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Diagnosis of submucosal tumor of the upper GI tract by endoscopic resection
Diagnosis of submucosal tumor of the upper GI tract by endoscopic resection Toshihiro Kojima, MD, Hiroshi Takahashi, MD, Adolfo Parra-Blanco, MD, Kenzo Kohsen, MD, Rikiya Fujita, MD Yokohama, Japan
Background: Submucosal tumors are frequent findings during endoscopy, although definitive diagnosis based on histologic confirmation presents some difficulties. The aim of this study was to evaluate the efficacy and safety of endoscopic resection based on endoscopic ultrasonography (EUS) findings to reach a definitive diagnosis of submucosal tumor. Methods: Fifty-four submucosal tumors of the upper gastrointestinal (GI) tract were included in this study. EUS was performed to determine the layer of origin and location of the lesion and to rule out malignancy. En bloc resection was attempted for lesions originating in the muscularis mucosa or submucosa. For tumors originating in the muscularis propria, we performed partial resection limited to the covering mucosa to expose the lesion and obtained a sample with standard biopsy forceps. Results: Sufficient samples were obtained in all 54 cases. There was no perforation. Bleeding occurred in only 5 cases (9%) and was easily managed with endoscopic hemostatic methods. EUS and pathologic findings coincided in 74.1% of cases (40 of 54). Benign lesions (leiomyoma, aberrant pancreas, and others) were predominant (52 of 54), although 2 small lesions were confirmed at pathologic study to be malignant (leiomyosarcoma and leiomyoblastoma). Conclusions: Endoscopic resection based on EUS findings proved to be an effective and safe method to confirm the histologic diagnosis of submucosal tumor of the upper GI tract. Endoscopic resection should be considered a valuable choice for definitive management of benign submucosal tumors originating in the superficial layers. (Gastrointest Endosc 1999;50:516-22.)
Mass screening for gastric cancer in Japan was begun in the 1970s. The widespread use of panendoscopy led to the detection of many submucosal tumors (SMTs), relatively common lesions in the upper GI tract, with an incidence estimated to be about 0.3%.1 Most of these lesions do not cause symptoms and are found incidentally during radiographic or endoscopic examinations. Before the advent of therapeutic endoscopy, treatment consisted of surgical excision.2 A conservative attitude (endoscopic follow-up evaluation without pathologic diagnosis) has been the rule for asymptomatic lesions, and surgical resection has been considered appropriate for lesions that cause symptoms (pain, bleeding) and those larger than 3 cm in diameter because of risk for malignancy.3,4 Received September 1, 1998. For revision December 17, 1998. Accepted March 17, 1999. From the Division of Gastroenterology, Department of Internal Medicine, Fujigaoka Hospital, Showa University, Yokohama, Japan. Presented in a poster session at the annual meeting of the American Gastroenterological Association, May 17-20, 1998, New Orleans, Louisiana. Reprint requests: Hiroshi Takahashi MD, Endoscopy Unit, Fujigaoka Hospital, Showa University, 1-30 Fujigaoka, Aoba-ku, Yokohama, 227-8501, Japan. Copyright © 1999 by the American Society for Gastrointestinal Endoscopy 0016-5107/99/$8.00 + 0 37/1/98590 516
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EUS helps differentiate true SMTs from extrinsic lesions and large intraluminal and extraluminal vessels and helps determine the layer of origin in the GI tract. Although some of these tumors have distinct EUS features,5 definitive diagnosis is only by means of pathologic confirmation. Different biopsy techniques have been described to obtain tissue for pathologic examination, but sampling is not always sufficient for diagnosis.6-10 Endoscopic resection (ER) techniques by means of which large specimens can be obtained have been suggested for the diagnosis and management of SMTs.11-15 Nevertheless, such wide resections have associated risks. The aim of this study was to evaluate the diagnostic and therapeutic usefulness and safety of ER based on EUS findings in 54 cases of SMT of the upper GI tract. PATIENTS AND METHODS A total of 54 patients diagnosed with SMT of the upper GI tract who underwent ER from January 1986 to June 1998 were included in this study. There was no gender predominance (31 men, 23 women); the age range was 21 to 76 years (average 53.7 years). Written informed consent was obtained from each patient. All the patients underwent routine upper endoscopy (GIF Q10-XQ200-Q230; Olympus Optical Co., Tokyo, Japan) followed by EUS (Olympus GF-UM20, 7.5 to 12 MHz; Olympus UM3R, 20 MHz). Interpretation was based on the five-layer structure of the wall.16,17 From 1986 to 1992 the Olympus GFVOLUME 50, NO. 4, 1999
Diagnosis of upper GI tract submucosal tumor by endoscopic resection
UM20 system was used in all cases and thereafter the echoprobe UM3R (Olympus). The probe is easier to use and has improved axial resolution, but penetration depth is less than that with conventional EUS; therefore in the latter phases of the study, both the GF-UM20 and the UM3R were used for large lesions. The originating layer in the wall structure, echodensity, and shape and size of the tumor were assessed. None of the tumors exhibited any sign of malignancy at endoscopy or EUS. The ER method was based on the EUS layer of origin and location of the tumor. The en bloc technique, intended to resect the entire tumor in one piece, was attempted for lesions originating and located either at the muscularis mucosae or submucosal layers. The open biopsy method, intended to resect only the covering mucosa and obtain biopsy specimens directly from the exposed tumor, was attempted on lesions originating from the muscularis propria. En bloc resection was performed with a doublechannel videoscope (Olympus GIF 2T20-2T200). In brief, the technique is as follows. While the mucosa is lifted with a 19.4 mm grasping forceps (Olympus FG-47L-1), the tumor is stripped with a polypectomy snare (Olympus SD5L-1) inserted through the remaining accessory channel. The forceps is retrieved and saline solution (2 to 5 mL) is injected with a needle catheter (Olympus NM-8L) into the submucosa beneath the lesion. The tumor is resected with high-frequency electrosurgical current (blend wave, 60 W; Olympus PSD-10). Blended current was adopted to minimize risk for bleeding associated with pure cutting current and the burning effect associated with coagulation current. The open biopsy method is similar to en bloc resection but does not include injection of saline solution, which might push such lesions downward, preventing correct sampling. After resection of the overlying mucosa, several biopsy specimens are obtained from the exposed SMT, as in the combined technique of strip biopsy and bite biopsy described by Karita and Tada.18 Mechanical closure with hemoclips was performed after en bloc resection when the resulting ulcer was wide and the endoscopist was confident that complete resection had been accomplished.19 Endoscopy was performed 2 days after resection before initiation of oral feeding and 1 week later before discharge. Both studies were intended to assess healing and detect hemorrhagic signs such as exposed vessels. Followup endoscopy was performed every 6 months for the first year and annually thereafter.
RESULTS Samples sufficient for histopathologic confirmation were obtained in all 54 cases. Complete resection of the lesions was confirmed histopathologically. The total number of lesions in the esophagus was 26. Among them, EUS findings revealed 7 originating in the muscularis mucosae, 10 in the submucosa layer, and 9 in the muscularis propria (Table 1). En bloc resection was performed in 17 cases, and the open biopsy method was used for the remaining 9 deeper lesions (Fig. 1). There was no perforation; 2 cases (8%) were complicated by bleeding that was VOLUME 50, NO. 4, 1999
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A
B
C Figure 1. A, Endoscopic appearance of esophageal submucosal tumor. B, EUS image shows inhomogeneous, hypoechoic lesion arising from the third sonographic layer (sm). C, Photomicrograph of a low-power microscopic view. The 11 × 10 mm tumor was totally resected. Histopathologic findings were those of esophageal granular cell tumor. (H&E, orig. mag. ×4).
easily controlled with hemoclips. Among the 23 gastric SMTs, EUS showed that 3 lesions arose from the muscularis mucosae, 15 from the submucosa, and 5 from the muscularis propria (Table 2). En bloc resection was accomplished in 14 cases and open biopsy in the remaining 9. Mild bleeding occurred in only 1 case (4.7%) and was GASTROINTESTINAL ENDOSCOPY
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Diagnosis of upper GI tract submucosal tumor by endoscopic resection
Table 1. EUS and pathologic findings and resection method of esophageal submucosal tumors EUS Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26
Depth mm sm mm sm mp sm mm sm mm mp mp mm mp mp sm mm mm mp sm sm sm mp sm sm mp mp
Resection
Diagnosis Leiomyoma Granular cell Cyst Granular cell Leiomyoma Indefinite Indefinite Leiomyoma Indefinite Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Indefinite Leiomyoma Leiomyoma Leiomyoma Granular cell Granular cell Leiomyoma Leiomyoma Granular cell Granular cell Cyst Leiomyoma
Size (mm) tumor tumor
tumor tumor
tumor tumor
6 12.8 8 10 13 7 10 9 5 7 8 10 13 15 10 13 14 16 12 13 12 16 13 11 20 8.4
Pathologic finding Leiomyoma Granular cell Leiomyoma Granular cell Leiomyoma Granular cell Leiomyoma Cyst Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Granular cell Leiomyoma Leiomyoma Leiomyoma Granular cell Granular cell Leiomyoma Leiomyoma
tumor tumor tumor
tumor
tumor tumor
En bloc
Open biopsy
O — O O — O O — O O O O — — O O O — O O O — O O — —
— O — — O — — O — — — — O O — — — O — — — O — — O O
Complication — — — — Bleeding — — — — — Bleeding — — — — — — — — — — — — — — —
mm, Muscularis mucosae; sm, submucosa; mp, muscularis propria.
managed with hemoclips. There were 5 SMTs of the duodenum, all arising from the submucosa according to EUS findings (Table 3). En bloc resection was achieved in 3 cases, and bleeding easily controlled with hemoclips occurred in 2 cases. The average size of the tumors measured by means of EUS was 13.5 mm (range 5 to 28 mm). By anatomic location, the average sizes of the lesions were 11.2 ± 3.5 mm for the esophagus, 16.3 ± 5.1 mm for the stomach, and 12.2 ± 3.9 mm for the duodenum. None of the lesions had EUS findings indicating malignancy.3,20 There was no significant difference in difficulty with regard to technique between the various locations in the upper GI tract, though in some cases, in particular the posterior wall of the body, use of a side-viewing endoscope seemed to facilitate the procedure. Histopathologic examination showed that in the esophagus there was a predominance of leiomyoma (19 cases) (Table 1). Use of EUS led to correct diagnosis of 11 of 18 (61.1%) leiomyomas and 5 of 6 granular cell tumors. Histopathologic examination of gastric specimens revealed a predominance of benign lesions (Table 2), but there also was 1 case each of leiomyoblastoma, leiomyosarcoma, and granular cell tumor. The last 3 lesions were diagnosed at EUS as leiomyoma. With the aberrant 518
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pancreas lesions, positive correlation between EUS and histopathologic findings was obtained in all 6 cases. The final histopathologic diagnoses of duodenal SMTs are shown in Table 3. EUS findings coincided with pathologic findings in all the cases except the lipoma. There were 2 cases in which bleeding developed 1 and 7 days after resection; in both cases the bleeding was managed with hemoclips. Bleeding occurred in a total of 5 patients (4 immediate, 1 delayed), all of them treated successfully with hemoclipping; no transfusions were necessary. After resection, EUS findings and histopathologic diagnoses were compared. The overall accuracy of EUS regarding layer of origin and location of lesion was 79.6% (43 of 54); 6 lesions were located deeper in the GI wall than estimated with EUS, and 5 lesions more superficial. The EUS and pathologic diagnoses matched in 74.1% of cases (40 of 54). There was no recurrence during the follow-up period among the patients who underwent successful en bloc resection (including the gastric granular cell tumor), and no retreatment was performed in the other cases. The mean follow-up period was 14.6 months (range 3 to 70 months). The two malignant lesions (leiomyosarcoma and leiomyoblastoma) diagnosed by means of open biopsy were resected VOLUME 50, NO. 4, 1999
Diagnosis of upper GI tract submucosal tumor by endoscopic resection
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Table 2. EUS and pathologic findings and method of resection of gastric submucosal tumors EUS Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Depth
Diagnosis
sm mp mm mp sm sm sm sm sm sm sm mp sm mm sm mm sm mp sm sm sm mp sm
Leiomyoma Leiomyoma Indefinite Granular cell tumor Leiomyoma Indefinite Lipoma Aberrant pancreas Leiomyoma Aberrant pancreas Aberrant pancreas Leiomyoma Aberrant pancreas Aberrant pancreas Aberrant pancreas Leiomyoma Leiomyoma Leiomyoma Leiomyoma Lipoma Leiomyoma Leiomyoma Lipoma
Resection Size (mm) 13 18 15 28 12 21 19 21 12 8 13 17 15 12 12 10 15 15 25 14 20 25 15
Pathologic finding Leiomyoma Leiomyoma Neurofibroma Leiomyoma Neurinoma Lipoma Leiomyoma Aberrant pancreas Leiomyoma Aberrant pancreas Aberrant pancreas Leiomyoblastoma Aberrant pancreas Aberrant pancreas Aberrant pancreas Granular cell tumor Leiomyoma Leiomyoma Leiomyoma Lipoma Leiomyoma Leiomyosarcoma Leiomyoma
En bloc
Open biopsy
O — O — O O O O O O — — O O O O — O — — — — O
— O — O — — — — — — O O — — — — O — O O O O —
Complication — — — — — — — — — — — — bleeding — — — — — — — — — —
mm, Muscularis mucosae; sm, submucosa; mp, muscularis propria.
Table 3. EUS and pathologic findings and method of resection of duodenal submucosal tumors EUS Patient No.
Depth
1 2 3 4
sm sm sm sm
5
sm
Diagnosis Indefinite Carcinoid Carcinoid Brunner’s gland hyperplasia Carcinoid
Resection Size (mm)
Pathologic finding
13 18 15 28 12
Lipoma Carcinoid Carcinoid Brunner’s gland hyperplasia Carcinoid
En bloc
Open biopsy
Complication
O O — O
— — O —
— Bleeding — —
—
O
Bleeding
mm, Muscularis mucosae; sm, submucosa; mp, muscularis propria.
surgically. Neither of them had any malignant features at EUS and both were in an early stage (T1N0M0) without evidence of recurrence or distant metastasis after 9 and 50 months. DISCUSSION EUS is helpful in assessing the layer of origin, size, consistency, and extension of SMTs and differentiating them from extrinsic compressions.21-24 However, some studies have found no significant differences between benign and malignant lesions with regard to homogeneity of internal echo pattern or marginal echo pattern4; thus differentiation of leiomyoma from leiomyosarcoma by means of EUS is thought to be difficult or impossible unless there is local extension or metastasis.17,25 Histologic diagnosis is necessary not only to ascertain whether a lesion is benign or malignant—principally larger VOLUME 50, NO. 4, 1999
lesions with irregular borders, inhomogeneous areas, or eroded surfaces—but also to detect smaller lesions without malignant morphologic features. In the past some authors advised conservative management of benign gastric SMTs; others believed that endoscopic follow-up evaluation without surgery was not reasonable.26 Many techniques have been developed for definitive diagnosis of SMT. A radiologic technique, submucosography (based on injection of contrast medium into the submucosal layer), has been used to assess tumor growth pattern, but this procedure seems to present difficulties in interpretation and does not provide histologic confirmation.27,28 Wiersema et al.29 and Giovannini et al.30 separately described the combination of EUS and EUS-guided fine-needle aspiration as a diagnostic method for SMT. However, the relatively small specimens GASTROINTESTINAL ENDOSCOPY
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A
B Figure 2. A, Endoscopic view of 10 mm esophageal granular cell tumor. B, Endoscopic appearance after complete closure with hemoclips of the post-resection ulcer.
obtained with this method make it difficult to differentiate benign from malignant tumors. Therefore normal findings do not exclude the possibility of malignancy.6,7,29,30 The guillotine needle biopsy technique described by Caletti et al.9 is safe, although histologic confirmation would necessitate up to three consecutive procedures. Another study28 showed that endoscopic treatment including electrocauterization and topical injection of absolute ethanol as an alternative in the management of upper GI SMTs had few complications and that this is probably the best option for patients at high risk. A jumbo forceps can be used in conjunction with a tunneling technique to obtain sufficient sampling of some lesions. However, bleeding as a complication of this technique may be troublesome.8,31 Takahashi and Fujita11 and Yu et al.32 separately reported that ER is a safe method for obtaining tissue for histologic diagnosis. Kawamoto et al.33 found endoscopic submucosal tumorectomy to be useful but restricted the technique to lesions limited to the submucosa. 520
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Hyun et al.34 resected SMTs of the esophagus by means of two different endoscopic methods based on the diameter of the lesion. In our study the EUS findings were an important determinant of therapeutic method. We used a doublechannel endoscope and the technique described by Tada et al.35 for epithelial lesions. This technique allows both en bloc resection and procurement of biopsy specimens and seems to have few complications compared with other ER techniques.36 EUS has been shown to be more accurate than CT in assessing the exact local and regional extension of a tumor and in differentiating extraluminal compression.37-39 In our study the overall diagnostic accuracy of EUS was only 74.1%. This low percentage is undoubtedly due to the relatively small size of the lesions, especially the two malignant lesions that did not exhibit features suggestive of malignancy.3,20 Technical difficulties associated with EUS include inadequate positioning of the echoprobe or echoendoscope near the target lesion and problems interpreting EUS images because of the small field of view in some cases.25 We agree with others28,40 that, because of the possibility of perforation, complete resection of tumors originating in the muscularis propria should be avoided; for this reason, EUS is important in deciding which ER method to use. For tumors originating in the muscularis propria, only resection of the covering mucosa to expose the tumor and obtain tissue for histologic confirmation with an ordinary forceps should be performed. ER of SMTs arising in the muscularis propria had only diagnostic objectives. Mechanical closure with hemoclips was performed after en bloc resection when the resulting ulcer was wide and the endoscopist was confident that complete resection had been accomplished (Fig. 2). In our experience this prevents delayed bleeding and accelerates healing.19 None of the 27 patients in whom closure was performed had bleeding. Effective permanent hemostasis was achieved by means of hemoclipping in the 5 patients in whom bleeding developed (immediate in 4 cases and delayed in 1). We previously reported the utility of hemoclipping for bleeding after ER and for other causes of bleeding.41-43 We consider hemoclipping the method of first choice because it does not produce mucosal injury, as do other methods. Despite the low incidence, pathologic confirmation of malignant tumors was possible after ER in 2 cases, a leiomyosarcoma measuring 25 mm and a leiomyoblastoma measuring 17 mm. Neither was causing any symptoms. Lesions such as these have a more favorable prognosis than adenocarcinoma.25 The absence of malignant features at EUS might have led to endoscopic follow-up evaluations, in which VOLUME 50, NO. 4, 1999
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case the diagnosis would have been delayed. In conclusion, ER and tissue sampling based on EUS findings is a relatively low-risk procedure for definitive histologic diagnosis of SMT of the upper GI tract.
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19.
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41. Takahashi H, Fujita R, Sugiyama K, Suzuki S, Kohsen K, Seki M, et al. Endoscopic hemostasis in hemorrhagic gastric ulcer-effectiveness of the hemoclipping, ethanol injection and heat probe. Dig Endosc 1991;3:498-504. 42. Takahashi H, Ikeda T. Upper gastrointestinal bleeding and hemostatic effect of clip [Japanese with English abstract]. Prog Dig Endosc 1985;27:31-5. 43. Parra-Blanco A, Takahashi H, Mendez Jerez PV, Kojima T, Aksoz K, Kirihara K, et al. Endoscopic management of Dieulafoy lesions of the stomach: a case study of twenty six patients. Endoscopy 1997;29:834-9.
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Background: Submucosal tumors are frequent findings during endoscopy, although definitive diagnosis based on histologic confirmation presents some difficulties. The aim of this study was to evaluate the efficacy and safety of endoscopic resection based on endoscopic ultrasonography (EUS) findings to reach a definitive diagnosis of submucosal tumor. Methods: Fifty-four submucosal tumors of the upper gastrointestinal (GI) tract were included in this study. EUS was performed to determine the layer of origin and location of the lesion and to rule out malignancy. En bloc resection was attempted for lesions originating in the muscularis mucosa or submucosa. For tumors originating in the muscularis propria, we performed partial resection limited to the covering mucosa to expose the lesion and obtained a sample with standard biopsy forceps. Results: Sufficient samples were obtained in all 54 cases. There was no perforation. Bleeding occurred in only 5 cases (9%) and was easily managed with endoscopic hemostatic methods. EUS and pathologic findings coincided in 74.1% of cases (40 of 54). Benign lesions (leiomyoma, aberrant pancreas, and others) were predominant (52 of 54), although 2 small lesions were confirmed at pathologic study to be malignant (leiomyosarcoma and leiomyoblastoma). Conclusions: Endoscopic resection based on EUS findings proved to be an effective and safe method to confirm the histologic diagnosis of submucosal tumor of the upper GI tract. Endoscopic resection should be considered a valuable choice for definitive management of benign submucosal tumors originating in the superficial layers. (Gastrointest Endosc 1999;50:516-22.)
Mass screening for gastric cancer in Japan was begun in the 1970s. The widespread use of panendoscopy led to the detection of many submucosal tumors (SMTs), relatively common lesions in the upper GI tract, with an incidence estimated to be about 0.3%.1 Most of these lesions do not cause symptoms and are found incidentally during radiographic or endoscopic examinations. Before the advent of therapeutic endoscopy, treatment consisted of surgical excision.2 A conservative attitude (endoscopic follow-up evaluation without pathologic diagnosis) has been the rule for asymptomatic lesions, and surgical resection has been considered appropriate for lesions that cause symptoms (pain, bleeding) and those larger than 3 cm in diameter because of risk for malignancy.3,4 Received September 1, 1998. For revision December 17, 1998. Accepted March 17, 1999. From the Division of Gastroenterology, Department of Internal Medicine, Fujigaoka Hospital, Showa University, Yokohama, Japan. Presented in a poster session at the annual meeting of the American Gastroenterological Association, May 17-20, 1998, New Orleans, Louisiana. Reprint requests: Hiroshi Takahashi MD, Endoscopy Unit, Fujigaoka Hospital, Showa University, 1-30 Fujigaoka, Aoba-ku, Yokohama, 227-8501, Japan. Copyright © 1999 by the American Society for Gastrointestinal Endoscopy 0016-5107/99/$8.00 + 0 37/1/98590 516
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EUS helps differentiate true SMTs from extrinsic lesions and large intraluminal and extraluminal vessels and helps determine the layer of origin in the GI tract. Although some of these tumors have distinct EUS features,5 definitive diagnosis is only by means of pathologic confirmation. Different biopsy techniques have been described to obtain tissue for pathologic examination, but sampling is not always sufficient for diagnosis.6-10 Endoscopic resection (ER) techniques by means of which large specimens can be obtained have been suggested for the diagnosis and management of SMTs.11-15 Nevertheless, such wide resections have associated risks. The aim of this study was to evaluate the diagnostic and therapeutic usefulness and safety of ER based on EUS findings in 54 cases of SMT of the upper GI tract. PATIENTS AND METHODS A total of 54 patients diagnosed with SMT of the upper GI tract who underwent ER from January 1986 to June 1998 were included in this study. There was no gender predominance (31 men, 23 women); the age range was 21 to 76 years (average 53.7 years). Written informed consent was obtained from each patient. All the patients underwent routine upper endoscopy (GIF Q10-XQ200-Q230; Olympus Optical Co., Tokyo, Japan) followed by EUS (Olympus GF-UM20, 7.5 to 12 MHz; Olympus UM3R, 20 MHz). Interpretation was based on the five-layer structure of the wall.16,17 From 1986 to 1992 the Olympus GFVOLUME 50, NO. 4, 1999
Diagnosis of upper GI tract submucosal tumor by endoscopic resection
UM20 system was used in all cases and thereafter the echoprobe UM3R (Olympus). The probe is easier to use and has improved axial resolution, but penetration depth is less than that with conventional EUS; therefore in the latter phases of the study, both the GF-UM20 and the UM3R were used for large lesions. The originating layer in the wall structure, echodensity, and shape and size of the tumor were assessed. None of the tumors exhibited any sign of malignancy at endoscopy or EUS. The ER method was based on the EUS layer of origin and location of the tumor. The en bloc technique, intended to resect the entire tumor in one piece, was attempted for lesions originating and located either at the muscularis mucosae or submucosal layers. The open biopsy method, intended to resect only the covering mucosa and obtain biopsy specimens directly from the exposed tumor, was attempted on lesions originating from the muscularis propria. En bloc resection was performed with a doublechannel videoscope (Olympus GIF 2T20-2T200). In brief, the technique is as follows. While the mucosa is lifted with a 19.4 mm grasping forceps (Olympus FG-47L-1), the tumor is stripped with a polypectomy snare (Olympus SD5L-1) inserted through the remaining accessory channel. The forceps is retrieved and saline solution (2 to 5 mL) is injected with a needle catheter (Olympus NM-8L) into the submucosa beneath the lesion. The tumor is resected with high-frequency electrosurgical current (blend wave, 60 W; Olympus PSD-10). Blended current was adopted to minimize risk for bleeding associated with pure cutting current and the burning effect associated with coagulation current. The open biopsy method is similar to en bloc resection but does not include injection of saline solution, which might push such lesions downward, preventing correct sampling. After resection of the overlying mucosa, several biopsy specimens are obtained from the exposed SMT, as in the combined technique of strip biopsy and bite biopsy described by Karita and Tada.18 Mechanical closure with hemoclips was performed after en bloc resection when the resulting ulcer was wide and the endoscopist was confident that complete resection had been accomplished.19 Endoscopy was performed 2 days after resection before initiation of oral feeding and 1 week later before discharge. Both studies were intended to assess healing and detect hemorrhagic signs such as exposed vessels. Followup endoscopy was performed every 6 months for the first year and annually thereafter.
RESULTS Samples sufficient for histopathologic confirmation were obtained in all 54 cases. Complete resection of the lesions was confirmed histopathologically. The total number of lesions in the esophagus was 26. Among them, EUS findings revealed 7 originating in the muscularis mucosae, 10 in the submucosa layer, and 9 in the muscularis propria (Table 1). En bloc resection was performed in 17 cases, and the open biopsy method was used for the remaining 9 deeper lesions (Fig. 1). There was no perforation; 2 cases (8%) were complicated by bleeding that was VOLUME 50, NO. 4, 1999
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A
B
C Figure 1. A, Endoscopic appearance of esophageal submucosal tumor. B, EUS image shows inhomogeneous, hypoechoic lesion arising from the third sonographic layer (sm). C, Photomicrograph of a low-power microscopic view. The 11 × 10 mm tumor was totally resected. Histopathologic findings were those of esophageal granular cell tumor. (H&E, orig. mag. ×4).
easily controlled with hemoclips. Among the 23 gastric SMTs, EUS showed that 3 lesions arose from the muscularis mucosae, 15 from the submucosa, and 5 from the muscularis propria (Table 2). En bloc resection was accomplished in 14 cases and open biopsy in the remaining 9. Mild bleeding occurred in only 1 case (4.7%) and was GASTROINTESTINAL ENDOSCOPY
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Table 1. EUS and pathologic findings and resection method of esophageal submucosal tumors EUS Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26
Depth mm sm mm sm mp sm mm sm mm mp mp mm mp mp sm mm mm mp sm sm sm mp sm sm mp mp
Resection
Diagnosis Leiomyoma Granular cell Cyst Granular cell Leiomyoma Indefinite Indefinite Leiomyoma Indefinite Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Indefinite Leiomyoma Leiomyoma Leiomyoma Granular cell Granular cell Leiomyoma Leiomyoma Granular cell Granular cell Cyst Leiomyoma
Size (mm) tumor tumor
tumor tumor
tumor tumor
6 12.8 8 10 13 7 10 9 5 7 8 10 13 15 10 13 14 16 12 13 12 16 13 11 20 8.4
Pathologic finding Leiomyoma Granular cell Leiomyoma Granular cell Leiomyoma Granular cell Leiomyoma Cyst Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Leiomyoma Granular cell Leiomyoma Leiomyoma Leiomyoma Granular cell Granular cell Leiomyoma Leiomyoma
tumor tumor tumor
tumor
tumor tumor
En bloc
Open biopsy
O — O O — O O — O O O O — — O O O — O O O — O O — —
— O — — O — — O — — — — O O — — — O — — — O — — O O
Complication — — — — Bleeding — — — — — Bleeding — — — — — — — — — — — — — — —
mm, Muscularis mucosae; sm, submucosa; mp, muscularis propria.
managed with hemoclips. There were 5 SMTs of the duodenum, all arising from the submucosa according to EUS findings (Table 3). En bloc resection was achieved in 3 cases, and bleeding easily controlled with hemoclips occurred in 2 cases. The average size of the tumors measured by means of EUS was 13.5 mm (range 5 to 28 mm). By anatomic location, the average sizes of the lesions were 11.2 ± 3.5 mm for the esophagus, 16.3 ± 5.1 mm for the stomach, and 12.2 ± 3.9 mm for the duodenum. None of the lesions had EUS findings indicating malignancy.3,20 There was no significant difference in difficulty with regard to technique between the various locations in the upper GI tract, though in some cases, in particular the posterior wall of the body, use of a side-viewing endoscope seemed to facilitate the procedure. Histopathologic examination showed that in the esophagus there was a predominance of leiomyoma (19 cases) (Table 1). Use of EUS led to correct diagnosis of 11 of 18 (61.1%) leiomyomas and 5 of 6 granular cell tumors. Histopathologic examination of gastric specimens revealed a predominance of benign lesions (Table 2), but there also was 1 case each of leiomyoblastoma, leiomyosarcoma, and granular cell tumor. The last 3 lesions were diagnosed at EUS as leiomyoma. With the aberrant 518
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pancreas lesions, positive correlation between EUS and histopathologic findings was obtained in all 6 cases. The final histopathologic diagnoses of duodenal SMTs are shown in Table 3. EUS findings coincided with pathologic findings in all the cases except the lipoma. There were 2 cases in which bleeding developed 1 and 7 days after resection; in both cases the bleeding was managed with hemoclips. Bleeding occurred in a total of 5 patients (4 immediate, 1 delayed), all of them treated successfully with hemoclipping; no transfusions were necessary. After resection, EUS findings and histopathologic diagnoses were compared. The overall accuracy of EUS regarding layer of origin and location of lesion was 79.6% (43 of 54); 6 lesions were located deeper in the GI wall than estimated with EUS, and 5 lesions more superficial. The EUS and pathologic diagnoses matched in 74.1% of cases (40 of 54). There was no recurrence during the follow-up period among the patients who underwent successful en bloc resection (including the gastric granular cell tumor), and no retreatment was performed in the other cases. The mean follow-up period was 14.6 months (range 3 to 70 months). The two malignant lesions (leiomyosarcoma and leiomyoblastoma) diagnosed by means of open biopsy were resected VOLUME 50, NO. 4, 1999
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Table 2. EUS and pathologic findings and method of resection of gastric submucosal tumors EUS Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Depth
Diagnosis
sm mp mm mp sm sm sm sm sm sm sm mp sm mm sm mm sm mp sm sm sm mp sm
Leiomyoma Leiomyoma Indefinite Granular cell tumor Leiomyoma Indefinite Lipoma Aberrant pancreas Leiomyoma Aberrant pancreas Aberrant pancreas Leiomyoma Aberrant pancreas Aberrant pancreas Aberrant pancreas Leiomyoma Leiomyoma Leiomyoma Leiomyoma Lipoma Leiomyoma Leiomyoma Lipoma
Resection Size (mm) 13 18 15 28 12 21 19 21 12 8 13 17 15 12 12 10 15 15 25 14 20 25 15
Pathologic finding Leiomyoma Leiomyoma Neurofibroma Leiomyoma Neurinoma Lipoma Leiomyoma Aberrant pancreas Leiomyoma Aberrant pancreas Aberrant pancreas Leiomyoblastoma Aberrant pancreas Aberrant pancreas Aberrant pancreas Granular cell tumor Leiomyoma Leiomyoma Leiomyoma Lipoma Leiomyoma Leiomyosarcoma Leiomyoma
En bloc
Open biopsy
O — O — O O O O O O — — O O O O — O — — — — O
— O — O — — — — — — O O — — — — O — O O O O —
Complication — — — — — — — — — — — — bleeding — — — — — — — — — —
mm, Muscularis mucosae; sm, submucosa; mp, muscularis propria.
Table 3. EUS and pathologic findings and method of resection of duodenal submucosal tumors EUS Patient No.
Depth
1 2 3 4
sm sm sm sm
5
sm
Diagnosis Indefinite Carcinoid Carcinoid Brunner’s gland hyperplasia Carcinoid
Resection Size (mm)
Pathologic finding
13 18 15 28 12
Lipoma Carcinoid Carcinoid Brunner’s gland hyperplasia Carcinoid
En bloc
Open biopsy
Complication
O O — O
— — O —
— Bleeding — —
—
O
Bleeding
mm, Muscularis mucosae; sm, submucosa; mp, muscularis propria.
surgically. Neither of them had any malignant features at EUS and both were in an early stage (T1N0M0) without evidence of recurrence or distant metastasis after 9 and 50 months. DISCUSSION EUS is helpful in assessing the layer of origin, size, consistency, and extension of SMTs and differentiating them from extrinsic compressions.21-24 However, some studies have found no significant differences between benign and malignant lesions with regard to homogeneity of internal echo pattern or marginal echo pattern4; thus differentiation of leiomyoma from leiomyosarcoma by means of EUS is thought to be difficult or impossible unless there is local extension or metastasis.17,25 Histologic diagnosis is necessary not only to ascertain whether a lesion is benign or malignant—principally larger VOLUME 50, NO. 4, 1999
lesions with irregular borders, inhomogeneous areas, or eroded surfaces—but also to detect smaller lesions without malignant morphologic features. In the past some authors advised conservative management of benign gastric SMTs; others believed that endoscopic follow-up evaluation without surgery was not reasonable.26 Many techniques have been developed for definitive diagnosis of SMT. A radiologic technique, submucosography (based on injection of contrast medium into the submucosal layer), has been used to assess tumor growth pattern, but this procedure seems to present difficulties in interpretation and does not provide histologic confirmation.27,28 Wiersema et al.29 and Giovannini et al.30 separately described the combination of EUS and EUS-guided fine-needle aspiration as a diagnostic method for SMT. However, the relatively small specimens GASTROINTESTINAL ENDOSCOPY
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A
B Figure 2. A, Endoscopic view of 10 mm esophageal granular cell tumor. B, Endoscopic appearance after complete closure with hemoclips of the post-resection ulcer.
obtained with this method make it difficult to differentiate benign from malignant tumors. Therefore normal findings do not exclude the possibility of malignancy.6,7,29,30 The guillotine needle biopsy technique described by Caletti et al.9 is safe, although histologic confirmation would necessitate up to three consecutive procedures. Another study28 showed that endoscopic treatment including electrocauterization and topical injection of absolute ethanol as an alternative in the management of upper GI SMTs had few complications and that this is probably the best option for patients at high risk. A jumbo forceps can be used in conjunction with a tunneling technique to obtain sufficient sampling of some lesions. However, bleeding as a complication of this technique may be troublesome.8,31 Takahashi and Fujita11 and Yu et al.32 separately reported that ER is a safe method for obtaining tissue for histologic diagnosis. Kawamoto et al.33 found endoscopic submucosal tumorectomy to be useful but restricted the technique to lesions limited to the submucosa. 520
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Hyun et al.34 resected SMTs of the esophagus by means of two different endoscopic methods based on the diameter of the lesion. In our study the EUS findings were an important determinant of therapeutic method. We used a doublechannel endoscope and the technique described by Tada et al.35 for epithelial lesions. This technique allows both en bloc resection and procurement of biopsy specimens and seems to have few complications compared with other ER techniques.36 EUS has been shown to be more accurate than CT in assessing the exact local and regional extension of a tumor and in differentiating extraluminal compression.37-39 In our study the overall diagnostic accuracy of EUS was only 74.1%. This low percentage is undoubtedly due to the relatively small size of the lesions, especially the two malignant lesions that did not exhibit features suggestive of malignancy.3,20 Technical difficulties associated with EUS include inadequate positioning of the echoprobe or echoendoscope near the target lesion and problems interpreting EUS images because of the small field of view in some cases.25 We agree with others28,40 that, because of the possibility of perforation, complete resection of tumors originating in the muscularis propria should be avoided; for this reason, EUS is important in deciding which ER method to use. For tumors originating in the muscularis propria, only resection of the covering mucosa to expose the tumor and obtain tissue for histologic confirmation with an ordinary forceps should be performed. ER of SMTs arising in the muscularis propria had only diagnostic objectives. Mechanical closure with hemoclips was performed after en bloc resection when the resulting ulcer was wide and the endoscopist was confident that complete resection had been accomplished (Fig. 2). In our experience this prevents delayed bleeding and accelerates healing.19 None of the 27 patients in whom closure was performed had bleeding. Effective permanent hemostasis was achieved by means of hemoclipping in the 5 patients in whom bleeding developed (immediate in 4 cases and delayed in 1). We previously reported the utility of hemoclipping for bleeding after ER and for other causes of bleeding.41-43 We consider hemoclipping the method of first choice because it does not produce mucosal injury, as do other methods. Despite the low incidence, pathologic confirmation of malignant tumors was possible after ER in 2 cases, a leiomyosarcoma measuring 25 mm and a leiomyoblastoma measuring 17 mm. Neither was causing any symptoms. Lesions such as these have a more favorable prognosis than adenocarcinoma.25 The absence of malignant features at EUS might have led to endoscopic follow-up evaluations, in which VOLUME 50, NO. 4, 1999
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case the diagnosis would have been delayed. In conclusion, ER and tissue sampling based on EUS findings is a relatively low-risk procedure for definitive histologic diagnosis of SMT of the upper GI tract.
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19.
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41. Takahashi H, Fujita R, Sugiyama K, Suzuki S, Kohsen K, Seki M, et al. Endoscopic hemostasis in hemorrhagic gastric ulcer-effectiveness of the hemoclipping, ethanol injection and heat probe. Dig Endosc 1991;3:498-504. 42. Takahashi H, Ikeda T. Upper gastrointestinal bleeding and hemostatic effect of clip [Japanese with English abstract]. Prog Dig Endosc 1985;27:31-5. 43. Parra-Blanco A, Takahashi H, Mendez Jerez PV, Kojima T, Aksoz K, Kirihara K, et al. Endoscopic management of Dieulafoy lesions of the stomach: a case study of twenty six patients. Endoscopy 1997;29:834-9.
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