0016-5107/92/3806-0657$03.00 GASTROINTESTINAL ENDOSCOPY Copyright © 1992 by the American Society for Gastrointestinal Endoscopy
Endoscopic diagnosis of early carcinoma of the esophagus using Lugol's solution Keizo Sugimachi, MD, Kaoru Kitamura, MD Kinya Baba, MD, Masahiko Ikebe, MD Hiroyuki Kuwano, MD
Fukuoka, Japan Slnall esophageal lesions, particularly intraepithelial cancers, are extremely difficult to detect. We used Lugol's iodine solution with panendoscopic examination to detect the presence and spread of small squamous cell carcinomas of the esophagus. Serial histologic specimens of the surgically removed esophagus from 32 patients with Lugol's combined endoscopic diagnosis of early esophageal carcinoma were examined to determine the correlation between endoscopic and histologic findings. All of the early staged carcinomas clearly remained unstained by Lugol's solution. We believe that the application of Lugol's solution will greatly aid in instances when a suspicious mucosal lesion is noted, when the margin of the lesion is unclear, or when there is suspicion that a mucosal lesion may have been overlooked. (Gastrointest Endosc 1992;38:657-661)
Owing to the remarkable development and improvement of endoscopic techniques, and with the present widespread use of endoscopic esophageal biopsy under direct vision, early esophageal cancers are now being diagnosed with increasing frequency.l,2 Although only 0.75% (51 of 6719) of patients with esophageal carcinoma have either mucosal or submucosal carcinoma in Europe,3 since 1985 more than 20% of the patients undergoing a subtotal esophagectomy for carcinoma of the esophagus in our institution were diagnosed as having either mucosal or submucosal carcinoma of the esophagus.4 The diagnosis of early cancer of the esophagus by endoscopic examination may sometimes be difficult even for an experienced endoscopist. Therefore, in order not to overlook such lesions, a method of dyeing the esophageal mucosa with Lugol's solution has been devised. 5- 7 In patients with squamous cell carcinoma, Lugol's solution leads to a clear identification of the lesions. Normal squamous epithelium includes glycogen which interacts with the iodine in Lugol's solution and turns to a greenish brown hue, whereas squamous cell carcinoma does not include glycogen and does not become stained. The procedure described in this report Received September 30, 1991. For revision February 3, 1992. Accepted July 14, 1992. From the Department of Surgery II, Kyushu University, Fukuoka, Japan. Reprint requests: Keizo Sugimachi, MD, Department of Surg"ery II, Faculty of Medicine, Kyushu University, Fukuoka 812, Japan. VOLUME 38, NO.6, 1992
provides a reliable and accurate method for identifying small esophageal malignancies. PATIENTS AND METHODS
Between 1987 and 1990, a subtotal esophagectomy was performed on 156 patients with thoracic esophageal carcinoma in the Second Department of Surgery, Kyushu University Hospital. Of these, 32 patients (20.5%) with early stage squamous cell carcinoma of the esophagus were included in this study. There were 3 intraepithelial carcinomas, 10 mucosal carcinomas, and 19 submucosal carcinomas. Of these 32 patients, 10 had areas of dysplasia concomitant with the early stage carcinoma. There were 29 men and 3 women, and their ages ranged from 46 through 79 years, with an average of 64.3 ± 8.2 years. Both radiography and dye endoscopy with Lugol's solution' were performed on all patients pre-operatively. We instilled about 20 ml of 2% Lugol's solution via a polyethylene tube on the mucosal surface under direct vision, and biopsy specimens were taken from the unstained areas. Thereafter, various operations such as subtotal esophagectomy and lymph node dissection through a right thoracotomy and esophageal reconstruction with a gastric tube were carried out in one stage.s The resected specimens were stretched appropriately on a board with pins and fixed with 10% formalin. Subsequently, each specimen was serially sectioned into blocks 5-mm wide and 4-cm long. One side from each block was stained with hematoxylin and eosin and periodic acid-Schiff for histologic examination. We then conducted a comparative study on the pre-operative Lugol's combined endoscopy and postoperative histology. 657
RESULTS
None ofthe patients with intraepithelial or mucosal carcinoma had any symptoms (Table 1). On the other hand, 14 ofthe 19 patients with submucosal carcinoma Table 1. Chief complaints Depth of cancer invasion Complaints
epa (N
None Pyrosis Chest discomfort Slight dysphagia
= 3) 3
o o o
sm
mm (N
= 10) 10
o o
o
(N
= 19) 5 3 5 6
a ep, invasion limited to the epithelium; mm, invasion confined to the lamina muscularis mucosae; sm, invasion confined to submucosa.
did have symptoms; 3 had pyrosis, 5 had chest discomfort, and 6 had slight dysphagia. As for the 18 asymptomatic patients, in 6 cases early esophageal carcinoma was detected endoscopically at the time of a follow-up study for gastric ulcer. Endoscopic detection was done in the remaining 12 patients during a mass survey for gastric cancer. Table 2 shows the clinicopathologic findings in the 32 patients with early stage carcinoma, arranged in the order ofthe depth and size ofthe cancer. The sizes of early stage carcinomas ranged from 3 X 3 mm to 60 X 90 mm. The gross appearance of all of the cancers limited to the epithelium were of the superficial type. On the other hand, in the 29 patients with either mucosal cancer or submucosal cancer, there were 18 patients with an elevated type, 6 patients with a superficial type, and 5 patients with a depressed type. Of 32 early stage cancers, 9 were poorly differentiated
Table 2. Clinicopathologic findings in early stage carcinoma
Patient
Age/sex
Depth of cancer invasion
1 2 3 4b 5b 6b 7 8 9b
63/M 65/M 71/M 71/F 51/M 78/M 65/M 56/M 58/M 58/M 66/M 73/M 66/M 70/M 55/M 36/M 69/M 12/F 61/M 12/M 73/M 73/M 56/M 56/M 56/M 45/M 57/M 67/M 67/M 49/M 73/F 12/M
epa ep ep mm mm mm mm mm mm mm mm mm mm sm sm sm sm sm sm sm sm sm sm sm sm sm sm sm sm sm sm sm
lOb
11 12 13b 14 b 15 16 b 17 18 19 20 21 b 22 23 24 25 26 27 28 29b 30 31 32
Size of carcinoma (mm)
Gross type
Histopathologic findings
3x3 10 x 15 10 x 25 8 X 12 9 x 10 10 x 10 10 x 14 12 x 21 16 x 21 20 x 27 20 x 30 25 x 25 30 x 42 6x9 8 x 12 10 x 20 10 x 20 11 x 20 13 x 28 15 x 20 16 X 31 18 x 28 20 x 20 20 x 40 20 x 40 21 x 25 24 x 28 25 x 35 25 x 38 27 x 31 45 x 50 60 x 90
Superficial Superficial Superficial Superficial Superficial Superficial Superficial Elevated Depressed Superficial Superficial Elevated Depressed Depressed Elevated Elevated Elevated Elevated Elevated Elevated Elevated Elevated Elevated Elevated Depressed Depressed Elevated Elevated Elevated Elevated Elevated Elevated
Mod diff sq ca Mod diff sq ca Poor diff sq ca Mod diff sq ca Mod diff sq ca Well-diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Poorly diff sq ca Mod diff sq ca Poorly diff sq ca Poorly diff sq ca Poorly diff sq ca Well-diff sq ca Poorly diff sq ca Mod diff sq ca Poorly diff sq ca Mod diff sq ca Mod diff sq ca Poorly diff sq ca Mod diff sq ca Poorly diff sq ca Mod diff sq ca
a ep, invasion limited to the epithelium; mm, invasion confined to the lamina muscularis mucosae; sm, invasion confined to submucosa; mod diff sq ca, moderately differentiated squamous cancer; welldiff sq ca, well-differentiated squamous cancer; poorly diff sq ca, poorly differentiated squamous cancer. b Dysplasia was concomitant with cancer.
658
GASTROINTESTINAL ENDOSCOPY
squamous cell carcinomas, 21 moderately differentiated squamous cell carcinomas, and 2 well-differentiated squamous cell carcinomas. In 10 patients, areas of dysplasia were associated with early stage carcinoma. The dysplastic lesions were all superficial in type. Concerning the diagnosis of early stage cancer, 3 epithelial cancers and 10 dysplastic lesions showed no abnormal findings by double contrast radiography, regardless of size; no rigidity of the esophageal wall, no irregularity of the margin, and no ulceration (Table 3). Among the 10 cancers involving the lamina muscularis mucosa, no abnormal findings were recognized on radiography in case 4 (8 X 12 mm) and case 5 (9 X 12 mm). On the other hand, abnormal radiographic findings were found in 8 of 10 cases, suggesting that even in cancers with invasion only to the lamina Table 3. Diagnostic characteristics of early stage carcinoma and dysplasia Early carcinoma epa (N = 3) Radiography Rigidity of the wall Irregularity of margin Ulceration No abnormality Endoscopic findings Mucosal surface Smooth Granular Ulceration Elevated Margin Clear Unclear Gross type Elevated Superficial Depressed Lugol's stain Unstained Poorly stained Macroscopic findings of the resected specimen Mucosal surface Smooth Granular Ulceration Elevated Fine crinkles Disappeared Normal Recognition without Lugol Possible Impossible
0 0 0 3
mm sm (N = 10) (N = 19) 4
7 4
2
19 19 8 0
Figure 1. X-ray of the esophagus. Arrow shows an elevated lesion of the esophagus. 0 3 0 0
0 7 2 1
0 8 5 6
3 0
10 0
17 2
0 3 0
2 6 2
11
3 0
10 0
18 1
0 3 0 0
0 8 2 0
0 7 6 6
1 2
10 0
19 0
3 0
10 0
19 0
5
3
a ep, invasion limited to the epithelium; mm, invasion confined to the lamina muscularis mucosae; sm, invasion confined to submucosa.
VOLUME 38, NO.6, 1992
muscularis mucosa, larger lesions often yield some radiographic findings. In all of the submucosal cancers, abnormal radiographic findings were recognized. On the other hand, all of the early stage cancers, including three intraepithelial cancers, were accurately diagnosed pre-operatively by Lugol's combined endoscopic examination with biopsy. None of the mucosal surfaces of the early stage cancers observed by endoscopy were smooth, and all of the cancerous lesions were clearly not stained by Lugol's solution. The comparative study of pre-operative Lugol's combined endoscopic findings and histopathologic study of resected specimens confirmed that all of the cancerous lesions remained unstained by Lugol's solution, while some mucosal lesions with severe dysplasia also went unstained by Lugol's solution. Macroscopic findings of the resected specimens showed some abnormalities, such as granular surface, ulceration, elevation, disappearance of fine crinkles, and so forth, in all of the early stage cancers. As an illustrative case, patient 27, a 57-year-old man presented at our outpatient clinic complaining of slight dysphagia. X-rays of the esophagus revealed a 659
Figure 2. Endoscopic findings of the lesion. A, A tumor was found in the upper esophagus. B, When Lugol's solution was applied, an unstained lesion appeared on the oral side of the tumor (arrows). Not only the presence of the lesion, but also the spread of the lesion became clear.
Figure 4. The resected specimen. Spread of cancer invasion could not be judged exactly without Lugol's staining (A), whereas, when Lugol's solution was applied, the spread of invasion was clearly observed (B) (arrows).
tumorous lesion in the upper esophagus (Fig. 1). An elevated lesion was detected by endoscopy (Fig. 2A). When Lugol's stain was applied, an unstained lesion appeared at the oral site of the tumor (Fig. 2B). Not only the elevated lesion but also the unstained lesion were diagnosed to be moderately differentiated squamous cell carcinoma by biopsy (Fig. 3). A subtotal esophagectomy was performed, and the resected specimen was stretched on a board with pins (Fig. 4A) and Lugol's solution was then applied to the mucosal surface. The spread of the cancerous lesion became readily visible (Fig. 4B), and the size of the carcinoma was 24 x 28 mm. DISCUSSION
Figure 3. Biopsied specimen. Biopsy from the unstained lesion revealed moderately differentiated squamous cell carcinoma (H & E; original magnification x138).
660
The detection of carcinoma at an early stage is the most important factor in curing any cancer, and this is particularly so for patients with esophageal cancer. Before 1984, no mucosal or epithelial carcinoma was evident among our 99 patients who underwent esophagectomy. Since we began to apply Lugol's solution during the endoscopic examination in 1984, early stage GASTROINTESTINAL ENDOSCOPY
esophageal carcinomas now account for 20% of the operated esophageal carcinomas in our institution. These findings indicate that combined endoscopy with Lugol's solution and an endoscopic biopsy are the most efficient tools for detecting early carcinoma of the esophagus, in addition to helping to delineate the margin of involvement of carcinoma, many of which were not evident on the x-ray. The characteristics of early carcinoma on endoscopic examination are: (1) a granular change of the mucosal surface with a clear margin, (2) a slight ulceration or elevation, and (3) an unstained lesion with Lugol's solution. A Chinese team has also reported that cytology can be an extremely efficacious method of detecting invisible lesions,9 especially for screening. In contrast, Lugol's combined endoscopy is not a screening method, but was successfully applied to detect the presence of cancer and the spread of cancerous lesions in the esophagus. Early stage esophageal carcinoma has been reported to cause no symptoms in 16% to 34% of patients. 3 , 4, 10 When asymptomatic, it is usually detected by chance during an examination for another disease of the gastrointestinal tract or during a surveillance procedure. In the United States and Europe, early esophageal carcinoma is still rarely diagnosed. In one study, only 51 early esophageal carcinomas (0.75%) were identified out of 6719 esophageal carcinomas, in spite of the fact that endoscopy is widely used. 3 Since barium
VOLUME 38, NO.6, 1992
usually passes rapidly in the absence of esophageal stenosis, small esophageal lesions may easily be overlooked. An endoscopic diagnostic approach is therefore more effective, because the color of the lesion is generally distinct. In addition to the gross appearance, dye spraying with Lugol's solution during the procedure is very simple, and can provide more precise information regarding the presence and spread of small lesions.
REFERENCES 1. Misumi A, Harada K, Murakami A, et al. Early diagnosis of esophageal cancer. Ann Surg 1989;210:732-9. 2. Levine MS, Dillon EC, Saul SH, Laufer I. Early esophageal cancer. AJR 1986;146:507-12.
3. Froelicher P, Miller G. The European experience with esophageal cancer limited to the mucosa and submucosa. Gastrointest Endosc 1986;32:88-90. 4. Sugimachi K, Ohno S, Matsuda H, Mori M, Kuwano H. Lugolcombined endoscopic detection of minute malignant lesions of the thoracic esophagus. Ann Surg 1988;208:179-83. 5. Brodmerkel GJ. Shiller's test: an aid in esophagoscopic diagnosis. Gastroenterology 1971;60:813. 6. Nishizawa M, Okada T, Hosoi T, Makino T. Detecting early esophageal cancers, with special reference to the intraepithelial stage. Endoscopy 1984;16:92-4. 7. Shiozaki H, Tahara H, Kobayashi K, et al. Endoscopic screening of early esophageal cancer with the Lugol dye method in patients with head and neck cancers. Cancer 1990;66:2068-71. 8. Sugimachi K, Yaita A, Ueo H, Natsuda Y, Inokuchi K. A safer and more reliable operative technique for esophageal reconstruction using a gastric tube. Am J Surg 1980;140:471-4. 9. Yang G, Huang H, Qui S, Chang Y. Endoscopic diagnosis of 115 cases of early esophageal carcinoma. Endoscopy 1982;14:157-61. 10. Endo M, Takeshita K, Yoshida M. How can we diagnose the early stage of esophageal cancer? Endoscopy 1986;18:11-8.
661
Endoscopic diagnosis of early carcinoma of the esophagus using Lugol's solution Keizo Sugimachi, MD, Kaoru Kitamura, MD Kinya Baba, MD, Masahiko Ikebe, MD Hiroyuki Kuwano, MD
Fukuoka, Japan Slnall esophageal lesions, particularly intraepithelial cancers, are extremely difficult to detect. We used Lugol's iodine solution with panendoscopic examination to detect the presence and spread of small squamous cell carcinomas of the esophagus. Serial histologic specimens of the surgically removed esophagus from 32 patients with Lugol's combined endoscopic diagnosis of early esophageal carcinoma were examined to determine the correlation between endoscopic and histologic findings. All of the early staged carcinomas clearly remained unstained by Lugol's solution. We believe that the application of Lugol's solution will greatly aid in instances when a suspicious mucosal lesion is noted, when the margin of the lesion is unclear, or when there is suspicion that a mucosal lesion may have been overlooked. (Gastrointest Endosc 1992;38:657-661)
Owing to the remarkable development and improvement of endoscopic techniques, and with the present widespread use of endoscopic esophageal biopsy under direct vision, early esophageal cancers are now being diagnosed with increasing frequency.l,2 Although only 0.75% (51 of 6719) of patients with esophageal carcinoma have either mucosal or submucosal carcinoma in Europe,3 since 1985 more than 20% of the patients undergoing a subtotal esophagectomy for carcinoma of the esophagus in our institution were diagnosed as having either mucosal or submucosal carcinoma of the esophagus.4 The diagnosis of early cancer of the esophagus by endoscopic examination may sometimes be difficult even for an experienced endoscopist. Therefore, in order not to overlook such lesions, a method of dyeing the esophageal mucosa with Lugol's solution has been devised. 5- 7 In patients with squamous cell carcinoma, Lugol's solution leads to a clear identification of the lesions. Normal squamous epithelium includes glycogen which interacts with the iodine in Lugol's solution and turns to a greenish brown hue, whereas squamous cell carcinoma does not include glycogen and does not become stained. The procedure described in this report Received September 30, 1991. For revision February 3, 1992. Accepted July 14, 1992. From the Department of Surgery II, Kyushu University, Fukuoka, Japan. Reprint requests: Keizo Sugimachi, MD, Department of Surg"ery II, Faculty of Medicine, Kyushu University, Fukuoka 812, Japan. VOLUME 38, NO.6, 1992
provides a reliable and accurate method for identifying small esophageal malignancies. PATIENTS AND METHODS
Between 1987 and 1990, a subtotal esophagectomy was performed on 156 patients with thoracic esophageal carcinoma in the Second Department of Surgery, Kyushu University Hospital. Of these, 32 patients (20.5%) with early stage squamous cell carcinoma of the esophagus were included in this study. There were 3 intraepithelial carcinomas, 10 mucosal carcinomas, and 19 submucosal carcinomas. Of these 32 patients, 10 had areas of dysplasia concomitant with the early stage carcinoma. There were 29 men and 3 women, and their ages ranged from 46 through 79 years, with an average of 64.3 ± 8.2 years. Both radiography and dye endoscopy with Lugol's solution' were performed on all patients pre-operatively. We instilled about 20 ml of 2% Lugol's solution via a polyethylene tube on the mucosal surface under direct vision, and biopsy specimens were taken from the unstained areas. Thereafter, various operations such as subtotal esophagectomy and lymph node dissection through a right thoracotomy and esophageal reconstruction with a gastric tube were carried out in one stage.s The resected specimens were stretched appropriately on a board with pins and fixed with 10% formalin. Subsequently, each specimen was serially sectioned into blocks 5-mm wide and 4-cm long. One side from each block was stained with hematoxylin and eosin and periodic acid-Schiff for histologic examination. We then conducted a comparative study on the pre-operative Lugol's combined endoscopy and postoperative histology. 657
RESULTS
None ofthe patients with intraepithelial or mucosal carcinoma had any symptoms (Table 1). On the other hand, 14 ofthe 19 patients with submucosal carcinoma Table 1. Chief complaints Depth of cancer invasion Complaints
epa (N
None Pyrosis Chest discomfort Slight dysphagia
= 3) 3
o o o
sm
mm (N
= 10) 10
o o
o
(N
= 19) 5 3 5 6
a ep, invasion limited to the epithelium; mm, invasion confined to the lamina muscularis mucosae; sm, invasion confined to submucosa.
did have symptoms; 3 had pyrosis, 5 had chest discomfort, and 6 had slight dysphagia. As for the 18 asymptomatic patients, in 6 cases early esophageal carcinoma was detected endoscopically at the time of a follow-up study for gastric ulcer. Endoscopic detection was done in the remaining 12 patients during a mass survey for gastric cancer. Table 2 shows the clinicopathologic findings in the 32 patients with early stage carcinoma, arranged in the order ofthe depth and size ofthe cancer. The sizes of early stage carcinomas ranged from 3 X 3 mm to 60 X 90 mm. The gross appearance of all of the cancers limited to the epithelium were of the superficial type. On the other hand, in the 29 patients with either mucosal cancer or submucosal cancer, there were 18 patients with an elevated type, 6 patients with a superficial type, and 5 patients with a depressed type. Of 32 early stage cancers, 9 were poorly differentiated
Table 2. Clinicopathologic findings in early stage carcinoma
Patient
Age/sex
Depth of cancer invasion
1 2 3 4b 5b 6b 7 8 9b
63/M 65/M 71/M 71/F 51/M 78/M 65/M 56/M 58/M 58/M 66/M 73/M 66/M 70/M 55/M 36/M 69/M 12/F 61/M 12/M 73/M 73/M 56/M 56/M 56/M 45/M 57/M 67/M 67/M 49/M 73/F 12/M
epa ep ep mm mm mm mm mm mm mm mm mm mm sm sm sm sm sm sm sm sm sm sm sm sm sm sm sm sm sm sm sm
lOb
11 12 13b 14 b 15 16 b 17 18 19 20 21 b 22 23 24 25 26 27 28 29b 30 31 32
Size of carcinoma (mm)
Gross type
Histopathologic findings
3x3 10 x 15 10 x 25 8 X 12 9 x 10 10 x 10 10 x 14 12 x 21 16 x 21 20 x 27 20 x 30 25 x 25 30 x 42 6x9 8 x 12 10 x 20 10 x 20 11 x 20 13 x 28 15 x 20 16 X 31 18 x 28 20 x 20 20 x 40 20 x 40 21 x 25 24 x 28 25 x 35 25 x 38 27 x 31 45 x 50 60 x 90
Superficial Superficial Superficial Superficial Superficial Superficial Superficial Elevated Depressed Superficial Superficial Elevated Depressed Depressed Elevated Elevated Elevated Elevated Elevated Elevated Elevated Elevated Elevated Elevated Depressed Depressed Elevated Elevated Elevated Elevated Elevated Elevated
Mod diff sq ca Mod diff sq ca Poor diff sq ca Mod diff sq ca Mod diff sq ca Well-diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Mod diff sq ca Poorly diff sq ca Mod diff sq ca Poorly diff sq ca Poorly diff sq ca Poorly diff sq ca Well-diff sq ca Poorly diff sq ca Mod diff sq ca Poorly diff sq ca Mod diff sq ca Mod diff sq ca Poorly diff sq ca Mod diff sq ca Poorly diff sq ca Mod diff sq ca
a ep, invasion limited to the epithelium; mm, invasion confined to the lamina muscularis mucosae; sm, invasion confined to submucosa; mod diff sq ca, moderately differentiated squamous cancer; welldiff sq ca, well-differentiated squamous cancer; poorly diff sq ca, poorly differentiated squamous cancer. b Dysplasia was concomitant with cancer.
658
GASTROINTESTINAL ENDOSCOPY
squamous cell carcinomas, 21 moderately differentiated squamous cell carcinomas, and 2 well-differentiated squamous cell carcinomas. In 10 patients, areas of dysplasia were associated with early stage carcinoma. The dysplastic lesions were all superficial in type. Concerning the diagnosis of early stage cancer, 3 epithelial cancers and 10 dysplastic lesions showed no abnormal findings by double contrast radiography, regardless of size; no rigidity of the esophageal wall, no irregularity of the margin, and no ulceration (Table 3). Among the 10 cancers involving the lamina muscularis mucosa, no abnormal findings were recognized on radiography in case 4 (8 X 12 mm) and case 5 (9 X 12 mm). On the other hand, abnormal radiographic findings were found in 8 of 10 cases, suggesting that even in cancers with invasion only to the lamina Table 3. Diagnostic characteristics of early stage carcinoma and dysplasia Early carcinoma epa (N = 3) Radiography Rigidity of the wall Irregularity of margin Ulceration No abnormality Endoscopic findings Mucosal surface Smooth Granular Ulceration Elevated Margin Clear Unclear Gross type Elevated Superficial Depressed Lugol's stain Unstained Poorly stained Macroscopic findings of the resected specimen Mucosal surface Smooth Granular Ulceration Elevated Fine crinkles Disappeared Normal Recognition without Lugol Possible Impossible
0 0 0 3
mm sm (N = 10) (N = 19) 4
7 4
2
19 19 8 0
Figure 1. X-ray of the esophagus. Arrow shows an elevated lesion of the esophagus. 0 3 0 0
0 7 2 1
0 8 5 6
3 0
10 0
17 2
0 3 0
2 6 2
11
3 0
10 0
18 1
0 3 0 0
0 8 2 0
0 7 6 6
1 2
10 0
19 0
3 0
10 0
19 0
5
3
a ep, invasion limited to the epithelium; mm, invasion confined to the lamina muscularis mucosae; sm, invasion confined to submucosa.
VOLUME 38, NO.6, 1992
muscularis mucosa, larger lesions often yield some radiographic findings. In all of the submucosal cancers, abnormal radiographic findings were recognized. On the other hand, all of the early stage cancers, including three intraepithelial cancers, were accurately diagnosed pre-operatively by Lugol's combined endoscopic examination with biopsy. None of the mucosal surfaces of the early stage cancers observed by endoscopy were smooth, and all of the cancerous lesions were clearly not stained by Lugol's solution. The comparative study of pre-operative Lugol's combined endoscopic findings and histopathologic study of resected specimens confirmed that all of the cancerous lesions remained unstained by Lugol's solution, while some mucosal lesions with severe dysplasia also went unstained by Lugol's solution. Macroscopic findings of the resected specimens showed some abnormalities, such as granular surface, ulceration, elevation, disappearance of fine crinkles, and so forth, in all of the early stage cancers. As an illustrative case, patient 27, a 57-year-old man presented at our outpatient clinic complaining of slight dysphagia. X-rays of the esophagus revealed a 659
Figure 2. Endoscopic findings of the lesion. A, A tumor was found in the upper esophagus. B, When Lugol's solution was applied, an unstained lesion appeared on the oral side of the tumor (arrows). Not only the presence of the lesion, but also the spread of the lesion became clear.
Figure 4. The resected specimen. Spread of cancer invasion could not be judged exactly without Lugol's staining (A), whereas, when Lugol's solution was applied, the spread of invasion was clearly observed (B) (arrows).
tumorous lesion in the upper esophagus (Fig. 1). An elevated lesion was detected by endoscopy (Fig. 2A). When Lugol's stain was applied, an unstained lesion appeared at the oral site of the tumor (Fig. 2B). Not only the elevated lesion but also the unstained lesion were diagnosed to be moderately differentiated squamous cell carcinoma by biopsy (Fig. 3). A subtotal esophagectomy was performed, and the resected specimen was stretched on a board with pins (Fig. 4A) and Lugol's solution was then applied to the mucosal surface. The spread of the cancerous lesion became readily visible (Fig. 4B), and the size of the carcinoma was 24 x 28 mm. DISCUSSION
Figure 3. Biopsied specimen. Biopsy from the unstained lesion revealed moderately differentiated squamous cell carcinoma (H & E; original magnification x138).
660
The detection of carcinoma at an early stage is the most important factor in curing any cancer, and this is particularly so for patients with esophageal cancer. Before 1984, no mucosal or epithelial carcinoma was evident among our 99 patients who underwent esophagectomy. Since we began to apply Lugol's solution during the endoscopic examination in 1984, early stage GASTROINTESTINAL ENDOSCOPY
esophageal carcinomas now account for 20% of the operated esophageal carcinomas in our institution. These findings indicate that combined endoscopy with Lugol's solution and an endoscopic biopsy are the most efficient tools for detecting early carcinoma of the esophagus, in addition to helping to delineate the margin of involvement of carcinoma, many of which were not evident on the x-ray. The characteristics of early carcinoma on endoscopic examination are: (1) a granular change of the mucosal surface with a clear margin, (2) a slight ulceration or elevation, and (3) an unstained lesion with Lugol's solution. A Chinese team has also reported that cytology can be an extremely efficacious method of detecting invisible lesions,9 especially for screening. In contrast, Lugol's combined endoscopy is not a screening method, but was successfully applied to detect the presence of cancer and the spread of cancerous lesions in the esophagus. Early stage esophageal carcinoma has been reported to cause no symptoms in 16% to 34% of patients. 3 , 4, 10 When asymptomatic, it is usually detected by chance during an examination for another disease of the gastrointestinal tract or during a surveillance procedure. In the United States and Europe, early esophageal carcinoma is still rarely diagnosed. In one study, only 51 early esophageal carcinomas (0.75%) were identified out of 6719 esophageal carcinomas, in spite of the fact that endoscopy is widely used. 3 Since barium
VOLUME 38, NO.6, 1992
usually passes rapidly in the absence of esophageal stenosis, small esophageal lesions may easily be overlooked. An endoscopic diagnostic approach is therefore more effective, because the color of the lesion is generally distinct. In addition to the gross appearance, dye spraying with Lugol's solution during the procedure is very simple, and can provide more precise information regarding the presence and spread of small lesions.
REFERENCES 1. Misumi A, Harada K, Murakami A, et al. Early diagnosis of esophageal cancer. Ann Surg 1989;210:732-9. 2. Levine MS, Dillon EC, Saul SH, Laufer I. Early esophageal cancer. AJR 1986;146:507-12.
3. Froelicher P, Miller G. The European experience with esophageal cancer limited to the mucosa and submucosa. Gastrointest Endosc 1986;32:88-90. 4. Sugimachi K, Ohno S, Matsuda H, Mori M, Kuwano H. Lugolcombined endoscopic detection of minute malignant lesions of the thoracic esophagus. Ann Surg 1988;208:179-83. 5. Brodmerkel GJ. Shiller's test: an aid in esophagoscopic diagnosis. Gastroenterology 1971;60:813. 6. Nishizawa M, Okada T, Hosoi T, Makino T. Detecting early esophageal cancers, with special reference to the intraepithelial stage. Endoscopy 1984;16:92-4. 7. Shiozaki H, Tahara H, Kobayashi K, et al. Endoscopic screening of early esophageal cancer with the Lugol dye method in patients with head and neck cancers. Cancer 1990;66:2068-71. 8. Sugimachi K, Yaita A, Ueo H, Natsuda Y, Inokuchi K. A safer and more reliable operative technique for esophageal reconstruction using a gastric tube. Am J Surg 1980;140:471-4. 9. Yang G, Huang H, Qui S, Chang Y. Endoscopic diagnosis of 115 cases of early esophageal carcinoma. Endoscopy 1982;14:157-61. 10. Endo M, Takeshita K, Yoshida M. How can we diagnose the early stage of esophageal cancer? Endoscopy 1986;18:11-8.
661
