Alimentarni trakt i pankreas
ARCH GASTROENTEROHEPATOL 1999; 18 ( No 3 - 4 ):
 
 

IS COLONOSCOPIC POLYPECTOMY ADEQUATE TREATMENT IN PATIENTS WITH MALIGNANT ALTERED ADENOMAS?

DALI JE KOLONOSKOPSKA POLIPEKTOMIJA ODGOVARAJUCI IZBOR LECENJA  PACIJENATA SA MALIGNO IZMENJENIM ADENOMIMA?

(  accepted August 27¸ 1999 )

Aleksandar Nagorni, Clinic for Gastroenterology and Hepatology¸ Clinical Center Nis.

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ABSTRACT

Colorectal adenomas are the large bowel carcinoma precursors. Malignant alteration of adenomas is common finding after colonoscopic polypectomy. In prospective ten years study¸ 64  malgnant altered adenomas ( MAA ) in 61 patients were diagnosed and followed up. MAA prevailed in sigmoid colon. Submucosal MAA were discovered only distal to the splenic flexure.  In 20 ( 32.78% ) cases MAA were associated with multiple adenomas, another MAA¸ single or multiple colorectal carcinoma ( CRC ). Colonoscopic polypectomy was definitive and adequate treatment in 74.41% patients with intramucosal MAA and in 11.11% patients with submucosal MAA. Three patients refused surgery¸ and therefore  colonoscopic polypectomy was definitive treatment for 60.65% MAA patients. Follow - up colonoscopies should  be performed at 3 months interval during the first year after polypectomy of submucosal MAA  with favourable criteria¸ then every 6 months up to 5 years after the polypectomy and thereafter annually. After the colonoscopic polypectomy of intramucosal MAA we recommended follow up colonoscopy at 6 months interval up to 2 years¸ then anually up to 5 years¸ and thereafter every 2 years. Patients with MAA should be included in a stringent colonoscopic surveillance program.
 
 

Key words: intramucosal malignancy, adenoma, synchronous lesions, colonoscopy, polypectomy.

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Abbreviations used in this article: MAA malignant altered adenoma, CRC¸ colorectal carcinoma
 
 

INTRODUCTION

Adenomatous polyps are neoplastic precursors of colorectal cancer (CRC) (1). Malignant transformation of colorectal adenomas is in function of the the the size, histologic structure, grade of dysplastic changes and number of adenomas, synchronous or metachronous ( 2¸3,4 ).

In literature malignant transformation of colorectal adenomas was reported differently. “Malignant polyp” is an adenoma in which cancer cells have penetrated through the muscularis mucosa into the submucosa (pedicle) of the adenoma (5). If cells which have all of the morphologic characteristics of cancer are present in the mucosal layer alone and have not invaded through the muscularis mucosa, the cancer is “noninvasive” and the adenoma is therefore not a “malignant polyp” (6-11). Other terms used for “noninvasive” carcinoma are: carcinoma in situ and intramucosal carcinoma. Fenoglio and Pascal were reported two subgroups of malignant transformation of colorectal adenomas dependening on whether the carcinoma focus are limited to the mucosa (intramucosal type) or pn the submucosa level (submucosal type) ( 12 ). It seems that biological behavior, not only  the age of lesion influence progression from intramucosal to submucosal type. Some authors reported a small adenoma with foci of submucosal carcinoma and a big adenoma with foci of intramucosal carcinoma (13).

Haggitt et al. defined the level of invasion of the colorectal carcinoma according to the following criteria: Level 0 – carcinoma in situ or intramucosal carcinoma or both¸ are not defined as invasive because they have not extended below the muscularis mucosa; level 1 – carcinoma invading through the muscularis mucosa into submucosa but limited to the head of the polyp (i.e., above the junction of the adenoma and its stalk); level 2 – carcinoma invading to the level of the neck of the adenoma ( the junction of adenoma and its stalk); level 3 – carcinoma invading any part of the stalk; level 4 – carcinoma invading into the submucosa of the large bowel wall below the stalk of the polyp but above the muscularis propria ( 10 ). According to the above mentioned criteria , invasive carcinoma arising in a pedunculated adenoma could be classified from level 1 to 4, but invasive carcinoma arising in a sessile, broad based adenoma is by definition a level 4 lesion because it involves the submucosa of the underlying large bowel wall. The level of invasion is  the main factor in  determining the prognosis of malignant alterated adenoma (MAA).

The frequency of malignant transformation of colorectal adenomas is 2.1-20% (7,14-21). The malignancy rate of colorectal adenomas is lower only when  endoscopically removed adenomas were considered, and is remarkably higher when surgical material is included. In the case of endoscopic removal the rate of malignant alteration was between 0.4 and 4.9%, average 3.8%. Reported lower malignancy rate is probably in connected with the “courage” of the endoscopist to  decide whether to remove even the large polyps during the colonoscopy, because as a rule, adenomas removed in this way extend up to only 2 or 3 cm in diameter (17).

Reported malignancy rate of the colorectal adenomas is between 1.5 and 9.5% for tubular, 5.8-29.2% for tubulovillous and 8.8-55.9% for villous adenoma (16, 22-25). The frequency of malignancy of multiple colorectal adenomas is 3.7% for tubular, 19.3% for tubulovillous and 57.1% for multiple villous adenomas (16).

In adenomas less than 10 mm in diametr reported malignancy rate is 1-22.5% ¸ but in those between  10-20 mm, and more than 20 mm, malignancy rate is 3.1-30% and 16.3-68.1%, respectively (7¸6¸14¸15¸21¸23,14,15,21,27 - 30). In adenomas  greater than 30 mm in diamter malignancy rate is up to 75.8% (25, 31). Malignant transformation of sessile colorectal adenomas is more frequent than pedunculated (14,32) and semipedunculated adenomas (32).

MAA of the large bowel represents a form of early CRC. These lesions are often removed via colonoscopic polypectomy. After examination by a the pathologist and the diagnosis of MAA, the clinician has to decide whether polypectomy itself is the adequate therapy or  the patient needs a subsequent definitive surgical resection (33).

We undertook prospective study of colonoscopically removed MAA to determine  the parameters which provide information and what is the best for a patient with endoscopically resected MAA.
 

MATERIAL AND METHODS
In prospective, ten years study we evaluated 61 patients with malignant transformation of colorectal adenoma(39 males, 22 females, age range 37-80 years, mean 61.1 years). Patients with incomplete colonoscopy, inflammatory bowel disease, history of benign and malignant colorectal tumors and patients with familial history of CRC, breast or ovarian cancer were excluded from the study.

Colonoscopy were performed with Olympus colonoscope CF 20HI and CF 30HI. All polypoid lesions were completely removed by standard or “piece meal” polypectomy technique. Polyps were resected with polypectomy snare using electrosurgical unit and standard diathermic snares (Olympus). Classic HE (hematoxilin-eozin) staining for confirmation of pathohistologic processes and histochemic’s stainings (AB-PAS, HID/AB) for mucins were used.

In submucosal MAA pathologist evaluated: the level of invasion according to Haggitt’ s criteria, distance between resection margin and carcinoma, differentiation of adenocarcinoma, lymphomatous and venous invasion.

The first control colonoscopy was done within 4 weeks to evaluate residual adenoma.Follow up colonoscopies were performed at 3 months intervals up to two years from the initial intervention, twice per year up to five years, and than annually. Patients who refused surgery of MAA with submucosal invasion and patients with high operative risk were followed-up at 3 months intervals up to two years, after that in a 6 months intervals up to five years from polypectomy, and than once a year.

For statistical analysis Student’s t test and c2 test were applied.
 

RESULTS
In 61 patients there were 64 MAA. Fifty nine patients had single, but in 2 females there were synchronous (two and three) MAA. Intramucosal MAA were diagnosed in 46 (71.87%), but submucosal MAA in 18 (28.13%) cases (p<0.01). Intramucosal MAA were more frequent in males (65.21%), but frequency of submucosal MAA was equal (50%) in both, males and females (Table 1).

MAA prevailed in sigmoid colon (table 2). In rectum, sigmoid and descending colon there were 92.19% of total number of MAA. Frequency of MAA localized distal to the splenic flexure were significantly higher than those localized in the right colon (7.81%), p<0.001.

Intramucosal MAA prevailed in sigmoid colon (52.17%), too¸ and were statistically  more frequent than rectal, intramucosal MAA (23.91%), p<0.05. The similar frequency of intramucosal MAA located distal to the splenic flexure as a group in total, in relation to the right colon, was observed too (89.13%), p<0.001.

Submucosal MAA were detected only in rectum, sigmoid and descending colon.

Pedunculated MAA (57.81%) were more frequent than sessile MAA (42.19%), p>0.05. Pedunculated intramucosal MAA were more frequent (67.39%), than sessile (32.61%). On the contrary, sessile submucosal MAA were more frequent (66.67%), than pedunculated (33.33%). Observed differences were statistically significant (p<0.05).

The size of removed MAA  varied from 6 to 50 mm (Table 3). Most of MAA were 11-20 mm in diameter (45.31%), less than  10 mm (23.43%), and 21-30 mm (21.87%). Mean diameter of removed MAA was 19.71 mm. Submucosal MAA were larger than intramucosal MAA (24.55 mm versus 17.82 mm), p>0.05. Tubulo-villous type of MAA was the most frequent pathological finding (table 4).In relation  to the villous MAA observed difference was statistically significant (p<0.01). In intramucosal group the difference is even higher , but in submucosal group, villous MAA prevailed. Tubulo-villous MAA prevailed in rectum and sigmoid. In ascending and transverse colon tubulo-villous MAA were the only finding (Table 5).  The most frequent segment of localization of tubulo-villous and villous MAA was sigmoid colon (56.25% and 57.14%, respectively).

Pedunculated MAA  up to 20 mm in diameter  (78.37%) are statistically more frequent (p<0.01) than pedunculated MAA with diameter greater than 20 mm (21.63%).

Sessile MAA were up to 20 mm in diameter  in 55.56% cases. In 44.44% of cases  their diameter  exceeded  20 mm  (p>0.05).

Peduncular macroscopic growth pattern was similar in tubular (60%), tubulo-villous (57.89%) and villous (57.14%) MAA.

Mean dimeter of tubular MAA was 20 mm (range 8-30 mm), tubulo-villous 16.36 mm (range 8-40 mm), and villous MAA 25.71 mm (range 6-50 mm). The smallest MAA had villous histologic structure, pedunculated pattern of growth, and were located in descending colon.

MAA up to 20 mm in diametr were mostly pedunculated (65.90%). Those   MAA were more than 30 mm in diameter, except one were sessile (83.33%). Frequency of pedunculated and sessile MAA  21-30 mm in diametr was equal (50%). Table 6.

The most of tubulovillous (84.21%) MAA had diameters up to 20 mm. In 60% of cases tubular MAA had diameter up to 20 mm, while 61.90% of villous MAA  diameters were larger than than 20 mm. One third of the total villous MAA had diameters 21-30 mm, but 23.80% diamaters more than 30 mm (Table 7). The largest MAA (50 mm) was villous, submucosal MAA

Tubular MAA were more frequent in females, but tubulo-villous MAA in males. Villous MAA were similar in frequency in males and in females, 33.33% versus 32% (Table 8).

Some characteristics of patients and adenoma with submucosal MAA are shown in table 9.

In 16 (88.88%) patients¸ resection margin was involved. Vessels invasion was detected in 7 (38.88%) patients, but poorly differentiated adenocarcinoma in 8 (47.05%) patients. In 5 (27.78%)  patients all unfavorable criteria were recorded.

In 20 (32.78%) patients synchronous neoplasms were diagnosed. In eleven (18.03%) patients MAA were associated with CRC (table 10) but in 9 (14.75%) with multiple colorectal adenomas. In patients with synchronous CRC most of MAA ( 81.18% ) were in sigmoid colon. All, except one patient (No. 4) had intramucosal MAA. Two synchronous CRC were associated with three intramucosal MAA (No. 8).

In patients with MAA which diameters varied between 5-9 mm, multiple colorectal adenomas (2-5) of tubular and tubulo-villous histologic structures were detected in the surrounding are of MAA (five patients) and in distant large bowel segment (three patients).

In 32 (74.41%) of 43 patients with intramucosal MAA colonoscopic polypectomy was definitive treatment. In one fourth (25.59%) of patients additional surgical procedure was required because of synchronous submucosal MAA (one patient) and CRC (ten patients). During additional radical colorectal surgery in 4 patients¸ segments with previously removed intramucosal MAA were resected: two patients with synchronous intarmucosal MAA  and CRC (left hemicolectomy), one patient with two synchronous CRC and three intramucosal MAA (subtotal colectomy) and one patient with synchronous intarmucosal and submucosal MAA (left hemicolectomy).

Additional surgical procedures were performed in 13 (72.22%) patients with submucosal MAA. Lymph node metastasis was detected in one patient (7.69%). Two (11.11%) patients had favorable criteria and colonoscopic polypectomy was definitive treatment, but three (16.67%) patients refused surgery.

Colonoscopic polypectomy was definitive treatment for 37 (60.65%) patients with MAA.

There were no fatal complications during colonoscopic polypectomy. Early post-polypectomy bleeding was observed in two patients with sessile submucosal MAA and controlled by   injection hemostasis.

Because of cardio-pulmonary complication one patient with submucosal MAA  died 24 hours after the surgery.

Patients with intramucosal MAA were followed up 24-96 months (mean 64,3 months). Eighteen months after the subtotal colectomy because of two synchronous CRC and three intramucosal MAA¸ distant metastasis were detected. In the remaining patients there were no residual tumors, recurrent MAA, or distant metastasis. In 10 patients 12-60 months with mild or moderate dysplasia after polypectomy metachronous adenomas were observed.

Patients with submucosal MAA were followed up by colonoscopy 12-84 months (mean 43 months).

The shortest follow up period had three patients who refused surgery (12-18 months). In one patient metastasis were detected after 12 months of refusing the surgical procedure. Recurrence and distant metastasis was discovered in one patient with involved resection margin, with vessels invasion and poorly differentiated adenocarcinoma, 48 months after the surgery. Metachronous adenoma was observed in one patient 24 months after the surgery, too.
 

DISCUSSION
Colorectal adenomas are benign tumors.They are considered to be the precursor lesions of  CRC. Most CRC are believed to originate from preexisting adenomas. The adenoma-carcinoma sequence plays a major role in secondary prevention of CRC. sessile and pedunculated adenomas are a common precursor of colonic and rectal carcinoma, and are easily detected by colonoscopy. The colonoscopic removal of adenomatous premalignant polyps may prevent CRC and reduce its incidence. The adenoma-to-carcinoma evolution time varies from five to ten years, however most adenomas do not transform to CRC and CRC may arise without a precursor adenoma (34).

Although there is no doubt about the existence of flat neoplastic lesions and “de novo” carcinomas, there is still controversy about their participation  in the genesis of advanced CRC (35).

The National Polyp Study in 1993 showed that resecting all adenomas found during the colonoscopy reduced the subsequent incidence of CRC to 76-90% (36).

The annual incidence of all CRC in the United States is approximately 150 000 cases. Koretz  estimated that 725 000 people in the US harbor at least one malignant adenoma ( 37 ).

Even if all 150 000 cases of CRC were associated with symptoms and began as malignant adenomas, the average latent phase is 4.8 years. If  some CRC are removed while the patient is still asymptomatic (discovered on screening examination) and because at least some CRC arise de novo from the intact mucosa, the average latent phase must be even longer. This may  suggest that it cannot be assumed that the histologic finding of carcinoma in adenoma that has been observed for many years represents “malignant degeneration” of a previously benign neoplasm; such a malignancy may have had that histologic characteristic from the start. Further on, histologically ominous lesions (malignant adenomas) may often have prolonged benign clinical courses.

The risk of MAA is 2.1-20% (7,14-21,38). Frequency of MAA with submucosal invasion (invasive carcinoma) varies between 0.2% and 9.4% (39,30,40-42,7). The rate of invasive carcinoma in adenomas depends on the investigated sample composition (16). The lowest rates (0.6-1.7%) were found in screening studies involving asymptomatic patients. In autopsy studies the malignancy rate is between 1.1% and 3.6% ( 43¸45-49,14).Endoscopic studies have demonstrated a lower malignancy rate (0.4-4.9%) than surgical investigations, 6.3-22.9% (3¸16¸23¸ 50-52).

The frequency rate for submucosal MAA, proximal to the sigmoid colon is 4.1% but in rectum and sigmoid 17.8% and 7.8%, respectively (16).

After colonoscopic polypectomy diagnosis of MAA is exclusively histologic. Friability, ulceration, firmness, “dunce cap” sign, asymmetry, lobularity of adenoma surface could be endoscopic criteria for MAA (53,54).

Intramucosal MAA are more commonly diagnosed  than submucosal MAA. In our study there were 43 patients with 46 (71.87%) intramucosal MAA and 18 patients with single submucosal MAA (28.13%).

According to our study intramucosal MAA were discovered in all segments of the large bowel, except cecum. The most frequent segment of localization of intramucosal MAA was sigmoid colon (52.17%).

Submucosal MAA were detected in the left colon and rectum, only. Submucosal MAA were larger than intramucosal MAA (6-40 mm, mean 17.82 mm vs 10-50 mm, mean 24.55 mm). Our findings confirm findings in literature. Chanterau et al. (55) were found that very small adenomas not exceeding 5 mm in diameter carry no risk of harboring a carcinoma. None of the 5027 adenomas of this size located throughout the entire colorectum was found to contain submucosal MAA (25).

Most colorectal adenomas and CRC are found in the distal large bowel segments.This  may be explained by a higher concentration of carcinogenic agents in this region. However, differences in the embriological origin of the epithelium of the proximal and distal large bowel segments may also affect differences in susceptibility to exogenous carcinogenesis (56) and may explain finding that submucosal MAA in our study was found distal to the splenic flexure, only.

Molecular genetic studies provide support for the theory that initiation and progression of left-sided and right-sided CRC may involve different genetic mechanisms (57-59).

The risk of submucosal MAA increases with increasing adenoma size. In our study, 60% of adenoma 31-40 mm in diameter and only adenoma 41-50 mm in diameter were of submucosal type of MAA. The relationship between adenoma size and the risk of submucosal MAA is significantly modified by the site of the adenoma. For medium-sized lesions, the increase in risk is much greater in the rectum than in the right or left colon. Large adenoma of diameter  greater than 35 mm, in contrast carry a significantly higher risk when located in the right or left colon  than in  the rectum. When the histologic structure is also taken into account, this relationship in large adenomas is modified, and there is a higher risk for tubulo-villous adenomas located in the right colon and for tubular adenomas in the left colon and rectum (25).

In intramucosal MAA where there is no invasion into the submucosa of the adenoma and where the malignant cells are confined to the mucosal layer, the malignant cells have neither potential for recurrence once the adenoma is resected nor the potential for metastasis. This is true whether adenoma is sessile or pedunculated. International consensus is that  intramucosal MAA is completely cured by polypectomy (5,9).

In our study patients with intramucosal MAA  were reffered for surgery because of synchronous lesions (submucosal MAA, CRC). During the follow up there were distant metastasis in female patient with synchronous CRC (two) and intramucosal MAA (three). During colonoscopic follow up, metachronous adenomas were removed in 10 (25.64%) patients with intramucosal MAA. In 39 (90.69%) patients polypectomy excised intramucosal MAA, but in some patients additional surgery was neccessary  because of synchronous CRC. .

In 32.78% patients with MAA we detected synchronous lesions (CRC, another MAA or multiple adenomas. Pines et al. (60) reported that there were significantly (p<0.01) more patients with multiple colonic lesions in patients with intramucosal and submucosal MAA than in the patients with benign adenoma or CRC. Coexisting adenomas were much closer to the index growth and demonstrated more severe dysplastic changes in the case of cancerous adenomas than those associated with benign adenoma or CRC.

The treatment for submucosal MAA is controversial. Submucosal MAA were designated as having favorable (well or moderatelly well differentiated adenocarcinoma with at least a 2 mm free resection margin, without lymphomatous or vascular invasion) or unfavorable (poorly differentiated adenocarcinoma with an unassessable resection margin, or a margin of <2 mm with lymphomatous or venous  invasion) criteria (6,7,61,62). Deeper invasion and lower differentiation are associated with a higher rate of lymph node involvement (63).

Colonoscopic polypectomy is definitive treatment for submucosal MAA with favorable criteria (6,7). Recurrence of submucosal MAA or advanced CRC, after polypectomy, in patients with unfavorable histologic  criteria were detected in 19.7% patients (6,9,28,30,64-66). In patients with favorable histologic criteria recurrence or advanced CRC were not observed (61). We detected only one recurrent CRC 48 months after polypectomy of MAA with unfavorable criteria.

Because of the orderly progression of CRC (67) from intramucosal MAA (carcinoma in situ) to invasive carcinoma in an adenoma (submucosal MAA) to subsequent invasion of the colon wall, there is little doubt that an adenoma which contains noninvasive carcinoma would probably progress to invasive carcinoma with time. That sequence is interrupted and completely terminated by endoscopic polypectomy (5,6,68).

When carcinoma invades the submucosa of pedunculated adenoma, it was considered that the pedicle acts as a physiological barrier to spreading of malignant cells into the submucosa of the colon wall because of the increased distance between the submucosa in the adenoma head and the submucosa of the colon wall. This pedicle “buffer zone” is not present in a sessile adenoma (5).

Incidence of metastasis in lymph nodes in MAA is 2.3-25% (10,40,69-71). Metastatic potential of intramucosal MAA is 2-5% (6). Completely removed submucosal MAA with favorable criteria have  low rate of metastasis in lymph nodes. Rate of metastasis in lymph nodes is in correlation with the size of submucosal MAA. The mean diameter of submucosal MAA is greater in patients with positive lymph nodes metastasis compared with patients without lymph nodes metastasis (71).

The risk of residual submucosal MAA or nodal carcinoma, in patients with favorable criteria is 0.3% for pedunculated, but 1.5% for sessile MAA (7).

The risk of residual CRC is usually lower than the danger of further cancer surgery when: 1) the adenoma is considered endoscopically fully resected, 2) histologically the line of resection is not involved with cancer cells¸ 3)  there is no evidence of the other unfavorable criteria (72).

Submucosal MAA of tubular histologic structure have a low, but villous, submucosal MAA a high incidence rate of lymph nodes metastasis (25%). Peduncular, tubulovillous submucosal MAA in relation to lymph nodes metastasis have a feature of tubular MAA, sessile tubulovillous MAA a features of  villous MAA (69).

During the follow up period of 4-10.6 years there were no metastasis in patients with favorable criteria in relation to 42% of metastasis in patients with unfavorable criteria (7). Similar results were reported in Switzerland study (73).

There were no adverse outcome in patients with favorable criteria (only two patients) during follow up period 48-72 months. Distant metastases were detected in patients who refused surgery in follow up period of 12 months. Recurrence and distant metastasis were observed 48 months after the  surgery in patients with all unfavorable criteria.

The criteria of completeness of polypectomy was discussed by several investigators (6,7,10,66). Christie (74) term them the Morson criteria. Morson criteria for curative endoscopic treatment alone of malignant colorectal polyps are:

1.       Proper microscopic examination of entire malignant adenoma confirming:

a)       absence of malignancy at resection margin

b)      absence of malignancy within lymphatics

c)       absence of poor differentiation

2. Visual confirmation of completeness of polypectomy.

Colonoscopic polypectomy is definitive and adequate treatment for intramucosal and submucosal MAA with favorable histologic criteria, except if synchronous CRC is detected in adjacent large bowel segment when additional surgery should be performed. In 60.56% patients with MAA colonosocpic polypectomy was definitive treatment. In individual patients the risk from laparotomy is correlated with the risk of recurrence after polypectomy of submucosal MAA.

Colonoscopic polypectomy of pedunculated, submucosal MAA with unfavorable criteria is inadequate therapy and subsequent surgery should be done. Sessile submucosal MAA because of the failure of physiologic barrier (pedicle) are in group of patients with unfavorable criteria.

There was opinion that the management of intramucosal MAA after colonoscopic polypectomy is the same as for benign adenoma (75). We recommend more strict and seriouis approach to the patients with MAA then it was reported. After colonoscopic polypectomy of intramucosal MAA we recommend follow up colonoscopy at 6 months interval up to two years, then annualy up to five years, and then every two years.

Follow up colonoscopies should be done at 3 months interval during the first year from polypectomy of submucosal MAA with favorable criteria, then every 6 months up to five years from polypectomy and then annually.

Patients with MAA should be included in a serious colonoscopic surveillance programme because of the risk of missed colorectal tumors (especially CRC) and metachronous polyps.
 

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Table 1. Type of MAA in dependence of sex

Table 2. Localisation of MAA
 

Localisation	Intramucosal MAA	Submucosal MAA	Total
rectum	11 (23.91%)	8 (44.44%)	19 (29.69%)
sigmoid	24 (52.17%)	8 (44.44%)	32 (50%)
descending	6 (13.05%)	2 (11.12%)	8 (12.50%)
transverse	3 (6.52%)	_	3 (4.69%)
ascending	2 (4.35%)	_	2 (3.12%)
cecum	_	_	_
total	46 (100%)	18 (100%)	64 (100%)

Table 3. Diameters of MAA
 

Diameter (mm)	Intramucosal MAA	Submucosal MAA	Total
< 10	11 (23.91%)	4 (22.22%)	15 (23.43%)
11-20	24 (52.17%)	5 (27.78%)	29 (45.31%)
21-30	9 (19.57%)	5 (27.78%)	14 (21.87%)
31-40	2 (4.35%)	3 (16.67%)	5 (7.81%)
41-50	_	1 (5.55%)	1 (1.58%)
Total	46 (100%)	18 (100%)	64 (100%)
Mean diameter (mm)	17.82	24.55	19.71

Table 4. Histologic structure of MAA
 

Histologic structure	Intramucosal MAA	Submucosal MAA	Total
Tubular	2 (4.45%)	3 (15.80%)	5 (7.82%)
Tubulo-villous	32 (71.11%)	6 (31.57%)	38 (59.37%)
Villous	11(24.44%)	10 (52.63%)	21 (32.81%)
Total	46 (100%)	18 (100%)	64 (100%)

Table 5. Distribution of histologic structure of MAA in different segments of the large bowel

Table 6. Diameters of MAA and macroscopic pattern of growth
 

Diameter (mm)	Pattern of growth		Total
	Pedunculated MAA	Sessile MAA
< 10 mm	11 (73.33%)	4 (26.67%)	15 (100%)
11-20 mm	18 (62.06%)	11 (37.94%)	29 (100%)
21-30 mm	7 (50%)	7 (50%)	14 (100%)
31-40 mm	1 (20%)	4 (80%)	5 (100%)
41-50 mm	_	1 (100%)	1 (100%)
Total	37	27	64 (100%)

Table 7. Diameters of MAA and histologic structure
 

Diamater (mm)	Histologic structures of MAA			Total
	Tubular	Tub.villous	Villous
< 10 mm	1 (20%)	11 (28.94%)	3 (14.28%)	15
11-20 mm	2 (40%)	21 (55.26%)	6 (28.57%)	29
21-30 mm	2 (40%)	5 (13.15%)	7 (33.33%)	14
31-40 mm	_	1 (2.65%)	4 (19.04%)	5
41-50 mm	_	_	1 (4.78%)	1
Total	5 (100%)	38 (100%)	21 (100%)	64

Table 8. Sex and histologic structure of MAA

Table 9. Characteristics of submucosal MAA
 

No.of pts	Sex/ age	Growth	Size mm	Localization	Histology	Distance from resection margin	Vessels invasion	Differentiation	Surgery	Follow-up (months)
1	F/72	sessile	10	sigmoid+ ssimTV	TV	involved	-	moderate well	+	60
2	M/63	sessile	40	rectum	TV	involved	+	poor	+	30
3	M/68	pedunc.	10	sigmoid	V	3 mm	-	well	-	72
4	M/56	sessile	40	sigmoid	V	involved	-	moderate well	+	84
5	M/65	pedunc.	15	sigmoid	V	involved	-	poor	+	postoper. dead
6	F/54	pedunc	15	rectum	TV	involved	-	moderate well	refused	18
7	F/63	pedunc.	10	rectum	TV	3 mm	-	moderate well	-	48
8	F/68	sessile	30	rectum	V	involved	+	poor	+	30
9	F/80	sessile	50	rectum	V	involved	+	poor	refused	12 (metastasis)
10	M/71	sessile	30	rectum	V	involved	+	poor	+	48 (recurrence +metastasis)
11	F/57	sessile	12	sigmoid	V	involved	+	moderate well	+	60
12	F/77	sessile	30	sigmoid	T	involved	+	moderate well	+	24 (metachron. adenoma)
13	M/46	sessile	20	rectum	TV	involved	-	well	+	36
14	F/53	sessile	20	descending	T	involved	-	moderate well	+	60
15	M/71	pedunc.	10	sigmoid+ scCRC	V	involved	+	poor	+	48
16	M/72	sessile	40	rectum	V	involved	-	poor	+	36
17	F/62	pedunc.	30	descending	T	involved	-	poor	refused	18
18	M/61	sessile	30	sigmoid	TV	involved	-	moderate well	+	48

T-tubular, TV-tubulovillous, V-villous

Table 10. Some characteristics of patients and synchronous MAA and CRC