Photodiagnosis and Photodynamic Therapy (2007) 4, 179—183
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Solitary rectal ulcer syndrome—–The role of autofluorescence colonoscopy Wojciech Latos, Aleksandra Kawczyk-Krupka, Aleksandra Ledwo´ n MD ∗, Karolina Siero´ n-Stołtny, Aleksander Siero´ n Center for Laser Diagnostics and Therapy, Chair and Clinic of Internal Diseases, Angiology and Physical Medicine, Silesian Medical University, 15 Batory Street, PL-41902 Bytom, Poland Available online 16 May 2007
KEYWORDS Solitary rectal ulcer syndrome; Autofluorescence colonoscopy
Summary Background: Solitary rectal ulcer syndrome (SRUS) is a rare disorder of the rectum but it causes differential diagnosis problems. Aim: To determine the potential use of autofluorescence colonoscopy (AFC) in diagnosis of SRUS. Material and methods: We performed 1618 colonoscopies. After the medical history was taken white light colonoscopy was performed. The tissue samples were taken for routine pathological examination. When SRUS was histopathologically confirmed AFC was performed by means of OncoLIFE. The mean time lapse between the two colonoscopies was 4 weeks. During AFC numerical colour value (NCV) of autofluorescence of SRUS lesions was noted. Results: During 1618 colonoscopies six persons were diagnosed as having solitary rectal ulcer syndrome (0.37%). The mean age was 43.8 years. There were two men and four women. In our material the endoscopic spectrum was: three (50%) polypoid lesions, two (33.33%) flat ulcers and one case (16.66%) of isolated, local erythema with hyperemia. We did not observe decrease of fluorescence in case of polipoid and flat ulcer lesions (NCV 0.39—0.67; mean 0.525) and little decrease of fluorescence in case of erythema lesion (NCV −0.94). Conclusion: Autofluorescence colonoscopy by means of OncoLIFE appears to be a promising approach in diagnosis of SRUS. The estimation of numerical colour value which is an objective test of autofluorescence intensity, facilitates the differential diagnosis and helps to chose the right management of SRUS. © 2007 Elsevier B.V. All rights reserved.
Introduction Solitary rectal ulcer syndrome (SRUS) is a chronic, benign disease of the rectum often related to straining or abnormal defecation [1,2]. Although SRUS is found most often in young
∗
Corresponding author. Tel.: +48 32 7861 630; fax: +48 32 7861 630. E-mail address: [email protected] (A. Ledwo´ n).
adults (most common in the third decade in men and in the fourth decade in women) a few paediatric cases have been reported [3—5]. The patients usually complain of bleeding, chronic constipation, rectal pain, tenesmus, mucous discharge and straining at defecation [6,7], however, up to 26% of patients can be asymptomatic [8]. The pathogenesis of solitary rectal ulcer syndrome is not well established. Multiple factors, which contribute to its development are taken into consideration. The most acknowledged theories relate to direct trauma or local ischaemia causes.
1572-1000/$ — see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.pdpdt.2007.03.002
180
W. Latos et al.
Lengthened straining at stool and difficulty initiating defecation in patients with constipation may lead to direct trauma to the mucosa [9]. Inappropriate contraction of the puborectalis muscle and mucosal prolapse, overt or occult, is the most common pathogenic mechanism in SRUS. Self-induced trauma caused by rectal digitation is suspected in some cases [10]. Morphology of SRUS varies from ulcerative lesions and polypoid lesions to edematous, nonulcerated, hyperemic mucosa [8,11]. The diagnosis of SRUS includes symptomatology in combination with the endoscopic and histologic findings. Defecography, transrectal ultrasonography and manometry are suitable to detect the underlying pathophysiology and are helpful to select the adequate treatment for patients with SRUS [12,13]. There are several treatment options, such as behavioural modification to topical treatment, biofeedback and surgery. The choice depends on acuteness of symptoms and whether there is an underlying rectal prolapse or not [9]. Although SRUS is a benign condition there are studies which suggest that chronic ischaemia which occurs in the solitary ulcer syndrome may lead to so-called ‘‘transitional mucosa’’ that is similar to that adjacent to colorectal carcinomas and adenomas [14] and may lead to colorectal dysplasia and carcinoma development [15]. We want to indicate the potential use of autofluorescence colonoscopy in diagnosis of SRUS presenting six cases of solitary rectal ulcer syndrome diagnosed during 1618 colonoscopies. Autofluorescence colonoscopy uses the natural ability of tissues to fluoresce after exposition to a specific wavelength of light. Progression to cancer decreases the fluorescence. This change in fluorescence between normal and progression to cancer allows the physician to see subtle areas of abnormality for targeted biopsy and early intervention. OncoLIFE is the latest device of Xillix Inc., which incorporates autofluorescence imaging together with conventional white light endoscopy. OncoLIFE works in real time and permits the estimation of the autofluorescence intensity by analysis of numerical colour value (NCV). Our recent studies suggest that there is a significant correlation between dysplasia grade and intensity of autofluorescence. Figure 1
(a and b) The lesions in white light colonoscopy.
Material and methods Results We performed 1618 colonoscopies in the Central Endoscopy Laboratory and in Center for Laser Diagnostics and Therapy, Chair and Clinic of Internal Diseases, Angiology and Physical Medicine, Silesian Medical University. Before the examination, medical history was taken. The examinations were performed by means of videocolonoscopes Olympus CF-Q 165 produced by Olympus Optical Co. Ltd., Tokyo. By means of biopsy forceps specimens from the lesions found were sampled for histopathological examination. The obtained tissue specimen was examined after embedding in paraffin and haematoxylin and eosin staining. When the solitary rectal ulcer syndrome was histopathologically confirmed autofluorescence colonoscopy (AFC) was performed by means of OncoLIFE (Xillix Inc., Richmond, BC, Canada), which works in real time. The mean time lapse between the two colonoscopies was 4 weeks. During AFC, NCV of autofluorescence of SRUS lesions was noted.
During 1618 colonoscopies six persons were diagnosed as having solitary rectal ulcer syndrome. The mean age was 43.8 years. There were two men in the age 31 and 57 years and four women in the age from 27 to 68 years. In our material the endoscopic spectrum was: three (50%) polypoid lesions, two (33.33%) ulcers and one case (16.66%) of isolated, local erythema with hyperemia. Table 1 shows sex, age of patients, passage of blood per rectum or/and defecation disturbance, macroscopic appearance, diameter, localization and numerical colour value of lesions. Fig. 1 show the lesions in white light, Fig. 2 in autofluorescence. Among six patients with SRUS four confirmed defecation disturbance, five confirmed passage of blood per rectum. In one case the course of disease was asymptomatic. The lesions were found nearby terminal haustra
SRUS- the role of autofluorescence colonoscopy
181 ulcer lesions (NCV 0.39—0.67; mean value 0.525). Little decrease of autofluorescence in case of erythema (NCV −0.94) resulted from hyperemia.
Discussion
Figure 2 (a and b) The lesions in autofluorescence colonoscopy.
of the rectum, on the posterior rectum wall most often. In all cases of SRUS confirmed histopathologically autofluorescence colonoscopy was performed. We did not observe autofluorescence decrease in case of polipoid and flat
Solitary rectal ulcer syndrome is a rare disorder with an estimated prevalence of one in 100,000 persons per year [9]. The diagnosis of SRUS is based on symptoms together with the endoscopic and histologic findings. The endoscopic appearance of SRUS may vary from patchy mucosal erythema to small or giant ulcers to polypoid lesions. In our study polyps represented 50% of SRUS lesions and flat ulcers represented 33.33%. Because of the wide-endoscopic spectrum of SRUS and the necessity of differential diagnosis, biopsy specimens from the involved area must be taken. The histologic findings: fibrosis of the lamina propria, superficial mucosal ulceration, muscularis mucosae hypertrophy and submucosal fibrosis should confirm diagnosis of SRUS [16]. However, similar changes are observed in patients with colitis cystica profunda [17]. The presence of a diffuse excess of mucosal collagen in rectal biopsies differentiate SRUS from idiopathic ulcerative colitis, Crohn’s disease and other inflammatory bowel diseases [18]. In case of SRUS, differential diagnosis has the fundamental meaning. In differential diagnosis such entities should be taken into consideration: inflammatory bowel disease, infectious (amebiasis, lymphogranuloma venerum, secondary syphilis), chronic vascular insufficiency (chronic ischemic colitis), endometriosis, colitis cystica profunda, drug-induced (e.g. ergotamine tartrate-containing, suppositories), stercocoral ulcer, trauma, idiopathic [9,19,20]. The exclusion of malignancy is the most important aim. Although SRUS is a benign disorder there are studies, which draw the physicians attention to an increased propensity for neoplastic progression in certain cases of SRUS. Ball et al. [21] observed that up to 38% of patients with SRUS have histologic changes that mimic sessile serrated polyps (SSPs)—–epithelial proliferative lesions that seem to act as a unique pathway to colorectal carcinogenesis. Moreover, in 20% of these serrated lesions the focal loss of hMLH1 gene expression was ascertained, which indicates a potential of
Table 1 Sex, age of patients, passage of blood per rectum or/and defecation disturbance, macroscopic appearance, diameter, localization and numerical colour value of lesions Patient
K.
B.S.
P.P.
G.W.
B.B.
B.B.
Age (years) Sex Passage of blood per rectum Defecation disturbance Macroscopic appearance
27 Female Yes/often Yes Polipoid
43 Female Yes/rarely Yes Polipoid
31 Male Yes/often Yes Polipoid
68 Female Yes/often Yes Flat ulcer
57 Male No No Flat ulcer
Diameter of lesion (mm) Distance from anal verge (cm) Localization/rectum wall NCV in AFC
65 15 Posterior 0.56
20 10 Posterior 0.39
35 8 Posterior 0.67
30 7 Anterior 0.58
15 5 Posterior 0.61
37 Female Yes/rarely No Erythema with hyperemia 20 12 Anterior 0.94
182 preneoplastic change. Tsuchida et al. [15] describe a case of carcinoma in solitary rectal ulcer syndrome. The authors suggest the malignant transformation from SRUS, similar to that in case of longstanding chronic idiopathic colitis and colorectal dysplasia. The results from the study by Franzin et al. [14] indicate that chronic ischaemia which occurs in SRUS leads to so-called ‘transitional mucosa’, which later maturation could lead to metaplastic changes. Li et al. [22] report seven patients with rectal infiltrating carcinoma whose initial biopsy specimens showed only histopathologic changes of SRUS, carcinoma was established in subsequent specimens. The proper diagnosis of malignancy was delayed from 1 week to 18 months in six patients; in one patient the suggestion of infiltrating carcinoma was made on the first biopsy specimen by immunochemistry for cytokeratin. Three of the patients had primary adenocarcinoma, two had metastatic carcinoma from stomach or ovary and two had direct invasion of anal squamous cell carcinoma or prostatic carcinoma. Taking that all into consideration one can say that the diagnosis of SRUS must be established very cautiously in order not to miss the malignancy. Autofluorescence colonoscopy by means of Xillix OncoLIFE is a new and promising tool in physicians hands. Tissue autofluorescence is based on the excitation of endogenous fluorophores by light. These fluorophores absorb light of specific wavelengths and re-emit it partially at longer wavelength as fluorescence. Normal tissue exhibits a strong fluorescence response, progression to cancer causes decrease of autofluorescence. This change in fluorescence between normal and progression to cancer allows the physician to see subtle areas of abnormality for targeted biopsy and early intervention. As a result precancerous lesions and cancer, often missed in white light, after exposition to the blue light are seen. According to the results of the study by Hixson et al. [23], about 15% of colorectal neoplastic polyps less than 10 mm in size in the setting of adequate bowel preparation may be missed by an experienced colonoscopist. Autofluorescence colonoscopy can diminish the risk. Brand et al. [24] define the specificity of conventional white-light endoscopy at 80%, of fluorescence colonoscopy at 90% and the sensitivity of fluorescence endoscopy at 91%. It is important to mention that a prototype light-induced fluorescence endoscopy (LIFE) system was used in this investigation. Since 1999, the LIFE equipment has been improved considerably. Dacosta et al. [25] conclude that new optical technologies, among others fluorescence endoscopic imaging, enable diagnosis of early lesions by allowing for targeted mucosal excisional biopsies. Autofluorescence endoscopy has the capability to detect the presence and dimension of occult malignant and premalignant gastrointestinal tract lesions [26], may be sufficient to differentiate benign (hyperplastic) from preneoplastic and neoplastic (adenomatous) colonic intramucosal lesions [27] and allows to identify dysplasia associated with adenomatous polyps [28]. It is worth to remind that about 25% of SRUS may appear as a polypoid lesion. The greatest problem is that non-neoplastic inflammatory lesions also synthesize significant concentration of porphyrins, resulting in a high number of false positive outcomes. Therefore, it is very important to cure associate inflammatory state. In such circumstances the ability
W. Latos et al. to localize cancer-transformating dysplasia is remarkably increased. OncoLIFE is the latest device of Xillix Inc. which incorporates specialized light source to induce autofluorescence and a sensitive camera which are connected to an endoscope. By means of OncoLIFE we can objective estimate the intensity of autofluorescence noting numerical colour value (NCV) of autofluorescence of the lesions. On the basis of studies carried out in our centre which have not been published anywhere yet [29], we can state that there is significant correlation between dysplasia grade and intensity of autofluorescence defined using NCV. The dysplasia grade was confirmed histopathologically. The mean NCV of lesions with no dysplasia was 0.7, with low-grade dysplasia 1.38, with high-grade dysplasia 2.94; the mean NCV of healthy mucosa was 0.43. In case of SRUS in our study numerical colour value (mean 0.57) was approximated to numerical colour value of healthy mucosa. Taking that all into consideration OncoLIFE allows to reveal subtle areas within the lesions of more intense autofluorescence and localizes the potential cancertransformating dysplasia. In such circumstances the most representative place, connected with highest risk of preor cancerous changes, for biopsy specimen is indicated. Summing up: NCV in the range 0.4—1.0 and SRUS in histopathological findings of biopsy specimen taken from the areas of greatest NCV enables the physicians to advise treatment recommended in SRUS. This subject of potential use of OncoLIFE in diagnosis and follow-up of patients having SRUS demands further investigation.
Conclusions SRUS is a rare disorder but may lead to colorectal dysplasia and carcinoma development. Exclusion of primary or metastatic malignancy in the SRUS lesions is the most important aim in the differential diagnosis. One cannot forget that the term SRUS is a misnomer because ulcers are found in 40% of patients and the rest vary in shape and size. The most common reason for incorrect diagnosis are inadequate tissue specimens. Autofluorescence colonoscopy by means of OncoLIFE indicates the most representative place for biopsy specimen.
Acknowledgement The work was supported by grant PBZ-KBN-098/T09/2003.
References [1] Meurette G, Regenet N, Frampas E, Sagan C, Le Borgne J, Lehur PA. The solitary rectal ulcer syndrome. Gastroenterol Clin Biol 2006;30(3):382—90. [2] Vaizey CJ, van den Bogaerde JB, Emmanuel AV, Talbot IC, Nicholls RJ, Kamm MA. Solitary rectal ulcer syndrome. Br J Surg 1998;85(12):1617—23. [3] Gabra HO, Roberts JP, Variend S, Shawis RN. Solitary rectal ulcer syndrome in children. A report of three cases. Eur J Pediatr Surg 2005;15(3):213—6.
SRUS- the role of autofluorescence colonoscopy [4] Godbole P, Botterill I, Newell SJ, Sagar PM, Stringer MD. Solitary rectal ulcer syndrome in children. J R Coll Surg Edinb 2000;45(6):411—4. [5] Kiristioglu I, Balkan E, Kilic N, Dogruyol H. Solitary rectal ulcer syndrome in children. Turk J Pediatr 2000;42(1):56—60. [6] Keighley MR, Shouler P. Clinical and manometric features of the solitary rectal ulcer syndrome. Dis Colon Rectum 1984;27(8):507—12. [7] Niv Y, Bat L. Solitary rectal ulcer syndrome—–clinical, endoscopic and histological spectrum. Am J Gastroenterol 1986;81(6):486—91. [8] Tjandra JJ, Fazio VW, Church JM, Lavery IC, Oakley JR, Milsom JW. Clinical conundrum of solitary rectal ulcer. Dis Colon Rectum 1992;35(3):227—34. [9] Sharara AI, Azar C, Amr SS, Haddad M, Eloubeidi MA. Solitary rectal ulcer syndrome: Endoscopic spectrum and review of the literature. Gastrointest Endosc 2005;62(5):755—62. [10] Contractor TQ, Contractor QQ. Traumatic solitary rectal ulcer in Saudi Arabia. A distinct entity? J Clin Gastroenterol 1995;21(4):298—300. [11] Choi HJ, Shin EJ, Hwang YH, Weiss EG, Nogueras JJ, Wexner SD. Clinical presentation and surgical outcome in patients with solitary rectal ulcer syndrome. Surg Innov 2005;12(4):307—13. [12] Simsek A, Yagci G, Gorgulu S, Zeybek N, Kaymakcioglu N, Sen D. Diagnostic features and treatment modalities in solitary rectal ulcer syndrome. Acta Chir Belg 2004;104(1):92—6. [13] Velasco FJ, Lopez R, Pujol J, Sancho F, Llaurado JM, Lluis F. The use of anorectal manometry and dynamic proctography in patients for diagnosis of solitary rectal ulcer syndrome. Rev Esp Enferm Dig 1998;90(6):454—8. [14] Franzin G, Scarpa A, Dina R, Novelli P. ‘‘Transitional’’ and hyperplastic-metaplastic mucosa occurring in solitary ulcer of the rectum. Histopathology 1981;5(5):527—33. [15] Tsuchida K, Okayama N, Miyata M, et al. Solitary rectal ulcer syndrome accompanied by submucosal invasive carcinoma. Am J Gastroenterol 1998;93(11):2235—8. [16] Malik AK, Bhaskar KV, Kochhar R, et al. Solitary ulcer syndrome of the rectum—–a histopathologic characterization of 33 biopsies. Indian J Pathol Microbiol 1990;33(3):216—20. [17] Yamagiwa H. Protruded variants in solitary ulcer syndrome of the rectum. Acta Pathol Jpn 1988;38(4):471—8. [18] Levine DS, Surawicz CM, Ajer TN, Dean PJ, Rubin CE. Diffuse excess mucosal collagen in rectal biopsies facilitates differ-
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ential diagnosis of solitary rectal ulcer syndrome from other inflammatory bowel diseases. Dig Dis Sci 1988;33(11):1345—52. Daya D, O’Connell G, DeNardi F. Rectal endometriosis mimicking solitary rectal ulcer syndrome. Mod Pathol 1995;8(6):599—602. Tjandra JJ, Fazio VW, Petras RE, et al. Clinical and pathologic factors associated with delayed diagnosis in solitary rectal ulcer syndrome. Dis Colon Rectum 1993;36(2):146—53. Ball CG, Dupre MP, Falck V, Hui S, Kirkpatrick AW, Gao ZH. Sessile serrated polyp mimicry in patients with solitary rectal ulcer syndrome: is there evidence of preneoplastic change? Arch Pathol Lab Med 2005;129(8):1037—40. Li SC, Hamilton SR. Malignant tumours in the rectum simulating solitary rectal ulcer syndrome in endoscopic biopsy specimens. Am J Surg Pathol 1998;22(1):106—12. Hixson LJ, Fennerty MB, Sampliner RE, McGee D, Garewal H. Prospective study of the frequency and size distribution of polyps missed by colonoscopy. J Natl Cancer Inst 1990;82(22):1769—72. Brand S, Stepp H, Ochsenkuhn T, et al. Detection of colonic dysplasia by light-induced fluorescence endoscopy: a pilot study. Int J Colorectal Dis 1999 Feb;14(1):63—8. Dacosta RS, Wilson BC, Marcon NE. New optical technologies for earlier endoscopic diagnosis of premalignant gastrointestinal lesions. J Gastroenterol Hepatol 2002;17(Suppl.):S85—104. Haringsma J, Tytgat GN, Yano H, et al. Autofluorescence endoscopy: Feasibility of detection of GI neoplasms unapparent to white light endoscopy with an evolving technology. Gastrointest Endosc 2001;53(6):642—50. DaCosta RS, Andersson H, Cirocco M, Marcon NE, Wilson BC. Autofluorescence characterisation of isolated whole crypts and primary cultured human epithelial cells from normal, hyperplastic, and adenomatous colonic mucosa. J Clin Pathol 2005;58(7):766—74. Wang TD, Crawford JM, Feld MS, Wang Y, Itzkan I, Van Dam J. In vivo identification of colonic dysplasia using fluorescence endoscopic imaging. Gastrointest Endosc 1999;49(4 Pt 1):447—55. Latos W, Kawczyk-Krupka A, Ziele´znik W, et al. Autofluorescence endoscopy for detection of dysplasia in diagnosis of digestive tract’s flat lesions. In: Proceedings of the 6th International Symposium on Photodynamic Diagnosis and Therapy in Clinical Practice. Brixen/Bressanone 10—14 October, 2006 [Abstracts: P-27].
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Solitary rectal ulcer syndrome—–The role of autofluorescence colonoscopy Wojciech Latos, Aleksandra Kawczyk-Krupka, Aleksandra Ledwo´ n MD ∗, Karolina Siero´ n-Stołtny, Aleksander Siero´ n Center for Laser Diagnostics and Therapy, Chair and Clinic of Internal Diseases, Angiology and Physical Medicine, Silesian Medical University, 15 Batory Street, PL-41902 Bytom, Poland Available online 16 May 2007
KEYWORDS Solitary rectal ulcer syndrome; Autofluorescence colonoscopy
Summary Background: Solitary rectal ulcer syndrome (SRUS) is a rare disorder of the rectum but it causes differential diagnosis problems. Aim: To determine the potential use of autofluorescence colonoscopy (AFC) in diagnosis of SRUS. Material and methods: We performed 1618 colonoscopies. After the medical history was taken white light colonoscopy was performed. The tissue samples were taken for routine pathological examination. When SRUS was histopathologically confirmed AFC was performed by means of OncoLIFE. The mean time lapse between the two colonoscopies was 4 weeks. During AFC numerical colour value (NCV) of autofluorescence of SRUS lesions was noted. Results: During 1618 colonoscopies six persons were diagnosed as having solitary rectal ulcer syndrome (0.37%). The mean age was 43.8 years. There were two men and four women. In our material the endoscopic spectrum was: three (50%) polypoid lesions, two (33.33%) flat ulcers and one case (16.66%) of isolated, local erythema with hyperemia. We did not observe decrease of fluorescence in case of polipoid and flat ulcer lesions (NCV 0.39—0.67; mean 0.525) and little decrease of fluorescence in case of erythema lesion (NCV −0.94). Conclusion: Autofluorescence colonoscopy by means of OncoLIFE appears to be a promising approach in diagnosis of SRUS. The estimation of numerical colour value which is an objective test of autofluorescence intensity, facilitates the differential diagnosis and helps to chose the right management of SRUS. © 2007 Elsevier B.V. All rights reserved.
Introduction Solitary rectal ulcer syndrome (SRUS) is a chronic, benign disease of the rectum often related to straining or abnormal defecation [1,2]. Although SRUS is found most often in young
∗
Corresponding author. Tel.: +48 32 7861 630; fax: +48 32 7861 630. E-mail address: [email protected] (A. Ledwo´ n).
adults (most common in the third decade in men and in the fourth decade in women) a few paediatric cases have been reported [3—5]. The patients usually complain of bleeding, chronic constipation, rectal pain, tenesmus, mucous discharge and straining at defecation [6,7], however, up to 26% of patients can be asymptomatic [8]. The pathogenesis of solitary rectal ulcer syndrome is not well established. Multiple factors, which contribute to its development are taken into consideration. The most acknowledged theories relate to direct trauma or local ischaemia causes.
1572-1000/$ — see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.pdpdt.2007.03.002
180
W. Latos et al.
Lengthened straining at stool and difficulty initiating defecation in patients with constipation may lead to direct trauma to the mucosa [9]. Inappropriate contraction of the puborectalis muscle and mucosal prolapse, overt or occult, is the most common pathogenic mechanism in SRUS. Self-induced trauma caused by rectal digitation is suspected in some cases [10]. Morphology of SRUS varies from ulcerative lesions and polypoid lesions to edematous, nonulcerated, hyperemic mucosa [8,11]. The diagnosis of SRUS includes symptomatology in combination with the endoscopic and histologic findings. Defecography, transrectal ultrasonography and manometry are suitable to detect the underlying pathophysiology and are helpful to select the adequate treatment for patients with SRUS [12,13]. There are several treatment options, such as behavioural modification to topical treatment, biofeedback and surgery. The choice depends on acuteness of symptoms and whether there is an underlying rectal prolapse or not [9]. Although SRUS is a benign condition there are studies which suggest that chronic ischaemia which occurs in the solitary ulcer syndrome may lead to so-called ‘‘transitional mucosa’’ that is similar to that adjacent to colorectal carcinomas and adenomas [14] and may lead to colorectal dysplasia and carcinoma development [15]. We want to indicate the potential use of autofluorescence colonoscopy in diagnosis of SRUS presenting six cases of solitary rectal ulcer syndrome diagnosed during 1618 colonoscopies. Autofluorescence colonoscopy uses the natural ability of tissues to fluoresce after exposition to a specific wavelength of light. Progression to cancer decreases the fluorescence. This change in fluorescence between normal and progression to cancer allows the physician to see subtle areas of abnormality for targeted biopsy and early intervention. OncoLIFE is the latest device of Xillix Inc., which incorporates autofluorescence imaging together with conventional white light endoscopy. OncoLIFE works in real time and permits the estimation of the autofluorescence intensity by analysis of numerical colour value (NCV). Our recent studies suggest that there is a significant correlation between dysplasia grade and intensity of autofluorescence. Figure 1
(a and b) The lesions in white light colonoscopy.
Material and methods Results We performed 1618 colonoscopies in the Central Endoscopy Laboratory and in Center for Laser Diagnostics and Therapy, Chair and Clinic of Internal Diseases, Angiology and Physical Medicine, Silesian Medical University. Before the examination, medical history was taken. The examinations were performed by means of videocolonoscopes Olympus CF-Q 165 produced by Olympus Optical Co. Ltd., Tokyo. By means of biopsy forceps specimens from the lesions found were sampled for histopathological examination. The obtained tissue specimen was examined after embedding in paraffin and haematoxylin and eosin staining. When the solitary rectal ulcer syndrome was histopathologically confirmed autofluorescence colonoscopy (AFC) was performed by means of OncoLIFE (Xillix Inc., Richmond, BC, Canada), which works in real time. The mean time lapse between the two colonoscopies was 4 weeks. During AFC, NCV of autofluorescence of SRUS lesions was noted.
During 1618 colonoscopies six persons were diagnosed as having solitary rectal ulcer syndrome. The mean age was 43.8 years. There were two men in the age 31 and 57 years and four women in the age from 27 to 68 years. In our material the endoscopic spectrum was: three (50%) polypoid lesions, two (33.33%) ulcers and one case (16.66%) of isolated, local erythema with hyperemia. Table 1 shows sex, age of patients, passage of blood per rectum or/and defecation disturbance, macroscopic appearance, diameter, localization and numerical colour value of lesions. Fig. 1 show the lesions in white light, Fig. 2 in autofluorescence. Among six patients with SRUS four confirmed defecation disturbance, five confirmed passage of blood per rectum. In one case the course of disease was asymptomatic. The lesions were found nearby terminal haustra
SRUS- the role of autofluorescence colonoscopy
181 ulcer lesions (NCV 0.39—0.67; mean value 0.525). Little decrease of autofluorescence in case of erythema (NCV −0.94) resulted from hyperemia.
Discussion
Figure 2 (a and b) The lesions in autofluorescence colonoscopy.
of the rectum, on the posterior rectum wall most often. In all cases of SRUS confirmed histopathologically autofluorescence colonoscopy was performed. We did not observe autofluorescence decrease in case of polipoid and flat
Solitary rectal ulcer syndrome is a rare disorder with an estimated prevalence of one in 100,000 persons per year [9]. The diagnosis of SRUS is based on symptoms together with the endoscopic and histologic findings. The endoscopic appearance of SRUS may vary from patchy mucosal erythema to small or giant ulcers to polypoid lesions. In our study polyps represented 50% of SRUS lesions and flat ulcers represented 33.33%. Because of the wide-endoscopic spectrum of SRUS and the necessity of differential diagnosis, biopsy specimens from the involved area must be taken. The histologic findings: fibrosis of the lamina propria, superficial mucosal ulceration, muscularis mucosae hypertrophy and submucosal fibrosis should confirm diagnosis of SRUS [16]. However, similar changes are observed in patients with colitis cystica profunda [17]. The presence of a diffuse excess of mucosal collagen in rectal biopsies differentiate SRUS from idiopathic ulcerative colitis, Crohn’s disease and other inflammatory bowel diseases [18]. In case of SRUS, differential diagnosis has the fundamental meaning. In differential diagnosis such entities should be taken into consideration: inflammatory bowel disease, infectious (amebiasis, lymphogranuloma venerum, secondary syphilis), chronic vascular insufficiency (chronic ischemic colitis), endometriosis, colitis cystica profunda, drug-induced (e.g. ergotamine tartrate-containing, suppositories), stercocoral ulcer, trauma, idiopathic [9,19,20]. The exclusion of malignancy is the most important aim. Although SRUS is a benign disorder there are studies, which draw the physicians attention to an increased propensity for neoplastic progression in certain cases of SRUS. Ball et al. [21] observed that up to 38% of patients with SRUS have histologic changes that mimic sessile serrated polyps (SSPs)—–epithelial proliferative lesions that seem to act as a unique pathway to colorectal carcinogenesis. Moreover, in 20% of these serrated lesions the focal loss of hMLH1 gene expression was ascertained, which indicates a potential of
Table 1 Sex, age of patients, passage of blood per rectum or/and defecation disturbance, macroscopic appearance, diameter, localization and numerical colour value of lesions Patient
K.
B.S.
P.P.
G.W.
B.B.
B.B.
Age (years) Sex Passage of blood per rectum Defecation disturbance Macroscopic appearance
27 Female Yes/often Yes Polipoid
43 Female Yes/rarely Yes Polipoid
31 Male Yes/often Yes Polipoid
68 Female Yes/often Yes Flat ulcer
57 Male No No Flat ulcer
Diameter of lesion (mm) Distance from anal verge (cm) Localization/rectum wall NCV in AFC
65 15 Posterior 0.56
20 10 Posterior 0.39
35 8 Posterior 0.67
30 7 Anterior 0.58
15 5 Posterior 0.61
37 Female Yes/rarely No Erythema with hyperemia 20 12 Anterior 0.94
182 preneoplastic change. Tsuchida et al. [15] describe a case of carcinoma in solitary rectal ulcer syndrome. The authors suggest the malignant transformation from SRUS, similar to that in case of longstanding chronic idiopathic colitis and colorectal dysplasia. The results from the study by Franzin et al. [14] indicate that chronic ischaemia which occurs in SRUS leads to so-called ‘transitional mucosa’, which later maturation could lead to metaplastic changes. Li et al. [22] report seven patients with rectal infiltrating carcinoma whose initial biopsy specimens showed only histopathologic changes of SRUS, carcinoma was established in subsequent specimens. The proper diagnosis of malignancy was delayed from 1 week to 18 months in six patients; in one patient the suggestion of infiltrating carcinoma was made on the first biopsy specimen by immunochemistry for cytokeratin. Three of the patients had primary adenocarcinoma, two had metastatic carcinoma from stomach or ovary and two had direct invasion of anal squamous cell carcinoma or prostatic carcinoma. Taking that all into consideration one can say that the diagnosis of SRUS must be established very cautiously in order not to miss the malignancy. Autofluorescence colonoscopy by means of Xillix OncoLIFE is a new and promising tool in physicians hands. Tissue autofluorescence is based on the excitation of endogenous fluorophores by light. These fluorophores absorb light of specific wavelengths and re-emit it partially at longer wavelength as fluorescence. Normal tissue exhibits a strong fluorescence response, progression to cancer causes decrease of autofluorescence. This change in fluorescence between normal and progression to cancer allows the physician to see subtle areas of abnormality for targeted biopsy and early intervention. As a result precancerous lesions and cancer, often missed in white light, after exposition to the blue light are seen. According to the results of the study by Hixson et al. [23], about 15% of colorectal neoplastic polyps less than 10 mm in size in the setting of adequate bowel preparation may be missed by an experienced colonoscopist. Autofluorescence colonoscopy can diminish the risk. Brand et al. [24] define the specificity of conventional white-light endoscopy at 80%, of fluorescence colonoscopy at 90% and the sensitivity of fluorescence endoscopy at 91%. It is important to mention that a prototype light-induced fluorescence endoscopy (LIFE) system was used in this investigation. Since 1999, the LIFE equipment has been improved considerably. Dacosta et al. [25] conclude that new optical technologies, among others fluorescence endoscopic imaging, enable diagnosis of early lesions by allowing for targeted mucosal excisional biopsies. Autofluorescence endoscopy has the capability to detect the presence and dimension of occult malignant and premalignant gastrointestinal tract lesions [26], may be sufficient to differentiate benign (hyperplastic) from preneoplastic and neoplastic (adenomatous) colonic intramucosal lesions [27] and allows to identify dysplasia associated with adenomatous polyps [28]. It is worth to remind that about 25% of SRUS may appear as a polypoid lesion. The greatest problem is that non-neoplastic inflammatory lesions also synthesize significant concentration of porphyrins, resulting in a high number of false positive outcomes. Therefore, it is very important to cure associate inflammatory state. In such circumstances the ability
W. Latos et al. to localize cancer-transformating dysplasia is remarkably increased. OncoLIFE is the latest device of Xillix Inc. which incorporates specialized light source to induce autofluorescence and a sensitive camera which are connected to an endoscope. By means of OncoLIFE we can objective estimate the intensity of autofluorescence noting numerical colour value (NCV) of autofluorescence of the lesions. On the basis of studies carried out in our centre which have not been published anywhere yet [29], we can state that there is significant correlation between dysplasia grade and intensity of autofluorescence defined using NCV. The dysplasia grade was confirmed histopathologically. The mean NCV of lesions with no dysplasia was 0.7, with low-grade dysplasia 1.38, with high-grade dysplasia 2.94; the mean NCV of healthy mucosa was 0.43. In case of SRUS in our study numerical colour value (mean 0.57) was approximated to numerical colour value of healthy mucosa. Taking that all into consideration OncoLIFE allows to reveal subtle areas within the lesions of more intense autofluorescence and localizes the potential cancertransformating dysplasia. In such circumstances the most representative place, connected with highest risk of preor cancerous changes, for biopsy specimen is indicated. Summing up: NCV in the range 0.4—1.0 and SRUS in histopathological findings of biopsy specimen taken from the areas of greatest NCV enables the physicians to advise treatment recommended in SRUS. This subject of potential use of OncoLIFE in diagnosis and follow-up of patients having SRUS demands further investigation.
Conclusions SRUS is a rare disorder but may lead to colorectal dysplasia and carcinoma development. Exclusion of primary or metastatic malignancy in the SRUS lesions is the most important aim in the differential diagnosis. One cannot forget that the term SRUS is a misnomer because ulcers are found in 40% of patients and the rest vary in shape and size. The most common reason for incorrect diagnosis are inadequate tissue specimens. Autofluorescence colonoscopy by means of OncoLIFE indicates the most representative place for biopsy specimen.
Acknowledgement The work was supported by grant PBZ-KBN-098/T09/2003.
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