o c e d u r e o f H i r a o et al.,6 for gastric t u m o r s located in t h e lesser c u r v a t u r e of t h e u p p e r t h i r d of t h e stomach. We prospectively e v a l u a t e d its clinical u s e f u l n e s s in c o m p a r i s o n w i t h LC-EMR. PATIENTS AND METHODS From January to December in 1994, we performed EMR in 43 patients with gastric tumors (52 lesions) at Tenri Hospital. The 52 lesions consisted of 13 early cancers, 33 adenomas, and 6 submucosal tumors. Ten of these 52 lesions were located in the lesser curvature of the upper third of the stomach. We randomly performed LC-EMR or C-EMR in 10 patients with 10 gastric tumors and prospectively analyzed the efficacy of these procedures. Randomization was performed using closed envelopes. The 10 patients included 8 men and 2 women ranging in age from 53 to 78 years with an average age of 70 years. The 10 lesions consisted of 4 early cancers and 6 adenomas. Endoscopic ultrasonography (EUS) with a radially scanning transducer (GF-UM20/EU-M20, frequency 7.5 or 12 MHz; Olympus, Tokyo, Japan) was performed before resection in Received February 20, 1996. For revision April 16, 1996. Accepted December 26, 1996. From the Department of Gastroenterology, Tenri Hospital, Nara, Japan. Reprint requests: Mitsunobu Matsushita, MD, Gastroenterology, Tenri Hospital, 200 Mishima-cho, Tend, Nara 632, Japan. 0016-5107/97/4506-051255.00 + 0 GASTROINTESTINAL ENDOSCOPY Copyright © 1997 by the American Society for Gastrointestinal Endoscopy 37/69/80212

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Figure 1. lib-type (superficial flat type) early gastric cancer, located in the lesser curvature of the upper third of the stomach (case 9). The tumor is slightly paler than the surrounding mucosa (arrows).

all patients. The diagnosis of mucosal lesions was based on endoscopic and EUS findings. The lesion was considered to be limited within the mucosa when the third layer, corresponding to the submucosa, was shown by EUS scanning to be preserved. LC-EMR was performed in 5 of the 10 patients, and C-EMR in the others. First, a side-viewing endoscope (GF-200; Olympus) was introduced into the stomach under local pharyngeal anesthesia. The tumor extent was confirmed by careful observation and a topical spray of methylene blue delineated the tumor margin (Fig. 1). The tumor size was determined by measuring forceps (M2-4K; Olympus) and several spots were marked 5 to 10 m m outside the tumor margin by a needle knife with high-frequency coagulation current (Fig. 2). Second, the endoscope was switched to a double-channel front-viewing endoscope (GIF-2T200; Olympus). More than 20 ml of 3.65% hypertonic saline solution was locally injected into the submucosal layer around the target lesion to induce an artificial hemispherical protrusion of the tumor and to separate the mucosal layer from the underlying muscle layer, thus enabling the safe use of the needle knife and snare in the next step. Since hypertonic saline with epinephrine solution has produced chest discomfort in some patients, we prefer to use saline solution without epinephrine. In LC-EMR, the lesion was then elevated by retraction of grasping forceps (FG-9L; Olympus) that was passed through the loop of the snare forceps. After snaring and confirming the size and shape of the snared mucosa to ensure procedural safety, the lesion was extensively resected with highfrequency cutting current. In C-EMR, circumferential incision of the mucosa as deep as the superficial submucosal layer was performed along the marking spots by the needle knife with high-frequency cutting current (Fig. 3). If the depth of incision was adequate, the surface of the muscle layer with a flow of saline solution could be observed. When the incision was completed, the lesion was snared along the incision and resected with high-frequency cutting current. During C-EMR, we used only one channel of the endoscope. VOLUME 45, NO. 6, 1997

Figure 2. Marking of the lesion, 5 to 10 mm outside the tumor

Figure 3. Circumferential incision of the mucosa along the

margin.

marking spots.

The resected material was withdrawn using grasping or snare forceps. Finally, we replaced the side-viewing endoscope and washed and stretched the artificial ulcer base with a water jet to ensure successful resection and no bleeding (Fig. 4). If any residual tumor was found, additional resections were carried out using the double-channel endoscope on the same day. Resected specimens were stretched and pinned on to a rubber slab immediately after resection, fixed in 10% formalin for 24 hours, and sliced into several pieces parallel with the first incision between the center of the lesion and its closest margin. All specimens were examined histologically. The tumor was completely resected if the lateral and basal margins were free of tumor in all sections. In patients with submucosal gastric cancers, laparotomy was added because of possible lymph node metastasis. In the others, follow-up examinations with endoscopy and multiple biopsies were performed for the subsequent year. In case of positive biopsy for tumor cells, additional therapy was performed.

RESULTS T h e patients' characteristics are s u m m a r i z e d in Table 1. Histologically, four lesions were classified as well-differentiated adenocarcinomas and six as adenomas. T h e t u m o r size of the LC-EMR group and of the C-EMR group was, on the average, 13.2 m m a n d 17.4 mm, respectively. Although a single-step resection is ideal, a stepwise resection was n e c e s s a r y in some cases. Single resections were p e r f o r m e d in two lesions of the LC-EMR group and four lesions of the C-EMR group. Stepwise resections were p e r f o r m e d in the other four lesions. Only one lesion of the LC-EMR group a n d four lesions of t h e C-EMR group were resected completely. The lateral and basal m a r g i n s were t u m o r free in these five cases; lateral m a r g i n s were positive for t u m o r tissue in the o t h e r Five cases. All lesions of the LC-EMR group were resected VOLUME 45, NO. 6, 1997

Figure 4. Extensive mucosal defect after resection of the tumor. The smooth surface of the muscularis propria is left intact without bleeding. w i t h o u t a n y complications. Bleeding developed d u r i n g C-EMR in two cases, b u t was a r r e s t e d by endoscopic hemostasis of local injection of 3.65% hypertonic saline with 0.005% e p i n e p h r i n e solution. In this comp a r a t i v e s t u d y of two procedures, E M R was safely p e r f o r m e d in all cases w i t h o u t severe bleeding, perforation, or a n y other complications. In the four carcinoma cases, the t u m o r was limited w i t h i n the mucosa in two lesions (cases 4 a n d 8), while the d e p t h of invasion was submucosal in the remaining two lesions (cases 7 and 9). Although the lateral a n d basal m a r g i n s were t u m o r free, proximal gastrect o m y with l y m p h node dissection was p e r f o r m e d in the two patients with submucosal gastric cancers. Histologically, resected specimens revealed no residual adenocarcinoma or l y m p h node involvement, indicating complete resection in the two cases with C-EMR. Endoscopic follow-up studies were p e r f o r m e d in the others for the s u b s e q u e n t year. No r e c u r r e n c e of t u m o r s was found in the C-EMR group. In the LCGAS~"ROINTESTINAL E N D O S C O P Y

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Table 1. Characteristics of 10 patients with gastric tumors located in the lesser curvature of the upper third of the stomach Case

Age (y)

Sex

Histology

Size (mm)

Single resection

Complete resection

Complication

Lift-and-cut (LC-EMR) 1 77 M Adenoma 18 No No None 2 66 F Adenoma 10 Yes No None 3 53 M Adenoma 13 No No None 4 70 F AC(IIa) 3 Yes Yes None 5 77 M Adenoma 22 No No None Cutting (C-EMR) 6 78 M Adenoma 25 No No Bleeding 7 63 M AC(IIa)* 18 Yes Yes None 8 67 M AC(IIb) 15 Yes Yes None 9 75 M AC(IIc)* 16 Yes Yes Bleeding 10 74 M Adenoma 13 Yes Yes None AC, Adenocarcinoma;Ila, superficial elevated type; lib, superficial flat type; IIc, superficial depressed type. *Subsequent submucosal carcinoma. ~No residual carcinoma or lymph node involvementin surgicallyresected specimens. EMR group, three of the five cases showed residual tumors. In two of the five cases of incomplete resection (cases 2 and 6), no residual tumors were revealed.

DISCUSSION The development of EMR presented a major advance in the t r e a t m e n t of gastrointestinal mucosal lesions, either slightly elevated or depressed.1 Recently, various kinds of endoscopic modalities have been introduced to tr eat small mucosal carcinoma and borderline malignancy. 2 LC-EMR is most widely used and is very useful for obtaining large specimens and for curative endoscopic resection of mucosal tumors. 7 From the technical point of curability, tumor location is one of the most important factors. In LC-EMR, the rate of incomplete resection is highest in lesions located in the lesser curvature, s When tumors are located parallel to the endoscope, as in the lesser curvature of the upper third of the stomach, it is difficult to elevate the tumor with grasping forceps. 9 Even if the tumor is lifted, the snare m a y slip on the mucosa resulting in incomplete resection. In C-EMR, we avoid these problems by performing circumferential incision of the mucosa without lifting up the lesion and snaring along the incision without slipping on the mucosa. In lesions of the lesser curvature of the upper stomach, identifying the entire margin by a front-viewing endoscope may also be difficult because of the endoscope getting too close to the lesion and the oblique view of the lesion. For these reasons, it is difficult to ensure the resected margin adequately with a frontviewing endoscope. In our study, the difficulty could be resolved using a side-viewing endoscope before resection to achieve better visualization. To achieve more precise delineation of the tumor extent, an endoscopic application of dye is usually recommended. Although a single-step resection is ideal, a stepwise 514 GASTROINTESTINAL ENDOSCOPY

Follow-up biopsy Positive Negative Positive Negative Positive Negative Nonet Negative Nonet Negative

resection was performed in 4 of the 10 cases (in lesions larger t h a n 10 m m in three cases in the LC-EMR group and 25 m m in 1 case in the C-EMR group). We believe that a single-step resection is impossible in lesions larger than 10 mm with LC-EMR and in those larger than 20 mm with C-EMR using a single-channel endoscope only. With C-EMR using the double-channel endoscope, lesions larger than 20 mm could be resected by a single step with retraction by grasping forceps. For the purpose of curative endoscopic surgery, histologic diagnosis ofresected specimens is important to ensure t hat excised margins are free of tumor. Incomplete resections occurred in 5 of the 10 cases, 4 of the LC-EMR group and 1 of the C-EMR group, attributed to mismarking of the lesion in case 2, insufficient lifting of the lesion in cases 1 and 3, and the tumor size in cases 5 and 6. In all lesions in which the stepwise resection was used, incomplete resections resulted. Therefore, the stepwise resection directly influenced the incomplete therapy. However, 2 of the 5 cases of incomplete resection (cases 2 and 6) were tumor free by follow-up studies with endoscopy and biopsies. In both cases, the margin of resected specimens was tumor cell-positive at one section only, and at several sections in the others. Therefore, a cure can be expected for gastric mucosal tumors if only one section of the specimens has tumor cell-positive margin. We recommend follow-up studies in such cases. The safety of EMR is as important as its diagnostic and therapeutic efficacies. The incidence of severe complications related to EMR is reported from 1% to 14%: perforation of the stomach occurs in up to 8%. 6 Perforation and massive bleeding are attributed to the ensnarem ent of the muscularis propria and large int ram ural vessels. In our study, we encountered no severe complications from separation of the mucosal layer from the underlying muscle layer with local inVOLUME 45, NO. 6, 1997

jection of h y p e r t o n i c saline solution. E U S p e r m i t s a n excellent v i s u a l i z a t i o n of the i n t r a m u r a l state. I n all cases, a p r e t h e r a p e u t i c E U S r e v e a l e d no large subm u c o s a l vessels n e a r t h e lesion. Such i n f o r m a t i o n is v e r y useful to avoid complications. E U S is also t h e b e s t p r o c e d u r e for confirming t h e d e p t h of t u m o r i n v a s i o n a n d l y m p h node involvemerit. 1° A l t h o u g h the diagnosis of t u m o r infiltration b y E U S h a s b e e n a c c u r a t e enough, it is not a l w a y s e a s y to d i s t i n g u i s h m u c o s a l t u m o r s f r o m s u b m u c o s a l ones, especially in those located in the cardia or prepylorus. 11 In fact, we misdiagnosed submucosal cancers as mucosal ones (cases 7 a n d 9) because of the location of the tumors. Recently, a m i n i a t u r e ultrasonic probe, u n d e r direct endoscopic control through the ins t r u m e n t channel of a s t a n d a r d endoscope, h a s become available, p e r m i t t i n g reliable scanning of the t a r g e t a r e a a n d revealing the structure of the gastric wall more clearly t h a n before. 12 We consider the probe to be highly useful for the diagnosis of the depth of t u m o r invasion in cases of t u m o r s located in the u p p e r third of the stomach. The m i n i a t u r e probe will not only ensure a correct diagnosis of submucosal cancer in the n e a r future b u t also avoid u n n e c e s s a r y endoscopic intervention. I n t h e cure of e a r l y gastric cancers, p r o b l e m s of c o m p l e t e n e s s of local resection a n d l y m p h node m e t a s t a s i s m u s t be settled. Well-differentiated adenoc a r c i n o m a limited w i t h i n t h e m u c o s a u s u a l l y does not d e m o n s t r a t e e i t h e r l y m p h nodes i n v o l v e m e n t or vasc u l a r invasions. 13 I n such cases, a local excision of the t u m o r s is considered to be a d e q u a t e . T h e incidence of l y m p h node m e t a s t a s e s in s u b m u c o s a l cancers is f a r h i g h e r t h a n m u c o s a l ones.13 F r o m a n a n a l y s i s of m a n y s p e c i m e n s of surgically r e s e c t e d gastric cancers, the r a t e of l y m p h node m e t a s t a s i s w a s 11% to 40% in pat i e n t s w i t h s u b m u c o s a l cancers. 14 I f s u b m u c o s a l invasion is found on t h e histologic study, t h e p a t i e n t s should u n d e r g o a g a s t r e c t o m y b e c a u s e of possible l y m p h node i n v o l v e m e n t , e v e n if t h e endoscopic resection a p p e a r s to be complete on t h e basis of t u m o r free m a r g i n s . We s u b s e q u e n t l y p e r f o r m e d gastrect o m y w i t h l y m p h node dissection in two p a t i e n t s w i t h s u b m u c o s a l cancers (cases 7 a n d 9). An e n t i r e m u c o s a l resection provides t h e definite a d v a n t a g e of c o n t r i b u t i n g to a c c u r a t e histopathologic analysis compared with other local t r e a t m e n t s such as laser a n d radiation therapies, z5 LC-EMR requires grasping epithelial tumors, which are usually v e r y fragile, resulting in the mucosal damage. In contrast, the resected specimens h a d a smooth surface with no signs of injury in C-EMR, a n d the entire mucosal a n d submucosal specimens were widely resected, including the surrounding n o r m a l mucosa. The specimens with m i n i m a l tissue d a m a g e are better for the accurate histologic determination of the depth of invasion a n d vascular involvement t h a n those obtained with LC-EMR. VOLUME 45, NO. 6, 1997

We h a v e applied C - E M R for difficult-to-remove gastric t u m o r s . T h e m e t h o d , which completely resects t h e lesion a n d does not injure t h e m u c o s a l surface, can solve several p r o b l e m s e n c o u n t e r e d w i t h L C - E M R a n d achieve a radical cure o f m u c o s a l t u m o r s . C u t t i n g w a s p e r f o r m e d along t h e m a r k i n g line w i t h o u t lifting u p t h e lesion, a n d t h e c u t t i n g line p r e v e n t e d slipping of the snare. C - E M R is not limited to lesions less t h a n 1 cm in d i a m e t e r . T h i s t e c h n i q u e allows resection a t a n y p a r t of t h e gastric m u c o s a u n d e r topical a n e s t h e sia w i t h o u t m a j o r complications. We i n t e n d to e x p a n d its application to decrease i n c o m p l e t e resections of difficult-to-remove gastric t u m o r s . C - E M R is a useful m o d a l i t y for c u r a t i v e ,endoscopic resection of m u c o s a l t u m o r s , e v e n located in t h e lesser c u r v a t u r e of t h e upp e r t h i r d of t h e stomach. O u r r e s u l t s showed C - E M R as a p o t e n t i a l l y c u r a t i v e t r e a t m e n t for gastric m u c o s a l t u m o r s . We r e c o m m e n d a p p l y i n g C-EMR, especially in gastric t u m o r s of t h e h i g h lesser c u r v a t u r e . REFERENCES

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