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Re: High-magnification-chromoscopic-colonoscopy as a screening tool in acromegaly

Dear Editor

We read with great interest the paper by Jenkins et al.[1] regarding screening guidelines for colorectal cancer and polyps in patients with acromegaly and the subsequent discussion by Renehan addressing screening inconsistencies as compared to other high risk groups.[2,3]

The optimal colorectal screening modality and frequency in this group however requires clarification. Colonoscopy in this patient group is technically demanding and often complicated by inadequate bowel preperation.[1,4] However, despite current controversies regarding true colorectal cancer risk categorization in acromegaly, previous data from the largest published series showed a trend for adenoma and carcinoma formation in the right-hemi-colon.[5] This is an important observation for many reasons.

Flat adenomas and carcinomas can be difficult to detect by conventional colonoscopy alone, often presenting as subtle mucosal erythema, mucosal pallor, fold convergence, interruption of innominate grooves, air-induced deformation or loss of vascular net pattern.[6] The neoplastic risk for this morphologically distinct group has additionally been shown by many authors to be higher when compared to exophytic polypoid lesions and exhibit a propensity for the right colon.[7-10] De novo neoplastic lesions and ‘minute’ colorectal cancers are also associated with an increased risk of lymph node metastasis due to early invasion of the submucosal layer.[11] Tada et al. found extensive submucosal invasion in a cohort of flat colorectal neoplasms,[12] with Shimoda’s series corroborating this data with submucosal invasion demonstrable in 69% of flat carcinomas compared to only 35% of sessile and broad based polypoid carcinomas.[13]

Morphologically flat and depressed lesions are also known to occur in chronic ulcerative colitis (CUC)[14] where the need for colorectal cancer screening with total colonoscopy and now adjunctive chromoscopy is adopted by many centers. Failure to detect such lesions may impart account for those cases of CRC which occurred in Winawers study, despite clearance of all exophytic polyps and thus stresses the requirement for accurate diagnosis and definitive treatment of these high risk lesions.[15]

Given the lack of standardized and uniform reporting regarding morphology of colorectal lesions in many of the existing prevalence studies of adenomas and CRC in acromegaly however, at present we can only hypothesis that the high incidence of right-hemi-colonic neoplasia may be an indicator of an alternative morphologically distinct lesion such as the flat adenoma and carcinoma with a trend toward a de novo pathogenic sequence.

In our prospective study, 38 patients with acromegaly underwent total colonoscopy by a single endoscopist using the Olympus C240Z magnifying colonoscope. Preparation was with 4 litres of Kleanprep 24 hours prior to procedure. Pan-colonic chromoscopy using 0.5% indigo carmine sprayed onto the colonic mucosa using an Olympus diffusion catheter (CS12890) was applied. Identified lesions were morphologically grouped according to the Japanese Research Society Classification (JRSC).[16,17] A flat lesions was defined as mucosal change with a flat or rounded surface combined with a height of less than half the diameter of the lesion.[18] High magnification views of all suspected lesions were then obtained and reported according to the modified Kudo criteria.[19] Tissue sampling was performed with cold biopsy or endoscopic mucosal resection (EMR) following exclusion of a Kudo type V(n)/IIIs invasive crypt pattern which suggests deep submucosal invasion. Mean intubation and extubation times were recorded. Neoplastic change was classified according to Vienna criteria.[20]

Caecal intubation was achieved in 37/38 (97%) of patients with 36/38(94%) receiving confirmatory terminal-ileal biopsies. Males represented 14/37 (37% of the cohort, mean age 64 years (range 40-75). The mean duration of intubation to the caecum was 16.5 minutes (range 3-31) and extubation (excluding interventional procedures) 35 minutes (range 20-55). There were no complications.

A total of 28 lesions were identified in 15 patients. A total of 22 hyperplastic lesions were identified (79%) of which 17(77%) were flat (JRSC II). Twenty (91%) were located in the left colon and rectum. Of the 5 adenomas identified, 4(80%) were present in the right colon with 4/ 5(80%) being of JRSC II morphology. A single adenoma with high-grade dysplasia was present in the right colon and was flat with a small area of central depression. No invasive carcinomas were diagnosed. Results are summarized in table 1.

Table 1 Lesion demographics

Low grade Dysplasia (LGD)
High grade Dysplasia (HGD)

Although the numbers entering this study are small, our results show a clear prevalence for JRSC class II lesions in this select patient group. Although only one adenoma with HGD was detected, it was small (5mm) and was not identified prior to chromoscopic and magnification enhancement, and therefore carries major clinical connotations.

We suggest that further large prospective studies are required to establish the true prevalence of flat and depressed colorectal lesion in acromegaly, so the optimal screening modality and frequency can finally be established. Furthermore colonoscopists require training in chromoscopic techniques if a higher endoscopically ‘treatable’ lesional frequency is to be detected at a screening level, so as to avoid the high apparent incidence of interval neoplasms.

References

(1) Jenkins PJ, Fairclough PD. Screening guidelines for colorectal cancer and polyps in patients with acromegaly. Gut 2002;51:V13-14.

(2) Renehan AG, O'Dwyer ST, Shalet SM. Colorectal neoplasia in acromegaly: the reported increased prevalence is overestimated. Gut 2000;46:440.

(3) Renehan AG, O'Dwyer ST, Shalet SM. Guidelines for colonoscopic screening in acromegaly are inconsistent with those for other high risk groups. Gut 2003;52:1071-1072.

(4) Veysey MJ, Mills TD, Thomas LA et al. Prolonged large bowel transit increases serum deoxycholic acid: a risk factor for octreotide induced gallstones. Gut 1999;44:675-681.

(5) Jenkins PJ, Fairclough PD, Richards T et al. Acromegaly, colonic polyps and carcinoma. Clin Endocrinol 1997;47:17-22.

(6) Hurlstone DP, Fujii T, Lobo AJ. Early detection of colorectal cancer using high-magnification chromoscopic colonoscopy. Br J Surg 2002;89:272-82.

(7) Rembacken BJ, Fujii T, Cairns A et al. Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK. Lancet 2000;355:1211- 1214.

(8) Tsuda S, Veress B, Toth E et al. Flat and depressed colorectal tumours in a southern Swedish population: a prospective chromoendoscopic and histopathological study. Gut 2002;51:550-555.

(9) Saitoh Y, Waxman I, West AB et al. Prevalence and distinctive biologic features of flat colorectal adenomas in a North American population. Gastroenterology 2001;120:1657-1665.

(10) Adachi M, Okinaga K, Muto T. Flat adenoma of the large bowel: re-evaluation with special reference to central depression. Dis Colon Rectum 2000;43:782- 787.

(11) Kudo S, Tamura S, Hirota S et al. The problem of de novo colorectal carcinoma. Eur J Cancer 1995;31A:1118-20.

(12) Tada S, Yao T, Iida M et al. A clinicopathologic study of small flat colorectal carcinoma. Cancer 1994;74:2430-2435.

(13) Shimoda T, Ikegami M, Fujisaki J et al. Early colorectal carcinoma with special reference to its development de novo. Cancer 1989;64:1138-1146.

(14) Kiesslich R, Fritsch J, Holtmann M et al. Methylene Blue-Ailed Chromoendoscopy for the Detection of Intraepitheial Neoplasia and Colon Cancer in Ulcerative Colitis. Gastroenterology 2003;124:880-888.

(15) Winawer SJ, Zauber AG, Ho MN et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993;329:1977-1981.

(16) General rules for clinical and pathological studies on cancer of the colon, rectum and anus. Part I. Clinical classification. Japanese Research Society for Cancer of the Colon and Rectum. Jpn J Surg 1983;13:557-73.

(17) General rules for clinical and pathological studies on cancer of the colon, rectum and anus. Part II. Histopathological classification. Japanese Research Society for Cancer of the Colon and Rectum. Jpn J Surg 1983;13:574-98.

(18) Kudo S, Kashida H, Tamura T et al. Colonoscopic diagnosis and management of nonpolypoid early colorectal cancer. World J Surg 2000;24:1081-1090.

(19) Kudo S, Rubio CA, Teixeira CR et al. Pit pattern in colorectal neoplasia: endoscopic magnifying view. Endoscopy 2001;33:367-373.

(20) Schlemper RJ, Riddell RH, Kato Y et al. The Vienna classification of gastrointestinal neoplasia. Gut 2000;47:251-255.