Cancer-associated alterations of blood group antigen expression in human colorectal polyps

Human colorectal carcinoma tissues may exhibit several patterns of altered blood group substance (BGS) expression: reappearance of A, B, H, or Lewisb antigens in distal colon; deletion of BGS in the proximal colon with or without precursor substance accumulation; and incompatible BGS expression in proximal or distal colon. The present study evaluated these cancer-associated alterations in colorectal polyps with different malignant potential. With respect to ABH antigens, hyperplastic polyps (HPs), considered to have no malignant potential, did not exhibit incompatibility and only a few cases demonstrated BGS reappearance or deletion. Adenomatous polyps (APs) however, frequently reexpressed ABH antigens or expressed incompatible BG-A or B in 27% of polyps; one specimen demonstrated BG-B deletion. Precursor expression was not found in HPs but was frequently observed in APs. Reappearance of ABH in distal polyps was significantly correlated with increasing grade of dysplasia, but was not significantly correlated with polyp size or histological type. With respect to Lewis antigen expression, Lewisb reappearance occurred in almost every distal polyp, and Lewisa-Lewisb coexpression was also quite common. Lea deletion was frequently noted, especially in HP, but the significance of this finding is unclear. This study indicates that several antigenic alterations that occur in colorectal cancer tissues also appear in premalignant polyps, and often in early stages of the neoplastic process. The observation that incompatible expression of BG-A or B occurs only in AP and cancer tissues (as well as mucosa adjacent to cancer) but not in fetal colonic mucosa, adult normal colonic mucosa, or HP, suggests that this may be a cancer-specific phenomenon.     

Relationship between breast cancer and colorectal adenomatous polyps. A case-control study.

Although there is a known reciprocal association between breast and colorectal cancer in women, few studies have investigated whether a similar association exists between breast cancer and colorectal adenomatous polyps, known to be precursor lesions for colon cancer. A case-control study was conducted on patients in three colonoscopy practices in New York to determine possible risk factors for adenomatous polyps. Among women studied, there were 128 patients with incident adenomatous polyps and 284 control subjects who underwent colonoscopy and had no colorectal neoplasia. No significant association between the incidence of an adenomatous polyp in the colon or rectum and a history of breast cancer was found (odds ratio, 0.71; 95% confidence interval, 0.34 to 1.64). If shared risk factors for breast and colorectal cancer are the reasons for the concurrence of these two malignant lesions, these results suggest that these factors act at the level of promoting adenomatous polyps of the colon and rectum into colorectal cancer.     

大肠息肉1884例患者的临床观察及恶变特征分析

目的:了解大肠息肉的临床表现,探讨息肉的恶变特征。方法:对6144例有下消化道症状患者进行结肠镜检查,记录大肠息肉患者的临床表现以及年龄、性别等资料,对大肠息肉的发生率、内镜下表现、病理类型进行分析。结果:发现结肠息肉患者1884例,检出率30·66%。男性占61·68%,女性占38·32%。年龄>60岁者占64·12%。临床症状中便血占56·26%。息肉直径0·2~3·8cm不等,恶变和重度不典型增生息肉直径>2cm者占79·73%。息肉发生于左半结肠者占67·41%。癌变和重度不典型增生息肉发生于左半结肠占85·42%(375/439)。病理类型:腺瘤性息肉42·00%,炎性息肉38·30%,错构瘤性息肉5·92%,增生性息肉6·45%,幼年性息肉7·40%。炎性息肉2例(2枚)癌变。腺瘤伴轻至中度不典型增生460枚占15·98%,重度不典型增生106枚占5·56%,癌变279枚占9·69%。腺瘤性息肉中管状腺瘤占37·46%(1078/2878),绒毛状腺瘤31·51%(907/2878),混合性腺瘤31·03%(893/2878)。重度不典型增生和癌变率在上述三种腺瘤中分别为6·68%(72/1078)、24·15%(219/907)和16·57%(148/893)。结论:肠息肉临床症状以便血最多。多见于>60岁的男性。息肉分布于左半结肠者多见,癌变息肉和重度不典型增生息肉也易发生于左半结肠,癌变和重度不典型增生多发生于腺瘤性息肉。管状腺瘤发生重度不典型增生和癌变率最低,绒毛状腺瘤最高。     

Accuracy of FDG-PET/CT for Detection of Incidental Pre-Malignant and Malignant Colonic Lesions - Correlation with Colonoscopic and Histopathologic Findings

Purpose: We evaluated all PET/CTs acquired for patients without a primary diagnosis of colorectal cancer, and compared results for those who had subsequent colonoscopy within 6 months, to assess the accuracy of FDG PET/CT for detection of incidental pre-malignant polyps and malignant colon cancers. Materials and Methods: Medical records of 9,545 patients who underwent F-18 FDG PET/CT studies over 3.5 years were retrospectively reviewed. Due to pre-existing diagnosis of colorectal cancer, 818 patients were excluded. Of the remainder, 157 patients had colonoscopy within 6 months (79 males; mean age 61). We divided the colon into 4 regions and compared PET/CT results for each region with colonoscopy and histopathologic findings. True positive lesions included colorectal cancer, villous adenoma, tubulovillous adenoma, tubular adenoma and serrated hyperplastic polyp/hyperplastic polyposis. Results: Of 157 patients, 44 had incidental colonic uptake on PET/CT (28%). Of those, 25 had true positive (TP) uptake, yielding a 48% positive predictive value (PPV); 9% (4/44) were adenocarcinoma. There were 23 false positive (FP) lesions of which 4 were hyperplastic polyp, one was juvenile polyp and 7 were explained by diverticulitis. Fifty eight patients had false negative PET scans but colonoscopy revealed true pre-malignant and malignant pathology, yielding 23% sensitivity. The specificity, negiative predictive value (NPV) and accuracy were 96%, 90% and 87%, respectively. The average SUVmax values of TP, FP and FN lesions were 7.25, 6.11 and 2.76, respectively. There were no significant difference between SUVmax of TP lesions and FP lesions (p>0.95) but significantly higher than in FN lesions (p<0.001). The average size (by histopathology and colonoscopy) of TP lesions was 18.1 mm, statistically different from that of FN lesions which was 5.9 mm (p<0.001). Fifty-one percent of FN lesions were smaller than 5 mm (29/57) and 88% smaller than 10 mm (50/57). Conclusions: The high positive predictive value of incidental focal colonic FDG uptake of 48% for colonic neoplasia suggests that colonoscopy follow-up is warranted with this finding. We observed a low sensitivity of standardly acquired FDG-PET/CT for detecting small polyps, especially those less than 5 mm. Clinician and radiologists should be aware of the high PPV of focal colonic uptake reflecting pre-malignant and malignant lesions, and the need for appropriate follow up.     

Sporadic colorectal cancers with microsatellite instability and their possible origin in hyperplastic polyps and serrated adenomas

BACKGROUND: Microsatellite instability (MSI) is seen in 10%-15% of sporadic colorectal cancers mostly in the right colon, but the precursors of cancers with MSI remain unknown. We examined whether sporadic cancers with MSI arise from pre-existing benign proliferative lesions (such as hyperplastic polyps or serrated adenomas [together denoted as "serrated polyps"]). METHODS: The frequency of benign epithelial lesions (serrated polyps and conventional adenomas) was determined by histologic review of resection specimens from individuals (n = 29) with sporadic colorectal cancer with MSI and from a matched control group (n = 29) with cancer showing microsatellite stability (MSS). MSI status, expression of mismatch repair enzyme (product of the human mut-L homologue 1 [hMLH1] gene), and hMLH1 gene promoter methylation in the benign lesions were determined. Data were analyzed by the chi-square test, by Wilcoxon's rank-sum test, and by conditional logistic regression as appropriate, and a two-sided probability less than.05 was considered to be statistically significant. RESULTS: Individuals with cancers showing MSI were more likely to harbor at least one serrated polyp than individuals with cancers showing MSS (odds ratio = 4.0; 95% confidence interval = 1.1 to 14.2; P =.03), but the frequency of conventional adenomas was the same in both groups (P =.52, Mann-Whitney test). Loss of hMLH1 protein expression was seen in lesions from 10 of 13 patients with MSI, but no loss was seen in lesions from four patients with MSS (P =.02, Fisher's exact test). Loss of hMLH1 protein expression was associated with MSI in assessable lesions. The hMLH1 promoter was methylated in all assessable serrated polyps from patients with cancers showing MSI but in none of the lesions from patients with MSS cancers. CONCLUSIONS: Some right-sided hyperplastic polyps may give rise to sporadic colorectal carcinomas with MSI. Methylation of the hMLH1 gene promoter within neoplastic cell subpopulations may be a critical step in the progression to carcinoma. The frequency with which benign lesions progress to cancer with MSI is unknown.     

Cytogenetic comparisons of synchronous carcinomas and polyps in patients with colorectal cancer.

Thirty tumorous lesions from seven patients with colorectal cancer were short-term cultured and cytogenetically analysed: 16 non-adenomatous polyps, six adenomas, seven carcinomas, including one in polyp, and one lymph node metastasis. Clonal chromosome aberrations were found in 20 samples in 100% of the carcinomas, in 100% of the adenomas and in 37.5% of the non-adenomatous polyps, i.e. all ten lesions with a normal karyotype were histologically diagnosed as hyperplastic polyps. Although adenomas and carcinomas shared several karyotypic features, two chromosome aberrations, der(8;17)(q10;q10) and -14, were found in carcinomas but not in adenomas, indicating that they might be specifically associated with carcinoma development in the large bowel mucosa. The karyotypic similarity seen between the malignant and benign tumours in the same patient, and also sometimes among non-malignant polyps in the same case, indicates that these microscopically distinct lesions may be part of a single neoplastic clonal expansion.     

结肠高危性腺瘤的临床分析及Decorin 在腺瘤中的表达与意义

目的:探讨结肠高危性腺瘤的临床病理特征及Decorin在结肠腺瘤中的表达与意义。方法:对安徽医科大学第一附属医院2005年1 月～2008年11月收治的结肠息肉患者按照2006年美国《大肠息肉切除术后随访指南》进行风险分层并进行临床病理分析;采用免疫组化方法分别检测Decorin蛋白在20例正常组织、18例结肠癌和86例结肠息肉中的表达情况。结果:583 例结肠息肉患者中,非腺瘤性息肉243 例,低危腺瘤83例,高危腺瘤257 例。腺瘤性息肉组平均年龄（58.9±13.3）岁,高于非腺瘤性息肉组（55.5 ± 15.7）岁（P<0.05）;腺瘤性息肉组中其息肉直径≥1cm和数量≥3 个者均高于非腺瘤性息肉组（P<0.01）;腺瘤性息肉癌变率为9.1%,非腺瘤性息肉为0.8%（P<0.001）。 高危腺瘤较非高危腺瘤组便血症状更多,在内镜下更易观察到黏膜改变和表面分叶（P<0.05）。 Decorin在正常组织和非腺瘤性息肉以及管状腺瘤中呈高表达,而在含绒毛状结构、高度异型性的腺瘤和癌组织中低表达;Decorin的表达与腺瘤的病理类型与异型增生程度呈相关性（P<0.05）。 结论:结肠高危息肉在临床症状及内镜下都具有一定形态特征,对结肠息肉切除后的规范筛查、诊断和合理随访具有指导意义;Decorin蛋白的检测可作为一种有价值的指标,用于息肉恶性程度的评价。      

Clinicopathologic Features of Colorectal Polyps in Shahid Beheshti University of Medical Sciences (SBMU)

Aim: This study was designed to report epidemiologic findings of polyps in Iranian patients, and predict histology of polyp regarding to demographic and colonoscopic findings. Background: Classification of colorectal polyps had been revised in the past two decades and there is a need for polyp categorization in the Iranian Health System. Patients and methods: In this retrospective study, the medical records of patients with colonoscopic diagnosis of polyp in pathology departments of SBMU affiliated teaching hospitals were reviewed. Patient’s slides evaluated and demographics findings were assessed. The anatomical location, macroscopic appearance including size and histological assessment of all polyps were recorded. Results: From total number of 1106 polyps (detected in 862 patients), adenomatous polyps (638 [57.7%]) were the most prevalent findings, followed by colon mucosal tag (184[16.6%]), hyperplastic and serrated polyps (122[11%]), inflammatory polyps (110[9.9%]), hamartomatous (21[1.9%]), and malignant lesions (13[1.2%]). Multivariate logistic regression showed age (each one year increasing age; odds ratio [OR] = 1.026, 95%confidence interval [CI] = 1.016–1.036, p < 0.0001), location of polyp (right colon; OR = 1.905, 95%CI = 1.366–2.656, p < 0.0001), and polyp size of 5-10 mm (OR = 1.662, 95%CI = 1.214–2.276, p = 0.002), and polyp size of >10 mm (OR = 2.778, 95%CI = 1.750–4.411, p< 0.0001) were independently associated with neoplastic polyps. Also, polyp size of >10 mm (OR= 2.613, 95%CI= 1.083-6.307, p=0.033), tubulovillous pattern of polyp (OR= 3.508, 95%CI= 1.666-7.387, p=0.001) and villous pattern of polyp (OR= 10.444, 95%CI= 4.211-25.905, p     

Serrated Polyps of Colon and Rectum: a Clinicopathologic Review

Background

In the past decade, there have been significant changes in the classification and nomenclature of colorectal polyps. Previously, only two groups of lesions were widely recognized, the adenoma and the hyperplastic polyp. Adenomas were considered the only precursor of colorectal cancer, and hyperplastic polyps were considered innocent with no malignant potential. However, recent discoveries about molecular pathways of colorectal cancers have significantly changed our understanding of these neoplasms. Serrated polyps—previously uniformly called hyperplastic polyps—are now known to comprise a heterogeneous family of neoplasms united by their characteristic saw tooth morphology but differing in many important ways, including their malignant potential and molecular profile. This group of neoplasms includes both hyperplastic polyps and the more recently recognized serrated adenomas. Serrated adenomas can be subdivided into the traditional serrated adenoma and the sessile serrated adenoma/polyp. Both of these lesions show characteristic molecular changes, which differ from traditional colorectal adenomatous polyps.

Objectives

In this review, we will discuss the morphologic features of serrated colorectal lesions, the molecular alterations that characterize them, and their role in colorectal cancer development.

Material and Methods

The English literature regarding the new nomenclature will be reviewed and the key diagnostic points will be recorded.

Results and discussion

This large group of polyps has recently been better classified which needs specific attention by pathologists, gastroenterologists and even surgeons.

     

Microsatellite instability in hyperplastic and adenomatous polyps of the stomach.

BACKGROUND: Few studies have focused on the presence and significance of microsatellite instability (MSI) in gastric polyps, and the results on record are conflicting. The aim of the current study was to address this issue, taking into consideration the 2 main types of gastric polyps, the coexistence of foci of malignant transformation, and the expression of p53 and ERBB-2. METHODS: Six hyperplastic polyps, 10 adenomatous polyps, and 4 adenomatous polyps displaying foci of malignant transformation (intestinal-type carcinoma) were studied for MSI. The authors analyzed a mononucleotide repeat microsatellite (BAT-26) and 5 dinucleotide repeats in microdissected formalin fixed, paraffin embedded tissue sections that were representative of the lesions. Expression of p53 and ERBB-2 were evaluated by immunohistochemistry. RESULTS: BAT-26 positivity was detected in 1 of 6 hyperplastic polyps (16.7%) and in 2 of 10 adenomas (20%) without malignant transformation. In the 4 adenomatous polyps with carcinomatous foci, BAT-26 positivity was detected in 2 cases (50%) in both (adenomatous and carcinomatous) components of the lesions. p53 immunoreactivity was observed in 6 adenomatous polyps, 2 of them with malignant transformation. Overexpression of the ERBB-2 protein was detected in 1 adenomatous polyp with malignant transformation. CONCLUSIONS: Replication error (RER+) phenotype occurs in both hyperplastic and adenomatous polyps of the stomach. The highest frequency is observed in adenomatous polyps with carcinomatous foci, suggesting that MSI may play a role in the process of malignant transformation in this setting. No significant association was observed between RER+ phenotype and overexpression of p53 or ERBB-2 proteins.     

Precancerous lesions of the colon and rectum

We discussed significance of various kinds of precancerous lesions of the colon and rectum. Colonic adenoma was most important as a histogenetic background of colonic carcinoma, as it has been widely accepted. The first malignant transformation of adenoma seemed to occur at the relatively superficial layer of the central portion of adenoma in many cases. Growth rate of adenoma largely depended on cellular atypia. Six of twenty-seven patients with Peutz-Jeghers syndrome had advanced carcinoma and/or carcinoma in Peutz-Jeghers polyp. In general, malignant transformation in the polyp was higher in frequency in polyps more than 3.0 cm in the largest dimension. Significance of precancerous lesions in juvenile polyp, hyperplastic polyp, ulcerative colitis, Crohn's disease and radiation colitis was briefly presented.     

Expression of LeY and extended LeY blood group-related antigens in human malignant, premalignant, and nonmalignant colonic tissues

The LeY determinant, a difucosylated type 2 blood group-related antigen, is a positional isomer of the Leb blood group antigen and a fucosylated derivative of the LeX antigen. The LeX antigen behaves like an oncodevelopmental tumor-associated antigen in human colon cancer, and extended polyfucosyl LeX antigens are more specific for colon cancer tissues than are simple, monofucosyl LeX antigens. The present investigation compared the expression of simple and extended LeY antigens in a variety of malignant and nonmalignant human colonic tissues to gain insight into the normal distribution and cancer-associated expression of these antigens. Monoclonal antibody AH-6, which recognizes the LeY epitope irrespective of its carrier carbohydrate chain, stained the majority of specimens regardless of malignant potential or location within the colon. In contrast, CC-1 and CC-2 monoclonal antibodies, which recognize extended LeY structures, and KH-1, which is specific to trifucosyl LeY, preferentially stained malignant colonic tissues and rarely stained normal colonic mucosae. Mucosa immediately adjacent to cancer usually stained with AH-6 but not with KH-1, CC-1, or CC-2. Extended or trifucosyl LeY antigen expression was limited exclusively to premalignant (adenomatous) polyps and was invariably absent from nonpremalignant (hyperplastic) polyps. Moreover, among adenomatous polyps, extended LeY antigen expression tended to correlate with three parameters of malignant potential: larger polyp size; villous histology, and severe dysplasia. AH-6 failed to distinguish between hyperplastic and adenomatous polyps. In second-trimester fetal colonic mucosa, AH-6 bound to both proximal and distal segments whereas KH-1, CC-1, and CC-2 bound only to proximal segments. We conclude that in human colon, the LeY hapten is an oncodevelopmental cancer-associated antigen and extended LeY antigens are highly specific markers for malignancy and premalignancy.     

The Association Between Cigarette Smoking and Colorectal Polyp Recurrence (United States)

Objective Although evidence exists linking smoking to precancerous colorectal adenomatous polyps, few studies have examined the association between cigarette smoking and recurrence of colorectal polyps. This association was investigated prospectively with data from the Polyp Prevention Trial. Methods Cigarette smoking data were collected through baseline interviews. The study was completed by 1872 men and women with presence of adenomas at baseline colonoscopy. Multiple logistic regression analysis was used to examine the association between cigarette smoking and polyp recurrence (adenomatous and hyperplastic) up to four years from baseline. Results Adenoma recurrence was not related to cigarette smoking. Current smokers had increased odds of hyperplastic polyps at follow-up compared to never smokers (OR 2.88, 95% CI 2.06–4.01). Current smoking was associated with subsequent distal (OR 3.44, 95% CI 2.38–4.95) and rectal (OR 3.53, 95% CI 2.15–5.78) hyperplastic polyps, but not subsequent proximal hyperplastic polyps. Cigarette smoking was associated with subsequent multiple and small size (4 mm) hyperplastic polyps. Significant linear trends were observed between development of subsequent hyperplastic polyps and all smoking variables. Conclusions Although no association with recurrent adenomas was observed, cigarette smoking was significantly associated with hyperplastic polyp development, except for those in the proximal colon. This prospective study confirms that cigarette smoking has a significant effect on the development of hyperplastic colorectal polyps. Other Members of the Polyp Prevention Trial Study Groups are listed in the Appendix     

High c-myc protein expression in benign colorectal lesions correlates with the degree of dysplasia.

Sections of normal colon (n = 14), hyperplastic polyps (n = 31) ulcerative colitis (n = 97) and tubular adenomas (n = 40) were examined by immunohistochemistry for the expression of the c-myc proto-oncogene product in order to assess its potential diagnostic value in predicting the malignant potential of these lesions. We compared the degree of epithelial abnormality in these colorectal specimens with the extent of immunoperoxidase staining for c-myc oncoprotein, we found that high c-myc protein expression correlated with the degree of epithelial alteration in ulcerative colitis and tubular adenoma groups. Weakly positive staining was found in 10 out of 14 normal colon samples and 28 out of 31 hyperplastic polyps. High tissue expression of c-myc protein, when combined with histologic dysplasia, may prove to be an additional factor in the evaluation of malignant potential in ulcerative colitis specimens and adenomas.     

The probability of malignant degeneration of stomach polyps

A retrospective analysis of the endoscopic diagnostic data on 151 cases of gastric polyps of various histological structure was carried out. A relationship between the risk of malignant transformation of gastric polyps, on the one hand, and their histology, presence and degree of dysplasia, on the other, was established. Epithelial dysplasia, in pronounced degree included, was observed in 33.7% of patients with hyperplastic polyps and in all cases of gastric adenoma. Epithelial dysplasia of hyperplastic polyps was mild or moderate in most cases while that of adenomatous polyps was moderate or grave. Gastric cancer as a consequence of malignant transformation of polyps was detected in 15 (9.9%) patients (hyperplastic polyps--2; adenomatous polyps--13). No objective endoscopic criteria for establishing the risk of polyp transformation were developed. Grave epithelial dysplasia, i.e. precancerous lesions in the gastric mucosa, may be suggested as such criterion. Moderate or grave dysplasia of the polyp epithelium should be considered in forming the group at risk first and foremost.     

Expression of LewisX and sialylated LewisX antigens in human colorectal polyps

The LewisX (LeX) antigen [characterized by trisaccharide Gal beta 1----4 (Fuc alpha 1----3)N-acetylglucosamine] is an oncodevelopmental antigen in the human colon. Monoclonal antibodies (MoAbs), anti-SSEA-1 and AH8-183, which recognize LeX antigen either on short oligosaccharide side chains or as a terminal immunodeterminant on longer carbohydrate side chains of glycoconjugates, bind to most colon cancer tissues but also to some normal colon mucosae. However, the monoclonal antibodies FH1, FH4, FH6, and IB9, which recognize extended difucosylated and trifucosylated LeX structures or their sialylated derivatives, are more cancer-associated because they rarely bind to normal colon mucosa. In the present study, these MoAbs were used to compare the expression of various LeX-related antigens in premalignant (adenomatous) and nonpremalignant (hyperplastic) colorectal polyps. Antigen expression in polyps was also compared to antigen expressions of normal colon mucosa and colon cancer tissues. The four MoAbs recognizing extended LeX antigens bound to adenomatous polyps (APs) significantly more than to hyperplastic polyps (HPs). In contrast, anti-SSEA-1 and AH8-183 recognizing monofucosyl LeX were less able to distinguish between APs and HPs. In APs, staining with the four MoAbs recognizing extended LeX antigens correlated with the premalignant parameters of larger polyp size, more severe dysplasia, and increased villose component. However, staining with AH8-183 correlated only with polyp size, and anti-SSEA-1 correlated only with polyp size and degree of dysplasia. In general, the staining frequency of HPs was similar to that of normal colon mucosa, although FH6, which did not stain any specimens of normal mucosa, stained a few HPs. The staining frequency of APs was less than that of colon cancer tissues, but these differences were generally not statistically significant. In conclusion, extended LeX antigens and their sialylated derivatives are cancer-associated antigens that are expressed preferentially in premalignant colon polyps, that tend to correlate with malignant potential in these polyps, and that may eventually help to define mechanisms involved in the polyp-to-cancer sequence.     

Tobacco smoking and colorectal hyperplastic and adenomatous polyps.

Colorectal adenomas and possibly some hyperplastic polyps are precursors of colorectal cancer. Tobacco use is associated in epidemiologic studies with these polyps, although links between smoking and colorectal cancer are less consistent. To characterize the role of tobacco in early colorectal carcinogenesis, we compared tobacco use among 4,383 subjects with histologically verified benign (hyperplastic or adenomatous) polyps of the distal colon (descending colon, sigmoid, and rectum) with tobacco use among 33,667 subjects who were endoscopy negative for distal colon tumors, in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Trial, a randomized trial of flexible sigmoidoscopy. Risks, estimated by the odds ratio (OR), associated with current cigarette use were OR = 4.4 [95% confidence interval (95% CI), 3.7-5.2] for hyperplastic polyps only, OR = 1.8 (95% CI, 1.5-2.1) for adenomas only, and OR = 6.2 (95% CI, 4.7-8.3) for subjects with both hyperplastic and adenomatous polyps concurrently. Effects were weaker among ex smokers; the smoking-associated ORs remained consistently higher for hyperplastic polyps. This pattern was also seen in relation to cigarettes smoked per day, smoking duration, and pack-years. Tobacco-associated risks for multiple polyps were also stronger when hyperplastic disease was involved. In conclusion, tobacco use, particularly recent use, increases risk for both adenomatous and hyperplastic polyps, but the risks are substantially greater for hyperplastic lesions.     

Differential expression of difucosyl type 2 chain (LeY) defined by monoclonal antibody AH6 in different locations of colonic epithelia, various histological types of colonic polyps, and adenocarcinomas

The expression of LeY (Fuc alpha 1----2Gal beta 1----4 [Fuc alpha 1----3]GlcNAc beta 1----R) (in which Fuc is fucose, Gal is galactose, and GlcNAc is N-acetylglucosamine) defined by monoclonal antibody AH6 in various locations of human colonic epithelia, colonic polyps, and adenocarcinomas has been studied. In normal colonic mucosa, strong staining by AH6 was observed in the proximal regions such as the terminal ileum and cecum. The staining was, however, greatly reduced in the epithelia of the ascending colon and became very weak in the epithelia of transverse, descending, and sigmoidal colon as well as the rectum. Of 481 crypts in 40 biopsy samples of the epithelia of normal sigmoidal colon, 421 crypts did not show any staining, and only a weak staining of the lowest crypt area was observed in 60 crypts (12%); of 474 crypts in 40 biopsy samples of normal rectal epithelia, 110 crypts (26%) showed a weak staining. At the fetal stage, the LeY staining was much more intense in all locations of the colon than in corresponding locations of adult epithelia, and staining was observed in the epithelia of the sigmoidal colon and rectum. A strong staining was observed in 24 of 25 cases of colorectal adenocarcinomas, irrespective of their original location. The expression of LeY in polyps was correlated with histological type as well as the degree of dysplasia of the polyps. Of various adenomas examined, tubular adenomas, many of which showed mild or moderate dysplasia and less malignant potentials, displayed the least LeY expression. Tubulovillous and villous adenomas, which have higher malignant potential and showed a higher incidence of severe dysplasia, showed a greater area and intensity of LeY expression. No LeY was detectable in juvenile polyps, and only a very weak staining was observed in the dysplastic area of hyperplastic polyps. The extent and intensity of staining in various adenocarcinomas and adenomas could not be correlated with blood group ABO status of the hosts nor with location of the tumors. These results suggest that LeY in colonic adenocarcinomas and polyps at the distal region of the colon and rectum is a typical oncofetal antigen and is a useful marker for diagnosis of colonic cancer. Its expression in colonic polyps can be correlated with the degree of dysplasia and may indicate the degree of malignant potential of the polyp. Thus, LeY expression in polyps may have prognostic value.     

The value of colonoscopic surveillance following a diagnosis of colorectal cancer or adenomatous polyp

Conventional follow-up of patients with colonic neoplasia will at best only identify symptomatic lesions and those visible with a sigmoidoscope, and will therefore fail to identify new malignant lesions in time for effective treatment. In 1980 we began a prospective study of the efficacy and feasibility of replacing conventional outpatient follow-up with annual colonoscopic surveillance. One hundred and fifty-eight patients, attending one surgeon, have been entered: 74 patients who had a curative resection for colorectal carcinoma and 84 patients who had endoscopic or local resection of an adenoma. In the carcinoma group (mean follow-up 4.3 years, range 1-21), 40 of 237 colonoscopies were positive (17%) in 27 patients (36%). Forty-eight polyps were removed endoscopically and two asymptomatic recurrent carcinomas identified. In the adenomatous polyp group (mean follow-up 4 years, range 1-11), 40 of 252 colonoscopies were positive (16%) in 29 patients (34%). Fifty polyps were removed endoscopically, including two which had become malignant. All patients were also screened by Haemoccult stool testing, in the hope that it would identify these lesions and allow the frequency of colonoscopy to be reduced. Unfortunately, Haemoccult testing failed to identify many lesions, including one carcinoma and one malignant polyp. Our experience suggests that colonoscopic follow-up of all patients with colonic neoplasia attending one surgeon is a feasible exercise which can and should replace outpatient appointments for clinical examination.     

The Importance of Increased Serrated Polyp Detection Rate

Based on the World Health Organization (WHO) criteria, serrated lesions were classified as sessile serrated adenoma/polyp (SSA/P), traditional serrated adenoma (TSA), and hyperplastic polyp (HP). Large serrated lesions are found to be associated with advanced colonic adenoma in the colon. Serrated lesions of the colorectum are believed to account for 15–20 % of all colorectal cancers via the “serrated neoplastic pathway” with SSA/P being the main precursor lesion. Serrated lesions are also thought to account for around 30 % of cancers that develop after a negative colonoscopy or the interval cancers. While serrated lesions are often flat or sessile and inconspicuous on conventional white light colonoscopy, missed lesions are not uncommon. Increased detection of serrated lesions may potentially reduce the incidence and mortality of colorectal cancers, especially the risk of interval cancers. Further research shall be directed to improve detection of serrated lesions by colonoscopy.