代谢综合征对结直肠管状绒毛状腺瘤的影响因素分析

目的分析结直肠管状绒毛状腺瘤与代谢综合征的关系。 方法收集2017年6月至2020年12月南方医科大学附属惠阳医院经手术病理确诊的271例患者。其中管状腺瘤患者203例，管状绒毛状腺瘤患者68例。比较结直肠管状腺瘤与管状绒毛状腺瘤患者纤维结肠内镜检查的基本情况，结直肠息肉一般特征、数目、病理，以及代谢综合征相关指标水平等。采用Logistic多因素回归分析山田分型、最大息肉直径、代谢综合征相关指标与结直肠管状绒毛状腺瘤的关系。 结果累计息肉数目最多部位、最大息肉好发部位、病理为管状绒毛状腺瘤/管状腺瘤好发部位均为乙状结肠。结直肠管状腺瘤与管状绒毛状腺瘤患者山田分型、最大息肉直径、血清甘油三酯水平差异均有统计学意义（P均<0.01），而高血压、脂肪肝、空腹血糖受损或糖尿病情况及总胆固醇水平、血清尿酸水平、癌胚抗原水平差异均无统计学意义（P>0.05）。Logistic多因素回归分析结果显示，山田分型及最大息肉直径与结直肠管状绒毛状腺瘤有关联[Wald χ²=5.756，Exp（B）=2.494，P=0.016；Wald χ²=23.173，Exp（B）=12.842，P<0.001]，而血清甘油三酯水平与结直肠管状绒毛状腺瘤无关联。 结论与结直肠管状腺瘤患者相比，代谢综合征与结直肠管状绒毛状腺瘤发病并无直接关联，但息肉直径大小及山田分型与结直肠管状绒毛状腺瘤发病有关联。     

结肠镜诊疗大肠息肉1537例体会

大肠息肉是常见的肠粘膜病变,其大多数是被视为癌前病变的腺瘤。通过结肠镜检出大肠息肉并加以除,打断腺瘤一腺癌的进程,是防治大肠癌的重要措施。1992年1月至1999年12月8年间,我院7246例结肠镜检查检出大肠息肉1537例(2378枚),检出率21．2％。本对这些患的临床资料进行回顾性分析,希望能力大肠息肉的诊疗及大肠癌的防治工作提供一些有用的资料。     

Disappearance of a Sessile Tuhulovillous Adenoma in the Rectosigmoid Colon during Radiation Therapy for Cervical Carcinoma

Colonoscopic polypectomy is the usual treatment for an adenomatous colorectal polyp. We report a case of a sessile tubulovillous adenoma in the rectosigmoid colon disappearing during a course of radiation therapy for an unrelated cervical cancer. This case report illustrates that at least some colonic polyps are radiosensitive and can be eradicated during radiation therapy.     

Efficacy, risk factors and complications of endoscopic polypectomy： Ten year experience at a single center

AIM： To examine the efficacy and complications of colonoscopic resection of colorectal polypoid lesions. METHODS： We retrospectively reviewed 1354 polypectomies performed on 1038 patients over a ten- year period. One hundred and sixty of these were performed for large polyps, those measuring ≥ 20 mm. Size, shape, location, histology, the technique of polypectomy used, complications, drugs assumption and associated intestinal or extra intestinal diseases were analyzed. For statistical analysis, the Pearson χ2 test, NPC test and a Binary Logistic Regression were used. RESULTS： The mean patient age was 65.9 ± 12.4 years, with 671 men and 367 women. The mean size of polyps removed was 9.45 ± 9.56 mm while the size of large polyps was 31.5 ± 10.8 mm. There were 388 pedunculated and 966 sessile polyps and the most common location was the sigmoid colon （41.3%）. The most frequent histology was tubular adenoma （55.9%） while for the large polyps was villous （92/160 -57.5%）. Coexistent malignancy was observed in 28 polyps （2.1%） and of these, 20 were large polyps. There were 17 procedural bleeding （1.3%） and one perforation. The statistical analysis showed that cancer is correlated to polyp size （P 〈 0.0001）; sessile shape （P 〈 0.0001） and bleeding are correlated to cardiac disease （P = 0.034）, tubular adenoma （P = 0.016） and polyp size.CONCLUSION： The endoscopic resection is a simple and safe procedure for removing colon rectal neoplastic lesions and should be considered the treatment of choice for large colorectal polyps. The polyp size is an important risk factor for malignancy and for bleeding.     

Pathology of the adenoma-carcinoma sequence: from aberrant crypt focus to invasive carcinoma

The adenoma-carcinoma sequence postulates that colorectal carcinomas arise from precursor lesions, called adenomas. All adenomas contain dysplastic epithelium that arises from mutations in either the adenomatous polyposis coli gene or DNA mismatch repair genes. The earliest lesion detected with dysplasia is the aberrant crypt focus. Over time, as this lesion acquires additional mutations, it evolves into a classic adenomatous polyp. Adenomatous polyps are classified as tubular, tubulovillous, or villous. Generally, as polyps increase in size, the degree of dysplasia worsens, the villous component increases, the number of genetic abnormalities increases, and the likelihood of harboring invasive carcinoma increases. Carcinomas associated with DNA mismatch repair mutations are more likely to be poorly differentiated and incite a host lymphocytic response. These tumors seem to have a better prognosis, stage for stage, than typical colorectal carcinomas.     

大肠息肉与大肠癌的演变关系（附494例分析）

本组息肉患者４９４例，癌变者１０１例，随着息肉的增大，其癌变率也增加。恶变息肉主要分布在直肠（５７．４％），次为乙状结肠（１９．８％）。管状腺瘤瘤体较小，恶变率较低，绒毛型腺瘤瘤体较大，恶变率较高，且呈重度不典型增生多见。单发息肉癌变率１３．１％，２－５个息肉者癌变率２４．４％，６个以上者癌变率３８．０％，腺瘤病１２例全部癌变。息肉癌变时间１至１５年。癌变术后标本病理均见癌旁组织残存良性管状腺瘤或绒毛型腺瘤成份，从组织学上证明了息肉癌变过程。     

The relationship between cyclooxygenase-2 expression and characteristics of malignant transformation in human colorectal adenomas

BACKGROUND AND AIMS: Cyclooxygenase 2 (COX-2) is a target of aspirin and other non-steroidal anti-inflammatory drugs and is implicated in the pathogenesis of colorectal cancer. The objective of this study was to evaluate the extent of COX-2 in pre-malignant colorectal polyps and to assess the relationship between COX-2 and the level of dysplasia in these lesions. METHODS: Whole polypectomy specimens were retrieved from 123 patients by endoscopic or surgical resection. Following formalin fixation and paraffin embedding, the polyps were evaluated histologically for size, type and grade of dysplasia. The extent of COX-2 expression was measured by the avidin-biotin immunohistochemical technique using a monoclonal COX-2 antibody. The extent of COX-2 expression was graded according to percentage epithelial COX-2 expression. RESULTS: The polyps were of the following histological types: 10 hyperplastic, 35 tubular adenomas, 61 tubulovillous adenomas and 17 villous adenomas. Twenty showed mild dysplasia, 65 moderate dysplasia, and 28 focal or severe dysplasia (including eight with focal invasion). The average polyp size was 1.7 cm. Nine hyperplastic polyps were COX-2-negative and one was COX-2-positive. COX-2 expression was more extensive in larger polyps and in polyps with a higher villous component. There was a significant increase in the extent of COX-2 protein with increasing severity of dysplasia. Within a polyp, there was a focal corresponding increase in COX-2 expression within epithelium showing a higher grade of dysplasia. CONCLUSIONS: COX-2 expression is related directly to colorectal adenomatous polyp size, type and grade of dysplasia. This suggests that the role of COX-2 in colorectal cancer may be at an early stage in the adenoma-to-carcinoma sequence and supports the suggestion that inhibition of COX-2 may be useful chemoprevention for this disease.     

Total colonic polyp diameter: a marker for the risk of malignancy?

BACKGROUND/AIMS: The correlation of the risk of malignancy with the sum of the diameters of small colonic polyps is unknown, and data regarding this topic are lacking. In this study, the relationship between the sum of the diameters of the total number of colonic polyps and poor histopathologic characteristics was examined. METHODS: A total of 920 neoplastic colon polyps were evaluated in 480 patients. The "total polyp diameter" (i.e. the sum of all polyp diameters identified during colonoscopy), which was calculated in each patient by adding the diameter of each polyp to a sum, was categorized as "small" (<10mm in diameter) or "large" (> or =10mm in diameter). The polyps were further categorized by histopathologic component as "unfavorable" or "favorable" and were divided into 2 groups: group 1 (those identified as carci noma, carcinoma in situ, villous adenoma, and tubulovillous adenoma with a villous component of more than 25%) and group 2 (mixed adenomatous polyps with various degrees of hyperplastic or inflammatory components and adenomas with a tubular component of more than 75%). RESULTS: Large polyps that had a total diameter greater than or equal to 10mm tended to have poor histopathologic characteristics (p<0.05). Polyps generally tended to localize in the left portion of the colon, and malignant polyps or those at risk for malignancy in particular tended to localize in the left colon (p<0.05). CONCLUSIONS: Polypectomy is recommended for patients in whom the sum of the diameter of all colonic polyps exceeds 10mm.     

结直肠锯齿状腺瘤内镜表现和病理学特征分析

目的探讨锯齿状腺瘤（SA）内镜下表现和病理学特征。方法回顾分析滨州医学院附属医院2000年1月～2008年5月检出的大肠息肉病例,了解SA的检出率、内镜形态和病理学特征。结果8726例肠镜检查共检出大肠息肉1062例（1457枚）,检出率为12．17％,其中SA32例（60枚）,检出率为0．37％,占息肉构成比为3．01％。SA直径〉1cm者占21．63％,明显大于增生性息肉（8．57％）;SA表现为有蒂息肉所占的比例（8．33％）略高于增生性息肉（5．71％）,但都低于腺瘤性息肉（40．84％）。SA癌变率介于管状腺瘤和绒毛状腺瘤之间,接近于管状绒毛状腺瘤。结论SA内镜形态、病理学特点提示SA是兼有增生性息肉形态学特征和腺瘤性息肉组织学特点的息肉,具有恶变潜能.     

The risk of advanced histology in small-sized colonic polyps: are non-invasive colonic imaging modalities good enough?

Purpose

The study aims to evaluate the risk of advanced histology within small colonic polyps and assess whether this risk warrants different recommendation for surveillance and treatment of such polyps.

Methods

A retrospective study of all patients undergoing their first ever colonoscopy and polypectomy in a tertiary hospital for one of three indications: screening, positive family history, and positive occult blood in stool. The histological reports of all resected polyps were retrieved and stratified according to the various polyps’ sizes. Advanced neoplasia was defined as tubular adenoma ≥10?mm or any size polyp with advanced histology, i.e., villous or tubulovillous adenoma, high-grade dysplasia, intramucosal carcinoma, or invasive cancer.

Results

Seven hundred forty-one patients who had a total of 1,192 resected polyps were included. Of polyps ≤5?mm in size, 1.6% harbored invasive cancer or high-grade dysplasia, and additional 4.1% contained villous component. The rate of advanced histology for polyps sized 6–9?mm was over 15%. The rate of advanced histology in polyps ≤5?mm was not significantly different when employing sensitivity analysis accounting for possible under or overestimation of polyp sizes by 1 and 2?mm. However, 4.6% of polyps sized 6–9?mm were found to harbor an invasive or high-grade dysplasia component when taken into account a 2-mm overestimation.

Conclusions

A non-negligible fraction of small polyps harbor advanced histology. This finding suggests that expectant follow-up by non-invasive colonic imaging modalities for small polyps or not reporting them may put more than 5% of patients at risk of dysplasia progression.     

Mixed colorectal polyps. An immunohistologic and mucin-histochemical study

The morphology of mixed colorectal polyps was analysed. Thirteen such polyps were found out of 2700 colorectal polyps (0.5%). Histology showed a spectrum of hyperplastic crypts from almost pure goblet cell population (two polyps) to hypermature serrated epithelium with scanty goblet cells (seven polyps). Tubular adenomas occurred in 12 polyps, and a tubulovillous adenoma was found in the largest polyp. Moderate dysplasia was seen in the five large polyps. The border between neoplastic and hyperplastic cells was usually sharp. Mucin histochemistry showed similarities between the mixed polyps and colorectal carcinomas--namely, the reduction/absence of sialomucin in both mature hyperplastic crypts and adenomatous glands. The expression of carcinoembryonic antigen within the hyperplastic crypts and within the neoplastic crypts showing moderate dysplasia was similar to that seen in colorectal carcinomas, whereas it was normal within the neoplastic crypts with low-grade dysplasia. IgA was reduced or absent in both components. Blood group antigen was found only within the adenomatous component of the largest polyp showing also moderate dysplasia.     

Clinical significance of small colorectal adenoma less than 10 mm: the KASID study

BACKGROUND/AIMS: Polypectomy is the current modality of choice to prevent benign colorectal adenoma from progressing to an invasive cancer. However, in cases of small colorectal adenoma, it remains unclear as to whether polypectomy is actually an effective treatment modality. We evaluated the clinical significance of polypectomy in cases of small colorectal adenomas, measuring less than 10 mm. METHODOLOGY: All colonoscopies were performed at 11 Korean tertiary medical centers, between July 2003 and March 2004. A total of 5996 colorectal adenomas were detected and divided into 5 groups according to their size (Group 1; 1-5 mm, Group 2; 6-7 mm, Group 3; 8-9 mm, Group 4; 10-19 mm, Group 5; more than 20 mm). The term 'advanced adenoma' refers here to tubular adenomas with diameters of at least 10 mm, or to tubulovillous, villous, or high-grade dysplasia, irrespective of size. 'Cancer' here is defined as the invasion of malignant cells beyond the muscularis mucosa. RESULTS: As the sizes of the adenomas increased, the prevalence of advanced adenoma was also observed to increase. In Groups 2 and 3, the prevalence of tubulovillous or villous adenoma were higher than was expected (5.2% and 6.6%, p < 0.001). Interestingly enough, in Group 2, the prevalence of cancer was at least as high as in Group 4 (0.7% vs. 0.5%, p < 0.001). CONCLUSIONS: In cases of small colorectal adenomas, measuring between 6 and 9 mm, the prevalence of cancer was at least as high as that seen in the cases of colorectal adenomas measuring between 10 and 19 mm. Therefore, small colorectal adenomas measuring between 6 and 9 mm should not be ignored, in order to decrease the prevalence of colorectal cancer.     

腺瘤性息肉的癌变及治疗

为探讨已癌变的结肠腺瘤性息肉的最佳治疗选择，回顾性总结了内镜诊断和治疗的３１４例腺瘤性息肉中３７例癌变息肉的结果。３７例中为管状腺瘤癌变者２５例（占８．９％），绒毛状腺瘤癌变者１１例（占３６．３％），混合性腺瘤癌变１例。１８例仅行内镜下电切，电切后又追加手术８例，手术切除１１例。分期为原位癌１２例，早期浸润癌１３例，浸润癌１２例。１９例手术及术后病理证实的淋巴结转移者３例（１５．７％），包括１例绒毛状腺瘤恶变的早期浸润癌和２例浸润癌。认为除原位癌外，对电切后病理证实的早期浸润癌或浸润性癌，只要无手术禁忌，应追加外科手术治疗为妥。     

Clinicopathological characteristics of serrated polyps as precursors to colorectal cancer: Current status and management

Serrated polyps have long been thought to lack malignant potential in the human colorectum. However, identification of the serrated pathway to colorectal cancer based on molecular biology has improved our understanding of the pathogenesis of colorectal cancers. Accordingly, serrated polyps such as traditional serrated adenoma and sessile serrated adenoma/polyps (SSA/P) are now considered to be precursor lesions of the serrated pathway. Recently, serrated polyps were classified into three subtypes, consisting of hyperplastic polyp, SSA/P, and traditional serrated adenoma, according to the World Health Organization classification. It has been suggested that SSA/P in the proximal colon are a precursor lesion of pathogenesis of colorectal cancer and are characterized by BRAF mutation and a CpG island methylator phenotype with or without microsatellite instability. However, SSA/P is more challenging to detect by colonoscopy and is likely to account for some interval cancers, particularly in the proximal colon because it presents flat or sessile, isochroous appearance, and occasionally has a mucous cap. Furthermore, the possibility has been raised that pathologists misclassify SSA/P as hyperplastic polyp. It is important for gastroenterologists to recognize the endoscopic features of serrated polyps to facilitate their detection and removal and also to establish postpolypectomy surveillance guidelines. In this review, we discuss the recent classification of serrated polyps; the molecular characteristics of the serrated pathway; appropriate diagnostic methods using endoscopy, including a new image‐enhanced endoscopic technique; and management of these lesions.     

Histologic characteristics of gastric polyps in Korea： Emphasis on discrepancy between endoscopic forceps biopsy and endoscopic mucosal resection specimen

AIM: To investigate histological characteristics of gastric polyps in the Korean population. METHODS: We reviewed endoscopic photographs and medical records of patients with gastric polyps who underwent endoscopic mucosal resection from April 1996 through February 2003. RESULTS: A total of 85 gastric polyps from 74 patients were reviewed. Male-to-female ratio was 1:1.96. Mean age was 59.9±10.8 years. Multiple polyps were observed in 10.8%. Gastric polyps occurred most frequently in the antrum (58.8%). Pathological results on resected specimens were as follows: tubular adenoma 45.9%, hyperplastic polyp 31.8%, inflammatory polyp 9.4%, hamartoma 3.5%, fundic gland polyp 2.4%, tubulovillous adenoma 2.4%, adenocarcinoma 2.4%, dysplasia 1.1%, and mucosal pseudolipomatosis 1.1%. Discrepancy rate between endoscopic biopsy and pathology of resected specimens was 27.1%. There was no relationship between the size of the polyp and concordance rate. CONCLUSION: There is considerable discrepancy in histologic findings between endoscopic forceps biopsy and resected specimens. Approaches to review of the histology of an entire polyp should be performed, especially when an adenoma is suspected.     

Correlation of Ki-67, p53, and Adnab-9 immunohistochemical staining and ploidy with clinical and histopathologic features of severely dysplastic colorectal adenomas

Variations of Ki-67, p53, and Adnab-9 monoclonal antibody reactions in colonic adenomas may be associated with colonic cancer risk. We studied the predictive value of these markers for adverse behavior in severely dysplastic colorectal adenomas, such as an associated carcinoma, multiplicity of adenomas, and subsequent development of adenomas. For this purpose we compared the clinical, gross, and histologic characteristics of highly dysplastic index polyps in 42 patients with Ki 67, p53, and Adnab-9 immunostaining and other molecular markers. Polyps were removed endoscopically, and severely dysplastic polyps were stained immunohistochemically with Ki-67, Adnab-9, and p53 protein by the avidin biotin conjugate (ABC) technique. Quantitative DNA (QDNA) was analyzed by computer-assisted image analysis. Ki-67 immunohistochemistry showed reversal of normal distribution of nuclear staining from the normal basal position to the upper third of the colonic crypts. This abnormality of immunostaining in dysplastic adenomas was the earliest detected by the panel we used. A statistically significant correlation was seen between invasiveness of carcinoma in the index polyp and polyp size (P = 0.003), sessile morphology (P = 0.037), and villous or tubulovillous histology (P = 0.019). In the index adenoma, p53 positivity was correlated with multiplicity at initial examination (P = 0.053), villous histology (P = 0.053), invasiveness of carcinoma (P < 0.003), and recurrence of colorectal adenomas (P = 0.025). Although p53 positivity and aneuploidy were correlated with invasiveness of carcinoma in the index polyp (P = 0.025), Adnab-9 positivity was not. However, Adnab-9 positivity in the index polyp was associated with multiplicity of adenomas (P = 0.04) as well as recurrence of adenomas (P < 0.024). In conclusion, in addition to the morphologic and histologic markers already known, Ki-67, Adnab-9 antibody, and p53 protein may be prognostic indicators useful in follow-up of patients with severely dysplastic colorectal adenomas. Adnab-9 antibody may identify a field defect in above-average-risk adenoma-bearing patients.     

Pathologist agreement in the interpretation of colorectal polyps

Practicing physicians commonly perform flexible sigmoidoscopy in their offices. Polyploid lesions are frequently biopsied and sent to community hospitals for pathological interpretation. The pathologist's opinion often determines the course of medical follow-up for the patient, especially in cases in which early malignancy is suspected. This paper addresses the agreement of community-based pathologists regarding the interpretation of colorectal polyp pathology. Ten pathological slide sections were sent to 22 different community-based pathologists in southeast Michigan. These pathologists were asked to record their diagnosis of the specific histologies represented in each of the slides. The results indicated a high level of agreement of histologies in the dichotomous categories of hyperplasia versus adenoma. However, there was considerable disagreement on the presence of moderate or severe atypia. The results of this study indicate that clinicians performing biopsies on patients at risk for colorectal cancer should be aware of the potential for diagnostic variability among pathologists, and should plan follow-up strategies which may include seeking second pathological opinions when a significant patient management decision must be made.     

Frequency of polyps in patients undergoing surgery for colorectal cancer

INTRODUCTION: Epidemiologic and molecular biologic studies have already demonstrated that adenomatous colonic polyps are precancerous diseases. The main indication of the colonoscopy in the surveillance of colorectal cancer treated patients is the diagnosis and resection of adenomatous polyps. AIM: To study the frequency of adenomatous polyps after surgically resection of colorectal cancer. MATERIAL AND METHODS: Sixty eight patients, mean age 59 years old, with total resection of colorectal cancer, submitted to various colonoscopies during the follow up were studied retrospectively. The histological type and the characteristics of the polyp were described. RESULTS: The frequency of polyps was 18%, being higher in the patients with more than 45 years (20%). The site of the polyps was in the left colon in 38% of the patients with cancer. The histological type of adenomas was tubular in 61%, villous in 22% and mixed in 17%. DISCUSSION: As described by other authors, the incidence of polyps were higher after 45 years old and more than a half of them were tubular. The frequency of polyps was higher in the first two years of follow up.     

Predictive value of morphologic characteristics in rectosigmoid adenomatous polyps for the probability of synchronous polyps or cancer in the proximal colon.

BACKGROUND/AIMS: Sigmoidoscopy is performed more frequently than colonoscopy, especially for screening purposes and searching for colorectal neoplasm. The necessity of colonoscopy in patients with an adenoma ofor=11 mm) polyps. These groups were compared regarding the presence of proximal adenoma and advanced proximal neoplasia (>10 mm adenoma and/or villous histology and/or high grade dysplasia or cancer). Polyps found in the rectum and sigmoid colon were considered as distal polyps and polyps other than these were considered as proximal polyps. RESULTS: In this study, of 1124 consecutive patients who underwent colonoscopy between April 1997 and January 2002, 184 (16%) had 258 adenomatous polyps in the rectosigmoid area. The polyps were diminutive (or=11 mm) in 33 patients. Forty-one of the patients (39%) with diminutive polyps, 20 of the patients (43%) with small polyps and 19 of the patients (57%) with large polyps had neoplasm in the proximal bowel. In these patients, advanced proximal neoplasm was found in 8 (8%), in 6 (13%) and in 11 (33%), respectively. There was no difference regarding the presence of neoplasm in the proximal colon between these groups. The rate of advanced proximal neoplasm was found to be significantly higher in the group with large polyps in the rectosigmoid area than in the groups with small and diminutive polyps (p<0.05). In 104 patients (57%) with polyp(s) in rectum and sigmoid colon, no associated polyp or cancer was encountered in the proximal colon. CONCLUSION: Colonoscopy is indicated when adenomatous polyp, regardless of size, is found on rectosigmoidoscopy performed because of symptoms.     

转化生长因子-β1、Smad3、Smad4和Smad7在结直肠癌发生中的作用

结直肠腺瘤-腺癌序列是目前公认的结直肠癌发生学说，但关于结直肠腺瘤，特别是高危型结直肠腺瘤中转化生长因子（TGF）-β1通路蛋白表达的临床研究较少。目的：探讨TGF—β1、Smad3、Smad4和Smad7在结直肠癌发生中的作用。方法：选取2000年8月-2006年12月六安市人民医院结直肠息肉标本110例（包括腺瘤性和非腺瘤性息肉）、结直肠癌40例和正常结直肠组织20例，以免疫组化染色检测TGF—β1、Smad3、Smad4和Smad7在各组中的表达．并分析高危型腺瘤中TGF-IM、Smad3、Smad4和Smad7表达与临床病理特征的关系。结果：TGF-IM、Smad3、Smad4、Smad7在息肉组、结直肠癌组和对照组中的表达有显著差异（P〈0．05），其表达与高危型腺瘤患者的临床病理特征均不相关。高危型腺瘤和DukesA期结直肠癌中TGF-IM、Smad3、Smad7的表达有显著差异（P〈0．05），而Smad4表达无显著差异。结论：TGF—β1通路可能参与了结直肠癌的发生过程，TGF—β1、Smad3和Smad7可能在结直肠腺瘤的癌变早期起作用。