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Original article

Fuji Intelligent Chromo Endoscopy and staining technique for the diagnosis of colon tumor

LIU, Yun-xiang; HUANG, Liu-ye; BIAN, Xiao-ping; CUI, Jun; XU, Ning; WU, Cheng-rong

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Abstract

Colon cancer is a common malignant tumor seen in the clinic. In recent years its incidence rate is increasing in our country and the key point to improve the survival rate is the diagnosis and treatment at an early stage.1,2 Ordinary magnifying colonoscopy can only detect some characteristics of the lesion. It can not detect the pit pattern and mucosal blood capillaries and the endoscopic diagnostic rate does not coincide well with pathologic diagnosis. With the popularity of chromoendoscopy and magnifying colonoscopy, the differential diagnosis of tumor and non-tumor became important to guide clinical therapy.3–5

While chromoendoscopy is time consuming and tedious. Fuji Intelligent Chromo Endoscopy (FICE) technique adopts a nanometer spectro technique; it simulates chromoendoscopy and can detect microstructure and blood capillaries of the mucosal membrane. The microstructure and blood capillaries of the colon mucosal membrane could be detected with FICE, which helps in the differential diagnosis of tumor and non-tumor lesions. The diagnosis of colon lesion with FICE was reported abroad. However, no data was reported in domestic clinics on this topic. The purpose of this study was to explore the accuracy of FICE for the differential diagnosis of colon tumors and non-tumor lesions.

METHODS

Patients

From March to November 2007, 654 patients were examined with ordinary colonoscopy in the Yantai Yuhuangding Hospital (Shandong, China) by the same doctor with an extensive experience in endoscopy. Consent was signed before the study for every patient. Among those examined 223 patients with colon neoplasm or polypoid lesions were included.

Excluding criteria

Patients with inflammatory bowel disease and familial large intestine adenomatosis were excluded; patients whose ileocecal valve was not reached with colonoscopy were also excluded.

Instruments and reagent

The Fujinon EC-590ZM magnifying endoscope (Fujinon Company, Japan) was used and 0.4% ceruleinum was used for colorectal staining.

Procedure

Scopolamine butylbromide 20 mg were injected intra-muscularly before examination and the following procedures were preformed: (1) the endoscope was inserted to the ileocecal valve, when abnormal mucous membrane was detected, the pit pattern was observed with magnification of 40–100 times to evaluate whether it was tumor and the form of the lesion was recorded; (2) it was changed to a FICE pattern with a panel switch and the mucous membrane was observed with 10 kinds of pre-set RGB wave-lengths until the image was clear and satisfying. The wave-length used was recorded and the image was then magnified to 40–100 times to observe the pit pattern and the form of the blood capillaries and the pit pattern was classified; (3) the lesion was stained with 0.4% indigo carmine, the range and form of the lesion was recorded, then it was magnified to 40–100 times to observe pit pattern and its type; (4) the lesion was biopsied at several points and pathologic diagnosis was made by a pathologist with extensive experience.

Pit pattern

The typing of the pit pattern adopts the methods of Kudo and Nagata (Table 1).6,7

Table 1
Table 1:
Pit pattern method of Nagata (1996)

The sub-classification of V: (1) VA (un-commitment) pit: the mix of IIIs, III and IV; (2) VN (non-structure) pit: no pit or few pits at local site, however the pit pattern could not be classified.

Result evaluation: lesions with pit patterns of types I and II were confirmed as non-tumor lesion, lesions with pit patterns of type IIIL, IV and V were confirmed as tumor lesions. Lesions with a pathologic diagnosis of inflammation or hyperplasia was recognized as a non-tumor lesion, lesion with a pathologic diagnosis of adenoma or cancer was recognized as a tumor lesion. The final diagnosis depends on the pathologic diagnosis.

The score of pit pattern and blood capillary

The score of the pit pattern and blood capillary was as follow: 1 point: obscure; 2 points: clouding; 3 points: more clear; 4 points: clear.

Statistical analysis

SPSS10.0 was used for statistical analysis, the method of chi-square test and rank sum test were used, P <0.05 was considered statistically significant.

RESULTS

Basic data

Total 223 patients with colon neoplasm or polypoid lesions were included; 132 males and 91 females, age range 20–85 years, mean (57.3±11.3) years. 451 lesions were detected, including 242 polyps, 188 adenoma and 21 cancers, among them there were 4 laterally spreading tumor (LST).

The comparison of magnifying ordinary colonoscopy, FICE and chromoendoscopy for lesion detection

The lesion detection rate of magnifying ordinary colonoscopy, FICE and chromoendoscopy were 411 (91.1%), 447 (99.1%) and 451 (100%), respectively. Among the 21 carcinoma lesions, there were 5 early carcinomas and 16 advanced carcinomas. Advanced colon cancer was detected with magnifying ordinary colonoscopy, FICE and chromoendoscopy. Lesion detection and omission are listed in Table 2. Flat lesions were detected with magnifying chromoendoscopy; among these were 92 IIa, 6 IIb and 34 IIc. Flat lesions were also detected with magnifying FICE, there were 92 IIa, 4 IIb and 32 IIc. Flat lesions that were detected with the magnifying ordinary colonoscopy included 75 IIa, 1 IIb and 16 IIc. The images of normal mucosal membrane by ordinary colonoscopy and FICE are listed in Figure 1. The images of LST by ordinary colonoscopy and FICE are listed in Figure 2.

Table 2
Table 2:
Lesion detected and missed with the three methods
Figure 1.
Figure 1.:
Images of normal colon mucosal membrane shown by ordinary colonoscopy and Fuji Intelligent Chromo Endoscopy (FICE). A: vessels were red on ordinary colonscopy. B: blood capillaries are light brown shown by FICE, sub-mucosal vessel is heavy brown, superficial structure and blood capillaries are clearer than ordinary colonoscopy (R: 540 nm, G: 440 nm, B: 415 nm).
Figure 2.
Figure 2.:
Images of laterally spreading tumor shown by ordinary colonoscopy and FICE. A: images of ordinary colonoscopy, the color of the tumor was similar to that of the surrounding tissue, the terminal line was unclear. B: FICE images showed the tumor was obvious compared with surrounding tissue; it was staged as a high-differentiating adenocarcinoma by pathology (R: 540 nm, G: 480 nm, B: 415 nm).

The comparison of magnifying FICE and chromoendoscopy for the differential diagnosis of tumor and non-tumor

In a comparison of image acuity of magnifying FICE and chromoendoscopy, FICE was superior to ordinary colonoscopy for the diagnosis of pit pattern. FICE could demonstrate the form of blood capillaries more clearly (P <0.01), while there was no statistical difference in the demonstration of pit pattern (Table 3).

Table 3
Table 3:
The comparison of image acuity of magnifying FICE and chromoendoscopy

The pit pattern of lesions detected with magnifying chromoendoscopy were 19 I and 224 II, that is 243 non-tumorous lesions; 138 IIIL, 41 IV, 8 VA and 21 VN, that is 208 tumor lesions. For the lesions with pit patterns of I and II, they were diagnosed as hyperplastic polyps and inflammatory polyps. Tumor vessels were not observed with FICE, the color of the lesion was similar to the color of surrounding mucosal membrane and no branched blood net was observed with magnifying FICE. Lesions with pit patterns of III, IV and V were almost tumors and tumor vessels could be observed with FICE.

A branched blood capillary net could be observed with magnifying FICE that was also seen in some polyps with serious inflammation. Lesions with pit patterns of V N were diagnosed as cancer lesions. Cancer vessels could be observed with FICE and a branched blood capillary net could be observed with magnifying FICE, the vessels were large and disordered. Pit pattern and blood capillaries could be observed with FICE, 246 lesions with pit patterns of I and II had no branched blood capillaries or less superficial blood capillaries, they were defined as non-tumor lesions.

Totally 205 lesions with pit patterns of IIIL, IV and V had tumor vessels; they were defined as tumor lesions. The pit pattern of depressed tumor lesions could be IIIL, IV or V and the color of the lesion and surrounding tissue differed greatly while several large vessels could be observed around the tumor. One case was diagnosed as adenoma with ordinary colonoscopy, its pit pattern was in disorder when observed with FICE, large and twisted blood capillaries could be observed and it was confirmed as cancer with a pathologic biopsy. The pit pattern and blood capillaries of magnifying FICE are listed in Figure 3. The comparison of images of magnifying FICE and chromoendoscopy of tumor lesions are shown in Figures 4, 5, and 6. The pit pattern and form of blood capillaries of early colon cancer are shown in Figure 7, the terminal line between the lesion and surrounding tissue was visible.

Figure 3.
Figure 3.:
Pit pattern images of magnifying Fuji Intelligent Chromo Endoscopy (FICE). A: pit pattern of type II, some light brown blood capillary are shown (R: 540 nm, G: 440 nm, B: 415 nm). B: pit pattern of type IIIL, branch brown blood capillary are shown (R: 560 nm, G: 460 nm, B: 415 nm). C: pit pattern of type IV, much heavy brown branch blood capillary net are shown, the vessel is large in diameter (R: 550 nm, G: 440 nm, B: 415 nm). D: pit pattern of type V, heavy brown blood capillary net are shown, it is in disorder, some vessels were destroyed (R: 550 nm, G: 450 nm, B: 415 nm).
Figure 4.
Figure 4.:
Images of flat lesion shown by magnifying FICE and chromoendoscopy. A: pit pattern of type IIIL shown by FICE, branch light brown blood capillary is shown; it is staged as a tubular adenoma by pathology (R: 530 nm, G: 460 nm, B: 415 nm). B: pit pattern is clear shown by magnifying chromoendoscopy, but blood capillaries are unclear.
Figure 5.
Figure 5.:
Images of tumor lesion shown by magnifying FICE and chromoendoscopy. A: pit patterns are types IV and V shown by magnifying FICE, tumor vessels are in the shape of branch and curvature (R: 560 nm, G: 480 nm, B: 410 nm), it is as villous adenoma by pathology. B: pit pattern is type IV shown by magnifying chromoendoscopy, tumor vessels are indistinct, the form of the vessel is unclear and it is identified as a villous adenoma by pathology.
Figure 6.
Figure 6.:
Images of LST shown by magnifying FICE and chromoendoscopy. A: pit pattern is type V shown by magnifying FICE, the terminal line between the tumor and surrounding tissue is clear, tumor vessels are large and torturous, blood capillaries are dense (R: 560 nm, G: 480 nm, B: 430 nm). B: terminal line of the tumor is clear, but tumor vessels are unclear.
Figure 7.
Figure 7.:
Images of eminent lesions shown by ordinary colonoscopy and magnifying FICE. A: the terminal line of the tumor and the surrounding tissue are obscure on images from ordinary colonoscopy. B: images of magnifying FICE, pit pattern is type V, some heavy brown blood capillary nets are shown, the terminal line of the tumor and surrounding tissue is clear (R: 540 nm, G: 480 nm, B: 415 nm) and it is identified as an early colon cancer by pathology.

The coincident rate, sensitivity and specificity of FICE for the diagnosis of colon tumors were 91.6% (413/451), 91.5% (225/246) and 91.7% (188/205), respectively: the values for chromoendoscopy were 82.0% (370/451), 83.1% (202/243) and 80.8% (168/208), respectively. There was a statistically significant difference in the diagnosis of colon tumors with FICE and chromoendoscopy (Table 4) with FICE being superior to chromoendoscopy (P <0.01).

Table 4
Table 4:
The comparison of FICE and chromoendoscopy for the diagnosis of colon tumor

DISCUSSION

FICE is a new kind of endoscopic diagnostic method based on the theory of spectrum analysis. Ordinary endoscopic images are processed with spectrum analysis and spectrum images with certain wave-lengths are produced. Spectrum images with a single wave-length are defined as red (R), green (G) or blue (B). FICE images were produced after imaging with different component RGB spectrum images were processed with FICE technique. Wave-lengths can be selected in the range of 400–600 nm with intervals of 5 nm. Different colors and depth can be produced with different component RGB, which helps to demonstrate the superficial structure of the mucosal membrane. The form of the blood capillaries can reflect mini-changes in the mucosal membrane. The visibility of the vessels and other structures is obvious on FICE images.

A suitable wave-length range is selected according to the structure observed by the doctor. FICE can solve some problems which can not be solved with chromoendoscopy. FICE can mainly detect the forms of the pit pattern and capillary pattern and it helps in the detection of lesions which could not be detected with ordinary endoscopy. It allows an exact biopsy to be made and the accurate diagnosis to be confirmed for the lesion. Histological changes, hyperplasia and early cancer of the mucosal membrane can be accurately diagnosed.

FICE has two working models of ordinary endoscopy and FICE and allows for the rapid switch between the two models and is easily operated. It can be controlled with a panel or an endoscopy switch or with a foot switch. Compared with ordinary chromoendoscopy, staining was unnecessary and the pit pattern of the mucosal membrane can be clearly observed; so it is called electronic staining. Pit pattern and micro-vessels of the mucosal membrane can be observed with FICE and more reliable diagnostic information can be afforded with FICE.

Colon cancer is a type of tumor common in our country. As the food in our country gets closer to that in western countries the incidence rate has increased significantly. Statistical analysis predicts that in the near future, the incidence rate of colon cancer will surpass that of gastric cancer and colon cancer will become the major reason leading to death from gastrointestinal tumors. Therefore, the early diagnosis and treatment of colon cancer becomes a major objective. Colonscopy is one of the methods for the early diagnosis of colon cancer, but flat and depressed colon lesions are difficult to observe with ordinary colonoscopy.

In recent years, with the use of chromoendoscopy and magnifying endoscopy in the clinic, the detection rate of colon cancer increased dramatically. The colon mucosal membrane can be observed with ordinary endoscopy after staining. Pit patterns can be observed with magnifying colonoscophy and the diagnosis of a tumor and the infiltrating range of the tumor can be determined.8–12

In this study FICE, chromoendoscopy and ordinary colonoscopy were used to detect colon neoplasms. Of the 451 neoplasms, 40 neoplasms were not detected with ordinary colonoscopy, while they were detected with FICE. It was demonstrated in this study that the detection rate of the abnormal mucosal membrane with FICE (99.1%) was higher than with ordinary colonoscopy (91.1%); FICE was especially good for flat neoplasms. The majority of colon neoplasms were prominent and flat neoplasms were rare. However, the flat neoplasm was closely related to the occurrence of colon cancer and flat neoplasms can be misdiagnosed when examined with ordinary colonoscopy.13–14 FICE can detect more neoplasms without the use of a stain and the diagnostic rate of early cancer can be improved. The 5 neoplasms misdiagnosed with FICE were all flat. The reasons are listed as follows. (1) Bowel preparation was not successful, the color of stool and neoplasm were similar, so the neoplasm could not be demonstrated. (2) FICE is a new kind of technique; doctors do not have enough experience with wave-length selection. (3) Not all the pit patterns could be detected with FICE, because it was affected by the form and site of the neoplasm, there was a limit when diagnosed with ordinary colonoscopy.

Colon mucosal membrane is mainly composed of mucosal membrane and vessels, superficial microstructure and the form of blood capillaries were vital for the diagnosis of neoplasm. With the combination of chromoendoscopy and magnifying endoscopy, according to the pit pattern of the colon, the coincident rate of endoscopic diagnosis and pathologic diagnosis reaches 90%.15–18 The pit pattern and form of the blood capillaries could be clearly demonstrated with FICE, which helps with the diagnostic accuracy.

In this study, the endoscopic diagnosis and pathologic diagnosis of FICE and chromoendoscopy were compared, it demonstrated that FICE is superior to chromoendoscopy for the diagnosis of tumor and non-tumor lesions; for which the sensitivity and specificity of FICE is 91.5% and 91.7%, respectively. With the combination of magnifying endoscopy, FICE could detect early mini-lesions which could be misdiagnosed with ordinary colonoscopy. The infiltrating range of flat lesions, notch lesions and laterally spreading tumors could not be clearly demonstrated with ordinary colonoscopy. With the combination of chromoendoscopy and magnifying endoscopy, the infiltrating range could be deteceted.19–21 It was demonstrated in this study that the combination of FICE and magnifying endoscopy could also demonstrate the microstructure of the lesion which helps to define the infiltrating range, which is significant for clinical therapy.

It was demonstrated in this study that FICE was superior to ordinary endoscopy for the observation of pit pattern and the form of blood capillaries, which was similar to chromoendoscopy. We selected for FICE; R=(540±20) nm, G=(460±25) nm, B=(415±15) nm. The superficial structure of the mucosal membrane was demonstrated with FICE, with the combination of magnifying endoscopy the pit pattern could be demonstrated clearly. As the absorption wave of ferrohemoglobin is at about 415 nm, the form of the superficial blood capillaries could be clearly demonstrated. The color of the tumor vessels was more obvious than the non-tumor vessels on FICE. Additionally, tumor vessels were seen to be in disorder as part of the vessel net was destroyed.

FICE could observe the pit pattern and blood capillaries in the colon and it helped with the diagnostic accuracy of tumor and non-tumor. Although the combination of chromoendoscopy with magnifying endoscopy could demonstrate the pit pattern, it could not demonstrate the form of blood capillaries as well, and it was time-consuming and tedious and required significant technical skill on the part of the doctor; so its application was restricted. FICE could overcome the limitations listed above, as it can be easily operated and changed-over quickly and the images were clear, which helps to target the biopsy.

In summary, FICE is a kind of new endoscopic technique; it can simulate chromoendoscopy and demonstrate microstructure and the form of blood capillary bed. Lesions which are invisible on ordinary endoscopy can be detected with FICE and it helps to target the biopsy and improves the diagnostic accuracy of the neoplasm.

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Keywords:

Fuji Intelligent Chromo Endoscopy; colon tumor; diagnosis

© 2008 Chinese Medical Association